KR20070052207A - Novel inhibitors of protein kinase - Google Patents

Novel inhibitors of protein kinase Download PDF

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KR20070052207A
KR20070052207A KR1020060112622A KR20060112622A KR20070052207A KR 20070052207 A KR20070052207 A KR 20070052207A KR 1020060112622 A KR1020060112622 A KR 1020060112622A KR 20060112622 A KR20060112622 A KR 20060112622A KR 20070052207 A KR20070052207 A KR 20070052207A
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pyridin
methyl
thiazolo
amino
ylamino
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KR1020060112622A
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Korean (ko)
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윤승현
주현우
송정욱
김영관
구선영
양소연
김경희
황진아
조흥수
박태교
김민정
최세현
최환근
조기원
김민형
김지은
김정인
임동철
송지수
윤혜성
홍상용
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주식회사 엘지생명과학
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis

Abstract

본 발명은 브이이지에프 수용체2 키나아제(VEGFR2 kinase, KDR)의 활성을 억제하는 하기 화학식의 화합물, 그것의 제조방법, 그것의 용도 및 그것을 약리학적 유효량으로 포함하는 약제 조성물에 관한 것이다. 본 발명에 따른 화합물들은, 바람직하지 못한 KDR 활성으로 인한 질병들, 예를 들어, 암, 건선, 류마티스성 관절염, 당뇨병성 망막증 등과 같이 신생혈관생성에 관련된 질병들의 치료 및 억제에 효능을 나타낸다.The present invention relates to a compound of the formula below which inhibits the activity of VEGFR2 kinase (KDR), a method for its preparation, its use, and a pharmaceutical composition comprising the same in a pharmacologically effective amount. The compounds according to the invention show efficacy in the treatment and inhibition of diseases due to undesired KDR activity, for example diseases related to angiogenesis such as cancer, psoriasis, rheumatoid arthritis, diabetic retinopathy and the like.

Figure 112006083464511-PAT00001
Figure 112006083464511-PAT00001

상기 식에서 R1, R2, X 및 Y 는 명세서에서 정의된 바와 같다.Wherein R 1 , R 2 , X and Y are as defined in the specification.

Description

신규한 ＫＤＲ 억제제 {NOVEL INHIBITORS OF PROTEIN KINASE}NOVEL INHIBITORS OF PROTEIN KINASE

본 발명은 아미노티아졸 구조를 가지고 있는 신규 화합물에 관한 것으로서, 더욱 상세하게는 화학식 1로 표현되는, 신규한 브이이지에프 수용체2 키나아제(VEGFR2 kinase 또는 KDR, 이하 "KDR"이라 함) 활성 저해를 위한 화합물, 약제학적으로 허용 가능한 그것의 염 등을 제공한다. 본 발명에 따른 화합물은 바람직하지 못한 KDR 활성으로 인한 질병들, 예를 들어, 암, 건선, 류마티스성 관절염, 당뇨병성 망막증 등과 같이 신생혈관생성에 관련된 질병의 치료 및 억제에 유용하다.The present invention relates to a novel compound having an aminothiazole structure, and more particularly, to inhibit the novel VGF receptor2 kinase (VEGFR2 kinase or KDR, hereinafter referred to as "KDR") activity represented by the formula (1). Compounds, pharmaceutically acceptable salts thereof, and the like. The compounds according to the invention are useful for the treatment and inhibition of diseases due to undesired KDR activity, such as diseases related to angiogenesis such as cancer, psoriasis, rheumatoid arthritis, diabetic retinopathy and the like.

신생혈관생성(Angiogenesis)은 세포 생존에 있어서 필요한 양분과 산소를 공급하고 대사물을 배출하는 통로인 혈관을 새로이 만들어내는 기작으로 성인의 경우 평상시에는 혈관세포의 0.01% 정도만이 증식하여 혈관내의 여러 상처를 복구하고 있다 (Carmeliet et al., 2000, Nature 407:249-257). Angiogenesis is a mechanism that creates new blood vessels, a pathway for supplying nutrients, oxygen, and metabolites for cell survival. In adults, only about 0.01% of blood vessel cells normally proliferate, resulting in various wounds in blood vessels. Is recovering (Carmeliet et al ., 2000, Nature 407 : 249-257).

그러나, 고형암(Solid Tumor)과 같은 빠른 성장을 하는 조직에서는 더 많은 양분과 산소가 요구되며, 그 결과 새로운 신생혈관 형성을 더욱 필요로 하게 된다. 실제로 새로운 혈관형성 없이 고형암은 어느 크기(직경 100 에서 200 ㎛) 이상의 성장이 불가능하다. 그 이유는 산소나 양분이 혈관을 떠나 확산에 의해서 세포에 도달할 수 있는 거리에 한계(Diffusion limit)가 있기 때문이다 (Carmeliet et al., 2000, Nature 407:249-257). However, fast-growing tissues such as solid tumours require more nutrients and oxygen, which in turn requires more new neovascularization. Indeed, solid tumors cannot grow beyond a certain size (100 to 200 μm in diameter) without new angiogenesis. This is because there is a limit on the distance that oxygen or nutrients can leave the blood vessels and reach the cells by diffusion (Carmeliet et al ., 2000, Nature 407 : 249-257).

혈관에서 떨어진 곳에 존재하는 암세포들은 산소의 공급부족으로 저산소 상태(Hypoxia)의 환경에 놓이게 된다. 이러한 조건에서 암이나 기질세포(stromal cell)로부터 여러 종류의 신생혈관형성 유도인자(pro-angiogenic factors)를 분비하여 신생혈관 형성을 고형암 내부로 유도하게 된다. 이러한 신생혈관형성을 유도하는 인자들 중에는 VEGF(Vascular Endothelial Growth Factor), bFGF(basic Fibroblast Growth factor), PDGF(Platelet-derived growth factor) 등이 있다. 이러한 성장자극 인자(growth factor)들에 의해서 신생혈관형성이 활성화되며, 그 결과로 암세포가 활발히 증식하게 된다(Carmeliet P., 2000, Nature Medicine 6:389-395, Yancopoulos et al., 2000, Nature 407:242-248). Cancer cells away from blood vessels are placed in a hypoxia environment due to a lack of oxygen. Under these conditions, a variety of pro-angiogenic factors are secreted from cancer or stromal cells to induce neovascularization into solid cancer. Among the factors that induce such angiogenesis are Vascular Endothelial Growth Factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF). Angiogenesis is activated by these growth stimulating factors, resulting in active proliferation of cancer cells (Carmeliet P., 2000, Nature Medicine 6 : 389-395, Yancopoulos et. al ., 2000, Nature 407 : 242-248).

암 이외의 신생혈관형성 관련 질병으로서 관절염은 만성 염증성 질환으로 진행되는 과정에서 형성된 신생모세혈관이 관절을 침습하여 연골을 파괴하는 신생혈관형성 관련 질환이다. 또한, 당뇨병성 망막증은 모세혈관이 망막의 초자체에 침습하여 생기는 질환으로, 그것의 원인은 허혈의 망막으로부터 혈관신생을 자극하는 인자가 방출되어 이런 질병을 야기한다고 알려져 있다. 눈은 가장 혈관이 없는 조직이므로 혈관이 성장하게 되면 곧 실명된다. 따라서, 혈관신생을 막아야만 근본적인 치료가 가능하다 (Carmeliet P., 2000, Nature Medicine 6: 389-395, Aiello L. P., 2000, Nature Medicine 6: 379-381). As angiogenesis-related diseases other than cancer, arthritis is an angiogenesis-related disease in which neocapillaries formed during the course of a chronic inflammatory disease invade joints and destroy cartilage. In addition, diabetic retinopathy is a disease caused by the capillary invasion of the retina's vitreous body, and its cause is known to cause the disease by releasing factors that stimulate angiogenesis from the ischemic retina. The eye is the tissue without the most blood vessels, and as soon as the blood vessels grow, they become blind. Thus, the fundamental treatment is only possible by preventing angiogenesis (Carmeliet P., 2000, Nature Medicine 6 : 389-395, Aiello LP, 2000, Nature Medicine 6 : 379-381).

신생혈관형성 유도인자의 수용체인 VEGFR2(KDR), FGFR1, PDGFR-β 등의 신생혈관형성 RTK(Receptor Tyrosine Kinase)들은 신생혈관형성 억제제(anti-angiogenesis drug)의 개발에 대한 타겟으로 관심을 모으고 있다. 그러한 억제제는 VEGFR2(KDR)의 키나아제 활성을 억제하며 동시에 다른 신생혈관형성 RTK 계열의 활성도 억제하는 효능을 보인다. 이러한 복합적인 억제 효능은 신생혈관 억제 효능을 증폭시키는 한가지 기작으로 알려져 있다 (Adams et al., 2002, Current Opinion in Chemical Biology, 6:486-492). 따라서, 이를 이용하여 암, 류마티스성 관절염, 당뇨병성 망막증 등과 같은 신생혈관생성에 관련된 질병의 억제 및 치료제로서 사용될 수 있는 화합물들에 대한 많은 연구가 행해지고 있다.Receptor Tyrosine Kinases (RTKs) such as VEGFR2 (KDR), FGFR1, and PDGFR-β, which are receptors for angiogenesis inducers, are attracting attention as targets for the development of anti-angiogenesis drugs. . Such inhibitors exhibit the effect of inhibiting the kinase activity of VEGFR2 (KDR) while simultaneously inhibiting the activity of other angiogenic RTK families. This complex inhibitory effect is known as one mechanism for amplifying neovascular suppression efficacy (Adams et al., 2002, Current Opinion in Chemical Biology, 6 : 486-492). Therefore, many studies have been conducted using compounds which can be used as agents for inhibiting and treating diseases related to angiogenesis such as cancer, rheumatoid arthritis, diabetic retinopathy and the like.

KDR의 키나아제 활성을 억제하는 화합물의 대표적인 예로는, 2-인돌리논 유도체(WO 98/050356), 퀴나졸린 유도체(EP 0566266 A1), 트리아졸 유도체(WO 02/057240), 디아미노티아졸(WO 00/075120), 벤조티아졸 유도체(WO 01/057008) 등이 알려져 있으나, 이들은 본 발명에 따른 화합물과 구조적인 연관성이 없다.Representative examples of compounds that inhibit the kinase activity of KDR include 2-indolinone derivatives (WO 98/050356), quinazoline derivatives (EP 0566266 A1), triazole derivatives (WO 02/057240), diaminothiazole (WO 00/075120), benzothiazole derivatives (WO 01/057008) and the like, although these are not structurally related to the compounds according to the invention.

본 출원의 발명자들은 심도 있는 연구와 다양한 실험들을 계속한 끝에, KDR의 활성을 저해하는 신규한 화합물을 합성할 수 있었고, 그 저해능을 평가해 본 결과, 화학식 1의 화합물이 바람직하지 못한 KDR 활성으로 인한 질병들, 예를 들어, 암, 건선, 류마티스성 관절염, 당뇨병성 망막증 등 신생혈관생성에 관련된 질병들의 치료에 사용될 수 있음을 발견하고, 본 발명을 완성하기에 이르렀다.After further studies and various experiments, the inventors of the present application were able to synthesize a novel compound that inhibits the activity of KDR, and as a result of evaluating the inhibitory activity, the compound of Formula 1 was found to have undesirable KDR activity. It has been found that the present invention can be used for the treatment of diseases related to angiogenesis, such as cancer, psoriasis, rheumatoid arthritis, diabetic retinopathy, etc., and has completed the present invention.

따라서, 본 발명은 하기 화학식 1의 화합물, 또는 약제학적으로 허용되는 그것의 염을 제공한다.Accordingly, the present invention provides a compound of formula 1, or a pharmaceutically acceptable salt thereof.

Figure 112006083464511-PAT00002
(1)
Figure 112006083464511-PAT00002
(One)

상기 식에서,Where

A) R1 은 수소 또는 C1-C10 알킬이며, A) R 1 is hydrogen or C 1 -C 10 alkyl,

B) A1 및 A2 는 각각 독립적으로 탄소 또는 질소이며,B) A 1 and A 2 are each independently carbon or nitrogen,

C) R2 는 수소, 할로겐, 시아노, -CF3 및 C1-C10 알킬로 이루어진 군에서 선택되며, C) R 2 is hydrogen, halogen, cyano, -CF 3 and Selected from the group consisting of C 1 -C 10 alkyl,

D) Ar1 은 5각 또는 6각 고리형의 방향족 또는 헤테로방향족이며,D) Ar 1 is a 5 or 6 cyclic aromatic or heteroaromatic,

E) X 는 각각 독립적으로 하기 치환기들로 이루어진 군에서 선택되며,E) X is each independently selected from the group consisting of the following substituents,

I) 수소, 할로겐, 시아노, 히드록시, -CF3, 임의적으로 치환된 C1-C10 알킬;I) hydrogen, halogen, cyano, hydroxy, -CF 3 , optionally substituted C 1 -C 10 alkyl;

II) -OR3, -SR3, -NHR3, -N(R3)2, 여기서, R3는 수소 또는 임의적으로 치환된 C1-C10 알킬이고;II) -OR 3 , -SR 3 , -NHR 3 , -N (R 3 ) 2 , wherein R 3 is hydrogen or optionally substituted C 1 -C 10 alkyl;

III) -C(=O)R4, -NR5C(=O)NR4R6, -NR5C(=S)NR4R6, III) -C (= 0) R 4 , -NR 5 C (= 0) NR 4 R 6 , -NR 5 C (= S) NR 4 R 6 ,

여기서, R4 는 Where R 4 Is

i) 히드록시;i) hydroxy;

ii) 임의적으로 치환된 C1-C10 알킬;ii) optionally substituted C 1 -C 10 alkyl;

iii) 임의적으로 치환된 C1-C10 알콕시;iii) optionally substituted C 1 -C 10 alkoxy;

iv) -NR7R8 또는 -N(-R7)OR8, 여기서, R7 및 R8 은 각각 독립적으로 수소, 임의적으로 치환된 C1-C10 알킬, 임의적으로 치환된 알릴, 임의적으로 치환된 술폰, 또는 임의적으로 치환된 아민이고, R7 및 R8 은 상호 연결되어 환 구조를 이룰 수 있으며;iv) -NR 7 R 8 or -N (-R 7 ) OR 8 , wherein R 7 And R 8 Are each independently hydrogen, optionally substituted C 1 -C 10 alkyl, optionally substituted allyl, optionally substituted sulfone, or optionally substituted amine, and R 7 And R 8 Are interconnected to form a ring structure;

v) -(CH2)n1NR9-(CH2)n2-NR7R8, 여기서, R7 및 R8 은 상기 정의한 바와 같고, R9 는 수소이거나 임의적으로 치환된 C1-C10 알킬이며, n1 은 0 또는 1 내지 5의 정수이고, n2 는 1 내지 5의 정수이며;v)-(CH 2 ) n1 NR 9- (CH 2 ) n2 -NR 7 R 8 , wherein R 7 And R 8 Is as defined above, R 9 is hydrogen or optionally substituted C 1 -C 10 alkyl, n 1 Is 0 or an integer from 1 to 5, n 2 Is an integer from 1 to 5;

R5 및 R6 은 각각 독립적으로 수소, 히드록시, 임의적으로 치환된 C1-C10 알킬, 임의적으로 치환된 알릴, 임의적으로 치환된 술폰 알킬, 또는 임의적으로 치환된 아민이고;R 5 And R 6 Are each independently hydrogen, hydroxy, optionally substituted C 1 -C 10 alkyl, optionally substituted allyl, optionally substituted sulfone alkyl, or optionally substituted amine;

R4, R5 및 R6 중 선택된 두 개의 치환기는 상호 연결되어 환 구조를 이룰 수 있으며;R 4 , R 5 And two substituents selected from R 6 may be connected to each other to form a ring structure;

F) n 은 0 또는 1 ~ 5의 정수이며,F) n is 0 or an integer from 1 to 5,

G) E 는 산소 또는 황이며;G) E is oxygen or sulfur;

H) Ar2 는 수소 또는 하기 화학식 2로 표현되는 5각 또는 6각의 방향족 고리 화합물이며,H) Ar 2 is hydrogen or a 5- or 6-membered aromatic ring compound represented by the following formula (2),

Figure 112006083464511-PAT00003
(2)
Figure 112006083464511-PAT00003
(2)

여기서,here,

Q 는 탄소, 질소, 산소 및 황으로 이루어진 군에서 선택되며,Q is selected from the group consisting of carbon, nitrogen, oxygen and sulfur,

l(엘) 은 3 ~ 4의 정수이며,l (L) is an integer from 3 to 4,

I) m 은 0 또는 1 ~ 4의 정수이며,I) m is 0 or an integer from 1 to 4,

J) Y 는 각각 독립적으로 하기 치환기들로 이루어진 군에서 선택되며,J) Y is each independently selected from the group consisting of the following substituents,

I) 할로겐, 시아노, 니트로, 히드록시, -CF3 및 임의적으로 치환된 몰포린;I) halogen, cyano, nitro, hydroxy, -CF 3 and optionally substituted morpholine;

II) -R, -OR, -SR', -NHR' 및 -NR'R", 여기서 R, R' 및 R"는 수소, 또는 임의적으로 치환된 C1-C10 직쇄, 분지형 또는 환형의 포화 또는 불포화 알킬이며; 및II) -R, -OR, -SR ', -NHR' and -NR'R ", wherein R, R 'and R" are hydrogen or optionally substituted C 1 -C 10 straight, branched or cyclic Saturated or unsaturated alkyl; And

III) 하기 일반식(i~ vi)으로 표시되는 치환체들:III) substituents represented by the following general formulas (i to vi):

Figure 112006083464511-PAT00004
(i)
Figure 112006083464511-PAT00004
(i)

Figure 112006083464511-PAT00005
(ii)
Figure 112006083464511-PAT00005
(ii)

Figure 112006083464511-PAT00006
(iii)
Figure 112006083464511-PAT00006
(iii)

Figure 112006083464511-PAT00007
(iv)
Figure 112006083464511-PAT00007
(iv)

Figure 112006083464511-PAT00008
(v)
Figure 112006083464511-PAT00008
(v)

Figure 112006083464511-PAT00009
(vi)
Figure 112006083464511-PAT00009
(vi)

여기서,here,

n1 은 0 또는 1 ~ 5의 정수이며; n 1 is 0 or an integer of 1 to 5;

J1 는 수소, -(C=O)-, -N-, -O- 및 -S- 로 이루어진 군에서 선택되거나 직접 결합이며;J 1 is selected from hydrogen, — (C═O) —, —N—, —O— and —S— or is a direct bond;

J2 및 J3 는 각각 독립적으로 -N-, -O-, -CR'- 및 -S- 로 이루어진 군에서 선택되거나 직접 결합이며, 여기서 R' 는 상기 정의한 바와 같으며;J 2 and J 3 are each independently selected from the group consisting of —N—, —O—, —CR′— and —S—, or a direct bond, wherein R ′ is as defined above;

J4 및 J5 는 각각 독립적으로 -(C=O)-, -NR'-, -(C=O)-NR'-, -(C=O)-NR'-R-, -O-, -S- -NR'-(C=O)-, -(C=S)-, -(C=S)-NR'-, -(C=S)-NR'-R-, -NR'-(C=S)- 및 -SO2-로 이루어진 군에서 선택되고, 여기서 R 및 R' 는 상기 정의한 바와 같으며;J 4 And J 5 are each independently — (C═O) —, —NR′—, — (C═O) —NR′—, — (C═O) —NR′—R—, —O—, —S -NR '-(C = O)-,-(C = S)-,-(C = S) -NR'-,-(C = S) -NR'-R-, -NR'-(C = S)-and -SO 2- , wherein R and R 'are as defined above;

n2 및 n6 는 0 또는 1 ~ 3의 정수이며; n 2 and n 6 Is 0 or an integer of 1 to 3;

n3 및 n4 는 각각 독립적으로 0 또는 1 ~ 3 중에서 선택되고, 0 인 경우에는 아무것도 아니거나 직접결합이며; n 3 and n 4 Are each independently selected from 0 or 1 to 3, and when 0 is nothing or a direct bond;

n5 는 0 또는 1 ~ 3 중에서 선택되고, 0 인 경우에는 아무것도 아니거나 직접결합이며; n 5 Is selected from 0 or 1 to 3, and when 0 is nothing or a direct bond;

G 및 G' 는 각각 독립적으로 수소, -R', -CF3, -(C=O)R', -OR', -CO2R', -SO2R', -CONHR', -CONRR', -CONR'OR, -CN, 할로겐, -NH2, -NRR', -NHCOR', -NHCO2R', -C(R')OH, -C(R)OR', -NR(C=O)R'OR"-, -C(=O)ROR'-, 임의적으로 치환된 C3-C8 시클로알킬 또는 헤테로 시클로알킬, 및 임의적으로 치환된 5각 또는 6각의 방향족 또는 헤테로 방향족으로 이루어진 군에서 선택되며, 여기서 R, R' 및 R"는 상기 정의한 바와 같다.G and G 'are each independently hydrogen, -R', -CF 3 ,-(C = O) R ', -OR', -CO 2 R ', -SO 2 R', -CONHR ', -CONRR' , -CONR'OR, -CN, halogen, -NH 2 , -NRR ', -NHCOR', -NHCO 2 R ', -C (R') OH, -C (R) OR ', -NR (C = O) R'OR "-, -C (= 0) ROR'-, optionally substituted C 3 -C 8 cycloalkyl or heterocycloalkyl, and optionally substituted 5- or 6-membered aromatic or heteroaromatic And R, R 'and R "are as defined above.

본 명세서에서 사용된 용어에 대해 간략히 설명한다.The terms used herein are briefly described.

용어 "약제학적으로 허용되는 염"은, 화합물이 투여되는 유기체에 심각한 자극을 유발하지 않고 화합물의 생물학적 활성과 물성들을 손상시키지 않는, 화합물의 제형을 의미한다. 상기 약제학적 염은, 본 발명의 화합물을, 염산, 브롬산, 황산, 질산, 인산 등의 무기산, 메탄술폰산, 에탄술폰산, p-톨루엔술폰산 등의 술폰산, 타타르산, 포름산, 시트르산, 아세트산, 트리클로로아세트산, 트리플루오로아세트산, 카프릭산, 이소부탄산, 말론산, 석신산, 프탈산, 글루콘산, 벤조산, 락트 산, 푸마르산, 말레인산, 살리실산 등과 같은 유기 카본산과 반응시켜 얻어질 수 있다. 또한, 본 발명의 화합물을 염기와 반응시켜, 암모니움 염, 나트륨 또는 칼륨 염 등의 알칼리 금속염, 칼슘 또는 마그네슘 염 등의 알칼리 토금속염 등의 염, 디시클로헥실아민, N-메틸-D-글루카민, 트리스(히드록시메틸) 메틸아민 등의 유기 염기들의 염, 및 아르기닌, 리신 등의 아미노산 염을 형성함으로써 얻어질 수도 있다.The term "pharmaceutically acceptable salt" means a formulation of a compound that does not cause severe irritation to the organism to which the compound is administered and does not impair the biological activity and properties of the compound. The pharmaceutical salt is a compound of the present invention, such as hydrochloric acid, bromic acid, sulfuric acid, nitric acid, inorganic acids such as phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid and the like, sulfonic acid, tartaric acid, formic acid, citric acid, acetic acid, trichloro It can be obtained by reaction with organic carboxylic acids such as roacetic acid, trifluoroacetic acid, capric acid, isobutanoic acid, malonic acid, succinic acid, phthalic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, salicylic acid and the like. In addition, the compounds of the present invention are reacted with a base, such as alkali metal salts such as ammonium salts, sodium or potassium salts, and alkaline earth metal salts such as calcium or magnesium salts, dicyclohexylamine, N-methyl-D-glu It may be obtained by forming salts of organic bases such as carmine, tris (hydroxymethyl) methylamine, and amino acid salts such as arginine and lysine.

이하에서 별도의 설명이 없는 한, 용어 "본 발명에 따른 화합물" 또는 "화학식 1의 화합물"은, 화합물 그 자체와, 약제학적으로 허용되는 그것의 염을 모두 포함하는 개념으로 사용되고 있다.Unless otherwise stated, the term "compound according to the present invention" or "compound of formula 1" is used in the concept including both the compound itself and its pharmaceutically acceptable salts.

별도로 설명되어 있지 않다면, 치환체가 "임의적으로 치환되어(optionally substituted)" 있다는 것은, 치환체가, 알킬, 시클로알킬, 헤테로시클로알킬, 알켄일, 시클로알켄일, 아릴, 헤테로아릴, 헤테로알리시클릭, 히드록시, 알콕시, 아릴옥시, 메르켑토, 알킬티오, 아릴티오, 옥소, 시아노, 할로겐, 카르보닐, 티오카르보닐, O-카르바밀, N-카르바밀, O-티오카르바밀, N-티오카르바밀, C-아미도, N-아미도, S-술폰아미도, N-술폰아미도, 임의적으로 치환된 술포닐, C-카르복시, O-카르복시, 이소시아네이토, 티오시아네이토, 이소티오시아네이토, 니트로, 시릴, 트리할로메탄술포닐, 피롤리디닐, 피페리디닐, 피페라지닐, 피리디닐, 몰포리닐, 퓨릴, 티아졸리딘, 이소옥사졸, 아제티디닐, 디옥솔란, 피라지닐, 티에닐, 아지리딘, 옥사졸리딘, 이미다졸, 피페리딘-온-옥심, 모노- 및 디-치환 아미노 그룹들을 포함한 아미노, 및 이들의 보호 유도체들로부터 개별적으로 그리고 독립적으로 선택된 하나 또는 그 이상의 그룹으로 치환된 경우를 포함한다는 의미로 사용되고 있다. 이들 치환체들 역시 임의적으로 치환될 수 있음은 물론이다. Unless stated otherwise, the fact that a substituent is "optionally substituted" means that the substituent is alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl, heteroalicyclic, Hydroxy, alkoxy, aryloxy, merceto, alkylthio, arylthio, oxo, cyano, halogen, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thio Carbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, optionally substituted sulfonyl, C-carboxy, O-carboxy, isocyanato, thiocyanato, Isothiocyanato, nitro, cyryl, trihalomethanesulfonyl, pyrrolidinyl, piperidinyl, piperazinyl, pyridinyl, morpholinyl, furyl, thiazolidine, isoxazole, azetidinyl, Dioxolane, pyrazinyl, thienyl, aziridine, oxazolidine, imidazole, piperidine-on-oxime, It is used as amino, and separately from the protected derivative thereof, and means to independently include the selected one or more groups when substituted by a substituted amino group, including - a no-and di. These substituents may also be optionally substituted.

용어 "알킬(alkyl)"은 지방족 탄화수소 그룹을 의미한다. 알킬 부위는 어떠한 알켄이나 알킨 부위를 포함하고 있지 않음을 의미하는 "포화 알킬(saturated alkyl)" 그룹일 수 있다. 알킬 부위는 적어도 하나의 알켄 또는 알킨 부위를 포함하고 있는 있음을 의미하는 "불포화 알킬(unsaturated alkyl)" 부위일 수도 있다. "알켄(alkene)" 부위는 적어도 두 개의 탄소원자가 적어도 하나의 탄소-탄소 이중 결합으로 이루어진 그룹을 의미하며, "알킨(alkyne)"은 부위는 적어도 두 개의 탄소원자가 적어도 하나의 탄소-탄소 삼중 결합으로 이루어진 그룹을 의미한다. 포화이든 불포화이든 간에 알킬 부위는 분지형, 직쇄형 또는 환형일 수 있다. The term "alkyl" refers to an aliphatic hydrocarbon group. The alkyl moiety can be a "saturated alkyl" group, meaning that it does not contain any alkenes or alkyne moieties. The alkyl moiety may be an "unsaturated alkyl" moiety, meaning that it contains at least one alkene or alkyne moiety. "Alkene" moiety means a group of at least two carbon atoms consisting of at least one carbon-carbon double bond, and "alkyne" is a moiety wherein at least two carbon atoms contain at least one carbon-carbon triple bond Means a group consisting of. The alkyl moiety, whether saturated or unsaturated, may be branched, straight chain or cyclic.

본 발명에서 탄소수 1 내지 10 개의 저급알킬은 선형(linear), 가지형(branched), 고리형(cyclic) 또는 부분적인 고리형을 포함한다. 부분적인 고리형 알킬 그룹이라 함은, 알킬 그룹 중에 어느 부분이든 고리형을 가진 치환체의 총칭이며, 예를 들어 메틸시클로프로필메틸, 시클로프로필비닐, 2,2-디메틸시클로프로필메틸 등의 경우이다. 상기 저급 알킬에는 1 내지 5 개의 이중 결합 또는 3 중 결합을 갖는 구조도 포함한다.Lower alkyl having 1 to 10 carbon atoms in the present invention includes linear, branched, cyclic or partially cyclic. The partial cyclic alkyl group is a generic term for a substituent having any cyclic in any of the alkyl groups, for example, methylcyclopropylmethyl, cyclopropylvinyl, 2,2-dimethylcyclopropylmethyl and the like. The lower alkyl also includes a structure having 1 to 5 double bonds or triple bonds.

"할로겐"은 -F, -Cl, -Br, -I 를 총칭한다."Halogen" generically refers to -F, -Cl, -Br, -I.

상기 치환기 X는 5각 또는 6각 고리형의 방향족 또는 헤테로방향족인 치환기 Ar1과 결합하고 있으므로, 하나 또는 두 개 이상일 수 있다. X가 두 개 이상인 경 우, 이들은 서로 동일한 치환기일 수도 있고, 서로 다른 치환기들일 수도 있다. 예를 들어, Ar1이 페닐이고 여기에 치환기 X가 두 개 결합되어 있는 경우, 하나는 할로겐이고, 나머지 하나는 -C(=O)R일 수 있다. Since the substituent X is bonded to the substituent Ar 1 which is a 5- or 6-membered cyclic aromatic or heteroaromatic group, it may be one or two or more. When X is two or more, they may be the same substituents, or may be different substituents. For example, when Ar 1 is phenyl and two substituents X are bonded thereto, one may be halogen and the other may be -C (= 0) R.

한편, 상기 화학식 1에서, R1 은 바람직하게는 수소 또는 메틸이며, 더욱 바람직하게는 메틸이다.Meanwhile, in Chemical Formula 1, R 1 Is preferably hydrogen or methyl, more preferably methyl.

A1 및 A2 는 바람직하게는 탄소이다.A 1 and A 2 are preferably carbon.

R2 는 바람직하게는 수소 또는 할로겐이며, 더욱 바람직하게는 수소이다.R 2 Is preferably hydrogen or halogen, more preferably hydrogen.

Ar1 은 바람직하게는 6각 고리형의 방향족 또는 헤테로방향족이며, 더욱 바람직하게는 페닐이다.Ar 1 Is preferably hexagonal cyclic aromatic or heteroaromatic, more preferably phenyl.

n 은 바람직하게는 0 또는 1 ~ 4의 정수이며, 더욱 바람직하게는 0 또는 1 ~ 3의 정수이다. n is preferably 0 or an integer of 1 to 4, and more preferably 0 or an integer of 1 to 3.

E 는 바람직하게는 황이다.E is preferably sulfur.

화학식 2에서, Q 는 바람직하게는 탄소 또는 질소이며, l(엘) 은 바람직하게는 3 또는 4이고 더욱 바람직하게는 4이다.In the formula (2), Q is preferably carbon or nitrogen, and l (L) is preferably 3 or 4 and more preferably 4.

상기 화학식 1에서, R4, R5 및 R6 중 선택된 두 개의 치환기가 상호 연결되어 환 구조를 이루는 경우, R7 및 R8이 상호 연결되어 환 구조를 이루는 경우, 또는 헤테로 시클로알킬인 경우, 그러한 환 구조는 특별히 제한되는 것은 아니고, 예를 들 어, 3각 내지 8각 고리형을 형성할 수 있으며, 바람직하게는 아지리딘, 피롤리딘, 피페라진, 피페리딘, 몰포린일 수 있다In Formula 1, R 4 , R 5 And when two substituents selected from R 6 are interconnected to form a ring structure, R 7 And when R 8 is interconnected to form a ring structure, or is heterocycloalkyl, such ring structure is not particularly limited, and may form, for example, a triangular to octagonal cyclic ring, preferably Can be aziridine, pyrrolidine, piperazine, piperidine, morpholine

본 발명의 대표적인 화합물에는 하기 화합물들이 포함된다.Representative compounds of the invention include the following compounds.

1. N5-(4-플루오로페닐)-N5-메틸-N2-(6-메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민1. N 5 - (4-fluorophenyl) -N 5 - methyl -N 2 - (6- methyl-pyridin-2-yl) thiazolo [5,4-b] pyridine-2,5-diamine

2. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-메탄올2. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -methanol

3. N5-메틸-N2-(3-몰포린-4-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민3. N 5 -Methyl-N 2- (3-morpholin-4-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5- Diamine

4. N5-메틸-N2-[3-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민4. N 5 -Methyl-N 2- [3- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -p-tolyl-thiazolo [5,4-b] Pyridine-2,5-diamine

5. N5-메틸-N2-[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-N5-페닐-티아졸로[5,4-b]피리딘-2,5-디아민5. N 5 -Methyl-N 2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -phenyl-thiazolo [5,4-b] pyridine- 2,5-diamine

6. N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-N5-페닐-l-티아졸로[5,4-b]피리딘-2,5-디아민6. N 5 -Methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -N 5 -phenyl-l-thiazolo [5,4-b] pyridine-2,5- Diamine

7. 4-{2-[5-(메틸-페닐-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-카르복실산 메틸아미드7. 4- {2- [5- (Methyl-phenyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine-1-carboxyl Acid methylamide

8. 4-{2-[5-(메틸-페닐-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-카르복실산 디메틸아미드8. 4- {2- [5- (Methyl-phenyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine-1-carboxyl Acid Dimethylamide

9. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-메탄올9. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -methanol

10. 1-(4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-에타논 10. 1- (4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine -1-yl) -ethanone

11. N2-(4-디에틸아미노메틸-피리딘-2-일)-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민11. N 2 - (4- diethylamino-methyl-pyridin-2-yl) -N 5 - methyl -N 5 -p- tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

12. N5-메틸-N2-(4-피롤리딘-1-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민12.N 5 -Methyl-N 2- (4-pyrrolidin-1-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5 -Diamine

13. N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민13.N 5 -Methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5- Diamine

14. N5-메틸-N2-[4-(4-메틸-피페라딘-1-일메틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민14.N 5 -Methyl-N 2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -p-tolyl-thiazolo [5,4-b ] Pyridine-2,5-diamine

15. (4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-에탄올15. (4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine-1 -Yl) -ethanol

16. (4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-아세트산 에틸 에스테르16. (4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine-1 -Yl) -acetic acid ethyl ester

17. (4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-아세트산17. (4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine-1 -Yl) -acetic acid

18. N,N-디메틸-2-(4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-아세트아미드18. N, N-dimethyl-2- (4- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4- Monomethyl} -piperazin-1-yl) -acetamide

19. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트산 에틸 에스테르19. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -acetic acid ethyl ester

20. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트산20. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -acetic acid

21. 1-(4-메틸-피페라진-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-에타논21. 1- (4-Methyl-piperazin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -ethanone

22. N-(2-디에틸아미노-에틸)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드22. N- (2-Diethylamino-ethyl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine -4-yl} -acetamide

23. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-N-(2-몰포린-4-일-에틸)-아세트아미드23. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -N- (2-mol Forin-4-yl-ethyl) -acetamide

24. N-(2-히드록시-에틸)-N-메틸-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드24. N- (2-hydroxy-ethyl) -N-methyl-2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -acetamide

25. N-(2-히드록시-에틸)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드25. N- (2-hydroxy-ethyl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine- 4-yl} -acetamide

26. 6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코티노니트릴26. 6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -nicotinonitrile

27. N2-(5-디에틸아미노메틸-피리딘-2-일)-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민27. N 2 - (5--diethylamino-methyl-pyridin-2-yl) -N 5 - methyl -N 5 -p- tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

28. N5-메틸-N2-(5-피페리딘-1-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민28.N 5 -Methyl-N 2- (5-piperidin-1-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5 -Diamine

29. N5-메틸-N2-[5-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민29. N 5 -Methyl-N 2- [5- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -p-tolyl-thiazolo [5,4-b] Pyridine-2,5-diamine

30. N5-메틸-N2-(5-몰포린-4-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민30.N 5 -Methyl-N 2- (5-morpholin-4-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5- Diamine

31. 1-(4-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-피페라진-1-일)-에타논31. 1- (4- {6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -piperazine -1-yl) -ethanone

32. N5-메틸-N2-(5-피롤리딘-1-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민32.N 5 -Methyl-N 2- (5-pyrrolidin-1-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5 -Diamine

33. 4-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-피페라진-1-카르복실산 디메틸아미드33. 4- {6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -piperazin-1- Carboxylic Acid Dimethylamide

34. ({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-아세트산 메틸 에스테르34. ({6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) -acetic acid methyl ester

35. 2-({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-아세트아미드35. 2-({6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) -acet amides

36. 2-({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-프로피온산 메틸 에스테르36. 2-({6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) -propionic acid Methyl ester

37. ({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-아세트산37. ({6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) -acetic acid

38. 2-({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-프로피온산38. 2-({6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) -propionic acid

39. 6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코틴산 메틸 에스테르39. 6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -nicotinic acid methyl ester

40. 6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코틴산40. 6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -nicotinic acid

41. (4-메틸-피페라진-1-일)-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-메타논41. (4-Methyl-piperazin-1-yl)-{6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine- 3-day} -Methanone

42. N-(1-메틸-피페리딘-4-일메틸)-6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코틴아미드42. N- (1-Methyl-piperidin-4-ylmethyl) -6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] Nicotinamide

43. {6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-몰포린-4-일-메타논43. {6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -morpholin-4-yl-meta Paddy field

44. {6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-아세트산 에틸 에스테르44. {6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -acetic acid ethyl ester

45. {6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-아세트산45. {6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -acetic acid

46. 1-(4-메틸-피페라진-1-일)-2-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피 리딘-2-일아미노]-피리딘-3-일}-에타논46. 1- (4-Methyl-piperazin-1-yl) -2- {6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-yl Amino] -pyridin-3-yl} -ethanone

47. N-(1-메틸-피페리딘-4-일메틸)-2-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-아세트아미드47. N- (1-Methyl-piperidin-4-ylmethyl) -2- {6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine-2- Ylamino] -pyridin-3-yl} -acetamide

48. N5-(4-플루오로-페닐)-N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민48. N 5- (4-Fluoro-phenyl) -N 5 -methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine -2,5-diamine

49. N5-(4-플루오로-페닐)-N5-메틸-N2-[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민49. N 5- (4-Fluoro-phenyl) -N 5 -methyl-N 2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -thiazolo [5 , 4-b] pyridine-2,5-diamine

50. 1-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논50. 1- [4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-yl Methyl) -piperazin-1-yl] -ethanone

51. 4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 tert-부틸 에스테르51. 4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl)- Piperazine-1-carboxylic acid tert-butyl ester

52. 4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 메틸아미드52. 4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl)- Piperazine-1-carboxylic acid methylamide

53. 4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 디메틸아미드53. 4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl)- Piperazine-1-carboxylic acid dimethylamide

54. 1-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-2-히드록시-에타논54. 1- [4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-yl Methyl) -piperazin-1-yl] -2-hydroxy-ethanone

55. N5-(4-플루오로-페닐)-N2-{4-[4-(4-플루오로-페닐)-피페라진-1-일메틸]-피리 딘-2-일}-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민55. N 5 - (4- fluoro-phenyl) -N 2 - {4- [4- (4- fluoro-phenyl) -piperazin-1-ylmethyl] pyrimidin-2-yl} -N 5 -Methyl-thiazolo [5,4-b] pyridine-2,5-diamine

56. 1-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페리딘-3-카르복실산 디에틸아미드56. 1- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl)- Piperidine-3-carboxylic acid diethylamide

57. 3-[(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-메틸-아미노]-프로피온니트릴57. 3-[(2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl) -Methyl-amino] -propionnitrile

58. N5-(4-플루오로-페닐)-N2-(4-{[(2-메톡시-에틸)-메틸-아미노]-메틸}-피리딘-2-일)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민58. N 5 - (4-fluoro-phenyl) -N 2 - (4 - { [(2- methoxy-ethyl) -methyl-amino] -methyl} -pyridin-2-yl) -N 5 - methyl -Thiazolo [5,4-b] pyridine-2,5-diamine

59. 2-[(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-메틸-아미노]-에탄올59. 2-[(2- {5-[(4-fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl) -Methyl-amino] -ethanol

60. N2-[4-(2,6-디메틸-몰포린-4-일메틸)-피리딘-2-일]-N5-(4-플루오로-페닐)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민60. N 2 - [4- (2,6- Dimethyl-morpholine-4-ylmethyl) -pyridin-2-yl] -N 5 - (4-fluoro-phenyl) -N 5-methyl-thiazolo [5,4-b] pyridine-2,5-diamine

61. 1-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페리딘-4-카르복실산 에틸 에스테르61. 1- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl)- Piperidine-4-carboxylic acid ethyl ester

62. N5-(4-플루오로-페닐)-N5-메틸-N2-(4-피페라진-1-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민62. N 5- (4-Fluoro-phenyl) -N 5 -methyl-N 2- (4-piperazin-1-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine -2,5-diamine

63. 1-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-2-메톡시-에타논63. 1- [4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-yl Methyl) -piperazin-1-yl] -2-methoxy-ethanone

64. 시클로프로필-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피 리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-메타논64. Cyclopropyl- [4- (2- {5-[(4-fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine-4 -Ylmethyl) -piperazin-1-yl] -methanone

65. 1-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-프로판-1-온65. 1- [4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-yl Methyl) -piperazin-1-yl] -propan-1-one

66. N5-(4-플루오로-페닐)-N5-메틸-N2-(5-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민66. N 5- (4-Fluoro-phenyl) -N 5 -methyl-N 2- (5-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine -2,5-diamine

67. N5-(4-플로오로-페닐)-N5-메틸-N2-[5-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민67. N 5 - (4- flow oro-phenyl) -N 5 - methyl -N 2 - [5- (4- methyl-piperazin-1-ylmethyl) -pyridin-2-yl] - thiazolo [5 , 4-b] pyridine-2,5-diamine

68. 1-[4-(6-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페라진-1-일]-에타논68. 1- [4- (6- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperazin-1-yl] -ethanone

69. 1-(6-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페리딘-4-올69. 1- (6- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-ylmethyl)- Piperidine-4-ol

70. N2-[5-(4-에틸-피페라진-1-일메틸)-피리딘-2-일]-N5-(4-플루오로-페닐)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민70. N 2- [5- (4-ethyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5- (4-fluoro-phenyl) -N 5 -methyl-thiazolo [5 , 4-b] pyridine-2,5-diamine

71. N2-[5-(3-디메틸아미노-피롤리딘-1-일메틸)-피리딘-2-일]-N5-(4-플루오로-페닐)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민71. N 2 - [5- (3- dimethylamino-pyrrolidin-1-ylmethyl) -pyridin-2-yl] -N 5 - (4-fluoro-phenyl) -N 5-methyl-thiazolo [5,4-b] pyridine-2,5-diamine

72. 2-[(6-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-아미노]-부탄-1-올72. 2-[(6- {5-[(4-fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-ylmethyl) -Amino] -butan-1-ol

73. N5-(4-플루오로-페닐)-N2-[5-(4-메탄설포닐-피페라진-1-일메틸)-피리딘-2-일]-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민73. N 5- (4-Fluoro-phenyl) -N 2- [5- (4-methanesulfonyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -methyl-thiazolo [5,4-b] pyridine-2,5-diamine

74. N2-{5-[4-(2-플루오로-에틸)-피페라진-1-일메틸]-피리딘-2-일}-N5-(4-플루오로-페닐)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아진 74. N 2 - {5- [4- (2- fluoro-ethyl) -piperazin-1-ylmethyl] -pyridin-2-yl} -N 5 - (4-fluorophenyl) -N 5 -Methyl-thiazolo [5,4-b] pyridine-2,5-diazine

75. N2-[5-(2,6-디메틸-몰포린-4-일메틸)-피리딘-2-일]-N5-(4-플루오로-페닐)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민75. N 2- [5- (2,6-Dimethyl-morpholin-4-ylmethyl) -pyridin-2-yl] -N 5- (4-fluoro-phenyl) -N 5 -methyl-thiazolo [5,4-b] pyridine-2,5-diamine

76. 1-(6-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페리딘-4-카르복실산 아미드76. 1- (6- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-ylmethyl)- Piperidine-4-carboxylic acid amide

77. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민77. N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4- b] pyridine-2,5-diamine

78. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민78.N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -thia Zolo [5,4-b] pyridine-2,5-diamine

79. 1-[4-(2-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논79. 1- [4- (2- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine- 4-ylmethyl) -piperazin-1-yl] -ethanone

80. 4-(2-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 디메틸아미드80. 4- (2- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazole [5,4-b] pyridin-2-ylamino} -pyridin-4-yl Methyl) -piperazine-1-carboxylic acid dimethylamide

81. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-(5-몰포린-4-일메틸-피리딘-2-일)-티아 졸로[5,4-b]피리딘-2,5-디아민81.N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- (5-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4- b] pyridine-2,5-diamine

82. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-[5-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민82.N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- [5- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -thia Zolo [5,4-b] pyridine-2,5-diamine

83. 1-[4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페라진-1-일]-에타논83. 1- [4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine- 3-ylmethyl) -piperazin-1-yl] -ethanone

84. 2-[(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티이졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-메틸-아미노]-에탄올84. 2-[(6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -tizolo [5,4-b] pyridin-2-ylamino} -pyridine-3- Monomethyl) -methyl-amino] -ethanol

85. N5-(2,4-디플루오로-페닐)-N2-(5-{[(2-메톡시-에틸)-메틸-아미노]-메틸}-피리딘-2-일)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민85.N 5- (2,4-Difluoro-phenyl) -N 2- (5-{[(2-methoxy-ethyl) -methyl-amino] -methyl} -pyridin-2-yl) -N 5 -Methyl-thiazolo [5,4-b] pyridine-2,5-diamine

86. N5-(2,4-디플루오로-페닐)-N2-[5-(2,6-디메틸-몰포린-4-일메틸)-피리딘-2-일]-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민86. N 5- (2,4-Difluoro-phenyl) -N 2- [5- (2,6-dimethyl-morpholin-4-ylmethyl) -pyridin-2-yl] -N 5 -methyl -Thiazolo [5,4-b] pyridine-2,5-diamine

87. 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페리딘-4-올87. 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperidin-4-ol

88. N5-(2,4-디플루오로-페닐)-N2-[5-(3-디메틸아미노-피롤리딘-1-일메틸)-피리딘-2-일]-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민88. N 5- (2,4-Difluoro-phenyl) -N 2- [5- (3-dimethylamino-pyrrolidin-1-ylmethyl) -pyridin-2-yl] -N 5 -methyl -Thiazolo [5,4-b] pyridine-2,5-diamine

89. 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피롤리딘-2-카르복실산 메틸 에스테르89. 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -pyrrolidine-2-carboxylic acid methyl ester

90. 4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페라진-1-카르복실산 메틸아미드90. 4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperazine-1-carboxylic acid methylamide

91. 4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페라진-1-카르복실산 디메틸아미드91. 4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperazine-1-carboxylic acid dimethylamide

92. 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페리딘-4-카르복실산 메틸 에스테르92. 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperidine-4-carboxylic acid methyl ester

93. 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페리딘-4-카르복실산93. 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperidine-4-carboxylic acid

94. 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피롤리딘-2-카르복실산94. 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -pyrrolidine-2-carboxylic acid

95. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-(5-피페라진-1-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민95. N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- (5-piperazin-1-ylmethyl-pyridin-2-yl) -thiazolo [5,4- b] pyridine-2,5-diamine

96. (6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-몰포린-4-일-메타논96. (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl)- Morpholin-4-yl-methanone

97. (6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-(4-메틸-피페라진-1-일)-메타논97. (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl)- (4-Methyl-piperazin-1-yl) -methanone

98. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-(1-메틸-피페리딘-4-일메틸)-니코틴아미드98. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N- (1-methyl-py Ferridin-4-ylmethyl) -nicotinamide

99. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미 노}-N-(2-히드록시-에틸)-니코틴아미드99. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N- (2-hydroxy -Ethyl) -nicotinamide

100. (6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-(4-히드록시-피페리딘-1-일)-메타논100. (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl)- (4-hydroxy-piperidin-1-yl) -methanone

101. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-(2-몰포린-4-일-에틸)-니코틴아미드101. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N- (2-morpholin- 4-yl-ethyl) -nicotinamide

102. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-(2-히드록시-에틸)-N-메틸-니코틴아미드102. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N- (2-hydroxy- Ethyl) -N-methyl-nicotinamide

103. N-(2-디에틸아미노-에틸)-6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-니코틴아미드103. N- (2-Diethylamino-ethyl) -6- {5-[(2,4-difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridine-2- Monoamino} -nicotinamide

104. 4-[(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-카보닐)-아미노]-피페리딘-1-카르복실산tert-부틸 에스테르104. 4-[(6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine-3- Carbonyl) -amino] -piperidine-1-carboxylic acid tert-butyl ester

105. tert-부틸[1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-카보닐)-피페리딘-4-일]-카바메이트105. tert-Butyl [1- (6- {5-[(2,4-difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine -3-carbonyl) -piperidin-4-yl] -carbamate

106. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-피페리딘-4-일-니코틴아미드106. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N-piperidine-4- Mono-nicotinamide

107. (4-아미노-피페리딘-1-일)-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-메타논107. (4-Amino-piperidin-1-yl)-(6- {5-[(2,4-difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridine -2-ylamino} -pyridin-3-yl) -methanone

108. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-(1-메틸-피페리딘-4-일)-니코틴아미드108. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N- (1-methyl-pi Ferridin-4-yl) -nicotinamide

109. (6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아 미노}-피리딘-3-일)-(4-디메틸아미노-피페리딘-1-일)-메타논109. (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl)- (4-dimethylamino-piperidin-1-yl) -methanone

110. N5-(4-클로로-2-플루오로-페닐)-N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민110. N 5- (4-Chloro-2-fluoro-phenyl) -N 5 -methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4 -b] pyridine-2,5-diamine

111. N5-(4-클로로-2-플루오로-페닐)-N5-메틸-N2-[4-(4-메틸-피레라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민111.N 5- (4-Chloro-2-fluoro-phenyl) -N 5 -methyl-N 2- [4- (4-methyl-pyrazin-1-ylmethyl) -pyridin-2-yl]- Thiazolo [5,4-b] pyridine-2,5-diamine

112. 1-[4-(2-{5-[(4-클로로-2-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논112. 1- [4- (2- {5-[(4-Chloro-2-fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine -4-ylmethyl) -piperazin-1-yl] -ethanone

113. N5-(4-클로로페닐)-N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민113. N 5- (4-Chlorophenyl) -N 5 -methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine-2 , 5-diamine

114. N5-(4-클로로-페닐)-N5-메틸-N2-[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민114. N 5- (4-Chloro-phenyl) -N 5 -methyl-N 2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -thiazolo [5, 4-b] pyridine-2,5-diamine

115. 1-[4-(2-{5-[(4-클로로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논115. 1- [4- (2- {5-[(4-Chloro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl ) -Piperazin-1-yl] -ethanone

116. 4-(2-{5-[(4-클로로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 디메틸아미드116. 4- (2- {5-[(4-Chloro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl) -pipe Razine-1-carboxylic acid dimethylamide

117. 1-[4-(2-{5-[(3,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논117. 1- [4- (2- {5-[(3,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine- 4-ylmethyl) -piperazin-1-yl] -ethanone

118. 6-{5-[(3,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미 노}-니코틴산 메틸 에스테르118. 6- {5-[(3,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -nicotinic acid methyl ester

119. [4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일)-피페라진-1-일]-아세트산 에틸 에스테르119. [4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyrimidine-4 -Yl) -piperazin-1-yl] -acetic acid ethyl ester

120. 2-[4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일)-피페라진-1-일]-에탄올120. 2- [4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyrimidine -4-yl) -piperazin-1-yl] -ethanol

121. 2-[(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일)-메틸-아미노]-에탄올121. 2-[(6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyrimidine-4 -Yl) -methyl-amino] -ethanol

122. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-[6-(2-몰포린-4-일-에틸아미노)-피리미딘-4-일]-티아졸로[5,4-b]피리딘-2,5-디아민122. N 5 - (2,4- difluoro-phenyl) -N 5 - methyl -N 2 - [6- (2- morpholine-4-yl-ethylamino) -pyrimidin-4-yl] - Thiazolo [5,4-b] pyridine-2,5-diamine

123. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-{6-[3-(4-메틸-피페라진-1-일)-프로필아미노]-피리미딘-4-일}-티아졸로[5,4-b]피리딘-2,5-디아민123. N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- {6- [3- (4-methyl-piperazin-1-yl) -propylamino] -pyrimidine -4-yl} -thiazolo [5,4-b] pyridine-2,5-diamine

124. 2-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일아미노)-에탄올124. 2- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyrimidine-4- Monoamino) -ethanol

125. 2-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일)-피페리딘-1-카르복실산 에틸 에스테르125. 2- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyrimidine-4- Yl) -piperidine-1-carboxylic acid ethyl ester

126. 4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-2-온 126. 4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine-2- On

127. 1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피롤리딘-3-올 127. 1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -pyrrolidine-3 -All

128. ((S)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피롤리딘-2-일)-메탄올128. (( S ) -1- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Pyrrolidin-2-yl) -methanol

129. N5-메틸-N2-[4-(4-메틸-[1,4]디아제판-1-일메틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민 129. N 5 -Methyl-N 2- [4- (4-methyl- [1,4] diazepane-1-ylmethyl) -pyridin-2-yl] -N 5 -p-tolyl-thiazolo [5 , 4-b] pyridine-2,5-diamine

130. 1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페리딘-4-온130. 1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperidine-4 -On

131. (R)-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산 메틸 에스테르131. ( R ) -2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid methyl ester

132. (S)-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산 메틸 에스테르132. ( S ) -2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid methyl ester

133. ({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-아세트산 에틸 에스테르133. ({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -acetic acid ethyl ester

134. 1-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-시클로프로판 카르복실산 메틸 에스테르134. 1-({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -cyclo Propane carboxylic acid methyl ester

135. 2-메틸-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산 메틸 에스테르135. 2-methyl-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid methyl ester

136. 2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로판-1,3-디올136. 2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -propane -1,3-diol

137. (S)-2-(메틸-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미 노]-피리딘-4-일메틸}-아미노)-프로피온산 메틸 에스테르137. ( S ) -2- (methyl- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl Methyl} -amino) -propionic acid methyl ester

138. 2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-에탄올138. 2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -ethanol

139. 1-(1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페리딘-4-일)-에타논139. 1- (1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperi Din-4-yl) -ethanone

140. N2-[4-(4-메탄설포닐-피페리딘-1-일메틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민140. N 2- [4- (4-methanesulfonyl-piperidin-1-ylmethyl) -pyridin-2-yl] -N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4 -b] pyridine-2,5-diamine

141. N2-[4-(4-메탄설포닐-피페라진-1-일메틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민141. N 2 - [4- (4- methanesulfonyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 - methyl -N 5 -p- tolyl-thiazolo [5,4- b] pyridine-2,5-diamine

142. N2-(4-{[2-(2,5-디메틸-옥사졸-4-일)-에틸아미노]-메틸}-피리딘-2-일)-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민 142. N 2 - (4 - { [2- (2,5- dimethyl-4-yl) -ethyl-amino] -methyl} -pyridin-2-yl) -N 5 - methyl -N 5 -p -Tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

143. 4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-카르복실산 에틸 에스테르143. 4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazin-1- Carboxylic acid ethyl ester

144. 3-히드록시-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산 메틸 에스테르144. 3-hydroxy-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -Amino) -propionic acid methyl ester

145. 3-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로판-1,2-디올145. 3-({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -propane -1,2-diol

146. [1-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘 -4-일메틸}-아미노)-시클로펜틸]-메탄올146. [1-({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino)- Cyclopentyl] -methanol

147. 2-메틸-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로판-1-올147. 2-Methyl-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propan-1-ol

148. N2-[4-(4-이소프로필-피페라진-1-일메틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민148. N 2- [4- (4-Isopropyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4-b ] Pyridine-2,5-diamine

149. N2-[4-(4-시클로프로필-피페라진-1-일메틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민149. N 2- [4- (4-cyclopropyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4-b ] Pyridine-2,5-diamine

150. N5-메틸-N2-(4-페페라진-1-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민150.N 5 -Methyl-N 2- (4-peperazin-1-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5- Diamine

151. 1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페리딘-4-온 옥심151. 1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperidine-4 -On oxime

152. 1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페리딘-4-온 O-메틸-옥심152. 1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperidine-4 -One O-methyl-oxime

153. N5-메틸-N2-(4-피라졸-1-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민153. N 5 -Methyl-N 2- (4-pyrazol-1-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5- Diamine

154. 2-히드록시-1-(4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-에타논154. 2-hydroxy-1- (4- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl Methyl} -piperazin-1-yl) -ethanone

155. 4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘- 4-일메틸}-피페라진-1-카르복실산 시클로프로필아미드155. 4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin- 4-ylmethyl} -piperazine-1- Carboxylic Acid Cyclopropylamide

156. (S)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피롤리딘-2-카르복실산156. (S) -1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -py Lolidine-2-carboxylic acid

157. (S)-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산157. ( S ) -2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid

158. ({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-아세트산158. ({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -acetic acid

159. (R)-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산159. ( R ) -2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid

160. 1-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-시클로프로판카르복실산160. 1-({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -cyclo Propanecarboxylic acid

161. 2-메틸-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산161. 2-Methyl-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid

162. (S)-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산162. ( S ) -2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid

163. 1-메틸-4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-2-온163. 1-Methyl-4- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -pipe Razin-2-one

164. (R)-N-메톡시-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온아미드164. (R) -N-methoxy-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4 -Ylmethyl} -amino) -propionamide

165. N-메톡시-2-메틸-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2- 일아미노]-피리딘-4-일메틸}-아미노)-프로피온아미드165. N-methoxy-2-methyl-2 - ({2- [5- (-p- tolyl-amino) thiazolo [5,4-b] pyridin-2-ylamino] -pyridin -4 -Ylmethyl} -amino) -propionamide

166. N5-메틸-N2-(4-메틸아미노메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민166. N 5 -Methyl-N 2- (4-methylaminomethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

167. N2-(4-아미노메틸-피리딘-2-일)-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민167. N 2- (4-Aminomethyl-pyridin-2-yl) -N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

168. 2-메탄술포닐-N-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아세트아미드168. 2-Methanesulfonyl-N- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} Acetamide

169. 2-히드록시-N-{2-[5-메틸-p-톨릴-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸}-아세트아미드169. 2-hydroxy-N- {2- [5-methyl-p-tolyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl} -acet amides

170. 5-옥소-피롤리딘-2-카르복실산 {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미드170. 5-oxo-pyrrolidine-2-carboxylic acid {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine- 4-ylmethyl} -amide

171. 1-메탄술포닐-피페리딘-4-카르복실산 {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미드171. 1-Methanesulfonyl-piperidine-4-carboxylic acid {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino]- Pyridin-4-ylmethyl} -amide

172. 2-디메틸아미노-N-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아세트아미드172. 2-Dimethylamino-N- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Acetamide

173. N-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-3-피페리딘-1-일-프로피온아미드173. N- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -3-piperidine -1-yl-propionamide

174. 1-메틸-피롤리딘-2-카르복실산 {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미드174. 1-Methyl-pyrrolidine-2-carboxylic acid {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine- 4-ylmethyl} -amide

175. 피롤리딘-2-카르복실산 {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미드175. Pyrrolidine-2-carboxylic acid {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl }-amides

176. N2-[4-(1,1-디옥소-16-티오모폴린-4-일메틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민176. N 2 - [4- (1,1- dioxo-6 -1 - T Omo morpholin-4-ylmethyl) -pyridin-2-yl] -N 5 - methyl -N 5 -p- tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

177. N-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-메탄술폰아미드177. N - {2- [5- (methyl -p- tolyl-amino) thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} - methanesulfonamide

178. 1-시클로프로필-3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-우레아178. 1-Cyclopropyl-3- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Urea

179. (S)-N-히드록시-2-(메틸-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온아미드179. ( S ) -N-hydroxy-2- (methyl- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine -4-ylmethyl} -amino) -propionamide

180. N,N-디메틸-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드 180. N, N-dimethyl-2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl}- Acetamide

181. 1-(4-아세틸-피페라진-1-일)-2-{2-[5-(메틸-p-톨릴-아미노) -티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에타논181. 1- (4-acetyl-piperazin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -ethanone

182. N-시클로프로필-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드182. N-cyclopropyl-2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -acet amides

183. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-1-피페리딘-1-일-에타논183. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-piperidine- 1-Day-Ethanon

184. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘- 4-일}-1-피롤리딘-1-일-에타논184. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-pyrrolidine- 1-Day-Ethanon

185. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-1-모폴린-4-일-에탄온185. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-morpholine-4 -Sun-Ethanon

186. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세트아미드186. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl} -acetamide

187. N-[2-(4-아세틸-피페라진-1-일)-에틸]-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세트아미드187. N- [2- (4-acetyl-piperazin-1-yl) -ethyl] -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] Pyridin-2-ylarmano] -pyridin-4-yl} -acetamide

188. N-메틸-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드 188. N-Methyl-2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -acetamide

189. N-[2-(2,5-디메틸-옥사졸-4-일)-에틸]-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세트아미드189. N- [2- (2,5-Dimethyl-oxazol-4-yl) -ethyl] -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4- b] pyridin-2-ylarmano] -pyridin-4-yl} -acetamide

190. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로 [5,4-b]피리딘-2-일아마노]-피리딘-4-일}-1-피페라진-1-일-에타논190. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-piperazine-1 -Sun-Ethanon

191. N-(1-히드록시메틸-프로필)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세트아미드191.N- (1-Hydroxymethyl-propyl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine -4-yl} -acetamide

192. 1-(4-에틸-피페라진-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에타논192. 1- (4-Ethyl-piperazin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -ethanone

193. 1-(4-이소프로필-피페라진-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에탄온193. 1- (4-Isopropyl-piperazin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-yl Amano] -pyridin-4-yl} -ethanone

194. 3-히드록시-2-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아 마노]-피리딘-4-일}-아세틸아미노)-피로피온산 메틸 에스테르194. 3-hydroxy-2- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl } -Acetylamino) -pyrionic acid methyl ester

195. 1-((S)-3-아미노-피롤리딘-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에타논195. 1-((S) -3-Amino-pyrrolidin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine -2-ylarmano] -pyridin-4-yl} -ethanone

196. 1-((R)-3-아미노-피롤리딘-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에타논196. 1-((R) -3-Amino-pyrrolidin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine -2-ylarmano] -pyridin-4-yl} -ethanone

197. N-[(R)-1-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세틸)-피롤리딘-3-일]-아세트아미드197. N-[(R) -1- (2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine-4 -Yl} -acetyl) -pyrrolidin-3-yl] -acetamide

198. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-모폴린-4-일-메타논198. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl} -morpholin-4-yl-meta Paddy field

199. (4-메틸-피페라진-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논199. (4-Methyl-piperazin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine- 4-day} -Methanone

200. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-피페라진-1-일-메타논200. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -piperazin-1-yl-meta Paddy field

201. (3-히드록시-피롤리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-피페라진-1-일-메타논203- (3-hydroxy-pyrrolidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino]- Pyridin-4-yl} -piperazin-1-yl-methanone

202. (3-디메틸아미노-피롤리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논202. (3-Dimethylamino-pyrrolidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino]- Pyridin-4-yl} -methanone

203. N-[3-(4-메틸-피페라진-1-일)-프로필]-2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-이소니코틴아미드203. N- [3- (4-Methyl-piperazin-1-yl) -propyl] -2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine-2 -Yl-amino] -isonicotinamide

204. N-[2-(4-아세틸-피페리딘-1-일)-에틸]-2-[5-(메틸-p-톨릴-아미노)-티아졸 로[5,4-b]피리딘-2-일아마노]-이소니코틴아미드204. N- [2- (4-acetyl-piperidin-1-yl) -ethyl] -2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine -2-yl-amino] -isonicotinamide

205. N-((R)-1-히드록시메틸-프로필)-2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-이소니코틴아미드205. N-(( R ) -1-hydroxymethyl-propyl) -2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino]- Isonicotinamide

206. (4-아미노-피페리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논206. (4-Amino-piperidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine -4-yl} -methanone

207. (4-디메틸아미노-피페리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논207. (4-Dimethylamino-piperidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano]- Pyridin-4-yl} -methanone

208. ((S)-3-아미노-피롤리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논208. ((S) -3-Amino-pyrrolidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-yl Amano] -pyridin-4-yl} -methanone

209. N-((S)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-카르보닐}-피롤리딘-3-일)-아세트아미드209. N-((S) -1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4-carbonyl } -Pyrrolidin-3-yl) -acetamide

210. ((R)-3-아미노-피롤리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논210. ((R) -3-Amino-pyrrolidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-yl Amano] -pyridin-4-yl} -methanone

211. N-((R)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-카르보닐}-피롤리딘-3-일)-아세트아미드211.N-((R) -1- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4-carbonyl } -Pyrrolidin-3-yl) -acetamide

212. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에탄올212. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl} -ethanol

213. 1-[4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에틸)-피페라진-1-일]-에타논213. 1- [4- (2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl}- Ethyl) -piperazin-1-yl] -ethanone

214. 4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리 딘-4-일}-에틸)-피페라진-2-온214. 4- (2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -ethyl) Piperazine-2-one

215. N5-메틸-N2-{4-[2-(4-메틸-피페라진-1-일)-에틸]-피리딘-2-일}-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민215. 5 N-Methyl -N 2 - {4- [2- ( 4- methyl-piperazin-1-yl) ethyl] pyridin-2-yl} -N 5 -p- tolyl-thiazolo [5, , 4-b] pyridine-2,5-diamine

216. N5-메틸-N2-[4-(2-몰폴린-4-일-에틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민216. 5 N-Methyl -N 2 - [4- (2- morpholin-4-yl-ethyl) -pyridin-2-yl] -N 5 -p- tolyl-thiazolo [5,4-b] pyridine -2,5-diamine

217. N5-메틸-N2-[4-(2-피롤리딘-1-일-에틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민217. 5 N-Methyl -N 2 - [4- (2- pyrrolidin-1-yl-ethyl) -pyridin-2-yl] -N 5 -p- tolyl-thiazolo [5,4-b] Pyridine-2,5-diamine

218. N5-메틸-N2-[4-(2-피페라진-1-일-에틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민218. 5 N-Methyl -N 2 - [4- (2- piperazin-1-yl-ethyl) -pyridin-2-yl] -N 5 -p- tolyl-thiazolo [5,4-b] pyridine -2,5-diamine

219. 2-[메틸-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘 -4-일}-에틸)-아미노]-에탄올219. 2- [Methyl- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl}- Ethyl) -amino] -ethanol

220. N2-[4-(2-디메틸아미노-에틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민220. N 2 - [4- (2- dimethylamino-ethyl) -pyridin-2-yl] -N 5 - methyl -N 5 -p- tolyl-thiazolo [5,4-b] pyridine-2,5 -Diamine

221. N5-메틸-N2-[4-(2-피페리딘-1-일-에틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민221. 5 N-Methyl -N 2 - [4- (2- piperidin-1-yl-ethyl) -pyridin-2-yl] -N 5 -p- tolyl-thiazolo [5,4-b] Pyridine-2,5-diamine

222. N5-메틸-N2-{4-[2-(2-몰폴린-4-일-에틸아미노)-에틸]-피리딘-2-일}-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민222. 5 N-Methyl -N 2 - {4- [2- ( 2- morpholin-4-yl-ethylamino) -ethyl] -pyridin-2-yl} -N 5 -p- tolyl-thiazolo [ 5,4-b] pyridine-2,5-diamine

223. 2-히드록시-1-[4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-에틸)-피페라진-1-일]-에타논223. 2-hydroxy-1- [4- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine- 4-yl} -ethyl) -piperazin-1-yl] -ethanone

224. 2-히드록시-2-메틸-1-[4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-에틸)-피페라진-1-일]프로판-1-온224. 2-hydroxy-2-methyl-1- [4- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -ethyl) -piperazin-1-yl] propan-1-one

225. 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로피온산 메틸 에스테르225. 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -propionic acid methyl ester

226. 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로피온산226. 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -propionic acid

227. 1-(4-아세틸-피페라진-1-일)-3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로판-1-온227. 1- (4-acetyl-piperazin-1-yl) -3- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -propan-1-one

228. 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-1-몰폴린-4-일-프로판-1-온228. 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-morpholine-4 -Yl-propane-1-one

229. 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-1-피페라진-1-일-프로판-1-온229. 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-piperazin-1 -Yl-propane-1-one

230. 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로판-1-올230. 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -propan-1-ol

231. 1-[4-(3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로필)-피페라진-1-일]-에타논231. 1- [4- (3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl}- Propyl) -piperazin-1-yl] -ethanone

232. N5-메틸-N2-{4-[3-(4-메틸-피페라진-1-일)-프로필]-피리딘-2-일}-N5-p-톨릴- 티아졸로[5,4-b]피리딘-2,5-디아민232. N 5 -Methyl-N 2- {4- [3- (4-methyl-piperazin-1-yl) -propyl] -pyridin-2-yl} -N 5 -p-tolyl-thiazolo [5 , 4-b] pyridine-2,5-diamine

233. 4-(3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로필)-피페라진-1-카르복실산 메틸아미드233. 4- (3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -propyl)- Piperazine-1-carboxylic acid methylamide

234. 2-클로로-5-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-벤조산 메틸 에스테르234. 2-Chloro-5-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino}-methyl benzoate ester

235. 2-클로로-5-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-벤조산235. 2-Chloro-5-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -benzoic acid

236. 2-클로로-5-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-N-메톡시-벤즈아미드236. 2-Chloro-5-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -N- Methoxy-benzamide

237. 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5237. 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5

,4-b]-피리딘-5-일}-메틸-아미노)-2-클로로-N-메톡시-벤즈아미드, 4-b] -pyridin-5-yl} -methyl-amino) -2-chloro-N-methoxy-benzamide

238. 2-클로로-N-메톡시-5-{메틸-[2-(4-몰포린-4-일메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-아미노}-벤즈아미드238. 2-Chloro-N-methoxy-5- {methyl- [2- (4-morpholin-4-ylmethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridine-5 -Yl] -amino} -benzamide

239. 2-클로로-N-메톡시-5-(메틸-{2-[4-(4-메틸-피레라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-아미노)-벤즈아미드239. 2-Chloro-N-methoxy-5- (methyl- {2- [4- (4-methyl-pyrazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4 -b] pyridin-5-yl} -amino) -benzamide

240. 3-[(2-아미노-티아졸로[5,4-b]피리딘-5-일)-메틸-아미노]-N-메톡시-벤즈아미드240. 3-[(2-amino-thiazolo [5,4-b] pyridin-5-yl) -methyl-amino] -N-methoxy-benzamide

241. 3-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-N-메톡시-벤즈아미드241. 3-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -methyl -Amino) -N-methoxy-benzamide

242. N-메톡시-3-{메틸-[2-(4-몰포린-4-일메틸-피리딘-2-일아미노)-티아졸로[5,4- b]피리딘-5-일]-아미노}-벤즈아미드242. N-methoxy-3- {methyl- [2- (4-morpholin-4-ylmethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl]- Amino} -benzamide

243. N-메톡시-3-(메틸-{2-[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-아미노)-벤즈아미드243. N-methoxy-3- (methyl- {2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridine -5-yl} -amino) -benzamide

244. 3-{[2-(4-디메틸아미노메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-N-메톡시-벤즈아미드244. 3-{[2- (4-Dimethylaminomethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -N-methoxy-benz amides

245. 3-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-N,N-디메틸-벤즈아미드245. 3-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -N, N-dimethyl- Benzamide

246. 3-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-N-메틸-벤즈아미드246. 3-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -N-methyl-benzamide

247. 3-{[2-(4-디메틸카바모일메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-N-메톡시-벤즈아미드247. 3-{[2- (4-Dimethylcarbamoylmethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -N-methoxy- Benzamide

248. 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-2-플루오로-벤조산 에틸 에스테르248. 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -methyl -Amino) -2-fluoro-benzoic acid ethyl ester

249. 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-2-플루오로-N-메톡시-벤즈아미드249. 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -methyl -Amino) -2-fluoro-N-methoxy-benzamide

250. 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-2-플루오로-N-메틸-벤즈아미드250. 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -methyl -Amino) -2-fluoro-N-methyl-benzamide

본 발명은 또한 상기 화학식 1의 화합물을 제조하는 방법을 제공한다. 이후 설명하는 제조예들과 실시예들에서도 알 수 있는 바와 같이, 본 발명에 따른 화합 물의 제조방법은 매우 다양한 방법들에 의해 제조될 수 있다. 하기의 제조방법들은 그것의 예시적인 방법들에 지나지 않으며, 유기합성 분야의 기술에 근간한 다양한 방법들에 의해 제조될 수 있음은 물론이다. 따라서, 본 발명의 범주가 이들만으로 한정되는 것은 아니다. The present invention also provides a method for preparing the compound of Formula 1. As can be seen in the production examples and examples described below, the method for producing a compound according to the present invention can be prepared by a wide variety of methods. The following preparation methods are merely exemplary methods thereof, and of course, may be prepared by various methods based on the art of organic synthesis. Therefore, the scope of the present invention is not limited only to these.

첫 번째 제조예에서, 화학식 1의 화합물은 하기 화학식 3의 화합물과 화학식 2의 방향족 고리 화합물을 팔라듐 촉매 하에서 반응시켜 제조될 수 있다. 예를 들어, 하기 반응식 1에 따라 화학식 3의 화합물과 하기 화학식 2-1의 화합물을 결합하여 하기 화학식 1-1의 화합물을 제조할 수 있다.In a first preparation, the compound of Formula 1 may be prepared by reacting a compound of Formula 3 with an aromatic ring compound of Formula 2 under a palladium catalyst. For example, the compound of Formula 3 may be prepared by combining the compound of Formula 3 and the compound of Formula 2-1 according to Scheme 1 below.

[반응식 1] [Reaction Scheme 1]

Figure 112006083464511-PAT00010
Figure 112006083464511-PAT00010

상기 식에서, dba 는 디벤질리덴아세톤을 나타내고, Xanphos 는 9,9-디메틸-4,5-비스(디페닐포스피노)잔틴이다.Wherein dba represents dibenzylideneacetone and Xanphos is 9,9-dimethyl-4,5-bis (diphenylphosphino) xanthine.

아미노티아졸 구조를 갖는 화학식 3의 화합물은 한국 특허출원 제2004-117617호의 방법으로 합성할 수 있으며, 여기서 Ar 은 상기 정의된 방향족 화합물을 나타낸다. 상기 출원의 내용은 참조로서 본 발명의 내용에 합체된다.The compound of formula 3 having an aminothiazole structure can be synthesized by the method of Korean Patent Application No. 2004-117617, wherein Ar represents an aromatic compound as defined above. The contents of this application are incorporated into the contents of the present invention by reference.

두 번째 제조예에서, 화학식 1의 화합물의 제조방법은 하기 반응식 2에 따라, (a) 화학식 3의 화합물과 하기 반응식 3에서 얻을 수 있는 화학식 2-2의 화합 물을 팔라듐 촉매하에서 결합반응시켜 하기 화학식 4의 화합물을 합성하는 단계, (b) ⅰ) 암모늄 플루오라이드(NH4F)로 벤질알콜의 보호기(OTBDMS)를 제거한 이후, ⅱ) 포스포러스옥시클로라이드(POCl3)로 반응시켜 화학식 5의 화합물을 합성하는 단계, 및 (c) 다양한 아민들과 아미드화 반응시켜 화학식 1-2의 화합물을 합성하는 단계를 포함하는 것으로 구성될 수 있다.In a second preparation example, the method for preparing a compound of Formula 1 is according to the following Scheme 2, by (a) combining the compound of Formula 3 and the compound of Formula 2-2 obtained in Scheme 3 under a palladium catalyst Synthesizing the compound of Formula 4, (b) iii) removing the protecting group (OTBDMS) of benzyl alcohol with ammonium fluoride (NH 4 F), and ii) reacting with phosphorus oxychloride (POCl 3 ) Synthesizing the compound, and (c) amidating the various amines to synthesize the compound of formula 1-2.

[반응식 2] [Reaction Scheme 2]

Figure 112006083464511-PAT00011
Figure 112006083464511-PAT00011

여기서, 상기 화학식 2-2의 화합물을 하기 반응식 3의 방법으로 제조할 수 있다.Here, the compound of Chemical Formula 2-2 may be prepared by the method of Scheme 3 below.

[반응식 3] [Reaction Scheme 3]

Figure 112006083464511-PAT00012
Figure 112006083464511-PAT00012

상기 반응식 3을 참조하면, (a) 화학식 2-2-1의 2-클로로-이소니코틴산을 출발물질로 하여 에스테르화하여 화학식 2-2-2의 화합물을 만든 다음, (b) 리튬알루미늄하이드라이드(LiAlH4)로 환원반응하여 화학식 2-2-3의 화합물을 만든 후, (c) 알킬실릴 화합물로 보호화 반응하여 화학식 2-2의 화합물을 얻을 수 있다.Referring to Scheme 3, (a) esterification with 2-chloro-isonicotinic acid of formula 2-2-1 as a starting material to make a compound of formula 2-2-2, and (b) lithium aluminum hydride Reduction with (LiAlH 4 ) to form a compound of formula (2-2-3), and then (c) the protection reaction with an alkylsilyl compound to obtain a compound of formula (2-2).

세 번째 제조예에서, 화학식 1의 화합물의 제조방법은 하기 반응식 4에 따라, (a) 화학식 3의 화합물을 팔라듐 촉매 하에 화학식 2-3의 메틸 벤조에이트와 반응시켜 화학식 6을 얻는 단계, (b) 화학식 6의 화합물을 수산화리튬으로 가수분해하여 화학식 7의 화합물을 얻는 단계, 및 (c) 화학식 7의 화합물을 다양한 아민들과 아미드화 반응시켜 화학식 1-3의 화합물을 얻는 단계를 포함하는 것으로 구성될 수 있다.In a third preparation, the method for preparing a compound of Formula 1 is according to Scheme 4 below: (a) reacting the compound of Formula 3 with methyl benzoate of Formula 2-3 under a palladium catalyst to obtain Formula 6, (b Hydrolyzing the compound of formula 6 with lithium hydroxide to obtain a compound of formula 7, and (c) amidating the compound of formula 7 with various amines to obtain a compound of formula 1-3. Can be configured.

[반응식 4] [Reaction Scheme 4]

Figure 112006083464511-PAT00013
Figure 112006083464511-PAT00013

네 번째 제조예에서, 화학식 1의 화합물의 제조방법은 하기 반응식 5에 따라, (a) 반응식 2에서 얻는 화학식 5의 화합물을 팔라듐 아세테이트(Pd(Oac)2) 및 트리페닐포스핀(PPh3)의 존재하에서 일산화탄소와 반응시켜 화학식 8의 화합물을 얻는 단계, (b) 화학식 8의 화합물을 수산화리튬으로 가수분해하여 화학식 9의 화합물을 얻는 단계, 및 (c) 화학식 9의 페닐아세트산을 다양한 아민들과 아미드화 반응시켜 화학식 1-4의 화합물을 얻는 단계를 포함하는 것으로 구성될 수 있다.In a fourth preparation, the method for preparing a compound of Formula 1 is prepared according to Scheme 5 below: (a) Palladium acetate (Pd (Oac) 2 ) and triphenylphosphine (PPh 3 ) Reacting with carbon monoxide in the presence of to obtain a compound of formula 8, (b) hydrolyzing the compound of formula 8 with lithium hydroxide to obtain a compound of formula 9, and (c) phenylacetic acid of formula 9 to various amines And amidation reaction to obtain a compound of Formula 1-4.

[반응식 5] [Reaction Scheme 5]

Figure 112006083464511-PAT00014
Figure 112006083464511-PAT00014

본 발명이 속하는 분야에서 통상의 지식을 가진 자라면, 본 발명에 따른 화합물의 제조를 위한 구체적인 반응조건 등을 추후 설명하는 제조예들과 실시예들을 통해 확인할 수 있으므로, 그에 대한 자세한 설명은 생략한다. Those skilled in the art to which the present invention pertains can check the specific reaction conditions for the preparation of the compound according to the present invention through the preparation examples and examples which will be described later, and thus the detailed description thereof will be omitted. .

본 발명에 따른 화합물들은, 신생혈관생성과 관련된 질병과 같이, 바람직하지 않은 KDR 활성으로 인한 질병들의 치료 및 예방에 특히 유효하다. 이러한 질병들의 예로는, 하기의 것으로 한정되는 것은 아니지만, 암, 건선, 류마티스성 관절 염, 당뇨병성 망막증, 국소 빈혈성 심장병, 죽상경화증, 카포시 육종 등을 들 수 있다. 따라서, 본 발명은 화학식 1의 화합물을 사용하여 KDR 활성으로 인한 질병을 치료 및 예방하는 방법을 제공한다.The compounds according to the invention are particularly effective for the treatment and prevention of diseases due to undesirable KDR activity, such as diseases associated with angiogenesis. Examples of such diseases include, but are not limited to, cancer, psoriasis, rheumatoid arthritis, diabetic retinopathy, ischemic heart disease, atherosclerosis, Kaposi's sarcoma, and the like. Accordingly, the present invention provides a method of treating and preventing a disease due to KDR activity using a compound of Formula 1.

본 발명은 또한, (a) 약리학적 유효량의 화학식 1의 화합물; 및 (b) 약제학적으로 허용되는 담체, 희석제, 또는 부형제, 또는 이들의 조합;을 포함하는 것으로 구성된 약제 조성물을 제공한다.The present invention also provides a pharmaceutical composition comprising (a) a pharmacologically effective amount of a compound of formula 1; And (b) a pharmaceutically acceptable carrier, diluent, or excipient, or a combination thereof.

용어 "약제 조성물(pharmaceutical composition)"은 본 발명의 화합물과 희석제 또는 담체와 같은 다른 화학 성분들의 혼합물을 의미한다. 약제 조성물은 생물체내로 화합물의 투여를 용이하게 한다. 화합물을 투여하는 다양한 기술들이 존재하며, 여기에는 경구, 주사, 에어로졸, 비경구, 및 국소 투여 등이 포함되지만, 이들만으로 한정되는 것은 아니다. 약제 조성물은 염산, 브롬산, 황산, 질산, 인산, 메탄술폰산, p-톨루엔술폰산, 살리실산 등과 같은 산 화합물들을 반응시켜서 얻어질 수도 있다. 통상적으로, 환자에게 투여되는 조성물의 선량 범위는 환자 체중의 약 0.5 내지 1000 mg/kg 일 수 있다. 투여량은, 환자에게 요구되는 정도에 따라, 한번에 또는 하루 또는 그 이상의 과정으로 일련의 둘 또는 그 이상으로 제공될 수도 있다.The term "pharmaceutical composition" means a mixture of a compound of the invention with other chemical components such as diluents or carriers. The pharmaceutical composition facilitates administration of the compound into the organism. There are a variety of techniques for administering compounds, including but not limited to oral, injection, aerosol, parenteral, and topical administration. Pharmaceutical compositions may also be obtained by reacting acid compounds such as hydrochloric acid, bromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like. Typically, the dose range of the composition administered to the patient may be about 0.5 to 1000 mg / kg of the patient's body weight. Dosages may be given in a series of two or more, one at a time or in a day or more, depending on the extent required by the patient.

본 발명은 하기 제조예, 실시예 및 실험예들에 의해 더욱 구체적으로 설명되지만, 본 발명의 범주가 그것에 의해 어떤 식으로든 제한되는 것은 아니다.The present invention is explained in more detail by the following Preparation Examples, Examples and Experimental Examples, but the scope of the present invention is not limited in any way by this.

실시예 1: NExample 1: N 55 -(4-플루오로페닐)-N-(4-fluorophenyl) -N 55 -메틸-N-Methyl-N 22 -(6-메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-(6-methyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00015
Figure 112006083464511-PAT00015

한국 특허출원 제2004-117617호에서 합성한 N5-(4-플루오로페닐)-N5-메틸-티아졸[5,4-b]피리딘-2,5-디아민 2.5 g(9.11 mmol)과 2-클로로-6-메틸피리딘 1.63 g(12.8 mmol)을 톨루엔 50 ml에 녹이고, 탄산나트륨 1.35 g(12.8 mmol)과 비스(디벤질리덴아세톤)디팔라듐 500 mg(0.547 mmol), 그리고 4,5-비스(디페닐포스피노)-9,9-디메틸잔틴 470 mg(0.820 mmol)을 가하고 4 시간 동안 환류교반하였다. 반응완결후 에틸 아세테이트 40 ml를 가하고 셀라이트에 여과하여 고체를 제거한 후 여과된 고체를 물 40 ml를 사용하여 씻어 주었다. 농축하고 관 크로마토그래피로 분리하여(전개액; 에틸아세테이트:노르말 헥산 = 1:2) 목적 화합물 2.25 g(6.16 mmol, 수율; 68%)을 얻었다.2.5 g (9.11 mmol) of N 5- (4-fluorophenyl) -N 5 -methyl-thiazole [5,4-b] pyridine-2,5-diamine synthesized in Korean Patent Application No. 2004-117617; Dissolve 1.63 g (12.8 mmol) of 2-chloro-6-methylpyridine in 50 ml of toluene, 1.35 g (12.8 mmol) of sodium carbonate, 500 mg (0.547 mmol) of bis (dibenzylideneacetone) dipalladium, and 4,5- 470 mg (0.820 mmol) of bis (diphenylphosphino) -9,9-dimethylxanthine were added and stirred under reflux for 4 hours. After completion of the reaction, 40 ml of ethyl acetate was added, the solid was removed by filtration through celite, and the filtered solid was washed with 40 ml of water. Concentration and separation by column chromatography (eluent; ethyl acetate: normal hexane = 1: 2) gave 2.25 g (6.16 mmol, yield; 68%) of the title compound.

1H NMR (CDCl3, ppm); δ 10.10 (1H, bs), 7.58 (1H, d), 7.46 (1H, t), 7.27 (2H, m), 7.13 (2H, t), 6.76 (1H, d), 6.65 (1H, d), 6.52 (1H, d), 3.51 (3H, s), 2.57 (3H, s) 1 H NMR (CDCl 3 , ppm); δ 10.10 (1H, bs), 7.58 (1H, d), 7.46 (1H, t), 7.27 (2H, m), 7.13 (2H, t), 6.76 (1H, d), 6.65 (1H, d), 6.52 (1H, d), 3.51 (3H, s), 2.57 (3H, s)

FAB MS(m/e) = 366 [M+1] FAB MS (m / e) = 366 [M + 1]

제조예Production Example 1: 6- 1: 6- 클로로피리딘Chloropyridine -2--2- 카르복실산Carboxylic acid 메틸methyl 에스테르의 제조 Preparation of ester

6-클로로피리딘-2-카르복실산 6.5 g(41.2 mmol)을 메탄올 100 ml에 녹인 후 2N 메탄올 염산 용액을 5 ml 가한 후 15 시간 동안 환류교반하였다. 반응 완결 후 농축하고 물 100 ml을 가한 후 1N 가성소다 수용액을 사용하여 중화시켰다. 에틸 아세테이트로 70 ml씩 두번 추출하고 농축하여 목적 화합물 6.69 g(39.1 mmol, 수율; 95%)을 얻었다. 6.5 g (41.2 mmol) of 6-chloropyridine-2-carboxylic acid was dissolved in 100 ml of methanol, and 5 ml of a 2N methanolic acid hydrochloric acid solution was added thereto, followed by stirring under reflux for 15 hours. After completion of the reaction, the reaction mixture was concentrated, 100 ml of water was added thereto, and neutralized with 1N aqueous sodium hydroxide solution. Extracted twice with 70 ml of ethyl acetate and concentrated to give 6.69 g (39.1 mmol, yield; 95%) of the title compound.

1H NMR (CDCl3, ppm); δ 7.71(1H, d), 7.33(1H, t), 7.14(1H, d), 3.65(3H, s) 1 H NMR (CDCl 3 , ppm); δ 7.71 (1H, d), 7.33 (1H, t), 7.14 (1H, d), 3.65 (3H, s)

FAB MS(m/e) = 172 [M+1]FAB MS (m / e) = 172 [M + 1]

제조예Production Example 2: (6- 2: (6- 클로로피리딘Chloropyridine -2-일)-메탄올의 제조2-yl) -Methanol Preparation

제조예 1에서 얻은 화합물 6.67 g(39.0 mmol)을 무수 테트라히드로퓨란 90 ml에 녹인 후 -45℃로 냉각하였다. 이 용액에 1몰 리튬알루미늄하이드라이드 테트라히드로퓨란 용액 40 ml를 30 분간 적가하였다. 30 분 교반 후 0℃로 온도를 올린 후 30 분 더 교반하여준 후 1N 가성소다 수용액 15 ml을 적가하였다. 용액을 셀라이트에 여과하여 고체를 제거한 후 여과된 용액을 농축하여 목적 화합물 5.08 g(35.4 mmol, 수율; 91%)을 얻었다. 6.67 g (39.0 mmol) of the compound obtained in Preparation Example 1 was dissolved in 90 ml of anhydrous tetrahydrofuran, and then cooled to -45 ° C. 40 ml of 1 mol lithium aluminum hydride tetrahydrofuran solution was added dropwise to this solution for 30 minutes. After stirring for 30 minutes, the temperature was raised to 0 ° C., and after stirring for 30 minutes, 15 ml of 1N aqueous sodium hydroxide solution was added dropwise. The solution was filtered through celite to remove solids and the filtered solution was concentrated to give 5.08 g (35.4 mmol, yield; 91%) of the title compound.

1H NMR (CDCl3, ppm); δ 7.61(1H, d), 7.30(1H, t), 7.04(1H, d), 3.72(2H, s) 1 H NMR (CDCl 3 , ppm); δ 7.61 (1H, d), 7.30 (1H, t), 7.04 (1H, d), 3.72 (2H, s)

FAB MS(m/e) = 144 [M+1]FAB MS (m / e) = 144 [M + 1]

제조예Production Example 3: 2-( 3: 2- ( terttert -부틸-디메틸--Butyl-dimethyl- 실라닐옥시메틸Silanyloxymethyl )-6-) -6- 클로로Chloro -피리딘의 제조Preparation of Pyridine

제조예 2에서 얻은 화합물 5.0 g(35.0 mmol)을 디클로로메탄 120 ml에 녹인 후 이미다졸 4.76 g(69.9 mmol)과 t-부틸디메틸실릴 클로라이드 5.80 g(38.5 mmol)을 가하고 상온에서 2 시간 교반하였다. 반응완결 후 물 100 ml를 사용하여 씻고, 포화탄산수소나트륨 수용액 40 ml를 사용하여 한 번 더 씻은 후 농축하여 목적 화합물 8.45 g(32.9 mmol, 수율; 94%)을 얻었다. After dissolving 5.0 g (35.0 mmol) of the compound obtained in Preparation Example 2 in 120 ml of dichloromethane, 4.76 g (69.9 mmol) of imidazole and 5.80 g (38.5 mmol) of t-butyldimethylsilyl chloride were added thereto, followed by stirring at room temperature for 2 hours. After completion of the reaction, the mixture was washed with 100 ml of water, washed once more with 40 ml of saturated aqueous sodium hydrogen carbonate solution and concentrated to give 8.45 g (32.9 mmol, yield; 94%) of the title compound.

1H NMR (CDCl3, ppm); δ 7.62(1H, d), 7.31(1H, t), 7.05(1H, d), 4.68(2H, s), 0.92(9H, s), 0.10(6H, s) 1 H NMR (CDCl 3 , ppm); δ 7.62 (1H, d), 7.31 (1H, t), 7.05 (1H, d), 4.68 (2H, s), 0.92 (9H, s), 0.10 (6H, s)

FAB MS(m/e) = 258 [M+1]FAB MS (m / e) = 258 [M + 1]

제조예 4: NPreparation Example 4 N 22 -[3-(tert-부틸-디메틸-실라닐옥시메틸)-피리딘-2-일]-N-[3- (tert-butyl-dimethyl-silanyloxymethyl) -pyridin-2-yl] -N 55 -메틸-N-Methyl-N 55 -p-톨릴--p-tolyl- 티아졸로[5,4-b]피리딘Thiazolo [5,4-b] pyridine -2,5--2,5- 디아민의Diamine 제조 Produce

한국 특허출원 제2004-117617호에서 합성한 N5-메틸-N5-(N5-메틸-N5)-p-톨릴-티아졸[5,4-b]피리딘-2,5-디아민와 제조예 3에서 얻은 화합물을 이용하여 실시예 1의 방법으로 반응시켜 목적 화합물을 얻었다. Preparation with N 5 -methyl-N 5- (N 5 -methyl-N 5 ) -p-tolyl-thiazole [5,4-b] pyridine-2,5-diamine synthesized in Korean Patent Application No. 2004-117617 It reacted by the method of Example 1 using the compound obtained in Example 3, and obtained the target compound.

1H NMR (CDCl3, ppm); δ 8.31 (1H, d), 7.50 (1H, d), 7.41 (1H, d), 7.20 (4H, m), 6.86 (1H, t), 6.56 (1H, d), 4.87 (2H, bs), 3.82 (3H, s), 2.38 (3H, s), 0.93(9H, s), 0.10(6H, s) 1 H NMR (CDCl 3 , ppm); δ 8.31 (1H, d), 7.50 (1H, d), 7.41 (1H, d), 7.20 (4H, m), 6.86 (1H, t), 6.56 (1H, d), 4.87 (2H, bs), 3.82 (3H, s), 2.38 (3H, s), 0.93 (9H, s), 0.10 (6H, s)

FAB MS(m/e) = 492 [M+1]FAB MS (m / e) = 492 [M + 1]

실시예 2: {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-메탄올의 제조Example 2: Preparation of {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -methanol

Figure 112006083464511-PAT00016
Figure 112006083464511-PAT00016

제조예 4에서 얻은 화합물 1.8 g(3.67 mmol)을 메탄올 30 ml에 녹이고 암모늄 플루오라이드 540 mg(14.7 mmol)을 가하고 3 시간 동안 환류 교반하였다. 반응완결 후 여과하고 건조하여 목적 화합물 1.09 g(2.90mol, 수율; 79%)을 얻었다. 1.8 g (3.67 mmol) of the compound obtained in Preparation Example 4 were dissolved in 30 ml of methanol, and 540 mg (14.7 mmol) of ammonium fluoride was added thereto, and the mixture was stirred under reflux for 3 hours. After completion of the reaction, the mixture was filtered and dried to obtain 1.09 g (2.90 mol, yield; 79%) of the title compound.

1H NMR (CDCl3, ppm); δ 8.30 (1H, d), 7.52 (1H, d), 7.40 (1H, d), 7.20 (4H, m), 6.86 (1H, t), 6.56 (1H, d), 4.87 (2H, bs), 3.51 (3H, s), 2.38 (3H, s) 1 H NMR (CDCl 3 , ppm); δ 8.30 (1H, d), 7.52 (1H, d), 7.40 (1H, d), 7.20 (4H, m), 6.86 (1H, t), 6.56 (1H, d), 4.87 (2H, bs), 3.51 (3H, s), 2.38 (3H, s)

FAB MS(m/e) = 378 [M+1]FAB MS (m / e) = 378 [M + 1]

제조예 5: NPreparation Example 5 N 55 -(클로로메틸-피리딘-2-일)-N-(Chloromethyl-pyridin-2-yl) -N 55 -메틸-N-Methyl-N 55 -p-톨릴-티아졸[5,4-b]피리딘-2,5-디-p-tolyl-thiazole [5,4-b] pyridine-2,5-di 아Ah 민의 제조Manufacture of private

실시예 2에서 얻은 화합물 0.95 g(2.52 mmol)을 디클로로메탄 50 ml에 녹이고 N,N-디메틸포름아미드 0.59 ml(7.56 mmol)과 포스포러스옥시클로라이드 0.69 ml(7.56 mmol)을 가하고 상온에서 10 시간 교반하였다. 반응 완결 후 여과하고 여과된 고체를 물 100 ml에 녹인 후 탄산수소나트륨으로 중화하여 생긴 고체를 다시 여과하여 목적 화합물 0.81 g(2.05 mmol, 수율; 81%)을 얻었다. 0.95 g (2.52 mmol) of the compound obtained in Example 2 was dissolved in 50 ml of dichloromethane, 0.59 ml (7.56 mmol) of N, N-dimethylformamide and 0.69 ml (7.56 mmol) of phosphorus oxychloride were added thereto, followed by stirring at room temperature for 10 hours. It was. After completion of the reaction, the resultant was filtered, and the filtered solid was dissolved in 100 ml of water, and the solid formed by neutralization with sodium bicarbonate was filtered again to obtain 0.81 g (2.05 mmol, yield; 81%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 8.31 (1H, d), 7.51 (1H, d), 7.42 (1H, d), 7.21 (4H, m), 6.86 (1H, t), 6.56 (1H, d), 3.53(2H, s), 3.51 (3H, s), 2.38 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.31 (1H, d), 7.51 (1H, d), 7.42 (1H, d), 7.21 (4H, m), 6.86 (1H, t), 6.56 (1H, d), 3.53 (2H, s), 3.51 (3H, s), 2.38 (3H, s)

FAB MS(m/e) = 396 [M+1]FAB MS (m / e) = 396 [M + 1]

실시예 3: NExample 3: N 55 -메틸-N-Methyl-N 22 -(3-몰포린-4-일메틸-피리딘-2-일)-N-(3-morpholin-4-ylmethyl-pyridin-2-yl) -N 55 -p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of -p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00017
Figure 112006083464511-PAT00017

제조예 5에서 얻은 화합물 50 mg(0.127 mmol)을 디메틸설폭사이드 0.8 ml에 녹이고 몰포린 0.044 ml(0.508 mmol)을 가하고 상온에서 4 시간 교반하였다. 반응완결 후 물 30 ml를 가한 후 에틸 아세테이트로 20 ml씩 두번 추출하고 농축하였다. 관 크로마토그래피로 분리하여(전개액; 10% 메탄올/디클로로메탄) 목적 화합물 45 mg(0.101 mmol, 수율; 79%)을 얻었다. 50 mg (0.127 mmol) of the compound obtained in Preparation Example 5 was dissolved in 0.8 ml of dimethyl sulfoxide, 0.044 ml (0.508 mmol) of morpholine was added thereto, and the mixture was stirred at room temperature for 4 hours. After completion of the reaction, 30 ml of water was added, and 20 ml of ethyl acetate was extracted twice, and concentrated. Separation by column chromatography (eluent; 10% methanol / dichloromethane) gave 45 mg (0.101 mmol, yield; 79%) of the title compound.

1H NMR (CDCl3, ppm); δ 11.04 (1H, bs), 8.30 (1H, d), 7.57 (1H, d), 7.40 (1H, d), 7.20 (4H, m), 6.84 (1H, t), 6.56 (1H, d), 3.83 (4H, m), 3.65 (2H, s), 3.51 (3H, s), 2.55 (4H, bs), 2.37 (3H, s) 1 H NMR (CDCl 3 , ppm); δ 11.04 (1H, bs), 8.30 (1H, d), 7.57 (1H, d), 7.40 (1H, d), 7.20 (4H, m), 6.84 (1H, t), 6.56 (1H, d), 3.83 (4H, m), 3.65 (2H, s), 3.51 (3H, s), 2.55 (4H, bs), 2.37 (3H, s)

FAB MS(m/e) = 447 [M+1]FAB MS (m / e) = 447 [M + 1]

실시예 4: NExample 4: N 55 -메틸-N-Methyl-N 22 -[3-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-N-[3- (4-Methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 55 -p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of -p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00018
Figure 112006083464511-PAT00018

실시예 3에서 몰포린 대신 N-메틸피레라진을 사용하여 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. In Example 3, the reaction was carried out in the same manner as in Example 3, using N-methylpyrrazine instead of morpholine to obtain a target compound.

1H NMR (CDCl3, ppm); δ 11.06 (1H, bs), 8.30 (1H, d), 7.57 (1H, d), 7.40 (1H, d), 7.20 (4H, m), 6.84 (1H, t), 6.56 (1H, d), 3.65 (2H, s), 3.51 (3H, s), 2.61 (8H, bs), 2.38 (2H, bs), 2.37 (3H, s) 1 H NMR (CDCl 3 , ppm); δ 11.06 (1H, bs), 8.30 (1H, d), 7.57 (1H, d), 7.40 (1H, d), 7.20 (4H, m), 6.84 (1H, t), 6.56 (1H, d), 3.65 (2H, s), 3.51 (3H, s), 2.61 (8H, bs), 2.38 (2H, bs), 2.37 (3H, s)

FAB MS(m/e) = 460 [M+1]FAB MS (m / e) = 460 [M + 1]

제조예Production Example 6: 4-( 6: 4- ( terttert -부틸-디메틸--Butyl-dimethyl- 실라닐옥시메틸Silanyloxymethyl )-2-)-2- 클로로Chloro -피리딘의 제조Preparation of Pyridine

제조예 1에서 6-클로로피리딘-2-카르복실산 대신 6-클로로이소니코틴산을 이 용하여 제조예 1의 방법으로 반응하고, 계속하여 제조예 2 및 제조예 3의 방법으로 순차적으로 반응하여 목적 화합물을 얻었다. In Preparation Example 1, 6-chloroisonicotinic acid was used instead of 6-chloropyridine-2-carboxylic acid to react with the method of Preparation Example 1, and then sequentially by the methods of Preparation Example 2 and Preparation Example 3 to react the target compound. Got.

1H NMR (CDCl3, ppm); δ 8.31(1H, d), 7.30(1H, s), 7.14(1H, d), 4.71(2H, s), 0.94(9H, s), 0.11(6H, s) 1 H NMR (CDCl 3 , ppm); δ 8.31 (1H, d), 7.30 (1H, s), 7.14 (1H, d), 4.71 (2H, s), 0.94 (9H, s), 0.11 (6H, s)

FAB MS(m/e) = 258 [M+1]FAB MS (m / e) = 258 [M + 1]

제조예 7: NPreparation Example 7 N 22 -(4-클로로메틸-피리딘-2-일)-N-(4-chloromethyl-pyridin-2-yl) -N 55 -메틸-N-Methyl-N 55 -페닐-티아졸로[5,4-b]피리딘-2,5-디-Phenyl-thiazolo [5,4-b] pyridine-2,5-di 아Ah 민의 제조Manufacture of private

제조예 6에서 얻은 화합물과 N5-메틸-N5-페닐-티아졸로[5,4-b]피리딘-2,5-디아민 (한국 특허출원 제2004-117617호)을 이용하여 실시예 1, 실시예 2 및 제조예 5의 방법으로 순차적으로 반응하여 목적 화합물을 얻었다. Example 1, using the compound obtained in Preparation Example 6 and N 5 -methyl-N 5 -phenyl-thiazolo [5,4-b] pyridine-2,5-diamine (Korean Patent Application No. 2004-117617) It reacted sequentially by the method of Example 2 and manufacture example 5, and obtained the target compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 7.62(1H, s), 7.39(2H, t), 7.28(2H, d), 7.16(1H, t), 7.05(1H, s), 6.87(1H, d), 6.57(1H, d), 3.71(2H, s), 3.40(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 7.62 (1H, s), 7.39 (2H, t), 7.28 (2H, d), 7.16 (1H, t), 7.05 (1H, s), 6.87 (1H, d), 6.57 (1H, d), 3.71 (2H, s), 3.40 (3H, s)

FAB MS(m/e) = 382 [M+1]FAB MS (m / e) = 382 [M + 1]

실시예 5: NExample 5: N 55 -메틸-N-Methyl-N 22 -[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-N-[4- (4-Methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 55 -페닐-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of -phenyl-thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00019
Figure 112006083464511-PAT00019

제조예 7에서 얻은 화합물을 이용하여 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. It reacted by the method of Example 3 using the compound obtained in manufacture example 7, and obtained the target compound.

1H NMR (DMSO-d6, ppm); δ 11.2(1H, s), 8.20(1H, d), 7.63(1H, d), 7.40-7.37(2H, m), 7.28-7.27(2H, m), 7.17(1H, t), 6.68(1H, d), 6.59(1H, d), 3.42(3H, s), 3.34(2H, s), 3.22-3.12(4H, m), 2.36-2.21(4H, m), 2.13(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.2 (1H, s), 8.20 (1H, d), 7.63 (1H, d), 7.40-7.37 (2H, m), 7.28-7.27 (2H, m), 7.17 (1H, t), 6.68 (1H , d), 6.59 (1H, d), 3.42 (3H, s), 3.34 (2H, s), 3.22-3.12 (4H, m), 2.36-2.21 (4H, m), 2.13 (3H, s)

FAB MS(m/e) = 446 [M+1]FAB MS (m / e) = 446 [M + 1]

실시예 6: NExample 6: N 55 -메틸-N-Methyl-N 22 -(4-몰포린-4-일메틸-피리딘-2-일)-N-(4-morpholin-4-ylmethyl-pyridin-2-yl) -N 55 -페닐-l-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of -phenyl-l-thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00020
Figure 112006083464511-PAT00020

실시예 5에서 N-메틸피페라진 대신 몰포린을 사용하여 목적 화합물을 얻었다. In Example 5, morpholine was used instead of N-methylpiperazine to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.3(1H, s), 7.63(1H, s), 7.39(2H, t), 7.28(2H, d), 7.18(1H, t), 7.08(1H, s), 6.89(1H, d), 6.57(1H, d), 3.58-3.56(4H, m), 3.44(2H, s), 3.40(3H, s), 2.37-2.30(4H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.3 (1H, s), 7.63 (1H, s), 7.39 (2H, t), 7.28 (2H, d), 7.18 (1H, t), 7.08 (1H, s), 6.89 (1H, d), 6.57 (1H, d), 3.58-3.56 (4H, m), 3.44 (2H, s), 3.40 (3H, s), 2.37-2.30 (4H, m)

FAB MS(m/e) = 433 [M+1]FAB MS (m / e) = 433 [M + 1]

제조예Production Example 8: 피페라진-1- 8: piperazine-1- 카르복실산Carboxylic acid 메틸아미드의Methylamide 제조 Produce

N-부틸록시카보닐피페라진 11 g (59 mmol)을 무수 테트라히드로퓨란 250 ml에 녹인 후 N,N-디이소프로필에틸아민 20.6 ml(118 mmol)과 4-니트로페닐클로로포메이트 13.1 g (64.9 mmol)을 가하고 상온에서 1 시간 교반한다. 이 용액에 메틸아민(2M 테트라히드로퓨란용액) 177 ml를 가하고 30 시간 동안 환류교반하였다. 반응 완결 후 농축하고 물 100 ml를 가하고 디클로로메탄을 사용하여 100 ml씩 두번 추출한 후 4N 염산/1,4-디옥산 용액 30 ml를 가하고 상온에서 5 시간 교반하였다. 반응완결 후 생긴 고체를 여과하고 건조하여 목적 화합물의 염산염 형태로 9.53 g(53 mmol, 수율; 90%)을 얻었다. 11 g (59 mmol) of N-butyloxycarbonylpiperazine was dissolved in 250 ml of anhydrous tetrahydrofuran, followed by 20.6 ml (118 mmol) of N, N-diisopropylethylamine and 13.1 g of 4-nitrophenylchloroformate ( 64.9 mmol) is added and stirred at room temperature for 1 hour. 177 ml of methylamine (2M tetrahydrofuran solution) was added to the solution, and the mixture was stirred under reflux for 30 hours. After completion of the reaction, the reaction solution was concentrated, 100 ml of water was added, 100 ml of extraction was performed twice with dichloromethane, and 30 ml of 4N hydrochloric acid / 1,4-dioxane solution was added thereto, followed by stirring at room temperature for 5 hours. The solid formed after completion of the reaction was filtered and dried to obtain 9.53 g (53 mmol, yield; 90%) in the form of the hydrochloride of the target compound.

1H NMR (DMSO-d6, ppm); δ 9.28 (1H, bs), 7.94 (1H, bs), 3.52 (4H, m), 3.01 (4H, m), 2.57 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 9.28 (1H, bs), 7.94 (1H, bs), 3.52 (4H, m), 3.01 (4H, m), 2.57 (3H, s)

FAB MS(m/e) = 144 [M+1]FAB MS (m / e) = 144 [M + 1]

실시예 7: 4-{2-[5-(메틸-페닐-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-카르복실산 메틸아미드의 제조Example 7: 4- {2- [5- (methyl-phenyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazin-1- Preparation of Carboxylic Acid Methylamide

Figure 112006083464511-PAT00021
Figure 112006083464511-PAT00021

제조예 7에서 얻은 화합물과 제조예 8에서 얻은 화합물을 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 7 and the compound obtained in Preparation Example 8 were reacted by the method of Example 3 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.1(1H, s), 8.21(1H, d), 7.65(1H, d), 7.40-7.37(2H, m), 7.28-7.27(2H, m), 7.15(1H, t), 6.65(1H, d), 6.57(1H, d), 3.43(3H, s), 3.34(2H, s), 3.22-3.12(4H, m), 2.46-2.31(4H, m), 2.65(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.1 (1H, s), 8.21 (1H, d), 7.65 (1H, d), 7.40-7.37 (2H, m), 7.28-7.27 (2H, m), 7.15 (1H, t), 6.65 (1H , d), 6.57 (1H, d), 3.43 (3H, s), 3.34 (2H, s), 3.22-3.12 (4H, m), 2.46-2.31 (4H, m), 2.65 (3H, s)

FAB MS(m/e) = 489 [M+1]FAB MS (m / e) = 489 [M + 1]

제조예Production Example 9: 피페라진-1- 9: piperazine-1- 카르복실산Carboxylic acid 디메틸아미드의 제조 Preparation of Dimethylamide

제조예 8에서 메틸아민 대신 디메틸아민을 사용하여 제조예 8의 방법으로 반응하여 목적 화합물을 얻었다. In Preparation Example 8, dimethylamine was used in place of methylamine to react with Preparation Example 8 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ9.93 (2H, bs), 3.58 (4H, bs), 3.22 (4H, bs), 2.84 (6H, s) 1 H NMR (DMSO-d 6 , ppm); δ9.93 (2H, bs), 3.58 (4H, bs), 3.22 (4H, bs), 2.84 (6H, s)

FAB MS(m/e) = 158 [M+1]FAB MS (m / e) = 158 [M + 1]

실시예 8: 4-{2-[5-(메틸-페닐-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-카르복실산 디메틸아미드의 제조Example 8: 4- {2- [5- (methyl-phenyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazin-1- Preparation of Carboxylic Acid Dimethylamides

Figure 112006083464511-PAT00022
Figure 112006083464511-PAT00022

제조예 7에서 얻은 화합물과 제조예 9에서 얻은 화합물을 사용하여 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained by reacting the compound obtained in Preparation Example 7 and the compound obtained in Preparation Example 9 by the method of Example 3.

1H NMR (DMSO-d6, ppm); δ11.27 (1H, bs), 8.21 (1H, d), 7.62 (1H, d), 7.38 (2H, t), 7.27 (2H, d), 7.18 (1H, t), 7.08 (1H, s), 6.90 (1H, d), 6.57 (1H, d), 3.47 (2H, s), 3.40 (3H, s), 3.10 (4H, s), 2.69 (6H, s), 2.36 (4H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.27 (1H, bs), 8.21 (1H, d), 7.62 (1H, d), 7.38 (2H, t), 7.27 (2H, d), 7.18 (1H, t), 7.08 (1H, s) , 6.90 (1H, d), 6.57 (1H, d), 3.47 (2H, s), 3.40 (3H, s), 3.10 (4H, s), 2.69 (6H, s), 2.36 (4H, s)

FAB MS(m/e) = 503 [M+1]FAB MS (m / e) = 503 [M + 1]

실시예 9: {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-메탄올의 제조Example 9: Preparation of {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -methanol

Figure 112006083464511-PAT00023
Figure 112006083464511-PAT00023

제조예 3에서 얻은 화합물 대신 제조예 6에서 얻은 화합물을 사용하여 제조예 4의 방법으로 반응하고 계속하여 실시예 2의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 6 was used instead of the compound obtained in Preparation Example 3 to react with the method of Preparation Example 4, and subsequently with the method of Example 2 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ11.29 (1H, bs), 8.21 (1H, d), 7.62 (1H, d), 7.20 (4H, m), 7.12 (1H, bs), 6.89 (1H, d), 6.52 (1H, d), 5.44 (1H, t), 4.52 (2H, d), 3.40 (3H, s), 2.33 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.29 (1H, bs), 8.21 (1H, d), 7.62 (1H, d), 7.20 (4H, m), 7.12 (1H, bs), 6.89 (1H, d), 6.52 (1H, d) , 5.44 (1H, t), 4.52 (2H, d), 3.40 (3H, s), 2.33 (3H, s)

FAB MS(m/e) = 378 [M+1]FAB MS (m / e) = 378 [M + 1]

제조예Production Example 10:  10: NN 22 -(4--(4- 클로로메틸Chloromethyl -피리딘-2-일)--Pyridin-2-yl)- NN 55 -- 메틸methyl -- NN 55 -p--p- 톨릴Tolyl -- 티아졸로[5,4-b]피리Thiazolo [5,4-b] pyrid 딘-2,5-Dean-2,5- 디아민의Diamine 제조 Produce

실시예 9에서 얻은 화합물을 제조예 5의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 9 was reacted by the method of Preparation Example 5 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.21(1H, s), 8.24(1H, d), 7.66(1H, d), 7.24(2H, d), 7.20(2H, d), 7.11(1H, s), 6.93(1H, d), 6.54(1H, d), 3.63 (2H, s), 3.41(3H, s), 2.34(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.21 (1H, s), 8.24 (1H, d), 7.66 (1H, d), 7.24 (2H, d), 7.20 (2H, d), 7.11 (1H, s), 6.93 (1H, d), 6.54 (1H, d), 3.63 (2H, s), 3.41 (3H, s), 2.34 (3H, s)

FAB MS(m/e) = 396 [M+1]FAB MS (m / e) = 396 [M + 1]

실시예 10: 1-(4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-에타논Example 10: 1- (4- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Piperazin-1-yl) -ethanone

Figure 112006083464511-PAT00024
Figure 112006083464511-PAT00024

제조예 10에서 얻은 화합물을 이용하여 실시예 3의 방법으로 목적 화합물을 얻었다. The target compound was obtained by the method of Example 3 using the compound obtained in Preparation Example 10.

1H NMR (CDCl3, ppm); δ 10.28(1H, bs), 8.30(1H, d), 7.57(1H, d), 7.19(4H, m), 6.95(1H, s), 6.87(1H, d), 6.56(1H, d), 3.68(2H, m), 3.51(3H, s), 3.45(2H, s), 3.36(2H, m), 2.38(7H, m), 2.07(3H, s). 1 H NMR (CDCl 3 , ppm); δ 10.28 (1H, bs), 8.30 (1H, d), 7.57 (1H, d), 7.19 (4H, m), 6.95 (1H, s), 6.87 (1H, d), 6.56 (1H, d), 3.68 (2H, m), 3.51 (3H, s), 3.45 (2H, s), 3.36 (2H, m), 2.38 (7H, m), 2.07 (3H, s).

FAB MS(m/e) = 488 [M+1]FAB MS (m / e) = 488 [M + 1]

하기 표 1은 제조예 10에서 얻은 화합물을 이용하여 실시예 3의 방법으로 소정의 목적 화합물들을 합성한 실시예들이다. Table 1 below shows examples of synthesizing desired compounds by the method of Example 3 using the compound obtained in Preparation Example 10.

[표 1]TABLE 1

Figure 112006083464511-PAT00025
Figure 112006083464511-PAT00025

실시예 17: (4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-아세트산의 제조Example 17: (4- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine Preparation of -1-yl) -acetic acid

Figure 112006083464511-PAT00026
Figure 112006083464511-PAT00026

실시예 16에서 얻은 화합물 450 mg(0.847 mmol)을 테트라히드로퓨란 30 ml에 녹이고 메탄올 10 ml를 가해 준 후, 리튬히드록사이드 1수화물 106 mg(2.54 mmol)을 물 10 ml에 녹여 가해주고 상온에서 3 시간 교반하였다. 반응완결 후 농축하고 물 20 ml를 가하고 1N 염산 수용액으로 중화하여 생긴 고체를 여과하고 건조하여 목적 화합물 400 mg(0.796 mmol, 수율; 94%)을 얻었다. 450 mg (0.847 mmol) of the compound obtained in Example 16 was dissolved in 30 ml of tetrahydrofuran and 10 ml of methanol was added thereto. Then, 106 mg (2.54 mmol) of lithium hydroxide monohydrate was dissolved in 10 ml of water and added at room temperature. Stir for 3 hours. After completion of the reaction, the resultant was concentrated, 20 ml of water was added thereto, and the solid formed by neutralization with 1N aqueous hydrochloric acid solution was filtered and dried to obtain 400 mg (0.796 mmol, yield; 94%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.2(1H, s), 8.25(1H, d), 7.64(1H, d), 7.26(2H, d), 7.21(2H, d), 7.11(1H, s), 6.93(1H, d), 6.54(1H, d), 3.53(4H, s), 3.49(2H, s), 3.41(3H, s), 2.66(4H, s), 2.46(2H, s), 2.34(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.2 (1H, s), 8.25 (1H, d), 7.64 (1H, d), 7.26 (2H, d), 7.21 (2H, d), 7.11 (1H, s), 6.93 (1H, d), 6.54 (1H, d), 3.53 (4H, s), 3.49 (2H, s), 3.41 (3H, s), 2.66 (4H, s), 2.46 (2H, s), 2.34 (3H, s)

FAB MS(m/e) = 504 [M+1]FAB MS (m / e) = 504 [M + 1]

실시예 18: N,N-디메틸-2-(4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-아세트아미드의 제조Example 18 N, N-dimethyl-2- (4- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine- Preparation of 4-ylmethyl} -piperazin-1-yl) -acetamide

Figure 112006083464511-PAT00027
Figure 112006083464511-PAT00027

실시예 17에서 얻은 화합물 50 mg(0.0994 mmol)을 N,N-디메틸포름아미드 3 ml에 녹인 후 디메틸아민(2M 테트라히드로퓨란 용액) 0.065 ml(0.129 mmol)과 1-히드록시벤조트리아졸 22.8 mg(0.170 mmol)과 1-(3-디메틸아미노프로필)-3-에틸카보디이미드 염산염 28.6 mg(0.149 mmol)을 가하고 상온에서 2 시간 교반하였다. 반응완결 후 농축하고 에틸 아세테이트 30 ml을 가하여 녹인 후 포화탄산수소나트륨 20 ml를 사용하여 씻은 후 농축하고 관 크로마토그래피로 분리하여 목적 화합물 43 mg(0.0811 mmol, 수율; 82%)을 얻었다. 50 mg (0.0994 mmol) of the compound obtained in Example 17 was dissolved in 3 ml of N, N-dimethylformamide, followed by 0.065 ml (0.129 mmol) of dimethylamine (2M tetrahydrofuran solution) and 22.8 mg of 1-hydroxybenzotriazole. (0.170 mmol) and 28.6 mg (0.149 mmol) of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride were added and stirred at room temperature for 2 hours. After completion of the reaction, the resultant was concentrated, dissolved in 30 ml of ethyl acetate, washed with 20 ml of saturated sodium hydrogen carbonate, concentrated and separated by column chromatography to obtain 43 mg (0.0811 mmol, yield; 82%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.3(1H, s), 8.24(1H, d), 7.64(1H, d), 7.22(2H, d), 7.19(2H, d), 7.11(1H, s), 6.92(1H, d), 6.54(1H, d), 3.53(4H, s), 3.49(2H, s), 3.41(3H, s), 2.66(4H, s), 2.55(6H, s), 2.46(2H, s), 2.34(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.3 (1H, s), 8.24 (1H, d), 7.64 (1H, d), 7.22 (2H, d), 7.19 (2H, d), 7.11 (1H, s), 6.92 (1H, d), 6.54 (1H, d), 3.53 (4H, s), 3.49 (2H, s), 3.41 (3H, s), 2.66 (4H, s), 2.55 (6H, s), 2.46 (2H, s), 2.34 (3H, s)

FAB MS(m/e) = 531 [M+1]FAB MS (m / e) = 531 [M + 1]

제조예Production Example 11: 2- 11: 2- 클로로Chloro -4--4- 클로로메틸Chloromethyl -피리딘의 제조Preparation of Pyridine

6-클로로피리딘-2-카르복실산 대신 6-클로로이소니코틴산을 이용하여 제조예 1의 방법으로 반응하고, 계속하여 제조예 2의 방법으로 반응하여 얻어진 2-크로로- 4-히드록시메틸피리딘 20.0 g(140 mmol)을 제조예 5의 방법으로 반응하여 목적 화합물 17.5 g(109 mmol, 수율; 78%)을 얻었다. 2-Chloro-4-hydroxymethylpyridine obtained by reacting by the method of Preparation Example 1 using 6-chloroisonicotinic acid instead of 6-chloropyridine-2-carboxylic acid, and subsequently by the method of Preparation Example 2. 20.0 g (140 mmol) was reacted by the method of Preparation Example 1 to obtain 17.5 g (109 mmol, yield; 78%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 8.34 (1H, d), 7.29 (1H, s), 7.16 (1H, d), 3.82 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.34 (1H, d), 7.29 (1H, s), 7.16 (1H, d), 3.82 (3H, s)

FAB MS(m/e) = 162 [M+1]FAB MS (m / e) = 162 [M + 1]

제조예Production Example 12: (2- 12: (2- 클로로Chloro -피리딘-4-일)-아세트산 에틸 에스테르의 제조Preparation of -pyridin-4-yl) -acetic acid ethyl ester

제조예 11에서 얻어진 화합물 19.5 g(121 mmol)을 에탄올 400 ml에 녹인 후 팔라듐 아세테이트 950 mg(6.05 mmol)과 트리페닐포스핀 3.17 g(12.1 mmol), 탄산칼슘 50.2 g(363 mmol)을 가한 후 1 기압의 일산화탄소 조건하에서 교반하였다. 반응완결 후 셀라이트에 여과하고 농축한 후 관 크로마토그래피로 분리하여 목적 화합물 19.0 g(95.5 mmol, 수율, 79%)을 얻었다. Dissolve 19.5 g (121 mmol) of the compound obtained in Preparation Example 11 in 400 ml of ethanol, and then add 950 mg (6.05 mmol) of palladium acetate, 3.17 g (12.1 mmol) of triphenylphosphine, and 50.2 g (363 mmol) of calcium carbonate. Stirred under 1 atm of carbon monoxide conditions. After completion of the reaction, the mixture was filtered through celite, concentrated and separated by column chromatography to obtain the title compound 19.0 g (95.5 mmol, yield, 79%).

1H NMR (CDCl3, ppm); δ 8.34 (1H, d), 7.29 (1H, s), 7.16 (1H, d), 4.18 (2H, q), 3.61 (3H, s), 1.27 (3H, t) 1 H NMR (CDCl 3 , ppm); δ 8.34 (1H, d), 7.29 (1H, s), 7.16 (1H, d), 4.18 (2H, q), 3.61 (3H, s), 1.27 (3H, t)

FAB MS(m/e) = 200 [M+1]FAB MS (m / e) = 200 [M + 1]

실시예 19: {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트산 에틸 에스테르의 제조Example 19 Preparation of {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -acetic acid ethyl ester

Figure 112006083464511-PAT00028
Figure 112006083464511-PAT00028

제조예 12에서 얻은 화합물을 N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민과 실시예 1의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 12 was reacted with N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine in the method of Example 1 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.3(1H, s), 8.21(1H, d), 7.64(1H, d), 7.22(2H, d), 7.19(2H, d), 6.97(1H, s), 6.85(1H, d), 6.53(1H, d), 3.52(2H, s), 3.11(2H, q), 2.34(3H, s), 2.19(3H, s), 1.23(3H, t) 1 H NMR (DMSO-d 6 , ppm); δ 11.3 (1H, s), 8.21 (1H, d), 7.64 (1H, d), 7.22 (2H, d), 7.19 (2H, d), 6.97 (1H, s), 6.85 (1H, d), 6.53 (1H, d), 3.52 (2H, s), 3.11 (2H, q), 2.34 (3H, s), 2.19 (3H, s), 1.23 (3H, t)

FAB MS(m/e) = 434 [M+1]FAB MS (m / e) = 434 [M + 1]

실시예 20: {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트산의 제조Example 20 Preparation of {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -acetic acid

Figure 112006083464511-PAT00029
Figure 112006083464511-PAT00029

실시예 19에서 얻어진 화합물을 실시예 17의 방법으로 가수분해하여 목적 화합물을 얻었다. The compound obtained in Example 19 was hydrolyzed by the method of Example 17 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.3(1H, s), 8.23(1H, d), 7.62(1H, d), 7.20(2H, d), 7.19(2H, d), 6.97(1H, s), 6.84(1H, d), 6.51(1H, d), 3.50(2H, s), 2.34(3H, s), 2.19(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.3 (1H, s), 8.23 (1H, d), 7.62 (1H, d), 7.20 (2H, d), 7.19 (2H, d), 6.97 (1H, s), 6.84 (1H, d), 6.51 (1H, d), 3.50 (2H, s), 2.34 (3H, s), 2.19 (3H, s)

FAB MS(m/e) = 406 [M+1]FAB MS (m / e) = 406 [M + 1]

실시예 21: 1-(4-메틸-피페라진-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-에타논의 제조Example 21 1- (4-Methyl-piperazin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine-2- Preparation of Ilamino] -pyridin-4-yl} -ethanone

Figure 112006083464511-PAT00030
Figure 112006083464511-PAT00030

실시예 20에서 얻어진 화합물과 N-메틸피페라진을 이용하여 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained by reacting the compound obtained in Example 20 with the method of Example 18 using N-methylpiperazine.

1H NMR (DMSO-d6, ppm); δ 11.3(1H, s), 8.24(1H, d), 7.64(1H, d), 7.21(2H, d), 7.19(2H, d), 6.98(1H, s), 6.86(1H, d), 6.52(1H, d), 3.89(3H, s), 3.50(2H, s), 3.40(4H, s), 2.34(3H, s), 2.30(4H, s), 2.19(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.3 (1H, s), 8.24 (1H, d), 7.64 (1H, d), 7.21 (2H, d), 7.19 (2H, d), 6.98 (1H, s), 6.86 (1H, d), 6.52 (1H, d), 3.89 (3H, s), 3.50 (2H, s), 3.40 (4H, s), 2.34 (3H, s), 2.30 (4H, s), 2.19 (3H, s)

FAB MS(m/e) = 488 [M+1]FAB MS (m / e) = 488 [M + 1]

실시예 22: N-(2-디에틸아미노-에틸)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드의 제조Example 22 N- (2-diethylamino-ethyl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] Preparation of -pyridin-4-yl} -acetamide

Figure 112006083464511-PAT00031
Figure 112006083464511-PAT00031

N-메틸피페라진 대신 3-디에틸아미노에틸아민을 이용하여 실시예 21의 방법으로 반응하여 목적 화합물을 얻었다. Reaction was carried out in the same manner as in Example 21 using 3-diethylaminoethylamine instead of N-methylpiperazine to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.3(1H, s), 8.12(1H, d), 7.76(1H, d), 7.26(2H, d), 7.23(2H, d), 7.03(1H, s), 6.89(1H, d), 6.52(1H, d), 3.89(3H, s), 3.50(2H, s), 3.32-3.21(4H, m), 2.97(2H, m), 2.74(2H, t), 2.33(3H, s), 1.18(3H, t), 1.01(3H, t) 1 H NMR (DMSO-d 6 , ppm); δ 11.3 (1H, s), 8.12 (1H, d), 7.76 (1H, d), 7.26 (2H, d), 7.23 (2H, d), 7.03 (1H, s), 6.89 (1H, d), 6.52 (1H, d), 3.89 (3H, s), 3.50 (2H, s), 3.32-3.21 (4H, m), 2.97 (2H, m), 2.74 (2H, t), 2.33 (3H, s) , 1.18 (3H, t), 1.01 (3H, t)

FAB MS(m/e) = 504 [M+1]FAB MS (m / e) = 504 [M + 1]

실시예 23: 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-N-(2-몰포린-4-일-에틸)-아세트아미드의 제조Example 23: 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -N- (2 Preparation of -morpholin-4-yl-ethyl) -acetamide

Figure 112006083464511-PAT00032
Figure 112006083464511-PAT00032

실시예 21에서 N-메틸피페라진 대신 2-몰포리노에틸아민을 이용하여 실시예 21의 방법으로 반응하여 목적 화합물을 얻었다.In Example 21, using the 2-morpholinoethylamine instead of N-methyl piperazine in the method of Example 21 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.2(1H, s), 8.23(1H, d), 7.64(1H, d), 7.26(2H, d), 7.19(2H, s), 7.01(1H, s), 6.90(1H, d), 6.54(1H, d), 3.57(4H, s), 3.40(2H, s), 2.97(2H, m), 2.74(2H, t), 2.39(4H, s), 2.3(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.2 (1H, s), 8.23 (1H, d), 7.64 (1H, d), 7.26 (2H, d), 7.19 (2H, s), 7.01 (1H, s), 6.90 (1H, d), 6.54 (1H, d), 3.57 (4H, s), 3.40 (2H, s), 2.97 (2H, m), 2.74 (2H, t), 2.39 (4H, s), 2.3 (3H, s)

FAB MS(m/e) = 518 [M+1]FAB MS (m / e) = 518 [M + 1]

실시예 24: N-(2-히드록시-에틸)-N-메틸-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드의 제조Example 24 N- (2-hydroxy-ethyl) -N-methyl-2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine-2- Preparation of Ilamino] -pyridin-4-yl} -acetamide

Figure 112006083464511-PAT00033
Figure 112006083464511-PAT00033

실시예 21에서 N-메틸피페라진 대신 1-메틸-2-히드록시에틸아민을 이용하여 실시예 21의 방법으로 반응하여 목적 화합물을 얻었다.In Example 21, 1-methyl-2-hydroxyethylamine was used instead of N-methylpiperazine to react in the same manner as in Example 21 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.3(1H, s), 8.23(1H, d), 7.62(1H, d), 7.27(2H, d), 7.20(2H, d), 6.98(1H, s), 6.85(1H, d), 6.55(1H, s), 4.82(1H, t), 3.79-3.57(4H, m), 3.40(2H, s), 3.27(3H, s), 2.88(3H, s), 2.34(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.3 (1H, s), 8.23 (1H, d), 7.62 (1H, d), 7.27 (2H, d), 7.20 (2H, d), 6.98 (1H, s), 6.85 (1H, d), 6.55 (1H, s), 4.82 (1H, t), 3.79-3.57 (4H, m), 3.40 (2H, s), 3.27 (3H, s), 2.88 (3H, s), 2.34 (3H, s)

FAB MS(m/e) = 463 [M+1]FAB MS (m / e) = 463 [M + 1]

실시예 25: N-(2-히드록시-에틸)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피 리딘-2-일아미노]-피리딘-4-일}-아세트아미드의 제조Example 25 N- (2-hydroxy-ethyl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] Preparation of -pyridin-4-yl} -acetamide

Figure 112006083464511-PAT00034
Figure 112006083464511-PAT00034

실시예 21에서 N-메틸피페라진 대신 2-히드록시에틸아민을 이용하여 실시예 21의 방법으로 반응하여 목적 화합물을 얻었다.In Example 21, the reaction of Example 21 was carried out using 2-hydroxyethylamine instead of N-methylpiperazine to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.30(1H, s), 8.23(1H, d), 7.64(1H, d), 7.27(2H, d), 7.19(2H, d), 7.03(1H, s), 6.91(1H, d), 6.52(1H, d), 4.72(1H, t), 3.70-3.65(2H, m), 3.40(2H, s), 3.28(3H, s), 3.16(2H, t), 2.34(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.30 (1H, s), 8.23 (1H, d), 7.64 (1H, d), 7.27 (2H, d), 7.19 (2H, d), 7.03 (1H, s), 6.91 (1H, d), 6.52 (1H, d), 4.72 (1H, t), 3.70-3.65 (2H, m), 3.40 (2H, s), 3.28 (3H, s), 3.16 (2H, t), 2.34 (3H, s)

FAB MS(m/e) = 518[M+1]FAB MS (m / e) = 518 [M + 1]

실시예 26: 6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코티노니트릴의 제조Example 26 Preparation of 6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -nicotinonitrile

Figure 112006083464511-PAT00035
Figure 112006083464511-PAT00035

N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민을 2-클로로-5-시아노피리딘과 실시예 1의 방법으로 반응하여 목적 화합물을 얻었다. N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine was reacted with 2-chloro-5-cyanopyridine by the method of Example 1 to obtain the target compound. Got it.

1H NMR (DMSO-d6, ppm); δ11.94 (1H, bs), 8.79 (1H, s), 8.11 (1H, d), 7.70 (1H, d), 7.23 (5H, m), 6.53 (1H, d), 3.41 (3H, s), 2.37(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.94 (1H, bs), 8.79 (1H, s), 8.11 (1H, d), 7.70 (1H, d), 7.23 (5H, m), 6.53 (1H, d), 3.41 (3H, s) , 2.37 (3H, s)

FAB MS(m/e) = 373 [M+1]FAB MS (m / e) = 373 [M + 1]

제조예Production Example 13: 5-( 13: 5- ( terttert -부틸-디메틸--Butyl-dimethyl- 실라닐옥시메틸Silanyloxymethyl )-2-)-2- 클로로Chloro -피리딘의 제조Preparation of Pyridine

제조예 6에서 6-클로로이소니코틴산 대신 6-클로로니코틴산을 사용하여 제조예 6의 방법으로 반응하여 목적 화합물을 얻었다. In Preparation Example 6, 6-chloronicotinic acid was used instead of 6-chloroisonicotinic acid to react in the same manner as in Preparation Example 6 to obtain a target compound.

1H NMR (CDCl3, ppm); δ 8.32(1H, s), 7.62(1H, d), 7.28(1H, d), 4.72(2H, s), 0.92(9H, s), 0.10(6H, s) 1 H NMR (CDCl 3 , ppm); δ 8.32 (1H, s), 7.62 (1H, d), 7.28 (1H, d), 4.72 (2H, s), 0.92 (9H, s), 0.10 (6H, s)

FAB MS(m/e) = 258 [M+1]FAB MS (m / e) = 258 [M + 1]

제조예 14: NPreparation Example 14 N 22 -(5-클로로메틸-피리딘-2-일)-N-(5-chloromethyl-pyridin-2-yl) -N 55 -메틸-N-Methyl-N 55 -p-톨릴-티아졸로[5,4-b]피리딘-2,5--p-tolyl-thiazolo [5,4-b] pyridine-2,5- 디아민의Diamine 제조 Produce

제조예 13에서 얻은 화합물을 이용하여 제조예 7의 방법으로 반응하여 목적 화합물을 얻었다. Using the compound obtained in Preparation Example 13, the reaction was carried out by the method of Preparation Example 7 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 8.30 (1H, bs), 7.57 (1H, d), 7.23 (5H, m), 7.00 (1H, d), 6.45(1H, d), 3.57(2H, s), 3.51 (3H, s), 2.42(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.30 (1H, bs), 7.57 (1H, d), 7.23 (5H, m), 7.00 (1H, d), 6.45 (1H, d), 3.57 (2H, s), 3.51 (3H, s), 2.42 (3H, s)

FAB MS(m/e) = 396 [M+1]FAB MS (m / e) = 396 [M + 1]

실시예 27: NExample 27: N 22 -(5-디에틸아미노메틸-피리딘-2-일)-N-(5-diethylaminomethyl-pyridin-2-yl) -N 55 -메틸-N-Methyl-N 55 -p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of -p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00036
Figure 112006083464511-PAT00036

제조예 14에서 얻은 화합물을 디에틸아민을 사용하여 실시예 3의 방법으로 반응시켜 목적 화합물을 얻었다. The compound obtained in Preparation Example 14 was reacted by the method of Example 3 using diethylamine to obtain the target compound.

1H NMR (CDCl3, ppm); δ 8.30 (1H, bs), 7.57 (1H, d), 7.23 (5H, m), 7.00 (1H, d), 6.46(1H, d), 3.51 (3H, s), 3.45 (2H, bs), 2.59 (4H, m), 2.42 (3H, s), 1.11 (6H, m) 1 H NMR (CDCl 3 , ppm); δ 8.30 (1H, bs), 7.57 (1H, d), 7.23 (5H, m), 7.00 (1H, d), 6.46 (1H, d), 3.51 (3H, s), 3.45 (2H, bs), 2.59 (4H, m), 2.42 (3H, s), 1.11 (6H, m)

FAB MS(m/e) = 433 [M+1]FAB MS (m / e) = 433 [M + 1]

하기 표 2는 제조예 14에서 얻은 화합물을 사용하여 실시예 27의 방법으로 반응하여 소정의 목적 화합물들을 합성한 실시예들이다. Table 2 below is an example in which the desired compound was synthesized by reacting by the method of Example 27 using the compound obtained in Preparation Example 14.

[표 2]TABLE 2

Figure 112006083464511-PAT00037
Figure 112006083464511-PAT00037

Figure 112006083464511-PAT00038
Figure 112006083464511-PAT00038

실시예 37: ({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-아세트산의 제조Example 37: ({6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) -acetic acid Manufacture

Figure 112006083464511-PAT00039
Figure 112006083464511-PAT00039

실시예 34에서 얻은 화합물을 실시예 17의 방법으로 가수분해하여 목적 화합물을 얻었다. The compound obtained in Example 34 was hydrolyzed by the method of Example 17 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ8.17 (1H, s), 7.65 (1H, m), 7.57 (1H, d), 7.15 (4H, m), 7.05 (1H, m), 6.47 (1H, d), 3.59 (2H, s), 3.36 (3H, s), 2.78 (2H, s), 2.29 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.17 (1H, s), 7.65 (1H, m), 7.57 (1H, d), 7.15 (4H, m), 7.05 (1H, m), 6.47 (1H, d), 3.59 (2H, s) , 3.36 (3H, s), 2.78 (2H, s), 2.29 (3H, s)

FAB MS(m/e) = 435 [M+1]FAB MS (m / e) = 435 [M + 1]

실시예 38: 2-({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-프로피온산의 제조Example 38: 2-({6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) Preparation of Propionic Acid

Figure 112006083464511-PAT00040
Figure 112006083464511-PAT00040

실시예 36에서 얻은 화합물을 실시예 17의 방법으로 가수분해하여 목적 화합물을 얻었다. The compound obtained in Example 36 was hydrolyzed by the method of Example 17 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ7.96 (1H, s), 7.32 (1H, d), 7.21 (1H, d), 7.09 (2H, d), 7.01 (2H, d), 6.62 (1H, d), 6.43 (1H, d), 3.47 (1H, q), 3.33 (5H, s), 2.24 (3H, s), 1.03 (3H, d) 1 H NMR (DMSO-d 6 , ppm); δ 7.96 (1H, s), 7.32 (1H, d), 7.21 (1H, d), 7.09 (2H, d), 7.01 (2H, d), 6.62 (1H, d), 6.43 (1H, d) , 3.47 (1H, q), 3.33 (5H, s), 2.24 (3H, s), 1.03 (3H, d)

FAB MS(m/e) = 449 [M+1]FAB MS (m / e) = 449 [M + 1]

실시예 39: 6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코틴산 메틸 에스테르의 제조Example 39 Preparation of 6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -nicotinic acid methyl ester

Figure 112006083464511-PAT00041
Figure 112006083464511-PAT00041

N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민을 메틸 6-클로로니코티네이트와 실시예 1의 방법으로 반응하여 목적 화합물을 얻었다. N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine was reacted with methyl 6-chloronicotinate by the method of Example 1 to obtain the target compound.

1H NMR (CDCl3, ppm); δ10.59 (1H, bs), 9.01 (1H, s), 8.13 (1H, d), 7.54 (1H, d), 7.20 (4H, m), 6.95 (1H, d), 6.55 (1H, d), 3.93 (3H, s), 3.51 (3H, s), 2.38 (3H, s) 1 H NMR (CDCl 3 , ppm); δ 10.59 (1H, bs), 9.01 (1H, s), 8.13 (1H, d), 7.54 (1H, d), 7.20 (4H, m), 6.95 (1H, d), 6.55 (1H, d) , 3.93 (3H, s), 3.51 (3H, s), 2.38 (3H, s)

FAB MS(m/e) = 406 [M+1]FAB MS (m / e) = 406 [M + 1]

실시예 40: 6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코틴산의 제조Example 40 Preparation of 6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -nicotinic acid

Figure 112006083464511-PAT00042
Figure 112006083464511-PAT00042

실시예 39에서 얻은 화합물을 실시예 17의 방법으로 가수분해하여 목적 화합물을 얻었다. The compound obtained in Example 39 was hydrolyzed by the method of Example 17 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.30(1H, s), 8.32(1H, s), 7.75(1H, d), 7.61(1H, d), 7.23(2H, d), 7.18(2H, d), 7.11(1H, d), 6.59(1H, d), 3.31(3H, s), 2.21(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.30 (1H, s), 8.32 (1H, s), 7.75 (1H, d), 7.61 (1H, d), 7.23 (2H, d), 7.18 (2H, d), 7.11 (1H, d), 6.59 (1H, d), 3.31 (3H, s), 2.21 (3H, s)

FAB MS(m/e) = 392 [M+1]FAB MS (m / e) = 392 [M + 1]

실시예 41: (4-메틸-피페라진-1-일)-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-메타논의 제조Example 41: (4-Methyl-piperazin-1-yl)-{6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino]- Preparation of Pyridin-3-yl} -Methanone

Figure 112006083464511-PAT00043
Figure 112006083464511-PAT00043

실시예 40에서 얻은 화합물을 N-메틸피페라진과 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 40 was reacted with N-methylpiperazine by the method of Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.30(1H, s), 8.32(1H, s), 7.75(1H, d), 7.61(1H, d), 7.23(2H, d), 7.18(2H, d), 7.11(1H, d), 6.59(1H, d), 3.50(4H, bs), 3.38(3H, s), 3.31(3H, s), 2.32(4H, bs), 2.20(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.30 (1H, s), 8.32 (1H, s), 7.75 (1H, d), 7.61 (1H, d), 7.23 (2H, d), 7.18 (2H, d), 7.11 (1H, d), 6.59 (1H, d), 3.50 (4H, bs), 3.38 (3H, s), 3.31 (3H, s), 2.32 (4H, bs), 2.20 (3H, s)

FAB MS(m/e) = 474 [M+1]FAB MS (m / e) = 474 [M + 1]

실시예 42: N-(1-메틸-피페리딘-4-일메틸)-6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코틴아미드의 제조Example 42 N- (1-methyl-piperidin-4-ylmethyl) -6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-yl Preparation of Amino] -nicotinamide

Figure 112006083464511-PAT00044
Figure 112006083464511-PAT00044

실시예 40에서 얻은 화합물을 1-메틸-4-(아미노메틸)피페리딘과 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 40 was reacted with 1-methyl-4- (aminomethyl) piperidine in the method of Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.2(1H, s), 8.76(1H, s), 8.46(1H, d), 8.10(1H, d), 7.63(1H, d), 7.29(2H, d), 7.17(2H, d), 7.11(1H, d), 6.50(1H, d), 5.77(1H, t), 3.31(3H, s), 2.97(2H, t), 2.85(2H, t), 2.34(3H, s), 2.23(3H, s), 1.97(2H, t), 1.63-1.60(2H, m), 1.39-1.35(1H, m), 1.19-1.14(2H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.2 (1H, s), 8.76 (1H, s), 8.46 (1H, d), 8.10 (1H, d), 7.63 (1H, d), 7.29 (2H, d), 7.17 (2H, d), 7.11 (1H, d), 6.50 (1H, d), 5.77 (1H, t), 3.31 (3H, s), 2.97 (2H, t), 2.85 (2H, t), 2.34 (3H, s), 2.23 (3H, s), 1.97 (2H, t), 1.63-1.60 (2H, m), 1.39-1.35 (1H, m), 1.19-1.14 (2H, m)

FAB MS(m/e) = 502 [M+1]FAB MS (m / e) = 502 [M + 1]

실시예 43: {6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-몰포린-4-일-메타논의 제조Example 43 {6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -morpholin-4-yl Preparation of Methanone

Figure 112006083464511-PAT00045
Figure 112006083464511-PAT00045

실시예 40에서 얻은 화합물을 몰포린과 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다.The compound obtained in Example 40 was reacted with morpholine in the method of Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.57(1H, s), 8.41(1H, s), 7.83(1H, d), 7.68(1H, d), 7.27(2H, d), 7.22(2H, d), 7.18(1H, d), 6.53(1H, d), 3.64(4H, s), 3.41(3H, s), 3.32(4H, s), 2.34(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.57 (1H, s), 8.41 (1H, s), 7.83 (1H, d), 7.68 (1H, d), 7.27 (2H, d), 7.22 (2H, d), 7.18 (1H, d), 6.53 (1H, d), 3.64 (4H, s), 3.41 (3H, s), 3.32 (4H, s), 2.34 (3H, s)

FAB MS(m/e) = 461 [M+1]FAB MS (m / e) = 461 [M + 1]

제조예Production Example 15: 2- 15: 2- 클로로Chloro -5--5- 클로로메틸Chloromethyl -피리딘의 제조Preparation of Pyridine

제조예 11에서 6-클로로이소니코틴산 대신 6-클로로니코틴산을 이용하여 제조예 11의 방법으로 반응하여 목적 화합물을 얻었다. In Preparation Example 11, 6-chloronicotinic acid was used instead of 6-chloronicotinic acid to react in the same manner as in Preparation Example 11, to obtain a target compound.

1H NMR (CDCl3, ppm); δ 8.32 (1H, s), 7.61 (1H, d), 7.33 (1H, d), 3.89(2H, s) 1 H NMR (CDCl 3 , ppm); δ 8.32 (1H, s), 7.61 (1H, d), 7.33 (1H, d), 3.89 (2H, s)

FAB MS(m/e) = 162 [M+1]FAB MS (m / e) = 162 [M + 1]

제조예Production Example 16: (6- 16: (6- 클로로Chloro -피리딘-3-일)-아세트산 에틸 에스테르의 제조Preparation of -pyridin-3-yl) -acetic acid ethyl ester

제조예 15에서 얻어진 화합물을 이용하여 제조예 12의 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained by reacting by the method of Preparation Example 12 using the compound obtained in Preparation Example 15.

1H NMR (CDCl3, ppm); δ 8.30 (1H, s), 7.62 (1H, d), 7.30 (1H, d), 4.16 (2H, q), 3.60 (2H, s), 1.26 (3H, t) 1 H NMR (CDCl 3 , ppm); δ 8.30 (1H, s), 7.62 (1H, d), 7.30 (1H, d), 4.16 (2H, q), 3.60 (2H, s), 1.26 (3H, t)

FAB MS(m/e) = 200 [M+1]FAB MS (m / e) = 200 [M + 1]

실시예 44: {6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-아세트산 에틸 에스테르의 제조Example 44 Preparation of {6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -acetic acid ethyl ester

Figure 112006083464511-PAT00046
Figure 112006083464511-PAT00046

제조예 16에서 얻은 화합물을 N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민과 실시예 1의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Production Example 16 was reacted with N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine in the method of Example 1 to obtain the target compound.

1H NMR (CDCl3, ppm); δ9.90 (1H, bs), 8.26 (1H, s), 7.56 (2H, s), 7.19 (4H, m), 6.96 (1H, d), 6.57 (1H, d), 4.16 (2H, q), 3.57 (2H, s), 3.50 (3H, s), 2.38 (3H, s), 1.26 (3H, t) 1 H NMR (CDCl 3 , ppm); δ9.90 (1H, bs), 8.26 (1H, s), 7.56 (2H, s), 7.19 (4H, m), 6.96 (1H, d), 6.57 (1H, d), 4.16 (2H, q) , 3.57 (2H, s), 3.50 (3H, s), 2.38 (3H, s), 1.26 (3H, t)

FAB MS(m/e) = 434 [M+1]FAB MS (m / e) = 434 [M + 1]

실시예 45: {6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-아세트산의 제조Example 45 Preparation of {6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -acetic acid

Figure 112006083464511-PAT00047
Figure 112006083464511-PAT00047

실시예 44에서 얻은 화합물을 실시예 17의 방법으로 가수분해하여 목적 화합물을 얻었다. The compound obtained in Example 44 was hydrolyzed by the method of Example 17 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 8.10 (1H, s), 7.63 (2H, t), 7.20 (4H, m), 7.10 (1H, d), 6.51 (1H, d), 3.58 (2H, s), 2.32 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.10 (1H, s), 7.63 (2H, t), 7.20 (4H, m), 7.10 (1H, d), 6.51 (1H, d), 3.58 (2H, s), 2.32 (3H, s)

FAB MS(m/e) = 406 [M+1]FAB MS (m / e) = 406 [M + 1]

실시예 46: 1-(4-메틸-피페라진-1-일)-2-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-에타논의 제조Example 46: 1- (4-Methyl-piperazin-1-yl) -2- {6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine-2- Preparation of Ilamino] -pyridin-3-yl} -ethanone

Figure 112006083464511-PAT00048
Figure 112006083464511-PAT00048

실시예 45에서 얻은 화합물을 N-메틸피페라진과 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 45 was reacted with N-methylpiperazine in the method of Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.21(1H, d), 7.61(1H, d), 7.40(2H, d), 7.28(2H, d), 7.17(1H, t), 7.07(1H, s), 6.89(1H, d), 6.59(1H, d), 6.38(1H, d), 3.43(2H, s), 3.40(3H, s), 3.26(4H, s), 2.46(3H, s), 2.43(3H, s), 2.30(4H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.21 (1H, d), 7.61 (1H, d), 7.40 (2H, d), 7.28 (2H, d), 7.17 (1H, t), 7.07 (1H, s), 6.89 (1H, d), 6.59 (1H, d), 6.38 (1H, d), 3.43 (2H, s), 3.40 (3H, s), 3.26 (4H, s), 2.46 (3H, s), 2.43 (3H, s), 2.30 (4H, s)

FAB MS(m/e) = 488 [M+1]FAB MS (m / e) = 488 [M + 1]

실시예 47: N-(1-메틸-피페리딘-4-일메틸)-2-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-아세트아미드의 제조Example 47 N- (1-methyl-piperidin-4-ylmethyl) -2- {6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine- Preparation of 2-ylamino] -pyridin-3-yl} -acetamide

Figure 112006083464511-PAT00049
Figure 112006083464511-PAT00049

실시예 45에서 얻은 화합물을 1-메틸-4-(아미노메틸)피페리딘과 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 45 was reacted with 1-methyl-4- (aminomethyl) piperidine in the method of Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 8.18(1H, s), 8.08(1H, t), 7.69-7.66(2H, m), 7.27(2H, d), 7.21(2H, d), 7.08(1H, d), 6.52(1H, d), 3.43(2H, s), 3.31(3H, s), 2.97(2H, t), 2.85(2H, t), 2.34(3H, s), 2.23(3H, s), 1.97(2H, t), 1.63-1.60(2H, m), 1.39-1.35(1H, m), 1.19-1.14(2H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 8.18 (1H, s), 8.08 (1H, t), 7.69-7.66 (2H, m), 7.27 (2H, d), 7.21 (2H, d), 7.08 (1H, d ), 6.52 (1H, d), 3.43 (2H, s), 3.31 (3H, s), 2.97 (2H, t), 2.85 (2H, t), 2.34 (3H, s), 2.23 (3H, s) , 1.97 (2H, t), 1.63-1.60 (2H, m), 1.39-1.35 (1H, m), 1.19-1.14 (2H, m)

FAB MS(m/e) = 516 [M+1]FAB MS (m / e) = 516 [M + 1]

제조예 17: NPreparation Example 17 N 22 -(4-클로로메틸-피리딘-2-일)-N-(4-chloromethyl-pyridin-2-yl) -N 55 -(4-플루오로-페닐)-N-(4-fluoro-phenyl) -N 55 -메틸-티아졸로[-Methyl-thiazolo [ 5,4-b]피리딘5,4-b] pyridine -2,5--2,5- 디아민의Diamine 제조 Produce

제조예 7에서 N5-메틸-N5-페닐-티아졸로[5,4-b]피리딘-2,5-디아민 대신 N5-메틸-N5-(4-플루오로-페닐)-티아졸로[5,4-b]피리딘-2,5-디아민을 이용하여 제조예 7의 방법으로 반응하여 목적 화합물을 얻었다. In Production Example 7 N 5 - (4-fluoro-phenyl) -N-methyl-5-phenyl-thiazolo [5,4-b] pyridine-2,5-diamine instead of N 5 -methyl -N 5 thiazolo It reacted by the method of Preparation Example 7 using [5,4-b] pyridine-2,5-diamine, and obtained the target compound.

1H NMR (DMSO-d6, ppm); δ 8.29 (1H, d), 7.57 (1H, d), 7.23 (2H, m), 7.07 (3H, m), 6.88 (1H, d), 6.49 (1H, d), 4.53 (2H, s), 3.48 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.29 (1H, d), 7.57 (1H, d), 7.23 (2H, m), 7.07 (3H, m), 6.88 (1H, d), 6.49 (1H, d), 4.53 (2H, s), 3.48 (3H, s)

FAB MS(m/e) = 400 [M+1]FAB MS (m / e) = 400 [M + 1]

실시예 48: NExample 48: N 55 -(4-플루오로-페닐)-N-(4-fluoro-phenyl) -N 55 -메틸-N-Methyl-N 22 -(4-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-(4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00050
Figure 112006083464511-PAT00050

제조예 17에서 얻은 화합물과 몰포린을 사용하여 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Production Example 17 and the morpholine were reacted by the method of Example 3 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 8.64 (1H, bs), 8.28 (1H, d), 7.47 (1H, d), 7.23 (2H, m), 7.08 (2H, t), 6.98 (1H, s), 6.93 (1H, d), 6.50(1H, d), 3.70 (4H, t), 3.49(3H, s), 3.47 (2H, s), 2.45 (4H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.64 (1H, bs), 8.28 (1H, d), 7.47 (1H, d), 7.23 (2H, m), 7.08 (2H, t), 6.98 (1H, s), 6.93 (1H, d), 6.50 (1H, d), 3.70 (4H, t), 3.49 (3H, s), 3.47 (2H, s), 2.45 (4H, s)

FAB MS(m/e) = 400 [M+1]FAB MS (m / e) = 400 [M + 1]

하기 표 3은 제조예 17에서 얻은 화합물을 이용하여 실시예 48의 방법으로 소정의 목적 화합물들을 합성한 실시예들이다. Table 3 below shows examples of synthesizing desired compounds by the method of Example 48 using the compound obtained in Preparation Example 17.

[표 3]TABLE 3

Figure 112006083464511-PAT00051
Figure 112006083464511-PAT00051

Figure 112006083464511-PAT00052
Figure 112006083464511-PAT00052

Figure 112006083464511-PAT00053
Figure 112006083464511-PAT00053

실시예 62: NExample 62: N 55 -(4-플루오로-페닐)-N-(4-fluoro-phenyl) -N 55 -메틸-N-Methyl-N 22 -(4-피페라진-1-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-(4-piperazin-1-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00054
Figure 112006083464511-PAT00054

실시예 51에서 얻은 화합물 250 mg(0.455 mmol)을 디클로로메탄 3 ml에 녹이고 4N 염산(1,4-디옥산)용액 1 ml를 가하고 상온에서 2 시간 교반하였다. 반응완결 후 농축하고, 물 10 ml를 가한 후 포화 탄산수소나트륨으로 중화하여 생긴 고체를 여과하여 목적 화합물 194 mg(0.432 mmol, 수율; 95%)을 얻었다. 250 mg (0.455 mmol) of the compound obtained in Example 51 were dissolved in 3 ml of dichloromethane, 1 ml of 4N hydrochloric acid (1,4-dioxane) solution was added, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the mixture was concentrated, 10 ml of water was added thereto, and the solid formed by neutralization with saturated sodium bicarbonate was filtered to obtain 194 mg (0.432 mmol, yield; 95%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.30(1H, s), 8.23(1H, d), 7.64(1H, d), 7.34(2H, t), 7.28(2H, t), 7.01(1H, s), 6.92(1H, t), 6.54(1H, d), 3.40(2H, s), 3.31(3H, s), 2.88(2H, t), 2,50-2.41(7H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.30 (1H, s), 8.23 (1H, d), 7.64 (1H, d), 7.34 (2H, t), 7.28 (2H, t), 7.01 (1H, s), 6.92 (1H, t), 6.54 (1H, d), 3.40 (2H, s), 3.31 (3H, s), 2.88 (2H, t), 2,50-2.41 (7H, m)

FAB MS(m/e) = 450 [M+1]FAB MS (m / e) = 450 [M + 1]

실시예 63: 1-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-2-메톡시-에타논의 제조Example 63: 1- [4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine-4 Preparation of -ylmethyl) -piperazin-1-yl] -2-methoxy-ethanone

Figure 112006083464511-PAT00055
Figure 112006083464511-PAT00055

실시예 62에서 얻은 화합물 메톡시아세트산과 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 62 was reacted with the method of Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.27 (1H, s), 8.21 (1H, d), 7.61 (1H, d), 7.31 (2H, q), 7.23 (2H, t), 7.08 (1H, s), 6.90 (1H, d), 6.49 (1H, d), 4.04 (2H, s), 3.48 (2H, s), 3.44 (4H, s), 3.37 (3H, s), 3.24 (3H, s), 2.33 (4H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.27 (1H, s), 8.21 (1H, d), 7.61 (1H, d), 7.31 (2H, q), 7.23 (2H, t), 7.08 (1H, s), 6.90 (1H, d), 6.49 (1H, d), 4.04 (2H, s), 3.48 (2H, s), 3.44 (4H, s), 3.37 (3H, s), 3.24 (3H, s), 2.33 (4H, s)

FAB MS(m/e) = 522 [M+1]FAB MS (m / e) = 522 [M + 1]

실시예 64: 시클로프로필-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-메타논의 제조Example 64 cyclopropyl- [4- (2- {5-[(4-fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine- Preparation of 4-ylmethyl) -piperazin-1-yl] -methanone

Figure 112006083464511-PAT00056
Figure 112006083464511-PAT00056

실시예 62에서 얻은 화합물을 시클로프로필카르복실산과 실시예 18의 방법으 로 반응하여 목적 화합물을 얻었다.The compound obtained in Example 62 was reacted with cyclopropylcarboxylic acid by the method of Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.22(1H, d), 7.36(2H, t), 7.24(2H, t), 7.12(1H, s), 6.95(1H, d), 6.51(1H, d), 3.79(2H, bs), 3.40(2H, s), 3.37(2H, bs), 3.30(3H, s), 2.43(2H, bs), 2.36(2H, bs), 1.98-1.94(1H, m), 0.73-0.69(4H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.22 (1H, d), 7.36 (2H, t), 7.24 (2H, t), 7.12 (1H, s), 6.95 (1H, d), 6.51 (1H, d), 3.79 (2H, bs), 3.40 (2H, s), 3.37 (2H, bs), 3.30 (3H, s), 2.43 (2H, bs), 2.36 (2H, bs), 1.98-1.94 (1H, m) , 0.73-0.69 (4H, m)

FAB MS(m/e) = 518 [M+1]FAB MS (m / e) = 518 [M + 1]

실시예 65: 1-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-프로판-1-온의 제조Example 65 1- [4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine-4 Preparation of -ylmethyl) -piperazin-1-yl] -propan-1-one

Figure 112006083464511-PAT00057
Figure 112006083464511-PAT00057

실시예 62에서 얻은 화합물을 프로피온산과 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 62 was reacted with propionic acid by the method of Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 8.25(1H, d), 7.67(1H, d), 7.37(2H, t), 7.26(2H, t), 7.11(1H, s), 6.69(1H, d), 6.51(1H, d), 3.50(2H, s), 3.46(4H, bs), 3.32(3H, s), 2.39(2H, bs), 2,34-2.27(4H, m), 0.97(3H, t) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 8.25 (1H, d), 7.67 (1H, d), 7.37 (2H, t), 7.26 (2H, t), 7.11 (1H, s), 6.69 (1H, d), 6.51 (1H, d), 3.50 (2H, s), 3.46 (4H, bs), 3.32 (3H, s), 2.39 (2H, bs), 2,34-2.27 (4H, m), 0.97 (3H, t)

FAB MS(m/e) = 506 [M+1]FAB MS (m / e) = 506 [M + 1]

제조예 18: NPreparation Example 18 N 22 -(5-클로로메틸-피리딘-2-일)-N-(5-chloromethyl-pyridin-2-yl) -N 55 -(4-플루오로-페닐)-N-(4-fluoro-phenyl) -N 55 -메틸-티아졸로[-Methyl-thiazolo [ 5,4-b]피리딘5,4-b] pyridine -2,5--2,5- 디아민의Diamine 제조 Produce

제조예 7에서 N5-메틸-N5-페닐-티아졸로[5,4-b]피리딘-2,5-디아민 대신 N5-메틸-N5-(4-플루오로-페닐)-티아졸로[5,4-b]피리딘-2,5-디아민을 이용하고, 제조예 6에서 얻어진 화합물 대신 제조예 13에서 얻어진 화합물을 이용하여 제조예 7의 방법으로 반응하여 목적 화합물을 얻었다. In Production Example 7 N 5 - (4-fluoro-phenyl) -N-methyl-5-phenyl-thiazolo [5,4-b] pyridine-2,5-diamine instead of N 5 -methyl -N 5 thiazolo The target compound was obtained by using [5,4-b] pyridine-2,5-diamine and reacting by the method of Preparation Example 7 using the compound obtained in Preparation Example 13 instead of the compound obtained in Preparation Example 6.

1H NMR (DMSO-d6, ppm); δ 8.45 (1H, s). 8.01 (1H, s), 7.85 (1H, d), 7.64 (1H, bs), 7.23 (2H, m), 7.16 (2H, t), 6.52 (1H, d), 4.61 (2H, s), 3.49 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.45 (1 H, s). 8.01 (1H, s), 7.85 (1H, d), 7.64 (1H, bs), 7.23 (2H, m), 7.16 (2H, t), 6.52 (1H, d), 4.61 (2H, s), 3.49 (3H, s)

FAB MS(m/e) = 400 [M+1]FAB MS (m / e) = 400 [M + 1]

실시예 66: NExample 66: N 55 -(4-플루오로-페닐)-N-(4-fluoro-phenyl) -N 55 -메틸-N-Methyl-N 22 -(5-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-(5-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00058
Figure 112006083464511-PAT00058

제조예 18에서 얻은 화합물을 몰포린과 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Production Example 18 was reacted with morpholine in the method of Example 3 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 9.12 (1H, bs), 8.26 (1H, s), 7.57 (1H, d), 7.55 (1H, d), 7.23 (2H, m), 7.09 (2H, t), 6.97 (1H, d), 6.49 (1H, d), 3.69 (4H, t), 3.49 (3H, s), 3.43 (2H, s), 2.45 (4H, s) 1 H NMR (DMSO-d 6 , ppm); δ 9.12 (1H, bs), 8.26 (1H, s), 7.57 (1H, d), 7.55 (1H, d), 7.23 (2H, m), 7.09 (2H, t), 6.97 (1H, d), 6.49 (1H, d), 3.69 (4H, t), 3.49 (3H, s), 3.43 (2H, s), 2.45 (4H, s)

FAB MS(m/e) = 451 [M+1]FAB MS (m / e) = 451 [M + 1]

하기 표 4는 제조예 18에서 얻은 화합물을 이용하여 실시예 66의 방법으로 소정의 목적 화합물들을 합성한 실시예들이다. Table 4 below shows examples of synthesizing desired compounds by the method of Example 66 using the compound obtained in Preparation Example 18.

[표 4]TABLE 4

Figure 112006083464511-PAT00059
Figure 112006083464511-PAT00059

Figure 112006083464511-PAT00060
Figure 112006083464511-PAT00060

제조예 19: NPreparation Example 19 N 22 -(4-클로로메틸-피리딘-2-일)-N-(4-chloromethyl-pyridin-2-yl) -N 55 -(2,4-디플루오로-페닐)-N-(2,4-difluoro-phenyl) -N 55 -메틸-티아졸로[-Methyl-thiazolo [ 5,4-b]피리딘5,4-b] pyridine -2,5--2,5- 디아민의Diamine 제조 Produce

제조예 7에서 N5-메틸-N5-페닐-티아졸로[5,4-b]피리딘-2,5-디아민 대신 N5-메틸-N5-(4-플루오로페닐)-티아졸로[5,4-b]피리딘-2,5-디아민을 이용하여 제조예 7의 방법으로 반응하여 목적 화합물을 얻었다.N 5 in Preparative Example 7-methyl-5 -N-phenyl-thiazolo [5,4-b] pyridine-2,5-diamine instead of N 5 -methyl -N 5 - (4-fluorophenyl) thiazolo [ 5,4-b] pyridine-2,5-diamine was reacted in the same manner as in Preparation Example 7 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 8.35 (1H, d), 7.61 (1H, d), 7.20 (1H, m), 7.20 (1H, s), 7.03 (1H, d), 6.96 (2H, m), 6.39 (1H, d), 4.52 (2H, s), 3.45 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.35 (1H, d), 7.61 (1H, d), 7.20 (1H, m), 7.20 (1H, s), 7.03 (1H, d), 6.96 (2H, m), 6.39 (1H, d), 4.52 (2H, s), 3.45 (3H, s)

FAB MS(m/e) = 418 [M+1]FAB MS (m / e) = 418 [M + 1]

실시예 77: NExample 77: N 55 -(2,4-디플루오로-페닐)-N-(2,4-difluoro-phenyl) -N 55 -메틸-N-Methyl-N 22 -(4-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-(4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00061
Figure 112006083464511-PAT00061

제조예 19에서 얻은 화합물을 몰포린을 이용하여 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 19 was reacted by the method of Example 3 using morpholine to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 9.19 (1H, bs), 8.27 (1H, d), 7.60 (1H, d), 7.31 (1H, m), 6.91 (4H, m), 6.35 (1H, d), 3.69 (4H, t), 3.45 (5H, s), 2.44 (4H, s) 1 H NMR (DMSO-d 6 , ppm); δ 9.19 (1H, bs), 8.27 (1H, d), 7.60 (1H, d), 7.31 (1H, m), 6.91 (4H, m), 6.35 (1H, d), 3.69 (4H, t), 3.45 (5H, s), 2.44 (4H, s)

FAB MS(m/e) = 469 [M+1]FAB MS (m / e) = 469 [M + 1]

실시예 78: NExample 78: N 55 -(2,4-디플루오로-페닐)-N-(2,4-difluoro-phenyl) -N 55 -메틸-N-Methyl-N 22 -[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-[4- (4-Methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00062
Figure 112006083464511-PAT00062

실시예 77에서 몰포린대신 1-메틸피페라진을 이용하여 목적 화합물을 얻었 다. In Example 77, 1-methylpiperazine was used instead of morpholine to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 9.09 (1H, bs), 8.26 (1H, d), 7.60 (1H, d), 7.31 (1H, m), 6.90 (4H, m), 6.36 (1H, d), 3.46 (2H, s), 3.45 (3H, s), 2.61 (4H, s), 2.48 (4H, bs), 2.28 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 9.09 (1H, bs), 8.26 (1H, d), 7.60 (1H, d), 7.31 (1H, m), 6.90 (4H, m), 6.36 (1H, d), 3.46 (2H, s), 3.45 (3H, s), 2.61 (4H, s), 2.48 (4H, bs), 2.28 (3H, s)

FAB MS(m/e) = 482 [M+1]FAB MS (m / e) = 482 [M + 1]

실시예 79: 1-[4-(2-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논의 제조Example 79: 1- [4- (2- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino}- Preparation of Pyridin-4-ylmethyl) -piperazin-1-yl] -ethanone

Figure 112006083464511-PAT00063
Figure 112006083464511-PAT00063

실시예 77에서 몰포린 대신 1-아세틸피페라진을 이용하여 목적 화합물을 얻었다.In Example 77, 1-acetylpiperazine was used instead of morpholine to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 9.09 (1H, bs), 8.28 (1H, d), 7.61 (1H, d), 7.31 (1H, m), 6.93 (3H, m), 6.90 (1H, d), 6.35 (1H, d), 3.61 (2H, t), 3.47 (2H, s), 3.45 (3H, s), 3.42 (2H, t), 2.42 (4H, s), 2.08 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 9.09 (1H, bs), 8.28 (1H, d), 7.61 (1H, d), 7.31 (1H, m), 6.93 (3H, m), 6.90 (1H, d), 6.35 (1H, d), 3.61 (2H, t), 3.47 (2H, s), 3.45 (3H, s), 3.42 (2H, t), 2.42 (4H, s), 2.08 (3H, s)

FAB MS(m/e) = 510 [M+1]FAB MS (m / e) = 510 [M + 1]

실시예 80: 4-(2-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 디메틸아미드의 제조Example 80: 4- (2- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazole [5,4-b] pyridin-2-ylamino} -pyridine-4 Preparation of -ylmethyl) -piperazine-1-carboxylic Acid Dimethylamide

Figure 112006083464511-PAT00064
Figure 112006083464511-PAT00064

실시예 77에서 몰포린 대신 1-(디메틸아미노)카보닐피페라진을 이용하여 목적 화합물을 얻었다.In Example 77, 1- (dimethylamino) carbonylpiperazine was used instead of morpholine to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.27 (1H, s), 8.19 (1H, s), 7.65 (1H, d), 7.49 (1H, q), 7.39 (1H, t), 7.16 (1H, t), 7.08 (1H, s), 6.89 (1H, d), 6.39 (1H, d), 3.46 (2H, s), 3.10 (4H, s), 2.69 (6H, s), 2.51 (3H, s), 2.36 (4H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.27 (1H, s), 8.19 (1H, s), 7.65 (1H, d), 7.49 (1H, q), 7.39 (1H, t), 7.16 (1H, t), 7.08 (1H, s), 6.89 (1H, d), 6.39 (1H, d), 3.46 (2H, s), 3.10 (4H, s), 2.69 (6H, s), 2.51 (3H, s), 2.36 (4H, s)

FAB MS(m/e) = 539 [M+1]FAB MS (m / e) = 539 [M + 1]

제조예 20: NPreparation Example 20 N 22 -(5-클로로메틸-피리딘-2-일)-N-(5-chloromethyl-pyridin-2-yl) -N 55 -(2,4-디플루오로-페닐)-N-(2,4-difluoro-phenyl) -N 55 -메틸-티아졸로[-Methyl-thiazolo [ 5,4-b]피리딘5,4-b] pyridine -2,5--2,5- 디아민의Diamine 제조 Produce

제조예 7에서 N5-메틸-N5-페닐-티아졸로[5,4-b]피리딘-2,5-디아민 대신 N5-메틸-N5-(2,4-디플루오로-페닐)-티아졸로[5,4-b]피리딘-2,5-디아민을 이용하고, 제조예 6에서 얻어진 화합물 대신 제조예 13에서 얻어진 화합물을 이용하여 제조예 7의 방법으로 반응하여 목적 화합물을 얻었다. N 5 in Preparative Example 7-methyl-5 -N-phenyl-thiazolo [5,4-b] pyridine-2,5-diamine instead of N 5 -methyl -N 5 - (2,4-difluoro-phenyl) Using the thiazolo [5,4-b] pyridine-2,5-diamine and the compound obtained in Preparation Example 13 instead of the compound obtained in Preparation Example 6, the reaction was carried out in the same manner as in Preparation Example 7 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 8.38 (1H, s), 7.73 (1H, d), 7.59 (1H, d), 7.29 (1H, m), 7.17 (1H, d), 6.95 (2H, m), 6.39 (1H, d), 4.59 (2H, s), 3.45 (3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.38 (1H, s), 7.73 (1H, d), 7.59 (1H, d), 7.29 (1H, m), 7.17 (1H, d), 6.95 (2H, m), 6.39 (1H, d), 4.59 (2H, s), 3.45 (3H, s)

FAB MS(m/e) = 418 [M+1]FAB MS (m / e) = 418 [M + 1]

실시예 81: NExample 81: N 55 -(2,4-디플루오로-페닐)-N-(2,4-difluoro-phenyl) -N 55 -메틸-N-Methyl-N 22 -(5-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-(5-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00065
Figure 112006083464511-PAT00065

제조예 20에서 얻어진 화합물과 몰포린을 이용하여 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained by reacting the compound obtained in Production Example 20 with morpholine by the method of Example 3.

1H NMR (DMSO-d6, ppm); δ 9.18 (1H, bs), 8.26 (1H, s), 7.59 (2H, t), 7.30 (1H, m), 6.94 (3H, t), 6.36 (1H, d), 3.70 (4H, s), 3.45 (5H, s), 2.45 (4H, s) 1 H NMR (DMSO-d 6 , ppm); δ 9.18 (1H, bs), 8.26 (1H, s), 7.59 (2H, t), 7.30 (1H, m), 6.94 (3H, t), 6.36 (1H, d), 3.70 (4H, s), 3.45 (5H, s), 2.45 (4H, s)

FAB MS(m/e) = 469 [M+1]FAB MS (m / e) = 469 [M + 1]

하기 표 5는 제조예 20에서 얻어진 화합물을 이용하여 실시예 81의 방법으로 소정의 목적 화합물들을 합성한 실시예들이다. Table 5 below shows examples of synthesizing desired compounds by the method of Example 81 using the compound obtained in Preparation Example 20.

[표 5]TABLE 5

Figure 112006083464511-PAT00066
Figure 112006083464511-PAT00066

Figure 112006083464511-PAT00067
Figure 112006083464511-PAT00067

실시예 93: 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페리딘-4-카르복실산의 제조Example 93: 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine-3 Preparation of -ylmethyl) -piperidine-4-carboxylic acid

Figure 112006083464511-PAT00068
Figure 112006083464511-PAT00068

실시예 92에서 얻은 화합물을 실시예 17의 방법으로 가수분해하여 목적 화합물을 얻었다. The compound obtained in Example 92 was hydrolyzed by the method of Example 17 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 8.02 (1H, bs), 7.44 (3H, bs), 7.24 (1H, bs), 7.07 (1H, bs), 6.92 (1H, bs), 6.30 (1H, bs), 3.27 (9H, bs), 2.69 (2H, bs), 1.83 (2H, t), 1.47 (2H, bs) 1 H NMR (DMSO-d 6 , ppm); δ 8.02 (1H, bs), 7.44 (3H, bs), 7.24 (1H, bs), 7.07 (1H, bs), 6.92 (1H, bs), 6.30 (1H, bs), 3.27 (9H, bs), 2.69 (2H, bs), 1.83 (2H, t), 1.47 (2H, bs)

FAB MS(m/e) = 511 [M+1]FAB MS (m / e) = 511 [M + 1]

실시예 94: 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피롤리딘-2-카르복실산의 제조Example 94: 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine-3 Preparation of -ylmethyl) -pyrrolidine-2-carboxylic acid

Figure 112006083464511-PAT00069
Figure 112006083464511-PAT00069

실시예 89에서 얻은 화합물을 실시예 17의 방법으로 가수분해하여 목적 화합물을 얻었다.The compound obtained in Example 89 was hydrolyzed by the method of Example 17 to obtain the target compound.

1H NMR (CDCl3, ppm); δ 8.56(1H, s), 8.24(1H, s), 7.66(1H, d), 7.58(1H, d), 7.32-7.28(2H, m), 6.94-6.91(3H, m), 6.37(1H, d), 3.83(1H, d), 3.52(1H, d), 3.45(3H, s), 3.25(1H, t), 3.07-3.04(1H, m), 2.41-2.39(1H, m), 2.19-2.15(1H, m), 1.98-1.82(2H, m) 1 H NMR (CDCl 3 , ppm); δ 8.56 (1H, s), 8.24 (1H, s), 7.66 (1H, d), 7.58 (1H, d), 7.32-7.28 (2H, m), 6.94-6.91 (3H, m), 6.37 (1H) , d), 3.83 (1H, d), 3.52 (1H, d), 3.45 (3H, s), 3.25 (1H, t), 3.07-3.04 (1H, m), 2.41-2.39 (1H, m), 2.19-2.15 (1H, m), 1.98-1.82 (2H, m)

FAB MS(m/e) = 497 [M+1]FAB MS (m / e) = 497 [M + 1]

제조예 21: 4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일Preparation 21: 4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-yl 아미army 노}-피리딘-3-No} -pyridine-3- 일메틸Methyl )-피페라진-1-) -Piperazine-1- 카르복실산Carboxylic acid terttert -부틸 에스테르의 Of butyl ester 제조Produce

제조예 20에서 얻은 화합물과 N-부톡시카보닐피페라진을 이용하여 실시예 81의 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained by reacting the compound obtained in Preparation Example 20 with N-butoxycarbonylpiperazine by the method of Example 81.

1H NMR (DMSO-d6, ppm); δ 8.24 (1H, s), 7.59 (2H, d), 7.30 (1H, q), 6.93 (3H, m), 6.33 (1H, d), 3.45 (5H, s), 2.87 (4H, s), 2.41(4H, s), 1.54(9H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.24 (1H, s), 7.59 (2H, d), 7.30 (1H, q), 6.93 (3H, m), 6.33 (1H, d), 3.45 (5H, s), 2.87 (4H, s), 2.41 (4H, s), 1.54 (9H, s)

FAB MS(m/e) = 568 [M+1]FAB MS (m / e) = 568 [M + 1]

실시예 95: NExample 95: N 55 -(2,4-디플루오로-페닐)-N-(2,4-difluoro-phenyl) -N 55 -메틸-N-Methyl-N 22 -(5-피페라진-1-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-(5-piperazin-1-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00070
Figure 112006083464511-PAT00070

제조예 21에서 얻은 화합물 400 mg(0.705 mmol)을 실시예 62의 방법으로 반 응하여 목적 화합물 306 mg(0.656 mmol, 수율; 93%)을 얻었다. 400 mg (0.705 mmol) of the compound obtained in Preparation Example 21 were reacted by the method of Example 62, to obtain 306 mg (0.656 mmol, yield; 93%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 8.25 (1H, s), 7.59 (2H, d), 7.31 (1H, q), 6.94 (3H, m), 6.35 (1H, d), 3.45 (5H, s), 2.87 (4H, s), 2.41(4H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.25 (1H, s), 7.59 (2H, d), 7.31 (1H, q), 6.94 (3H, m), 6.35 (1H, d), 3.45 (5H, s), 2.87 (4H, s), 2.41 (4H, s)

FAB MS(m/e) = 468 [M+1]FAB MS (m / e) = 468 [M + 1]

제조예 22: 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-니코틴산 Preparation Example 22 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -nicotinic acid 메틸methyl 에스테르의 제조 Preparation of ester

N5-메틸-N5-(2,4-디플루오로페닐)-티아졸로[5,4-b]피리딘-2,5-디아민을 메틸 6-클로로니코티네이트와 실시예 1의 방법으로 반응하여 목적 화합물을 얻었다. N 5 -Methyl-N 5- (2,4-difluorophenyl) -thiazolo [5,4-b] pyridine-2,5-diamine by the method of Example 1 with methyl 6-chloronicotinate Reaction gave the target compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 7.83(1H, d), 7.78(1H, d), 7.56-7.53(1H, m), 7.45-7.40(1H, m), 7.21-7.17(2H, m), 6.45(1H, d), 3.67(3H, s), 3.32(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 7.83 (1H, d), 7.78 (1H, d), 7.56-7.53 (1H, m), 7.45-7.40 (1H, m), 7.21-7.17 (2H, m), 6.45 (1H, d), 3.67 (3H, s), 3.32 (3H, s)

FAB MS(m/e) = 428 [M+1]FAB MS (m / e) = 428 [M + 1]

제조예 23: 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-니코틴산의 제조Preparation Example 23 Preparation of 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -nicotinic acid

제조예 22에서 얻은 화합물을 실시예 17의 방법으로 가수분해하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 22 was hydrolyzed by the method of Example 17 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 7.83(1H, d), 7.78(1H, d), 7.56-7.53(1H, m), 7.45-7.40(1H, m), 7.21-7.17(2H, m), 6.45(1H, d), 3.32(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 7.83 (1H, d), 7.78 (1H, d), 7.56-7.53 (1H, m), 7.45-7.40 (1H, m), 7.21-7.17 (2H, m), 6.45 (1H, d), 3.32 (3H, s)

FAB MS(m/e) = 414 [M+1]FAB MS (m / e) = 414 [M + 1]

실시예 96: (6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-몰포린-4-일-메타논의 제조Example 96: (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Preparation of) -morpholin-4-yl-methanone

Figure 112006083464511-PAT00071
Figure 112006083464511-PAT00071

제조예 23에서 얻은 화합물과 몰포린을 이용하여 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained by reacting the compound obtained in Preparation Example 23 with the method of Example 18 using morpholine.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.40(1H, d), 7.84(1H, d), 7.77(1H, d), 7.56-7.53(1H, m), 7.45-7.40(1H, m), 7.21-7.17(2H, m), 6.47(1H, d), 3.63(4H, bs), 3.32(3H, s), 3.25(4H, bs) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.40 (1H, d), 7.84 (1H, d), 7.77 (1H, d), 7.56-7.53 (1H, m), 7.45-7.40 (1H, m), 7.21-7.17 (2H, m), 6.47 (1H, d), 3.63 (4H, bs), 3.32 (3H, s), 3.25 (4H, bs)

FAB MS(m/e) = 483 [M+1]FAB MS (m / e) = 483 [M + 1]

하기 표 6은 제조예 23에서 얻은 화합물을 이용하여 실시예 96의 방법으로 소정의 목적 화합물들을 합성한 실시예들이다. Table 6 below shows examples of synthesizing desired compounds by the method of Example 96 using the compound obtained in Preparation Example 23.

[표 6]TABLE 6

Figure 112006083464511-PAT00072
Figure 112006083464511-PAT00072

Figure 112006083464511-PAT00073
Figure 112006083464511-PAT00073

실시예 106: 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-피페리딘-4-일-니코틴아미드의 제조Example 106 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N-piperidine- Preparation of 4-yl-nicotinamide

Figure 112006083464511-PAT00074
Figure 112006083464511-PAT00074

실시예 104에서 얻은 화합물을 실시예 62의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 104 was reacted by the method of Example 62 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.08(1H, s), 8.31(1H, d), 8.14(1H, d), 7.74(2H, d), 7.56-7.53(1H, m), 7.45-7.41(1H, m), 7.23-7.16(2H, m), 6.47(1H, d), 3.82-3.79(2H, m), 3.31(3H, s), 2.83(2H, d), 2.03(2H, t), 1.81-1.78(2H, m), 1.64-1.56(2H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.08 (1H, s), 8.31 (1H, d), 8.14 (1H, d), 7.74 (2H, d), 7.56-7.53 (1H, m), 7.45-7.41 (1H , m), 7.23-7.16 (2H, m), 6.47 (1H, d), 3.82-3.79 (2H, m), 3.31 (3H, s), 2.83 (2H, d), 2.03 (2H, t), 1.81-1.78 (2H, m), 1.64-1.56 (2H, m)

FAB MS(m/e) = 496 [M+1]FAB MS (m / e) = 496 [M + 1]

실시예 107: (4-아미노-피페리딘-1-일)-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-메타논의 제조Example 107: (4-Amino-piperidin-1-yl)-(6- {5-[(2,4-difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b ] Preparation of Pyridin-2-ylamino} -pyridin-3-yl) -methanone

Figure 112006083464511-PAT00075
Figure 112006083464511-PAT00075

실시예 105에서 얻은 화합물을 실시예 62의 방법으로 반응하여 목적 화합물을 얻었다.The compound obtained in Example 105 was reacted by the method of Example 62 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.30(1H, s), 8.37(1H, s), 7.81(1H, d), 7.72(1H, d), 7.57-7.53(1H, m), 7.46-7.43(1H, m), 7.23-7.19(2H, m), 6.43(1H, d), 3.81-3.82(1H, m), 3.32(3H, s), 2.98-2.85(4H, m), 1.82-1.80(2H, m), 1.46-1.39(2H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.30 (1H, s), 8.37 (1H, s), 7.81 (1H, d), 7.72 (1H, d), 7.57-7.53 (1H, m), 7.46-7.43 (1H, m), 7.23-7.19 (2H, m), 6.43 (1H, d), 3.81-3.82 (1H, m), 3.32 (3H, s), 2.98-2.85 (4H, m), 1.82-1.80 (2H, m), 1.46-1.39 (2H, m)

FAB MS(m/e) = 496 [M+1]FAB MS (m / e) = 496 [M + 1]

실시예 108: 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-(1-메틸-피페리딘-4-일)-니코틴아미드의 제조Example 108: 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N- (1-methyl Preparation of -piperidin-4-yl) -nicotinamide

Figure 112006083464511-PAT00076
Figure 112006083464511-PAT00076

실시예 106에서 얻은 화합물 25 mg(0.050 mmol)을 메탄올 1 ml와 N,N-디메틸포름아미드 2 ml에 녹인 후 포르말린 0.019 ml(0.25 mmol)과 소듐트리아세톡시보로하이드라이드 53 mg(0.25 mmol)을 가하고 상온에서 1 시간 교반하였다. 반응완결 후 농축하고, 물 10 ml를 가하고 에틸 아세테이트로 20 ml씩 두 번 추출하여 다시 농축한 후, 관크로마토그래피로 분리하여 목적 화합물 20 mg(0.039 mmol, 수율; 79%)을 얻었다. 25 mg (0.050 mmol) of the compound obtained in Example 106 was dissolved in 1 ml of methanol and 2 ml of N, N-dimethylformamide, followed by 0.019 ml (0.25 mmol) of formalin and 53 mg (0.25 mmol) of sodium triacetoxyborohydride. Was added and stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture was concentrated, 10 ml of water was added, 20 ml of ethyl acetate was extracted twice, and concentrated again, and then separated by column chromatography to obtain 20 mg (0.039 mmol, yield; 79%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 8.80(1H, s), 8.32(1H, d), 8.15(1H, d), 7.77(1H, d), 7.57-7.51(1H, m), 7.45-7.40(1H, m), 7.23-7.16(2H, m), 6.47(1H, d), 3.19-3.14(1H, m), 2.83(2H, d), 2.21(3H, s), 2.01(2H, t), 1.81-1.56(4H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 8.80 (1H, s), 8.32 (1H, d), 8.15 (1H, d), 7.77 (1H, d), 7.57-7.51 (1H, m), 7.45-7.40 (1H , m), 7.23-7.16 (2H, m), 6.47 (1H, d), 3.19-3.14 (1H, m), 2.83 (2H, d), 2.21 (3H, s), 2.01 (2H, t), 1.81-1.56 (4H, m)

FAB MS(m/e) = 510 [M+1]FAB MS (m / e) = 510 [M + 1]

실시예 109: (6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-(4-디메틸아미노-피페리딘-1-일)-메타논의 제조Example 109: (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Preparation of)-(4-dimethylamino-piperidin-1-yl) -methanone

Figure 112006083464511-PAT00077
Figure 112006083464511-PAT00077

실시예 107에서 얻은 화합물을 실시예 108의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 107 was reacted by the method of Example 108 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 8.38(1H, s), 7.82(1H, d), 7.73(1H, d), 7.57-7.53(1H, m), 7.46-7.43(1H, m), 7.23-7.19(2H, m), 6.45(1H, d), 3.81-3.82(1H, m), 3.32(3H, s), 2.98-2.85(4H, m), 2.27(6H, s), 1.82-1.80(2H, m), 1.46-1.39(2H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 8.38 (1H, s), 7.82 (1H, d), 7.73 (1H, d), 7.57-7.53 (1H, m), 7.46-7.43 (1H, m), 7.23-7.19 (2H, m), 6.45 (1H, d), 3.81-3.82 (1H, m), 3.32 (3H, s), 2.98-2.85 (4H, m), 2.27 (6H, s), 1.82-1.80 (2H , m), 1.46-1.39 (2H, m)

FAB MS(m/e) = 524 [M+1]FAB MS (m / e) = 524 [M + 1]

제조예 24: NPreparation Example 24 N 55 -(4-클로로-2-플루오로-페닐)-N-(4-chloro-2-fluoro-phenyl) -N 22 -(4-클로로메틸-피리딘-2-일)-N-(4-chloromethyl-pyridin-2-yl) -N 55 -메틸-티-Methyl-tee 아졸로[5,4-b]피리딘Azolo [5,4-b] pyridine -2,5--2,5- 디아민의Diamine 제조 Produce

제조예 7에서 N5-메틸-N5-페닐-티아졸로[5,4-b]피리딘-2,5-디아민대신 N5-메틸-N5-(4-클로로-2-플루오로)페닐-티아졸로[5,4-b]피리딘-2,5-디아민을 이용하여 제조예 7의 방법으로 반응하여 목적 화합물을 얻었다.N 5 -methyl-N 5 -phenyl-thiazolo [5,4-b] pyridine-2,5-diamine in Preparation Example 7 instead of N 5 -methyl-N 5- (4-chloro-2-fluoro) phenyl -Tiazolo [5,4-b] pyridine-2,5-diamine was reacted by the method of Preparation Example 7 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.26(1H, s), 8.24(1H, d), 7.73(1H, d), 7.54- 7.46(2H, m), 7.35(1H, d), 7.10(1H, s), 6.94(1H, d), 6.54(1H, d), 3.53(2H, s), 3.37(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.26 (1H, s), 8.24 (1H, d), 7.73 (1H, d), 7.54- 7.46 (2H, m), 7.35 (1H, d), 7.10 (1H, s), 6.94 (1H, d ), 6.54 (1H, d), 3.53 (2H, s), 3.37 (3H, s)

FAB MS(m/e) = 434 [M+1]FAB MS (m / e) = 434 [M + 1]

실시예 110: NExample 110: N 55 -(4-클로로-2-플루오로-페닐)-N-(4-chloro-2-fluoro-phenyl) -N 55 -메틸-N-Methyl-N 22 -(4-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-(4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00078
Figure 112006083464511-PAT00078

제조예 24에서 얻어진 화합물을 몰포린과 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Production Example 24 was reacted with morpholine in the method of Example 3 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.25(1H, d), 7.74(1H, d), 7.60(1H, d), 7.52(1H, t), 7.38(1H, d), 7.13(1H, s), 6.96(1H, d), 6.55(1H, d), 3.62(4H, bs), 3.49(2H, s), 3.31(3H, s), 2.40(4H, bs) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.25 (1H, d), 7.74 (1H, d), 7.60 (1H, d), 7.52 (1H, t), 7.38 (1H, d), 7.13 (1H, s), 6.96 (1H, d), 6.55 (1H, d), 3.62 (4H, bs), 3.49 (2H, s), 3.31 (3H, s), 2.40 (4H, bs)

FAB MS(m/e) = 485 [M+1]FAB MS (m / e) = 485 [M + 1]

실시예 111: NExample 111 N 55 -(4-클로로-2-플루오로-페닐)-N-(4-chloro-2-fluoro-phenyl) -N 55 -메틸-N-Methyl-N 22 -[4-(4-메틸-피레라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-[4- (4-Methyl-pyrerazin-1-ylmethyl) -pyridin-2-yl] -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00079
Figure 112006083464511-PAT00079

제조예 24에서 얻어진 화합물을 1-메틸피페라진과 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다.The compound obtained in Production Example 24 was reacted with 1-methylpiperazine in the method of Example 3 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 8.24(1H, d), 7.74(1H, d), 7.60(1H, d), 7.52(1H, t), 7.38(1H, d), 7.13(1H, s), 6.96(1H, d), 6.55(1H, d), 3.50(2H, s), 3.42(4H, bs), 3.37(3H, s), 2.45(4H, bs), 2.19(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 8.24 (1H, d), 7.74 (1H, d), 7.60 (1H, d), 7.52 (1H, t), 7.38 (1H, d), 7.13 (1H, s), 6.96 (1H, d), 6.55 (1H, d), 3.50 (2H, s), 3.42 (4H, bs), 3.37 (3H, s), 2.45 (4H, bs), 2.19 (3H, s)

FAB MS(m/e) = 498 [M+1]FAB MS (m / e) = 498 [M + 1]

실시예 112: 1-[4-(2-{5-[(4-클로로-2-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논의 제조Example 112: 1- [4- (2- {5-[(4-Chloro-2-fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} Preparation of Pyridin-4-ylmethyl) -piperazin-1-yl] -ethanone

Figure 112006083464511-PAT00080
Figure 112006083464511-PAT00080

제조예 24에서 얻어진 화합물을 1-아테틸피페라진과 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다.The compound obtained in Production Example 24 was reacted with 1-tetylpiperazine with the method of Example 3 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.27(1H, s), 8.25(1H, d), 7.74(1H, d), 7.54- 7.46(2H, m), 7.36(1H, d), 7.11(1H, s), 6.95(1H, d), 6.54(1H, d), 3.51(2H, s), 3.46(4H, bs), 3.37(3H, s), 2.40(2H, bs), 2.34(2H, bs), 2.00(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.27 (1H, s), 8.25 (1H, d), 7.74 (1H, d), 7.54- 7.46 (2H, m), 7.36 (1H, d), 7.11 (1H, s), 6.95 (1H, d ), 6.54 (1H, d), 3.51 (2H, s), 3.46 (4H, bs), 3.37 (3H, s), 2.40 (2H, bs), 2.34 (2H, bs), 2.00 (3H, s)

FAB MS(m/e) = 526 [M+1]FAB MS (m / e) = 526 [M + 1]

제조예 25: NPreparation Example 25 N 22 -(4-클로로메틸-피리딘-2-일)-N-(4-chloromethyl-pyridin-2-yl) -N 55 -(4-클로로-페닐)-N-(4-chloro-phenyl) -N 55 -메틸-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of -methyl-thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00081
Figure 112006083464511-PAT00081

제조예 7에서 N5-메틸-N5-페닐-티아졸로[5,4-b]피리딘-2,5-디아민 대신 N5-메틸-N5-(4-클로로페닐)-티아졸로[5,4-b]피리딘-2,5-디아민을 이용하여 제조예 7의 방법으로 반응하여 목적 화합물을 얻었다.In Production Example 7 N 5-methyl-5 -N-phenyl-thiazolo [5,4-b] pyridine-2,5-diamine instead of N 5 - methyl -N 5 - (4- chlorophenyl) thiazolo [5, , 4-b] pyridine-2,5-diamine was reacted by the method of Preparation Example 7 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.21(1H, d), 7.72(1H, d), 7.44(2H, d), 7.32(2H, d), 7.11(1H, s), 6.94(1H, d), 6.72(1H, d), 3.51(2H, s), 3.31(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.21 (1H, d), 7.72 (1H, d), 7.44 (2H, d), 7.32 (2H, d), 7.11 (1H, s), 6.94 (1H, d), 6.72 (1H, d), 3.51 (2H, s), 3.31 (3H, s)

FAB MS(m/e) = 416 [M+1]FAB MS (m / e) = 416 [M + 1]

실시예 113: NExample 113: N 55 -(4-클로로페닐)-N-(4-chlorophenyl) -N 55 -메틸-N-Methyl-N 22 -(4-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-(4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00082
Figure 112006083464511-PAT00082

제조예 25에서 얻은 화합물을 몰포린과 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 25 was reacted with morpholine in the method of Example 3 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 8.26(1H, d), 7.72(1H, d), 7.46(2H, d), 7.34(2H, d), 7.12(1H, s), 6.95(1H, d), 6.74(1H, d), 3.51(2H, s), 3.40(3H, s), 3.29(4H, bs), 2.61(4H, bs) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 8.26 (1H, d), 7.72 (1H, d), 7.46 (2H, d), 7.34 (2H, d), 7.12 (1H, s), 6.95 (1H, d), 6.74 (1H, d), 3.51 (2H, s), 3.40 (3H, s), 3.29 (4H, bs), 2.61 (4H, bs)

FAB MS(m/e) = 467 [M+1]FAB MS (m / e) = 467 [M + 1]

실시예 114: NExample 114: N 55 -(4-클로로-페닐)-N-(4-chloro-phenyl) -N 55 -메틸-N-Methyl-N 22 -[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민의 제조Preparation of-[4- (4-Methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00083
Figure 112006083464511-PAT00083

제조예 25에서 얻은 화합물을 1-메틸피페라진과 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Production Example 25 was reacted with 1-methylpiperazine in the method of Example 3 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.26(1H, d), 7.73(1H, d), 7.46(2H, d), 7.34(2H, d), 7.14(1H, s), 6.97(1H, d), 6.74(1H, d), 3.63(4H, bs), 3.42(2H, s), 3.31(3H, s), 2.62(3H, s), 2.41(4H, bs) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.26 (1H, d), 7.73 (1H, d), 7.46 (2H, d), 7.34 (2H, d), 7.14 (1H, s), 6.97 (1H, d), 6.74 (1H, d), 3.63 (4H, bs), 3.42 (2H, s), 3.31 (3H, s), 2.62 (3H, s), 2.41 (4H, bs)

FAB MS(m/e) = 480 [M+1]FAB MS (m / e) = 480 [M + 1]

실시예 115: 1-[4-(2-{5-[(4-클로로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논의 제조Example 115: 1- [4- (2- {5-[(4-Chloro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine-4- Preparation of Ilmethyl) -piperazin-1-yl] -ethanone

Figure 112006083464511-PAT00084
Figure 112006083464511-PAT00084

제조예 25에서 얻은 화합물을 1-아세틸피페라진과 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Production Example 25 was reacted with 1-acetylpiperazine in the method of Example 3 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.35(1H, s), 8.21(1H, d), 7.73(1H, d), 7.43(2H, d), 7.34(2H, d), 7.13(1H, s), 6.96(1H, d), 6.72(1H, d), 3.52(2H, s), 3.50-3.46(4H, m), 3.31(3H, s), 2.42(2H, bs), 2.35(2H, bs), 2.05(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.35 (1H, s), 8.21 (1H, d), 7.73 (1H, d), 7.43 (2H, d), 7.34 (2H, d), 7.13 (1H, s), 6.96 (1H, d), 6.72 (1H, d), 3.52 (2H, s), 3.50-3.46 (4H, m), 3.31 (3H, s), 2.42 (2H, bs), 2.35 (2H, bs), 2.05 (3H, s)

FAB MS(m/e) = 508 [M+1]FAB MS (m / e) = 508 [M + 1]

실시예 116: 4-(2-{5-[(4-클로로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 디메틸아미드의 제조Example 116 4- (2- {5-[(4-Chloro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl) Preparation of Piperazine-1-carboxylic Acid Dimethylamide

Figure 112006083464511-PAT00085
Figure 112006083464511-PAT00085

제조예 25에서 얻은 화합물을 1-(디아틸아미노카보닐)페페라진과 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Production Example 25 was reacted with 1- (dithylaminocarbonyl) perazine with the method of Example 3 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.22(1H, d), 7.72(1H, d), 7.43(2H, d), 7.32(2H, d), 7.11(1H, s), 6.94(1H, d), 6.72(1H, d), 3.52(2H, s), 3.50-3.46(4H, m), 3.32(3H, s), 2.65(6H, s), 2.41(2H, bs), 2.32(2H, bs) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.22 (1H, d), 7.72 (1H, d), 7.43 (2H, d), 7.32 (2H, d), 7.11 (1H, s), 6.94 (1H, d), 6.72 (1H, d), 3.52 (2H, s), 3.50-3.46 (4H, m), 3.32 (3H, s), 2.65 (6H, s), 2.41 (2H, bs), 2.32 (2H, bs)

FAB MS(m/e) = 537 [M+1]FAB MS (m / e) = 537 [M + 1]

제조예 26: NPreparation Example 26 N 22 -(4-클로로메틸-피리딘-2-일)-N-(4-chloromethyl-pyridin-2-yl) -N 55 -(3,4-디플루오로-페닐)-N-(3,4-difluoro-phenyl) -N 55 -메틸-티아졸로[-Methyl-thiazolo [ 5,4-b]피리딘5,4-b] pyridine -2,5--2,5- 디아민의Diamine 제조 Produce

제조예 7에서 N5-페닐-N5-메틸-티아졸[5,4-b]피리딘-2,5-디아민 대신 N5-(3,4-디플루오로페닐)-N5-메틸-티아졸[5,4-b]피리딘-2,5-디아민을 이용하여 제조예 7의 방법으로 반응하여 목적 화합물을 얻었다.Phenyl -N 5 --methyl-thiazol [5,4-b] pyridine-2,5-diamine instead of N 5 - (3,4- difluorophenyl) -N 5 - N-methyl-5 in Preparative Example 7 It reacted by the method of manufacture example 7 using thiazole [5, 4-b] pyridine-2, 5- diamine, and obtained the target compound.

1H NMR (DMSO-d6, ppm); δ 11.33(1H, s), 8.21(1H, s), 7.68(1H, d), 7.42-7.38(2H, m), 7.12-7.09(2H, m), 6.91(1H, d), 6.61(1H, d), 3.53(2H, s), 3.42(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.33 (1H, s), 8.21 (1H, s), 7.68 (1H, d), 7.42-7.38 (2H, m), 7.12-7.09 (2H, m), 6.91 (1H, d), 6.61 (1H , d), 3.53 (2H, s), 3.42 (3H, s)

FAB MS(m/e) = 418 [M+1]FAB MS (m / e) = 418 [M + 1]

실시예 117: 1-[4-(2-{5-[(3,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논의 제조Example 117: 1- [4- (2- {5-[(3,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino}- Preparation of Pyridin-4-ylmethyl) -piperazin-1-yl] -ethanone

Figure 112006083464511-PAT00086
Figure 112006083464511-PAT00086

제조예 26에서 얻은 화합물을 1-아세틸페레라진과 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Production Example 26 was reacted with 1-acetylferrazine in the method of Example 3 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.33(1H, s), 8.22(1H, s), 7.69(1H, d), 7.42-7.38(2H, m), 7.12-7.09(2H, m), 6.90(1H, d), 6.69(1H, d), 3.48(2H, s), 3.42(3H, s), 3.29(4H, bs), 2.37(2H, bs), 2.30(2H, bs), 1.95(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.33 (1H, s), 8.22 (1H, s), 7.69 (1H, d), 7.42-7.38 (2H, m), 7.12-7.09 (2H, m), 6.90 (1H, d), 6.69 (1H , d), 3.48 (2H, s), 3.42 (3H, s), 3.29 (4H, bs), 2.37 (2H, bs), 2.30 (2H, bs), 1.95 (3H, s)

FAB MS(m/e) = 510 [M+1]FAB MS (m / e) = 510 [M + 1]

실시예 118: 6-{5-[(3,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-니코틴산 메틸 에스테르의 제조Example 118: Preparation of 6- {5-[(3,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -nicotinic acid methyl ester

Figure 112006083464511-PAT00087
Figure 112006083464511-PAT00087

N5-(3,4-디플루오로페닐)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민과 메틸 6-클로로니코티네이트를 이용하여 실시예 1의 방법으로 반응하여 목적 화합물을 얻었다. Example 1 using N 5- (3,4-difluorophenyl) -N 5 -methyl-thiazolo [5,4-b] pyridine-2,5-diamine and methyl 6-chloronicotinate Reaction was carried out to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 8.21(1H, s), 7.68(1H, d), 7.42-7.38(2H, m), 7.12-7.09(2H, m), 6.90(1H, d), 6.69(1H, d), 3.67(3H, s), 3.35(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 8.21 (1H, s), 7.68 (1H, d), 7.42-7.38 (2H, m), 7.12-7.09 (2H, m), 6.90 (1H, d), 6.69 (1H , d), 3.67 (3H, s), 3.35 (3H, s)

FAB MS(m/e) = 428 [M+1]FAB MS (m / e) = 428 [M + 1]

제조예 27: NPreparation Example 27 N 22 -(6-클로로-피리미딘-4-일)-N-(6-chloro-pyrimidin-4-yl) -N 55 -(2,4-디플루오로-페닐)-N-(2,4-difluoro-phenyl) -N 55 -메틸-티아졸로-[5,4-b]피리딘-2,5--Methyl-thiazolo- [5,4-b] pyridine-2,5- 디아민의Diamine 제조 Produce

N5-(2,4-디플루오로페닐)-N5-메틸-티아졸[5,4-b]피리딘-2,5-디아민과 4,6-디클로로피리미딘을 이용하여 실시예 1의 방법으로 반응하여 목적 화합물을 얻었다. Example 1 using N 5- (2,4-difluorophenyl) -N 5 -methyl-thiazole [5,4-b] pyridine-2,5-diamine and 4,6-dichloropyrimidine Reaction was carried out to obtain the target compound.

1H NMR (CDCl3, ppm); δ 10.4 (1H, bs), 8.41 (1H, s), 7.63 (1H, d), 7.31 (1H, m), 6.99 (2H, m), 6.34 (1H, d), 6.17 (1H, s), 3.45 (3H, s) 1 H NMR (CDCl 3 , ppm); δ 10.4 (1H, bs), 8.41 (1H, s), 7.63 (1H, d), 7.31 (1H, m), 6.99 (2H, m), 6.34 (1H, d), 6.17 (1H, s), 3.45 (3H, s)

FAB MS(m/e) = 405 [M+1]FAB MS (m / e) = 405 [M + 1]

실시예 119: [4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일)-피페라진-1-일]-아세트산 에틸 에스테르의 제조Example 119: [4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyrimidine Preparation of -4-yl) -piperazin-1-yl] -acetic acid ethyl ester

Figure 112006083464511-PAT00088
Figure 112006083464511-PAT00088

제조예 27에서 얻은 화합물 80 mg(0.198 mmol)을 1,4-디옥산 5 ml에 녹인 후 1-(에톡시카보닐메틸)피페라진 170 mg(0.990 mmol)을 가하고 4 시간 동안 환류 교반하였다. 반응완결 후 물 50 ml를 가하여 생긴 고체를 여과하고 건조하여 목적 화합물 98 mg(0.182 mmol, 수율; 92%)을 얻었다. 80 mg (0.198 mmol) of the compound obtained in Preparation Example 27 was dissolved in 5 ml of 1,4-dioxane, and 170 mg (0.990 mmol) of 1- (ethoxycarbonylmethyl) piperazine was added thereto, followed by stirring at reflux for 4 hours. After completion of the reaction, 50 ml of water was added to the resulting solid, which was filtered and dried to obtain 98 mg (0.182 mmol, yield; 92%) of the title compound.

1H NMR (CDCl3, ppm); δ10.4 (1H, bs), 8.42 (1H, s), 7.64 (1H, d), 7.30 (1H, m), 6.99 (2H, m), 6.34 (1H, d), 6.17 (1H, s), 4.20 (2H, m), 3.60 (4H, m), 3.45 (3H, s), 3.23 (2H, s), 2.60 (6H, m), 1.27 (3H, m) 1 H NMR (CDCl 3 , ppm); δ10.4 (1H, bs), 8.42 (1H, s), 7.64 (1H, d), 7.30 (1H, m), 6.99 (2H, m), 6.34 (1H, d), 6.17 (1H, s) , 4.20 (2H, m), 3.60 (4H, m), 3.45 (3H, s), 3.23 (2H, s), 2.60 (6H, m), 1.27 (3H, m)

FAB MS(m/e) = 541 [M+1]FAB MS (m / e) = 541 [M + 1]

실시예 120: 2-[4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일)-피페라진-1-일]-에탄올의 제조Example 120: 2- [4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino}- Preparation of Pyrimidin-4-yl) -piperazin-1-yl] -ethanol

Figure 112006083464511-PAT00089
Figure 112006083464511-PAT00089

실시예 119에서 얻은 화합물 80 mg(0.148 mmol)을 무수테트라히드로퓨란 20 ml에 녹이고 -40℃로 냉각 후, 1N 리튬알루미늄하이드라이드 용액 0.15 ml를 10 분간 적가하였다. 30 분 동안 더 교반시켜준 후, 0℃로 온도를 상승시킨 후 1N 가성소다수용액을 가하여 생긴 고체를 셀라이트에 여과하였다. 여과된 용액을 농축하고 관크로마토그래피로 분리하여 목적 화합물 64 mg(0.129 mmol, 수율; 87%)을 얻었다. 80 mg (0.148 mmol) of the compound obtained in Example 119 was dissolved in 20 ml of anhydrous tetrahydrofuran, cooled to −40 ° C., and 0.15 ml of 1N lithium aluminum hydride solution was added dropwise for 10 minutes. After 30 minutes of further stirring, the temperature was raised to 0 ° C., and 1N caustic soda solution was added to the resulting solid and filtered through Celite. The filtered solution was concentrated and separated by tube chromatography to give 64 mg (0.129 mmol, yield; 87%) of the title compound.

1H NMR (CDCl3, ppm); δ 10.3 (1H, bs), 8.43 (1H, s), 7.64 (1H, d), 7.32 (1H, m), 6.98 (2H, m), 6.34 (1H, d), 6.19 (1H, s), 3.67 (2H, m), 3.56 (4H, m), 3.45 (3H, s), 2.60 (2H, m), 2.55 (4H, m) 1 H NMR (CDCl 3 , ppm); δ 10.3 (1H, bs), 8.43 (1H, s), 7.64 (1H, d), 7.32 (1H, m), 6.98 (2H, m), 6.34 (1H, d), 6.19 (1H, s), 3.67 (2H, m), 3.56 (4H, m), 3.45 (3H, s), 2.60 (2H, m), 2.55 (4H, m)

FAB MS(m/e) = 499 [M+1]FAB MS (m / e) = 499 [M + 1]

하기 표 7은 제조예 27에서 얻은 화합물을 실시예 119의 방법으로 반응하여 소정의 목적 화합물들을 합성한 실시예들이다. Table 7 below is an example in which the compound obtained in Preparation 27 was reacted by the method of Example 119 to synthesize predetermined target compounds.

[표 7]TABLE 7

Figure 112006083464511-PAT00090
Figure 112006083464511-PAT00090

실시예 126: 4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-2-온의 제조Example 126: 4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine- Preparation of 2-one

Figure 112006083464511-PAT00091
Figure 112006083464511-PAT00091

제조예 10에서 얻은 화합물을 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Production Example 10 was reacted by the method of Example 3, to obtain the target compound.

1H NMR (CDCl3, ppm); δ 8.29(1H, bs), 7.52(1H, d), 7.20(4H, m), 7.01(1H, s), 6.91(1H, d), 6.55(1H, d), 6.05(1H, s), 3.56(2H, s), 3.49(3H, s), 3.37(2H, m), 3.20(2H, s), 2.65(2H, m), 2.37(3H, s) 1 H NMR (CDCl 3 , ppm); δ 8.29 (1H, bs), 7.52 (1H, d), 7.20 (4H, m), 7.01 (1H, s), 6.91 (1H, d), 6.55 (1H, d), 6.05 (1H, s), 3.56 (2H, s), 3.49 (3H, s), 3.37 (2H, m), 3.20 (2H, s), 2.65 (2H, m), 2.37 (3H, s)

FAB MS(m/e) = 460 [M+1]FAB MS (m / e) = 460 [M + 1]

하기 표 8은 제조예 10에서 얻은 화합물을 실시예 3의 방법으로 반응하여 소정의 목적 화합물들을 합성한 실시예들이다.Table 8 below is an example in which the compound obtained in Preparation Example 10 was reacted by the method of Example 3 to synthesize predetermined target compounds.

[표 8]TABLE 8

Figure 112006083464511-PAT00092
Figure 112006083464511-PAT00092

Figure 112006083464511-PAT00093
Figure 112006083464511-PAT00093

Figure 112006083464511-PAT00094
Figure 112006083464511-PAT00094

Figure 112006083464511-PAT00095
Figure 112006083464511-PAT00095

실시예 151: 1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페리딘-4-온 옥심Example 151: 1- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperidine 4-one oxime

Figure 112006083464511-PAT00096
Figure 112006083464511-PAT00096

실시예 130에서 얻은 화합물 100 mg(0.218 mmol)을 에탄올 10 ml에 녹이고, 히드록실아민 18 mg(0.30 mmol)과 칼륨 아세테이트 26 mg(0.3 mmol)을 가하고 4 시간 동안 환류교반하였다. 반응 완결 후, 농축하고 물 20 ml를 가한 후, 에틸 아세테이트로 20 ml씩 두 번 추출하여 농축하였다. 관 크로마토그래피로 분리하여 목적 화합물 87 mg(0.183 mmol, 수율; 84%)을 얻었다. 100 mg (0.218 mmol) of the compound obtained in Example 130 was dissolved in 10 ml of ethanol, and 18 mg (0.30 mmol) of hydroxylamine and 26 mg (0.3 mmol) of potassium acetate were added and refluxed for 4 hours. After completion of the reaction, it was concentrated, 20 ml of water was added, and 20 ml of ethyl acetate was extracted twice and concentrated. Separation by column chromatography gave 87 mg (0.183 mmol, yield; 84%) of the title compound.

1H NMR (CDCl3, ppm); δ 8.27(1H, d), 7.51(1H, d), 7.15-7.21(4H, m), 6.93(1H, s), 6.83(1H, d), 6.53(1H, d), 3.56(2H, s), 3.49(3H, s), 2.75(2H, t), 2.61(4H, q), 2.48(2H, t), 2.37(3H, s) 1 H NMR (CDCl 3 , ppm); δ 8.27 (1H, d), 7.51 (1H, d), 7.15-7.21 (4H, m), 6.93 (1H, s), 6.83 (1H, d), 6.53 (1H, d), 3.56 (2H, s ), 3.49 (3H, s), 2.75 (2H, t), 2.61 (4H, q), 2.48 (2H, t), 2.37 (3H, s)

FAB MS(m/e) = 474[M+1]+ FAB MS (m / e) = 474 [M + 1] +

실시예 152: 1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페리딘-4-온 O-메틸-옥심Example 152: 1- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperidine 4-one O-methyl-oxime

Figure 112006083464511-PAT00097
Figure 112006083464511-PAT00097

히드록실아민 대신 메톡실아민을 사용하였다는 점을 제외하고 실시예 151과 동일한 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained in the same manner as in Example 151, except that methoxylamine was used instead of hydroxylamine.

1H NMR (CDCl3, ppm); δ 8.27(1H, d), 7.54(1H, d), 7.16-7.22(4H, m), 6.98(1H, s), 6.91(1H, d), 6.54(1H, d), 3.72(3H, s), 3.49(3H, s), 3.48(2H, s), 2.55(4H, m), 2.48(2H, m), 2.37(3H, s), 2.32(2H, m) 1 H NMR (CDCl 3 , ppm); δ 8.27 (1H, d), 7.54 (1H, d), 7.16-7.22 (4H, m), 6.98 (1H, s), 6.91 (1H, d), 6.54 (1H, d), 3.72 (3H, s ), 3.49 (3H, s), 3.48 (2H, s), 2.55 (4H, m), 2.48 (2H, m), 2.37 (3H, s), 2.32 (2H, m)

FAB MS(m/e) = 488[M+1]+ FAB MS (m / e) = 488 [M + 1] +

실시예 153: NExample 153: N 55 -메틸-N-Methyl-N 22 -(4-피라졸-1-일메틸-피리딘-2-일)-N-(4-pyrazol-1-ylmethyl-pyridin-2-yl) -N 55 -p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민-p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00098
Figure 112006083464511-PAT00098

피라졸 34 mg(0.505 mmol)을 테트라히드로퓨란 10 ml에 녹이고 소듐 하이드라이드 20 mg(60%, 0.505 mmol)을 가하고 10 분간 교반하였다. 제조예 10에서 얻은 화합물 100 mg(0.252 mmol)을 가하고 상온에서 1 시간 교반하였다. 반응 완결 후 물 20 ml를 가하고 에틸 아세테이트 20 ml를 사용하여 추출한 후 농축하였다. 관 크로마토그래피로 분리하여 목적 화합물 80 mg(0.186 mmol, 수율; 74%)을 얻었다. 34 mg (0.505 mmol) of pyrazole was dissolved in 10 ml of tetrahydrofuran and 20 mg (60%, 0.505 mmol) of sodium hydride were added and stirred for 10 minutes. 100 mg (0.252 mmol) of the compound obtained in Preparation Example 10 were added thereto, followed by stirring at room temperature for 1 hour. After completion of the reaction, 20 ml of water was added, extracted with 20 ml of ethyl acetate, and concentrated. Separation by column chromatography gave 80 mg of the target compound (0.186 mmol, yield; 74%).

1H NMR (CDCl3, ppm); δ 8.25(1H, d), 7.56(1H, s), 7.50(1H, d), 7.42(1H, s), 7.15-7.22(4H, m), 6.69(1H, s), 6.65(1H, d), 6.53(1H, d), 6.31(1H, s), 3.47(5H, s), 2.37(3H, s) 1 H NMR (CDCl 3 , ppm); δ 8.25 (1H, d), 7.56 (1H, s), 7.50 (1H, d), 7.42 (1H, s), 7.15-7.22 (4H, m), 6.69 (1H, s), 6.65 (1H, d ), 6.53 (1H, d), 6.31 (1H, s), 3.47 (5H, s), 2.37 (3H, s)

FAB MS(m/e) = 428[M+1]+ FAB MS (m / e) = 428 [M + 1] +

실시예 154: 2-히드록시-1-(4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-에타논Example 154: 2-hydroxy-1- (4- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4 -Ylmethyl} -piperazin-1-yl) -ethanone

Figure 112006083464511-PAT00099
Figure 112006083464511-PAT00099

실시예 150에서 얻어진 화합물과 1-히드록시아세트산을 이용하여 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained by reacting the compound obtained in Example 150 with the method of Example 18 using 1-hydroxyacetic acid.

1H NMR (DMSO-d6, ppm); δ 8.21(1H, d), 7.58(1H, d), 7.15-7.22(4H, m), 7.08(1H, s), 6.90(1H, d), 6.48(1H, d), 4.49(1H, t), 4.04(2H, d), 3.47(4H, d), 3.36(3H, s), 3.13(2H, d), 2.46(4H, s), 2.29(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.21 (1H, d), 7.58 (1H, d), 7.15-7.22 (4H, m), 7.08 (1H, s), 6.90 (1H, d), 6.48 (1H, d), 4.49 (1H, t ), 4.04 (2H, d), 3.47 (4H, d), 3.36 (3H, s), 3.13 (2H, d), 2.46 (4H, s), 2.29 (3H, s)

FAB MS(m/e) = 504[M+1]+ FAB MS (m / e) = 504 [M + 1] +

실시예 155: 4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-카르복실산 시클로프로필아미드Example 155: 4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine- 1-carboxylic acid cyclopropylamide

Figure 112006083464511-PAT00100
Figure 112006083464511-PAT00100

실시예 150에서 얻은 화합물 200 mg(0.505 mmol)을 디클로로메탄 20 ml에 녹이고, N,N-디이소프로필에틸아민 0.18 ml(1.01 mmol)을 가하고 0℃로 냉각하였다. 트리포스겐 75 mg(0.253 mmol)을 가하고 30 분간 교반 후 시클로프로필아민 0.14 ml(2.02 mmol)을 가하고 상온으로 온도를 올려 30 분간 교반하였다. 반응 완결 후, 농축하고 물 30 ml를 가하고 에틸아세테이트로 30 ml씩 두번 추출하여 유기층을 농축하였다. 관 크로마토그래피로 분리하여 목적 화합물 170 mg(0.321 mmol, 수율; 64%)을 얻었다. 200 mg (0.505 mmol) of the compound obtained in Example 150 were taken up in 20 ml of dichloromethane, and 0.18 ml (1.01 mmol) of N, N-diisopropylethylamine were added and cooled to 0 ° C. Triphosgene 75 mg (0.253 mmol) was added thereto, stirred for 30 minutes, and then 0.14 ml (2.02 mmol) of cyclopropylamine was added thereto, and the mixture was heated to room temperature and stirred for 30 minutes. After completion of the reaction, the mixture was concentrated, 30 ml of water was added thereto, and 30 ml of ethyl acetate was extracted twice, and the organic layer was concentrated. Separation by column chromatography gave 170 mg (0.321 mmol, yield; 64%) of the title compound.

1H NMR (CDCl3, ppm); δ 8.58(1H, s), 8.27(1H, d), 7.53(1H, d), 7.16-7.22(4H, m), 6.97(1H, s), 6.90(1H, d), 6.54(1H, d), 4.65(1H, s), 3.49(3H, s), 3.47(2H, s), 3.34(4H, t), 2.64(1H, m), 2.42(4H, m), 2.37(3H, s), 0.70(2H, m), 0.46(2H, m) 1 H NMR (CDCl 3 , ppm); δ 8.58 (1H, s), 8.27 (1H, d), 7.53 (1H, d), 7.16-7.22 (4H, m), 6.97 (1H, s), 6.90 (1H, d), 6.54 (1H, d ), 4.65 (1H, s), 3.49 (3H, s), 3.47 (2H, s), 3.34 (4H, t), 2.64 (1H, m), 2.42 (4H, m), 2.37 (3H, s) , 0.70 (2H, m), 0.46 (2H, m)

FAB MS(m/e) = 529[M+1]+ FAB MS (m / e) = 529 [M + 1] +

제조예 28: (S)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-Preparation Example 28: (S) -1- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4- 일메틸Methyl }-}- 피롤리딘Pyrrolidine -2--2- 카르복실산Carboxylic acid 메틸methyl 에스테르 ester

제조예 10에서 얻은 화합물과 (S)-피롤리딘-2-카르복실산 메틸 에스테르를 사용하여 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Production Example 10 and (S) -pyrrolidine-2-carboxylic acid methyl ester were reacted by the method of Example 3 to obtain the target compound.

1H NMR (CDCl3, ppm); δ 9.01(1H, s), 8.27(1H, d), 7.54(1H, d), 7.15-7.22(4H, m), 6.95(1H, s), 6.91(1H, d), 6.54(1H, d), 3.89(1H, d), 3.66(3H, s), 3.48(4H, m), 3.29(1H, m), 3.02(1H, m), 2.36(3H, s), 2.13(1H, m), 1.97(1H, m), 1.89(1H, m), 1.87(1H, m) 1 H NMR (CDCl 3 , ppm); δ 9.01 (1H, s), 8.27 (1H, d), 7.54 (1H, d), 7.15-7.22 (4H, m), 6.95 (1H, s), 6.91 (1H, d), 6.54 (1H, d ), 3.89 (1H, d), 3.66 (3H, s), 3.48 (4H, m), 3.29 (1H, m), 3.02 (1H, m), 2.36 (3H, s), 2.13 (1H, m) , 1.97 (1H, m), 1.89 (1H, m), 1.87 (1H, m)

FAB MS(m/e) = 489[M+1]+ FAB MS (m / e) = 489 [M + 1] +

실시예 156: (S)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피롤리딘-2-카르복실산Example 156: (S) -1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -Pyrrolidine-2-carboxylic acid

Figure 112006083464511-PAT00101
Figure 112006083464511-PAT00101

제조예 28에서 얻은 화합물을 실시예 17의 방법으로 가수 분해하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 28 was hydrolyzed by the method of Example 17 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 7.94(1H, d), 7.09(1H, d), 7.00-7.10(4H, m), 6.58(1H, s), 6.48(1H, s), 6.43(1H, d), 3.98(1H, d), 3.29(3H, s), 3.08(1H, m), 2.78(2H, m), 2.24(3H, s), 2.06(1H, m), 1.55-1.82(4H, m) 1 H NMR (DMSO-d 6 , ppm); δ 7.94 (1H, d), 7.09 (1H, d), 7.00-7.10 (4H, m), 6.58 (1H, s), 6.48 (1H, s), 6.43 (1H, d), 3.98 (1H, d ), 3.29 (3H, s), 3.08 (1H, m), 2.78 (2H, m), 2.24 (3H, s), 2.06 (1H, m), 1.55-1.82 (4H, m)

FAB MS(m/e) = 475[M+1]+ FAB MS (m / e) = 475 [M + 1] +

하기 표 9는 실시예 17의 방법으로 가수 분해하여 합성한 실시예들이다. Table 9 shows the examples synthesized by hydrolysis by the method of Example 17.

[표 9]TABLE 9

Figure 112006083464511-PAT00102
Figure 112006083464511-PAT00102

실시예 163: 1-메틸-4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-2-온Example 163: 1-methyl-4- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} Piperazine-2-one

Figure 112006083464511-PAT00103
Figure 112006083464511-PAT00103

실시예 126에서 얻은 화합물 145 mg(0.315 mmol)을 N,N-디메틸포름아미드 10 ml에 녹이고, 0℃로 냉각한 후 소듐 하이드라이드 14 mg(0.345 mmol)을 가하고 5분간 교반하였다. 반응용액에 요오드화메탄 21 uL(0.345 mmol)을 가하고 1 시간 교반하였다. 반응 완결 후, 물 1 ml를 가한 후 농축하였다. 물 20 ml를 가하고, 에틸 아세테이트로 20 ml씩 두번 추출한 후 농축하였다. 관 크로마토그래피로 분리하여 목적 화합물 110 mg(0.233 mmol)을 얻었다. 145 mg (0.315 mmol) of the compound obtained in Example 126 was dissolved in 10 ml of N, N-dimethylformamide, cooled to 0 ° C., and 14 mg (0.345 mmol) of sodium hydride were added thereto and stirred for 5 minutes. 21 uL (0.345 mmol) of methane iodide was added to the reaction solution, and the mixture was stirred for 1 hour. After completion of the reaction, 1 ml of water was added and concentrated. 20 ml of water were added, extracted twice with 20 ml of ethyl acetate and concentrated. Separation by column chromatography gave 110 mg (0.233 mmol) of the title compound.

1H NMR (CDCl3, ppm); δ 8.29(1H, d), 7.53(1H, d), 7.16-7.22(4H, m), 6.98(1H, s), 6.90(1H, d), 6.54(1H, d), 3.51(2H, s), 3.49(3H, s), 3.27(2H, t), 3.18(2H, s), 2.95(3H, s), 2.65(2H, t), 2.37(3H, s) 1 H NMR (CDCl 3 , ppm); δ 8.29 (1H, d), 7.53 (1H, d), 7.16-7.22 (4H, m), 6.98 (1H, s), 6.90 (1H, d), 6.54 (1H, d), 3.51 (2H, s ), 3.49 (3H, s), 3.27 (2H, t), 3.18 (2H, s), 2.95 (3H, s), 2.65 (2H, t), 2.37 (3H, s)

FAB MS(m/e) = 474[M+1]+ FAB MS (m / e) = 474 [M + 1] +

실시예 164: (R)-N-메톡시-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온아미드Example 164: (R) -N-methoxy-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine -4-ylmethyl} -amino) -propionamide

Figure 112006083464511-PAT00104
Figure 112006083464511-PAT00104

실시예 159에서 얻은 화합물과 메톡실아민을 이용하여 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained by reacting the compound obtained in Example 159 with the method of Example 18 using methoxylamine.

1H NMR (CDCl3, ppm); δ 9.31(1H, s), 8.28(1H, s), 7.54(1H, d), 7.16-7.22(4H, m), 7.04(1H, s), 6.84(1H, s), 6.54(1H, d), 3.75(5H, s), 3.49(3H, s), 3.24(1H, m), 2.34(3H, s), 1.35(3H, d) 1 H NMR (CDCl 3 , ppm); δ 9.31 (1H, s), 8.28 (1H, s), 7.54 (1H, d), 7.16-7.22 (4H, m), 7.04 (1H, s), 6.84 (1H, s), 6.54 (1H, d ), 3.75 (5H, s), 3.49 (3H, s), 3.24 (1H, m), 2.34 (3H, s), 1.35 (3H, d)

FAB MS(m/e) = 478[M+1]+ FAB MS (m / e) = 478 [M + 1] +

실시예 165: N-메톡시-2-메틸-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온아미드Example 165 N-methoxy-2-methyl-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine -4-ylmethyl} -amino) -propionamide

Figure 112006083464511-PAT00105
Figure 112006083464511-PAT00105

실시예 161에서 얻은 화합물과 메톡실아민을 이용하여 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained by reacting the compound obtained in Example 161 with the method of Example 18 using methoxylamine.

1H NMR (CDCl3, ppm); δ 10.69(1H, s), 9.52(1H, s), 8.28(1H, s), 7.54(1H, d), 7.15-7.21(4H, m), 7.00(1H, s), 6.82(1H, s), 6.52(1H, d), 3.70(3H, s), 3.61(2H, s), 3.48(3H, s), 2.36(3H, s), 1.35(6H, s) 1 H NMR (CDCl 3 , ppm); δ 10.69 (1H, s), 9.52 (1H, s), 8.28 (1H, s), 7.54 (1H, d), 7.15-7.21 (4H, m), 7.00 (1H, s), 6.82 (1H, s ), 6.52 (1H, d), 3.70 (3H, s), 3.61 (2H, s), 3.48 (3H, s), 2.36 (3H, s), 1.35 (6H, s)

FAB MS(m/e) = 492[M+1]+ FAB MS (m / e) = 492 [M + 1] +

실시예: 166 NExample: 166 N 55 -메틸-N-Methyl-N 22 -(4-메틸아미노메틸-피리딘-2-일)-N-(4-methylaminomethyl-pyridin-2-yl) -N 55 -p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민-p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00106
Figure 112006083464511-PAT00106

제조예 10에서 얻은 화합물을 메틸아민과 실시예 3의 방법으로 반응하여 목적 화합물을 얻었다.The compound obtained in Production Example 10 was reacted with methylamine in the method of Example 3 to obtain the target compound.

1H NMR (CDCl3, ppm); δ 8.27(1H, d), 7.53(1H, d), 7.16-7.21(4H, m), 6.96(1H, s), 6.87(1H, d), 6.54(1H, d), 3.75(2H, s), 3.49(3H, s), 2.46(3H, s), 2.37(3H, s) 1 H NMR (CDCl 3 , ppm); δ 8.27 (1H, d), 7.53 (1H, d), 7.16-7.21 (4H, m), 6.96 (1H, s), 6.87 (1H, d), 6.54 (1H, d), 3.75 (2H, s ), 3.49 (3H, s), 2.46 (3H, s), 2.37 (3H, s)

FAB MS(m/e) = 391[M+1]+ FAB MS (m / e) = 391 [M + 1] +

실시예 167: NExample 167: N 22 -(4-아미노메틸-피리딘-2-일)-N-(4-aminomethyl-pyridin-2-yl) -N 55 -메틸-N-Methyl-N 55 -p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민-p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00107
Figure 112006083464511-PAT00107

제조예 10에서 얻은 화합물 2.5 g(6.31 mmol)을 디메틸설폭사이드 20 ml에 녹인 후, 소듐 아지드 1.64 g(25.2 mmol)을 가하고 상온에서 5 시간 교반하였다. 반응완결 후, 물 300 ml를 가하여 생긴 고체를 여과하고 건조하여 아지드 형태의 중간체 2.16 g(5.36 mmol)을 얻었다. 이 중간체를 메탄올 150 ml에 녹이고, 10% 팔라듐/카본 300 mg을 가하고 대기압의 수소존재하에서 환원 반응을 진행하였다. 반응 완결 후, 셀파이트에 고체를 여과하고 여과액을 농축하여 생기는 고체를 디에틸에테르 20 ml와 노르말 헥산 50 ml를 가하여 20분 교반하고 여과하고 건조하여 목적화합물 1.90 g(5.05 mmol, 수율; 89%)을 얻었다.2.5 g (6.31 mmol) of the compound obtained in Preparation Example 10 was dissolved in 20 ml of dimethyl sulfoxide, and then 1.64 g (25.2 mmol) of sodium azide was added thereto, followed by stirring at room temperature for 5 hours. After completion of the reaction, 300 ml of water was added, and the resulting solid was filtered and dried to yield 2.16 g (5.36 mmol) of an intermediate in the form of azide. This intermediate was dissolved in 150 ml of methanol, 300 mg of 10% palladium / carbon was added, and a reduction reaction was carried out in the presence of hydrogen at atmospheric pressure. After completion of the reaction, the solids were filtered through a cellite, the filtrate was concentrated, and 20 ml of diethyl ether and 50 ml of normal hexane were added thereto, followed by stirring for 20 minutes, followed by filtration and drying, to obtain 1.90 g (5.05 mmol, yield; 89) of the target compound. %) Was obtained.

1H NMR (DMSO-d6, ppm); δ 8.22(1H, d), 7.63(1H, d), 7.16-7.21(4H, m), 7.11(1H, s), 6.97(1H, d), 6.54(1H, d), 3.74(2H, s), 3.41(3H, s), 2.34(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.22 (1H, d), 7.63 (1H, d), 7.16-7.21 (4H, m), 7.11 (1H, s), 6.97 (1H, d), 6.54 (1H, d), 3.74 (2H, s ), 3.41 (3H, s), 2.34 (3H, s)

FAB MS(m/e) = 377[M+1]+ FAB MS (m / e) = 377 [M + 1] +

실시예 168: 2-메탄술포닐-N-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아세트아미드Example 168 2-methanesulfonyl-N- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl Methyl} -acetamide

Figure 112006083464511-PAT00108
Figure 112006083464511-PAT00108

실시예 167에서 얻은 화합물 110 mg(0.292 mmol)을 디클로로메탄 5 ml에 녹인 후, N,N-디이소프로필에틸아민 0.13 ml(0.73 mmol)을 가하고, 메탄설포닐-아세틸 클로라이드 50 mg(0.321 mmol)을 가하고 30분간 교반하였다. 반응 완결 후, 물 20 ml를 가하고, 디클로로메탄 20 ml를 가하여 추출하였다. 농축하고 관 크로마토그래피로 분리하여 목적 화합물 126 mg(0.254 mmol)을 얻었다. 110 mg (0.292 mmol) of the compound obtained in Example 167 was dissolved in 5 ml of dichloromethane, and then 0.13 ml (0.73 mmol) of N, N-diisopropylethylamine was added, and 50 mg (0.321 mmol) of methanesulfonyl-acetyl chloride was added. ) Was added and stirred for 30 minutes. After completion of the reaction, 20 ml of water was added, followed by extraction with 20 ml of dichloromethane. Concentration and separation by column chromatography gave 126 mg (0.254 mmol) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.93(1H, t), 8.21(1H, d), 7.58(1H, d), 7.15-7.22(4H, m), 6.98(1H, s), 6.86(1H, d), 6.48(1H, d), 4.30(2H, d), 4.13(2H, s), 3.36(3H, s), 3.10(3H, s), 2.29(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.93 (1H, t), 8.21 (1H, d), 7.58 (1H, d), 7.15-7.22 (4H, m), 6.98 (1H, s), 6.86 (1H, d ), 6.48 (1H, d), 4.30 (2H, d), 4.13 (2H, s), 3.36 (3H, s), 3.10 (3H, s), 2.29 (3H, s)

FAB MS(m/e) = 497[M+1]+ FAB MS (m / e) = 497 [M + 1] +

하기 표 10은 실시예 167에서 얻은 화합물을 사용하여 실시예 167의 방법으로 반응하여 소정의 목적 화합물들을 합성한 실시예들이다.Table 10 below shows examples of synthesizing desired compounds by reacting by the method of Example 167 using the compound obtained in Example 167.

[표 10]TABLE 10

Figure 112006083464511-PAT00109
Figure 112006083464511-PAT00109

제조예 29: 2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피 리딘-4-Preparation Example 29 2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4- 일메틸Methyl }} 카바모일Cabamo )-)- 피롤리딘Pyrrolidine -1--One- 카르복실산Carboxylic acid 티-부틸 에스테르 Thi-butyl ester

실시예 167에서 얻은 화합물 250 mg(0.664 mmol)과 피롤리딘-1,2-디카르복실산 1-tert-부틸 에스테르를 이용하여 실시예 18의 방법으로 반응하여 목적 화합물 323 mg(0.564 mmol, 수율; 85%)을 얻었다. 250 mg (0.664 mmol) of the compound obtained in Example 167 and pyrrolidin-1,2-dicarboxylic acid 1-tert-butyl ester were reacted by the method of Example 18 to obtain 323 mg (0.564 mmol, Yield: 85%).

1H NMR (CDCl3, ppm); δ 8.33(1H, d), 7.68(1H, t), 7.56(1H, d), 7.20-7.26(4H, m), 6.98(1H, s), 6.87(1H, d), 6.58(1H, d), 4.50(2H, s), 3.54(3H, s), 3.04(2H, m), 2.41(3H, s), 1.69-2.31(2H, m), 1.83(2H, m), 1.4(9H, s) 1 H NMR (CDCl 3 , ppm); δ 8.33 (1H, d), 7.68 (1H, t), 7.56 (1H, d), 7.20-7.26 (4H, m), 6.98 (1H, s), 6.87 (1H, d), 6.58 (1H, d ), 4.50 (2H, s), 3.54 (3H, s), 3.04 (2H, m), 2.41 (3H, s), 1.69-2.31 (2H, m), 1.83 (2H, m), 1.4 (9H, s)

FAB MS(m/e) = 574[M+1]+ FAB MS (m / e) = 574 [M + 1] +

실시예 175: 피롤리딘-2-카르복실산 {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미드Example 175 Pyrrolidine-2-carboxylic acid {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4- Monomethyl} -amide

Figure 112006083464511-PAT00110
Figure 112006083464511-PAT00110

제조예 29에서 얻은 화합물을 이용하여 실시예 62의 방법으로 반응하여 목적 화합물을 얻었다. Using the compound obtained in Preparation Example 29, the reaction was carried out by the method of Example 62 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 8.61(1H, s), 8.30(1H, d), 7.68(1H, t), 7.21-7.27(4H, m), 7.12(1H, s), 6.69 (1H, d), 6.54(1H, d), 4.28(2H, m), 3.42(3H, s), 3.32(2H, m), 2.43(1H, m), 2.34(3H, s), 2.03(1H, m), 1.93(2H, m) 1 H NMR (DMSO-d 6 , ppm); δ 8.61 (1H, s), 8.30 (1H, d), 7.68 (1H, t), 7.21-7.27 (4H, m), 7.12 (1H, s), 6.69 (1H, d), 6.54 (1H, d ), 4.28 (2H, m), 3.42 (3H, s), 3.32 (2H, m), 2.43 (1H, m), 2.34 (3H, s), 2.03 (1H, m), 1.93 (2H, m)

FAB MS(m/e) = 474[M+1]+ FAB MS (m / e) = 474 [M + 1] +

실시예 176: NExample 176: N 22 -[4-(1,1-디옥소-1-[4- (1,1-dioxo-1) 66 -티오모폴린-4-일메틸)-피리딘-2-일]-N-Thiomorpholin-4-ylmethyl) -pyridin-2-yl] -N 55 -메틸-N-Methyl-N 55 -p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민-p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00111
Figure 112006083464511-PAT00111

실시예 167에서 얻은 화합물 134 mg(0.355 mmol)을 메탄올 20 ml에 녹인 후, 디바이닐설폰 62 uL(0.374 mmol)을 가하고 상온에서 두 시간 동안 교반하였다. 반응완결 후 농축하고 물 30 ml를 가한 후 에틸 아세테이트로 20 ml씩 두 번 추출한 후 농축하였다. 관 크로마토그리피로 분리하여 목적 화합물 147 mg(0.298 mmol, 수율; 84%)을 얻었다. After dissolving 134 mg (0.355 mmol) of the compound obtained in Example 167 in 20 ml of methanol, 62 uL (0.374 mmol) of divinyl sulfone was added and stirred at room temperature for 2 hours. After completion of the reaction, the mixture was concentrated, 30 ml of water was added thereto, and 20 ml of ethyl acetate was extracted twice. Separation by column chromatography gave 147 mg (0.298 mmol, yield; 84%) of the title compound.

1H NMR (CDCl3, ppm); δ 9.02(1H, s), 8.30(1H, d), 7.54(1H, d), 7.16-7.22(4H, m), 7.04(1H, s), 6.88(1H, d), 6.55(1H, d), 3.62(2H, s), 3.50(3H, s), 3.05(4H, d), 3.00(4H, d), 2.37(3H, s) 1 H NMR (CDCl 3 , ppm); δ 9.02 (1H, s), 8.30 (1H, d), 7.54 (1H, d), 7.16-7.22 (4H, m), 7.04 (1H, s), 6.88 (1H, d), 6.55 (1H, d ), 3.62 (2H, s), 3.50 (3H, s), 3.05 (4H, d), 3.00 (4H, d), 2.37 (3H, s)

FAB MS(m/e) = 495[M+1]+ FAB MS (m / e) = 495 [M + 1] +

실시예 177: Example 177: NN -{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-메탄술폰아미드-{2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -methanesulfonamide

Figure 112006083464511-PAT00112
Figure 112006083464511-PAT00112

메탄설포닐-아세틸 클로라이드대신 메탄설포닐 클로라이드를 사용하였다는 점을 제외하고는 실시예 168과 같은 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained in the same manner as in Example 168, except that methanesulfonyl chloride was used instead of methanesulfonyl-acetyl chloride.

1H NMR (CDCl3, ppm); δ 8.29(1H, s), 7.50(1H, d), 7.15-7.21(4H, m), 7.12(1H, s), 6.89(1H, d), 6.52(1H, d), 3.49(2H, s), 3.48(3H, s), 2.98(3H, s), 2.37(3H, s) 1 H NMR (CDCl 3 , ppm); δ 8.29 (1H, s), 7.50 (1H, d), 7.15-7.21 (4H, m), 7.12 (1H, s), 6.89 (1H, d), 6.52 (1H, d), 3.49 (2H, s ), 3.48 (3H, s), 2.98 (3H, s), 2.37 (3H, s)

FAB MS(m/e) = 455[M+1]+ FAB MS (m / e) = 455 [M + 1] +

실시예 178: 1-시클로프로필-3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-우레아Example 178: 1-cyclopropyl-3- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl } -Urea

Figure 112006083464511-PAT00113
Figure 112006083464511-PAT00113

실시예 167에서 얻은 화합물 135 mg(0.359 mmol)을 디클로로메탄 20ml에 녹인 후 N,N-디이소프로필에틸아민 0.13 ml(0.72 mmol)을 가하고 0℃로 냉각하였다. 반응 용액에 트리포스겐 53 mg(0.18 mmol)을 가하고 1 시간 동안 교반하였다. 반응 용액에 시클로프로필 아민 75 uL(1.08 mmol)을 가하고 1 시간 동안 교반하였다. 반응 완결 후, 물 20 ml를 사용하여 씻고 유기층을 농축하였다. 관 크리마토그래피로 분리하여 목적 화합물 124 mg(0.269 mmol, 수율; 75%)을 얻었다. 135 mg (0.359 mmol) of the compound obtained in Example 167 were dissolved in 20 ml of dichloromethane, and 0.13 ml (0.72 mmol) of N, N-diisopropylethylamine was added thereto and cooled to 0 ° C. 53 mg (0.18 mmol) of triphosgene was added to the reaction solution, and the mixture was stirred for 1 hour. 75 uL (1.08 mmol) of cyclopropyl amine was added to the reaction solution, and the mixture was stirred for 1 hour. After completion of the reaction, it was washed with 20 ml of water and the organic layer was concentrated. Isolation by column chromatography gave 124 mg (0.269 mmol, yield; 75%) of the title compound.

1H NMR (CDCl3, ppm); δ 8.27(1H, d), 7.44(1H, d), 7.15-7.21(4H, m), 7.04(1H, s), 6.81(1H, d), 6.52(1H, d), 5.54(1H, t), 4.42(2H, d), 3.48(3H, s), 2.46(1H, m), 2.36(3H, s), 0.76(2H, m), 0.62(2H, m) 1 H NMR (CDCl 3 , ppm); δ 8.27 (1H, d), 7.44 (1H, d), 7.15-7.21 (4H, m), 7.04 (1H, s), 6.81 (1H, d), 6.52 (1H, d), 5.54 (1H, t ), 4.42 (2H, d), 3.48 (3H, s), 2.46 (1H, m), 2.36 (3H, s), 0.76 (2H, m), 0.62 (2H, m)

FAB MS(m/e) = 460[M+1]+ FAB MS (m / e) = 460 [M + 1] +

실시예 179: (Example 179: ( SS )-N-히드록시-2-(메틸-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온아미드) -N-hydroxy-2- (methyl- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl Methyl} -amino) -propionamide

Figure 112006083464511-PAT00114
Figure 112006083464511-PAT00114

실시예 162에서 얻은 화합물을 실시예 164의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 162 was reacted by the method of Example 164 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.21(1H, s), 10.44(1H, s), 8.80(1H, s), 8.19(1H, d), 7.58(1H, d), 7.15-7.22(4H, m), 7.04(1H, s), 6.94(1H, d), 6.47(1H, d), 3.46-3.66(2H, m), 3.36(3H, s), 3.30(1H, q), 2.29(3H, s), 2.12(3H, s), 1.15(3H, d) 1 H NMR (DMSO-d 6 , ppm); δ 11.21 (1H, s), 10.44 (1H, s), 8.80 (1H, s), 8.19 (1H, d), 7.58 (1H, d), 7.15-7.22 (4H, m), 7.04 (1H, s ), 6.94 (1H, d), 6.47 (1H, d), 3.46-3.66 (2H, m), 3.36 (3H, s), 3.30 (1H, q), 2.29 (3H, s), 2.12 (3H, s), 1.15 (3H, d)

FAB MS(m/e) = 492[M+1]+ FAB MS (m / e) = 492 [M + 1] +

실시예 180: N,N-디메틸-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드Example 180 N, N-dimethyl-2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl } -Acetamide

Figure 112006083464511-PAT00115
Figure 112006083464511-PAT00115

실시예 20에서 얻은 화합물을 사용하여 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다.Reaction was carried out in the same manner as in Example 18 using the compound obtained in Example 20 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 8.23(1H, d), 7.63(1H, d), 7.23(4H, m), 6.98(1H, s), 6.84(1H, d), 6.53(1H, d), 3.73(2H, s), 3.03(3H, s), 2.86(3H, s), 2.33(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.23 (1H, d), 7.63 (1H, d), 7.23 (4H, m), 6.98 (1H, s), 6.84 (1H, d), 6.53 (1H, d), 3.73 (2H, s), 3.03 (3H, s), 2.86 (3H, s), 2.33 (3H, s)

FAB MS(m/e) = 433 [M+1]+ FAB MS (m / e) = 433 [M + 1] +

실시예 181: 1-(4-아세틸-피페라진-1-일)-2-{2-[5-(메틸-p-톨릴-아미노) - 티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에타논Example 181 1- (4-acetyl-piperazin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine-2- Ylamino] -pyridin-4-yl} -ethanone

Figure 112006083464511-PAT00116
Figure 112006083464511-PAT00116

실시예 20에서 얻은 화합물을 사용하여 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다.Reaction was carried out in the same manner as in Example 18 using the compound obtained in Example 20 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.29(1H, bs), 8.19(1H, d), 7.58(1H, d), 7.19(4H, m), 6.93(1H, s), 6.49(1H, d), 6.48(1H, d), 3.76(2H, m), 3.48~3.36(8H, m), 3.30(3H, s), 2.29(3H, s), 1.98(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.29 (1H, bs), 8.19 (1H, d), 7.58 (1H, d), 7.19 (4H, m), 6.93 (1H, s), 6.49 (1H, d), 6.48 (1H, d), 3.76 (2H, m), 3.48-3.36 (8H, m), 3.30 (3H, s), 2.29 (3H, s), 1.98 (3H, s)

FAB MS(m/e) = 516[M+1]+ FAB MS (m / e) = 516 [M + 1] +

하기 표 11은 실시예 20에서 얻은 화합물을 사용하여 실시예 18의 방법으로 반응하여 소정의 목적 화합물들을 합성한 실시예들이다.Table 11 below shows examples of synthesizing desired compounds by reacting by the method of Example 18 using the compound obtained in Example 20.

[표 11]TABLE 11

Figure 112006083464511-PAT00117
Figure 112006083464511-PAT00117

Figure 112006083464511-PAT00118
Figure 112006083464511-PAT00118

제조예 30: [(S)-1-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세틸)-Preparation 30: [(S) -1- (2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4 -Yl} -acetyl)- 피롤리딘Pyrrolidine -3-일]--3 days]- 카르바믹산Carbamic acid terttert -부틸 에스테르-Butyl ester

실시예 20에서 얻은 화합물을 (S)-피롤리딘-3-일-카바믹산 tert-부틸 에스테르와 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 20 was reacted with (S) -pyrrolidin-3-yl-carbamic acid tert-butyl ester by the method of Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.41(1H, s), 8.42(1H, br), 8.23(1H, d), 7.62(1H, d), 7.22(2H, d), 7.16(2H, d), 7.05(1H, s), 6.90(1H, d), 6.51(1H, d), 3.73-3.70(1H, m), 3.68(2H, s), 3.52-3.40(4H, m), 3.37(3H, s), 2.27(3H, s), 2.27-1.98(2H, m), 1.34(9H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.41 (1H, s), 8.42 (1H, br), 8.23 (1H, d), 7.62 (1H, d), 7.22 (2H, d), 7.16 (2H, d), 7.05 (1H, s), 6.90 (1H, d), 6.51 (1H, d), 3.73-3.70 (1H, m), 3.68 (2H, s), 3.52-3.40 (4H, m), 3.37 (3H, s), 2.27 (3H, s), 2.27-1.98 (2H, m), 1.34 (9H, s)

FAB MS(m/e) = 574[M+1]+ FAB MS (m / e) = 574 [M + 1] +

실시예 195: 1-((S)-3-아미노-피롤리딘-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에타논Example 195 1-((S) -3-Amino-pyrrolidin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b ] Pyridin-2-ylarmano] -pyridin-4-yl} -ethanone

Figure 112006083464511-PAT00119
Figure 112006083464511-PAT00119

제조예 30에서 얻은 화합물을 실시예 62의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 30 was reacted by the method of Example 62, to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.34(1H, s), 8.33(2H, br), 8.22(1H, d), 7.65(1H, d), 7.23(2H, d), 7.18(2H, d), 7.06(1H, s), 6.90(1H, d), 6.51(1H, d), 3.73-3.70(1H, m), 3.68(2H, s), 3.52-3.40(4H, m), 3.34(3H, s), 2.29(3H, s), 2.27-1.98(2H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.34 (1H, s), 8.33 (2H, br), 8.22 (1H, d), 7.65 (1H, d), 7.23 (2H, d), 7.18 (2H, d), 7.06 (1H, s), 6.90 (1H, d), 6.51 (1H, d), 3.73-3.70 (1H, m), 3.68 (2H, s), 3.52-3.40 (4H, m), 3.34 (3H, s), 2.29 (3H, s), 2.27-1.98 (2H, m)

FAB MS(m/e) = 474[M+1]+ FAB MS (m / e) = 474 [M + 1] +

제조예 31: [(R)-1-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세틸)-Preparation 31: [(R) -1- (2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4 -Yl} -acetyl)- 피롤리딘Pyrrolidine -3-일]--3 days]- 카르바믹산Carbamic acid terttert -부틸 에스테르-Butyl ester

실시예 20에서 얻은 화합물을 (R)-피롤리딘-3-일-카바믹산 tert-부틸 에스테르와 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다.The compound obtained in Example 20 was reacted with (R) -pyrrolidin-3-yl-carbamic acid tert-butyl ester in the same manner as in Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.36(1H, s), 8.43(1H, s), 8.23(1H, d), 7.66(1H, d), 7.22(2H, d), 7.18(2H, d), 7.06(1H, s), 6.94(1H, d), 6.52(1H, d), 3.81-3.74(1H, m), 3.70(2H, s), 3.53-3.42(4H, m), 3.34(3H, s), 2.28(3H, s), 2.23-1.92(2H, m), 1.32(9H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.36 (1H, s), 8.43 (1H, s), 8.23 (1H, d), 7.66 (1H, d), 7.22 (2H, d), 7.18 (2H, d), 7.06 (1H, s), 6.94 (1H, d), 6.52 (1H, d), 3.81-3.74 (1H, m), 3.70 (2H, s), 3.53-3.42 (4H, m), 3.34 (3H, s), 2.28 (3H, s), 2.23-1.92 (2H, m), 1.32 (9H, s)

FAB MS(m/e) = 574[M+1]+ FAB MS (m / e) = 574 [M + 1] +

실시예 196: 1-((R)-3-아미노-피롤리딘-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에타논Example 196 1-((R) -3-Amino-pyrrolidin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b ] Pyridin-2-ylarmano] -pyridin-4-yl} -ethanone

Figure 112006083464511-PAT00120
Figure 112006083464511-PAT00120

제조예 30에서 얻은 화합물을 실시예 62의 방법으로 반응하여 목적 화합물을 얻었다.The compound obtained in Preparation Example 30 was reacted by the method of Example 62, to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.33(2H, br), 8.22(1H, d), 7.67(1H, d), 7.23(2H, d), 7.18(2H, d), 7.09(1H, s), 6.93(1H, d), 6.52(1H, d), 3.82-3.75(1H, m), 3.71(2H, s), 3.53-3.41(4H, m), 3.37(3H, s), 2.29(3H, s), 2.23-1.87(2H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.33 (2H, br), 8.22 (1H, d), 7.67 (1H, d), 7.23 (2H, d), 7.18 (2H, d), 7.09 (1H, s), 6.93 (1H, d), 6.52 (1H, d), 3.82-3.75 (1H, m), 3.71 (2H, s), 3.53-3.41 (4H, m), 3.37 (3H, s), 2.29 (3H, s), 2.23-1.87 (2H, m)

FAB MS(m/e) = 474[M+1]+ FAB MS (m / e) = 474 [M + 1] +

실시예 197: N-[(R)-1-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세틸)-피롤리딘-3-일]-아세트아미드Example 197 N-[(R) -1- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine -4-yl} -acetyl) -pyrrolidin-3-yl] -acetamide

Figure 112006083464511-PAT00121
Figure 112006083464511-PAT00121

실시예 196에서 얻은 화합물을 디클로로메탄 10 ml에 녹이고, N,N-디이소프로필아민을 첨가한 후 0℃로 냉각하였다. 무수초산을 가하고 30분간 교반 후 물로 씻은 후, 유기층을 농축하였다. 관 크로마토그래피로 분리하여 목적 화합물을 얻었다. The compound obtained in Example 196 was dissolved in 10 ml of dichloromethane, and cooled to 0 ° C. after adding N, N-diisopropylamine. Acetic anhydride was added thereto, stirred for 30 minutes, washed with water, and the organic layer was concentrated. Separation by column chromatography gave the target compound.

1H NMR (DMSO-d6, ppm); δ 11.26(1H, s), 8.19(1H, s), 8.10(1H, d), 7.59(1H, d), 7.19(2H, d), 7.16(2H, d), 6.94(1H, s), 6.80(1H, d), 6.47(1H, d), 4.23-4.15(1H, m), 3.61(2H, s), 3.58-3.41(2H, m), 3.32(3H, s), 3.20-3.11(2H, m), 2.28(3H, s), 2.05-1.97(1H, m), 1.79(3H, s), 1.76-1.69(1H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.26 (1H, s), 8.19 (1H, s), 8.10 (1H, d), 7.59 (1H, d), 7.19 (2H, d), 7.16 (2H, d), 6.94 (1H, s), 6.80 (1H, d), 6.47 (1H, d), 4.23-4.15 (1H, m), 3.61 (2H, s), 3.58-3.41 (2H, m), 3.32 (3H, s), 3.20-3.11 ( 2H, m), 2.28 (3H, s), 2.05-1.97 (1H, m), 1.79 (3H, s), 1.76-1.69 (1H, m)

FAB MS(m/e) = 516[M+1]+ FAB MS (m / e) = 516 [M + 1] +

제조예 32: 2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-이소니코틴산 Preparation 32: 2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -isonicotinic acid 메틸methyl 에스테르 ester

N5-메틸-N5-(4-메틸페닐)-티아졸로[5,4-b]피리딘-2,5-디아민을 메틸 2-클로로이소니코티네이트와 실시예 1의 방법으로 반응하여 목적 화합물을 얻었다. N 5 -methyl-N 5- (4-methylphenyl) -thiazolo [5,4-b] pyridine-2,5-diamine was reacted with methyl 2-chloroisonicotinate by the method of Example 1 to obtain the target compound. Got it.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.10(1H, d), 7.60(1H, d), 7.17(2H, d), 7.14(2H, d), 6.93(1H, s), 6.80(1H, d), 6.47(1H, d), 3.92(3H, s), 3.34(3H, s), 2.29(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.10 (1H, d), 7.60 (1H, d), 7.17 (2H, d), 7.14 (2H, d), 6.93 (1H, s), 6.80 (1H, d), 6.47 (1H, d), 3.92 (3H, s), 3.34 (3H, s), 2.29 (3H, s)

FAB MS(m/e) = 406[M+1]+ FAB MS (m / e) = 406 [M + 1] +

제조예Production Example 33: 2-[5-( 33: 2- [5- ( 메틸methyl -p--p- 톨릴Tolyl -아미노)--Amino)- 티아졸로[5,4-b]피리딘Thiazolo [5,4-b] pyridine -2--2- 일아미노Monoamino ]-]- 이소니Isoni 코틴산Cortinic acid

제조예 32에서 얻은 화합물을 실시예 17의 방법으로 가수분해하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 32 was hydrolyzed by the method of Example 17 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 13.57(1H, s), 11.27(1H, s), 8.11(1H, d), 7.61(1H, d), 7.16(2H, d), 7.14(2H, d), 6.92(1H, s), 6.81(1H, d), 6.46(1H, d), 3.32(3H, s), 2.28(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 13.57 (1H, s), 11.27 (1H, s), 8.11 (1H, d), 7.61 (1H, d), 7.16 (2H, d), 7.14 (2H, d), 6.92 (1H, s), 6.81 (1H, d), 6.46 (1H, d), 3.32 (3H, s), 2.28 (3H, s)

FAB MS(m/e) = 392[M+1]+ FAB MS (m / e) = 392 [M + 1] +

하기 표 12은 상기 제조예 33에서 얻은 화합물을 사용하여 실시예 18의 방법으로 반응하여 소정의 목적 화합물들을 합성한 실시예들이다.Table 12 below shows examples of synthesizing desired compounds by reacting by the method of Example 18 using the compound obtained in Preparation Example 33.

[표 12]TABLE 12

Figure 112006083464511-PAT00122
Figure 112006083464511-PAT00122

Figure 112006083464511-PAT00123
Figure 112006083464511-PAT00123

제조예 34: (1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-카르보닐}-피페리딘-4-일)-Preparation 34: (1- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine-4-carbonyl} -piperi Din-4-yl)- 카르바믹산Carbamic acid terttert -부틸 에스테르-Butyl ester

제조예 33에서 얻은 화합물을 피페리딘-4-일-카르바믹산 tert-부틸 에스테르와 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 33 was reacted with piperidin-4-yl-carbamic acid tert-butyl ester in the same manner as in Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 8.42(1H, d), 8.34(1H, s), 7.68(1H, d), 7.26(2H, d), 7.22(2H, d), 7.11(1H, s), 6.94(1H, d), 6.55(1H, d), 4.60-4.49(2H, m), 3.57-3.50(1H, m), 3.42(3H, s), 3.38-3.31(1H, m), 3.15-2.91(1H, m), 2.33(3H, s), 2.03(1H, m), 1.92(1H, m), 1.60-1.42(2H, m), 1.38(9H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 8.42 (1H, d), 8.34 (1H, s), 7.68 (1H, d), 7.26 (2H, d), 7.22 (2H, d), 7.11 (1H, s), 6.94 (1H, d), 6.55 (1H, d), 4.60-4.49 (2H, m), 3.57-3.50 (1H, m), 3.42 (3H, s), 3.38-3.31 (1H, m), 3.15- 2.91 (1H, m), 2.33 (3H, s), 2.03 (1H, m), 1.92 (1H, m), 1.60-1.42 (2H, m), 1.38 (9H, s)

FAB MS(m/e) = 574[M+1]+ FAB MS (m / e) = 574 [M + 1] +

실시예 206: (4-아미노-피페리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논Example 206: (4-Amino-piperidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -Pyridin-4-yl} -methanone

Figure 112006083464511-PAT00124
Figure 112006083464511-PAT00124

제조예 34에서 얻은 화합물을 실시예 62의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 34 was reacted by the method of Example 62, to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.33(1H, s), 8.42(1H, d), 8.14(2H, br), 7.69(1H, d), 7.27(2H, d), 7.22(2H, d), 7.12(1H, s), 6.94(1H, d), 6.55(1H, d), 4.60-4.49(2H, m), 3.57-3.50(1H, m), 3.41(3H, s), 3.38-3.31(1H, m), 3.15-2.91(1H, m), 2.34(3H, s), 2.03(1H, m), 1.92(1H, m), 1.60-1.42(2H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.33 (1H, s), 8.42 (1H, d), 8.14 (2H, br), 7.69 (1H, d), 7.27 (2H, d), 7.22 (2H, d), 7.12 (1H, s), 6.94 (1H, d), 6.55 (1H, d), 4.60-4.49 (2H, m), 3.57-3.50 (1H, m), 3.41 (3H, s), 3.38-3.31 (1H, m), 3.15- 2.91 (1H, m), 2.34 (3H, s), 2.03 (1H, m), 1.92 (1H, m), 1.60-1.42 (2H, m)

FAB MS(m/e) = 474[M+1]+ FAB MS (m / e) = 474 [M + 1] +

실시예 207: (4-디메틸아미노-피페리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논Example 207: (4-Dimethylamino-piperidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -methanone

Figure 112006083464511-PAT00125
Figure 112006083464511-PAT00125

실시예 206에서 얻은 화합물 97 mg(0.205 mmol)을 디클로로에탄 20 ml에 녹이고, 포르말린 61 uL(0.819 mmol)을 가하고 상온에서 5분 교반 후, 나트륨 트리아세톡시보로하이드라이드 174 mg(0.819 mmol)을 가하고 상온에서 4 시간 교반하였다. 반응 완결 후, 디클로로메탄 20 ml를 가하고 포화탄산수소나트륨 수용액 20 ml를 사용하여 씻고 유기층을 농축하였다. 관 크로마토그래피로 분리하여 목적 화 합물 90 mg(0.178 mmol, 수율; 87%)을 얻었다. 97 mg (0.205 mmol) of the compound obtained in Example 206 were dissolved in 20 ml of dichloroethane, formalin 61 uL (0.819 mmol) was added thereto, and stirred at room temperature for 5 minutes, followed by 174 mg (0.819 mmol) of sodium triacetoxyborohydride. It was added and stirred at room temperature for 4 hours. After completion of the reaction, 20 ml of dichloromethane was added, washed with 20 ml of saturated aqueous sodium hydrogen carbonate solution, and the organic layer was concentrated. Separation by column chromatography gave 90 mg (0.178 mmol, yield; 87%) of the target compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.39(1H, d), 7.67(1H, d), 7.27(2H, d), 7.22(2H, d), 7.10(1H, s), 6.97(1H, d), 6.55(1H, d), 4.42(2H, m), 3.50(1H, m), 3.42(3H, s), 3.05-2.84(1H, m), 2.42(1H, m), 2.34(3H, s), 2.22(6H, s), 2.03(1H, m), 1.92(1H, m), 1.60-1.42(2H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.39 (1H, d), 7.67 (1H, d), 7.27 (2H, d), 7.22 (2H, d), 7.10 (1H, s), 6.97 (1H, d), 6.55 (1H, d), 4.42 (2H, m), 3.50 (1H, m), 3.42 (3H, s), 3.05-2.84 (1H, m), 2.42 (1H, m), 2.34 (3H, s) , 2.22 (6H, s), 2.03 (1H, m), 1.92 (1H, m), 1.60-1.42 (2H, m)

FAB MS(m/e) = 502[M+1]+ FAB MS (m / e) = 502 [M + 1] +

제조예 35: ((S)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-카르보닐}-Preparation 35: ((S) -1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine-4-carbonyl }- 피롤리딘Pyrrolidine -3-일)--3 days)- 카르바믹산Carbamic acid terttert -부틸 에스테르-Butyl ester

제조예 33 에서 얻은 화합물을 (S)-피롤리딘-3-일-카르바믹산 tert-부틸 에스테르와 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다.The compound obtained in Preparation Example 33 was reacted with (S) -pyrrolidin-3-yl-carbamic acid tert-butyl ester in the same manner as in Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 8.47(1H, s), 8.36(1H, d), 7.69(1H, d), 7.27(2H, d), 7.21(2H, d), 7.09(1H, s), 6.93(1H, d), 6.52(1H, d), 3.82(1H, m), 3.64-3.54(2H, m), 3.36(3H, s), 2.27(3H, s), 2.21-2.13(2H, m), 2.08-1.99(2H, m), 1.34(9H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 8.47 (1H, s), 8.36 (1H, d), 7.69 (1H, d), 7.27 (2H, d), 7.21 (2H, d), 7.09 (1H, s), 6.93 (1H, d), 6.52 (1H, d), 3.82 (1H, m), 3.64-3.54 (2H, m), 3.36 (3H, s), 2.27 (3H, s), 2.21-2.13 (2H, m), 2.08-1.99 (2H, m), 1.34 (9H, s)

FAB MS(m/e) = 560[M+1]+ FAB MS (m / e) = 560 [M + 1] +

실시예 208: ((S)-3-아미노-피롤리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸 로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논Example 208: ((S) -3-Amino-pyrrolidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine- 2-ylamino] -pyridin-4-yl} -methanone

Figure 112006083464511-PAT00126
Figure 112006083464511-PAT00126

제조예 35에서 얻은 화합물을 실시예 62의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Preparation Example 35 was reacted by the method of Example 62, to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.33(1H, s), 8.38(1H, d), 8.15(2H, br), 7.66(1H, d), 7.27(2H, d), 7.22(2H, d), 7.11(1H, s), 6.96(1H, d), 6.54(1H, d), 3.83(1H, m), 3.64-3.56(2H, m), 3.34(3H, s), 2.28(3H, s), 2.21-2.13(2H, m), 2.08-1.99(2H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.33 (1H, s), 8.38 (1H, d), 8.15 (2H, br), 7.66 (1H, d), 7.27 (2H, d), 7.22 (2H, d), 7.11 (1H, s), 6.96 (1H, d), 6.54 (1H, d), 3.83 (1H, m), 3.64-3.56 (2H, m), 3.34 (3H, s), 2.28 (3H, s), 2.21-2.13 (2H, m), 2.08-1.99 (2H, m)

FAB MS(m/e) = 460[M+1]+ FAB MS (m / e) = 460 [M + 1] +

실시예 209: N-((S)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-카르보닐}-피롤리딘-3-일)-아세트아미드Example 209: N-((S) -1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4- Carbonyl} -pyrrolidin-3-yl) -acetamide

Figure 112006083464511-PAT00127
Figure 112006083464511-PAT00127

실시예 208에서 얻은 화합물 85 mg(0.185 mmol)을 디클로로메탄 10 ml에 녹 이고, N,N-디이소프로필에틸아민 80 uL(0.370 mmol)을 가하고 0℃로 냉각하였다. 반응용액에 무수초산 17.5 uL(0.185 mmol)을 가하고 1 시간 교반하였다. 반응 완결 후, 물 10 ml를 사용하여 씻고 유기층을 농축하였다. 관 크로마토그래피로 분리하여 목적 화합물 81 mg(0.161 mmol, 수율; 87%)을 얻었다. 85 mg (0.185 mmol) of the compound obtained in Example 208 were dissolved in 10 ml of dichloromethane, and 80 uL (0.370 mmol) of N, N-diisopropylethylamine was added and cooled to 0 ° C. 17.5 uL (0.185 mmol) of acetic anhydride was added to the reaction solution, and the mixture was stirred for 1 hour. After completion of the reaction, washed with 10 ml of water and concentrated the organic layer. Separation by column chromatography gave 81 mg (0.161 mmol, yield; 87%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.40(1H, s), 8.31(1H, d), 7.67(1H, d), 7.27(2H, d), 7.21(2H, d), 7.11(1H, s), 6.96(1H, d), 6.54(1H, d), 3.83(1H, m), 3.64-3.56(2H, m), 3.37(3H, s), 2.29(3H, s), 2.21-2.13(2H, m), 2.08-1.99(2H, m), 1.89(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.40 (1H, s), 8.31 (1H, d), 7.67 (1H, d), 7.27 (2H, d), 7.21 (2H, d), 7.11 (1H, s), 6.96 (1H, d), 6.54 (1H, d), 3.83 (1H, m), 3.64-3.56 (2H, m), 3.37 (3H, s), 2.29 (3H, s), 2.21-2.13 (2H, m), 2.08-1.99 (2H, m), 1.89 (3H, s)

FAB MS(m/e) = 502[M+1]+ FAB MS (m / e) = 502 [M + 1] +

제조예 36: ((R)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-카르보닐}-Preparation 36: ((R) -1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine-4-carbonyl }- 피롤리딘Pyrrolidine -3-일)--3 days)- 카르바믹산Carbamic acid terttert -부틸 에스테르-Butyl ester

제조예 33 에서 얻은 화합물을 (R)-피롤리딘-3-일-카바믹산 tert-부틸 에스테르와 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다.The compound obtained in Production Example 33 was reacted with the (R) -pyrrolidin-3-yl-carbamic acid tert-butyl ester in the same manner as in Example 18 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.30(1H, s), 8.61(1H, s), 8.32(1H, d), 7.65(1H, d), 7.26(2H, d), 7.20(2H, d), 7.10(1H, s), 6.96(1H, d), 6.54(1H, d), 3.82(1H, m), 3.62-3.56(2H, m), 3.37(3H, s), 2.29(3H, s), 2.21-2.13(2H, m), 2.08-1.99(2H, m), 1.82(9H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.30 (1H, s), 8.61 (1H, s), 8.32 (1H, d), 7.65 (1H, d), 7.26 (2H, d), 7.20 (2H, d), 7.10 (1H, s), 6.96 (1H, d), 6.54 (1H, d), 3.82 (1H, m), 3.62-3.56 (2H, m), 3.37 (3H, s), 2.29 (3H, s), 2.21-2.13 (2H, m), 2.08-1.99 (2H, m), 1.82 (9H, s)

FAB MS(m/e) = 560[M+1]+ FAB MS (m / e) = 560 [M + 1] +

실시예 210: ((R)-3-아미노-피롤리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논Example 210: ((R) -3-amino-pyrrolidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine-2 -Ylamino] -pyridin-4-yl} -methanone

Figure 112006083464511-PAT00128
Figure 112006083464511-PAT00128

제조예 36에서 얻은 화합물을 실시예 62의 방법으로 반응하여 목적 화합물을 얻었다.The compound obtained in Preparation Example 36 was reacted by the method of Example 62, to obtain the target compound.

1H NMR (DMSO-d6, ppm); 11.27(1H, s), 8.31(1H, d), 8.29(2H, br), 7.65(1H, d), 7.27(2H, d), 7.21(2H, d), 7.12(1H, s), 6.95(1H, d), 6.52(1H, d), 3.81(1H, m), 3.62-3.57(2H, m), 3.34(3H, s), 2.27(3H, s), 2.21-2.13(2H, m), 2.09-1.98(2H, m) 1 H NMR (DMSO-d 6 , ppm); 11.27 (1H, s), 8.31 (1H, d), 8.29 (2H, br), 7.65 (1H, d), 7.27 (2H, d), 7.21 (2H, d), 7.12 (1H, s), 6.95 (1H, d), 6.52 (1H, d), 3.81 (1H, m), 3.62-3.57 (2H, m), 3.34 (3H, s), 2.27 (3H, s), 2.21-2.13 (2H, m ), 2.09-1.98 (2H, m)

FAB MS(m/e) = 460[M+1]+ FAB MS (m / e) = 460 [M + 1] +

실시예 211: N-((R)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-카르보닐}-피롤리딘-3-일)-아세트아미드Example 211: N-((R) -1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4- Carbonyl} -pyrrolidin-3-yl) -acetamide

Figure 112006083464511-PAT00129
Figure 112006083464511-PAT00129

실시예 210에서 얻은 화합물을 실시예 209의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 210 was reacted by the method of Example 209 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.34(1H, s), 8.51(1H, d), 8.32(1H, s), 7.66(1H, d), 7.28(2H, d), 7.23(2H, d), 7.11(1H, s), 6.94(1H, d), 6.51(1H, d), 3.81(1H, m), 3.63-3.56(2H, m), 3.37(3H, s), 2.29(3H, s), 2.21-2.13(2H, m), 2.11-1.99(2H, m), 1.83(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.34 (1H, s), 8.51 (1H, d), 8.32 (1H, s), 7.66 (1H, d), 7.28 (2H, d), 7.23 (2H, d), 7.11 (1H, s), 6.94 (1H, d), 6.51 (1H, d), 3.81 (1H, m), 3.63-3.56 (2H, m), 3.37 (3H, s), 2.29 (3H, s), 2.21-2.13 (2H, m), 2.11-1.99 (2H, m), 1.83 (3H, s)

FAB MS(m/e) = 502[M+1]+ FAB MS (m / e) = 502 [M + 1] +

실시예 212: 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에탄올Example 212: 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl} -ethanol

Figure 112006083464511-PAT00130
Figure 112006083464511-PAT00130

실시예 19에서 얻은 화합물을 제조예 2의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 19 was reacted by the method of Preparation Example 2 to obtain the target compound.

1H NMR (CDCl3, ppm); δ 9.11(1H, s), 8.26(1H, d), 7.53(1H, d), 7.16-7.22(4H, m), 6.88(1H, s), 6.81(1H, d), 6.55(1H, d), 3.89(2H, t), 3.49(3H, s), 2.82(2H, t), 2.37(3H, s) 1 H NMR (CDCl 3 , ppm); δ 9.11 (1H, s), 8.26 (1H, d), 7.53 (1H, d), 7.16-7.22 (4H, m), 6.88 (1H, s), 6.81 (1H, d), 6.55 (1H, d ), 3.89 (2H, t), 3.49 (3H, s), 2.82 (2H, t), 2.37 (3H, s)

FAB MS(m/e) = 392[M+1]+ FAB MS (m / e) = 392 [M + 1] +

실시예 213: 1-[4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에틸)-피페라진-1-일]-에타논Example 213: 1- [4- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl } -Ethyl) -piperazin-1-yl] -ethanone

Figure 112006083464511-PAT00131
Figure 112006083464511-PAT00131

실시예 212에서 얻은 화합물 150 mg(0.383 mmol)을 디클로로메탄 10 ml로 녹이고 Dess-Martin 시약 2.17 g(0.766 mmol, 15 wt% 디클로로메탄 용액)을 넣는다. 상온에서 2 시간 동안 교반하고, 포화 티오황산나트륨 수용액 5 ml를 가한다. 디클로로메탄을 사용하여 20 ml씩 두번 추출하여 농축한다. 얻어진 알데히드를 디클로로에탄 15 ml를 사용하여 녹이고, 아세틸피페라진 98 mg (0.766 mmol)과 소듐 트리아세톡시보로하이드라이드 162 mg (0.766 mmol)을 가하고 상온에서 12 시간동안 교반하고, 메탄올로 반응을 종결한다. 반응 완결 후 디클로로메탄 30 ml를 사용하여 추출하고 농축한다. 관 크로마토그래피로 분리하여 목적 화합물 129 mg(0.257 mmol, 수율; 67%)을 얻었다.150 mg (0.383 mmol) of the compound obtained in Example 212 are dissolved with 10 ml of dichloromethane, and 2.17 g (0.766 mmol, 15 wt% dichloromethane solution) of Dess-Martin reagent is added thereto. Stir for 2 hours at room temperature and add 5 ml of saturated aqueous sodium thiosulfate solution. Concentrate by extracting twice with 20 ml with dichloromethane. The obtained aldehyde was dissolved using 15 ml of dichloroethane, 98 mg (0.766 mmol) of acetylpiperazine and 162 mg (0.766 mmol) of sodium triacetoxyborohydride were added thereto, stirred at room temperature for 12 hours, and the reaction was terminated with methanol. do. After completion of the reaction, extracted with 30 ml of dichloromethane and concentrated. Separation by column chromatography gave 129 mg (0.257 mmol, yield; 67%) of the title compound.

1H NMR (CDCl3, ppm); δ 8.95(1H, s), 8.24(1H, d), 7.53(1H, d), 7.16-7.22(4H, m), 6.85(1H, s), 6.77(1H, d), 6.54(1H, d), 3.62(2H, m), 3.49(3H, s), 3.44(2H, m), 2.63(2H, t), 2.61(2H, t), 2.45(4H, m), 2.37(3H, s), 2.09(3H, s) 1 H NMR (CDCl 3 , ppm); δ 8.95 (1H, s), 8.24 (1H, d), 7.53 (1H, d), 7.16-7.22 (4H, m), 6.85 (1H, s), 6.77 (1H, d), 6.54 (1H, d ), 3.62 (2H, m), 3.49 (3H, s), 3.44 (2H, m), 2.63 (2H, t), 2.61 (2H, t), 2.45 (4H, m), 2.37 (3H, s) , 2.09 (3H, s)

FAB MS(m/e) = 502[M+1]+ FAB MS (m / e) = 502 [M + 1] +

실시예 214: 4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에틸)-피페라진-2-온Example 214: 4- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl} -ethyl ) -Piperazine-2-one

Figure 112006083464511-PAT00132
Figure 112006083464511-PAT00132

실시예 213에서 N-아세틸피페라진 대신 피페라진-2-온을 사용하여 같은 방법으로 반응하여 목적 화합물을 얻었다. In Example 213, the reaction was performed in the same manner using piperazine-2-one instead of N-acetylpiperazine to obtain the target compound.

1H NMR (CDCl3, ppm); δ 10.23(1H, s), 8.22(1H, d), 7.44(1H, d), 7.15-7.20(4H, m), 6.89(1H, s), 6.74(1H, d), 6.52(1H, d), 3.48(3H, s), 3.33(2H, t), 3.24(2H, s), 2.72-2.78(4H, m), 2.66(2H, t), 2.36(3H, s) 1 H NMR (CDCl 3 , ppm); δ 10.23 (1H, s), 8.22 (1H, d), 7.44 (1H, d), 7.15-7.20 (4H, m), 6.89 (1H, s), 6.74 (1H, d), 6.52 (1H, d ), 3.48 (3H, s), 3.33 (2H, t), 3.24 (2H, s), 2.72-2.78 (4H, m), 2.66 (2H, t), 2.36 (3H, s)

FAB MS(m/e) = 475[M+1]+ FAB MS (m / e) = 475 [M + 1] +

실시예 215: NExample 215: N 55 -메틸-N-Methyl-N 22 -{4-[2-(4-메틸-피페라진-1-일)-에틸]-피리딘-2-일}-N-{4- [2- (4-Methyl-piperazin-1-yl) -ethyl] -pyridin-2-yl} -N 55 -p-톨 릴-티아졸로[5,4-b]피리딘-2,5-디아민-p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

Figure 112006083464511-PAT00133
Figure 112006083464511-PAT00133

실시예 21에서 얻은 화합물 110 mg (0.226 mmol)을 무수 테트라히드로퓨란 20 ml에 녹이고, 리튬알루미늄하이드라이드 34 mg (0.902 mmol)을 가하고 6 시간 동안 환류 교반하였다. 반응 완결 후 0℃로 냉각한 후 물 0.3 ml, 15% 가성소다 수용액 0.3 ml, 다시 물 0.9 ml를 가하여 천천히 가하고 20분동안 교반하였다. 셀라이트에 여과하여 고체를 제거하고 여과액을 농축한 후 관크로마토그래피로 분리하여 목적 화합물 65 mg (0.138 mmol, 수율; 61%)을 얻었다. 110 mg (0.226 mmol) of the compound obtained in Example 21 were dissolved in 20 ml of anhydrous tetrahydrofuran, 34 mg (0.902 mmol) of lithium aluminum hydride was added thereto, and the mixture was stirred under reflux for 6 hours. After completion of the reaction, the mixture was cooled to 0 ° C., 0.3 ml of water, 0.3 ml of 15% aqueous sodium hydroxide solution, and 0.9 ml of water were added thereto, and the mixture was slowly added thereto and stirred for 20 minutes. The solid was removed by filtration through celite, and the filtrate was concentrated and separated by column chromatography to obtain 65 mg (0.138 mmol, yield; 61%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 10.41(1H, s), 8.23(1H, d), 7.54(1H, d), 7.15-7.20(4H, m), 6.78(1H, s), 6.74(1H, d), 6.55(1H, d), 3.50(3H, s), 2.54(2H, t), 2.36(3H, s), 2.28(2H, t), 2.25(3H, s), 2.24-2.62(8H, m) 1 H NMR (DMSO-d 6 , ppm); δ 10.41 (1H, s), 8.23 (1H, d), 7.54 (1H, d), 7.15-7.20 (4H, m), 6.78 (1H, s), 6.74 (1H, d), 6.55 (1H, d ), 3.50 (3H, s), 2.54 (2H, t), 2.36 (3H, s), 2.28 (2H, t), 2.25 (3H, s), 2.24-2.62 (8H, m)

FAB MS(m/e) = 474[M+1]+ FAB MS (m / e) = 474 [M + 1] +

하기 표 13은 상기 실시예들에서 얻은 화합물을 사용하여 실시예 215의 방법으로 반응하여 소정의 목적 화합물들을 합성한 실시예들이다.Table 13 below shows examples of synthesizing desired compounds by reacting by the method of Example 215 using the compound obtained in the above examples.

[표 13]TABLE 13

Figure 112006083464511-PAT00134
Figure 112006083464511-PAT00134

실시예 223: 2-히드록시-1-[4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리 딘-2-일아미노]-피리딘-4-일}-에틸)-피페라진-1-일]-에타논Example 223: 2-hydroxy-1- [4- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -Pyridin-4-yl} -ethyl) -piperazin-1-yl] -ethanone

Figure 112006083464511-PAT00135
Figure 112006083464511-PAT00135

실시예 218에서 얻어진 화합물과 히드록시아세트산을 이용하여 실시예 18의 방법으로 반응하여 목적 화합물을 얻었다. The target compound was obtained by reacting the compound obtained in Example 218 with the method of Example 18 using hydroxyacetic acid.

1H NMR (CDCl3, ppm); δ 8.29(1H, d), 7.58(1H, d), 7.20-7.27(4H, m), 6.93(1H, s), 6.82(1H, d), 6.58(1H, d), 4.20(2H, s), 3.73(2H, t), 3.54(3H, s), 3.32(2H, t), 2.79(2H, t), 2.69(2H, t), 2.54(4H, t), 2.41(3H, s) 1 H NMR (CDCl 3 , ppm); δ 8.29 (1H, d), 7.58 (1H, d), 7.20-7.27 (4H, m), 6.93 (1H, s), 6.82 (1H, d), 6.58 (1H, d), 4.20 (2H, s ), 3.73 (2H, t), 3.54 (3H, s), 3.32 (2H, t), 2.79 (2H, t), 2.69 (2H, t), 2.54 (4H, t), 2.41 (3H, s)

FAB MS(m/e) = 518[M+1]+ FAB MS (m / e) = 518 [M + 1] +

실시예 224: 2-히드록시-2-메틸-1-[4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-에틸)-피페라진-1-일]프로판-1-온Example 224: 2-hydroxy-2-methyl-1- [4- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine-2- Ylamino] -pyridin-4-yl} -ethyl) -piperazin-1-yl] propan-1-one

Figure 112006083464511-PAT00136
Figure 112006083464511-PAT00136

실시예 223에서 히드록시아세트산 대신 2-히드록시-2-메틸-프로피온산을 이용하여 같은 방법으로 반응하여 목적 화합물을 얻었다. In Example 223, the reaction was carried out in the same manner using 2-hydroxy-2-methyl-propionic acid instead of hydroxyacetic acid to obtain the target compound.

1H NMR (CDCl3, ppm); δ 8.28(1H, d), 7.57(1H, d), 7.20-7.27(4H, m), 6.92(1H, s), 6.81(1H, d), 6.57(1H, d), 3.73(4H, t), 3.54(3H, s), 2.84(1H, d), 2.80(2H, d), 2.66(2H, t), 2.53(4H, t), 2.40(3H, s), 1.53(6H, s) 1 H NMR (CDCl 3 , ppm); δ 8.28 (1H, d), 7.57 (1H, d), 7.20-7.27 (4H, m), 6.92 (1H, s), 6.81 (1H, d), 6.57 (1H, d), 3.73 (4H, t ), 3.54 (3H, s), 2.84 (1H, d), 2.80 (2H, d), 2.66 (2H, t), 2.53 (4H, t), 2.40 (3H, s), 1.53 (6H, s)

FAB MS(m/e) = 546[M+1]+ FAB MS (m / e) = 546 [M + 1] +

실시예 225: 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로피온산 메틸 에스테르Example 225: 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -propionic acid methyl ester

Figure 112006083464511-PAT00137
Figure 112006083464511-PAT00137

실시예 9에서 얻은 화합물 1.4 g(3.7 mmol)을 디클로로메탄 25 mL로 녹이고 Dess-Martin 시약 16 g (5.6 mmol, 15 wt% in 디클로로메탄)을 넣는다. 상온에서 2 시간 동안 교반하고, 포화 티오황산나트륨 수용액 5 ml를 가하고 디클로로메탄을 20 ml를 이용하여 추출하여 농축하여 알데히드 형태의 중간체를 얻었다. 불꽃 건조된 둥근 플라스크에 소듐 하이드라이드 440 mg(11.1 mmol)을 넣고 무수의 테트라하이드로퓨란 30 ml를 넣는다. 온도를 0℃로 낮춘 다음, 트리에틸 포스포노아세테이트 2.49 g(11.1 mmol)을 무수의 테트라하이드로퓨란 20 ml에 녹여 넣어 준다. 온도를 상온으로 올려 1 시간 동안 교반하고, 다시 온도를 0℃로 낮춰 앞에서 얻은 알데히드를 무수의 테트라하이드로 퓨란 20 ml에 녹여 30 분간 천천히 넣어 준다. 온도를 상온으로 올려 12 시간 동안 교반한다. 물 5 ml를 가해 반응을 종결하고, 감압하에서 용매를 제거한다. 에틸 아세테이트로 30 ml씩 두번 추출하여 농축하였 다. 얻은 물질에 메탄올 40 ml를 넣고, 10% 팔라듐/탄소 300 mg을 넣고, 수소 가스를 충전하여 3 일 동안 교반한다. 유리 필터에 셀라이트를 깔고 용액을 여과한다. 여과액을 농축하고 물 30 ml를 가하고 에틸 아세테이트로 30 ml씩 두번 추출하고 다시 농축하였다. 관 크로마토그래피로 분리하여 목적 화합물 1.07 g(2.48 mmol, 수율; 67%)을 얻었다. 1.4 g (3.7 mmol) of the compound obtained in Example 9 were dissolved in 25 mL of dichloromethane, and 16 g (5.6 mmol, 15 wt% in dichloromethane) of Dess-Martin reagent was added thereto. After stirring for 2 hours at room temperature, 5 ml of saturated sodium thiosulfate aqueous solution was added, dichloromethane was extracted with 20 ml, and concentrated to obtain an aldehyde intermediate. Into a flame-dried round flask, 440 mg (11.1 mmol) of sodium hydride was added and 30 ml of anhydrous tetrahydrofuran was added. After the temperature was lowered to 0 ° C., 2.49 g (11.1 mmol) of triethyl phosphonoacetate was dissolved in 20 ml of anhydrous tetrahydrofuran. The temperature was raised to room temperature and stirred for 1 hour. The temperature was lowered to 0 ° C., and the aldehyde obtained above was dissolved in 20 ml of anhydrous tetrahydrofuran and slowly added for 30 minutes. The temperature is raised to room temperature and stirred for 12 hours. 5 ml of water is added to terminate the reaction and the solvent is removed under reduced pressure. Extracted 30 ml twice with ethyl acetate and concentrated. 40 ml of methanol was added to the obtained material, 10 mg of palladium / carbon was added thereto, and hydrogen gas was charged and stirred for 3 days. Celite is placed on the glass filter and the solution is filtered. The filtrate was concentrated, 30 ml of water was added, extracted twice with 30 ml of ethyl acetate and concentrated again. Separation by column chromatography gave 1.07 g (2.48 mmol, yield; 67%) of the title compound.

1H NMR (CDCl3, ppm); δ 9.51(1H, s), 8.25(1H, d), 7.55(1H, d), 7.16-7.22(4H, m), 6.83(1H, s), 6.77(1H, d), 6.56(1H, d), 3.65(3H, s), 3.50(3H, s), 2.90(2H, t), 2.62(2H, t), 2.36(3H, s) 1 H NMR (CDCl 3 , ppm); δ 9.51 (1H, s), 8.25 (1H, d), 7.55 (1H, d), 7.16-7.22 (4H, m), 6.83 (1H, s), 6.77 (1H, d), 6.56 (1H, d ), 3.65 (3H, s), 3.50 (3H, s), 2.90 (2H, t), 2.62 (2H, t), 2.36 (3H, s)

FAB MS(m/e) = 434[M+1]+ FAB MS (m / e) = 434 [M + 1] +

실시예 226: 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로피온산 Example 226: 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -propionic acid

Figure 112006083464511-PAT00138
Figure 112006083464511-PAT00138

실시예 225에서 얻은 화합물을 실시예 17의 방법으로 가수 분해하여 목적 화합물을 얻었다. The compound obtained in Example 225 was hydrolyzed by the method of Example 17 to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.23(1H, s), 8.12(1H, d), 7.56(1H, d), 7.16-7.22(4H, m), 6.94(1H, s), 6.81(1H, d), 6.49(1H, d), 3.35(3H, s), 2.74(2H, t), 2.41(2H, t), 2.30(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.23 (1H, s), 8.12 (1H, d), 7.56 (1H, d), 7.16-7.22 (4H, m), 6.94 (1H, s), 6.81 (1H, d), 6.49 (1H, d ), 3.35 (3H, s), 2.74 (2H, t), 2.41 (2H, t), 2.30 (3H, s)

FAB MS(m/e) = 420[M+1]+ FAB MS (m / e) = 420 [M + 1] +

하기 표 14은 실시예 226에서 얻은 화합물을 사용하여 실시예 18의 방법으로 반응하여 소정의 목적 화합물들을 합성한 실시예들이다.Table 14 below shows examples of synthesizing desired compounds by reacting by the method of Example 18 using the compound obtained in Example 226.

[표 14]TABLE 14

Figure 112006083464511-PAT00139
Figure 112006083464511-PAT00139

실시예 230: 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로판-1-올Example 230: 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -propane-1- Come

Figure 112006083464511-PAT00140
Figure 112006083464511-PAT00140

실시예 225에서 얻은 화합물을 제조예 2의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 225 was reacted by the method of Preparation Example 2 to obtain the target compound.

1H NMR (CDCl3, ppm); δ 8.22(1H, s), 7.52(1H, d), 7.16-7.22(4H, m), 6.89(1H, s), 6.79(1H, d), 6.54(1H, d), 3.74(2H, t), 3.49(3H, s), 2.68(2H, t), 2.37(3H, s), 1.92(2H, m) 1 H NMR (CDCl 3 , ppm); δ 8.22 (1H, s), 7.52 (1H, d), 7.16-7.22 (4H, m), 6.89 (1H, s), 6.79 (1H, d), 6.54 (1H, d), 3.74 (2H, t ), 3.49 (3H, s), 2.68 (2H, t), 2.37 (3H, s), 1.92 (2H, m)

FAB MS(m/e) = 406[M+1]+ FAB MS (m / e) = 406 [M + 1] +

제조예 37: NPreparation Example 37 N 22 -[4-(3-클로로-프로필)-피리딘-2-일]-N-[4- (3-Chloro-propyl) -pyridin-2-yl] -N 55 -메틸-N-Methyl-N 55 -p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민-p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine

실시예 230에서 얻은 화합물을 제조예 5의 방법으로 반응하여 목적 화합물을 얻었다. The compound obtained in Example 230 was reacted by the method of Preparation Example 5 to obtain the target compound.

1H NMR (CDCl3, ppm); δ 8.23(1H, s), 7.51(1H, d), 7.16-7.22(4H, m), 7.11(1H, d), 6.89(1H, d), 6.53(1H, d), 3.54(2H, t), 3.48(3H, s), 2.81(2H, t), 2.38(3H, s), 2.10(2H, m) 1 H NMR (CDCl 3 , ppm); δ 8.23 (1H, s), 7.51 (1H, d), 7.16-7.22 (4H, m), 7.11 (1H, d), 6.89 (1H, d), 6.53 (1H, d), 3.54 (2H, t ), 3.48 (3H, s), 2.81 (2H, t), 2.38 (3H, s), 2.10 (2H, m)

FAB MS(m/e) = 424[M+1]+ FAB MS (m / e) = 424 [M + 1] +

하기 표 15은 제조예 37에서 얻은 화합물을 사용하여 실시예 3의 방법으로 반응하여 소정의 목적 화합물들을 합성한 실시예들이다.Table 15 below shows examples of synthesizing desired compounds by reacting by the method of Example 3 using the compound obtained in Preparation Example 37.

[표 15]TABLE 15

Figure 112006083464511-PAT00141
Figure 112006083464511-PAT00141

제조예Production Example 38: 2- 38: 2- 클로로Chloro -5-[-5- [ 메틸methyl -(5-니트로-피리딘-2-일)-아미노]-벤조산 -(5-nitro-pyridin-2-yl) -amino] -benzoic acid 메틸methyl 에스테르 ester

메탄올 200 ml에 아세틸 클로라이드 4.3 ml(60 mmol)을 가하고 상온에서 15분간 교반한 후, 5-아미노-2-클로로-벤조산 메틸 에스테르 30 g(162 mmol)과 2-클 로로-5-니트로피리딘 23.9 g(150 mmol)을 가하고 20 시간 동안 환류교반하였다. 반응완결 후 농축하고 물 500 ml을 가하여 생긴 고체를 여과하고 건조하여 2-클로로-5-(5-니트로-피리딘-2-일아미노)-벤조산 메틸 에스테르 40.2 g(130 mmol, 수율; 87%)을 얻었다. 이 중간체 40 g(130 mmol)을 N,N-디메틸포름아미드 150ml에 녹이고, 0℃로 온도를 낮춘 후, 소듐 하이드라이드 6.76 g(60%, 169 mmol)을 가하고 20 분 교반 후, 메틸 요오드 10.5 ml(169 mmol)를 10분간 가하고 두 시간 동안 교반하였다. 반응 완결 후, 물 50 ml을 10분 간 가한 후, 농축하였다. 물 400 ml를 가하여 생긴 고체를 여과하고 건조하여 목적 화합물 39.5 g(123 mmol, 수율; 94%)을 얻었다. 4.3 ml (60 mmol) of acetyl chloride was added to 200 ml of methanol and stirred at room temperature for 15 minutes, followed by 30 g (162 mmol) of 5-amino-2-chloro-benzoic acid methyl ester and 2-chloro-5-nitropyridine 23.9. g (150 mmol) was added and stirred under reflux for 20 hours. After completion of the reaction, the resultant was concentrated, 500 ml of water was added, the solid formed was filtered and dried to afford 40.2 g (130 mmol, yield; 87%) of 2-chloro-5- (5-nitro-pyridin-2-ylamino) -benzoic acid methyl ester. Got. Dissolve 40 g (130 mmol) of this intermediate in 150 ml of N, N-dimethylformamide, lower the temperature to 0 ° C, add 6.76 g (60%, 169 mmol) of sodium hydride, stir for 20 minutes, and then methyl iodine 10.5. ml (169 mmol) was added for 10 minutes and stirred for two hours. After completion of the reaction, 50 ml of water was added for 10 minutes, and then concentrated. 400 ml of water was added thereto, and the resulting solid was filtered and dried to afford 39.5 g (123 mmol, yield; 94%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 8.23(1H, d), 7.81(1H, s), 7.66 (1H, d), 7.43(1H, s), 7.25(1H, m), 6.52(1H, s), 4.10(3H, s), 3.41(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.23 (1H, d), 7.81 (1H, s), 7.66 (1H, d), 7.43 (1H, s), 7.25 (1H, m), 6.52 (1H, s), 4.10 (3H, s), 3.41 (3H, s)

FAB MS(m/e) = 322[M+1]+ FAB MS (m / e) = 322 [M + 1] +

제조예 39: 5-[(2-아미노-티아졸로[5,4-b]피리딘-5-일)-메틸-아미노]-2-클로로-벤조산 Preparation 39: 5-[(2-amino-thiazolo [5,4-b] pyridin-5-yl) -methyl-amino] -2-chloro-benzoic acid 메틸methyl 에스테르 ester

제조예 38에서 얻은 화합물 39.0 g(121 mmol)을 에틸 아세테이트 500 ml에 녹이고 0℃로 온도를 낮춘 후, 디클로로주석 이수화물 110 g(486 mmol)과 진한염산 수용액 5 ml를 가하고 20 시간 동안 서서히 온도를 상온으로 올리면서 교반하였다. 반응 완결 후, 다시 0℃로 온도를 낮추고 암모니아수를 이용하여 중화하였다. 이 때 생기는 고체를 셀라이트에 여과하고 에틸 아세테이트 800 ml를 사용하여 씻어 주었다. 여과액을 농축하고 다시 초산 300 ml를 사용하여 녹였다. 반응용액을 다시 0℃로 온도를 낮춘 후, 칼륨 이소티오시아네이트 58.8 g(605 mmol)을 가하고 10분 교반 후, 브롬 9.3 ml를 초산 100 ml에 묽혀 4 시간 동안 서서히 적가하였다. 적가 완결 후, 서서히 온도를 상온으로 올려가며 20 시간 동안 교반하였다. 반응 완결 후, 반응액을 90℃로 올린 후 셀라이트에 여과하여 반응중에 생긴 고체를 여과하고 초산 150 ml를 사용하여 씻어 주었다. 여과액을 다시 농축하고, 포화탄산수소나트륨 수용액을 사용하여 중화한 후, 테트라히드로퓨란을 사용하여 300 ml씩 3번 추출하였다. 유기층을 농축하고 관 크로마토그리피로 분리하여 목적 화합물 22.8 g(65.3 mmol, 수율; 54%)을 얻었다. 39.0 g (121 mmol) of the compound obtained in Preparation Example 38 was dissolved in 500 ml of ethyl acetate, and the temperature was reduced to 0 ° C. Then, 110 g (486 mmol) of dichlorotin dihydrate and 5 ml of concentrated hydrochloric acid solution were added, and the temperature was gradually decreased for 20 hours. It was stirred while raising to room temperature. After completion of the reaction, the temperature was lowered to 0 ° C. and neutralized with ammonia water. The solid produced at this time was filtered through celite and washed with 800 ml of ethyl acetate. The filtrate was concentrated and dissolved again using 300 ml of acetic acid. After the reaction solution was cooled to 0 ° C., 58.8 g (605 mmol) of potassium isothiocyanate was added thereto, and after stirring for 10 minutes, 9.3 ml of bromine was diluted with 100 ml of acetic acid and slowly added dropwise thereto for 4 hours. After completion of the dropwise addition, the temperature was slowly raised to room temperature and stirred for 20 hours. After completion of the reaction, the reaction solution was raised to 90 ℃ and filtered through celite to filter the solid formed during the reaction and washed with 150 ml of acetic acid. The filtrate was concentrated again, neutralized with saturated aqueous sodium hydrogen carbonate solution, and then extracted three times with 300 ml each with tetrahydrofuran. The organic layer was concentrated and separated by column chromatography to give 22.8 g (65.3 mmol, yield; 54%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 7.81(1H, d), 7.66 (1H, d), 7.43(1H, m), 7.25(2H, m), 7.16(1H, t), 6.52(1H, d), 3.91(3H, s), 3.51(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 7.81 (1H, d), 7.66 (1H, d), 7.43 (1H, m), 7.25 (2H, m), 7.16 (1H, t), 6.52 (1H, d), 3.91 (3H, s), 3.51 (3H, s)

FAB MS(m/e) = 349[M+1]+ FAB MS (m / e) = 349 [M + 1] +

제조예 40: 5-({2-[4-(tert-부틸-디메틸-실라닐옥시메틸)-피리딘-2-일아미노]-티아졸로[Preparation Example 40: 5-({2- [4- (tert-butyl-dimethyl-silanyloxymethyl) -pyridin-2-ylamino] -thiazolo [ 5,4-b]피리딘5,4-b] pyridine -5-일}--5 days}- 메틸methyl -아미노)-2--Amino) -2- 클로로Chloro -벤조산 -Benzoic acid 메틸methyl 에스테르 ester

제조예 39에서 얻은 화합물 15 g(43.1 mmol)과 4-(tert-부틸-디메틸-실라닐옥시메틸)-2-클로로-피리딘 14.4 g(56.0 mmol)을 톨루엔 300 ml에 녹인 후, 탄산칼륨 6.85 g(64.6 mmol)과 트리스(디벤질리덴아세톤)디팔라듐 2.37 g(2.59 mmol), 잔 포스 2.24 g(3.86 mmol)을 가하고 30분 동안 질소를 불어 주며 교반하고, 다시 8 시간 동안 환류교반하였다. 반응 완결 후, 셀라이트에 고체를 여과한 후, 여과액을 물 300 ml로 씻고 유기층을 농축하였다. 관 크로마토그래피로 분리하여 목적 화합물 16.4 g(28.8 mmol, 수율; 67%)을 얻었다. 15 g (43.1 mmol) of the compound obtained in Preparation Example 39 and 14.4 g (56.0 mmol) of 4- (tert-butyl-dimethyl-silanyloxymethyl) -2-chloro-pyridine were dissolved in 300 ml of toluene, followed by potassium carbonate 6.85. g (64.6 mmol), 2.37 g (2.59 mmol) of tris (dibenzylideneacetone) dipalladium and 2.24 g (3.86 mmol) of xantose were added thereto, stirred with blowing with nitrogen for 30 minutes, and then stirred under reflux for 8 hours. After completion of the reaction, the solid was filtered through celite, and then the filtrate was washed with 300 ml of water and the organic layer was concentrated. Separation by column chromatography gave 16.4 g (28.8 mmol, yield; 67%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.23(1H, d), 7.72(1H, d), 7.62(1H, s), 7.50(1H, d), 7.42(1H, d), 7.09(1H, s), 6.88(1H, s), 6.81(1H, s), 4.49(2H, s), 3.80(3H, s), 3.41(3H, s), 0.92(9H, s), 0.10(6H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.23 (1H, d), 7.72 (1H, d), 7.62 (1H, s), 7.50 (1H, d), 7.42 (1H, d), 7.09 (1H, s), 6.88 (1H, s), 6.81 (1H, s), 4.49 (2H, s), 3.80 (3H, s), 3.41 (3H, s), 0.92 (9H, s), 0.10 (6H, s)

FAB MS(m/e) = 570[M+1]+ FAB MS (m / e) = 570 [M + 1] +

실시예 234: 2-클로로-5-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-벤조산 메틸 에스테르Example 234: 2-Chloro-5-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino}- Benzoic acid methyl ester

Figure 112006083464511-PAT00142
Figure 112006083464511-PAT00142

제조예 39에서 얻은 화합물 10.5 g(18.4 mmol)을 메탄올 100 ml를 사용하여 녹인 후, 암모늄 플루오라이드 2.73 g(73.7 mmol)을 가하고 3 시간 동안 환류 교반하였다. 반응 완결 후, 물 400 ml를 가하여 생기는 고체를 여과하고 건조하여 목적 화합물 7.81 g(17.1 mmol, 수율; 93%)을 얻었다. After dissolving 10.5 g (18.4 mmol) of the compound obtained in Preparation Example 39 using 100 ml of methanol, 2.73 g (73.7 mmol) of ammonium fluoride was added thereto, and the mixture was stirred under reflux for 3 hours. After completion of the reaction, 400 ml of water was added to the resulting solid, which was filtered and dried to yield 7.81 g (17.1 mmol, yield; 93%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.38(1H, s), 8.19(1H, d), 7.73(1H, d), 7.61(1H, s), 7.51(1H, d), 7.45(1H, d), 7.09(1H, s), 6.86(1H, s), 6.81(1H, s), 5.42(1H, t), 4.49(2H, d), 3.80(3H, s), 3.41(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.38 (1H, s), 8.19 (1H, d), 7.73 (1H, d), 7.61 (1H, s), 7.51 (1H, d), 7.45 (1H, d), 7.09 (1H, s), 6.86 (1H, s), 6.81 (1H, s), 5.42 (1H, t), 4.49 (2H, d), 3.80 (3H, s), 3.41 (3H, s)

FAB MS(m/e) = 456[M+1]+ FAB MS (m / e) = 456 [M + 1] +

실시예 235: 2-클로로-5-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-벤조산Example 235: 2-Chloro-5-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino}- Benzoic acid

Figure 112006083464511-PAT00143
Figure 112006083464511-PAT00143

실시예 234에서 얻은 화합물 7.6 g(16.7 mmol)을 테트라히드로퓨란 150 ml와 메탄올 50 ml에 녹이고, 리튬 하이드라이드 일수화물 2.80 g(66.7 ml)를 물 50 ml에 녹여 가하고 20 시간 동안 50℃에서 교반하였다. 반응 완결 후, 감압증류하여 테트라히드로퓨란과 메탄올을 제거 한 후, 0℃로 냉각하고 2노르말 염산 수용액으로 중화하여 생긴 고체를 여과 건조하여 목적 화합물 6.94 g(15.7 mmol, 수율; 94%)을 얻었다. 7.6 g (16.7 mmol) of the compound obtained in Example 234 were dissolved in 150 ml of tetrahydrofuran and 50 ml of methanol, and 2.80 g (66.7 ml) of lithium hydride monohydrate was added to 50 ml of water and stirred at 50 ° C for 20 hours. It was. After completion of the reaction, the mixture was distilled under reduced pressure to remove tetrahydrofuran and methanol, which was then cooled to 0 ° C. and neutralized with a 2-normal hydrochloric acid aqueous solution. The resulting solid was filtered and dried to obtain 6.94 g (15.7 mmol, Yield; 94%) of the title compound. .

1H NMR (DMSO-d6, ppm); δ 12.97(1H, s), 11.32(1H, s), 8.18(1H, d), 7.72(1H, d), 7.63(1H, s), 7.51(1H, d), 7.44(1H, d), 7.09(1H, s), 6.84(1H, s), 6.79(1H, s), 5.42(1H, t), 4.49(2H, d), 3.38(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 12.97 (1H, s), 11.32 (1H, s), 8.18 (1H, d), 7.72 (1H, d), 7.63 (1H, s), 7.51 (1H, d), 7.44 (1H, d), 7.09 (1H, s), 6.84 (1H, s), 6.79 (1H, s), 5.42 (1H, t), 4.49 (2H, d), 3.38 (3H, s)

FAB MS(m/e) = 442[M+1]+ FAB MS (m / e) = 442 [M + 1] +

실시예 236: 2-클로로-5-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-N-메톡시-벤즈아미드Example 236 2-chloro-5-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino}- N-methoxy-benzamide

Figure 112006083464511-PAT00144
Figure 112006083464511-PAT00144

실시예 235에서 얻은 화합물 5.0 g(11.3 mmol)을 N,N-디메틸포름아미드 70ml에 녹이고, 메톡실아민 염산염 1.42 g(17.0 mmol), 1-히드록시벤조트리아졸 3.05 g(22.6 mmol), N-(3-디메틸아미노프로필)-N'-에틸카보디이미드 3.68 g(19.2 mmol), 트리에틸아민 2.36 ml(17.0 mmol)을 가하고 상온에서 4 시간 동안 교반하였다. 반응 완결 후 농축하고, 물 200 ml를 가하여 생기는 고체를 여과하고 건조하여 목적 화합물 4.87 g(10.3 mmol, 수율; 92%)을 얻었다. 5.0 g (11.3 mmol) of the compound obtained in Example 235 were dissolved in 70 ml of N, N-dimethylformamide, 1.42 g (17.0 mmol) of methoxylamine hydrochloride, 3.05 g (22.6 mmol) of 1-hydroxybenzotriazole, N 3.68 g (19.2 mmol) of-(3-dimethylaminopropyl) -N'-ethylcarbodiimide and 2.36 ml (17.0 mmol) of triethylamine were added and stirred at room temperature for 4 hours. After completion of the reaction, the mixture was concentrated, and 200 ml of water was added, and the resulting solid was filtered and dried to yield 4.87 g (10.3 mmol, yield; 92%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.27(1H, s), 8.20(1H, d), 7.72(1H, d), 7.44(1H, d), 7.33(1H, d), 7.30(1H, s), 7.08(1H, s), 6.86(1H, d), 6.78(1H, d), 5.42(1H, t), 4.49(2H, d), 3.67(3H, s), 3.40(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.27 (1H, s), 8.20 (1H, d), 7.72 (1H, d), 7.44 (1H, d), 7.33 (1H, d), 7.30 (1H, s), 7.08 (1H, s), 6.86 (1H, d), 6.78 (1H, d), 5.42 (1H, t), 4.49 (2H, d), 3.67 (3H, s), 3.40 (3H, s)

FAB MS(m/e) = 471[M+1]+ FAB MS (m / e) = 471 [M + 1] +

제조예 41: 2-클로로-5-{[2-(4-클로로메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-Preparation 41: 2-Chloro-5-{[2- (4-chloromethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl]- 메틸methyl -아미노}-N--Amino} -N- 메톡시Methoxy -- 벤즈아미드Benzamide

실시예 236에서 얻은 화합물 4.70 g(9.98 mmol)을 디클로로메탄 70 ml에 녹이고, N,N-디메틸포름아미드 3.86 ml(49.9 mmol)과 포스포러스 옥시클로라이드 4.57 ml(49.9 mmol)을 가하고 상온에서 15 시간 교반하였다. 반응 완결 후 농축하고, 디에틸에테르 50 ml를 가하고 10분 교반 후 건조하여 목적 화합물 4.10 g(8.38 mmol, 수율; 84%)을 얻었다. 4.70 g (9.98 mmol) of the compound obtained in Example 236 are dissolved in 70 ml of dichloromethane, and 3.86 ml (49.9 mmol) of N, N-dimethylformamide and 4.57 ml (49.9 mmol) of phosphorus oxychloride are added thereto at room temperature for 15 hours. Stirred. After completion of the reaction, the reaction mixture was concentrated, 50 ml of diethyl ether was added, stirred for 10 minutes, and dried to obtain 4.10 g (8.38 mmol, yield; 84%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.21(1H, d), 7.74(1H, d), 7.47(1H, d), 7.36(1H, d), 7.31(1H, s), 7.07(1H, s), 6.84(1H, d), 6.77(1H, d), 3.88(2H, s), 3.67(3H, s), 3.40(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.21 (1H, d), 7.74 (1H, d), 7.47 (1H, d), 7.36 (1H, d), 7.31 (1H, s), 7.07 (1H, s), 6.84 (1H, d), 6.77 (1H, d), 3.88 (2H, s), 3.67 (3H, s), 3.40 (3H, s)

FAB MS(m/e) = 489[M+1]+ FAB MS (m / e) = 489 [M + 1] +

실시예 237: 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-2-클로로-N-메톡시-벤즈아미드Example 237: 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -Methyl-amino) -2-chloro-N-methoxy-benzamide

Figure 112006083464511-PAT00145
Figure 112006083464511-PAT00145

제조예 41에서 얻은 화합물 100 mg(0.204 mmol)을 디메틸설폭사이드 1 ml에 녹이고 N-아세틸피페라진 105 mg(0.817 mmol)을 가하고 상온에서 5 시간 동안 교반하였다. 반응 완결 후, 물 30 ml를 가하여 생기는 고체를 여과하고 건조하여 목적 화합물 102 mg(0.175 mmol, 수율; 86%)을 얻었다. 100 mg (0.204 mmol) of the compound obtained in Preparation Example 41 was dissolved in 1 ml of dimethyl sulfoxide, 105 mg (0.817 mmol) of N-acetylpiperazine was added thereto, and the resultant was stirred at room temperature for 5 hours. After completion of the reaction, 30 ml of water was added to the resulting solid, which was filtered and dried to yield 102 mg (0.175 mmol, yield; 86%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 8.28(1H, s), 7.62(1H, d), 7.46(1H, s), 7.34(1H, d), 7.30(1H, d), 6.90-6.87(2H, m), 6.68(1H, d), 3.93(3H, s), 3.51(5H, m), 3.42-3.36(4H, m), 2.37(4H, m), 2.03(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 8.28 (1H, s), 7.62 (1H, d), 7.46 (1H, s), 7.34 (1H, d), 7.30 (1H, d), 6.90-6.87 (2H, m ), 6.68 (1H, d), 3.93 (3H, s), 3.51 (5H, m), 3.42-3.36 (4H, m), 2.37 (4H, m), 2.03 (3H, s)

FAB MS(m/e) = 581[M+1]+ FAB MS (m / e) = 581 [M + 1] +

실시예 238: 2-클로로-N-메톡시-5-{메틸-[2-(4-몰포린-4-일메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-아미노}-벤즈아미드Example 238: 2-Chloro-N-methoxy-5- {methyl- [2- (4-morpholin-4-ylmethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridine -5-yl] -amino} -benzamide

Figure 112006083464511-PAT00146
Figure 112006083464511-PAT00146

실시예 237에서 N-아세틸피페라진 대신 몰포린을 사용하여 같은 방법으로 반응하여 목적 화합물을 얻었다. In Example 237, the reaction was carried out in the same manner using morpholine instead of N-acetylpiperazine to obtain the target compound.

1H NMR (DMSO-d6, ppm); δ 11.42(1H, s), 8.21(1H, d), 7.72(1H, d), 7.45(1H, d), 7.35(1H, d), 7.30(1H, s), 7.08(1H, s), 6.90(1H, d), 6.78(1H, d), 3.67(3H, s), 3.56(2H, s), 3.44-3.40(4H, m), 3.29(3H, s), 2.35(4H, m) 1 H NMR (DMSO-d 6 , ppm); δ 11.42 (1H, s), 8.21 (1H, d), 7.72 (1H, d), 7.45 (1H, d), 7.35 (1H, d), 7.30 (1H, s), 7.08 (1H, s), 6.90 (1H, d), 6.78 (1H, d), 3.67 (3H, s), 3.56 (2H, s), 3.44-3.40 (4H, m), 3.29 (3H, s), 2.35 (4H, m)

FAB MS(m/e) = 540[M+1]+ FAB MS (m / e) = 540 [M + 1] +

실시예 239: 2-클로로-N-메톡시-5-(메틸-{2-[4-(4-메틸-피레라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-아미노)-벤즈아미드Example 239 2-chloro-N-methoxy-5- (methyl- {2- [4- (4-methyl-pyrazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5 , 4-b] pyridin-5-yl} -amino) -benzamide

Figure 112006083464511-PAT00147
Figure 112006083464511-PAT00147

실시예 237에서 N-아세틸피페라진 대신 N-메틸피페라진을 사용하여 같은 방법으로 반응하여 목적 화합물을 얻었다.In Example 237, using the N-methyl piperazine instead of N-acetyl piperazine in the same manner to give the target compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.20(1H, d), 7.71(1H, d), 7.42(1H, d), 7.34(1H, d), 7.31(1H, s), 7.06(1H, s), 6.91(1H, d), 6.75(1H, d), 3.69(2H, s), 3.43-3.38(7H, m), 3.32(3H, s), 2.45(4H, m), 2.16(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.20 (1H, d), 7.71 (1H, d), 7.42 (1H, d), 7.34 (1H, d), 7.31 (1H, s), 7.06 (1H, s), 6.91 (1H, d), 6.75 (1H, d), 3.69 (2H, s), 3.43-3.38 (7H, m), 3.32 (3H, s), 2.45 (4H, m), 2.16 (3H, s)

FAB MS(m/e) = 553[M+1]+ FAB MS (m / e) = 553 [M + 1] +

제조예Production Example 42: 3-[(2-아미노- 42: 3-[(2-amino- 티아졸로[5,4-b]피리딘Thiazolo [5,4-b] pyridine -5-일)--5 days)- 메틸methyl -아미노]-벤조산 에틸 에스테르-Amino] -benzoic acid ethyl ester

제조예 38에서 5-아미노-2-클로로-벤조산 메틸 에스테르 대신 3-아미노-벤조산 에틸 에스테르를 사용하여 제조예 38의 방법으로 반응하고, 계속하여 제조예 39의 방법으로 반응하여 총 46%의 수율로 목적 화합물 14.6 g(44.5 mmol)을 얻었다. In Preparation Example 38, using 3-amino-benzoic acid ethyl ester instead of 5-amino-2-chloro-benzoic acid methyl ester, was reacted by the method of Preparation Example 38, followed by the method of Preparation Example 39, and the total yield was 46%. 14.6 g (44.5 mmol) of the title compound was obtained.

1H NMR (DMSO-d6, ppm); δ 7.46(1H, d), 7.41-7.39(2H, m), 7.32(1H, s), 7.26(1H, d), 6.62(1H, d), 4.40(2H, q), 3.51(3H, s), 1.37(3H, t) 1 H NMR (DMSO-d 6 , ppm); δ 7.46 (1H, d), 7.41-7.39 (2H, m), 7.32 (1H, s), 7.26 (1H, d), 6.62 (1H, d), 4.40 (2H, q), 3.51 (3H, s ), 1.37 (3H, t)

FAB MS(m/e) = 329[M+1]+ FAB MS (m / e) = 329 [M + 1] +

실시예 240: 3-[(2-아미노-티아졸로[5,4-b]피리딘-5-일)-메틸-아미노]-N-메톡시-벤즈아미드Example 240: 3-[(2-amino-thiazolo [5,4-b] pyridin-5-yl) -methyl-amino] -N-methoxy-benzamide

Figure 112006083464511-PAT00148
Figure 112006083464511-PAT00148

제조예 42에서 얻은 화합물 3.5 g(10.7 mmol)을 실시예 235의 방법으로 가수분해하여 산을 얻은 후, 다시 실시예 236의 방법으로 반응하여 목적 화합물 2.67 g(8.10 mmol)을 총 76%의 수율로 얻었다. 3.5 g (10.7 mmol) of the compound obtained in Preparation Example 42 was hydrolyzed by the method of Example 235 to obtain an acid, and then reacted by the method of Example 236 to yield 2.67 g (8.10 mmol) of the target compound in a total yield of 76%. Got it.

1H NMR (DMSO-d6, ppm); δ 7.48(1H, d), 7.41-7.39(2H, m), 7.31(1H, s), 7.26(1H, d), 6.62(1H, d), 3.84(3H, s), 3.41(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 7.48 (1H, d), 7.41-7.39 (2H, m), 7.31 (1H, s), 7.26 (1H, d), 6.62 (1H, d), 3.84 (3H, s), 3.41 (3H, s )

FAB MS(m/e) = 330[M+1]+ FAB MS (m / e) = 330 [M + 1] +

제조예 43: 3-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-Preparation Example 43 3-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl]- 메틸methyl -아미노}-벤조산 에틸 에스테르-Amino} -benzoic acid ethyl ester

제조예 42에서 얻은 화합물 9.5 g(28.9 mmol)을 사용하여 제조예 40, 실시예 234의 방법으로 순차적으로 반응하여 목적 화합물 7.2 g(16.5 mmol)을 총 57%의 수 율로 얻었다. Using 9.5 g (28.9 mmol) of the compound obtained in Preparation Example 42, the reaction was carried out in the same manner as in Preparation Example 40 and Example 234 to obtain 7.2 g (16.5 mmol) of the target compound in a total yield of 57%.

1H NMR (DMSO-d6, ppm); δ 11.31(1H, s), 8.21(1H, d), 7.78(1H, s), 7.71(1H, d), 7.54-7.50(2H, m), 7.05(1H, s), 6.90(1H, d), 6.72(1H, d), 5.42(1H, t), 4.48(2H, d), 3.43(2H, q), 3.34(3H, s), 1.45(3H, t) 1 H NMR (DMSO-d 6 , ppm); δ 11.31 (1H, s), 8.21 (1H, d), 7.78 (1H, s), 7.71 (1H, d), 7.54-7.50 (2H, m), 7.05 (1H, s), 6.90 (1H, d ), 6.72 (1H, d), 5.42 (1H, t), 4.48 (2H, d), 3.43 (2H, q), 3.34 (3H, s), 1.45 (3H, t)

FAB MS(m/e) = 436[M+1]+ FAB MS (m / e) = 436 [M + 1] +

제조예Production Example 44: 3-{[2-(4- 44: 3-{[2- (4- 클로로메틸Chloromethyl -피리딘-2-Pyridine-2- 일아미노Monoamino )-)- 티아졸로[5,4-b]피리딘Thiazolo [5,4-b] pyridine -5-일]--5 days]- 메틸methyl -아미노}-N--Amino} -N- 메톡시Methoxy -- 벤즈아미드Benzamide

제조예 43에서 얻은 화합물 4.7 g(10.3 mmol)을 사용하여 실시예 235, 실시예 236, 제조예 41의 방법으로 순차적으로 반응하여 목적 화합물 3.32 g(7.30 mmol)을 총 71%의 수율로 얻었다. 4.7 g (10.3 mmol) of the compound obtained in Preparation Example 43 was reacted sequentially in the same manner as in Example 235, Example 236, and Preparation 41 to obtain 3.32 g (7.30 mmol) of the title compound in a yield of 71% in total.

1H NMR (DMSO-d6, ppm); δ 11.34(1H, s), 8.20(1H, d), 7.77(1H, s), 7.70(1H, d), 7.54-7.50(2H, m), 7.02(1H, s), 6.90(1H, d), 6.71(1H, d), 4.31(2H, s), 3.47(3H, s), 3.32(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.34 (1H, s), 8.20 (1H, d), 7.77 (1H, s), 7.70 (1H, d), 7.54-7.50 (2H, m), 7.02 (1H, s), 6.90 (1H, d ), 6.71 (1H, d), 4.31 (2H, s), 3.47 (3H, s), 3.32 (3H, s)

FAB MS(m/e) = 455[M+1]+ FAB MS (m / e) = 455 [M + 1] +

하기 표 16은 제조예 44에서 얻은 화합물을 사용하여 실시예 237의 방법으로 반응하여 소정의 목적 화합물들을 합성한 실시예들이다.Table 16 below shows examples of synthesizing desired compounds by reacting by the method of Example 237 using the compound obtained in Preparation 44.

[표 16]TABLE 16

Figure 112006083464511-PAT00149
Figure 112006083464511-PAT00149

제조예Production Example 45: 3-{[2-(4- 45: 3-{[2- (4- 히드록시메틸Hydroxymethyl -피리딘-2-Pyridine-2- 일아미노Monoamino )-)- 티아졸로[5,4-b]피리딘Thiazolo [5,4-b] pyridine -5-일]--5 days]- 메틸methyl -아미노}-벤조산-Amino} -benzoic acid

제조예 43에서 얻은 화합물 3.2 g(7.34 mmol)을 실시예 235의 방법으로 가수 분해하여 목적 화합물 2.82 g(6.92 mmol, 수율; 94%)을 얻었다. 3.2 g (7.34 mmol) of the compound obtained in Preparation Example 43 were hydrolyzed by the method of Example 235 to obtain 2.82 g (6.92 mmol, yield; 94%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 12.79(1H, s), 11.34(1H, s), 8.42(1H, d), 8.17(1H, d), 7.70(1H, s), 7.65(1H, d), 7.58(1H, d), 7.45-7.42(2H, m), 7.08(1H, s), 6.86(1H, d), 6.64(1H, d), 5.42(1H, t), 4.48(2H, d), 3.42(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 12.79 (1H, s), 11.34 (1H, s), 8.42 (1H, d), 8.17 (1H, d), 7.70 (1H, s), 7.65 (1H, d), 7.58 (1H, d), 7.45-7.42 (2H, m), 7.08 (1H, s), 6.86 (1H, d), 6.64 (1H, d), 5.42 (1H, t), 4.48 (2H, d), 3.42 (3H, s)

FAB MS(m/e) = 408[M+1]+ FAB MS (m / e) = 408 [M + 1] +

하기 표 17은 제조예 45에서 얻은 화합물을 사용하여 실시예 236의 방법으로 반응하여 소정의 목적 화합물들을 합성한 실시예들이다.Table 17 below shows examples of synthesizing desired compounds by reacting by the method of Example 236 using the compound obtained in Preparation Example 45.

[표 17]TABLE 17

Figure 112006083464511-PAT00150
Figure 112006083464511-PAT00150

제조예 46: (2-{5-[(3-메톡시카바모일-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일Preparation 46: (2- {5-[(3-methoxycarbamoyl-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-yl 아미army 노}-피리딘-4-일)-초산 에틸 에스테르No} -pyridin-4-yl) -acetic acid ethyl ester

실시예 240에서 얻은 화합물 2.3 g(6.98 mmol)과 (2-클로로-피리딘-4-일)-아세트산 에틸 에스테르 1.81 g(9.08 mmol)을 톨루엔 80 ml에 녹인 후, 탄산칼륨 1.10 g(10.5 mmol)과 트리스(디벤질리덴아세톤)디팔라듐 0.38 g(0.42 mmol), 잔포스 0.36 g(0.63 mmol)을 가하고 30분 동안 질소를 불어 주며 교반하고, 다시 5 시간 동안 환류교반하였다. 반응 완결 후, 셀라이트에 고체를 여과한 후, 여과액을 물 60 ml로 씻고 유기층을 농축하였다. 관 크로마토그래피로 분리하여 목적 화합물 1.65 g(3.35 mmol, 수율; 48%)을 얻었다.2.3 g (6.98 mmol) of the compound obtained in Example 240 and 1.81 g (9.08 mmol) of (2-chloro-pyridin-4-yl) -acetic acid ethyl ester were dissolved in 80 ml of toluene, followed by 1.10 g (10.5 mmol) of potassium carbonate. 0.38 g (0.42 mmol) of tris (dibenzylideneacetone) dipalladium and 0.36 g (0.63 mmol) of xantose were added thereto, followed by stirring with nitrogen for 30 minutes, followed by stirring under reflux for 5 hours. After completion of the reaction, the solid was filtered through celite, and then the filtrate was washed with 60 ml of water and the organic layer was concentrated. Separation by column chromatography gave 1.65 g (3.35 mmol, yield; 48%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.32(1H, s), 8.24(1H, s), 7.82(1H, d), 7.74(1H, s), 7.52(1H, d), 7.46(1H, d), 6.97(1H, s), 6.82(1H, d), 6.67(1H, d), 3.75(3H, s), 3.69(2H, s), 3.48(2H, q), 3.40(3H, s), 1.43(3H, t) 1 H NMR (DMSO-d 6 , ppm); δ 11.32 (1H, s), 8.24 (1H, s), 7.82 (1H, d), 7.74 (1H, s), 7.52 (1H, d), 7.46 (1H, d), 6.97 (1H, s), 6.82 (1H, d), 6.67 (1H, d), 3.75 (3H, s), 3.69 (2H, s), 3.48 (2H, q), 3.40 (3H, s), 1.43 (3H, t)

FAB MS(m/e) = 493[M+1]+ FAB MS (m / e) = 493 [M + 1] +

실시예 247: 3-{[2-(4-디메틸카바모일메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-N-메톡시-벤즈아미드Example 247: 3-{[2- (4-dimethylcarbamoylmethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -N-meth Oxy-benzamide

Figure 112006083464511-PAT00151
Figure 112006083464511-PAT00151

제조예 46에서 얻은 화합물 1.10 g(2.23 mmol)을 실시예 235의 방법으로 가수분해하여 산 형태의 중간체를 0.96 g(2.08 mmol, 수율; 93%)을 얻었다. 이 중 120 mg(0.258 mmol)와 N,N-디메틸아민을 사용하여 실시예 236의 방법으로 반응하여 목적 화합물 110 mg(0.224 mmol, 수율; 87%)을 얻었다. 1.10 g (2.23 mmol) of the compound obtained in Preparation Example 46 were hydrolyzed by the method of Example 235 to obtain 0.96 g (2.08 mmol, yield; 93%) of the intermediate in the acid form. 120 mg (0.258 mmol) and N, N-dimethylamine were reacted in the same manner as in Example 236 to obtain 110 mg (0.224 mmol, yield; 87%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 11.37(1H, s), 8.25(1H, s), 7.80(1H, d), 7.70(1H, s), 7.54(1H, d), 7.48(1H, d), 6.99(1H, s), 6.87(1H, d), 6.69(1H, d), 3.75(3H, s), 3.69(2H, s), 3.40(3H, s), 3.04(3H, s), 2.87(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 11.37 (1H, s), 8.25 (1H, s), 7.80 (1H, d), 7.70 (1H, s), 7.54 (1H, d), 7.48 (1H, d), 6.99 (1H, s), 6.87 (1H, d), 6.69 (1H, d), 3.75 (3H, s), 3.69 (2H, s), 3.40 (3H, s), 3.04 (3H, s), 2.87 (3H, s)

FAB MS(m/e) = 492[M+1]+ FAB MS (m / e) = 492 [M + 1] +

제조예 47: 5-[(2-아미노-티아졸로[5,4-b]피리딘-5-일)-메틸-아미노]-2-플루오로-벤조산 에틸 에스테르Preparation 47: 5-[(2-Amino-thiazolo [5,4-b] pyridin-5-yl) -methyl-amino] -2-fluoro-benzoic acid ethyl ester

제조예 42에서 3-아미노-벤조산 에틸 에스테르 대신 5-아미노-2-플루오로-벤조산 에틸 에스테르를 사용하여 제조예 42의 방법으로 반응하여 총 48%의 수율로 목적 화합물 8.7 g(25. 1 mmol)을 얻었다. In the preparation 42, using the 5-amino-2-fluoro-benzoic acid ethyl ester instead of 3-amino-benzoic acid ethyl ester in the same manner as in Preparation 42, 8.7 g (25. 1 mmol) of the target compound in a yield of 48% in total )

1H NMR (DMSO-d6, ppm); δ 7.82(1H, d), 7.66 (1H, d), 7.43(1H, m), 7.25(2H, br), 7.16(1H, t), 6.52(1H, d), 4.40(2H, q), 3.51(3H, s), 1.37(3H, t) 1 H NMR (DMSO-d 6 , ppm); δ 7.82 (1H, d), 7.66 (1H, d), 7.43 (1H, m), 7.25 (2H, br), 7.16 (1H, t), 6.52 (1H, d), 4.40 (2H, q), 3.51 (3H, s), 1.37 (3H, t)

FAB MS(m/e) = 347[M+1]+ FAB MS (m / e) = 347 [M + 1] +

제조예 48: 5-{[2-(4-시클로메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-Preparation 48: 5-{[2- (4-cyclomethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl]- 메틸methyl -아미노}-2--Amino} -2- 플루오로Fluoro -벤조산 에틸 에스테르-Benzoic acid ethyl ester

제조예 47에서 얻은 화합물 3.2 g(6.98 mmol)을 이용하여 제조예 39, 실시예 234, 및 제조예 41의 방법으로 순차적으로 반응하여 목적 화합물 1.58 g(3.35 mmol, 총수율; 48%)을 얻었다.Using the compound 3.2 g (6.98 mmol) obtained in Preparation Example 47, the reaction was carried out in the same manner as in Preparation Example 39, Example 234, and Preparation Example 41 to obtain 1.58 g (3.35 mmol, total yield; 48%) of the title compound. .

1H NMR (CDCl3, ppm); δ 8.71(1H, br), 8.28(1H, d), 7.82(1H, dd), 7.61(1H, d), 7.46(1H, m), 7.15(1H, t), 6.95(1H, s), 6.91(1H, d), 6.56(1H, d), 5.11(2H, s), 4.40(2H, q), 1.39(3H, t) 1 H NMR (CDCl 3 , ppm); δ 8.71 (1H, br), 8.28 (1H, d), 7.82 (1H, dd), 7.61 (1H, d), 7.46 (1H, m), 7.15 (1H, t), 6.95 (1H, s), 6.91 (1H, d), 6.56 (1H, d), 5.11 (2H, s), 4.40 (2H, q), 1.39 (3H, t)

FAB MS(m/e) = 472[M+1]+ FAB MS (m / e) = 472 [M + 1] +

실시예 248: 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-2-플루오로-벤조산 에틸 에스테르Example 248: 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -Methyl-amino) -2-fluoro-benzoic acid ethyl ester

Figure 112006083464511-PAT00152
Figure 112006083464511-PAT00152

제조예 48에서 얻은 화합물 0.9 g(1.91 mmol)을 이용하여 실시예 237의 방법으로 반응하여 목적 화합물 0.89 g(1.58 mmol, 수율; 83%)을 얻었다. 0.9 g (1.91 mmol) of the compound obtained in Preparation Example 48 were used to obtain 0.89 g (1.58 mmol, yield; 83%) of the title compound.

1H NMR (CDCl3, ppm); δ 8.69(1H, br), 8.30(1H, d), 7.84(1H, dd), 7.62(1H, d), 7.45(1H, m), 7.16(1H, t), 6.99(1H, s), 6.93(1H, d), 6.57(1H, d), 4.40(2H, q), 3.63(2H, m), 3.50(5H, m), 3.46(2H, m), 2.44(4H, m), 2.10(3H, s), 1.39(3H, t) 1 H NMR (CDCl 3 , ppm); δ 8.69 (1H, br), 8.30 (1H, d), 7.84 (1H, dd), 7.62 (1H, d), 7.45 (1H, m), 7.16 (1H, t), 6.99 (1H, s), 6.93 (1H, d), 6.57 (1H, d), 4.40 (2H, q), 3.63 (2H, m), 3.50 (5H, m), 3.46 (2H, m), 2.44 (4H, m), 2.10 (3H, s), 1.39 (3H, t)

FAB MS(m/e) = 564[M+1]+ FAB MS (m / e) = 564 [M + 1] +

제조예Production Example 49: 5-({2-[4-(4-아세틸-피페라진-1- 49: 5-({2- [4- (4-acetyl-piperazine-1- 일메틸Methyl )-피리딘-2-) -Pyridine-2- 일아미노Monoamino ]-]- 티아졸Thiazole 로[in[ 5,4-b]피리딘5,4-b] pyridine -5-일}--5 days}- 메틸methyl -아미노)-2--Amino) -2- 플루오로Fluoro -벤조산-Benzoic acid

실시예 248에서 얻은 화합물 0.85 g(1.51 mmol)을 이용하여 실시예 235의 방 법으로 가수분해하여 목적 화합물 0.74 g(1.39 mmol, 수율; 92%)을 얻었다. 0.85 g (1.51 mmol) of the compound obtained in Example 248 was hydrolyzed in the same manner as in Example 235 to obtain 0.74 g (1.39 mmol, yield; 92%) of the title compound.

1H NMR (DMSO-d6, ppm); δ 8.72(1H, br), 8.31(1H, d), 7.82(1H, dd), 7.61(1H, d), 7.46(1H, m), 7.16(1H, t), 6.99(1H, s), 6.92(1H, d), 6.57(1H, d), 3.63(2H, m), 3.50(5H, m), 3.46(2H, m), 2.44(4H, m), 2.10(3H, s) 1 H NMR (DMSO-d 6 , ppm); δ 8.72 (1H, br), 8.31 (1H, d), 7.82 (1H, dd), 7.61 (1H, d), 7.46 (1H, m), 7.16 (1H, t), 6.99 (1H, s), 6.92 (1H, d), 6.57 (1H, d), 3.63 (2H, m), 3.50 (5H, m), 3.46 (2H, m), 2.44 (4H, m), 2.10 (3H, s)

FAB MS(m/e) = 536[M+1]+ FAB MS (m / e) = 536 [M + 1] +

실시예 249: 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-2-플루오로-N-메톡시-벤즈아미드Example 249: 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -Methyl-amino) -2-fluoro-N-methoxy-benzamide

Figure 112006083464511-PAT00153
Figure 112006083464511-PAT00153

제조예 49에서 얻은 화합물을 이용하여 실시예 236의 방법으로 반응하여 목적 화합물을 얻었다. Using the compound obtained in Preparation Example 49, the reaction was carried out by the method of Example 236 to obtain the target compound.

1H NMR (CDCl3, ppm); δ 11.00(1H, br), 9.82(1H, br), 8.30(1H, d), 7.91(1H, d), 7.62(1H, d), 7.42(1H, m), 7.14(1H, t), 6.92(1H, s), 6.88(1H, d), 6.55(1H, d), 3.92(3H, m), 3.50(5H, m), 3.41(2H, s), 3.35(2H, s), 2.37(4H, m), 2.06(3H, s) 1 H NMR (CDCl 3 , ppm); δ 11.00 (1H, br), 9.82 (1H, br), 8.30 (1H, d), 7.91 (1H, d), 7.62 (1H, d), 7.42 (1H, m), 7.14 (1H, t), 6.92 (1H, s), 6.88 (1H, d), 6.55 (1H, d), 3.92 (3H, m), 3.50 (5H, m), 3.41 (2H, s), 3.35 (2H, s), 2.37 (4H, m), 2.06 (3H, s)

FAB MS(m/e) = 565[M+1]+ FAB MS (m / e) = 565 [M + 1] +

실시예 250: 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-2-플루오로-N-메틸-벤즈아미드Example 250: 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -Methyl-amino) -2-fluoro-N-methyl-benzamide

Figure 112006083464511-PAT00154
Figure 112006083464511-PAT00154

실시예 249에서 메톡실아민 염산염 대신 메틸아민 염산염을 사용하여 실시예 249의 방법으로 반응하여 목적 화합물을 얻었다. In Example 249, the reaction of Example 249 was carried out using methylamine hydrochloride instead of methoxylamine hydrochloride to obtain the target compound.

1H NMR (CDCl3, ppm); δ 9.20(1H, br), 8.30(1H, d), 8.01(1H, dd), 7.62(1H, d), 7.38(1H, m), 7.14(1H, t), 6.97(1H, s), 6.92(1H, d), 6.81(1H, m), 6.60(1H, d), 3.60(2H, m), 3.52(3H, s), 3.48(2H, m), 3.43(2H, m), 3.05(3H, s), 2.43(4H, m), 2.06(3H, s) 1 H NMR (CDCl 3 , ppm); δ 9.20 (1H, br), 8.30 (1H, d), 8.01 (1H, dd), 7.62 (1H, d), 7.38 (1H, m), 7.14 (1H, t), 6.97 (1H, s), 6.92 (1H, d), 6.81 (1H, m), 6.60 (1H, d), 3.60 (2H, m), 3.52 (3H, s), 3.48 (2H, m), 3.43 (2H, m), 3.05 (3H, s), 2.43 (4H, m), 2.06 (3H, s)

FAB MS(m/e) = 549[M+1]+ FAB MS (m / e) = 549 [M + 1] +

실험예Experimental Example 1: 여러 종류의  1: several kinds RTKRTK (( ReceptorReceptor TyrosineTyrosine KinaseKinase )들에 대한 활성억제 효능 시험Activity inhibitory efficacy test

본 발명에 따른 화합물들의 타이로신 키나아제 활성 억제 효능을 확인하기 위하여, 5 종의 RTK들에 대해서 다음과 같은 생체외(in vitro) 키나아제 활성 억제 에 대한 실험을 행하였다. 우선 GST fusion 또는 His-tag 형태로 KDR, FLT-3, EGFR, FGFR1 및 PDGFR-β의 키나아제 도메인만을 곤충 세포(SF21)에서 발현하여 정제하였다. In order to confirm the inhibitory effect of tyrosine kinase activity of the compounds according to the present invention, the following in vitro kinase activity inhibition was performed on five RTKs. First, only kinase domains of KDR, FLT-3, EGFR, FGFR1 and PDGFR-β in the form of GST fusion or His-tag were expressed and purified in insect cells (SF21).

KDR의 경우, 20 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 1 mM MnCl2 , 2 mM DTT, 0.1 mM Sodium Orthovanadate, 10 μM ATP, 0.2 μCi [γ-P32]-ATP, 69 ㎍/ml Poly Glu:Tyr peptide (4:1) (Sigma) 및 3 ㎍/ml의 정제된 GST:KDR 단백질을 사용하여 다음과 같은 조건에서 반응을 진행하였다. 20 ㎕의 반응 부피를 사용하여 지정된 화합물들의 농도를 포함한 5%의 DMSO 존재하에서 30℃에서 10 분간 반응을 진행시킨 뒤 10%의 인산으로 중지시켰다. 그런 다음, 반응액을 96-well format의 Immobilon-PVDF막(Milipore)으로 옮긴 후, 0.5% 인산으로 4회 씻어 내고 Phosphorimager (Molecular Dynamics)로 막에 남아 있는 방사능량를 정량화하였다. IC50 값은 총 활성의 50%를 억제하는 화합물의 농도로 3 번 이상 반복한 실험의 평균값을 Linear regression analysis로 결정하였다. For KDR, 20 mM Tris-HCl, pH 7.5, 10 mM MgCl 2 , 1 mM MnCl 2 , 2 mM DTT, 0.1 mM Sodium Orthovanadate, 10 μM ATP, 0.2 μCi [γ-P 32 ] -ATP, 69 μg Reaction was performed under the following conditions using / ml Poly Glu: Tyr peptide (4: 1) (Sigma) and 3 μg / ml of purified GST: KDR protein. The reaction volume of 20 μl was used to run the reaction at 30 ° C. for 10 minutes in the presence of 5% DMSO containing the concentrations of the designated compounds and then stopped with 10% phosphoric acid. Then, the reaction solution was transferred to an Immobilon-PVDF membrane (Milipore) in 96-well format, washed four times with 0.5% phosphoric acid, and the amount of radioactivity remaining on the membrane was quantified with Phosphorimager (Molecular Dynamics). The IC 50 value was determined by the linear regression analysis of the average value of the experiment repeated three or more times with the concentration of compound that inhibits 50% of the total activity.

FLT3의 경우, 20 mM Tris-HCl (pH 7.5), 3 mM MgCl2, 7 mM MnCl2 , 2 mM DTT, 0.1 mM Sodium Orthovanadate(Sigma), 8 μM ATP, 0.2 μCi [γ-P32]-ATP, 69 ㎍/ml Poly Glu:Tyr peptide (4:1) (Sigma), 및 8 ㎍/ml 의 정제된 His-Tag:FLT3 단백질을 사용하여, KDR과 동일한 조건하에 15 분간 반응을 진행하였다. For FLT3, 20 mM Tris-HCl (pH 7.5), 3 mM MgCl 2 , 7 mM MnCl 2 , 2 mM DTT, 0.1 mM Sodium Orthovanadate (Sigma), 8 μM ATP, 0.2 μCi [γ-P 32 ] -ATP , 69 μg / ml Poly Glu: Tyr peptide (4: 1) (Sigma), and 8 μg / ml of purified His-Tag: FLT3 protein were used for 15 minutes under the same conditions as KDR.

EGFR의 경우, 20 mM Tris-HCl (pH 7.4), 10 mM MgCl2, 1 mM MnCl2 , 2 mM DTT, 0.1 mM Sodium Orthovanadate, 10 μM ATP, 0.2 μCi [γ-P32]-ATP, 690 ㎍/ml Poly Glu:Tyr peptide (4:1) (Sigma) 및 5 ㎍/ml 의 정제된 His-Tag:EGFR 을 사용하여, KDR과 동일한 조건하에서 20 분간 반응을 진행하였다.For EGFR, 20 mM Tris-HCl (pH 7.4), 10 mM MgCl 2 , 1 mM MnCl 2 , 2 mM DTT, 0.1 mM Sodium Orthovanadate, 10 μM ATP, 0.2 μCi [γ-P 32 ] -ATP, 690 μg Reaction was performed for 20 minutes under the same conditions as KDR using / ml Poly Glu: Tyr peptide (4: 1) (Sigma) and 5 μg / ml of purified His-Tag: EGFR.

FGFR1의 경우, 20 mM Tris-HCl (pH 7.5), 3 mM MgCl2, 3 mM MnCl2 , 2 mM DTT, 10 μM Sodium Orthovanadate, 0.25 mg/ml PEG3350, 8 μM ATP, 0.2 μCi [γ-P32]-ATP , 69 μM Poly Glu:Tyr peptide (4:1) (Sigma) 및 6.25 ㎍/ml 의 정제된 GST:FGFR1 단백질을 사용하여, KDR과 동일한 조건하에서 10 분간 반응을 진행하였다.For FGFR1, 20 mM Tris-HCl (pH 7.5), 3 mM MgCl 2 , 3 mM MnCl 2 , 2 mM DTT, 10 μM Sodium Orthovanadate, 0.25 mg / ml PEG3350, 8 μM ATP, 0.2 μCi [γ-P 32 ] -ATP, 69 μM Poly Glu: Tyr peptide (4: 1) (Sigma) and 6.25 μg / ml of purified GST: FGFR1 protein were used for 10 minutes under the same conditions as KDR.

PDGFRβ의 경우, 25 mM HEPES (pH 7.4), 150 mM NaCl, 10 mM MnCl2 , 2 mM DTT, 0.2 mM Sodium Orthovanadate, 2 μM ATP, 0.2 μCi [γ-P32]-ATP, 690 ㎍/ml Poly Glu:Tyr peptide (4:1) (Sigma) 및 8 ㎍/ml 의 정제된 GST:PDGFRβ를 사용하여, KDR과 동일한 조건하여 10 분간 반응을 진행하였다.For PDGFRβ, 25 mM HEPES (pH 7.4), 150 mM NaCl, 10 mM MnCl 2 , 2 mM DTT, 0.2 mM Sodium Orthovanadate, 2 μM ATP, 0.2 μCi [γ-P 32 ] -ATP, 690 μg / ml Poly Glu: Tyr peptide (4: 1) (Sigma) and 8 μg / ml of purified GST: PDGFRβ were used for 10 minutes under the same conditions as KDR.

실험예 2: 본 발명에 따른 화합물들의 VEGF 의존 HUVEC(Human Umbilical Vein Endothelial Experimental Example 2: VEGF-dependent HUVECs (Human Umbilical Vein Endothelial) of Compounds According to the Present Invention CellCell ) 성장 억제 효능 시험Growth Inhibition Effect Test

태반에서 분리된 HUVEC 세포(5×103 cells/well)를 0.3% Gelatin-코팅된 96-well 배양용기에 접종하고 하루동안 M199 세포 배양 배지(Gibco BRL) (10% FBS, 30 ㎍/ml ECGS, 50 ㎍/ml Heparin, 1× Penicillin/Sterptomycin 및 0.5 mM Glutamine 을 포함)에서 세포배양기 내 5% CO2, 37℃ 조건으로 배양하였다. 그 뒤 M199 starvation 배지(0.5% FBS)에서 24 시간 동안 serum starvation을 수행하였다. 그 후 starvation 배지를 단계별로 희석한 화합물들을 포함하는 working 배지로 바꾸고, 2 시간 후 10 ng/ml의 VEGF(R&D systems)로 처리하였다. 이틀 동안 배양한 후, BrdU Cell Proliferation ELISA(Roche)를 제조사의 지시에 따라 실행하였다. IC50 값은 총 VEGF에 의해 유도되는 세포성장의 50%를 억제하는 화합물의 농도로 3 번 이상 반복한 실험의 평균값을 Linear regression analysis로 결정하였다.HUVEC cells (5 × 10 3 cells / well) isolated from the placenta were inoculated in a 0.3% Gelatin-coated 96-well culture vessel and for one day M199 cell culture medium (Gibco BRL) (10% FBS, 30 μg / ml ECGS). , 50 μg / ml Heparin, 1 × Penicillin / Sterptomycin, and 0.5 mM Glutamine) were incubated at 37 ° C. in 5% CO 2 in a cell culture. Then, serum starvation was performed for 24 hours in M199 starvation medium (0.5% FBS). The starvation medium was then changed to a working medium containing the diluted compounds in stages and treated with 10 ng / ml VEGF (R & D systems) after 2 hours. After incubation for two days, BrdU Cell Proliferation ELISA (Roche) was performed according to the manufacturer's instructions. The IC 50 value was determined by the linear regression analysis of the average value of the experiment repeated three or more times at the concentration of the compound that inhibits 50% of the total cell growth induced by VEGF.

실험예Experimental Example 3: 본 발명에 따른 화합물들의  3: of the compounds according to the invention HUVECHUVEC 의 튜브 형성 억제 효능 시험Tube formation inhibitory efficacy test

패시지 5의 HUVEC(사람신생혈관세포)를 100 mm 배양용기에 70 ~ 80% 차도록 세포배양기 내에서 5% CO2, 37℃ 조건으로 배양한 뒤 트립신으로 처리하고, 0.2% BSA(Sigma)를 포함한 M199로 중화시킨 뒤, 10 mg/ml의 Matrigel(R&D systems)로 코팅한 24 well 배양용기에 4×104 cells/well과 단계별로 희석한 화합물들을 포함하는 배지로 접종한 뒤 FBS를 5%로 첨가하였다. 17 시간 후 조심스럽게 배지를 제거하고 100 ㎕의 3.7% Paraformaldehyde/PBS로 고정한 뒤, 현미경하에서 화면를 잡고 KS Lite software를 이용하여 형성된 튜브의 길이를 정량화하였다.Passage 5 HUVEC (human neovascular cells) in a 100 mm culture vessel was incubated at 5% CO 2 , 37 ° C in a cell culture incubator with trypsin and 0.2% BSA (Sigma) Neutralized with M199, inoculated in a 24 well culture vessel coated with 10 mg / ml Matrigel (R & D systems) with medium containing 4 × 10 4 cells / well and compound diluted in stages, followed by 5% FBS Added. After 17 hours, the medium was carefully removed and fixed with 100 μl of 3.7% Paraformaldehyde / PBS, the screen was taken under a microscope and the length of the formed tube was quantified using KS Lite software.

실험예 4: 본 발명에 따른 화합물들의 HCT116에 대한 SRB(Sulforhodamine B) 성장 억제 효과 시험Experimental Example 4: SRB (Sulforhodamine B) growth inhibitory effect test on HCT116 of the compounds according to the invention

HCT116 세포(3×103 cells/well: ATCC)을 100 ㎕ 부피로 96-well 배양 용기에 접종하고 하루 동안 RPMI1640 배양배지(5% FBS, 1X Penicillin/Sterptomycin 및 0.5 mM Glutamine를 포함: Gibco BRL)에서 세포배양기 내 5% CO2, 37℃ 조건으로 배양하였다. 그 후 배지에 단계별로 희석한 화합물들을 처리하였다. 이틀 동안 배양 후 4% Formaldehyde(Sigma)로 3-4 시간 동안 고정을 행하였다. PBS로 5 회정도 씻어 낸 뒤, 55℃ 오븐에서 10 분간 건조시켰다. 1% 초산에 녹인 0.4%(w/v) SRB(Sigma) 용액 50 ㎕를 각 well에 넣어 30 분간 상온에 방치한 뒤 1% 초산으로 씻어 내었다. 그런 다음, 55℃ 오븐에서 10 분간 다시 건조시켰다. 100 mL의 10 mM Tris-HCl(pH 10.5)로 20 분간 셰이커 위에서 녹여낸 뒤, 530 nm에서 흡광도를 측정하여 세포의 양을 정량화하였다. GI50 값은 총 세포성장을 50%를 억제하는 화합물의 농도로 3 번 이상 반복한 실험의 평균값을 Linear regression analysis로 결정하였다.Inoculate HCT116 cells (3 × 10 3 cells / well: ATCC) into 96-well culture vessels in 100 μl volume and in RPMI1640 culture medium (containing 5% FBS, 1X Penicillin / Sterptomycin and 0.5 mM Glutamine: Gibco BRL) for one day. Was cultured in a 5% CO 2 , 37 ℃ condition in the cell culture. The medium was then treated with the compounds diluted in stages. After incubation for 2 days, fixation was performed with 4% Formaldehyde (Sigma) for 3-4 hours. After washing 5 times with PBS, it was dried for 10 minutes in a 55 ℃ oven. 50 μl of 0.4% (w / v) SRB (Sigma) solution dissolved in 1% acetic acid was added to each well and left at room temperature for 30 minutes and washed with 1% acetic acid. It was then dried again in a 55 ° C. oven for 10 minutes. Dissolve on the shaker for 20 minutes with 100 mL of 10 mM Tris-HCl (pH 10.5) and measure the absorbance at 530 nm to quantify the amount of cells. The GI 50 value was determined by the linear regression analysis of the average value of the experiment repeated three or more times at the concentration of the compound inhibiting 50% of total cell growth.

실험예Experimental Example 5 : 본 발명에 따른 화합물들의  5: of the compounds according to the invention inin vivovivo 암세포 성장 억제 효과 시험 Cancer cell growth inhibitory effect test

5 ~ 6 주령의 암컷 BALB/c 누드마우스를 미국 Harlan사에서 구입하여 청정 동물실 HEPA filter가 설치된 cage에서 사육하면서 일주일 정도의 적응기간을 주었다. 시험을 위해 선택한 인체종양세포를 각 조건에 맞게 배양한 후 적정농도의 세포를 (5 ~ 10×106 cells/100 uL) 누드마우스에 피하로 접종하였다. Regression model을 위해 종양의 크기가 90 ~ 120 mm3로 자라게 한 후, 시험의 투여용량에 따라 경구로 1 일 1 회 반복 투여하였다. 매 3 일 마다 종양크기와 체중을 측정하고 매일 1 ~ 2 회 임상증상을 관찰 기록하였다. 종양크기는 종양의 가로, 세로, 높이의 길이를 각각 측정하여 (가로 x 세로 x 높이)π/6 공식으로 계산한 부피값으로 나타내었다. 시험은 15 ~ 18 일간 진행하였다. Female BALB / c nude mice, 5-6 weeks old, were purchased from Harlan, USA, and housed in cages with a clean animal room HEPA filter for a week of acclimatization. Human tumor cells selected for the test were cultured according to each condition, and then cells of appropriate concentration (5-10 × 10 6 cells / 100 uL) were inoculated subcutaneously into nude mice. For the regression model, the tumors were grown to 90-120 mm 3 and then orally administered once a day according to the test dose. The tumor size and body weight were measured every 3 days, and the clinical symptoms were observed and recorded 1-2 times daily. Tumor size was expressed as a volume value calculated by measuring the length, width and height of the tumor, respectively (width x length x height) π / 6. The test was run for 15-18 days.

종양성장억제 효과는 하기 두 지표(IR%: Inhibition Rate, %T/C)로 평가하였다.Tumor growth inhibition effect was evaluated by the following two indicators (IR%: Inhibition Rate,% T / C).

IR% = (1 - 투여군 평균 종양 크기/ 대조군 평균 종양 크기) X 100, IR% = (1-group mean tumor size / control group mean tumor size) X 100,

%T/C = {(특정일 투여군 평균 종양크기- 투여개시일 투여군 평균 종양크기) / (특정일 대조군 평균 종양크기- 투여개시일 대조군 평균 종양크기)} X 100% T / C = {(average tumor size on specific day group-mean tumor size on start date) / (average tumor size on specific day-mean tumor size on start date)} X 100

화학식 1의 대표적인 화합물들과 그들의 KDR 및 HUVEC에 대해 측정된 효소활성 저해능력을 IC50 값으로 나타낸 결과가 하기 표 18에 개시되어 있다.Representative compounds of Formula 1 and their enzyme activity inhibition capacity measured for KDR and HUVEC as shown in the IC 50 value are shown in Table 18 below.

[표 18]TABLE 18

Figure 112006083464511-PAT00155
Figure 112006083464511-PAT00155

Figure 112006083464511-PAT00156
Figure 112006083464511-PAT00156

Figure 112006083464511-PAT00157
Figure 112006083464511-PAT00157

Figure 112006083464511-PAT00158
Figure 112006083464511-PAT00158

Figure 112006083464511-PAT00159
Figure 112006083464511-PAT00159

Figure 112006083464511-PAT00160
Figure 112006083464511-PAT00160

Figure 112006083464511-PAT00161
Figure 112006083464511-PAT00161

화학식 1의 일부 화합물들의 HCT116 세포와 bFGF 의존적인 HUVEC 그리고 PDGF 의존적인 PASMC의 성장 저해능력을 IC50으로 나타낸 결과가 하기 표 19에 개시 되어 있다. The results showing the growth inhibition of the HCT116 cells, bFGF-dependent HUVEC and PDGF-dependent PASMC of some compounds of Formula 1 as IC 50 are shown in Table 19 below.

[표 19]TABLE 19

Figure 112006083464511-PAT00162
Figure 112006083464511-PAT00162

화학식 1의 화합물들이 누드마우스를 이용한 in vivo 종양세포 성장 억제효과 실험에서 유의적인 성장 억제 효과를 보였다(IR > 50%).Compounds of formula (1) using nude mouse in vivo Tumor cell growth inhibitory effect showed a significant growth inhibitory effect (IR> 50%).

이상의 결과로부터, 본 발명에 따른 화합물들은 KDR 활성을 억제하고, HUVEC의 성장을 억제하며, in vivo에서 암세포의 성장 억제에 매우 효과적임을 확인할 수 있다.From the above results, the compounds according to the present invention inhibit KDR activity, inhibit the growth of HUVEC, in It can be seen that it is very effective in inhibiting the growth of cancer cells in vivo .

본 발명이 속한 분야에서 통상의 지식을 가진 자라면 상기 내용을 바탕으로 본 발명의 범주 내에서 다양한 응용 및 변형을 행하는 것이 가능할 것이다.Those skilled in the art to which the present invention pertains will be able to perform various applications and modifications within the scope of the present invention based on the above contents.

Claims (7)

하기 화학식 1의 화합물, 또는 약제학적으로 허용되는 그것의 염:A compound of Formula 1, or a pharmaceutically acceptable salt thereof:
Figure 112006083464511-PAT00163
(1)
Figure 112006083464511-PAT00163
(One) 상기 식에서,Where A) R1 은 수소 또는 C1-C10 알킬이며, A) R 1 is hydrogen or C 1 -C 10 alkyl, B) A1 및 A2 는 각각 독립적으로 탄소 또는 질소이며,B) A 1 and A 2 are each independently carbon or nitrogen, C) R2 는 수소, 할로겐, 시아노, -CF3 및 C1-C10 알킬로 이루어진 군에서 선택되며, C) R 2 is selected from the group consisting of hydrogen, halogen, cyano, -CF 3 and C 1 -C 10 alkyl, D) Ar1 은 5각 또는 6각 고리형의 방향족 또는 헤테로방향족이며,D) Ar 1 is a 5 or 6 cyclic aromatic or heteroaromatic, E) X 는 각각 독립적으로 하기 치환기들로 이루어진 군에서 선택되며,E) X is each independently selected from the group consisting of the following substituents, I) 수소, 할로겐, 시아노, 히드록시, -CF3, 임의적으로 치환된 C1-C10 알킬;I) hydrogen, halogen, cyano, hydroxy, -CF 3 , optionally substituted C 1 -C 10 alkyl; II) -OR3, -SR3, -NHR3, -N(R3)2, 여기서, R3는 수소 또는 임의적으로 치환된 C1-C10 알킬이고;II) -OR 3 , -SR 3 , -NHR 3 , -N (R 3 ) 2 , wherein R 3 is hydrogen or optionally substituted C 1 -C 10 alkyl; III) -C(=O)R4, -NR5C(=O)NR4R6, -NR5C(=S)NR4R6, III) -C (= 0) R 4 , -NR 5 C (= 0) NR 4 R 6 , -NR 5 C (= S) NR 4 R 6 , 여기서, R4 는 Where R 4 Is i) 히드록시;i) hydroxy; ii) 임의적으로 치환된 C1-C10 알킬;ii) optionally substituted C 1 -C 10 alkyl; iii) 임의적으로 치환된 C1-C10 알콕시;iii) optionally substituted C 1 -C 10 alkoxy; iv) -NR7R8 또는 -N(-R7)OR8, 여기서, R7 및 R8 은 각각 독립적으로 수소, 임의적으로 치환된 C1-C10 알킬, 임의적으로 치환된 알릴, 임의적으로 치환된 술폰, 또는 임의적으로 치환된 아민이고, R7 및 R8 은 상호 연결되어 환 구조를 이룰 수 있으며;iv) -NR 7 R 8 or -N (-R 7 ) OR 8 , wherein R 7 And R 8 Are each independently hydrogen, optionally substituted C 1 -C 10 alkyl, optionally substituted allyl, optionally substituted sulfone, or optionally substituted amine, and R 7 And R 8 Are interconnected to form a ring structure; v) -(CH2)n1NR9-(CH2)n2-NR7R8, 여기서, R7 및 R8 은 상기 정의한 바와 같고, R9 는 수소이거나 임의적으로 치환된 C1-C10 알킬이며, n1 은 0 또는 1 내지 5의 정수이고, n2 는 1 내지 5의 정수이며;v)-(CH 2 ) n1 NR 9- (CH 2 ) n2 -NR 7 R 8 , wherein R 7 And R 8 Is as defined above, R 9 is hydrogen or optionally substituted C 1 -C 10 alkyl, n 1 Is 0 or an integer from 1 to 5, n 2 Is an integer from 1 to 5; R5 및 R6 은 각각 독립적으로 수소, 히드록시, 임의적으로 치환된 C1-C10 알킬, 임의적으로 치환된 알릴, 임의적으로 치환된 술폰 알킬, 또는 임의적으로 치환된 아민이고;R 5 And R 6 Are each independently hydrogen, hydroxy, optionally substituted C 1 -C 10 alkyl, optionally substituted allyl, optionally substituted sulfone alkyl, or optionally substituted amine; R4, R5 및 R6 중 선택된 두 개의 치환기는 상호 연결되어 환 구조를 이룰 수 있으며;R 4 , R 5 And two substituents selected from R 6 may be connected to each other to form a ring structure; F) n 은 0 또는 1 ~ 5의 정수이며,F) n is 0 or an integer from 1 to 5, G) E 는 산소 또는 황이며;G) E is oxygen or sulfur; H) Ar2 는 수소 또는 하기 화학식 2로 표현되는 5각 또는 6각의 방향족 고리 화합물이며,H) Ar 2 is hydrogen or a 5- or 6-membered aromatic ring compound represented by the following formula (2),
Figure 112006083464511-PAT00164
(2)
Figure 112006083464511-PAT00164
(2) 여기서,here, Q 는 탄소, 질소, 산소 및 황으로 이루어진 군에서 선택되며,Q is selected from the group consisting of carbon, nitrogen, oxygen and sulfur, l(엘) 은 3 ~ 4의 정수이며,l (L) is an integer from 3 to 4, I) m 은 0 또는 1 ~ 4의 정수이며,I) m is 0 or an integer from 1 to 4, J) Y 는 각각 독립적으로 하기 치환기들로 이루어진 군에서 선택되며,J) Y is each independently selected from the group consisting of the following substituents, I) 할로겐, 시아노, 니트로, 히드록시, -CF3 및 임의적으로 치환된 몰포린;I) halogen, cyano, nitro, hydroxy, -CF 3 and optionally substituted morpholine; II) -R, -OR, -SR', -NHR' 및 -NR'R", 여기서 R, R' 및 R"는 각각 독립적으로 수소, 또는 임의적으로 치환된 C1-C10 직쇄, 분지형 또는 환형의 포화 또는 불포화 알킬이며; 및II) -R, -OR, -SR ', -NHR' and -NR'R ", wherein R, R 'and R" are each independently hydrogen, or optionally substituted C 1 -C 10 straight chain, branched Or cyclic saturated or unsaturated alkyl; And III) 하기 일반식(i~ vi)으로 표시되는 치환체들:III) substituents represented by the following general formulas (i to vi):
Figure 112006083464511-PAT00165
(i)
Figure 112006083464511-PAT00165
(i)
Figure 112006083464511-PAT00166
(ii)
Figure 112006083464511-PAT00166
(ii)
Figure 112006083464511-PAT00167
(iii)
Figure 112006083464511-PAT00167
(iii)
Figure 112006083464511-PAT00168
(iv)
Figure 112006083464511-PAT00168
(iv)
Figure 112006083464511-PAT00169
(v)
Figure 112006083464511-PAT00169
(v)
Figure 112006083464511-PAT00170
(vi)
Figure 112006083464511-PAT00170
(vi) 여기서,here, n1 은 0 또는 1 ~ 5의 정수이며; n 1 is 0 or an integer of 1 to 5; J1 는 수소, -(C=O)-, -N-, -O- 및 -S- 로 이루어진 군에서 선택되거나 직접 결합이며;J 1 is selected from hydrogen, — (C═O) —, —N—, —O— and —S— or is a direct bond; J2 및 J3 는 각각 독립적으로 -N-, -O-, -CR'- 및 -S- 로 이루어진 군에서 선택되거나 직접 결합이며, 여기서 R' 는 상기 정의한 바와 같으며;J 2 and J 3 are each independently selected from the group consisting of —N—, —O—, —CR′— and —S—, or a direct bond, wherein R ′ is as defined above; J4 및 J5 는 각각 독립적으로 -(C=O)-, -NR'-, -(C=O)-NR'-, -(C=O)-NR'-R-, -O-, -S- -NR'-(C=O)-, -(C=S)-, -(C=S)-NR'-, -(C=S)-NR'-R-, -NR'-(C=S)-, 및 -SO2-로 이루어진 군에서 선택되고, 여기서 R 및 R' 는 상기 정의한 바와 같으며;J 4 And J 5 are each independently — (C═O) —, —NR′—, — (C═O) —NR′—, — (C═O) —NR′—R—, —O—, —S -NR '-(C = O)-,-(C = S)-,-(C = S) -NR'-,-(C = S) -NR'-R-, -NR'-(C = S)-, and -SO 2- , wherein R and R 'are as defined above; n2 및 n6 는 0 또는 1 ~ 3의 정수이며; n 2 and n 6 Is 0 or an integer of 1 to 3; n3 및 n4 는 각각 독립적으로 0 또는 1 ~ 3 중에서 선택되고, 0 인 경우에는 아무것도 아니거나 직접결합이며; n 3 and n 4 Are each independently selected from 0 or 1 to 3, and when 0 is nothing or a direct bond; n5 는 0 또는 1 ~ 3 중에서 선택되고, 0 인 경우에는 아무것도 아니거나 직접결합이며; n 5 Is selected from 0 or 1 to 3, and when 0 is nothing or a direct bond; G 및 G' 는 각각 독립적으로 수소, -R', -CF3, -(C=O)R', -OR', -CO2R', -SO2R', -CONHR', -CONRR', -CONR'OR, -CN, 할로겐, -NH2, -NRR', -NHCOR', -NHCO2R', -C(R')OH, -C(R)OR', -NR(C=O)R'OR"-, -C(=O)ROR'-, 임의적으로 치환된 C3-C8 시클로알킬 또는 헤테로 시클로알킬, 및 임의적으로 치환된 5각 또는 6각의 방향족 또는 헤테로 방향족으로 이루어진 군에서 선택되며, 여기서 R, R' 및 R"는 상기 정의한 바와 같다.G and G 'are each independently hydrogen, -R', -CF 3 ,-(C = O) R ', -OR', -CO 2 R ', -SO 2 R', -CONHR ', -CONRR' , -CONR'OR, -CN, halogen, -NH 2 , -NRR ', -NHCOR', -NHCO 2 R ', -C (R') OH, -C (R) OR ', -NR (C = O) R'OR "-, -C (= 0) ROR'-, optionally substituted C 3 -C 8 cycloalkyl or heterocycloalkyl, and optionally substituted 5- or 6-membered aromatic or heteroaromatic And R, R 'and R "are as defined above. 제 1 항에 있어서, R1 은 수소 또는 메틸이며, A1 및 A2 는 탄소이며, R2 는 수소 또는 할로겐이며, Ar1 은 6각 고리형의 방향족 또는 헤테로방향족이며, n 은 0 또는 1 ~ 4의 정수이며, E 는 황이며, Q 는 탄소 또는 질소이며, l(엘) 은 3 또는 4 인 것을 특징으로 하는 화합물, 또는 약제학적으로 허용되는 그것의 염.The compound of claim 1, wherein R 1 Is hydrogen or methyl, A 1 and A 2 are carbon, R 2 Is hydrogen or halogen, Ar 1 Is a hexagonal cyclic aromatic or heteroaromatic, n is 0 or an integer of 1 to 4, E is sulfur, Q is carbon or nitrogen, l (L) is 3 or 4, Or a pharmaceutically acceptable salt thereof. 제 1 항에 있어서, R1 은 메틸이며, R2 는 수소이며, Ar1 은 페닐이며, n 은 0 또는 1 ~ 3의 정수이며, l(엘)은 4인 것을 특징으로 하는 화합물, 또는 약제학적으로 허용되는 그것의 염.The compound of claim 1, wherein R 1 Is methyl and R 2 Is hydrogen, Ar 1 Is phenyl, n is 0 or an integer of 1 to 3, and l (L) is 4, or a pharmaceutically acceptable salt thereof. 제 1 항에 있어서, R4, R5 및 R6 중 선택된 두 개의 치환기가 상호 연결되어 환 구조를 이루는 경우, R7 및 R8이 상호 연결되어 환 구조를 이루는 경우, 또는 헤테로 시클로알킬인 경우, 이러한 환 구조는 임의적으로 치환된 아지리딘, 피롤리딘, 피페라진, 피페리딘 또는 몰포린인 것을 특징으로 하는 화합물, 또는 약제학적으로 허용되는 그것의 염.The compound of claim 1, wherein R 4 , R 5 And when two substituents selected from R 6 are interconnected to form a ring structure, R 7 And when R 8 is interconnected to form a ring structure, or is heterocycloalkyl, this ring structure is an optionally substituted aziridine, pyrrolidine, piperazine, piperidine or morpholine , Or a pharmaceutically acceptable salt thereof. 제 1 항에 있어서, 상기 화합물은 하기 화합물들인 것을 특징으로 하는 화합물, 또는 약제학적으로 허용되는 그것의 염:A compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that 1. N5-(4-플루오로페닐)-N5-메틸-N2-(6-메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민1. N 5 - (4-fluorophenyl) -N 5 - methyl -N 2 - (6- methyl-pyridin-2-yl) thiazolo [5,4-b] pyridine-2,5-diamine 2. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-메탄올2. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -methanol 3. N5-메틸-N2-(3-몰포린-4-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민3. N 5 -Methyl-N 2- (3-morpholin-4-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5- Diamine 4. N5-메틸-N2-[3-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민4. N 5 -Methyl-N 2- [3- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -p-tolyl-thiazolo [5,4-b] Pyridine-2,5-diamine 5. N5-메틸-N2-[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-N5-페닐-티아졸로[5,4-b]피리딘-2,5-디아민5. N 5 -Methyl-N 2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -phenyl-thiazolo [5,4-b] pyridine- 2,5-diamine 6. N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-N5-페닐-l-티아졸로[5,4-b]피리딘-2,5-디아민6. N 5 -Methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -N 5 -phenyl-l-thiazolo [5,4-b] pyridine-2,5- Diamine 7. 4-{2-[5-(메틸-페닐-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-카르복실산 메틸아미드7. 4- {2- [5- (Methyl-phenyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine-1-carboxyl Acid methylamide 8. 4-{2-[5-(메틸-페닐-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-카르복실산 디메틸아미드8. 4- {2- [5- (Methyl-phenyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine-1-carboxyl Acid Dimethylamide 9. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-메탄올9. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -methanol 10. 1-(4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-에타논 10. 1- (4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine -1-yl) -ethanone 11. N2-(4-디에틸아미노메틸-피리딘-2-일)-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민11. N 2 - (4- diethylamino-methyl-pyridin-2-yl) -N 5 - methyl -N 5 -p- tolyl-thiazolo [5,4-b] pyridine-2,5-diamine 12. N5-메틸-N2-(4-피롤리딘-1-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민12.N 5 -Methyl-N 2- (4-pyrrolidin-1-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5 -Diamine 13. N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민13.N 5 -Methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5- Diamine 14. N5-메틸-N2-[4-(4-메틸-피페라딘-1-일메틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민14.N 5 -Methyl-N 2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -p-tolyl-thiazolo [5,4-b ] Pyridine-2,5-diamine 15. -(4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-에탄올15.-(4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine- 1-yl) -ethanol 16. (4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-아세트산 에틸 에스테르16. (4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine-1 -Yl) -acetic acid ethyl ester 17. (4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-아세트산17. (4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine-1 -Yl) -acetic acid 18. N,N-디메틸-2-(4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-아세트아미드18. N, N-dimethyl-2- (4- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4- Monomethyl} -piperazin-1-yl) -acetamide 19. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트산 에틸 에스테르19. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -acetic acid ethyl ester 20. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트산20. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -acetic acid 21. 1-(4-메틸-피페라진-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-에타논21. 1- (4-Methyl-piperazin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -ethanone 22. N-(2-디에틸아미노-에틸)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피 리딘-2-일아미노]-피리딘-4-일}-아세트아미드22. N- (2-Diethylamino-ethyl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino]- Pyridin-4-yl} -acetamide 23. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-N-(2-몰포린-4-일-에틸)-아세트아미드23. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -N- (2-mol Forin-4-yl-ethyl) -acetamide 24. N-(2-히드록시-에틸)-N-메틸-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드24. N- (2-hydroxy-ethyl) -N-methyl-2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -acetamide 25. N-(2-히드록시-에틸)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드25. N- (2-hydroxy-ethyl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine- 4-yl} -acetamide 26. 6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코티노니트릴26. 6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -nicotinonitrile 27. N2-(5-디에틸아미노메틸-피리딘-2-일)-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민27. N 2 - (5--diethylamino-methyl-pyridin-2-yl) -N 5 - methyl -N 5 -p- tolyl-thiazolo [5,4-b] pyridine-2,5-diamine 28. N5-메틸-N2-(5-피페리딘-1-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민28.N 5 -Methyl-N 2- (5-piperidin-1-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5 -Diamine 29. N5-메틸-N2-[5-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민29. N 5 -Methyl-N 2- [5- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -p-tolyl-thiazolo [5,4-b] Pyridine-2,5-diamine 30. N5-메틸-N2-(5-몰포린-4-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민30.N 5 -Methyl-N 2- (5-morpholin-4-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5- Diamine 31. 1-(4-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리 딘-3-일메틸}-피페라진-1-일)-에타논31. 1- (4- {6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -pipe Razin-1-yl) -ethanone 32. N5-메틸-N2-(5-피롤리딘-1-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민32.N 5 -Methyl-N 2- (5-pyrrolidin-1-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5 -Diamine 33. 4-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-피페라진-1-카르복실산 디메틸아미드33. 4- {6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -piperazin-1- Carboxylic Acid Dimethylamide 34. ({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-아세트산 메틸 에스테르34. ({6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) -acetic acid methyl ester 35. 2-({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-아세트아미드35. 2-({6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) -acet amides 36. 2-({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-프로피온산 메틸 에스테르36. 2-({6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) -propionic acid Methyl ester 37. ({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-아세트산37. ({6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) -acetic acid 38. 2-({6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일메틸}-아미노)-프로피온산38. 2-({6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-ylmethyl} -amino) -propionic acid 39. 6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코틴산 메틸 에스테르39. 6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -nicotinic acid methyl ester 40. 6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코틴산40. 6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -nicotinic acid 41. (4-메틸-피페라진-1-일)-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘 -2-일아미노]-피리딘-3-일}-메타논41. (4-Methyl-piperazin-1-yl)-{6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine- 3-day} -Methanone 42. N-(1-메틸-피페리딘-4-일메틸)-6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-니코틴아미드42. N- (1-Methyl-piperidin-4-ylmethyl) -6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] Nicotinamide 43. {6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-몰포린-4-일-메타논43. {6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -morpholin-4-yl-meta Paddy field 44. {6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-아세트산 에틸 에스테르44. {6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -acetic acid ethyl ester 45. {6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-아세트산45. {6- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-3-yl} -acetic acid 46. 1-(4-메틸-피페라진-1-일)-2-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-에타논46. 1- (4-Methyl-piperazin-1-yl) -2- {6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-3-yl} -ethanone 47. N-(1-메틸-피페리딘-4-일메틸)-2-{6-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-3-일}-아세트아미드47. N- (1-Methyl-piperidin-4-ylmethyl) -2- {6- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine-2- Ylamino] -pyridin-3-yl} -acetamide 48. N5-(4-플루오로-페닐)-N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민48. N 5- (4-Fluoro-phenyl) -N 5 -methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine -2,5-diamine 49. N5-(4-플루오로-페닐)-N5-메틸-N2-[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민49. N 5- (4-Fluoro-phenyl) -N 5 -methyl-N 2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -thiazolo [5 , 4-b] pyridine-2,5-diamine 50. 1-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논50. 1- [4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-yl Methyl) -piperazin-1-yl] -ethanone 51. 4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 tert-부틸 에스테르51. 4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl)- Piperazine-1-carboxylic acid tert-butyl ester 52. 4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 메틸아미드52. 4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl)- Piperazine-1-carboxylic acid methylamide 53. 4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 디메틸아미드53. 4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl)- Piperazine-1-carboxylic acid dimethylamide 54. 1-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-2-히드록시-에타논54. 1- [4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-yl Methyl) -piperazin-1-yl] -2-hydroxy-ethanone 55. N5-(4-플루오로-페닐)-N2-{4-[4-(4-플루오로-페닐)-피페라진-1-일메틸]-피리딘-2-일}-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민55. N 5 - (4-fluoro-phenyl) -N 2 - {4- [4- (4- fluoro-phenyl) -piperazin-1-ylmethyl] -pyridin-2-yl} -N 5 -Methyl-thiazolo [5,4-b] pyridine-2,5-diamine 56. 1-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페리딘-3-카르복실산 디에틸아미드56. 1- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl)- Piperidine-3-carboxylic acid diethylamide 57. 3-[(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-메틸-아미노]-프로피온니트릴57. 3-[(2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl) -Methyl-amino] -propionnitrile 58. N5-(4-플루오로-페닐)-N2-(4-{[(2-메톡시-에틸)-메틸-아미노]-메틸}-피리딘-2-일)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민58. N 5 - (4-fluoro-phenyl) -N 2 - (4 - { [(2- methoxy-ethyl) -methyl-amino] -methyl} -pyridin-2-yl) -N 5 - methyl -Thiazolo [5,4-b] pyridine-2,5-diamine 59. 2-[(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-메틸-아미노]-에탄올59. 2-[(2- {5-[(4-fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl) -Methyl-amino] -ethanol 60. N2-[4-(2,6-디메틸-몰포린-4-일메틸)-피리딘-2-일]-N5-(4-플루오로-페닐)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민60. N 2 - [4- (2,6- Dimethyl-morpholine-4-ylmethyl) -pyridin-2-yl] -N 5 - (4-fluoro-phenyl) -N 5-methyl-thiazolo [5,4-b] pyridine-2,5-diamine 61. 1-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페리딘-4-카르복실산 에틸 에스테르61. 1- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl)- Piperidine-4-carboxylic acid ethyl ester 62. N5-(4-플루오로-페닐)-N5-메틸-N2-(4-피페라진-1-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민62. N 5- (4-Fluoro-phenyl) -N 5 -methyl-N 2- (4-piperazin-1-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine -2,5-diamine 63. 1-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-2-메톡시-에타논63. 1- [4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-yl Methyl) -piperazin-1-yl] -2-methoxy-ethanone 64. 시클로프로필-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-메타논64. Cyclopropyl- [4- (2- {5-[(4-fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine-4- Ylmethyl) -piperazin-1-yl] -methanone 65. 1-[4-(2-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-프로판-1-온65. 1- [4- (2- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-yl Methyl) -piperazin-1-yl] -propan-1-one 66. N5-(4-플루오로-페닐)-N5-메틸-N2-(5-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민66. N 5- (4-Fluoro-phenyl) -N 5 -methyl-N 2- (5-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine -2,5-diamine 67. N5-(4-플로오로-페닐)-N5-메틸-N2-[5-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민67. N 5 - (4- flow oro-phenyl) -N 5 - methyl -N 2 - [5- (4- methyl-piperazin-1-ylmethyl) -pyridin-2-yl] - thiazolo [5 , 4-b] pyridine-2,5-diamine 68. 1-[4-(6-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페라진-1-일]-에타논68. 1- [4- (6- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperazin-1-yl] -ethanone 69. 1-(6-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페리딘-4-올69. 1- (6- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-ylmethyl)- Piperidine-4-ol 70. N2-[5-(4-에틸-피페라진-1-일메틸)-피리딘-2-일]-N5-(4-플루오로-페닐)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민70. N 2- [5- (4-ethyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5- (4-fluoro-phenyl) -N 5 -methyl-thiazolo [5 , 4-b] pyridine-2,5-diamine 71. N2-[5-(3-디메틸아미노-피롤리딘-1-일메틸)-피리딘-2-일]-N5-(4-플루오로-페닐)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민71. N 2 - [5- (3- dimethylamino-pyrrolidin-1-ylmethyl) -pyridin-2-yl] -N 5 - (4-fluoro-phenyl) -N 5-methyl-thiazolo [5,4-b] pyridine-2,5-diamine 72. 2-[(6-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-아미노]-부탄-1-올72. 2-[(6- {5-[(4-fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-ylmethyl) -Amino] -butan-1-ol 73. N5-(4-플루오로-페닐)-N2-[5-(4-메탄설포닐-피페라진-1-일메틸)-피리딘-2-일]-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민73. N 5- (4-Fluoro-phenyl) -N 2- [5- (4-methanesulfonyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -methyl-thiazolo [5,4-b] pyridine-2,5-diamine 74. N2-{5-[4-(2-플루오로-에틸)-피페라진-1-일메틸]-피리딘-2-일}-N5-(4-플루오로-페닐)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아진 74. N 2 - {5- [4- (2- fluoro-ethyl) -piperazin-1-ylmethyl] -pyridin-2-yl} -N 5 - (4-fluorophenyl) -N 5 -Methyl-thiazolo [5,4-b] pyridine-2,5-diazine 75. N2-[5-(2,6-디메틸-몰포린-4-일메틸)-피리딘-2-일]-N5-(4-플루오로-페닐)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민75. N 2- [5- (2,6-Dimethyl-morpholin-4-ylmethyl) -pyridin-2-yl] -N 5- (4-fluoro-phenyl) -N 5 -methyl-thiazolo [5,4-b] pyridine-2,5-diamine 76. 1-(6-{5-[(4-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페리딘-4-카르복실산 아미드76. 1- (6- {5-[(4-Fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-ylmethyl)- Piperidine-4-carboxylic acid amide 77. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민77. N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4- b] pyridine-2,5-diamine 78. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민78.N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -thia Zolo [5,4-b] pyridine-2,5-diamine 79. 1-[4-(2-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논79. 1- [4- (2- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine- 4-ylmethyl) -piperazin-1-yl] -ethanone 80. 4-(2-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 디메틸아미드80. 4- (2- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazole [5,4-b] pyridin-2-ylamino} -pyridin-4-yl Methyl) -piperazine-1-carboxylic acid dimethylamide 81. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-(5-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민81.N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- (5-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4- b] pyridine-2,5-diamine 82. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-[5-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민82.N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- [5- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -thia Zolo [5,4-b] pyridine-2,5-diamine 83. 1-[4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페라진-1-일]-에타논83. 1- [4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine- 3-ylmethyl) -piperazin-1-yl] -ethanone 84. 2-[(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티이졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-메틸-아미노]-에탄올84. 2-[(6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -tizolo [5,4-b] pyridin-2-ylamino} -pyridine-3- Monomethyl) -methyl-amino] -ethanol 85. N5-(2,4-디플루오로-페닐)-N2-(5-{[(2-메톡시-에틸)-메틸-아미노]-메틸}-피리 딘-2-일)-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민85.N 5- (2,4-Difluoro-phenyl) -N 2- (5-{[(2-methoxy-ethyl) -methyl-amino] -methyl} -pyridin-2-yl)- N 5 -Methyl-thiazolo [5,4-b] pyridine-2,5-diamine 86. N5-(2,4-디플루오로-페닐)-N2-[5-(2,6-디메틸-몰포린-4-일메틸)-피리딘-2-일]-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민86. N 5- (2,4-Difluoro-phenyl) -N 2- [5- (2,6-dimethyl-morpholin-4-ylmethyl) -pyridin-2-yl] -N 5 -methyl -Thiazolo [5,4-b] pyridine-2,5-diamine 87. 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페리딘-4-올87. 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperidin-4-ol 88. N5-(2,4-디플루오로-페닐)-N2-[5-(3-디메틸아미노-피롤리딘-1-일메틸)-피리딘-2-일]-N5-메틸-티아졸로[5,4-b]피리딘-2,5-디아민88. N 5- (2,4-Difluoro-phenyl) -N 2- [5- (3-dimethylamino-pyrrolidin-1-ylmethyl) -pyridin-2-yl] -N 5 -methyl -Thiazolo [5,4-b] pyridine-2,5-diamine 89. 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피롤리딘-2-카르복실산 메틸 에스테르89. 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -pyrrolidine-2-carboxylic acid methyl ester 90. 4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페라진-1-카르복실산 메틸아미드90. 4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperazine-1-carboxylic acid methylamide 91. 4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페라진-1-카르복실산 디메틸아미드91. 4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperazine-1-carboxylic acid dimethylamide 92. 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페리딘-4-카르복실산 메틸 에스테르92. 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperidine-4-carboxylic acid methyl ester 93. 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일메틸)-피페리딘-4-카르복실산93. 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl Methyl) -piperidine-4-carboxylic acid 94. 1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일 아미노}-피리딘-3-일메틸)-피롤리딘-2-카르복실산94. 1- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-yl amino} -pyridin-3-yl Methyl) -pyrrolidine-2-carboxylic acid 95. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-(5-피페라진-1-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민95. N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- (5-piperazin-1-ylmethyl-pyridin-2-yl) -thiazolo [5,4- b] pyridine-2,5-diamine 96. (6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-몰포린-4-일-메타논96. (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl)- Morpholin-4-yl-methanone 97. (6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-(4-메틸-피페라진-1-일)-메타논97. (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl)- (4-Methyl-piperazin-1-yl) -methanone 98. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-(1-메틸-피페리딘-4-일메틸)-니코틴아미드98. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N- (1-methyl-py Ferridin-4-ylmethyl) -nicotinamide 99. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-(2-히드록시-에틸)-니코틴아미드99. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N- (2-hydroxy- Ethyl) -nicotinamide 100. (6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-(4-히드록시-피페리딘-1-일)-메타논100. (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl)- (4-hydroxy-piperidin-1-yl) -methanone 101. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-(2-몰포린-4-일-에틸)-니코틴아미드101. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N- (2-morpholin- 4-yl-ethyl) -nicotinamide 102. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-(2-히드록시-에틸)-N-메틸-니코틴아미드102. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N- (2-hydroxy- Ethyl) -N-methyl-nicotinamide 103. N-(2-디에틸아미노-에틸)-6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-니코틴아미드103. N- (2-Diethylamino-ethyl) -6- {5-[(2,4-difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridine-2- Monoamino} -nicotinamide 104. 4-[(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-카보닐)-아미노]-피페리딘-1-카르복실산tert-부틸 에스테르104. 4-[(6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine-3- Carbonyl) -amino] -piperidine-1-carboxylic acid tert-butyl ester 105. tert-부틸[1-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-카보닐)-피페리딘-4-일]-카바메이트105. tert-Butyl [1- (6- {5-[(2,4-difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine -3-carbonyl) -piperidin-4-yl] -carbamate 106. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-피페리딘-4-일-니코틴아미드106. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N-piperidine-4- Mono-nicotinamide 107. (4-아미노-피페리딘-1-일)-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-메타논107. (4-Amino-piperidin-1-yl)-(6- {5-[(2,4-difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridine -2-ylamino} -pyridin-3-yl) -methanone 108. 6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-N-(1-메틸-피페리딘-4-일)-니코틴아미드108. 6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -N- (1-methyl-pi Ferridin-4-yl) -nicotinamide 109. (6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-3-일)-(4-디메틸아미노-피페리딘-1-일)-메타논109. (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-3-yl)- (4-dimethylamino-piperidin-1-yl) -methanone 110. N5-(4-클로로-2-플루오로-페닐)-N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-티아졸로[5,4-b]피리딘-2,5-디아민110. N 5- (4-Chloro-2-fluoro-phenyl) -N 5 -methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4 -b] pyridine-2,5-diamine 111. N5-(4-클로로-2-플루오로-페닐)-N5-메틸-N2-[4-(4-메틸-피레라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민111.N 5- (4-Chloro-2-fluoro-phenyl) -N 5 -methyl-N 2- [4- (4-methyl-pyrazin-1-ylmethyl) -pyridin-2-yl]- Thiazolo [5,4-b] pyridine-2,5-diamine 112. 1-[4-(2-{5-[(4-클로로-2-플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논112. 1- [4- (2- {5-[(4-Chloro-2-fluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine -4-ylmethyl) -piperazin-1-yl] -ethanone 113. N5-(4-클로로페닐)-N5-메틸-N2-(4-몰포린-4-일메틸-피리딘-2-일)-티아졸 로[5,4-b]피리딘-2,5-디아민113. N 5- (4-Chlorophenyl) -N 5 -methyl-N 2- (4-morpholin-4-ylmethyl-pyridin-2-yl) -thiazolo [5,4-b] pyridine- 2,5-diamine 114. N5-(4-클로로-페닐)-N5-메틸-N2-[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일]-티아졸로[5,4-b]피리딘-2,5-디아민114. N 5- (4-Chloro-phenyl) -N 5 -methyl-N 2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-yl] -thiazolo [5, 4-b] pyridine-2,5-diamine 115. 1-[4-(2-{5-[(4-클로로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논115. 1- [4- (2- {5-[(4-Chloro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl ) -Piperazin-1-yl] -ethanone 116. 4-(2-{5-[(4-클로로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-카르복실산 디메틸아미드116. 4- (2- {5-[(4-Chloro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl) -pipe Razine-1-carboxylic acid dimethylamide 117. 1-[4-(2-{5-[(3,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸)-피페라진-1-일]-에타논117. 1- [4- (2- {5-[(3,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridine- 4-ylmethyl) -piperazin-1-yl] -ethanone 118. 6-{5-[(3,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-니코틴산 메틸 에스테르118. 6- {5-[(3,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -nicotinic acid methyl ester 119. [4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일)-피페라진-1-일]-아세트산 에틸 에스테르119. [4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyrimidine-4 -Yl) -piperazin-1-yl] -acetic acid ethyl ester 120. 2-[4-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일)-피페라진-1-일]-에탄올120. 2- [4- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyrimidine -4-yl) -piperazin-1-yl] -ethanol 121. 2-[(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일)-메틸-아미노]-에탄올121. 2-[(6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyrimidine-4 -Yl) -methyl-amino] -ethanol 122. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-[6-(2-몰포린-4-일-에틸아미노)-피리미딘-4-일]-티아졸로[5,4-b]피리딘-2,5-디아민122. N 5 - (2,4- difluoro-phenyl) -N 5 - methyl -N 2 - [6- (2- morpholine-4-yl-ethylamino) -pyrimidin-4-yl] - Thiazolo [5,4-b] pyridine-2,5-diamine 123. N5-(2,4-디플루오로-페닐)-N5-메틸-N2-{6-[3-(4-메틸-피페라진-1-일)-프로필아미노]-피리미딘-4-일}-티아졸로[5,4-b]피리딘-2,5-디아민123. N 5- (2,4-Difluoro-phenyl) -N 5 -methyl-N 2- {6- [3- (4-methyl-piperazin-1-yl) -propylamino] -pyrimidine -4-yl} -thiazolo [5,4-b] pyridine-2,5-diamine 124. 2-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일아미노)-에탄올124. 2- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyrimidine-4- Monoamino) -ethanol 125. 2-(6-{5-[(2,4-디플루오로-페닐)-메틸-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리미딘-4-일)-피페리딘-1-카르복실산 에틸 에스테르125. 2- (6- {5-[(2,4-Difluoro-phenyl) -methyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyrimidine-4- Yl) -piperidine-1-carboxylic acid ethyl ester 126. 4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-2-온 126. 4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazine-2- On 127. 1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피롤리딘-3-올 127. 1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -pyrrolidine-3 -All 128. ((S)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피롤리딘-2-일)-메탄올128. (( S ) -1- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Pyrrolidin-2-yl) -methanol 129. N5-메틸-N2-[4-(4-메틸-[1,4]디아제판-1-일메틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민 129. N 5 -Methyl-N 2- [4- (4-methyl- [1,4] diazepane-1-ylmethyl) -pyridin-2-yl] -N 5 -p-tolyl-thiazolo [5 , 4-b] pyridine-2,5-diamine 130. 1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페리딘-4-온130. 1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperidine-4 -On 131. (R)-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산 메틸 에스테르131. ( R ) -2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid methyl ester 132. (S)-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리 딘-4-일메틸}-아미노)-프로피온산 메틸 에스테르132. ( S ) -2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -Amino) -propionic acid methyl ester 133. ({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-아세트산 에틸 에스테르133. ({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -acetic acid ethyl ester 134. 1-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-시클로프로판 카르복실산 메틸 에스테르134. 1-({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -cyclo Propane carboxylic acid methyl ester 135. 2-메틸-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산 메틸 에스테르135. 2-methyl-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid methyl ester 136. 2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로판-1,3-디올136. 2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -propane -1,3-diol 137. (S)-2-(메틸-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산 메틸 에스테르137. ( S ) -2- (methyl- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl } -Amino) -propionic acid methyl ester 138. 2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-에탄올138. 2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -ethanol 139. 1-(1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페리딘-4-일)-에타논139. 1- (1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperi Din-4-yl) -ethanone 140. N2-[4-(4-메탄설포닐-피페리딘-1-일메틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민140. N 2- [4- (4-methanesulfonyl-piperidin-1-ylmethyl) -pyridin-2-yl] -N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4 -b] pyridine-2,5-diamine 141. N2-[4-(4-메탄설포닐-피페라진-1-일메틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민141. N 2 - [4- (4- methanesulfonyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 - methyl -N 5 -p- tolyl-thiazolo [5,4- b] pyridine-2,5-diamine 142. N2-(4-{[2-(2,5-디메틸-옥사졸-4-일)-에틸아미노]-메틸}-피리딘-2-일)-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민 142. N 2 - (4 - { [2- (2,5- dimethyl-4-yl) -ethyl-amino] -methyl} -pyridin-2-yl) -N 5 - methyl -N 5 -p -Tolyl-thiazolo [5,4-b] pyridine-2,5-diamine 143. 4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-카르복실산 에틸 에스테르143. 4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazin-1- Carboxylic acid ethyl ester 144. 3-히드록시-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산 메틸 에스테르144. 3-hydroxy-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -Amino) -propionic acid methyl ester 145. 3-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로판-1,2-디올145. 3-({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -propane -1,2-diol 146. [1-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-시클로펜틸]-메탄올146. [1-({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino)- Cyclopentyl] -methanol 147. 2-메틸-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로판-1-올147. 2-Methyl-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propan-1-ol 148. N2-[4-(4-이소프로필-피페라진-1-일메틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민148. N 2- [4- (4-Isopropyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4-b ] Pyridine-2,5-diamine 149. N2-[4-(4-시클로프로필-피페라진-1-일메틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민149. N 2- [4- (4-cyclopropyl-piperazin-1-ylmethyl) -pyridin-2-yl] -N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4-b ] Pyridine-2,5-diamine 150. N5-메틸-N2-(4-페페라진-1-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민150.N 5 -Methyl-N 2- (4-peperazin-1-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5- Diamine 151. 1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페리딘-4-온 옥심151. 1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperidine-4 -On oxime 152. 1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페리딘-4-온 O-메틸-옥심152. 1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperidine-4 -One O-methyl-oxime 153. N5-메틸-N2-(4-피라졸-1-일메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민153. N 5 -Methyl-N 2- (4-pyrazol-1-ylmethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5- Diamine 154. 2-히드록시-1-(4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-일)-에타논154. 2-hydroxy-1- (4- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl Methyl} -piperazin-1-yl) -ethanone 155. 4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-1-카르복실산 시클로프로필아미드155. 4- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -piperazin-1- Carboxylic Acid Cyclopropylamide 156. (S)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피롤리딘-2-카르복실산156. (S) -1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -py Lolidine-2-carboxylic acid 157. (S)-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산157. ( S ) -2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid 158. ({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-아세트산158. ({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -amino) -acetic acid 159. (R)-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산159. ( R ) -2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid 160. 1-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘- 4-일메틸}-아미노)-시클로프로판카르복실산160. 1-({2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin- 4-ylmethyl} -amino) -cyclo Propanecarboxylic acid 161. 2-메틸-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산161. 2-Methyl-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid 162. (S)-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온산162. ( S ) -2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Amino) -propionic acid 163. 1-메틸-4-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-피페라진-2-온163. 1-Methyl-4- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -pipe Razin-2-one 164. (R)-N-메톡시-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온아미드164. (R) -N-methoxy-2-({2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4 -Ylmethyl} -amino) -propionamide 165. N-메톡시-2-메틸-2-({2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온아미드165. N-methoxy-2-methyl-2 - ({2- [5- (-p- tolyl-amino) thiazolo [5,4-b] pyridin-2-ylamino] -pyridin -4 -Ylmethyl} -amino) -propionamide 166. N5-메틸-N2-(4-메틸아미노메틸-피리딘-2-일)-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민166. N 5 -Methyl-N 2- (4-methylaminomethyl-pyridin-2-yl) -N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine 167. N2-(4-아미노메틸-피리딘-2-일)-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민167. N 2- (4-Aminomethyl-pyridin-2-yl) -N 5 -methyl-N 5 -p-tolyl-thiazolo [5,4-b] pyridine-2,5-diamine 168. 2-메탄술포닐-N-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아세트아미드168. 2-Methanesulfonyl-N- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} Acetamide 169. 2-히드록시-N-{2-[5-메틸-p-톨릴-아미노]-티아졸로[5,4-b]피리딘-2-일아미노}-피리딘-4-일메틸}-아세트아미드169. 2-hydroxy-N- {2- [5-methyl-p-tolyl-amino] -thiazolo [5,4-b] pyridin-2-ylamino} -pyridin-4-ylmethyl} -acet amides 170. 5-옥소-피롤리딘-2-카르복실산 {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미드170. 5-oxo-pyrrolidine-2-carboxylic acid {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine- 4-ylmethyl} -amide 171. 1-메탄술포닐-피페리딘-4-카르복실산 {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미드171. 1-Methanesulfonyl-piperidine-4-carboxylic acid {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino]- Pyridin-4-ylmethyl} -amide 172. 2-디메틸아미노-N-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아세트아미드172. 2-Dimethylamino-N- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Acetamide 173. N-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-3-피페리딘-1-일-프로피온아미드173. N- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} -3-piperidine -1-yl-propionamide 174. 1-메틸-피롤리딘-2-카르복실산 {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미드174. 1-Methyl-pyrrolidine-2-carboxylic acid {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine- 4-ylmethyl} -amide 175. 피롤리딘-2-카르복실산 {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-아미드175. Pyrrolidine-2-carboxylic acid {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl }-amides 176. N2-[4-(1,1-디옥소-16-티오모폴린-4-일메틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민176. N 2 - [4- (1,1- dioxo-6 -1 - T Omo morpholin-4-ylmethyl) -pyridin-2-yl] -N 5 - methyl -N 5 -p- tolyl-thiazolo [5,4-b] pyridine-2,5-diamine 177. N-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-메탄술폰아미드177. N - {2- [5- (methyl -p- tolyl-amino) thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl} - methanesulfonamide 178. 1-시클로프로필-3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일메틸}-우레아178. 1-Cyclopropyl-3- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-ylmethyl}- Urea 179. (S)-N-히드록시-2-(메틸-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘 -2-일아미노]-피리딘-4-일메틸}-아미노)-프로피온아미드179. ( S ) -N-hydroxy-2- (methyl- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine -4-ylmethyl} -amino) -propionamide 180. N,N-디메틸-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드 180. N, N-dimethyl-2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl}- Acetamide 181. 1-(4-아세틸-피페라진-1-일)-2-{2-[5-(메틸-p-톨릴-아미노) -티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에타논181. 1- (4-acetyl-piperazin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -ethanone 182. N-시클로프로필-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드182. N-cyclopropyl-2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -acet amides 183. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-1-피페리딘-1-일-에타논183. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-piperidine- 1-Day-Ethanon 184. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-1-피롤리딘-1-일-에타논184. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-pyrrolidine- 1-Day-Ethanon 185. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-1-모폴린-4-일-에탄온185. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-morpholine-4 -Sun-Ethanon 186. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세트아미드186. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl} -acetamide 187. N-[2-(4-아세틸-피페라진-1-일)-에틸]-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세트아미드187. N- [2- (4-acetyl-piperazin-1-yl) -ethyl] -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] Pyridin-2-ylarmano] -pyridin-4-yl} -acetamide 188. N-메틸-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-아세트아미드 188. N-Methyl-2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -acetamide 189. N-[2-(2,5-디메틸-옥사졸-4-일)-에틸]-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸 로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세트아미드189. N- [2- (2,5-Dimethyl-oxazol-4-yl) -ethyl] -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4 -b] pyridin-2-ylarmano] -pyridin-4-yl} -acetamide 190. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로 [5,4-b]피리딘-2-일아마노]-피리딘-4-일}-1-피페라진-1-일-에타논190. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-piperazine-1 -Sun-Ethanon 191. N-(1-히드록시메틸-프로필)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세트아미드191.N- (1-Hydroxymethyl-propyl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine -4-yl} -acetamide 192. 1-(4-에틸-피페라진 -1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에타논192. 1- (4-Ethyl-piperazin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -ethanone 193. 1-(4-이소프로필-피페라진-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에탄온193. 1- (4-Isopropyl-piperazin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-yl Amano] -pyridin-4-yl} -ethanone 194. 3-히드록시-2-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세틸아미노)-피로피온산 메틸 에스테르194. 3-hydroxy-2- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl } -Acetylamino) -pyrionic acid methyl ester 195. 1-((S)-3-아미노-피롤리딘-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에타논195. 1-((S) -3-Amino-pyrrolidin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine -2-ylarmano] -pyridin-4-yl} -ethanone 196. 1-((R)-3-아미노-피롤리딘-1-일)-2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에타논196. 1-((R) -3-Amino-pyrrolidin-1-yl) -2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine -2-ylarmano] -pyridin-4-yl} -ethanone 197. N-[(R)-1-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-아세틸)-피롤리딘-3-일]-아세트아미드197. N-[(R) -1- (2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine-4 -Yl} -acetyl) -pyrrolidin-3-yl] -acetamide 198. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-모폴린-4-일-메타논198. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl} -morpholin-4-yl-meta Paddy field 199. (4-메틸-피페라진-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘 -2-일아마노]-피리딘-4-일}-메타논199. (4-Methyl-piperazin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine- 4-day} -Methanone 200. {2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-피페라진-1-일-메타논200. {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -piperazin-1-yl-meta Paddy field 201. (3-히드록시-피롤리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-피페라진-1-일-메타논203- (3-hydroxy-pyrrolidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino]- Pyridin-4-yl} -piperazin-1-yl-methanone 202. (3-디메틸아미노-피롤리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논202. (3-Dimethylamino-pyrrolidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino]- Pyridin-4-yl} -methanone 203. N-[3-(4-메틸-피페라진-1-일)-프로필]-2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-이소니코틴아미드203. N- [3- (4-Methyl-piperazin-1-yl) -propyl] -2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine-2 -Yl-amino] -isonicotinamide 204. N-[2-(4-아세틸-피페리딘-1-일)-에틸]-2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-이소니코틴아미드204. N- [2- (4-acetyl-piperidin-1-yl) -ethyl] -2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridine- 2-ylamino] -isonicotinamide 205. N-((R)-1-히드록시메틸-프로필)-2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-이소니코틴아미드205. N-(( R ) -1-hydroxymethyl-propyl) -2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino]- Isonicotinamide 206. (4-아미노-피페리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논206. (4-Amino-piperidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridine -4-yl} -methanone 207. (4-디메틸아미노-피페리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논207. (4-Dimethylamino-piperidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano]- Pyridin-4-yl} -methanone 208. ((S)-3-아미노-피롤리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논208. ((S) -3-Amino-pyrrolidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-yl Amano] -pyridin-4-yl} -methanone 209. N-((S)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]- 피리딘-4-카르보닐}-피롤리딘-3-일)-아세트아미드209. N-((S) -1- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4-carbonyl } -Pyrrolidin-3-yl) -acetamide 210. ((R)-3-아미노-피롤리딘-1-일)-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-메타논210. ((R) -3-Amino-pyrrolidin-1-yl)-{2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-yl Amano] -pyridin-4-yl} -methanone 211. N-((R)-1-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-카르보닐}-피롤리딘-3-일)-아세트아미드211.N-((R) -1- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine-4-carbonyl } -Pyrrolidin-3-yl) -acetamide 212. 2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에탄올212. 2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl} -ethanol 213. 1-[4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에틸)-피페라진-1-일]-에타논213. 1- [4- (2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamano] -pyridin-4-yl}- Ethyl) -piperazin-1-yl] -ethanone 214. 4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘-4-일}-에틸)-피페라진-2-온214. 4- (2- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -ethyl)- Piperazin-2-one 215. N5-메틸-N2-{4-[2-(4-메틸-피페라진-1-일)-에틸]-피리딘-2-일}-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민215. 5 N-Methyl -N 2 - {4- [2- ( 4- methyl-piperazin-1-yl) ethyl] pyridin-2-yl} -N 5 -p- tolyl-thiazolo [5, , 4-b] pyridine-2,5-diamine 216. N5-메틸-N2-[4-(2-몰폴린-4-일-에틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민216. 5 N-Methyl -N 2 - [4- (2- morpholin-4-yl-ethyl) -pyridin-2-yl] -N 5 -p- tolyl-thiazolo [5,4-b] pyridine -2,5-diamine 217. N5-메틸-N2-[4-(2-피롤리딘-1-일-에틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민217. 5 N-Methyl -N 2 - [4- (2- pyrrolidin-1-yl-ethyl) -pyridin-2-yl] -N 5 -p- tolyl-thiazolo [5,4-b] Pyridine-2,5-diamine 218. N5-메틸-N2-[4-(2-피페라진-1-일-에틸)-피리딘-2-일]-N5-p-톨릴-티아졸 로[5,4-b]피리딘-2,5-디아민218. 5 N-Methyl -N 2 - [4- (2- piperazin-1-yl-ethyl) -pyridin-2-yl] -N 5 -p- tolyl - [5,4-b] thiazole in Pyridine-2,5-diamine 219. 2-[메틸-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아마노]-피리딘 -4-일}-에틸)-아미노]-에탄올219. 2- [Methyl- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl}- Ethyl) -amino] -ethanol 220. N2-[4-(2-디메틸아미노-에틸)-피리딘-2-일]-N5-메틸-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민220. N 2 - [4- (2- dimethylamino-ethyl) -pyridin-2-yl] -N 5 - methyl -N 5 -p- tolyl-thiazolo [5,4-b] pyridine-2,5 -Diamine 221. N5-메틸-N2-[4-(2-피페리딘-1-일-에틸)-피리딘-2-일]-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민221. 5 N-Methyl -N 2 - [4- (2- piperidin-1-yl-ethyl) -pyridin-2-yl] -N 5 -p- tolyl-thiazolo [5,4-b] Pyridine-2,5-diamine 222. N5-메틸-N2-{4-[2-(2-몰폴린-4-일-에틸아미노)-에틸]-피리딘-2-일}-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민222. 5 N-Methyl -N 2 - {4- [2- ( 2- morpholin-4-yl-ethylamino) -ethyl] -pyridin-2-yl} -N 5 -p- tolyl-thiazolo [ 5,4-b] pyridine-2,5-diamine 223. 2-히드록시-1-[4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-에틸)-피페라진-1-일]-에타논223. 2-hydroxy-1- [4- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridine- 4-yl} -ethyl) -piperazin-1-yl] -ethanone 224. 2-히드록시-2-메틸-1-[4-(2-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-에틸)-피페라진-1-일]프로판-1-온224. 2-hydroxy-2-methyl-1- [4- (2- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -ethyl) -piperazin-1-yl] propan-1-one 225. 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로피온산 메틸 에스테르225. 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -propionic acid methyl ester 226. 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로피온산226. 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -propionic acid 227. 1-(4-아세틸-피페라진-1-일)-3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로판-1-온227. 1- (4-acetyl-piperazin-1-yl) -3- {2- [5- (methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino ] -Pyridin-4-yl} -propan-1-one 228. 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-1-몰폴린-4-일-프로판-1-온228. 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-morpholine-4 -Yl-propane-1-one 229. 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-1-피페라진-1-일-프로판-1-온229. 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -1-piperazin-1 -Yl-propane-1-one 230. 3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로판-1-올230. 3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -propan-1-ol 231. 1-[4-(3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로필)-피페라진-1-일]-에타논231. 1- [4- (3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl}- Propyl) -piperazin-1-yl] -ethanone 232. N5-메틸-N2-{4-[3-(4-메틸-피페라진-1-일)-프로필]-피리딘-2-일}-N5-p-톨릴-티아졸로[5,4-b]피리딘-2,5-디아민232. N 5 -Methyl-N 2- {4- [3- (4-methyl-piperazin-1-yl) -propyl] -pyridin-2-yl} -N 5 -p-tolyl-thiazolo [5 , 4-b] pyridine-2,5-diamine 233. 4-(3-{2-[5-(메틸-p-톨릴-아미노)-티아졸로[5,4-b]피리딘-2-일아미노]-피리딘-4-일}-프로필)-피페라진-1-카르복실산 메틸아미드233. 4- (3- {2- [5- (Methyl-p-tolyl-amino) -thiazolo [5,4-b] pyridin-2-ylamino] -pyridin-4-yl} -propyl)- Piperazine-1-carboxylic acid methylamide 234. 2-클로로-5-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-벤조산 메틸 에스테르234. 2-Chloro-5-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino}-methyl benzoate ester 235. 2-클로로-5-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-벤조산235. 2-Chloro-5-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -benzoic acid 236. 2-클로로-5-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-N-메톡시-벤즈아미드236. 2-Chloro-5-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -N- Methoxy-benzamide 237. 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5237. 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5 ,4-b]-피리딘-5-일}-메틸-아미노)-2-클로로-N-메톡시-벤즈아미드, 4-b] -pyridin-5-yl} -methyl-amino) -2-chloro-N-methoxy-benzamide 238. 2-클로로-N-메톡시-5-{메틸-[2-(4-몰포린-4-일메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-아미노}-벤즈아미드238. 2-Chloro-N-methoxy-5- {methyl- [2- (4-morpholin-4-ylmethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridine-5 -Yl] -amino} -benzamide 239. 2-클로로-N-메톡시-5-(메틸-{2-[4-(4-메틸-피레라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-아미노)-벤즈아미드239. 2-Chloro-N-methoxy-5- (methyl- {2- [4- (4-methyl-pyrazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4 -b] pyridin-5-yl} -amino) -benzamide 240. 3-[(2-아미노-티아졸로[5,4-b]피리딘-5-일)-메틸-아미노]-N-메톡시-벤즈아미드240. 3-[(2-amino-thiazolo [5,4-b] pyridin-5-yl) -methyl-amino] -N-methoxy-benzamide 241. 3-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-N-메톡시-벤즈아미드241. 3-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -methyl -Amino) -N-methoxy-benzamide 242. N-메톡시-3-{메틸-[2-(4-몰포린-4-일메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-아미노}-벤즈아미드242. N-methoxy-3- {methyl- [2- (4-morpholin-4-ylmethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl]- Amino} -benzamide 243. N-메톡시-3-(메틸-{2-[4-(4-메틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-아미노)-벤즈아미드243. N-methoxy-3- (methyl- {2- [4- (4-methyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridine -5-yl} -amino) -benzamide 244. 3-{[2-(4-디메틸아미노메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-N-메톡시-벤즈아미드244. 3-{[2- (4-Dimethylaminomethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -N-methoxy-benz amides 245. 3-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-N,N-디메틸-벤즈아미드245. 3-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -N, N-dimethyl- Benzamide 246. 3-{[2-(4-히드록시메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5-일]-메틸-아미노}-N-메틸-벤즈아미드246. 3-{[2- (4-hydroxymethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -N-methyl-benzamide 247. 3-{[2-(4-디메틸카바모일메틸-피리딘-2-일아미노)-티아졸로[5,4-b]피리딘-5- 일]-메틸-아미노}-N-메톡시-벤즈아미드247. 3-{[2- (4-Dimethylcarbamoylmethyl-pyridin-2-ylamino) -thiazolo [5,4-b] pyridin-5-yl] -methyl-amino} -N-methoxy- Benzamide 248. 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-2-플루오로-벤조산 에틸 에스테르248. 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -methyl -Amino) -2-fluoro-benzoic acid ethyl ester 249. 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-2-플루오로-N-메톡시-벤즈아미드249. 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -methyl -Amino) -2-fluoro-N-methoxy-benzamide 250. 5-({2-[4-(4-아세틸-피페라진-1-일메틸)-피리딘-2-일아미노]-티아졸로[5,4-b]피리딘-5-일}-메틸-아미노)-2-플루오로-N-메틸-벤즈아미드250. 5-({2- [4- (4-acetyl-piperazin-1-ylmethyl) -pyridin-2-ylamino] -thiazolo [5,4-b] pyridin-5-yl} -methyl -Amino) -2-fluoro-N-methyl-benzamide 바람직하지 않은 KDR 활성으로 인한 질병들을 치료 및 억제하기 위한 약리학적 유효량의 제 1 항에 따른 화합물; 및 약제학적으로 허용되는 담체, 희석제, 또는 부형제, 또는 이들의 조합;을 포함하는 것으로 구성된 약제학적 조성물.A pharmacologically effective amount of a compound according to claim 1 for treating and inhibiting diseases caused by undesirable KDR activity; And a pharmaceutically acceptable carrier, diluent, or excipient, or a combination thereof. 제 6 항에 있어서, 상기 질병은 암, 건선, 류마티스성 관절염, 당뇨병성 망막증, 국소 빈형성 심장병, 죽상경화증 또는 카포시 육종인 것을 특징으로 하는 조성물.7. The composition of claim 6, wherein the disease is cancer, psoriasis, rheumatoid arthritis, diabetic retinopathy, focal anemia, atherosclerosis or Kaposi's sarcoma.
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