RU2445312C2 - ПРОИЗВОДНЫЕ 2-МЕТИЛМОРФОЛИН ПИРИДО-, ПИРАЗО- И ПИРИМИДО-ПИРИМИДИНА В КАЧЕСТВЕ ИНГИБИТОРОВ mTOR - Google Patents

ПРОИЗВОДНЫЕ 2-МЕТИЛМОРФОЛИН ПИРИДО-, ПИРАЗО- И ПИРИМИДО-ПИРИМИДИНА В КАЧЕСТВЕ ИНГИБИТОРОВ mTOR Download PDF

Info

Publication number
RU2445312C2
RU2445312C2 RU2009110261/04A RU2009110261A RU2445312C2 RU 2445312 C2 RU2445312 C2 RU 2445312C2 RU 2009110261/04 A RU2009110261/04 A RU 2009110261/04A RU 2009110261 A RU2009110261 A RU 2009110261A RU 2445312 C2 RU2445312 C2 RU 2445312C2
Authority
RU
Russia
Prior art keywords
pharmaceutically acceptable
compound
compound according
formula
acceptable salt
Prior art date
Application number
RU2009110261/04A
Other languages
English (en)
Other versions
RU2009110261A (ru
Inventor
Хитер Мэри Эллен ДАГГАН (GB)
Хитер Мэри Эллен ДАГГАН
Фредерик Жорж Мари ЛЕРУ (GB)
Фредерик Жорж Мари Леру
Карин МАЛАГУ (GB)
Карин МАЛАГУ
Нилл Морриссон Барр МАРТИН (GB)
Нилл Морриссон Барр МАРТИН
Кейт Аллан МЕНИР (GB)
Кейт Аллан МЕНИР
Грейм Камерон Марри СМИТ (GB)
Грейм Камерон Марри Смит
Original Assignee
Кудос Фармасьютиклз Лимитед
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=38537521&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=RU2445312(C2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Кудос Фармасьютиклз Лимитед filed Critical Кудос Фармасьютиклз Лимитед
Publication of RU2009110261A publication Critical patent/RU2009110261A/ru
Application granted granted Critical
Publication of RU2445312C2 publication Critical patent/RU2445312C2/ru

Links

Classifications

    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D475/00—Heterocyclic compounds containing pteridine ring systems
    • C07D475/06—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4
    • C07D475/08—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D475/00—Heterocyclic compounds containing pteridine ring systems
    • C07D475/06—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4
    • C07D475/10—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4 with an aromatic or hetero-aromatic ring directly attached in position 2

Abstract

Настоящее изобретение относится к соединениям общей формулы (I)
Figure 00000223
или его фармацевтически приемлемым солям, которые действуют в качестве ингибиторов mTOR. Также заявляется получение фармацевтической композиции, содержащей терапевтически эффективное количество соединения формулы (I) и фармацевтически приемлемый носитель или разбавитель, а также заявляется применение соединения формулы (I) или его фармацевтически приемлемой соли для приготовления лекарственного средства предназначенного для получения противоракового действия. 4 н. и 7 з.п. ф-лы, 25 пр.

Description

Текст описания приведен в факсимильном виде.
Figure 00000001
Figure 00000002
Figure 00000003
Figure 00000004
Figure 00000005
Figure 00000006
Figure 00000007
Figure 00000008
Figure 00000009
Figure 00000010
Figure 00000011
Figure 00000012
Figure 00000013
Figure 00000014
Figure 00000015
Figure 00000016
Figure 00000017
Figure 00000018
Figure 00000019
Figure 00000020
Figure 00000021
Figure 00000022
Figure 00000023
Figure 00000024
Figure 00000025
Figure 00000026
Figure 00000027
Figure 00000028
Figure 00000029
Figure 00000030
Figure 00000031
Figure 00000032
Figure 00000033
Figure 00000034
Figure 00000035
Figure 00000036
Figure 00000037
Figure 00000038
Figure 00000039
Figure 00000040
Figure 00000041
Figure 00000042
Figure 00000043
Figure 00000044
Figure 00000045
Figure 00000046
Figure 00000047
Figure 00000048
Figure 00000049
Figure 00000050
Figure 00000051
Figure 00000052
Figure 00000053
Figure 00000054
Figure 00000055
Figure 00000056
Figure 00000057
Figure 00000058
Figure 00000059
Figure 00000060
Figure 00000061
Figure 00000062
Figure 00000063
Figure 00000064
Figure 00000065
Figure 00000066
Figure 00000067
Figure 00000068
Figure 00000069
Figure 00000070
Figure 00000071
Figure 00000072
Figure 00000073
Figure 00000074
Figure 00000075
Figure 00000076
Figure 00000077
Figure 00000078
Figure 00000079
Figure 00000080
Figure 00000081
Figure 00000082
Figure 00000083
Figure 00000084
Figure 00000085
Figure 00000086
Figure 00000087
Figure 00000088
Figure 00000089
Figure 00000090
Figure 00000091
Figure 00000092
Figure 00000093
Figure 00000094
Figure 00000095
Figure 00000096
Figure 00000097
Figure 00000098
Figure 00000099
Figure 00000100
Figure 00000101
Figure 00000102
Figure 00000103
Figure 00000104
Figure 00000105
Figure 00000106
Figure 00000107
Figure 00000108
Figure 00000109
Figure 00000110
Figure 00000111
Figure 00000112
Figure 00000113
Figure 00000114
Figure 00000115
Figure 00000116
Figure 00000117
Figure 00000118
Figure 00000119
Figure 00000120
Figure 00000121
Figure 00000122
Figure 00000123
Figure 00000124
Figure 00000125
Figure 00000126
Figure 00000127
Figure 00000128
Figure 00000129
Figure 00000130
Figure 00000131
Figure 00000132
Figure 00000133
Figure 00000134
Figure 00000135
Figure 00000136
Figure 00000137
Figure 00000138
Figure 00000139
Figure 00000140
Figure 00000141
Figure 00000142
Figure 00000143
Figure 00000144
Figure 00000145
Figure 00000146
Figure 00000147
Figure 00000148
Figure 00000149
Figure 00000150
Figure 00000151
Figure 00000152
Figure 00000153
Figure 00000154
Figure 00000155
Figure 00000156
Figure 00000157
Figure 00000158
Figure 00000159
Figure 00000160
Figure 00000161
Figure 00000162
Figure 00000163
Figure 00000164
Figure 00000165
Figure 00000166
Figure 00000167
Figure 00000168
Figure 00000169
Figure 00000170

Claims (11)

1. Соединение формулы I
Figure 00000171

или его фармацевтически приемлемая соль,
где X5 и X6 представляют собой СН;
X8 представляет собой N;
R7 выбирают из
Figure 00000172
Figure 00000173
Figure 00000174

Figure 00000175
Figure 00000176
Figure 00000177
Figure 00000178

Figure 00000179
Figure 00000180
Figure 00000181
Figure 00000182

Figure 00000183
Figure 00000184
Figure 00000185

Figure 00000186
Figure 00000187
Figure 00000188

Figure 00000189
и
Figure 00000190

и R2 представляет собой
Figure 00000191
или
Figure 00000192
или
Figure 00000193

или
Figure 00000194
или
Figure 00000195
2. Соединение по п.1, где соединение формулы I представляет собой соединение формулы Ia или Ib
Figure 00000196
Figure 00000197

или их фармацевтически приемлемую соль,
где X5 и X6 представляют собой СН, X8 представляет собой N, а остальные представляют собой СН;
R7 выбирают из
Figure 00000198
Figure 00000199
Figure 00000200

Figure 00000175
Figure 00000201
Figure 00000202
Figure 00000203

Figure 00000204
Figure 00000205
Figure 00000206
Figure 00000207

Figure 00000208
Figure 00000209
Figure 00000210

Figure 00000211
Figure 00000212
Figure 00000213

Figure 00000214
и
Figure 00000215

и R2 представляет собой
Figure 00000191
или
Figure 00000192
или
Figure 00000193

или
Figure 00000194
или
Figure 00000195
3. Соединение по п.1, где соединение формулы I представляет собой соединение формулы Ia
Figure 00000196

или его фармацевтически приемлемую соль
где X5 и X6 представляют собой СН, X8 представляет собой N, R7 выбирают из
Figure 00000198
Figure 00000199
Figure 00000200

Figure 00000175
Figure 00000201
Figure 00000202
Figure 00000203

Figure 00000204
Figure 00000205
Figure 00000206
Figure 00000207

Figure 00000208
Figure 00000209
Figure 00000210

Figure 00000211
Figure 00000212
Figure 00000213

Figure 00000214
и
Figure 00000215

и R2 представляет собой
Figure 00000216
или
Figure 00000217
или
Figure 00000218

или
Figure 00000219
или
Figure 00000220
4. Соединение по п.1, которое представляет собой
Figure 00000221

или его фармацевтически приемлемую соль.
5. Соединение по п.1, которое представляет собой
Figure 00000221
.
6. Соединение по п.1, которое представляет собой
Figure 00000222

или его фармацевтически приемлемую соль.
7. Соединение по п.1, которое представляет собой
Figure 00000222
8. Фармацевтическая композиция, обладающая активностью ингибитора mTOR, содержащая терапевтически эффективное количество соединения по п.1 и фармацевтически приемлемый носитель или разбавитель.
9. Соединение по п.1 или его фармацевтически приемлемая соль, обладающее активностью ингибитора mTOR.
10. Применение соединения по п.1 или его фармацевтически приемлемой соли для приготовления лекарственного средства, предназначенного для получения ингибирующего действия в отношении mTOR.
11. Применение соединения по п.1 или его фармацевтически приемлемой соли для приготовления лекарственного средства, предназначенного для получения противоракового действия.
RU2009110261/04A 2006-08-23 2007-08-21 ПРОИЗВОДНЫЕ 2-МЕТИЛМОРФОЛИН ПИРИДО-, ПИРАЗО- И ПИРИМИДО-ПИРИМИДИНА В КАЧЕСТВЕ ИНГИБИТОРОВ mTOR RU2445312C2 (ru)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US82331106P 2006-08-23 2006-08-23
US60/823,311 2006-08-23
US93877607P 2007-05-18 2007-05-18
US60/938,776 2007-05-18

Publications (2)

Publication Number Publication Date
RU2009110261A RU2009110261A (ru) 2010-09-27
RU2445312C2 true RU2445312C2 (ru) 2012-03-20

Family

ID=38537521

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2009110261/04A RU2445312C2 (ru) 2006-08-23 2007-08-21 ПРОИЗВОДНЫЕ 2-МЕТИЛМОРФОЛИН ПИРИДО-, ПИРАЗО- И ПИРИМИДО-ПИРИМИДИНА В КАЧЕСТВЕ ИНГИБИТОРОВ mTOR

Country Status (28)

Country Link
US (6) US7902189B2 (ru)
EP (1) EP2057156B1 (ru)
JP (2) JP5227321B2 (ru)
KR (1) KR101438245B1 (ru)
AR (1) AR062503A1 (ru)
AU (1) AU2007287430B2 (ru)
CA (1) CA2659851C (ru)
CL (1) CL2007002448A1 (ru)
CO (1) CO6150164A2 (ru)
CY (1) CY1119381T1 (ru)
DK (1) DK2057156T3 (ru)
ES (1) ES2648388T3 (ru)
HR (1) HRP20170627T1 (ru)
HU (1) HUE033894T2 (ru)
IL (1) IL196775A (ru)
LT (1) LT2057156T (ru)
MX (1) MX2009001946A (ru)
MY (1) MY148688A (ru)
NO (1) NO342383B1 (ru)
NZ (1) NZ575672A (ru)
PL (1) PL2057156T3 (ru)
PT (1) PT2057156T (ru)
RS (1) RS55881B1 (ru)
RU (1) RU2445312C2 (ru)
SA (1) SA07280461B1 (ru)
SI (1) SI2057156T1 (ru)
TW (1) TWI406863B (ru)
WO (1) WO2008023161A1 (ru)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2264819C (en) * 1996-09-04 2010-03-23 Intertrust Technologies Corp. Trusted infrastructure support systems, methods and techniques for secure electronic commerce, electronic transactions, commerce process control and automation, distributed computing, and rights management
RU2445312C2 (ru) * 2006-08-23 2012-03-20 Кудос Фармасьютиклз Лимитед ПРОИЗВОДНЫЕ 2-МЕТИЛМОРФОЛИН ПИРИДО-, ПИРАЗО- И ПИРИМИДО-ПИРИМИДИНА В КАЧЕСТВЕ ИНГИБИТОРОВ mTOR
BRPI0818426A2 (pt) * 2007-10-15 2017-06-13 Astrazeneca Ab produto de combinação, uso de um produto de combinação, e, método para tratar câncer
CN102014912A (zh) * 2008-02-21 2011-04-13 阿斯利康(瑞典)有限公司 联合疗法238
ES2398423T3 (es) 2008-06-20 2013-03-19 Astrazeneca Ab Composiciones con y procedimiento para pirido[2,3-D]pirimidinas sustituídas con metilmorfolina
JP2011529920A (ja) * 2008-07-31 2011-12-15 ジェネンテック， インコーポレイテッド ピリミジン化合物、組成物及び使用方法
PT2308877E (pt) 2008-08-05 2014-05-02 Daiichi Sankyo Co Ltd Derivados de imidazopiridin-2-ona
TWI378933B (en) 2008-10-14 2012-12-11 Daiichi Sankyo Co Ltd Morpholinopurine derivatives
UY32251A (es) 2008-11-20 2010-05-31 Glaxosmithkline Llc Compuestos quimicos
CA2751501C (en) * 2009-02-12 2018-01-16 Merck Serono S.A. 2-morpholino-pyrido[3,2-d]pyrimidines
CA2760932A1 (en) * 2009-05-04 2010-11-11 Thierry Nivaggioli Mtor pathway inhibitors for treating ocular disorders
WO2010151601A1 (en) * 2009-06-24 2010-12-29 Genentech, Inc. Oxo-heterocycle fused pyrimidine compounds, compositions and methods of use
US8242260B2 (en) 2009-08-28 2012-08-14 Novartis Ag Compounds and compositions as protein kinase inhibitors
RU2607635C2 (ru) 2009-11-12 2017-01-10 Ф.Хоффманн-Ля Рош Аг N-9-замещенные пуриновые соединения, композиции и способы применения
RU2515541C2 (ru) * 2009-11-12 2014-05-10 Ф.Хоффманн-Ля Рош Аг N-7 замещенные пурины и пиразолопиримидины, их композиции и способы применения
NZ599964A (en) 2009-11-18 2014-08-29 Novartis Ag Methods and compositions for treating solid tumors and other malignancies
WO2011067348A2 (en) 2009-12-03 2011-06-09 Novartis Ag Mek inhibitor salts and solvates thereof
WO2011067356A2 (en) 2009-12-03 2011-06-09 Novartis Ag Polymorphs of a mek inhibitor
KR20120123513A (ko) 2010-02-03 2012-11-08 시그날 파마소티칼 엘엘씨 Ｔｏｒ 키나제 억제자에 대한 민감성 예측 바이오마커로서 ｌｋｂ1 돌연변이의 동정
WO2011120911A1 (en) 2010-03-30 2011-10-06 Novartis Ag Pkc inhibitors for the treatment of b-cell lymphoma having chronic active b-cell-receptor signalling
RU2589696C2 (ru) 2010-04-13 2016-07-10 Новартис Аг КОМБИНАЦИЯ, ВКЛЮЧАЮЩАЯ ИНГИБИТОР ЦИКЛИНЗАВИСИМОЙ КИНАЗЫ 4 ИЛИ ЦИКЛИНЗАВИСИМОЙ КИНАЗЫ 6 (CDK4/6) И ИНГИБИТОР mTOR, ДЛЯ ЛЕЧЕНИЯ РАКА
CA2803055A1 (en) 2010-06-25 2011-12-29 Novartis Ag Heteroaryl compounds and compositions as protein kinase inhibitors
CN105859735B (zh) 2010-12-16 2018-03-09 霍夫曼-拉罗奇有限公司 三环pi3k抑制剂化合物和使用方法
WO2013003801A2 (en) 2011-06-29 2013-01-03 The Trustees Of Columbia University In The City Of New York Inhibitor of neuronal connectivity linked to schizophrenia susceptibility and cognitive dysfunction
WO2013019927A1 (en) 2011-08-03 2013-02-07 Signal Pharmaceuticals, Llc Identification of gene expression profile as a predictive biomarker for lkb1 status
WO2013174794A1 (en) 2012-05-23 2013-11-28 F. Hoffmann-La Roche Ag Compositions and methods of obtaining and using endoderm and hepatocyte cells
TWI663165B (zh) * 2012-09-28 2019-06-21 美商伊格尼塔公司 非典型蛋白質激酶ｃ之氮雜喹唑啉抑制劑
AU2013203714B2 (en) 2012-10-18 2015-12-03 Signal Pharmaceuticals, Llc Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity
WO2014114928A1 (en) 2013-01-23 2014-07-31 Astrazeneca Ab Chemical compounds
WO2014145857A1 (en) * 2013-03-15 2014-09-18 The Trustees Of Columbia University In The City Of New York TARGETING THE mTOR PATHWAY IN NEUROLOGICAL DISEASE
AU2014254052B2 (en) 2013-04-17 2019-06-06 Signal Pharmaceuticals, Llc Treatment of cancer with dihydropyrazino-pyrazines
NZ631082A (en) 2013-04-17 2017-06-30 Signal Pharm Llc Methods for treating cancer using tor kinase inhibitor combination therapy
SG10201708111YA (en) 2013-04-17 2017-11-29 Signal Pharm Llc Combination therapy comprising a dihydropyrazino-pyrazine compound and an androgen receptor antagonist for treating prostate cancer
TW201521725A (zh) 2013-04-17 2015-06-16 Signal Pharm Llc 使用ｔｏｒ激酶抑制劑組合療法以治療癌症之方法
BR112015026292B1 (pt) 2013-04-17 2022-04-12 Signal Pharmaceuticals, Llc Uso de 1-etil-7-(2-metil-6-(1h-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino [2,3-b]pirazin-2(1h)- ona e métodos in vitro
BR112015026297B1 (pt) 2013-04-17 2022-08-23 Signal Pharmaceuticals, Llc Uso de um inibidor da quinase tor e quinazolinona 5-substituída, composição farmacêutica que os compreende, e kit
JP2016516815A (ja) 2013-04-17 2016-06-09 シグナル ファーマシューティカルズ，エルエルシー １−エチル−７−（２−メチル−６−（１Ｈ−１，２，４−トリアゾール−３−イル）ピリジン−３−イル）−３，４−ジヒドロピラジノ［２，３−ｂ］ピラジン−２（１Ｈ）−オンに関する医薬製剤、プロセス、固形形態、及び使用方法
DE102013008118A1 (de) * 2013-05-11 2014-11-13 Merck Patent Gmbh Arylchinazoline
JP6286031B2 (ja) 2013-05-28 2018-02-28 アストラゼネカ アクチボラグ 化合物
CN109503591B (zh) 2013-05-29 2022-03-01 西格诺药品有限公司 二氢吡嗪并吡嗪化合物的药物组合物、其固体形式和它们的用途
US9512129B2 (en) 2014-04-16 2016-12-06 Signal Pharmaceuticals, Llc Solid forms comprising 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one and a coformer
NZ714742A (en) 2014-04-16 2017-04-28 Signal Pharm Llc Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use
TWI700283B (zh) * 2014-08-04 2020-08-01 德商拜耳製藥公司 ２-(嗎啉-４-基)-１,７-萘啶
CN106008559B (zh) * 2015-03-25 2020-10-16 中国科学院上海药物研究所 取代吡啶并嘧啶类化合物的合成工艺
WO2017031427A1 (en) * 2015-08-19 2017-02-23 3-V Biosciences, Inc. COMPOUNDS AND METHODS FOR INHIBITING mTOR
TW201726140A (zh) 2015-09-17 2017-08-01 瑞典商阿斯特捷利康公司 治療癌症之新型生物標記及方法
SG11201804170RA (en) * 2015-12-17 2018-06-28 Merck Patent Gmbh Polycyclic tlr7/8 antagonists and use thereof in the treatment of immune disorders
US10125135B2 (en) 2016-04-20 2018-11-13 Astrazeneca Ab Chemical compounds
WO2017182495A1 (en) 2016-04-20 2017-10-26 Astrazeneca Ab Indazole derivatives that down-regulate the estrogen receptor and possess anti-cancer activity
US10149839B2 (en) 2016-07-25 2018-12-11 Astrazeneca Ab Chemical compounds
SG11201909924VA (en) 2017-05-02 2019-11-28 Revolution Medicines Inc Rapamycin analogs as mtor inhibitors
MX2019015731A (es) 2017-06-22 2020-08-03 Celgene Corp Tratamiento de carcinoma hepatocelular caracterizado por infeccion por virus de hepatitis b.
EP3712157A4 (en) * 2017-11-06 2021-04-28 Medshine Discovery Inc. PYRIDOPYRIMIDINE COMPOUNDS ACTING AS DOUBLE KINASE MTORC 1/2 INHIBITORS
GB201720989D0 (en) * 2017-12-15 2018-01-31 Glaxosmithkline Ip Dev Ltd Chemical compounds
EP3762379A1 (en) 2018-03-07 2021-01-13 Bayer Aktiengesellschaft Identification and use of erk5 inhibitors
WO2019185117A1 (en) * 2018-03-26 2019-10-03 Fondazione Per L'istituto Oncologico Di Ricerca (Ior) New compounds with enhanced anti-tumor effects
RS64272B1 (sr) 2018-05-01 2023-07-31 Revolution Medicines Inc C40-, c28- i c-32-vezani analozi rapamicina kao inhibitori mtor
CN112368289B (zh) 2018-05-01 2024-02-20 锐新医药公司 作为mtor抑制剂的c26-连接的雷帕霉素类似物
NL2021185B1 (en) 2018-06-26 2020-01-06 Stichting Het Nederlands Kanker Inst Antoni Van Leeuwenhoek Ziekenhuis Combination Therapy and Use Thereof for Treating Cancer
MX2021004775A (es) 2018-11-05 2021-06-08 Iovance Biotherapeutics Inc Expansion de linfocitos infiltrantes de tumores (tils) usando inhibidores de la via de proteina cinasa b (akt).
CN113286594B (zh) * 2019-01-18 2023-12-15 南京明德新药研发有限公司 吡啶并嘧啶类化合物在制备治疗鼻咽癌药物中的应用
WO2020224585A1 (zh) 2019-05-06 2020-11-12 南京明德新药研发有限公司 一种mTORC1/2双激酶活性抑制剂的盐型、晶型及其制备方法
WO2021133509A1 (en) * 2019-12-27 2021-07-01 Angex Pharmaceutical, Inc. Heterocyclic compounds as mtor inhibitors
IL297845A (en) 2020-05-04 2023-01-01 Amgen Inc Heterocyclic compounds as a stimulating receptor expressed in myeloid cells 2 agonists and methods of use
TW202208355A (zh) 2020-05-04 2022-03-01 美商安進公司 作為骨髓細胞觸發受體2促效劑之雜環化合物及使用方法
CA3219215A1 (en) * 2021-05-04 2022-11-10 Vigil Neuroscience, Inc. Heterocyclic compounds as triggering receptor expressed on myeloid cells 2 agonists and methods of use
WO2023107592A1 (en) * 2021-12-08 2023-06-15 Kineta, Inc. Pyridopyrimidines and methods of their use

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1277738A1 (en) * 2000-04-27 2003-01-22 Yamanouchi Pharmaceutical Co. Ltd. Condensed heteroaryl derivatives
US6990117B1 (en) * 1999-11-24 2006-01-24 Denso Corporation CSMA wireless LAN having antenna device and terminal station
RU2009110255A (ru) * 2006-08-24 2010-09-27 Астразенека Аб (Se) Производные морфолинопиримидина, полезные для лечения пролиферативных нарушений

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4832899A (ru) 1971-08-28 1973-05-02
US4560685A (en) * 1984-06-18 1985-12-24 Dr. Karl Thomae Gesellschaft Mit Beschrankter Haftung 2-Piperazino-pteridines useful as antithrombotics and antimetastatics
DE3445298A1 (de) 1984-12-12 1986-06-12 Dr. Karl Thomae Gmbh, 7950 Biberach Neue pteridine, verfahren zu ihrer herstellung und deren verwendung als zwischenprodukte oder als arzneimittel
DE69626268T2 (de) 1995-05-10 2003-11-06 Nintendo Co Ltd Bildverarbeitungssystem mit analaogem steuerknüppel
GB9624482D0 (en) * 1995-12-18 1997-01-15 Zeneca Phaema S A Chemical compounds
US6184225B1 (en) * 1996-02-13 2001-02-06 Zeneca Limited Quinazoline derivatives as VEGF inhibitors
DE69709319T2 (de) * 1996-03-05 2002-08-14 Astrazeneca Ab 4-anilinochinazolin derivate
GB9718972D0 (en) * 1996-09-25 1997-11-12 Zeneca Ltd Chemical compounds
JP4367866B2 (ja) * 1997-02-12 2009-11-18 ザ リージェンツ オブ ジ ユニバーシティ オブ ミシガン 肺癌用のタンパク質マーカーおよびその使用
GB9714249D0 (en) * 1997-07-08 1997-09-10 Angiogene Pharm Ltd Vascular damaging agents
US5990117A (en) * 1998-04-15 1999-11-23 Cell Pathways, Inc. Method for inhibiting neoplastic cells and related conditions by exposure to quinazoline derivatives
GB9900334D0 (en) * 1999-01-07 1999-02-24 Angiogene Pharm Ltd Tricylic vascular damaging agents
GB9900752D0 (en) * 1999-01-15 1999-03-03 Angiogene Pharm Ltd Benzimidazole vascular damaging agents
ES2351699T3 (es) * 1999-02-10 2011-02-09 Astrazeneca Ab Derivados de quinazolina como inhibidores de la angiogénesis e intermedios de los mismos.
DE50008690D1 (de) 1999-09-07 2004-12-23 Syngenta Participations Ag p-Tolyl-Heterocyclen als Herbizide
KR100849151B1 (ko) 1999-11-05 2008-07-30 아스트라제네카 아베 Ｖｅｇｆ 억제제로서의 퀴나졸린 유도체
EP1255752B1 (en) * 2000-02-15 2007-08-08 Sugen, Inc. Pyrrole substituted 2-indolinone protein kinase inhibitors
JP2003535078A (ja) * 2000-05-31 2003-11-25 アストラゼネカ アクチボラグ 血管損傷活性のあるインドール誘導体
BR0112224A (pt) 2000-07-07 2003-06-10 Angiogene Pharm Ltd Composto, composição farmacêutica, uso de um composto ou de um sal, solvato ou pró-droga farmaceuticamente aceitável do mesmo, e, processo para preparar um composto
EP1301498A1 (en) 2000-07-07 2003-04-16 Angiogene Pharmaceuticals Limited Colchinol derivatives as angiogenesis inhibitors
US20030187026A1 (en) * 2001-12-13 2003-10-02 Qun Li Kinase inhibitors
DE10228103A1 (de) 2002-06-24 2004-01-15 Bayer Cropscience Ag Fungizide Wirkstoffkombinationen
ES2518316T3 (es) 2002-12-06 2014-11-05 Debiopharm International Sa Compuestos heterocíclicos, métodos de fabricación de los mismos y su uso en terapia
CA2524221A1 (en) 2003-04-30 2004-11-18 The Institutes For Pharmaceutical Discovery, Llc Substituted heteroaryls as inhibitors of protein tyrosine phosphatases
EP1769092A4 (en) 2004-06-29 2008-08-06 Europ Nickel Plc IMPROVED LIXIVIATION OF BASE METALS
GB0428475D0 (en) 2004-12-30 2005-02-02 4 Aza Bioscience Nv Pyrido(3,2-D)pyrimidine derivatives and pharmaceutical compositions useful as medicines for the treatment of autoimmune disorders
WO2007042554A2 (en) * 2005-10-12 2007-04-19 Cancer Research Technology Ltd. Methods and compositions for treating immune disorders
JP2008531538A (ja) * 2005-02-25 2008-08-14 クドス ファーマシューティカルズ リミテッド ２，４−ジアミノ−ピリドピリミジン誘導体とｍＴＯＲ阻害剤としてのその使用
EP1877388A2 (en) * 2005-02-25 2008-01-16 Kudos Pharmaceuticals Ltd Hydrazinomethyl, hydrazonomethyl and 5-membered heterocylic compounds which act as mtor inhibitors and their use as anti cancer agents
CA2612788A1 (en) 2005-06-24 2006-12-28 Steven Cesar Alfons De Jonghe Pyrido(3,2-d)pyrimidines and pharmaceutical compositions useful for treating hepatitis c
ES2360232T3 (es) 2005-06-29 2011-06-02 Compumedics Limited Conjunto sensor con puente conductor.
EP1954699B1 (en) 2005-11-22 2012-09-19 Kudos Pharmaceuticals Ltd PYRIDO-, PYRAZO- AND PYRIMIDOPYRIMIDINE DERIVATIVES AS mTOR INHIBITORS
RU2445312C2 (ru) * 2006-08-23 2012-03-20 Кудос Фармасьютиклз Лимитед ПРОИЗВОДНЫЕ 2-МЕТИЛМОРФОЛИН ПИРИДО-, ПИРАЗО- И ПИРИМИДО-ПИРИМИДИНА В КАЧЕСТВЕ ИНГИБИТОРОВ mTOR

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6990117B1 (en) * 1999-11-24 2006-01-24 Denso Corporation CSMA wireless LAN having antenna device and terminal station
EP1277738A1 (en) * 2000-04-27 2003-01-22 Yamanouchi Pharmaceutical Co. Ltd. Condensed heteroaryl derivatives
RU2009110255A (ru) * 2006-08-24 2010-09-27 Астразенека Аб (Se) Производные морфолинопиримидина, полезные для лечения пролиферативных нарушений

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Hayakawa M. et al. Synthesis and biological evalution of 4-morpholino-2-phenylquinazolines and related derivatives as novel PI3 kinase p110α inhibitors // Bioorganic & Medicinal Chemistry. - 2006, 14, p.6847-6858. *

Also Published As

Publication number Publication date
HUE033894T2 (en) 2018-01-29
HRP20170627T1 (hr) 2017-06-30
SI2057156T1 (sl) 2017-06-30
US8101602B2 (en) 2012-01-24
MY148688A (en) 2013-05-31
US20160067258A1 (en) 2016-03-10
US20170281637A1 (en) 2017-10-05
PL2057156T3 (pl) 2017-08-31
AU2007287430B2 (en) 2011-07-21
BRPI0715888A2 (pt) 2013-09-17
MX2009001946A (es) 2009-03-05
RS55881B1 (sr) 2017-08-31
BRPI0715888A8 (pt) 2018-04-17
AR062503A1 (es) 2008-11-12
PT2057156T (pt) 2017-05-04
DK2057156T3 (en) 2017-05-08
EP2057156B1 (en) 2017-02-01
US8435985B2 (en) 2013-05-07
JP5227321B2 (ja) 2013-07-03
CY1119381T1 (el) 2018-02-14
CO6150164A2 (es) 2010-04-20
CA2659851C (en) 2014-02-25
US20080081809A1 (en) 2008-04-03
CA2659851A1 (en) 2008-02-28
IL196775A (en) 2017-05-29
JP5629343B2 (ja) 2014-11-19
US20140135315A1 (en) 2014-05-15
KR101438245B1 (ko) 2014-09-04
NO20090443L (no) 2009-03-27
EP2057156A1 (en) 2009-05-13
US7902189B2 (en) 2011-03-08
WO2008023161A1 (en) 2008-02-28
US10034884B2 (en) 2018-07-31
US20110124638A1 (en) 2011-05-26
RU2009110261A (ru) 2010-09-27
US20120142673A1 (en) 2012-06-07
KR20090042855A (ko) 2009-04-30
TW200817395A (en) 2008-04-16
AU2007287430A1 (en) 2008-02-28
LT2057156T (lt) 2017-05-25
ES2648388T3 (es) 2018-01-02
NZ575672A (en) 2011-10-28
IL196775A0 (en) 2009-11-18
US9102670B2 (en) 2015-08-11
JP2010501535A (ja) 2010-01-21
NO342383B1 (no) 2018-05-14
JP2013107915A (ja) 2013-06-06
CL2007002448A1 (es) 2008-05-16
US9717736B2 (en) 2017-08-01
TWI406863B (zh) 2013-09-01
SA07280461B1 (ar) 2012-04-07

Similar Documents

Publication Publication Date Title
RU2445312C2 (ru) ПРОИЗВОДНЫЕ 2-МЕТИЛМОРФОЛИН ПИРИДО-, ПИРАЗО- И ПИРИМИДО-ПИРИМИДИНА В КАЧЕСТВЕ ИНГИБИТОРОВ mTOR
RU2401658C2 (ru) Гетероциклические ингибиторы аспартилпротеазы
RU2397168C2 (ru) Производные тиофена в качестве ингибиторов снк 1
RU2370495C2 (ru) Дополнительные гетероциклические соединения и их применение в качестве антагонистов метаботропного глутаматного рецептора
RU2379295C2 (ru) Производные пиридазинона в качестве агонистов рецептора тиреоидного гормона
RU2342367C2 (ru) Ненуклеозидные ингибиторы i обратной транскриптазы, предназначенные для лечения заболеваний, опосредованных вич
EA201500266A1 (ru) Ингибиторы репликации вирусов гриппа
CO5580767A2 (es) Compuestos de indazol y composiciones farmaceuticas para inhibir proteinquinasas y procedimientos para su uso
RU2009126767A (ru) Производное 1-фенил-1-тио-d-глюцитола
JP2009504763A5 (ru)
RU2013121788A (ru) Ингибиторы репликации вич
RU2013119129A (ru) Органические соединения
MY144655A (en) Pyrimidine urea derivatives as kinase inhibitors
RU2014122154A (ru) Композиции, пригодные для лечения вирусных заболеваний
EA200870302A1 (ru) 1,3-диоксанкарбоновые кислоты
JP2014505107A5 (ru)
RU2009111378A (ru) Терапевтические композиции, содержащие специфический антагонист рецептора эндотелина и ингибиторов pde5
BRPI0519057A2 (pt) derivados de hidantoÍna éteis como inibidores de metaloproteinase
AR039190A1 (es) Derivados de benzofurano, composicion farmaceutica y medicamento que comprende el compuesto
SE0402925D0 (sv) Novel Compounds
RU2009102270A (ru) Производные тиазолилмочевины в качестве ингибиторов фосфатидилинозитол-3-киназы
RU2010154417A (ru) Комбинация частичного агониста никотиновых рецепторов и ингибитора ацетилхолинетеразы, содержащая ее фармацетическая композиция, и ее применение в лечении когнитивных расстройств
RU2008129623A (ru) Ингибиторы ccr9 активности
RU2351329C2 (ru) Ингибиторы кинуренин 3-гидроксилазы для лечения диабета
EA200600377A1 (ru) Новая композиция