WO2006071095A1 - Quinazoline derivatives for the treatment and prevention of diabetes and obesity - Google Patents

Quinazoline derivatives for the treatment and prevention of diabetes and obesity Download PDF

Info

Publication number
WO2006071095A1
WO2006071095A1 PCT/KR2005/004664 KR2005004664W WO2006071095A1 WO 2006071095 A1 WO2006071095 A1 WO 2006071095A1 KR 2005004664 W KR2005004664 W KR 2005004664W WO 2006071095 A1 WO2006071095 A1 WO 2006071095A1
Authority
WO
WIPO (PCT)
Prior art keywords
amine compound
alkyl
compound
phenylquinazolino
ylquinazolino
Prior art date
Application number
PCT/KR2005/004664
Other languages
French (fr)
Inventor
Nam Kyu Lee
Jun Won Lee
Sukho Lee
Guang-Jin Im
Hye Young Han
Tae Kon Kim
Yong Hyuk Kim
Wie-Jong Kwak
Sang Woong Kim
Joohun Ha
Eon Kyum Kim
Jung Kyu Lee
Choong Yeul Yoo
Dae Yeon Lee
Original Assignee
Sk Chemicals Co., Ltd.
Leadgenex Inc.
Industry Academic Cooperation Foundation Of Kyunghee University
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
Application filed by Sk Chemicals Co., Ltd., Leadgenex Inc., Industry Academic Cooperation Foundation Of Kyunghee University filed Critical Sk Chemicals Co., Ltd.
Priority to EP05823851A priority Critical patent/EP1844023A1/en
Priority to JP2007549270A priority patent/JP2008526734A/en
Publication of WO2006071095A1 publication Critical patent/WO2006071095A1/en

Links

Classifications

    • 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
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
    • 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
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/93—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/94—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to novel quinazoline derivatives effective in lowering blood glucose level and reducing body weight, and a preparation for treatment and/ or prevention of diabetes and/ or obesity, which comprises the compound as an active ingredient.
  • Diabetes one of the most common modern diseases, is on the increase in Korea, too. Because of its severe symptoms and sequela, the disease is becoming a social problem. Improvement of living standards and environments resulting form economic development has led to lack of exercises, while calorie intake has increased significantly. As a result, obesity and type 2 diabetes are also on the increase. If diabetes persists, blood lipid level increases, not to mention the blood glucose level, leading to cardiovascular diseases such as arteriosclerosis and coronary heart disease and complications such as diabetic kidney and retinal diseases. Therefore, development of a treatment for the above disease is an important issue.
  • IDDM insulin-dependent diabetes mellitus
  • NIDDM non-insulin-dependent diabetes mellitus
  • IDDM insulin-dependent diabetes mellitus
  • NIDDM non-insulin-dependent diabetes mellitus
  • Insulin secretory defect refers to the condition in which the beta cells of the pancreas cannot secrete an adequate amount of insulin depending on the blood glucose level and includes both quantitative and functional secretory defects.
  • Insulin resistance refers to the condition in which target cells fail to respond to ordinary levels of circulating insulin. The cause of insulin resistance is generally thought of as hindered signal transfer after binding to the cell membrane receptor, resulting from genetic factors, obesity, reduced physical activity, hyperglycemia, abnormal blood lipid level, etc. What is important is that the two factors are related with each other. If there is insulin resistance, more insulin has to be secreted to overcome the resistance. And, hyperglycemia caused by insufficient secretion of insulin may aggravate the insulin resistance.
  • type 2 diabetes is related with obesity, but the exact mechanism of the interaction or interrelationship still needs to be elucidated.
  • the focus of the research on the cause of diabetes has recently shifted from "glucose metabolism” to "fatty acid metabolism.”
  • type 2 diabetes patients such lipid metabolism disturbances as increase in blood fatty acid level, increase in neutral fats, decrease in high-density lipoprotein cholesterol, accumulation of fats in muscles, increase in abdominal fats and fatty liver are frequently found, as well as hyperglycemia.
  • insulin resistance is thought to be the most important pathological cause of NIDDM. Insulin resistance is the condition in which glucose is not fully utilized even when there is a sufficient amount of insulin.
  • various hypoglycemic drugs are used to treat insulin resistance. The hypoglycemic drugs are classified as follows depending on the treatment mechanism and the target site:
  • Sulfonylurea based drugs promote the movement of insulin-containing granules in the beta cells of the pancreas, thereby promoting the secretion of insulin at second hand.
  • Sulfonylurea based drugs promote the movement of insulin-containing granules in the beta cells of the pancreas, thereby promoting the secretion of insulin at second hand.
  • Biguanide based drugs transfer glucose to muscle cells and inhibit gluconeogenesis in the liver. They are advantageous in that they do not cause hypoglycemia, but care should be taken for aged people and patients with cardiovascular diseases.
  • ⁇ -Glucosidase inhibitors inhibit the enzymatic action of glucose production in the small intestine, preventing abrupt increase of blood glucose level after meals. With few side effects, the drugs are used to treat mild cases of diabetes.
  • thiazolidione (TZD) based drugs are known to activate PPAR- ⁇ , which participates in the differentiation of fat cells.
  • these oral hypoglycemic drugs are not so effective in reducing blood glucose level and cause side effects, development of safer diabetic treatments is imminent.
  • search for new target proteins capable of regulating the signal transfer system and metabolism processes is essential for development of such treatment drugs.
  • AMPK 5'AMP-activated protein kinase
  • AMPK plays a variety of other roles in the body. Besides controlling insulin production in pancreatic cells, it inhibits activation of acetyl CoA carboxylase
  • ACC HMG-CoA reductase
  • AMPK plays a key role in energy homeostasis control and carbohydrate and lipid metabolism control, as activated by AMFs accumulated by muscle contraction, exercise or energy depletion in cells. Also, it is viewed as new target material for treating metabolic diseases, such as diabetes and obesity, caused by energy imbalance.
  • metabolic diseases such as diabetes and obesity
  • the importance of AMPK in glucose absorption during exercise is widely known.
  • the fact that the action of AMPK is independent of the insulin signal transfer system means that it can become a new target material for treatment of type 2 diabetics, most of whom show troubles with the insulin signal transfer system. Actually, a lot of type 2 diabetics could reduce their blood glucose level through exercise and the diabetic model animal test confirmed that exercise promotes activation of AMPK and decrease in blood glucose level.
  • metformin or thiazolidinedione (TZD) based drugs which are widely used as diabetic treatments at present, reduce blood sugar level partly by an AMPK-involved mechanism.
  • search of the drugs that can activate AMPK will lead to the development of a new-concept treatment that imitates the therapeutic effect of exercise on a variety of metabolic diseases.
  • the present inventors synthesized a novel material that has a remarkable effect in increase of AMPK activity and prevention and/ or treatment of obesity and diabetes and confirmed the effect.
  • the present inventors synthesized several compounds with quinazoline backbones and confirmed that they are superior in reducing blood glucose level and body weight.
  • a novel quinazoline compound effective in reducing blood sugar level and body weight, which is essential in treating diabetes and obesity.
  • a treatment for diabetes and obesity with no toxicity or side effects which comprises the novel quinazoline compound, a pharmaceutically available salt thereof or a pharmaceutically available prodrug thereof as an active ingredient.
  • the present invention relates to a quinazoline derivative, a pharmaceutically available salt thereof or a pharmaceutically available prodrug thereof effective in treating diabetes and obesity, which is represented by the formula 1 below:
  • R a is a substituent selected from hydrogen, (Ci-Ci8)alkyL (C 2 -Cs) alkenyl, (C2-C8)alkynyl, halogeno-(Ci-C6)alkyl, hydroxy-(Ci-C6)alkyl, (Ci-C6)alkoxy-(Ci-C6)alkyl, cyano-(Ci-C 6 )alkyl, amino-(Ci-C 6 )alkyl, (Ci-C6)alkylamino-(C 1 -C6)alkyl, di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl, (Ci-C6)alkylthio-(Ci-C 6 )alkyl / (Ci-C 6 )alkylsulfinyl-(Ci-C6)alkyl and (Ci-C 6 )alkylsulfonyl-(Ci-C6)alkyl
  • N-(Ci-C 6 )alkylsulfamoyl N,N-di-[(Ci-C 6 )alkyl]sulfamoyl
  • X 3 is a direct bonding or selected from O, S, SO, SO 2 , N(R 7 ), CO, CH(OR 7 ), CON(R 7 ), N(R 7 )CO, SO 2 N(R 7 ), N(R 7 )SO 2 , C(R 7 ) 2 O, C(R 7 ) 2 S, N(R 7 )C(R 7 ) 2 ,
  • R 7 is a hydrogen atom, (Ci-C 6 )alkyl, aryl, aryl-(C 1 -C 6 )alkyl / (C 3 -C 7 )CyClOaIlCyI, (C3-C 7 )cycloalkyl-(C 1 -C 6 )alkyl /
  • any aryl, heteroaryl or heterocyclyl of R a may have 0 to 3 substituents, which may be identical or different and are selected from halogeno, trifluoromethyl, cyano, nitro, hydroxy, amino, carboxyl, carbamoyl, (Ci-C6)alkyl, (C2-Cs)alkenyl, (C2-C8)alkynyl, (Ci-C 6 )alkoxy, (C2-C6)alkenyloxy, (C2-C6)alkynyloxy, (Ci-C6)alkylthio, (Ci-C6)alkylsulfiny
  • X 4 is a direct bonding or selected from O and N(R 9 ), wherein R 9 is a hydrogen atom or (Ci-C ⁇ )alkyl, and R 8 is selected from halogeno-(C 1 -C ⁇ )alkyl, hydroxy-(Ci-C6)alkyl
  • R b is a substituent selected from hydrogen, (C2-Cs)alkenyl, (C 2 -C 8 )alkynyl, halogeno-(d-C6)alkyl, hydroxy-(Ci-C 6 )alkyl,
  • (Ci-C 6 )alkylamino-(Ci-C 6 )alkyl di-[(Ci-C 6 )alkyl]amino-(Ci-C 6 )alkyl, (Ci-C 6 )alkylthio-(Ci-C 6 )alkyl, (Ci-C 6 )alkylsulfinyl-(Ci-C 6 )alkyl or
  • X 1 is a direct bonding or selected from O, S, SO, SO 2 , N(R 4 ), CO, CO 2 (R 4 ), CH(OR 4 ), CON(R 4 ), N(R 4 )CO, SO 2 N(R 4 ), N(R 4 )SO 2 , C(R 4 ) 2 O, C(R 4 ) 2 S, N(R 4 )C(R 4 ) 2 , N(R 4 )CON(R 4 ) and N(R 4 )CSN(R 4 ), wherein R 4 is a hydrogen atom, (Ci-QJalkyl, aryl, aryl-(Ci-C 6 )alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl, (C3-C7)
  • X 3 is a direct bonding or selected from O, S, SO, SO 2 , N(R 7 ), CO, CH(OR 7 ), CON(R 7 ), N(R 7 )CO, SO 2 N(R 7 ), N(R 7 )SO 2 , C(R 7 ) 2 O, C(R 7 ) 2 S, N(R 7 )C(R 7 ) 2 , N(R 7 )CON(R 7 ) and N(R 7 )CSN(R 7 ), wherein R 7 is a hydrogen atom, (Ci-C 6 )alkyl,
  • X 4 is a direct bonding or selected from O and N(R 9 ), wherein R 9 is a hydrogen atom or (Ci-C6)alkyl, and R 8 is selected from halogeno-(Ci-C6)alkyl, hydroxy-(Ci-C6)alkyl
  • CH 2 or HC ⁇ , selected from halogeno, carboxyl, carbamoyl, (Ci-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, amino-(Ci-C6)alkyl, (Ci-C 6 )alkylamino-(Ci-C6)alkyl and di-[(Ci-C 6 )alkyl]amino-(C 1 -C 6 )alkyl or -Q 5 -X 6 [wherein X 6 is a direct bonding or selected from CO and N(R 13 )CO, wherein R 13 is a hydrogen atom or (Ci-C 6 )alkyl, and Q 5 is aryl, aryl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(C; ⁇ -C6)alkyl, heterocyclyl or heterocyclyl
  • any aryl, heteroaryl or heterocyclyl of R c may have 1, 2 or 3 identical or different substituents selected from hydrogen, halogeno, trifluoromethyl, cyano, nitro, hydroxy, amino, carboxyl, carbamoyl, (Ci-C6)alkyl, (C 2 -Cs) alkenyl, (C2-C8)alkynyl, (Ci-C6)alkoxy, (C 2 -C ⁇ )alkenyloxy, (C 2 -C 6 ) alky nyloxy, (Ci-C 6 )alkylthio, (Ci-C6)alkylsulfinyl, (C 1 -C 6
  • N-(Ci-C6)alkyl-(C3-C 6 )alkynoylamino N-(Ci-C6)alkylsulfamoyl, N,N-di-[(Ci-C6)alkyl]sulfamoyl, (C 1 -C 6 )alkanesulfonylamino and
  • X 8 is a direct bonding or selected from O and N(R 16 ), wherein R 16 is a hydrogen atom or (Ci-C 6 )alkyl
  • R 15 is selected from halogeno-(Ci-C6)alkyl, hydroxy-(Ci-C6)alkyl, (Ci-C 6 )alkoxy-(Ci-C6)alkyl, cyano-(Ci-C 6 )alkyl, amino-(Ci-C6)alkyl, (Ci-C 6 )alkylamino-(C 1 -C 6 )alkyl and di-[(Ci-C 6 )alkyl]amino-(Ci-C 6 )alkyl or -X 9 -Q 7
  • X is a direct bonding or selected from O, S, SO, SO 2 and NR 5 , wherein R 5 is a hydrogen atom, (C 1 -C 6 )alkyl, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C 3 -C7)cycloalkyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C ⁇ )alkyl;
  • Ri is a substituent selected from hydrogen, (Ci-C8)alkyl, halogeno-(Ci-C 6 )alkyl, hydroxy-(d-C 6 )alkyl, (Ci-C 6 )alkoxy-(C 1 -C 6 )alkyl / amino-(Ci-C6)alkyl, (Ci-C6)alkylamino-(Ci-C 6 )alkyl, di-[(C 1 -C 6 )alkyl]amino-(C 1 -C 6 )alkyl and (Ci-C 6 )alkylsulfinyl or -X ⁇ -Q 1 [wherein X 1 is a direct bonding or selected from O, S and NR 5 and Q 1 and R 5 may be identical or different], the neighboring carbon atoms of (C2-C 6 )alkylene of Ri may be separated by a group selected from O, S and N(R 5 ), any CH 2 or CH3 of R 1 may
  • (C 1 -C6)alkoxycarbonyl, N-(d-C6)alkylcarbamoyl and N,N-di-[(C 1 -C6)alkyl]carbamoyl and heterocyclyl of R3 and R 4 may have 1 or 2 oxo or thioxo substituents.
  • X is O, S or NR 5 ;
  • R 1 is a hydrogen atom, C 1 -C 6 alkyl, C 1 -C 4 haloalkyl, C 1 -C 6 alkylhydroxy,
  • R 2 is Ci-Ci 8 alkyl, C 2 -C 8 haloalkyl, C 3 -C 7 cycloalkyl, (C 3 -C 7 )cycloalkyl
  • the compound represented by the formula 1 may form a pharmaceutically available salt, including an inorganic acid salt such as hydrochloride, sulfate, phosphate, bisphosphate, hydrobromate and nitrate or an organic acid salt such as malate, maleate, fumarate, tartrate, succinate, citrate, acetate, lactate, methanesulfonate, p-toluenesulfonate, palmitate, salicylate and stearate.
  • an inorganic acid salt such as hydrochloride, sulfate, phosphate, bisphosphate, hydrobromate and nitrate
  • an organic acid salt such as malate, maleate, fumarate, tartrate, succinate, citrate, acetate, lactate, methanesulfonate, p-toluenesulfonate, palmitate, salicylate and stearate.
  • Some of the compounds of the present invention may be crystallized or recrystallized using an aqueous or organic solvent. In that case, a solvate may be formed.
  • hydrates and other stoichiometric solvates belong to the scope of the present invention.
  • the compound represented by the formula 1 may be an enantiomer, a stereoisomer or a tautomer.
  • the isomers may be separated or decomposed by common methods or may be obtained by common stereospecific or asymmetrical synthesis methods.
  • the present invention also provides a preparation method of the quinazoline derivatives represented by the formula 1 and a pharmaceutically available salt thereof.
  • the present invention also provides a preparation method of the compound represented by the formula 1-1. As shown in the scheme 1 below, it may be synthesized from the subs titution reaction of a 4-chloro-2-substituted-quinazoline derivative represented by the formula 2 below and a compound represented by the formula 3 below: Scheme 1
  • the substitution reaction of the scheme 1 is carried out in the presence of a base and an organic polar solvent.
  • a base an organic base such as pyridine or an alkylamine or an inorganic base such as an alkali metal salt or an alkaline earth metal salt may be used.
  • the compound represented by the formula 1-1 may be prepared from the substitution reaction of a 2-chloro-4-substituted-quinazoline derivative represented by the formula 4 below and a compound represented by the formula 5 below, as shown in the scheme 2 below:
  • the substitution reaction of the scheme 2 is carried out in the presence of a base and an organic polar solvent.
  • a base an organic base such as pyridine or an alkylamine or an inorganic base such as an alkali metal salt or an alkaline earth metal salt may be used.
  • the compound represented by the formula 1-1 may be prepared from the substitution reaction of a 2-methyl-3H-quinazolino-4-one derivative represented by the formula 6 below, which is substituted by X at the number 4 position, and a compound represented by the formula 7 below, as shown in the scheme 3 below:
  • the substitution reaction of the scheme 3 is carried out in the presence of a base and an organic polar solvent.
  • a base an organic base such as pyridine or an alkylamine or an inorganic base such as an alkali metal salt or an alkaline earth metal salt may be used.
  • the compounds represented by the formulas 2 and 3 in the scheme 1, which are used as starting materials of the substitution reaction, may be prepared by the methods well known in the field of organic synthesis.
  • 2-ethylsulfanyl-3H-quinazolino-4-one is added thionyl chloride (SOCb) at -20 to 10 °C and reflux reaction is performed in the presence of an N,N-dimethylformamide catalyst in order to transform the ketone group at the C-4 position into chlorine (Cl).
  • SOCb thionyl chloride
  • R3 and R 4 are the same as defined in the formula 1.
  • an imidate compound is reacted with anthranilic acid and sodium methoxide (NaOMe) in the temperature range from room temperature to the reflux temperature of the solvent while stirring in order to prepare 3H-quinazolino-4-one with the substituent R 1 .
  • NaOMe sodium methoxide
  • phosphorus oxy chloride and diethylaniline are added and reaction is carried out in the temperature range from room temperature to the reflux temperature of the solvent while stirring to transform the ketone group at the C-4 position into chlorine (Cl).
  • R 1 is a hydrogen atom
  • alkyl or aryl may also be prepared by the scheme 6 below:
  • R 1 , R3 and R 4 are the same as defined in the formula 1.
  • an acyl halide is reacted with anthranyl amide and reflux reaction is carried out in the presence of NaOH to prepare 3H-quinazolino-4-one with the substituent R 1 .
  • phosphorus oxy chloride and diethylaniline are added and reaction is performed in the temperature range from room temperature to the reflux temperature of the solvent while stirring in order to transform the ketone group at the C-4 position into chlorine (Cl).
  • the compounds represented by the formulas 4 and 5 in the scheme 2, which are used as starting materials of the substitution reaction, may be prepared by the methods well known in the field of organic synthesis.
  • the compound represented by the formula 4 may be prepared by the scheme 7 below:
  • R 2 , R3, R4 and X are the same as defined in the formula 1.
  • the compound represented by the formula 3 may be used in excess as both organic solvent and reactant or another solvent may be used and the compound may be used stoichiometrically. And the reaction may be carried out in the presence of a base, if deemed necessary.
  • a base an organic base such as pyridine and an alkylamine or an inorganic base such as an alkali metal salt and an alkaline earth metal salt may be used.
  • the prepared intermediate compound and the target compound may be separated and purified by such common methods as chromatography and recrystallization.
  • the compounds of the present invention may be administered by an adequate administration method, for example, orally, intraorally, sublingually, rectally, vaginally, intranasally, locationally or non-orally (including intravenously, intracavernously, intramuscularly, subcutaneously and intraluminally).
  • an adequate administration method for example, orally, intraorally, sublingually, rectally, vaginally, intranasally, locationally or non-orally (including intravenously, intracavernously, intramuscularly, subcutaneously and intraluminally).
  • the general dosage of the compound represented by the formula 1 for treatment or prevention of diabetes and obesity is 0.1 to 400 mg/day for an adult weighing 70 kg.
  • the compound can be prepared into a tablet or capsule, using a pharmaceutically available excipient or vehicle, with the content of the compound of 0.05 to 200 mg, and administered once or several times a day.
  • the compound is administered in an amount of 0.01 to 100 mg.
  • the adequate dosage is determined by the doctor, considering the patient's age, body weight and other characteristics.
  • the aforementioned dosages are for general cases.
  • the dosage may be higher or lower from a patient to another.
  • the compound represented by the formula 1 may be administered alone or along with a pharmaceutical vehicle that is selected in consideration of the administration and other standard pharmaceutical practices.
  • the compound may be administered orally, intraorally or sublingually in the form of a tablet containing starch or lactose, ovules by itself or along with excipients or elixir or emulsion containing chemicals that offer specific flavors or colors.
  • the liquid preparation may be prepared by adding a pharmaceutically available additive such as a suspension (e.g., a mixture of semisynthetic glyceride like methylcellulose and witepsol or apricot kernel oil with PEG-6 ester or a glyceride mixture of PEG-8 and caprylic/capric glyceride). It may be administered non-orally, for example, intravenously, intracavernously, intramuscularly, subcutaneously or intraluminally. For non-oral administration, it is most preferable to use the compound in the form of sterile aqueous solution.
  • the solution may comprise other substances (for example, salts or monosaccharides such as mannitol and glucose) for isotonicity with blood.
  • the present invention provides a pharmaceutical composition comprising the compound represented by the formula 1 or a pharmaceutically available salt thereof, as an active ingredient, and a pharmaceutically available diluent or excipient.
  • the present invention also provides a pharmaceutical composition for medical use comprising the compound represented by the formula 1, a pharmaceutically available salt thereof or a pharmaceutically available prodrug thereof as an active ingredient.
  • FIG. 1 shows the result of Western blot analysis showing the degree of phosphorylation of the serine-79 for the compound of the present invention.
  • FIGs. 2a to 2g show the results of Western blot analysis showing the degree of phosphorylation of the serine-79 and threonine-172 for the compound of the present invention.
  • FIGs. 3a and 3b are graphs showing the change of blood glucose level when the compound of the present invention was abdominally administered to db/db mice.
  • FIGs. 4a and FIG. 4b are graphs showing the change of body weight when the compound of the present invention was abdominally administered to db/db mice.
  • FIGs. 5a, 5b and 5c are graphs showing the change of blood glucose level when the compound of the present invention was orally administered to db/db mice.
  • FIGs. 6a, 6b and 6c are graphs showing the change of body weight when the compound of the present invention was orally administered to db/db mice.
  • FIGs. 7a and 7b are graphs showing the change of body weight when the compound of the present invention was abdominally administered to ob/ob mice.
  • FIGs. 8a and 8b are graphs showing the change of blood glucose level when the compound of the present invention was abdominally administered to ob/ob mice.
  • FIG. 9 is a graph showing the change of body weight when the compound of the present invention was orally administered to ob/ob mice.
  • Example 4 Preparation of 4-substituted amine-2-phenylquinazoline (formula Ib) 4-Chloro-2-phenylquinazoline (formula 2b; 0.5 g, 2.08 mmol) was dissolved in 30 mL of THF. TEA (5 eq, 1.45 mL, 10.38 mmol) and amine (1.5 eq) were added and the mixture was stirred at room temperature overnight. When the starting materials disappeared, THF was removed by distillation under reduced pressure and the target compound was obtained with a yield of 90 % by column chromatography (silica gel; 230-400 mesh).
  • Example 9 Preparation of 2-substituted-3H-quinazolino-4-one (formula E) 2-(Substituted-carbonyl-amino)-benzamide (formula H; 45 mmol) was dissolved in 60 mL of 2.5N-NaOH and the mixture was refluxed for 1 hour. When the starting materials disappeared, the mixture was cooled to 0 "C and neutralized with 3N-HC1. The formed crystal was filtered and dried to obtain the target compound with a yield of 95 % (43 mmol).
  • the mixture was stirred at room temperature for 3 hours and ethanol was removed by distillation under reduced pressure when the starting materials disappeared.
  • the compound represented by the formula 1 may be prepared into a variety of preparation forms depending on the purpose. The following are non-limiting examples of some preparation forms comprising the compound represented by the formula 1 as an active ingredient.
  • a tablet for oral administration was prepared by wet granulation and dry granulation.
  • composition Active ingredient 200 mg, hard silicic anhydride 10 mg, magnesium stearate
  • composition Active ingredient 100 mg, mannitol 180 mg, dibasic sodium phosphate 25 mg, water for injection 2974 mg.
  • Experimental Example 1 Analysis of glucose absorption
  • C2C12 muscle cells were cultured in DMEM (Dulbecco's modified Eagle's medium) containing 10 % bovine calf serum. When the cell density increased to about 85 to 90 %, the culture medium was replaced with 1 % bovine calf serum and cell differentiation was induced for 6 days. Completely differentiated cells were cultured for 3 hours with Krebs-Ringer buffer (KRB) containing 5 mM glucose. The test materials were added at a concentration of 10 ⁇ M. 30 minutes later, 0.2 ⁇ Ci 2-deoxyglucose was added. KRB was removed 20 minutes later and the cells were washed for 3 times with cold PBS. The cells were lysed with 0.5N NaOH and counted using a radioactive counter.
  • KRB Krebs-Ringer buffer
  • C2C12 cells were cultured and differentiated in the same manner as in Experimental Example 1. Treatment with the test materials was also performed in the same manner as in Experimental Example 1 (10 ⁇ M for 50 minutes). The culture medium was removed and the cells were washed for 2 times with PBS and protein extracts were obtained using a lysis buffer (50 mM tris-HCl, pH 7.4, 1 % NP-40, 0.25 % sodium deoxycholate, 150 mM NaCl, 1 mM EDTA, 1 mM PMSF, 1 mM sodium o-vanadate, 1 mM NaF, 1 ⁇ g/ mL apronitin, 1 ⁇ g/mL leu-peptin, 1 ⁇ g/mL pepstatin). The AMPK activity was determined from Western blot analysis of the degree of phosphorylation of serine-79 by acetyl CoA carboxylase and the degree of phosphorylation of threonine-172. The amount of ERK
  • CMC carboxylmethylcellulose
  • CMC rosiglitazone dissolved in 0.5 % carboxylmethylcellulose
  • test material were administered orally or abdominally every afternoon to the negative control group, the positive control group and the test group, respectively.
  • Blood glucose level measurement was made just before the administration, at an interval of 3-4 days, by incising the tail vein. Body weight and the amount of feed were measured every day just before the administration.
  • test group to which the compound represented by the formula 1 had been administered abdominally or orally showed significant decrease in blood glucose level and body weight compared with the control group, which implies the preventive and therapeutic effect for diabetes and obesity.
  • mice 6- week old male ob/ob mice (Harlan) were accustomed to the environment of the animal breeding facility of SK for a week. During the period, the mice were freely given feed and water. The mice were grouped based on the body weight. The mice were grouped into the control group, the positive control group (sibutramine) and the test group. The administration dosage was 15 mg/kg for the positive control group and 200 mg/kg/10 mL for the test group. Administration was given abdominally using an insulin syringe. Administration was given once a day at 5 p.m. over a 4-week period. The control group was administered with 0.5 % carboxymethyl cellulose (CMC), at kg/ 1O mL.
  • CMC carboxymethyl cellulose
  • Body weight was measured over the 4-week period. The difference in the body weight of the control group and the body weight of the test group (g) and the increase of the body weight (%) were calculated to evaluate the inhibitive effect against body weight increase. Also, the amount of feed intake was measured in order to evaluate the inhibitive effect against feed intake.
  • Oral administration test was performed for the materials that showed effectiveness in Experimental Example 1. Grouping of the mice, administration dosage, administration period, etc. were the same as in Experimental Example 3-1. Forced oral administration was performed using a bouige.
  • FIGs. 8a and 8b and FIG. 9 the test group to which the compound represented by the formula 1 had been administered abdominally or orally showed significant decrease in blood glucose level and body weight compared with the control group, which implies the preventive and therapeutic effect for diabetes and obesity.
  • the compounds of the present invention are effective in lowering blood glucose level and body weight and can be used for treatment of diabetes and/ or obesity.

Abstract

The present invention relates to novel quinazoline derivatives effective in lowering blood glucose level and body weight, and a medicine for treatment and/ or prevention of diabetes and/ or obesity, which comprises the compound as an active ingredient.

Description

QUINAZOLINE DERIVATIVES FOR THE TREATMENT AND PREVENTION
OF DIABETES AND OBESITY
Technical Field
The present invention relates to novel quinazoline derivatives effective in lowering blood glucose level and reducing body weight, and a preparation for treatment and/ or prevention of diabetes and/ or obesity, which comprises the compound as an active ingredient.
Background Art
Diabetes, one of the most common modern diseases, is on the increase in Korea, too. Because of its severe symptoms and sequela, the disease is becoming a social problem. Improvement of living standards and environments resulting form economic development has led to lack of exercises, while calorie intake has increased significantly. As a result, obesity and type 2 diabetes are also on the increase. If diabetes persists, blood lipid level increases, not to mention the blood glucose level, leading to cardiovascular diseases such as arteriosclerosis and coronary heart disease and complications such as diabetic kidney and retinal diseases. Therefore, development of a treatment for the above disease is an important issue.
Diabetes is classified roughly into the insulin-dependent diabetes mellitus (hereunder referred to as "IDDM") and the non-insulin-dependent diabetes mellitus (hereunder referred to as "NIDDM"). The insulin-dependent diabetes mellitus (IDDM), or the type 1 diabetes, refers to a condition in which the beta cells of the pancreas produce little or no insulin due to immunological cause. In contrast, the non-insulin-dependent diabetes mellitus (NIDDM), or the type 2 diabetes, is caused by insulin secretory defect and insulin resistance and accounts for over 95 % of diabetes. Insulin secretory defect refers to the condition in which the beta cells of the pancreas cannot secrete an adequate amount of insulin depending on the blood glucose level and includes both quantitative and functional secretory defects. Insulin resistance refers to the condition in which target cells fail to respond to ordinary levels of circulating insulin. The cause of insulin resistance is generally thought of as hindered signal transfer after binding to the cell membrane receptor, resulting from genetic factors, obesity, reduced physical activity, hyperglycemia, abnormal blood lipid level, etc. What is important is that the two factors are related with each other. If there is insulin resistance, more insulin has to be secreted to overcome the resistance. And, hyperglycemia caused by insufficient secretion of insulin may aggravate the insulin resistance. Accordingly, extensive researches have been conducted to study insulin signal transfer system, glucose transfer and metabolism processes to accurately identify the cause of NIDDM. However, the exact pathological mechanism has yet to be found because the cause of NIDDM is very complicated and diverse and improvement of adequate treatment is being retarded.
It is well known that the type 2 diabetes (NIDDM) is related with obesity, but the exact mechanism of the interaction or interrelationship still needs to be elucidated. On the assumption that obesity and fatty acid metabolism disturbance resulting therefrom may be inseparably related with metabolic diseases, the focus of the research on the cause of diabetes has recently shifted from "glucose metabolism" to "fatty acid metabolism." In type 2 diabetes patients, such lipid metabolism disturbances as increase in blood fatty acid level, increase in neutral fats, decrease in high-density lipoprotein cholesterol, accumulation of fats in muscles, increase in abdominal fats and fatty liver are frequently found, as well as hyperglycemia. Of course, it is not certain as yet whether the trouble with lipid homeostasis results from hyperglycemia due to diabetes or it causes diabetes. Insulin resistance is preceded by excessive accumulation of neutral fats in target organs of insulin, including skeletal muscles, cardiac muscles and liver tissues, or fatty acid metabolism disturbance including increase of free fatty acids in fat tissues. When such a state persists, insulin resistance is aggravated and hyperglycemia occurs after meals or during fasting, which, in turn, aggravates the insulin resistance and fatty acid metabolism disturbance. Other metabolic diseases are induced as the cycle is repeated. This pathological phenomenon is corroborated with relative consistency in in vitro experiments, animal tests and human tests. However, it is still uncertain what causes the lipid metabolism disturbance or by what mechanism the insulin resistance is brought about, interfering with physiological homeostasis. At present, insulin resistance is thought to be the most important pathological cause of NIDDM. Insulin resistance is the condition in which glucose is not fully utilized even when there is a sufficient amount of insulin. Currently, various hypoglycemic drugs are used to treat insulin resistance. The hypoglycemic drugs are classified as follows depending on the treatment mechanism and the target site:
1) Sulfonylurea based drugs promote the movement of insulin-containing granules in the beta cells of the pancreas, thereby promoting the secretion of insulin at second hand. There was a report of severe side effects, including inducement of hypoglycemia, but recently, a drug with minimized side effects was developed. 2) Biguanide based drugs transfer glucose to muscle cells and inhibit gluconeogenesis in the liver. They are advantageous in that they do not cause hypoglycemia, but care should be taken for aged people and patients with cardiovascular diseases.
3) α-Glucosidase inhibitors inhibit the enzymatic action of glucose production in the small intestine, preventing abrupt increase of blood glucose level after meals. With few side effects, the drugs are used to treat mild cases of diabetes.
4) Recently developed thiazolidione (TZD) based drugs are known to activate PPAR-γ, which participates in the differentiation of fat cells. However, because these oral hypoglycemic drugs are not so effective in reducing blood glucose level and cause side effects, development of safer diabetic treatments is imminent. And, since the type 2 diabetes is caused by various reasons in insulin signal transfer system and carbohydrate and lipid metabolism processes, search for new target proteins capable of regulating the signal transfer system and metabolism processes is essential for development of such treatment drugs. Recently, as the role of 5'AMP-activated protein kinase (hereunder referred to as "AMPK") in carbohydrate and lipid metabolism and glucose absorption control is elucidated, the possibility of utilizing the activators of the enzyme as treatment for type 2 diabetes is proposed. The basis is as follows. 1) In the muscle cells of exercised mice, increase of AMP resulting from ATP consumption, which increases activity of AMPK, was found. As a result, increase in glucose absorption was observed.
2) The increase of glucose absorption caused by AMPK is independent of the insulin signal transfer system, which implies that it can be a new target material for most of type 2 diabetics showing abnormality in the insulin signal transfer system.
3) In fact, a lot of type 2 diabetics could reduce their blood glucose level through exercise. Also in the diabetic model animal test, it was found that exercise promotes activation of AMPK and decrease in blood glucose level.
4) AMPK plays a variety of other roles in the body. Besides controlling insulin production in pancreatic cells, it inhibits activation of acetyl CoA carboxylase
(ACC) and HMG-CoA reductase in fat cells, thereby inhibiting fat production and cholesterol synthesis. Thus, it is important in controlling obesity.
To conclude, AMPK plays a key role in energy homeostasis control and carbohydrate and lipid metabolism control, as activated by AMFs accumulated by muscle contraction, exercise or energy depletion in cells. Also, it is viewed as new target material for treating metabolic diseases, such as diabetes and obesity, caused by energy imbalance. The importance of AMPK in glucose absorption during exercise is widely known. The fact that the action of AMPK is independent of the insulin signal transfer system means that it can become a new target material for treatment of type 2 diabetics, most of whom show troubles with the insulin signal transfer system. Actually, a lot of type 2 diabetics could reduce their blood glucose level through exercise and the diabetic model animal test confirmed that exercise promotes activation of AMPK and decrease in blood glucose level. There is a report that metformin or thiazolidinedione (TZD) based drugs, which are widely used as diabetic treatments at present, reduce blood sugar level partly by an AMPK-involved mechanism. Thus, search of the drugs that can activate AMPK will lead to the development of a new-concept treatment that imitates the therapeutic effect of exercise on a variety of metabolic diseases.
However, there are a few reports about AMPK activators which are selectively effective against type 2 diabetes and obesity and significantly reduce blood glucose level in diabetic animal tests.
The present inventors synthesized a novel material that has a remarkable effect in increase of AMPK activity and prevention and/ or treatment of obesity and diabetes and confirmed the effect.
To solve the above-mentioned problems, the present inventors synthesized several compounds with quinazoline backbones and confirmed that they are superior in reducing blood glucose level and body weight.
Therefore, in an embodiment of the present invention there is provided a novel quinazoline compound effective in reducing blood sugar level and body weight, which is essential in treating diabetes and obesity. In an embodiment of the present invention there is provided a treatment for diabetes and obesity with no toxicity or side effects, which comprises the novel quinazoline compound, a pharmaceutically available salt thereof or a pharmaceutically available prodrug thereof as an active ingredient.
Disclosure of the Invention
The present invention relates to a quinazoline derivative, a pharmaceutically available salt thereof or a pharmaceutically available prodrug thereof effective in treating diabetes and obesity, which is represented by the formula 1 below:
Figure imgf000006_0001
wherein
Ra is a substituent selected from hydrogen, (Ci-Ci8)alkyL (C2-Cs) alkenyl, (C2-C8)alkynyl, halogeno-(Ci-C6)alkyl, hydroxy-(Ci-C6)alkyl, (Ci-C6)alkoxy-(Ci-C6)alkyl, cyano-(Ci-C6)alkyl, amino-(Ci-C6)alkyl, (Ci-C6)alkylamino-(C1-C6)alkyl, di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl, (Ci-C6)alkylthio-(Ci-C6)alkyl/ (Ci-C6)alkylsulfinyl-(Ci-C6)alkyl and (Ci-C6)alkylsulfonyl-(Ci-C6)alkyl or -X1-Q1 [wherein X1 is a direct bonding or selected from Ox S, SO, SO2/ N(R4), CO, CO2, CH(OR4), CON(R4), N(R4)CO, SO2N(R4), N(R4)SO2, C(R4)2O, C(R4)2S, N(R4)C(R4)2, N(R4)CON(R4) and N(R4)CSN(R4), wherein R4 is a group selected from hydrogen, (Ci-Cό)alkyl, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(C1-C6)alkyl, (C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(C1-C6)alkyl, heterocyclyl and heterocyclyl-(Ci-C6)alkyl, and Q1 and R4 may be identical or different], wherein the neighboring carbon atoms in (C2-Cό)alkylene of Ra may be separated by a group selected from the group consisting of O, S, SO, SO2, N(R5), CO, CH(OR5), CON(R5), N(R5)CO, SO2N(R5), N(R5)SO2, C(R5)=C(R5) and C≡C, wherein R5 is a hydrogen atom or (C1-C6)alkyl, any CH2=CH- or HC≡C- group of Ra may have a substituent, at the terminal or at CH2= or HC≡, selected from halogeno, carboxyl, carbamoyl, (Ci-C6)alkoxycarbonyl, N-(Ci -C6)alkylcarbamoyl, N,N-di-[(C1-C6)alkyl]carbamoyl, amino-(Ci-C6)alkyl, (Ci-C6)alkylamino-(Ci-C6)alkyl and di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl or -Q2-X2 [wherein X2 is a direct bonding or selected from CO and N(R6)CO, wherein R6 is a hydrogen atom or (Ci-C6)alkyl, and Q2 is aryl, aryl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl], any CH2 or CH3 of Ra may have a substituent selected from halogeno, (Ci-C6)alkyl, hydroxy, cyano, amino, carboxyl, carbamoyl, (Q-C6)alkoxy, (Ci-C6)alkylthio, (C1-C6)alkylsulfinyl, (Ci-C6)alkylsulfonyl, (C1 -C6) alky lamino, di- [(Ci -C6) alky 1] amino, (Ci-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, (C2-C6)alkanoyl, (C2-Cό)alkanoyloxy,
(C2-C6) alkanoylamino, N-(Ci -C6)alkyl-(C2-C6)alkanoylamino,
N-(Ci-C6)alkylsulfamoyl, N,N-di-[(Ci-C6)alkyl]sulfamoyl,
(C1-C6)alkanesulfonylamino and N-(C1-C6)alkyl-(Ci-C6)alkanesulfonylamino or -X3-Q3 [wherein X3 is a direct bonding or selected from O, S, SO, SO2, N(R7), CO, CH(OR7), CON(R7), N(R7)CO, SO2N(R7), N(R7)SO2, C(R7)2O, C(R7)2S, N(R7)C(R7)2,
N(R7)CON(R7) and N(R7)CSN(R7), wherein R7 is a hydrogen atom, (Ci-C6)alkyl, aryl, aryl-(C1-C6)alkyl/ (C3-C7)CyClOaIlCyI, (C3-C7)cycloalkyl-(C1-C6)alkyl/
(C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(C1-C6)alkyl/ heteroaryl, heteroaryl-(Ci-Cό)alkyl, heterocyclyl or heterocyclyl-(Ci-Cό)alkyl, and Q3 may be identical with or different from R7], any aryl, heteroaryl or heterocyclyl of Ra may have 0 to 3 substituents, which may be identical or different and are selected from halogeno, trifluoromethyl, cyano, nitro, hydroxy, amino, carboxyl, carbamoyl, (Ci-C6)alkyl, (C2-Cs)alkenyl, (C2-C8)alkynyl, (Ci-C6)alkoxy, (C2-C6)alkenyloxy, (C2-C6)alkynyloxy, (Ci-C6)alkylthio, (Ci-C6)alkylsulfinyl, (C1-C6)alkylsulfonyl, (Ci-C6)alkylamino, di-[(Ci-C6)alkyl]amino, (Ci-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N, N-di- [(Ci -C6) alky 1] carbamoyl, (C2-C6)alkanoyl, (C2-C6)alkanoyloxy, (C2-C6)alkanoylamino,
N-(d-C6)alkyl-(C2-C6)alkanoylamino, N-(Ci-C6)alkylsulfamoyl,
N,N-di-[(Ci-C6)alkyl]sulfamoyl, (C1-C6)alkanesulfonylamino and
N-(Ci-C6)alkyl-(Ci-C6)alkanesulfonylamino or -X4-R8 [wherein X4 is a direct bonding or selected from O and N(R9), wherein R9 is a hydrogen atom or (Ci-Cβ)alkyl, and R8 is selected from halogeno-(C1-Cό)alkyl, hydroxy-(Ci-C6)alkyl,
(Ci-C6)alkoxy-(d-C6)alkyl, cyano-(Ci-C6)alkyl, amino-(Ci-C6)alkyl,
(Ci-C6)alkylamino-(Ci-C6)alkyl, di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl,
(C2-C6)alkanoylamino-(Ci-C6)alkyl or (Ci-C6)alkoxycarbonylamino-(Ci-C6)alkyl] or -X5-Q4 [wherein X5 is a direct bonding or selected from O, CO and N(R10), wherein R10 is a hydrogen atom or (Ci-Cό)alkyl, and Q4 is aryl, aryl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl, which may have 1 or 2 identical or different substituents selected from halogeno, (Ci-Cό)alkyl and (Ci-Cό)alkoxy] and heterocyclyl of Ra may have 1 or 2 oxo or thioxo substituents;
Rb is a substituent selected from hydrogen,
Figure imgf000008_0001
(C2-Cs)alkenyl, (C2-C8)alkynyl, halogeno-(d-C6)alkyl, hydroxy-(Ci-C6)alkyl,
(Ci-C6)alkoxy-(Ci-C6)alkyl, cyano-(Ci-Cό)alkyl, amino-(Ci-C6)alkyl,
(Ci-C6)alkylamino-(Ci-C6)alkyl, di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl, (Ci-C6)alkylthio-(Ci-C6)alkyl, (Ci-C6)alkylsulfinyl-(Ci-C6)alkyl or
(C1-C6)alkylsulfonyl-(Ci-C6)alkyl or -X^Q1 [wherein X1 is a direct bonding or selected from O, S, SO, SO2, N(R4), CO, CO2(R4), CH(OR4), CON(R4), N(R4)CO, SO2N(R4), N(R4)SO2, C(R4)2O, C(R4)2S, N(R4)C(R4)2 , N(R4)CON(R4) and N(R4)CSN(R4), wherein R4 is a hydrogen atom, (Ci-QJalkyl, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl, (C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl, and Q1 and R4 may be identical or different, wherein the neighboring carbon atoms in (C2-Cό)alkylene of Rb may be separated by a group selected from O, S, SO, SO2 , N(R5), CO, CH(OR5), CON(R5), N(R5)CO, SO2N(R5), N(R5)SO2/ CH=CH and C≡C, wherein R5 is a hydrogen atom or (Ci-C6)alkyl, any CH2=CH- or HC≡C- of Rbmay have a substituent, at the terminal or at CH2= or HC≡, selected from halogeno, carboxyl, carbamoyl, (Ci-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, amino-(Ci-C6)alkyl, (Ci-C6)alkylamino-(Ci-C6)alkyl and di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl or -Q2-X2 [wherein X2 is a direct bonding or selected from CO and N(R6)CO, wherein R6 is a hydrogen atom or (C1-Cό)alkyl, and Q2 is aryl, aryl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(C1-C6)alkyl], any CH2 or CH3 of Rb may have at least one substituent selected from halogeno, (C1-C6)alkyl, hydroxy, cyano, amino, carboxyl, carbamoyl, (Ci-C6)alkoxy, (C1-C6)alkylthio, (C1-Cό)alkylsulfinyl, (C1-C6)alkylsulfonyl, (Ci-C6)alkylamino, di-[(C1-C6)alkyl]amino, (Ci-C6)alkoxycarbonyl, N-(C1-C6)alkylcarbamoyl,
N,N-di-[(Ci-C6)alkyl]carbamoyl, (C2-C6) alkanoyl, (C2-Ce)alkanoyloxy,
(C2-C6) alkanoylamino, N-(Ci-C6)alkyl-(C2-C6)alkanoylamino,
N^Q-C^alkylsulfamoyl, N,N-di-[(Ci-C6)alkyl]sulfamoyl, (Ci-C6)alkanesulfonylamino and N-(Ci-C6)alkyl-(Ci-C6)alkanesulfonylamino or -X3-Q3 [wherein X3 is a direct bonding or selected from O, S, SO, SO2, N(R7), CO, CH(OR7), CON(R7), N(R7)CO, SO2N(R7), N(R7)SO2, C(R7)2O, C(R7)2S, N(R7)C(R7)2, N(R7)CON(R7) and N(R7)CSN(R7), wherein R7 is a hydrogen atom, (Ci-C6)alkyl, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl, (C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl, and Q3 and R7 may be identical or different], any aryl, heteroaryl or heterocyclyl of Rb may have 1, 1 or 3 substituents, which may be identical or different and are selected from hydrogen, halogeno, trifluoromethyl, cyano, nitro, hydroxy, amino, carboxyl, carbamoyl, (Ci-Cβjalkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (Cι-C6)alkoxy, (C2-Ce) alkenyloxy, (C2-C6)alkynyloxy, (Ci-C6)alkylthio, (Ci-Cό)alkylsulfinyl, (Ci-C6)alkylsulfonyl, (C1-C6)alkylamino, di-[(Ci-C6)alkyl]amino, (Ci-C6)alkoxycarbonyl, N-(C1 -C6)alkylcarbamoyl,
N,N-di-[(Ci-C6)alkyl]carbamoyl, (C2-C6)alkanoyl, (C2-C6)alkanoyloxy,
(C2-C6)alkanoylamino, N-(Ci-C6)alkyl-(C2-C6)alkanoylamino, (C3-Cό)alkenoylamino, N-(Ci-C6)alkyl-(C3-Cό)alkenoylamino, (C3-C6)alkynoylamino,
N-(Ci-C6)alkyl-(C3-C6)alkynoylamino, N-(Ci-C6)alkylsulfamoyl,
N,N-di-[(Ci-C6)alkyl]sulfamoyl, (C1-Cό)alkanesulfonylamino and
N-(Ci-C6)alkyl-(Ci-C6)alkanesulfonylamino or -X4-R8 [wherein X4 is a direct bonding or selected from O and N(R9), wherein R9 is a hydrogen atom or (Ci-C6)alkyl, and R8 is selected from halogeno-(Ci-C6)alkyl, hydroxy-(Ci-C6)alkyl,
(C1-C6)alkoxy-(C1-C6)alkyl, cyano-(Ci-Cό)alkyl, amino-(Ci-C6)alkyl,
(Ci-C6)alkylamino-(Ci-C6)alkyl and di-[(C1-C6)alkyl]amino-(Ci-C6)alkyl] or -X^Q4 [wherein X5 is a direct bonding or selected from O, CO and N(R10), wherein R10 is a hydrogen atom or (C1-C6)alkyl, and Q4 is aryl, aryl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl, which may have 1 or 2 identical or different substituents selected from halogeno, (Ci-Cό)alkyl and (Q-C6)alkoxy]], heterocyclyl of Rb may have 1 or 2 oxo or thioxo substituents and any identical or different substituents of aryl, heteroaryl or heterocyclyl of Rb may bond with each other to form -CH=CH-CH=CH-, -N=CH-CH=CH-, -CH=N-CH=CH-, -CH=CH-N=CH-, CH=CH-CH=N-, -N=CH-N=CH-, -CH=N-CH=N-, -N=CH-CH=N-, -N=N-CH=CH-, -CH=CH-N=N-, -CH=CH-O-, -0-CH=CH-, -CH=CH-S-, -S-CH=CH-, -C(RIi)2-C(RiI)2-O-, -0-C(RH)2-C(RH)2-, -C(RH)2-C(RH)2-S-, -S-C(RH)2-C(RH)2-, -0-C(RH)2-O-, -O-C(RH)2-C(RΠ)2-O-, -S-C(RH)2-S-, -S-C(RH)2-C(RH)2-S-, -CH=CH-NH-, -NH-CH=CH-,
-C(RH)2-C(RH)2-NH-, -NH-C(RH)2-C(RH)2-, -N=CH-NH-, -NH-CH=N-, -NH-C(RH)2-NH-, -0-CH=N-, -N=CH-O-, -S-CH=N-, -N=CH-S-, -0-C(Rn)2-NH-, -NH-C(RH)2-O-, -S-C(R^)2-NH-, -NH-C(RH)2-S-, -O-N=CH-, -CH=N-O-, -S-N=CH-, -CH=N-S-, -0-NH-C(R^)2-, -C(RH)2-NH-O-, -S-NH-C(RH)2-, -C(RH)2-NH-S-, -NH-N=CH-, -CH=N-NH-, -NH-NH-C(RH)2-, -C(RH)2-NH-NH, -N=N-NH- or -NH-N=N- [wherein R11 is a hydrogen atom or (Ci-C6)alkyl]; m is 0, 1, 2, 3 or 4; and each Rc may be identical or different and is selected from hydrogen, halogeno, trifluoromethyl, cyano, isocyano, nitro, hydroxy, mercapto, amino, formyl, carboxyl, carbamoyl, (C1-Cό)alkyl, (C2-C8)alkenyl, (C2-Cs)alkynyl, (Ci-Ce)alkoxy, (C2-C6)alkenyloxy, (C2-C6)alkynyloxy, (Ci-C6)alkylthio, (Ci-C6)alkylsulfinyl, (Ci-C6)alkylsulfonyl, (Ci-C6)alkylamino, di-[ (C1 -C6) alky 1] amino,
(Ci-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, (C2-C6) alkanoyl, (C2-C6)alkanoyloxy, (C2-C6)alkanoylamino,
N-(Ci-C6)alkyl-(C2-C6)alkanoylamino, (C3-C6)alkenoylamino, N-(Ci -C6)alkyl-(C3-C6)alkenoylamino, (C3-C6)alkynoylamino,
N-(Ci-C6)alkyl-(C3-C6)alkynoylamino, N-(Ci-C6)alkylsulfamoyl,
N,N-di-[(Ci-C6)alkyl]sulfamoyl, (Ci-C6)alkanesulfonylamino,
N-(Ci-Cό)alkyl-(C1-C6)alkanesulfonylamino, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl, (C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl and heterocyclyl-(Ci-C6)alkyl; wherein the neighboring carbon atoms of (C2-C6) alky lene of Rc may be separated by a group selected from O, S, SO, SO2, N(R12), CO, CH(OR12), CON(R12), N(R12)CO, SO2N(R12), N(R12)SO2 , CH=CH and C≡C, wherein R12 is a hydrogen atom or (Ci-C6)alkyl, any CH2=CH- or HC=C- of Rc may have a substituent, at the terminal or at
CH2= or HC≡, selected from halogeno, carboxyl, carbamoyl, (Ci-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, amino-(Ci-C6)alkyl, (Ci-C6)alkylamino-(Ci-C6)alkyl and di-[(Ci-C6)alkyl]amino-(C1-C6)alkyl or -Q5-X6 [wherein X6 is a direct bonding or selected from CO and N(R13)CO, wherein R13 is a hydrogen atom or (Ci-C6)alkyl, and Q5 is aryl, aryl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(C;ι-C6)alkyl, heterocyclyl or heterocyclyl-(C1-C6)alkyl], any CH2 or CH3 of Rc may have at least one substituent selected from halogeno, (Ci-C6)alkyl, hydroxy, cyano, amino, carboxyl, carbamoyl, (Ci-C6)alkoxy, (Ci-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C6)alkylsulfonyl, (C1 -C6) alky lamino, di- [(Ci -C6)alkyl] amino, (O-C^alkoxycarbonyl, N-(d-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, (C2-C6) alkanoyl, (C2-C6)alkanoyloxy,
(C2-C6)alkanoylamino, N-(Ci-C6)alkyl-(C2-C6)alkanoylamino,
N-(Ci-C6)alkylsulfamoyl,
Figure imgf000012_0001
(C;i-C6)alkanesulfonylamino and N-(Ci-C6)alkyl-(Ci-C6)alkanesulfonylamino or -X7-Q6 [wherein X7 is a direct bonding or selected from O, S, SO, SO2, N(R14), CO, CH(OR14), CON(R14), N(R14)CO, SO2N(R14), N(R14)SO2, C(R14)2O, C(R14)2S and N(R14)C(R14)2, wherein R14 is a hydrogen atom or (Ci-C6)alkyl, and Q6 is aryl, aryl-(C1-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl,
(C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-Cό)alkyl], any aryl, heteroaryl or heterocyclyl of Rc may have 1, 2 or 3 identical or different substituents selected from hydrogen, halogeno, trifluoromethyl, cyano, nitro, hydroxy, amino, carboxyl, carbamoyl, (Ci-C6)alkyl, (C2-Cs) alkenyl, (C2-C8)alkynyl, (Ci-C6)alkoxy, (C2-Cό)alkenyloxy, (C2-C6) alky nyloxy, (Ci-C6)alkylthio, (Ci-C6)alkylsulfinyl, (C1 -C6) alky lsulfonyl, (Ci-C6)alkylamino, di-[(Ci-C6)alkyl]amino, (Q-C^alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, (C2-C6)alkanoyl, (C2-C6)alkanoyloxy, (C2-C6)alkanoylamino,
N-(Ci-C6)alkyl-(C2-C6)alkanoylamino, (C3-C6)alkenoylamino,
N-(Ci-C6)alkyl-(C3-C6)alkenoylamino, (C3-C6)alkynoylamino,
N-(Ci-C6)alkyl-(C3-C6)alkynoylamino, N-(Ci-C6)alkylsulfamoyl, N,N-di-[(Ci-C6)alkyl]sulfamoyl, (C1-C6)alkanesulfonylamino and
N-(Ci-C6)alkyl-(Ci-C6)alkanesulfonylamino or -X8-R15 [wherein X8 is a direct bonding or selected from O and N(R16), wherein R16 is a hydrogen atom or (Ci-C6)alkyl, and R15 is selected from halogeno-(Ci-C6)alkyl, hydroxy-(Ci-C6)alkyl, (Ci-C6)alkoxy-(Ci-C6)alkyl, cyano-(Ci-C6)alkyl, amino-(Ci-C6)alkyl, (Ci-C6)alkylamino-(C1-C6)alkyl and di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl or -X9-Q7
[wherein X9 is a direct bonding or selected from O, CO and N(R17), wherein R17 is a hydrogen atom or (Ci-C6)alkyl, and Q7 is aryl, aryl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(C1-C6)alkyl/ heterocyclyl or heterocyclyl-(Ci-C6)alkyl, which may have 1 or 2 identical or different substituents selected from halogeno, (C1-Cβ)alkyl and (Ci-C6)alkoxy, wherein any heterocyclyl of Q7 may have 1 or 2 oxo or thioxo substituents]], heterocyclyl of Rc may have 1 or 2 oxo or thioxo substituents and any identical or different substituents of aryl, heteroaryl or heterocyclyl of Rc may bond with each other to form -CH=CH-CH=CH-, -N=CH-CH=CH-, -CH=N-CH=CH-, -CH=CH-N=CH-, CH=CH-CH=N-, -N=CH-N=CH-, -CH=N-CH=N-, -N=CH-CH=N-, -N=N-CH=CH-, -CH=CH-N=N-, -CH=CH-O-, -0-CH=CH-, -CH=CH-S-, -S-CH=CH-, -C(R18)2-C(R18)2-O-, -O-C(R18)2-C(R18)2-, -C(R18)2-C(R18)2-S-, -S-C(R18)2-C(R18)2-, -O-C(R18)2-O-, -O-C(R18)2-C(R18)2-O-, -S-C(R18)2-S-, -S-C(R18)2-C(R18)2-S-, -CH=CH-NH-, -NH-CH=CH-,
-C(Ri8)2-C(R18)2-NH-, -NH-C(R18)2-C(Ri8)2-, -N=CH-NH-, -NH-CH=N-, -NH-C(R18)2-NH-, -O-CH=N-, -N=CH-O-, -S-CH=N-, -N=CH-S-, -O-C(R18)2-NH-, -NH-C(R18)2-O-, -S-C(R18)2-NH-, -NH-C(R18)2-S-, -O-N=CH-, -CH=N-O-, -S-N=CH-, -CH=N-S-, -O-NH-C(R18)2-, -C(R18)2-NH-O-, -S-NH-C(R18)2-, -C(R18)2-NH-S-, -NH-N=CH-, -CH=N-NH-, -NH-NH-C(R18)2-, -C(R18)2-NH-NH, -N=N-NH- or -NH-N=N- [wherein R18 is a hydrogen atom or (Ci-C6)alkyl]. Of the quinazoline compounds represented by the formula 1, the compound represented by the formula 1-1 below is preferred:
Figure imgf000013_0001
wherein
X is a direct bonding or selected from O, S, SO, SO2 and NR5, wherein R5 is a hydrogen atom, (C1-C6)alkyl, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-Cό)alkyl;
Ri is a substituent selected from hydrogen, (Ci-C8)alkyl, halogeno-(Ci-C6)alkyl, hydroxy-(d-C6)alkyl, (Ci-C6)alkoxy-(C1-C6)alkyl/ amino-(Ci-C6)alkyl, (Ci-C6)alkylamino-(Ci-C6)alkyl, di-[(C1-C6)alkyl]amino-(C1-C6)alkyl and (Ci-C6)alkylsulfinyl or -X^-Q1 [wherein X1 is a direct bonding or selected from O, S and NR5 and Q1 and R5 may be identical or different], the neighboring carbon atoms of (C2-C6)alkylene of Ri may be separated by a group selected from O, S and N(R5), any CH2 or CH3 of R1 may have at least one substituent selected from halogeno, (Ci-C6)alkyl substituent, hydroxy, amino, (Ci-C6)alkoxy (Ci-Cό)alkylthio, (Ci-C6)alkylsulfinyl, (Ci-C6)alkylamino and di-[(Ci-C6)alkyl]amino, any aryl, heteroaryl or heterocyclyl of Ri may have 0 to 3 identical or different substituents selected from halogeno, hydroxy, amino, (Ci-C6)alkyl, aryl, aryl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl, heterocyclyl-(C1-C6)alkyl, (Ci-C6)alkoxy, (Ci-C6)alkylthio and (d-C6)alkylsulfinyl and heterocyclyl of Ri may have 1 or 2 oxo or thioxo substituents; R2 is a substituent selected from hydrogen, (Ci-Ci8)alkyl, (C2-C8)alkenyl, halogeno-(d-C8)alkyl, hydroxy-(Ci-C8)alkyl, (Ci-C8)alkoxy-(Ci-C8)alkyl, amino-(Ci-C8)alkyl, (Ci-C8)alkylamino-(Ci-C8)alkyl, di-[(Ci-C8)alkyl]amino-(C1-C8)alkyl, (Ci-C8)alkylsulfinyl, aryl, aryl-(Ci-C8)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-Cs)alkyl, heteroaryl, heteroaryl-(Ci -Cs) alky 1, heterocyclyl and heterocyclyl-(C1-Cs)alkyl, wherein the neighboring carbon atoms of (C2-Cδ)alkylene of R2 may be separated by a group selected from O, S, N(R5), CO, CH(OR5), CON(R5), N(R5)CO, SO2N(R5), N(R5)SO2 and CH=CH, any CH2 or CH3 of R2 may have at least one substituent selected from halogeno, (Ci-C6)alkyl, hydroxy, cyano, amino, carboxyl, carbamoyl, (Ci-C6)alkoxy
(Ci-C6)alkylthio, (Ci-C6)alkylsulfinyl, (Ci-C6)alkylamino, di-[(Ci-C6)alkyl]amino,
(Ci-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl and heterocyclyl-(Ci-C6)alkyl, any aryl, heteroaryl or heterocyclyl of R2 may have 0 to 3 identical or different substituents selected from halogeno, trifluoromethyl, cyano, nitro, hydroxy, amino, carboxyl, carbamoyl,
Figure imgf000015_0001
aryl, aryl-(Q-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl, heterocyclyl-(Ci-C6)alkyl, (C2-Cs)alkenyl, (C2-C8)alkynyl, (C1-C6)alkoxy, (Ci-C6)alkylthio, (Ci-C6)alkylsulfinyl,
(Ci-C6)alkylamino, di- [(C1 -Cό)alkyl] amino, (Ci-C6)alkoxycarbonyl,
N-(Ci-C6)alkylcarbamoyl and N,N-di-[(C1-C6)alkyl]carbamoyl, heterocyclyl of R2 may have 1 or 2 oxo or thioxo substituents and any identical or different substituents of aryl, heteroaryl or heterocyclyl of R2 may bond with each other to form -CH=CH-CH=CH-, -N=CH-CH=CH-, -CH=N-CH=CH-, -CH=CH-N=CH-, CH=CH-CH=N-, -N=CH-N=CH-, -CH=N-CH=N-, -N=CH-CH=N-, -CH=CH-O-, -0-CH=CH-, -CH=CH-S-, -S-CH=CH-, -C(R6)2-C(R6)2-O-, -O-C(R6)2-C(R6)2-, -C(RS)2-C(RS)2-S-, -S-C(RO)2-C(RS)2-, -O-C(R6)2-O-, -O-C(RS)2-C(R6)2-O-, -S-C(R6)2-S-, -S-C(R6)2-C(R6)2-S-, -CH=CH-NH-, -NH-CH=CH-, -C(R6)2-C(R6)2-NH-, -NH-C(RS)2-C(RS)2-, -N=CH-NH-, -NH-CH=N-, -NH-C(RS)2-NH-, -O-CH=N-, -N=CH-O-, -S-CH=N-, -N=CH-S-, -O-C(R6)2-NH-, -NH-C(RS)2-O-, -S-C(RS)2-NH-, -NH-C(RS)2-S-, -N=N-NH- or -NH-N=N- [wherein RS is a hydrogen atom or (Ci-C3)alkyl]; and each of R3 and R4 is, identically or differently, selected from hydrogen, halogeno, trifluoromethyl, cyano, nitro, hydroxy, mercapto, amino, formyl, carboxyl, carbamoyl,(Ci-C6)alkyl, (C2-Cs)alkenyl, (C2-Ce)alkoxy, (Ci-Cό)alkylthio, (Ci-C6)alkylsulfinyl, (C1-C6)alkylamino, di-[(Ci-Cό)alkyl]amino,
(Ci-Cό)alkoxycarbonyl, N-(C1-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl and heterocyclyl-(Ci-C6)alkyl, wherein any CH2 or CH3 of R3 and R4 may have at least one substituent selected from halogeno, hydroxy, amino, carboxyl, carbamoyl, (C1-Cό)alkoxy, (Ci-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C6)alkylamino, di- [(Ci -C6)alkyl] amino, (Ci-Cό)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl and heterocyclyl-(d-C6)alkyl, any aryl, heteroaryl or heterocyclyl of R3 and R4 may have Ix 2 or 3 identical or different substituents selected from halogeno, trifluoromethyl, nitro, hydroxy, amino, (C1-C6)alkoxy, (C1 -C6) alky lthio, (Ci-C6)alkylamino/ di-[(Ci-C6)alkyl]amino/
(C1-C6)alkoxycarbonyl, N-(d-C6)alkylcarbamoyl and N,N-di-[(C1-C6)alkyl]carbamoyl and heterocyclyl of R3 and R4 may have 1 or 2 oxo or thioxo substituents.
More preferably, in the quinazoline compound represented by the formula 1-1:
X is O, S or NR5; R1 is a hydrogen atom, C1-C6 alkyl, C1-C4 haloalkyl, C1-C6 alkylhydroxy,
Ci-C6 alkylsulfanyl, phenyl, phenyl C1-Cs alkyl, pyridino, furano, thiopheno, C3-C7 cycloalkyl, pyrrolidino, piperidino, morpholino or N-(Ci-Cδ)alkylpiperazino; R2 is Ci-Ci8 alkyl, C2-C8 haloalkyl, C3-C7 cycloalkyl, (C3-C7)cycloalkyl Ci-C8 alkyl, C2-C8 alkenyl, (C3-C7)cycloalkenyl C1-C8 alkyl, (Ci-Cs)alkyl C1-Cs alkoxyalkyl, Ci-Cs hydroxyalkyl, hydroxy-(Ci-C8)alkyl-(d-Cs)alkoxy alkyl, phenyl, phenyl Ci-C8 alkyl, di-phenyl Ci-C8 alkyl, phenyl Ci-C8 alkylhydroxy, phenyl Ci-C8 alkenyl, piperidine C1-C8 alkyl, N-[phenyl-(Ci-C6)alkyl]piperidino, N-(Ci-Cό)alkylpiperidine Ci-C8 alkyl, pyrrolidinone N-(Ci-C8)alkyl, naphthalene Ci-C8 alkyl, morpholine Ci-C8 alkyl, piperazine Ci-C8 alkyl, N-(Ci-C6)alkylpiperazine Ci-Cs alkyl, pyridine Ci-C8 alkyl, pyrrolidine Ci-C8 alkyl, N-(Ci-C6)alkylpyrrolidine Ci-C8 alkyl, thiopene Ci-C8 alkyl or benzodioxol Ci-C8 alkyl; each of R3 and R4 is a hydrogen atom, nitro or Ci-C8 alkoxy; R5 is a hydrogen atom, Ci-C4 alkyl or C1-C8 hydroxyalkyl; and the substituent selected from C3-C7 cycloalkyl, phenyl, piperidine, naphthalene, morpholine, pyridine, pyrrolidine, pyrrolidinone, piperazine, thiopene and benzodioxol mentioned above has 1 to 3 substituents selected from Ci-C8 alkyl, halogen, hydroxy, Ci-C8 alkoxy, nitro and trifluoromethyl.
Specific examples of the compounds represented by the formula 1-1 are given in Table 1 below: Table 1
Figure imgf000017_0001
Figure imgf000018_0001
Figure imgf000019_0001
Figure imgf000020_0001
Figure imgf000021_0001
Figure imgf000022_0001
Figure imgf000023_0001
Figure imgf000024_0001
Figure imgf000025_0001
The compound represented by the formula 1 may form a pharmaceutically available salt, including an inorganic acid salt such as hydrochloride, sulfate, phosphate, bisphosphate, hydrobromate and nitrate or an organic acid salt such as malate, maleate, fumarate, tartrate, succinate, citrate, acetate, lactate, methanesulfonate, p-toluenesulfonate, palmitate, salicylate and stearate.
Some of the compounds of the present invention may be crystallized or recrystallized using an aqueous or organic solvent. In that case, a solvate may be formed. In addition to various water-containing compounds with different water contents that can be prepared by lyophilization, etc., hydrates and other stoichiometric solvates belong to the scope of the present invention.
The compound represented by the formula 1 may be an enantiomer, a stereoisomer or a tautomer. The isomers may be separated or decomposed by common methods or may be obtained by common stereospecific or asymmetrical synthesis methods.
Radioactive derivatives of the compound represented by the formula 1, which are useful for biological studies, also belong to the scope of the present invention.
The present invention also provides a preparation method of the quinazoline derivatives represented by the formula 1 and a pharmaceutically available salt thereof.
The present invention also provides a preparation method of the compound represented by the formula 1-1. As shown in the scheme 1 below, it may be synthesized from the subs titution reaction of a 4-chloro-2-substituted-quinazoline derivative represented by the formula 2 below and a compound represented by the formula 3 below: Scheme 1
Figure imgf000026_0001
(2) (3) (1-D
wherein Ri, R2, R3, R4 and X are the same as defined in the formula 1.
The substitution reaction of the scheme 1 is carried out in the presence of a base and an organic polar solvent. For the base, an organic base such as pyridine or an alkylamine or an inorganic base such as an alkali metal salt or an alkaline earth metal salt may be used.
Alternatively, the compound represented by the formula 1-1 may be prepared from the substitution reaction of a 2-chloro-4-substituted-quinazoline derivative represented by the formula 4 below and a compound represented by the formula 5 below, as shown in the scheme 2 below:
Scheme 2
Figure imgf000026_0002
wherein Ri, R2, R3, R4 and X are the same as defined in the formula 1.
The substitution reaction of the scheme 2 is carried out in the presence of a base and an organic polar solvent. For the base, an organic base such as pyridine or an alkylamine or an inorganic base such as an alkali metal salt or an alkaline earth metal salt may be used.
Alternatively, the compound represented by the formula 1-1 may be prepared from the substitution reaction of a 2-methyl-3H-quinazolino-4-one derivative represented by the formula 6 below, which is substituted by X at the number 4 position, and a compound represented by the formula 7 below, as shown in the scheme 3 below: Scheme 3
Figure imgf000027_0001
(6) (7) (1-1) wherein Ri, R2, R3, R4 and X are the same as defined in the formula 1 and Y is a leaving group selected from Cl, Br, I, OMs and OTs.
The substitution reaction of the scheme 3 is carried out in the presence of a base and an organic polar solvent. As a base, an organic base such as pyridine or an alkylamine or an inorganic base such as an alkali metal salt or an alkaline earth metal salt may be used. The compounds represented by the formulas 2 and 3 in the scheme 1, which are used as starting materials of the substitution reaction, may be prepared by the methods well known in the field of organic synthesis.
Of the quinazoline derivatives represented by the formula 2, one in which Ri is ethylsulfanyl may be prepared by the scheme 4 below:
Scheme 4
Figure imgf000027_0002
(2a) wherein R3 and R4 are the same as defined in the formula 1.
First, 2-mercapto-3H-quinazolino-4-one is reacted with sodium ethoxide (NaOEt) and ethyl iodide (EtI) in the temperature range from room temperature to the reflux temperature of the solvent in order to introduce the ethylsulfanyl group at the C-2 position. Subsequently, to the resultant
2-ethylsulfanyl-3H-quinazolino-4-one is added thionyl chloride (SOCb) at -20 to 10 °C and reflux reaction is performed in the presence of an N,N-dimethylformamide catalyst in order to transform the ketone group at the C-4 position into chlorine (Cl).
Of the quinazoline derivatives represented by the formula 2, one in which Ri is a hydrogen atom, alkyl or aryl may be prepared by the scheme 5 below:
Scheme 5
Figure imgf000028_0001
wherein R3 and R4 are the same as defined in the formula 1.
First, an imidate compound is reacted with anthranilic acid and sodium methoxide (NaOMe) in the temperature range from room temperature to the reflux temperature of the solvent while stirring in order to prepare 3H-quinazolino-4-one with the substituent R1. Subsequently, phosphorus oxy chloride and diethylaniline are added and reaction is carried out in the temperature range from room temperature to the reflux temperature of the solvent while stirring to transform the ketone group at the C-4 position into chlorine (Cl).
Of the quinazoline derivatives represented by the formula 2, one in which R1 is a hydrogen atom, alkyl or aryl may also be prepared by the scheme 6 below:
Scheme 6
Figure imgf000028_0002
(2) wherein R1, R3 and R4 are the same as defined in the formula 1. First, an acyl halide is reacted with anthranyl amide and reflux reaction is carried out in the presence of NaOH to prepare 3H-quinazolino-4-one with the substituent R1. Subsequently, phosphorus oxy chloride and diethylaniline are added and reaction is performed in the temperature range from room temperature to the reflux temperature of the solvent while stirring in order to transform the ketone group at the C-4 position into chlorine (Cl).
The compounds represented by the formulas 4 and 5 in the scheme 2, which are used as starting materials of the substitution reaction, may be prepared by the methods well known in the field of organic synthesis. For example, the compound represented by the formula 4 may be prepared by the scheme 7 below:
Scheme 7
Figure imgf000029_0001
(3) (4) wherein R2, R3, R4 and X are the same as defined in the formula 1. In the substitution reaction of the scheme 7, the compound represented by the formula 3 may be used in excess as both organic solvent and reactant or another solvent may be used and the compound may be used stoichiometrically. And the reaction may be carried out in the presence of a base, if deemed necessary. As a base, an organic base such as pyridine and an alkylamine or an inorganic base such as an alkali metal salt and an alkaline earth metal salt may be used.
The prepared intermediate compound and the target compound may be separated and purified by such common methods as chromatography and recrystallization.
The compounds of the present invention may be administered by an adequate administration method, for example, orally, intraorally, sublingually, rectally, vaginally, intranasally, locationally or non-orally (including intravenously, intracavernously, intramuscularly, subcutaneously and intraluminally).
For oral, intraoral or sublingual administration, the general dosage of the compound represented by the formula 1 for treatment or prevention of diabetes and obesity is 0.1 to 400 mg/day for an adult weighing 70 kg. Thus, the compound can be prepared into a tablet or capsule, using a pharmaceutically available excipient or vehicle, with the content of the compound of 0.05 to 200 mg, and administered once or several times a day.
For non-oral administration, the compound is administered in an amount of 0.01 to 100 mg. The adequate dosage is determined by the doctor, considering the patient's age, body weight and other characteristics. The aforementioned dosages are for general cases. The dosage may be higher or lower from a patient to another.
When administered to humans, the compound represented by the formula 1 may be administered alone or along with a pharmaceutical vehicle that is selected in consideration of the administration and other standard pharmaceutical practices. For example, the compound may be administered orally, intraorally or sublingually in the form of a tablet containing starch or lactose, ovules by itself or along with excipients or elixir or emulsion containing chemicals that offer specific flavors or colors.
The liquid preparation may be prepared by adding a pharmaceutically available additive such as a suspension (e.g., a mixture of semisynthetic glyceride like methylcellulose and witepsol or apricot kernel oil with PEG-6 ester or a glyceride mixture of PEG-8 and caprylic/capric glyceride). It may be administered non-orally, for example, intravenously, intracavernously, intramuscularly, subcutaneously or intraluminally. For non-oral administration, it is most preferable to use the compound in the form of sterile aqueous solution. The solution may comprise other substances (for example, salts or monosaccharides such as mannitol and glucose) for isotonicity with blood. Thus, the present invention provides a pharmaceutical composition comprising the compound represented by the formula 1 or a pharmaceutically available salt thereof, as an active ingredient, and a pharmaceutically available diluent or excipient.
The present invention also provides a pharmaceutical composition for medical use comprising the compound represented by the formula 1, a pharmaceutically available salt thereof or a pharmaceutically available prodrug thereof as an active ingredient.
Brief Description of the Drawings FIG. 1 shows the result of Western blot analysis showing the degree of phosphorylation of the serine-79 for the compound of the present invention. FIGs. 2a to 2g show the results of Western blot analysis showing the degree of phosphorylation of the serine-79 and threonine-172 for the compound of the present invention.
FIGs. 3a and 3b are graphs showing the change of blood glucose level when the compound of the present invention was abdominally administered to db/db mice.
FIGs. 4a and FIG. 4b are graphs showing the change of body weight when the compound of the present invention was abdominally administered to db/db mice. FIGs. 5a, 5b and 5c are graphs showing the change of blood glucose level when the compound of the present invention was orally administered to db/db mice.
FIGs. 6a, 6b and 6c are graphs showing the change of body weight when the compound of the present invention was orally administered to db/db mice. FIGs. 7a and 7b are graphs showing the change of body weight when the compound of the present invention was abdominally administered to ob/ob mice.
FIGs. 8a and 8b are graphs showing the change of blood glucose level when the compound of the present invention was abdominally administered to ob/ob mice. FIG. 9 is a graph showing the change of body weight when the compound of the present invention was orally administered to ob/ob mice.
Best Mode for Carrying Out the Invention
Hereinafter, the present invention is described in further detail through examples. However, the following examples are only for the understanding of the present invention and they should not be construed as limiting the scope of the present invention.
Examples 1 to 3 are for the case wherein X = NH and Ri = ethylsulfanyl.
Figure imgf000032_0001
(A) (B) (2a) Oa)
Example 1: Preparation of 2-ethylsulf anyl-3H-quinazolino-4-one (formula B)
2-Mercapto-3H-quinazolino-4-one (formula A; 3 g, 16.83 mmol) was dissolved in 100 mL of ethanol and NaOEt (1.5 eq, 9.4 mL, 25.25 mmol) and EtI (1.5 eq, 2.02 mL, 25.25 mmol) were added at room temperature. After 3 hours of reflux, ethanol was removed by distillation under reduced pressure from the mixture when the starting materials disappeared. Ethyl acetate was added and the mixture was washed with water and then dried with anhydrous magnesium sulfate. The organic solvent was removed by distillation under reduced pressure and the target compound was obtained with a yield of 80 % (2.78 g) by column chromatography (silica gel; 230-400 mesh).
1H NMR (CDCl3, 300 MHz) δ 8.27 (d, J=7.8 Hz, IH), 7.73 (t, J=7.5 Hz, IH), 7.71 (d, J=7.8 Hz, IH), 7.41 (t, J=7.5, IH), 3.34 (q, J=14.4 Hz, 2H), 1.49 (t, J=7.35 Hz, 3H).
Example 2. Preparation of 4-chloro-2-ethylsulf anylquinazoline (formula 2a)
To 2-ethylsulf anyl-3H-quinazolino-4-one (formula B; 1.5 g, 7.27 mmol) was slowly added 50 mL of thionyl chloride at 0 °C . After adding 2-3 drops of N,N-dimethylformamide, reflux was performed for 3-4 hours. When the starting materials disappeared, thionyl chloride was removed by distillation under reduced pressure. Residual thionyl chloride was washed with a saturated sodium carbonate solution. The mixture was extracted with ethyl acetate and the organic layer was washed with brine and dried with anhydrous magnesium sulfate. The organic solvent was removed by distillation under reduced pressure and the target compound was obtained with a yield of 79 % (1.29 g) by column chromatography.
1H NMR (CDCl3, 300 MHz) δ 8.02 (d, J=7.8 Hz, IH), 7.85 (m, 2H), 7.56 (t, J=7.5 Hz, IH), 3.29 (q, J=14.4 Hz, 2H), 1.49 (t, J=7.35 Hz, 3H). Example 3. Preparation of 4-substituted amine-2-ethylsulfanylquinazoline (formula Ia)
4-Chloro-2-ethylsulfanylquinazoline (1.0 g, 4.45 mmol) was dissolved in 40 mL of THF. Triethylamine (TEA; 3 eq, 1.86 mL, 13.35 mmol) and amine (1.5 eq) were added and the mixture was stirred at room temperature overnight. When the starting materials disappeared, THF was removed by distillation under reduced pressure and the target compound was obtained with a yield of 90 % by column chromatography (silica gel; 230-400 mesh).
Example 4 shows a case wherein X = NH and Ri = phenyl.
Figure imgf000033_0001
Example 4. Preparation of 4-substituted amine-2-phenylquinazoline (formula Ib) 4-Chloro-2-phenylquinazoline (formula 2b; 0.5 g, 2.08 mmol) was dissolved in 30 mL of THF. TEA (5 eq, 1.45 mL, 10.38 mmol) and amine (1.5 eq) were added and the mixture was stirred at room temperature overnight. When the starting materials disappeared, THF was removed by distillation under reduced pressure and the target compound was obtained with a yield of 90 % by column chromatography (silica gel; 230-400 mesh).
Examples 5 to 7 are cases wherein X = NH and Ri = hydrogen, alkyl or aryl.
Figure imgf000033_0002
(C) (D) (E) (2c) (1C)
Example 5. Preparation of 2-substituted-3ff-quinazolino-4-one (formula E) A hydrochloride of the imidate compound having the Ri substitute (formula C; 50 mmol) was dissolved in 100 mL of methanol and NaOMe (1.2 eq, 60 mmol) and anthranilic acid (formula D, 1.0 eq, 50 mmol) were slowly added at 0 "C . Reflux was performed overnight after slowly heating the mixture to the reflux temperature. After confirming with TLC that all the starting materials had disappeared, the mixture was cooled to 0 °C . Water (100 mL) was added to the mixture and the formed crystal was filtered and dried to obtain the target compound with a yield of 70 % (35 mmol).
Example 6. Preparation of 4-chloro-2-substituted-quinazoline (formula 2c)
2-Substituted-3H-quinazolino-4-one (formula E; 35 mmol) was dissolved in 100 mL of toluene and N,N-diethylaniline (1.5 eq, 52.5 mmol) and phosphorus oxy chloride (1.0 eq, 35 mmol) were added. The mixture was stirred at 80 °C for 3 hours and cooled to 0 °C when the starting materials disappeared. The mixture was washed with IN-NaOH and IN-HCl and dried with anhydrous sodium sulfate. The organic solvent was removed by distillation under reduced pressure and the target compound was obtained with a yield of 98 % (34 mmol) by column chromatography (silica gel; 230-400 mesh).
Example 7. Preparation of R2-(2-(Ri-substituted)-quinazolino-4-yl)-amine (formula Ic)
4-Chloro-2-substituted-quinazoline (formula 2c; 10 mmol) was dissolved in 30 mL of THF. Triethylamine (2 eq, 20 mmol) and amine (1.5 eq, 15 mmol) were added and the mixture was stirred at room temperature overnight. When the starting materials disappeared, THF was removed by distillation under reduced pressure. After adding chloroform, the mixture was washed with a saturated sodium carbonate solution and brine and dried with anhydrous sodium sulfate. The organic solvent was removed by distillation under reduced pressure and the target compound was obtained with a yield of 95 % (9.5 mmol) by column chromatography (silica gel; 230-400 mesh). Examples 8 and 9 are cases wherein R1 = H, alkyl or aryl.
Figure imgf000035_0001
(F) (G) (H) (E)
Example 8. Preparation of 2-(substituted-carbonyl-amino)-benzamide (formula H) An acyl chloride with the substituent Ri (formula F; 50 mmol), anthranilamide (1.0 eq, formula G, 50 mmol) and triethylamine (1.5 eq, 75 mmol) were dissolved in THF and the mixture was stirred at room temperature overnight. When the starting materials disappeared, THF was removed by distillation under reduced pressure. After adding chloroform, the mixture was washed with IN-NaOH and brine and dried with sodium sulfate. The organic solvent was removed by distillation under reduced pressure and the remainder was crystallized with diethyl ether to obtain the target compound with a yield of 95 % (48 mmol).
Example 9. Preparation of 2-substituted-3H-quinazolino-4-one (formula E) 2-(Substituted-carbonyl-amino)-benzamide (formula H; 45 mmol) was dissolved in 60 mL of 2.5N-NaOH and the mixture was refluxed for 1 hour. When the starting materials disappeared, the mixture was cooled to 0 "C and neutralized with 3N-HC1. The formed crystal was filtered and dried to obtain the target compound with a yield of 95 % (43 mmol). The prepared target compound (formula E) can be utilized in the preparation of the compound with X = NH and Ri = H, alkyl or aryl by the preparation processes of Examples 6 and 7.
Examples 10 and 11 are for the case wherein X = NH and Ri = amine.
Figure imgf000035_0002
Example 10. Preparation of (2-chloro-quinazolino-4-yl)-substituted-amine (formula 4a)
2,4-Dichloro-quinazoline (formula J; 10 mmol) was dissolved in 30 mL of
THF. Triethylamine (1.2 eq, 12 mmol) and an amine compound with the R2 substituent (formula 1, 1.05 eq, 10.5 mmol) were added and the mixture was stirred at room temperature for 3 hours. When the starting materials disappeared, the organic solvent was removed by distillation under reduced pressure. After adding ethyl acetate, the mixture was washed with a saturated sodium carbonate solution and brine and dried with anhydrous sodium sulfate. The organic solvent was removed by distillation under reduced pressure and the mixture was crystallized with diethyl ether to obtain the target compound with a yield of 100 %
(10 mmol).
Example 11. Preparation of (2-(R5-substituted-amine)-quinazolino-4-yl)-Ri-substituted-amine (Id)
(2-Chloro-quinazolino-4-yl)-substituted-amine (formula 4a; 1.5 mmol) and an amine with the Rs substituent (3 eq, 4.5 mmol) were dissolved in 15 mL of ethanol. The mixture was refluxed overnight while stirring. After confirming with TLC that all the starting materials had disappeared, the organic solvent was removed by distillation under reduced pressure. Ethyl acetate was added and the mixture was washed with a saturated sodium carbonate solution and brine and dried with anhydrous sodium sulfate. The organic solvent was removed by distillation under reduced pressure and the target compound was obtained with a yield of 95 % (1.4 mmol) by column chromatography (silica gel; 230-400 mesh).
Example 12 is a case wherein X = NH and Ri = alkoxy.
Figure imgf000036_0001
Example 12. Preparation of (2-(R5-substituted-alkoxy)-quinazolino-4-yl)-Ri-substituted-amine (Id)
(2-Chloro-quinazolino-4-yl)-substituted-amine (formula 4a; 1.5 mmol) was dissolved in 15 mL of ethanol and NaOEt (2 eq, 3.0 mmol) was added at 0 °C.
The mixture was stirred at room temperature for 3 hours and ethanol was removed by distillation under reduced pressure when the starting materials disappeared.
Ethyl acetate was added and the mixture was washed with water and dried with sodium sulfate. The organic solvent was removed by distillation under reduced pressure and the target compound was obtained with a yield of 85 % (1.3 mmol) by column chromatography (silica gel; 230-400 mesh).
Examples 13 and 14 are cases wherein X = S.
Figure imgf000037_0001
(E) (6a) (1f)
Example 13. Preparation of 2-substituted-3H-quinazolino-4-thione (formula 6a)
2-Substituted-3H-quinazolino-4-one (formula E; 3 mmol) and a Lawesson's reagent (0.5 eq, 1.5 mmol) were dissolved in 9 mL of toluene and the mixture was refluxed for 1 hour while stirring. When the starting materials disappeared, the organic solvent was removed by distillation under reduced pressure and the target compound was obtained with a yield of 95 % (2.9 mmol) by column chromatography (silica gel; 230-400 mesh).
Example 14. Preparation of 2-(Ri-substituted)-4-(R2-Sulfanyl)-quinazoline (formula If)
2-Substituted-3H-quinazolino-4-thione (formula 6a, 2 mmol) and potassium carbonate (1.5 eq, 3 mmol) were dissolved in 8 mL of N,N-dimethylformamide and an R2-substituted bromine compound (1.2 eq, 2.4 mmol) was added at room temperature. When the starting materials disappeared after 1 hour of stirring, the mixture was diluted with ethyl acetate, washed with water and brine and dried with anhydrous sodium sulfate. The organic solvent was removed by distillation under reduced pressure and the target compound was obtained with a yield of 95 % (1.9 mmol) by column chromatography (silica gel; 230-400 mesh).
Example 15 is a case wherein X = O.
Figure imgf000038_0001
Example 15. Preparation of 2-(Ri-substituted)-4-(R2-substituted-oxy)-quinazoline (formula Ig)
2-Substituted-3H-quinazolino-4-one (formula E; 3 mmol) and potassium carbonate (1.0 eq, 3 mmol) were dissolved in 9 mL of N,N-dimethylformamide and an R2-substituted bromine compound (1.5 eq, 4.5 mmol) was added at room temperature. When the starting materials disappeared after stirring overnight at room temperature, the mixture was diluted with ethyl acetate, washed with water and brine and dried with anhydrous sodium sulfate. The organic solvent was removed by distillation under reduced pressure and the target compound was obtained with a yield of 45 % (1.4 mmol) by column chromatography (silica gel; 230-400 mesh).
Example 16 is a case wherein X = O.
Figure imgf000038_0002
(2c) (1g)
Example 16. Preparation of 2-(Ri-substituted)-4-(R2-substituted-oxy)-quinazoline (formula Ig)
An R2-substituted alcohol compound (1.2 eq, 24 mmol) and sodium hydride (1.2 eq, 24 mmol) were dissolved in 60 mL of N,N-dimethylformamide at 0 0C and 4-chloro-2-substituted-quinazoline (formula 2c; 20 mmol) was added. After stirring overnight at room temperature, the mixture was diluted with ethyl acetate, washed with water and brine and dried with anhydrous sodium sulfate. The organic solvent was removed by distillation under reduced pressure and the target compound was obtained with a yield of 46 % (9.2 mmol) by column chromatography (silica gel; 230-400 mesh).
Those skilled in the art can easily prepare the compound represented by the formula 1 according to the preparation processes of Examples 1 to 4. Some examples of thus prepared compounds are as follows.
Compound No. 1: 2-[2-(2-Phenylquinazolino-4-ylamino)-ethoxy]-ethanol
1H NMR(CDCl3, 300 MHz) δ 8.56(m, 2H), 7.91(d, /=8.1 Hz, IH), 7.70(m, 2H), 7.50(m, 3H), 7.37(t, J=7.5 Hz, IH), 6.40(m, IH), 4.00(m, 2H), 3.82(m, 4H), 3.64(m, 2H), 2.83(br s, IH)
Compound No. 2: Isopropyl-(2-trichloromethylquinazolino-4-yl)-amine
Compound No. 3: Cyclopropyl-(2-trichloromethylquinazolino-4-yl)-amine
Compound No. 4: (2-Piperidino-l-ylethyl)-(2-trichloromethylquinazolino-4-yl)-amine
Compound No. 5: (1 -Phenyl ethyl)-(2-trichloromethylquinazolino-4-yl)-amine
Compound No. 6: (4-Phenylbutyl)-(2-trichloromethylquinazolino-4-yl)-amine
Compound No. 7: Propyl-(2-trichloromethylquinazolino-4-yl)-amine
Compound No. 8: (2-Ethylsulf anylquinazolino-4-yl)-isopropylamine Compound No. 9: (2-Ethylsulf anylquinazolino-4-yl)-(3-f luorobenzyl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.68(In, 3H), 7.30(m, 2H), 7.15(d, /=7.5 Hz, IH), 7.05(d, /=7.5 Hz, IH), 6.95(t, /=7.5 Hz, IH), 6.24(s, IH), 4.85(d, /=5.4 Hz, 2H), 3.15(q, /=14.4 Hz, 2H), 1.37(t, /=7.35 Hz, 3H)
Compound No. 10:
(2-Ethylsulf anylquinazolino-4-yl)-[2-(3-fluorophenyl)-ethyl]-amine
Compound No. 11:
(2-Ethylsulf anylquinazolino-4-yl)-(2-morpholino-4-ylethyl)-amine
Compound No. 12:
(2-Ethylsulf anylquinazolino-4-yl)-[2-(3-trifluoromethyl-phenyl)ethyl]-amine
Compound No.13: (6-Nitro-quinazolino-4-yl)-phenylamine
Compound No. 14: (6,7-Diethoxyquinazolino-4-yl)-naphthaleno-l-ylmethylamine
Compound No. 15:
(6,7-Diethoxyquinazolino-4-yl)-(3-morpholino-4-ylpropyl)-amine
Compound No. 16: Allyl-(6,7-diethoxyquinazolino-4-yl)-amine
Compound No. 17: (6,7-Diethoxyquinazolino-4-yl)-(2-pyridino-2-ylethyl)-amine
Compound No. 18: (4-Chlorobenzyl)-(6,7-diethoxyquinazolino-4-yl)-amine
Compound No. 19: Butyl-(2-ethylsulf anylquinazolino-4-yl)-amine
Compound No. 20: sec-Butyl-(2-ethylsulf anylquinazolino-4-yl)-amine Η NMR(CDCl3x 300 MHz) δ 7.86(d, /=7.5 Hz, IH), 7.61 (m, 2H), 7.30(d, /=7.5 Hz, IH), 6.57(s, IH), 4.42(m, IH), 3.23(q, /=14.4 Hz, 2H), 1.74(m, 2H), 1.47-1.22(m, 6H), 1.00(t, /=7.35 Hz, 3H)
Compound No. 21: (2-Ethylsulf anylquinazolino-4-yl)-isobutylamine
Compound No. 22: Benzyl-(2-ethylsulfanylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.65(m, 3H), 7.34(m, 6H), 6.01 (s, IH), 4.86(d, /=5.4 Hz, 2H), 3.65(q, /=14.4 Hz, 2H), 1.40(t, /=7.35 Hz, 3H)
Compound No. 23: (2-Ethylsulf anylquinazolino-4-yl)-(l-phenylethyl)-amine
Compound No. 24: (2-Ethylsulf anylquinazolino-4-yl)-(3-methoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.66(m, 3H), 7.29(m, 2H), 6.95(m, 2H), 6.88(m, IH), 6.02(s, IH), 4.82(d, /=5.5 Hz, 2H), 3.80(s, 3H), 3.20(q, /=14.4 Hz, 2H), 1.40(t, /=7.35 Hz, 3H)
Compound No. 25: (2-Ethylsulf anylquinazolino-4-yl)-(4-methoxybenzyl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.62(m, 3H), 7.33(m, 3H), 6.90(d, /=8.4 Hz, 2H), 4,78(d, /=5.7 Hz, 2H), 3.81(s, 3H), 3.23(q, /=14.4 Hz, 2H), 1.43(t, /=7.36 Hz, 3H)
Compound No. 26:
(2-Ethylsulf anylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.92(d, /=8.3 Hz, IH), 7.63(m, 4H), 7.55(m, 2H), 7.46(m, 2H), 7.33(m, IH), 4.94(d, /=5.4 Hz, 2H), 3.12(q, /=14.4 Hz, 2H), 1.30(t, /=7.35 Hz, 3H)
Compound No. 27: Cyclohexyl-(2-ethylsulf anylquinazolino-4-yl)-amine
Compound No. 28: Cyclopentyl-(2-ethylsulf any lquinazolino-4-yl) -amine
Compound No. 29: (2-Ethylsulf anylquinazolino-4-yl)-phenethylamine 1H NMR(CDCl3, 300 MHz) δ 7.66(m, 2H), 7.45(d, /=8.2 Hz, IH), 7.33(m, 6H), 5.84(br s, IH), 3.91(q, /=12.6 Hz, 2H), 3.26(q, /=14.4 Hz, 2H), 3.03(t, /=6.9 Hz, 2H), 1.47(t, /=7.36 Hz, 3H)
Compound No. 30: (2-Ethylsulfanylquinazolino-4-yl)-(4-phenylbutyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.61 (m, 3H), 7.30(m, 3H), 7.20(m, 3H), 5.74(br s, IH), 3.68(m, 2H), 3.23(q, /=14.4 Hz, 2H), 2.69(m, 2H), 1.76(m, 4H), 1.44(t, /=7.36 Hz, 3H)
Compound No. 31: (2-Ethylsulfanylquinazolino-4-yl)-propylamine
Compound No. 32: (2-Ethylsulf anylquinazoline4-yl)-(3-phenylpropyl)-amine
Compound No. 33: (2-Ethylsulf anylquinazolino-4-yl)-(3-isopropoxypropyl)-amine
Compound No. 34: (2-Ethylsulf anylquinazolino-4-yl)-(2-methoxy-ethyl)-amine
Compound No. 35:
(2-Ethylsulf anylquinazolino-4-yl)-naphthaleno-l-ylmethylamine
1H NMR(CDCl3, 300 MHz) δ 8.11(m, IH), 7.90(m, 2H), 7.65(m, 2H), 7.53(m, 5H), 7.24(m, IH), 5.92(br s, IH), 5.27(d, /=4.5 Hz, 2H), 3.26(q, /=14.4 Hz, 2H), 1.22(t, /=7.4 Hz, 3H)
Compound No. 36:
(2-Ethylsulf anylquinazolino-4-yl)-(3-morpholino-4-ylpropyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.93(m, IH), 7.70(m, 3H), 7.31(m, IH), 3.78(m, 6H), 3.22(q, /=14.4 Hz, 2H), 2.59(m, 6H), 1.87(m, 2H), 1.43(t, /=7.41 Hz, 3H)
Compound No. 37: Benzo[l,3]dioxol-5-ylmethyl-(2-ethylsulfanylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.66(m, 3H), 7.31(m, IH), 6.80(m, 3H), 5.97(s, 2H), 5.90(br s, IH), 4.76(d, /=5.1 Hz, 2H), 3.23(q, /=14.4 Hz, 2H), 1.44(t, /=7.36 Hz, 3H) Compound No. 38: (3,5-Dimethoxybenzyl)-(2-ethylsulfanylquinazolino-4-yl)-amine
Compound No. 39: (2-Ethylsulf anylquinazolino-4-yl)-(2-f luorobenzyl)-amine
Compound No. 40:
(2-Ethylsulf anylquinazolino-4-yl)-(l-methoxymethylpropyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.65(In, 3H), 7.32(m, IH), 5.96(d, /=7.5 Hz, IH), 4.48(d, /=3.6 Hz, IH), 3.60(m, 2H), 3.41(s, 3H), 3.20(q, /=14.4 Hz, 2H), 1.75(m, 2H), 1.44(t, /=7.4 Hz, 3H), 1.01(t, /=7.35 Hz, 3H)
Compound No. 41: (l-Benzyl-piperidino-4-yl)-(2-ethylsulfanylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.60(m, 3H), 7.34(m, 6H), 5.54(d, /=6.9 Hz, IH), 4.26(m, IH), 3.50(m, 2H), 3.22(q, /=14.4 Hz, 2H), 2.90(m, 2H), 2.17(m, 4H), 1.65(m, 2H), 1.22(t, /=7.35 Hz, 3H)
Compound No. 42: Allyl-(2-ethylsulfanylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 7.66(m, 3H), 7.33(m ,1H), 6.03(m, IH), 5.79(br s ,1H), 5.29(m, 2H), 4.31(t, /=5.55 Hz, 2H), 3.23(q, /=14.5 Hz, 2H), 1.44(t, /=7.35 Hz, 3H)
Compound No. 43: (2-Ethylsulf anylquinazolino-4-yl)-hexadecylamine
Compound No. 44:
(2-Ethylsulf anylquinazolino-4-yl)-(2-piperidino-l-ylethyl)-amine
Compound No. 45:
(2-Ethylsulf anylquinazolino-4-yl)-(2-pyrrolidino-l-ylethyl)-amine
Compound No. 46: (2-Ethylsulf anylquinazolino-4-yl)-(2-pyridino-2-ylethyl)-amine Compound No. 47: 2-(2-Ethylsulf anylquinazolino-4-ylamino)-ethanol
1H NMR(DMSO-d6/ 300 MHz) δ 8.33(m, IH), 8.14(d, /=8.2 Hz, IH), 7.67(t, /=7.5 Hz, IH), 7.48(d, /=8.1 Hz, IH), 7.36(t, /=7.6 Hz, IH), 4.81(br s, IH), 3.60(m, 4H), 3.13(q, /=14.4 Hz, 2H), 1.32(t, /=7.35 Hz, 3H)
Compound No. 48: (2-Ethylsulfanylquinazolino-4-yl)-[3-(2-methyl-piperidino-l-yl)-propyl]-amine
Compound No. 49:
(2-Chloro-6-fluorobenzyl)-(2-ethylsulfanylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.64(m, 3H), 7.25(m, 3H), 7.05(m, IH), 6.00(br s, IH), 5.06(d, /=5.6 Hz, 2H), 3.28(q, /=14.4 Hz, 2H), 1.46(t, /=7.35 Hz, 3H)
Compound No. 50: 2-[2-(2-Ethylsulfanylquinazolino-4-ylamino)-ethoxy]-ethanol 1H NMR(CDCl3, 300 MHz) δ 7.60(m, 3H), 7.27(m, IH), 6.50(br s, IH), 3.85(m, 4H), 3.78(m, 2H), 3.65(m, 2H), 3.20(q, /=14.4 Hz, 2H), 1.42(t, /=7.35 Hz, 3H)
Compound No. 51: Cyclohexyl-(2-phenylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 8.58(m, 4H), 7.93(m, IH), 7.72(m, 2H), 7.50(m, 4H), 5.58(d, /=7.2 Hz, IH), 4.43(m, IH), 2.27(m, 2H), 1.85(m, 3H), 1.54(m, 2H), 1.34(m, 3H)
Compound No. 52: (4-Phenylbutyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 53: (5-Phenyl-pentyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 54: (4-Methylbenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 55: Isobutyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 56: Butyl-(2-phenylquinazolino-4-yl)-amine Compound No. 57: Naphthaleno-l-ylmethyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 58: (2-Phenylquinazolino-4-yl)-pyridino-2-ylmethylamine Η NMR(CDCl3, 300 MHz) δ 8.61(m, 3H), 7.91(t, /=8.2 Hz, IH), 7.72(t, /=8.2 Hz, IH), 7.52(m, 6H), 7.28(m, IH), 5.07(d, /=4.5 Hz, 2H)
Compound No. 59: (l-Phenylquinazolino-4-yl)-thiopenyl-2-ylmethylamine
1H NMR(CDCl3, 300 MHz) δ 8.66(m, 2H), 7.96(d, /=8.1 Hz, IH), 7.69(m, 2H), 7.53(m, 3H), 7.41 (m, IH), 7.24(t, /=7.4 Hz, IH), 7.13(t, /=7.4 Hz, IH), 7.00(t, /=7.36 Hz, IH), 6.09(d, /=5.1 Hz, IH), 5.17(d, /=5.4 Hz, 2H),
Compound No. 60: Isopropyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 61: (2-Phenylquinazolino-4-yl)-propylamine
1H NMR(CDCl3, 300 MHz) δ 8.60(m, IH), 7.94(d, /=8.2 Hz, IH), 7.70(m, 2H), 7.41 (m, 4H), 5.78(t, /=5.4 Hz, IH), 3.76(q, /=13.2 Hz, 2H), 1.80(q, /=14.4 Hz, 2H), 1.08(t, /=8.4 Hz, 3H)
Compound No. 62: (3-Isopropoxypropyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 63: (3-Fluorobenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 64: (2-Phenylquinazolino-4-yl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amine
Η NMR(CDCl3, 300 MHz) δ 8.64(m, 2H), 7.95(d, /=8.3 Hz, IH), 7.74(t, /=7.4 Hz, IH), 7.50(m, 4H), 7.40(t, /=6.6 Hz, IH), 7.30(m, IH), 7.03(m, 3H), 5.85(t, /=5.4 Hz, IH), 4.03(q, /=13.2 Hz, 2H), 3.10(t, /=7.9 Hz, 2H)
Compound No. 65: Benzo[l,3]dioxol-5-ylmethyl-(2-phenylquinazolino-4-yl)-amine Compound No. 66: (2-Phenylquinazolino-4-yl)-(3-trif luoromethylbenzyl)-amine
Compound No. 67: (2-Methoxy-ethyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 68: Phenethyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 69: Phenyl-(2-phenylquinazolino-4-yl)-amine iH NMR(DMSO7 300 MHz) δ 11.56(br s, IH), 8.92(d, /=8.2 Hz, IH), 8.35(m, 3H), 8.09(t, /=7.4 Hz, IH), 7.83(m, 3H), 7.60(m, 5H), 7.38(d, /=8.4 Hz, IH)
Compound No. 70: (4-Methoxyphenyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 71: (2-Phenylquinazolino-4-yl)-o-tollylamine
Compound No. 72: (4-Isopropyl-phenyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(DMSO, 300 MHz) δ 11.45(br s, IH), 8.90(d, /=8.2 Hz, IH), 8.35(m, 3H), 8.08(t, /=7.4 Hz, IH), 7.80(m, 3H), 7.68(m, 3H), 7.41 (d, /=8.4 Hz, IH)
Compound No. 73: (2,4-Dimethyl-phenyl)-(2-phenylquinazolino-4-yl)-amine 1H NMR(DMSO, 300 MHz) δ 11.41(br s, IH), 8.82(d, /=8.2 Hz, IH), 8.33(d, /=8.2 Hz, IH), 8.18(m, 3H), 7.83(t, /=7.4 Hz, IH), 7.65(m, 3H), 7.38(d, /=8.1 Hz, IH), 7.19(m, 3H), 2.37(s, 3H), 2.27(s, 3H)
Compound No. 74: (2-Phenylquinazolino-4-yl)-(4-undecyl-phenyl)-amine
Compound No. 75: (4-Ethyl-phenyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 76: (4-Fluorophenyl)-(2-phenylquinazolino-4-yl)-amine
Η NMR(DMSO, 300 MHz) δ 11.42(br s, IH), 8.90(d, /=8.2 Hz, IH), 8.34(m, 3H), 8.09(t, /=7.4 Hz, IH), 7.86(m, 3H), 7.68(m, 3H), 7.40(m, 2H) Compound No. 77: (2-Methoxyphenyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 78: (2-Phenylquinazolino-4-yl)-(2,4,6-trimethyl-phenyl)-amine
1H NMR(DMSO, 300 MHz) δ 11.39(br s, IH), 8.83(d, /=8.2 Hz, IH), 8.27(t, /=7.4 Hz, IH), 8.11(m, 3H), 7.85(t, J=7.5 Hz, IH), 7.67(t, /=7.5 Hz, IH), 7.60(m, 2H), 7.07(s, 2H), 2.33(s, 3H), 2.18(s, 6H)
Compound No. 79: (4-Butyl-phenyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 80: (2-Phenoxy-phenyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(DMSO, 300 MHz) δ 11.62(br s, IH), 8.69(d, /=8.2 Hz, IH), 8.28(m, 3H), 8.09(t, /=7.5 Hz, IH), 7.79(t, /=7.5 Hz, IH), 7.68(m, 3H), 7.34(d, /=7.8 Hz, IH), 7.16(d, /=7.8 Hz, IH), 7.12(m, 3H), 6.90(m, 3H)
Compound No. 81: (3-Phenoxy-phenyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 82: (4-Phenoxy-phenyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 83: (3-Bromophenyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 84: 2-Methoxy-5-(2-phenylquinazolino-4-ylamino) phenol
1H NMR(DMSO, 300 MHz) δ 11.29(br s, IH), 9.45(br s, IH), 8.82(d, /=8.2 Hz, IH), 8.36(m, 2H), 8.25(d, /=8.1 Hz, IH), 8.06(t, /=7.4 Hz, IH), 7.79(t, /=7.4 Hz, IH), 7.64(m, 3H), 7.33(s, IH), 7.25(d, /=8.7 Hz, IH), 7.05(d, /=8.7 Hz, IH), 3.83(s, 3H)
Compound No. 85: 5-(2-Phenylquinazolino-4-ylamino)-pentane-l-ol
Compound No. 86: Benzyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 87: (l-Phenylethyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 88: (4-Chlorobenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 89: (3,4-Dichlorobenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 90: (3-Methoxybenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 91: (2-Methoxybenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 92: (3,5-Dimethoxybenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 93: (2,3-Dimethoxybenzyl)-(2-phenylquinazolino~4-yl)-amine
Compound No. 94: (2-Fluorobenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 95: Cyclopentyl-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3x 300 MHz) δ 8.61 (m, 2H)7 7.93(d, /=8.1 Hz, IH), 7.72(m, 2H), 7.50(m, 4H), 5.67(d, /=6.3 Hz, IH), 4.80(q, /=13.5 Hz, IH), 2.31 (m, 2H), 1.80(m, 4H), 1.65(m, 2H)
Compound No. 96: sec-Butyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 97: Allyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 98: (2-Phenylquinazolino-4-yl)-(2-trifluoromethylbenzyl)-amine
Compound No. 99: Hexadecyl-(2-phenylquinazolino-4-yl)-amine
Compound No.100: (2-Phenylquinazolino-4-yl)-(2-pyrrolidino-l-ylethyl)-amine
Compound No. 101: (2~Phenylquinazolino-4-yl)-(2-piperidino-l-ylethyl)-amine
Compound No. 102: (2-Phenylquinazolino-4-yl)-(2-pyridino-2-ylethyl)-amine Compound No. 103: [2-(3-Fluorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.59(dd, /2=7.8 Hz, J2=LS Hz, 2H), 7.93(d, /=8.1 Hz, IH), 7.72(t, /=7.5 Hz, IH), 7.47(m, 7H), 6.99(m, 3H), 5.76(br s, IH), 4.06(m, 2H), 3.12(t, /=7.2 Hz, 2H)
Compound No. 104: (l-Methoxymethylpropyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.56(t, /=3.8 Hz, 2H), 7.96(d /=8.3 Hz, IH), 7.72(m, 2H), 7.49-7.39(m, 5H), 6.06(d /=7.2 Hz, IH), 4.72(t /=3.8 Hz, IH), 3.65(m, 2H), 3.43(s, IH), 1.84(m, 2H), 1.06(t, /=7.4 Hz, 3H)
Compound No. 105: (l-Benzyl-piperidino-4-yl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.54(t /=6.7 Hz, 2H), 7.92(d, /=8.3 Hz, IH), 7.69(m, 2H), 7.50-2.27(m, 8H), 5.59(d /=7.1 Hz, IH), 4.46(m, IH), 3.61(s, 2H), 2.95(m, 2H), 2.68(s, IH), 2.30(m, 4H), 1.70(m, 2H)
Compound No. 106: (2-Morpholino-4-ylethyl)-(2-phenylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.56(t /=6.2 Hz, 2H), 7.92(d, /=8.5 Hz, 2H), 7.71(m, 2H), 7.49-7.26(m, 4H), 6.56 (s, IH), 3.86-3.74(m. 6H), 2.73(t, /=5.9 Hz 2H), 3.76(m, 4H)
Compound No. 107:
[2-(3,4-Dimethoxyphenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine iH NMR(CDCl3, 300 MHz) δ 8.60(t /=5.2 Hz, 2H), 7.93(d /=8.3 Hz, IH), 7.69(t /=7.5
Hz, IH), 7.57(t /=8.1 Hz, IH), 7.50(m, 3H), 7.36(t /=3.6 Hz, IH), 6.84(m, 3H), 5.96(s, IH), 4.12(m, 2H), 3.87(s, 3H), 3.81(s, 3H), 3.03(t, /=6.7 Hz, 2H)
Compound No. 108: (2,4-Dichlorobenzyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.53(m, 2H), 7.93(d, /=8.1 Hz, IH), 7.74(t, /=7.7Hz, 2H), 7.47(m, 6H), 7.17(dd, /2=8.4 Hz, /2=2.0Hz, IH), 6.17(br, IH), 5.06(d, /=6.0 Hz, 2H)
Compound No. 109: (2-Chlorobenzyl)-(2-phenylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.56(t, /=3.3 Hz, 2H), 7.95(d /=8.6 Hz, IH), 7.71(m, 2H), 7.55-7.37(m, 6H), 7.21 (t, /=3.6 Hz, 2H), 6.31 (s, IH), 5.09(d, /=5.8 Hz, 2H)
Compound No. 110: Cyclopropyl-(2-phenylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.63(d, /=7.3 Hz, 2H), 7.93(d, /=8.3 Hz, 2H), 7.70(m, 2H), 7.49(m, 3H), 7.37(t, /=7.5 Hz, IH), 6.03(s, IH), 3.17(m, IH), 0.97(m, 2H), 0.73(m, 2H)
Compound No. Ill: (2-Phenylquinazolino-4-yl)-pyridino-3-ylmethylamine
1H NMR(CDCl3, 300 MHz) δ 8.73(m, IH), 8.51(m, 3H), 8.04(d /=8.2 Hz, IH,), 7.94(d, /=8.2 Hz, IH), 7.85(d, /=7.1 Hz, IH), 7.67(t, J=7.7 Hz, IH), 7.47(m, 3H), 7.37(m, IH), 7.26(m, 2H), 5.03(d, /=5.1 Hz, 2H)
Compound No. 112: 2-(2-Phenylquinazolino-4-ylamino)-propane-l-ol
Η NMR(CDCl3, 300 MHz) δ 8.49(m, 2H), 7.93(t, /=7.8 Hz, 2H), 7.58(m, 5H), 7.34(t, /=7.6 Hz, IH), 7.71(t, J=7.7 Hz, IH), 3.91(m, 2H), 1.45(m, 4H)
Compound No. 113: 2-Methoxy-4-[(2-phenylquinazolino-4-ylamino)-methyl]-phenol
1H NMR(MeOD, 300 MHz) δ 8.35(d, /=2.2 Hz, 2H), 8.02(m, IH), 7.80(m,2H), 7.45(m, 4H), 7.07(s, IH), 6.89(t, /=8.0 Hz, IH), 6.75(t, /=8.0 Hz, IH), 4.85(s, 2H), 3.72(s, 3H)
Compound No. 114: (2-Fluoro-ethyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.53(m, 2H), 7.93(d, /=8.4 Hz, IH), 7.74(t, /=7.5Hz, 2H), 7.50(m, 4H), 6.03(br s, IH), 4.86(t, /=4.8Hz, IH), 4.70(t, /=5.1Hz, IH), 4.20(q, /=5.1Hz, IH), 4.10(q, /=5.1Hz, IH)
Compound No.115: (2,3-Dichlorobenzyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.52(t, /=3.7 Hz, 2H), 7.92(d, /=8.5 Hz, IH), 7.72(t, /=6.6 Hz, 2H), 7.42(m, 6H), 7.08(t, /=7.8 Hz, IH), 6.24(s, IH), 5.09(d, /=5.9 Hz, 2H)
Compound No. 116: (3-Nitrobenzyl)-(2-phenylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.46(In, 2H), 8.19(m, IH), 8.03(d, /=7.5 Hz, IH), 7.91(d, /=7.9 Hz, IH), 7.82(d, J=7.7 Hz, IH), 7.70(d, /=6.0 Hz, IH), 7.42(m, 5H), 6.54(s, IH), 4.96(d, /=4.4 Hz, 2H)
Compound No. 117:
(l-Ethyl-pyrrolidino-2-ylmethyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.47(d, /=5.6 Hz, 2H), 8.10(d, /=8.1 Hz, IH), 7.94(s, IH), 7.84(d, /=8.3 Hz, IH), 7.68(t, /=7.6 Hz, IH), 7.42(m, 4H), 5.97(s, IH), 4.08(m, 2H), 3.58(m, 2H), 3.01(t, /=4.7 Hz, IH), 2.67(m, 2H), 2.09-1.91(m, 4H), 1.19(m, 3H)
Compound No. 118: (3,4-Dimethoxybenzyl)-(2-phenylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.59(t, /=3.8 Hz, 2H), 7.93(d, /=8.1 Hz, IH), 7.71(m, 2H), 7.45(m, 3H), 7.36(t, /=7.6 Hz, IH), 7.04(s, IH), 6.97(d, /=8.4 Hz, IH), 6.80(t, /=4.1 Hz, IH), 6.21(s, IH), 4.90(d, /=5.2 Hz, 2H), 3.87(s, 3H), 3.78(s, 3H)
Compound No. 119: (2-Phenylquinazolino-4-yl)-(2-p-tollylethyl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.59(t, /=3.3 Hz, 2H), 7.93(d, /=8.4 Hz, IH), 7.69(t, /=7.6 Hz, IH), 7.55(m, 4H), 7.36(t, /=7.5 Hz, IH), 7.16(m, 4H), 5.91(s, IH), 4.01(m, 2H), 3.05(t, /=6.9 Hz, 2H), 2.43(s, 3H)
Compound No. 120:
[2-(3-Methoxyphenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.61(t, /=3.8 Hz, 2H), 7.93(d, /=8.3 H, IHz), 7.70(m, IH),
7.49(m, 4H), 7.30(m, 2H), 6.85(m, 3H), 5.90(s, IH), 4.02(m, 2H), 3.76(s, 3H), 3.05(t, /=6.9 Hz, 2H)
Compound No. 121: (l-Ethylpropyl)-(2-phenylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.55(t, /=3.5 Hz, 2H), 7.95(d, /=8.2 Hz, IH), 7.69(m, 2H), 7.46(m, 4H), 5.59(s, IH), 4.53(d, /=6.7 Hz, IH), 1.85-1.62(m, 4H), 1.00(m, 6H)
Compound No. 122: [2-(2,5-Dimethoxyphenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.59(t, /=3.2 Hz, 2H), 7.91(d, /=8.4 Hz, IH), 7.67(t, /=7.6 Hz, IH), 7.59(d, /=8.1 Hz, IH), 7.47(m, 3H), 7.36(t, /=7.5 Hz, IH), 6.80(m, 3H), 6.39(s, IH), 3.98(m, 2H), 3.86(s, 3H), 3.71(s, 3H), 3.08(t, /=6.5 Hz, 2H)
Compound No. 123: [2-(4-chlorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 8.57(t, /=3.6 Hz, 2H), 7.91 (m, IH), 7.69(m, IH), 7.53(m, 4H), 7.38(d, /=6.9 Hz, IH), 7.25(m, 2H), 7.18(m, 2H), 5.76(s, IH), 4.00(m, 2H), 3.05(m, 2H)
Compound No. 124:
[2-(4-Methoxyphenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.60(t, /=3.2 Hz, 2H), 7.93(d, /=8.3 Hz, IH), 7.69(t, /=7.6
Hz, IH), 7.50(m, 4H), 7.35(t, /=7.5 Hz, IH), 7.20(d, /=8.3 Hz, 2H), 6.87(d, /=8.3 Hz, 2H), 5.85(s, IH), 4.00(m, 2H), 3.79(s, 3H), 3.02(t, /=6.9 Hz, 2H)
Compound No. 125: (l,3-Dimethylbutyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.58(t, /=3.8 Hz, 2H), 7.93(d, /=8.5 Hz, IH), 7.69(m, 2H), 7.48-7.24(m, 4H), 5.52(d, /=6.9 Hz, IH), 4.80(t, /=6.86 Hz, IH), 1.78-1.63(m, 2H), 1.46(t, /=6.7 Hz, IH), 1.39(m, 3H), 0.97(m, 6H)
Compound No. 126: [2-(3-Chlorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.59(t, /=3.3 Hz, 2H), 7.93(d, /=8.3 Hz, IH), 7.69(m, IH), 7.58(m, IH), 7.49(m, 3H), 7.38(m, IH), 7.24(m, IH), 7.12(m, 2H), 7.11 (m, IH), 5.92(s, IH), 3.95(m, 2H), 3.02(t, /= 7.1 Hz, 2H)
Compound No. 127: [2-(2,4-Dichlorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.57(t, /=3.6 Hz, 2H), 7.92(d, /=8.2 Hz, IH), 7.70(m, IH), 7.59(d, /=8.1 Hz, IH), 7.47(m, 2H), 7.37(m, 2H), 7.18(m, 2H), 5.81(s, IH), 4.04(m, 2H), 3.23(, /=6.8 Hz, 2H) Compound No. 128: [2-(3,4-Difluorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.50(t, /=4.0 Hz, 2H), 7.93(d, /=8.6 Hz, IH), 7.72(m, 2H), 7.41(m, 4H), 7.22(t, /=8.8 Hz, IH), 7.07(m, 2H), 6.11(s, IH), 4.91(d, /=5.5 Hz, 2H)
Compound No. 129: (2-Phenylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.58(t, /=3.5 Hz, 2H), 7.96(d, /=8.4 Hz, 2H), 7.78(d, /=8.3 Hz, IH), 7.67(t, /=7.6 Hz, IH), 7.47(m, 3H), 7.36(t, /=7.6 Hz, IH), 6.73(s, 2H), 6.43(s, IH), 4.91(d, /=5.2 Hz, 2H), 3.86(d, /=6.6 Hz, 2H), 3.82(m, 9H)
Compound No.130: (3-Methylbutyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.57(t, /=3.4 Hz, 2H), 7.92(d, /=8.3 Hz, IH), 7.68(m, 2H), 7.46(m, 3H), 7.37(t, /=7.5 Hz, IH), 5.76(s, IH), 3.80(m, 2H), 1.76(m, IH), 1.65(m, 2H), 0.99(m, 6H)
Compound No. 131: (2-Cyclohex-l-enylethyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.57(t, /=3.4 Hz, 2H), 7.92(d, /=8.3 Hz, IH), 7.69(t, J=7.7 Hz, IH), 7.61 (d, /=8.1 Hz, IH), 7.49(m, 3H), 7.38(t, /=7.4 Hz, IH), 5.82(s, IH), 5.61(1H), 3.83(m, 2H), 2.39(t, /=6.6 Hz, 2H), 2.03(m, 4H), 1.62(m, 4H)
Compound No. 132: Cyclohexylmethyl-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.56(t, /=3.1 Hz, 2H), 7.92(d, /=8.7 Hz, IH), 7.69(t, /=6.1 Hz, 2H), 7.49(m, 4H), 5.85(s, IH), 3.64(t, /=6.1 Hz, 2H), 1.88-1.70(m, 6H), 1.29-1.05(m, 5H)
Compound No. 133: (2,2-Diphenylethyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.63(t, /=3.8 Hz, 2H), 7.93(d, /=8.4 Hz, IH), 7.67(t, /=7.5 Hz, IH), 7.51(m, 3H), 7.29(m, 12H), 5.73(s, IH), 4.56(t, J=7.7 Hz, IH), 4.42(t, /=6.5 Hz, 2H) Compound No. 134: (2,4-Difluorobenzyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.55(t, /=3.9 Hz, 2H), 7.93(d, /=8.4 Hz, IH), 7.71(m, 2H), 7.49(m, 5H), 6.80(m, 2H), 6.24(s, IH), 5.00(d, /=5.6 Hz, 2H)
Compound No. 135: (2,5-Difluorobenzyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.52(t, /=3.6 Hz, 2H), 7.93(d, /=8.4 Hz, IH), 7.72(t, /=7.9 Hz, 2H), 7.41 (m, 4H), 7.18(m, IH), 7.00(m, IH), 6.92(t, /=3.9 Hz, IH), 6.20(s, IH), 5.00(d, /=5.6 Hz, 2H)
Compound No. 136: (3,3-Diphenylpropyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.51 (m, 2H), 7.92(d, /=8.4 Hz, IH), 7.67(m, IH), 7.43(m, 3H), 7.34-7.20(m, 12H), 5.73(s, IH), 4.09(t, J=7.7 Hz, IH), 2.53(m, 2H)
Compound No. 137: [2-(4-Bromophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.57(t, 2.8 Hz, 2H), 7.92(d, /=8.4 Hz, IH), 7.71(m, IH), 7.50(m, 7H), 7.20(m, 2H), 5.75(s, IH), 3.98(m, 2H), 3.04(t, /=6.7 Hz, 2H)
Compound No. 138: Butylmethyl-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.55(dd,
Figure imgf000054_0001
Hz, 2H), 7.99-7.91(m, 2H), 7.67(m, IH), 7.46(m, 3H), 7.34(m, IH), 3.80(t, /=7.8 Hz, 2H), 3.41(s, 3H), 1.86(m, 2H), 1.43(m, 2H), 1.00(t, 3H, /=7.5 Hz)
Compound No. 139: (2-Phenylquinazolino-4-yl)-(4-trifluoromethylbenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.50(m, 2H), 7.96(d, /=8.1 Hz, IH), 7.75(m, 2H), 7.59(m, 4H), 7.46(m, 4H), 6.06(br, IH), 5.07(d, /=6.0 Hz, 2H)
Compound No. 140: [2-(2-Fluorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.60(t, /=3.5 Hz, 2H), 7.93(d, /=8.3 Hz, IH), 7.69(, /=7.6 Hzt, IH), 7.60(d, /=8.1 Hz, IH), 7.49(m, 3H), 7.36(t, /=7.5 Hz, IH), 7.24(t, /=7.2 Hz, 2H), 7.06(t, /=9.0 Hz, 2H), 4.00(m, 2H), 3.14(t, /=6.7 Hz, 2H) Compound No. 141: (2-Phenylquinazolino-4-yl)-pyridino-4-ylmethylamine
Η NMR(CDCl3, 300 MHz) δ 8.51(m, 2H), 8.42(t, /=3.4 Hz, 2H), 8.00(d, /=8.4 Hz, IH), 7.89(d, /=8.1 Hz, IH), 7.71(t, /=7.6 Hz, IH), 7.43(m, 4H), 7.31(m, 2H), 4.99(d, /=5.5 Hz, 2H)
Compound No. 142: (2-Phenylquinazolino-4-yl)-pyridino-2-ylmethylamine iH NMR(CDCl3, 300 MHz) δ 8.60(m, 2H), 7.91(m, 2H), 7.69(m, 3H), 7.43(m, 5H),
7.25(m, IH), 5.00(d, /=4.3 Hz, 2H)
Compound No. 143: (2,3-Dimethylcyclohexyl)-(2-phenylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.53(t, /=3.5 Hz, 2H), 7.92 (d, /=8.3 Hz, IH), 7.69(m, 2H), 7.41(m, 4H), 5.76(m, IH), 4.56(m, IH), 1.94-1.46(m, 7H), 1.00(m, 5H), 0.86(d, /=7.1 Hz, IH)
Compound No. 144: (2,4-Dimethoxybenzyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.60(m, 2H), 7.90(d, /=8.4 Hz, IH), 7.72-7.63(m, 2H), 7.48(m, 3H), 7.38(m, 2H), 6.51(d, IH, /=2.1 Hz), 6.45(dd, /2=81 Hz, J2=IA Hz, IH), 6.16(br, IH), 4.94(d, /=5.4 Hz, 2H), 3.90(s, 3H), 3.79(s, 3H)
Compound No. 145: (3-Chlorobenzyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.51(m, 2H), 7.92(d, /=8.8 Hz, IH), 7.71(m, 2H), 7.45(m, 5H), 7.27(m, 3H), 5.13(s, IH), 4.92(d, /=5.5 Hz, 2H)
Compound No. 146: l-Phenyl-2-(2-phenylquinazolino-4-ylamino)-ethanol 1H NMR(DMSOd6, 300 MHz) δ 8.49(m, 2H), 8.25(dH, /=8.3 Hz, 1), 7.74(m, 2H), 7.50-7.31(m, 7H), 7.23(t, /=7.1 Hz, IH), 5.62(d, /=4.3 Hz, IH), 5.05(m, IH), 4.01-3.90(m, 2H), 3.57(m, IH), 3.28(m, 2H)
Compound No. 147: (2,5-Dimethoxybenzyl)-(2-phenylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 8.60(dd, /2=8.1 Hz, /2=2.1 Hz, 2H), 7.91(d, /=8.4 Hz, IH), 7.67(m, 2H), 7.52-7.36(m, 4H), 7.10(d, /=3.0 Hz, IH), 6.85(d, /=9.0 Hz, IH), 6.78(dd, Hz, /2=3.0 Hz, IH), 6.272(br, IH), 4.99(d, /=6.0 Hz, 2H), 3.89(s, 3H), 3.71(s, 3H)
Compound No. 148: (4-Bromobenzyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.54(t, /=3.6 Hz, 2H), 7.92(d, /=8.3 Hz, IH), 7.71(t, /=6.6 Hz, IH), 7.44(m, 6H), 7.26(t, /=7.0 Hz, 2H), 6.09(s, IH), 4.91 (d, /=5.5 Hz, 2H)
Compound No. 149: [2-(3,4-Dichlorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.57(m, 2H), 7.94(d, /=8.4 Hz, IH), 7.74(m, IH), 7.59(d, /=7.8 Hz, IH), 7.55-7.37(m, 6H), 7.10(dd, /3=8.4 Hz, J2=I.8 Hz, IH), 5.75(br, IH), 4.03(q, /=7.2 Hz, 2H), 3.08(t, /=7.2 Hz, 2H)
Compound No. 150: l-[3-(2-Phenylquinazolino-4-ylamino)-propyl]-pyrrolidino-2-one 1H NMR(CDCl3, 300 MHz) δ 8.55(m, 2H), 8.00(d, /=8.1 Hz, IH), 7.89(d, /=8.6 Hz, IH), 7.69(d, /=7.3 Hz, IH), 7.59(s, IH), 7.44(m, 4H), 3.76(m, 2H), 3.41 (m, 4H), 2.45(t, /=8.1 Hz, 2H), 2.06(m, 2H), 1.87(m, 2H)
Compound No. 151: [2-(2-Chlorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.59(m, 2H), 7.92(d, /=8.4 Hz, IH), 7.71 (d, /=7.3 Hz, IH), 7.63(d, /=8.1 Hz, IH), 7.48(m, 3H), 7.37(t, /=7.2 Hz, 2H), 7.25(t, /=3.5 Hz, IH), 7.17(t, /=4.5 Hz, 2H), 5.99(s, IH), 4.05(m, 2H), 3.24(t, /=6.9 Hz, 2H)
Compound No.152: 2-[2-(2-Phenylquinazolino-4-ylamino)-ethyl]-phenol 1H NMR(DMSOd6, 300 MHz) δ 9.18(s, IH), 8.46(m, 3H), 8.19(d, /=8.1 Hz, IH), 7.73(m, 2H),7.47(m, 4H), 7.07(d, /=8.2 Hz, 2H), 6.66(d, /=8.2 Hz, 2H), 4.12(s, IH), 3.77(m, 2H), 2,91(t, /=7.4 Hz, 2H)
Compound No. 153: (3-Bromobenzyl)-(2-phenylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.52(m, 2H), 7.92(d, /=8.5 Hz, IH), 7.71(t, /=3.1 Hz, 2H), 7.56(s, IH), 7.45(m, 6H), 7.14(m, IH), 6.13(s, IH), 4.91(d, /=5.3 Hz, 2H) Compound No, 154: (2,6-Dimethoxybenzyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDC13/ 300 MHz) δ 8.70(m, 2H), 7.92(d, /=8.4 Hz, IH), 7.84(m, 2H), 7.51 (m, 3H), 7.46(m, IH), 7.23(m, IH), 6.58(d, /=8.4 Hz, 2H), 6.38(s, IH), 5.13(d, /=5.3 Hz, 2H), 3.88(s, 6H)
Compound No. 155: (2-Bromobenzyl)-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.56(t, /=3.8 Hz, 2H), 7.92(d, /=8.4 Hz, IH), 7.72(m, 2H), 7.50(m, 5H), 7.46(m, IH), 7.24(m, IH), 6.34(s, IH), 5.06(d, /=5.8 Hz, 2H)
Compound No. 156: (3-Morpholino-4-ylpropyl)-(2-phenylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 8.55(m, 2H), 7.89(d, /=8.3 Hz, IH), 7.78(d, /=8.1 Hz, IH), 7.68(m, 3H), 7.45(m, 3H), 3.81 (m, 6H), 2.57(m, 7H), 1.89(m, 2H)
Compound No.157: 2-[Butyl-(2-phenylquinazolino-4-yl)-amino]-ethanol
1H NMR(CDCl3, 300 MHz) δ 8.53(m, 2H), 8.18-7.91 (m,2H), 7.69(m, IH), 7.45(m, 4H), 4.85(t, /=5.2 Hz, IH), 4.01(s, 2H), 3.67(t, /=8.0 Hz, IH), 3.21(t, /=5.2 Hz, IH), 2.74(t, /=7.3 Hz, IH), 1.95(m, IH), 1.60(m, IH), 1.03-0.87(m, 3H)
Compound No. 158:
[2-(4-Methylpiperazino-l-yl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.51(t, /=3.9 Hz, 2H), 8.03(s, IH), 7.92(d, /=8.3 Hz, IH), 7.84(d, /=8.8 Hz, IH), 7.65(t, /=7.6 Hz, IH), 7.39(m, 4H), 5.84(br s, IH), 3.83(m, 2H), 2.98(m, 4H), 2.66(m, 10H), 2.33(s, 3H), 1.05(m, 2H), 1.29(m, 6H)
Compound No. 159: Cyclopentylmethyl-(2-phenylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 8.84(m, 2H), 7.98(t, /=8.1 Hz, 2H), 7.68(t, J=7.7 Hz, IH), 7.47(m, 3H), 7.35(t, /=7.6 Hz, IH), 4.99(t, J=7.7 Hz, IH), 3.26(s, 3H), 2.08(m, 2H), 1.71(m, 6H)
Compound No. 160: (2-Phenylquinazolino-4-yl)-(2-piperazino-l-ylethyl)-amine 1H NMR(CDC13/ 300 MHz) δ 8.54(Hi, 2H), 7.97(m, 2H), 7.74(In, IH), 7.46(m, 4H), 4.08(m, 4H), 3.06(m, 4H)
Compound No. 161: O-(4-Nitrobenzyl)-N-(2-phenylquinazolino-4-yl)-hydroxylamine . iH NMR(CDCl3, 300 MHz) δ 8.21(m, 3H), 7.97(m, 2H), 7.88(d, /=7.9 Hz, IH), 7.57(m, 8H), 7.28(m, IH)
Compound No. 162: (4-Chlorophenyl)-(2-phenylquinazolino-4-yl)-amine 1H NMR(DMSO-d6, 300 MHz) δ 9.92(s, IH), 8.53(d, /=8.3 Hz, IH), 8.41(t, /=3.9 Hz, 2H), 7.98(d, /=8.8 Hz, 2H), 7.85(d, /=3.8 Hz, 2H), 7.62-7.48(m, 6H)
Compound No. 163: Benzyl-(2-methylquinazolino-4-yl)-amine
1H NMR(DMSO-d6, 300 MHz) δ 9.69(s, IH), 8.47(d, /=8.1 Hz, IH), 8.20(t, /=7.2 Hz, 2H), 7.81(d, /=3.6 Hz, 2H), 7.55(t, /= 4.1 Hz, IH), 7.46-7.23(m, 7H), 2.22(s, 3H)
Compound No. 164: (3-Methoxybenzyl)-(2-methylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.77-7.63(m, 3H), 7.35(t, /=7.6 Hz, IH), 7.24(t, /=6.3 Hz, IH), 6.96(m, 2H), 6.82(m, IH), 6.32(s, IH), 4.84(m, 2H), 3.74(s, 3H), 2.62(s, 3H)
Compound No. 165: (4-Methoxybenzyl)-(2-methylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.74(d, /=8.2 Hz, IH), 7.67(m, 2H), 7.35(m, 3H), 6.86(d,
/=8.6 Hz, 2H), 6.12(s, IH), 4.77(d, /=4.0 Hz, 2H), 3.78(s, 3H), 2.64(s, 3H)
Compound No. 166: (2-Methylquinazolino-4-yl)-(3-tπfluoromethylbenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.82(m, 2H), 7.64(m, 2H), 7.52(m, IH), 7.35(m, 2H), 6.73(s, IH), 4.93(s, 2H), 2.63(s, 3H)
Compound No. 167: (2-Methylquinazolino-4-yl)-phenethylamine 1H NMR(CDCl3, 300 MHz) δ 7.77(d, /=8.3 Hz, IH), 7.60(m, 2H), 7.33(m, 3H), 7.24(m, 3H), 6.12(br, IH), 3.94(m, 2H), 3.01(t, /=6.9 Hz, 2H), 2.65(s, 3H) Compound No. 168: (2-Methylquinazolino-4-yl)-(4-phenylbutyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.70(Hi, 3H), 7.36(t, /=7.5 Hz, IH), 7.26(m, 2H), 7,17(m, 3H), 6.12(br, IH), 3.69(d, /=5.3 Hz, 2H), 2.68(t, /=6.8 Hz, 2H), 2.62(s, 3H), 1.75(t, /=3.4 Hz, 4H)
Compound No. 169: (2-Methylquinazolino-4-yl)-naphthaleno-l-ylmethylamine
1H NMR(CDCl3, 300 MHz) δ 8.07(m, IH), 7.86(m, 3H), 7.64(t, /=7.4 Hz, 2H), 7.55-7.42(m, 4H), 7.24(m, 2H), 6.22(br s, IH), 5.27(s, 2H), 2.70(s, 3H)
Compound No. 170:
Benzo[l,3]dioxol-5-ylmethyl-(2-methylquinazolino-4-yl)-amine iH NMR(CDCl3, 300 MHz) δ 7.74(m, 3H), 7.35(t, /=7.5 Hz, IH), 6.84(t, /=6.5 Hz, 2H),
6.74(d, /=7.8 Hz, IH), 6.24(br, IH), 5.92(s, 2H), 4.76(d, /=4.1 Hz, 2H), 2.65(s, 3H)
Compound No. 171: (3-Fluorobenzyl)-(2-methylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 7.79(m, 2H), 7.66(t, ]=7.7 Hz, IH), 7.37(t, /=7.5 Hz, IH), 7.26(t, /=3.9 Hz, IH), 7.14(m, 2H), 6.96 (m, IH), 6.51 (s, IH), 4.87(d, /=3.3 Hz, 2H), 2.63(s, 3H)
Compound No. 172: [2-(3-Fluorophenyl)-ethyl]-(2-methylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.78(d, /=8.5 Hz, IH), 7.65(t, /=7.3 Hz, 2H), 7.35(t, /=7.8 Hz, IH), 7.27(m, IH), 6.94(m, 3H), 6.24(br, IH), 3.93(m, 2H), 3.02(t, /=6.99 Hz, 2H), 2.65 (s, 3H)
Compound No. 173: 2-[2-(2-Methylquinazolino-4-ylamino)-ethoxy]-ethanol m NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.1 Hz, IH), 7.72(d, /=10.7 Hz, IH), 7.61(t,
/=7.1 Hz, IH), 7.30(t, /=6.5 Hz, IH), 6.96(br, IH), 3.82(m, 6H), 3.68(m, 2H), 2.60(s, 3H)
Compound No. 174: 2-(2-Methylquinazolino-4-ylamino)-ethanol
1H NMR(CDCl3, 300 MHz) δ 8.27(d, /=8.2 Hz, IH), 7.88(t, /=7.2 Hz, IH), 7.79(t, /=7.5 Hz, IH), 7.51 (m, IH), 3.93(m, 4H), 2.70(s, 3H)
Compound No. 175: Benzyl-(2-isopropylquinazolino-4-yl)-amine m NMR(CDCl3, 300 MHz) δ 7.82(d, /=7.8 Hz, IH), 7.71-7.63(m, 2H), 7.45-7.26(m, 6H), 5.88(br, IH), 4.90(d, /=5.4 Hz, 2H), 3.12(m, IH), 1.37(d, /=6.6 Hz, 6H)
Compound No. 176: (2-Isopropylquinazolino-4-yl)-(3-methoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.82(d, /=8.4 Hz, IH), 7.75(m, IH), 7.66(m, IH), 7.38(t, /=7.9 Hz, IH), 7.25(t, ]=7.7 Hz, IH), 7.00(m, 2H), 6.80(m, IH), 4.88(d, /=5.0 Hz, 2H), 3.77(s, 3H), 3.13(m, IH), 1.37(d, /=6.8 Hz, 6H)
Compound No. 177: (2-Isopropylquinazolino-4-yl)-(4-methoxybenzyl)-amine Η NMR(CDCl3, 300 MHz) δ 7.82(d, /=8.1 Hz, IH), 7.70-7.61(m, 2H), 7.35(m, 3H), 6.89(d, /=8.7 Hz, 2H), 5.86(br, IH), 4.83(d, /=5.4 Hz, 2H), 3.81(s, 3H), 3.14(m, IH), 1.38(d, /=6.6 Hz, 6H)
Compound No.178: (2-Isopropylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.87(m, 2H), 7.66(m, 3H), 7.51 (d, /=7.8 Hz, IH), 7.39(m, 2H), 4.96(d, /=5.0 Hz, 2H), 3.17 (m, IH), 1.33(d, /=6.8 Hz, 6H)
Compound No. 179: (2-Isopropylquinazolino-4-yl)-phenethylamine
Η NMR(CDCl3, 300 MHz) δ 7.82(d, /=8.1 Hz, IH), 7.67(m, IH), 7.55(d, /=7.8 Hz, IH), 7.38-7.21(m, 6H), 5.84(br, IH), 3.95(q, /=6.9 Hz, 2H), 3.16(m, IH), 3.05(t, /=6.9 Hz, 2H), 1.40(d, /=6.9 Hz, 6H)
Compound No. 180: (2-Isopropylquinazolino-4-yl)-(4-phenylbutyl)-amine iH NMR(CDCl3, 300 MHz) δ 7.83(d, /=7.9 Hz, IH), 7.75(d, J=7.7 Hz, IH), 7.65(t, /=7.6 Hz, IH), 7.35(t, /=7.6 Hz, IH), 7.25(m, 6H), 3.73(d, /=5.5 Hz, 2H), 3.14(m, IH), 2.68(d, /=6.5 Hz, 2H), 1.77(m, 4H), 1.36(d, /=6.8 Hz, 6H) Compound No. 181: (2-Isopropylquinazolino-4-yl)-naphthaleno-l-ylmethylamine
1H NMR(CDCl3, 300 MHz) δ 8.18(m, IH), 7.93-7.81 (m, 3H), 7.68-7.43(m, 6H), 7.30(m, IH), 5.85(br, IH), 5.35(d, /=5.1 Hz, 2H), 3.20(m, IH), 1.44(d, /=6.6 Hz, 6H)
Compound No. 182:
Benzo[l,3]dioxol-5-ylmethyl-(2-isopropylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.81(d, /=7.8 Hz, IH), 7.70-7.63(m, 2H), 7.66(m, IH), 6.94-6.87(m, 2H), 6.78(d, IH, /=7.8 Hz), 5.94(s, 2H), 5.90(br, IH), 4.80(d, /=5.4 Hz, 2H), 3.13(m, IH), 1.38(d, /=6.6 Hz, 6H)
Compound No. 183: (3-Fluorobenzyl)-(2-isopropylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.82(t, /=5.6 Hz, IH), 7.67(t, J=7.7 Hz, IH), 7.37(t, /=7.5 Hz, IH), 7.28-7.12(m, 3H), 6.95(t, /=7.3 Hz, IH), 6.34(br, IH), 4.89(d, /=3.5 Hz, 2H), 3.14(m, IH), 1.33(d, /=6.8 Hz, 6H)
Compound No. 184:
[2-(3-Fluorophenyl)-ethyl]-(2-isopropylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.7 Hz, IH), 7.66(t, /=7.2 Hz, 2H), 7.38-7.23(m,
2H), 6.89(m, 3H), 6.32(br, IH), 3.94(m, IH), 3.17(t, /=6.8 Hz, IH), 3.06(m, IH), 1.39(d, /=6.8 Hz, 6H)
Compound No. 185: 2-[2-(2-Isopropylquinazolino-4-ylamino)-ethoxy]-ethanol
1H NMR(MeOD, 300 MHz) δ 7.78(t, /=8.1 Hz, 2H), 7.61 (t, /=7.6 Hz, IH), 7.29(m, IH), 6.78(br, IH), 3.89(d, /=4.4 Hz, 2H), 3.80(m, 4H), 3.66(t, /=4.4 Hz, 2H), 3.11(m, IH), 1.33(d, /=6.8 Hz, 6H)
Compound No. 186: 2-(2-Isopropylquinazolino-4-ylamino)-ethanol
1H NMR(CDCl3+MeOD, 300 MHz) δ 7.85(d, /=8.2 Hz, IH), 7.64(m, 2H), 7.31(m, IH), 3.78(m, 4H), 3.02(m, IH), 1.27(d, /=6.8 Hz, 6H)
Compound No. 187: Benzyl-(2-£er£-butylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.90(d, /=8.2 Hz, IH), 7.12(d, /=5.3 Hz, IH), 7.53(t, /=7.6 Hz, IH), 7.36-7.25(m, 6H), 6.22(br, IH), 4.90(d, /=5.3 Hz, 2H), 1.44(s, 9H)
Compound No. 188: (2-ter£-Butylquinazolino-4-yl)-(3-methoxybenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.88(d, /=8.1 Hz, IH), 7.66(m, 2H), 7.44-7.23(m, 3H, 6.99(d, /=8.0 Hz, 2H), 6.84(t, /=4.2 Hz, IH), 6.16(br, IH), 4.87(d, /=5.3 Hz, 2H), 3.78(s, 3H), 1.44(s, 9H)
Compound No. 189: (2-fert-Butylquinazolino-4-yl)-(4-methoxybenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.86(m, IH), 7.64(m, 2H), 7.32(m, 3H), 6.99(d, /=8.7 Hz, IH), 6.86(d, /=5.6 Hz, 2H), 6.19(br, IH), 4.82 (d, /=5.4 Hz, 2H), 3.80(s, 3H), 1.44(s, 9H)
Compound No. 190: (2-tert-Butylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.91(d, /=8.3 Hz, IH), 7.79-7.61(m, 4H), 7.53(d, /=7.9 Hz, IH), 7.46-7.34(m, 2H), 6.21(br, IH), 4.95(d, /=5.3 Hz, 2H), 1.45(s, 9H)
Compound No. 191: (2-£er£-Butylquinazolino-4-yl)-phenethylamine
1H NMR(CDCl3, 300 MHz) δ 7.85(d, /=8.4 Hz, IH), 7.66(t, /=7.5 Hz, IH), 7.53(d, /=7.8 Hz, IH), 7.31(m, 6H), 5.72(br s, IH), 3.93(q, /=6.9 Hz, 2H), 3.05(t, /=7.2 Hz, 2H), 1.48(s, 9H)
Compound No. 192: (2-fer£-Butylquinazolino-4-yl)-(4-phenylbutyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.87(d, /=8.3 Hz, IH), 7.65(m, 2H), 7.37-7.25(m, 3H), 7.19(m, 3H), 5.98(br, IH), 3.71 (d, /=5.66 Hz, 2H), 2.68(d, /=6.5 Hz, 2H), 1.44(m, 4H), 1.44(s, 9H)
Compound No. 193: (2-ter£-Butylquinazolino-4-yl)-naphthaleno-l-ylmethylamine
1H NMR(CDCl3, 300 MHz) δ 8.20(d, /=9.4 Hz, IH), 7.89(m, 3H), 7.61 (m, 3H), 7.50(m, 3H), 6.10(br, IH), 5.35(d, /=5.1 Hz, 2H), 1.52(s, 9H) Compound No. 194: Benzo[l,3]dioxol-5-ylmethyl-(2-ter£-butylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.89(d, /=8.3Hz, IH), 7.66(m, 2H), 7.34(t, /=7.5 Hz, IH), 6.91(m, 2H), 6.76(d, /=7.9 Hz, IH), 6.21(br, IH), 5.93(s, 2H), 4.80(d, /=6.2 Hz, 2H), 1.44(s, 9H)
Compound No. 195: (2-tert-Butylquinazolino-4-yl)-(3-fluorobenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.89(d, /=8.3 Hz, IH), 7.69(m, 2H), 7.35(m, IH), 7.28(m, IH), 7.14(m, 2H), 6.94(d, /=5.4 Hz, IH), 6.24(br, IH), 4.99(d, /=6.2Hz, 2H), 1.45(s, 9H)
Compound No. 196:
(2-fer£-Butylquinazolino-4-yl)-[2-(3-fluorophenyl)-ethyl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.89(d, /=8.3 Hz, IH), 7.68(m, 2H), 7.33(m, IH), 7.25(m,
IH), 6.98(m, 2H), 6.01(br, IH), 3.93(m, 2H), 3.06(t, /=2.6 Hz, 2H), 1.45(s, 9H)
Compound No. 197: 2-[2-(2-£er£-Butylquinazolino-4-ylamino)-ethoxy]-ethanol 1H NMR(CDCl3, 300 MHz) δ 7.85(d, /=8.3 Hz, IH), 7.71(d, /=8.2 Hz, IH), 7.63(t, /=7.8 Hz, IH), 7.33(t, /=7.5 Hz, IH), 6.33(br, IH), 3.90(d, /=4.1 Hz, 2H), 3.80(t, /=4.6 Hz, 4H), 3.65(t, /=4.6 Hz, 2H), 1.44(s, 9H)
Compound No. 198: 2-(2-ter£-Butylquinazolino-4-ylamino)-ethanol
1H NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.0 Hz, IH), 7.69(t, /=7.6 Hz, 2H), 7.38(t, /=7.6
Hz, IH), 6.14(br, IH), 4.59(s, IH), 3.93-3.83(m, 4H), 1.44(s, 9H)
Compound No. 199: Benzyl-(2-cyclohexylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.0 Hz, IH), 7.68(m, 2H), 7.43(d, /=7.5 Hz, 2H), 7.31(m, 4H), 6.26(br, IH), 4.90((d, /=5.2 Hz, 2H), 2.82(t, /=11.5 Hz, IH), 1.97 (m, 2H), 1.73(m, 5H), 1.33(m, 3H)
Compound No. 200: (2-Cyclohexylquinazolino-4-yl)-(3-methoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.84(d, /=8.3 Hz, IH), 7.73(d, /=8.2 Hz, IH), 7.65(t, /=7.3 Hz, IH), 7.34(t, /=7.6 Hz, IH), 7.26(t, /=7.8 Hz, IH), 7.01 (d, /=7.3 Hz, 2H), 6.84(t, /=4.5 Hz, IH), 6.43(br, IH), 4.88(d, /=6.8 Hz, 2H), 3.78(s, 3H), 2.84(m, IH), 2.02(m, 2H), 1.85-1.66(m, 5H), 1.48-1.28(m, 3H)
Compound No. 201: (2-Cyclohexylquinazolino-4-yl)-(4-methoxybenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.84(d, /=8.3 Hz, IH), 7.73(d, /=8.2 Hz, IH), 7.64(t, /=7.4 Hz, IH), 7.36(m, 3H), 6.87(d, /=8.5 Hz, 2H), 6.48n (br, IH), 4.83(d, /=6.8 Hz, 2H), 3.80(s, 3H), 2.85(m, IH), 2.02(m, 2H), 2.04-1.69(m, 5H), 1.49-1.25(m, 3H)
Compound No. 202:
(2-Cyclohexylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.83(m, 2H), 7.78(m, IH), 7.64(m, 2H), 7.53(m, IH), 7.40(m, 2H), 6.67(br, IH), 4.93(d, /=5.0 Hz, 2H), 2.80 (m, IH), 1.90(m, 2H), 1.84-1.60(m, 5H), 1.45-1.25(m, 3H)
Compound No. 203: (2-Cyclohexylquinazolino-4-yl)-phenethylamine 1H NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.3 Hz, IH), 7.65(m, 2H), 7.28(m, 6H), 6.06(br, IH), 3.95(m, 2H), 3.05(t, /=7.0 Hz, 2H), 2.83(m, IH), 2.04(m, 2H), 1.88-1.71(m, 5H), 1.50-1.35(m, 3H)
Compound No. 204: (2-Cyclohexylquinazolino-4-yl)-(4-phenylbutyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.3 Hz, IH), 7.69(m, 2H), 7.37-7.17(m, 7H), 6.12(br, IH), 3.72(d, /=5.6 Hz, 2H), 2.78(t, /= 11.1 Hz, IH), 2.70(t, /=6.7 Hz, 2H), 2.00(m, 2H), 1.86-1.68(m, 9H), 1.44-1.28(m, 3H)
Compound No. 205:
(2-Cyclohexylquinazolino-4-yl)-naphthaleno-l-ylmethylamine
1H NMR(CDCl3, 300 MHz) δ 8.20 (d, /=9.4 Hz, IH), 7.87(m, 3H), 7.62(m, 3H), 7.50(m,
3H), 7.30(m, IH), 6.34(br, IH), 5.35(d, /=4.9 Hz, 2H), 2.92(m, IH), 2.08(m, 2H), 1.86-1.73(m, 5H), 1.47-1.25(m, 3H) Compound No. 206: Benzo[l,3]dioxol-5-ylmethyl-(2-cyclohexylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.4 Hz, IH), 7.73(d, /=8.2 Hz, IH), 7.65(t, /=7.5 Hz, 2H), 6.91 (m, 2H), 6.76(d, /=7.9 Hz, IH), 6.34(br, IH), 5.93(s, 2H), 4.80(d, /=5.2 Hz, 2H), 2.84(m, IH), 2.00(m, 2H), 1.86-1.68(m, 5H), 1.48-1.25(m, 3H)
Compound No. 207: (2-Cyclohexylquinazolino-4-yl)-(3-f luorobenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.80(m, IH), 7.66(t, /=7.6 Hz, IH), 7.35(m, IH), 7.27(m, 2H), 7.16(m, 2H), 6.95(d, /=8.4 Hz, IH), 6.47(br, IH), 4.90(d, /=5.2 Hz, 2H), 2.83(m, IH), 1.99(m, 2H), 1.84-1.63(m, 5H), 1.46-1.25(m, 3H)
Compound No. 208: (2-Cyclohexylquinazolino-4-yl)-[2-(3-fluorophenyl)-ethyl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.3 Hz, IH), 7.65(t, J=7.7 Hz, 2H), 7.30(m, 2H), 6.99(m, 3H), 6.15(br, IH), 3.94(m, 2H), 3.05(t, /=7.1 Hz, 2H), 2.83(m, IH), 2.00(m, 2H), 1.88-1.69(m, 5H), 1.46-1.25(m, 3H)
Compound No. 209: 2-[2-(2-Cyclohexylquinazolino-4-ylamino)-ethoxy]-ethanol
1H NMR(CDCl3, 300 MHz) δ 7.75(m, 2H), 7.62(t, /=7.6 Hz, IH), 7.31 (t, J=7.5 Hz, IH), 6.48(br, IH), 3.90(m, 2H), 3.80(m, 4H), 3.36(m, 2H), 2.78(m, IH), 1.90(m, 2H), 1.85-1.62(m, 5H), 1.47-1.27(m, 3H)
Compound No. 210: 2-(2-Cyclohexylquinazolino-4-ylamino)-ethanol
1H NMR(CDCl3, 300 MHz) δ 7.80(d, /=8.4 Hz, IH), 7.69(m, 2H), 7.40(t, /=7.0 Hz, IH), 6.20(br, IH), 5.08(br, IH), 3.93(m, 2H), 3.85(m, 2H), 2.77(m, IH), 1.97(m, 2H), 1.86-1.66(m, 5H), 1.47-1.25(m, 3H)
Compound No. 211: Benzyl-(2-benzylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.82(d, /=8.4 Hz, IH), 7.71 (m, 2H), 7.47(m, 2H), 7.29(m, 9H), 5.94(br, IH), 4.82(d, /=5.5 Hz, 2H), 4.19(s, 2H) Compound No. 212: (2-Benzylquinazolino-4-yl)-(3-methoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.82(d, /=8.1 Hzx IH), 7.69(t, /=6.9 Hz, IH), 7.60(d, /=8.1 Hz, IH), 7.45(d, /=7.2 Hz, 2H), 7.37(t, /=7.2 Hz, IH), 7.25(m, 4H), 6.85(m, 3H), 5.87(br, IH), 4.80(d, /=5.4 Hz, 2H), 4.19(s, 2H), 3.76(s, 3H)
Compound No. 213: (2-Benzylquinazolino-4-yl)-(4-methoxybenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.81(d, /=8.4 Hz, IH), 7.67(t, J=7.7 Hz, IH), 7.59(d, /=8.1 Hz, IH), 7.46(d, /=7.3 Hz, 2H), 7.35(t, /=7.6 Hz, IH), 7.23(m, 5H), 6.83(d, /=8.5 Hz, 2H), 5.87(br, IH), 4.74(d, /=5.3 Hz, 2H), 4.20(s, 2H), 3.80(s, 3H)
Compound No. 214: (2-Benzylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.80(m, 2H), 7.66(m, 2H), 7.49(m, 2H), 7.37(m, 4H), 7.20(m, 2H), 6.56(br, IH), 4.86(d, /=6.3 Hz, 2H), 4.18(s, 2H)
Compound No. 215: (2-Benzylquinazolino-4-yl)-phenethylamine
1H NMR(CDCl3, 300 MHz) δ 7.82(d, /=8.3 Hz, IH), 7.61 (m, 4H), 7.34-7.17(m, 6H), 6.12(br, IH), 4.21(s, 2H), 3.88(m, 2H), 2.94(t, /=7.2 Hz, 2H)
Compound No. 216: (2-Benzylquinazolino-4-yl)-(4-phenylbutyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.81(d, / = 8.3 Hz, IH), 7.63(t, / = 7.8 Hz, 2H), 7.46(d, / = 7.3 Hz, 2H), 7.33(m, 5H), 7.24(m, 4H), 5.98(br, IH), 4.18(s, 2H), 3.62(d, / = 5.7 Hz, 2H), 2.64(t, / = 5.1 Hz, 2H), 1.69(m, 2H)
Compound No. 217: (2-Benzylquinazolino-4-yl)-naphthaleno-l-ylmethylamine 1H NMR(CDCl3, 300 MHz) δ 8.01(d, /=8.3 Hz, IH), 7.85(m, 3H), 7.54(m, 2H), 7.52-7.39(m, 6H), 7.25(m, 4H), 6.32(br, IH), 5.28(d, /=5.0 Hz, 2H), 4.25(s, 2H)
Compound No. 218: Benzo[l,3]dioxol-5-ylmethyl-(2-benzylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.82(d, /=8.4 Hz, IH), 7.68(m, IH), 7.61 (d, /=8.1 Hz, IH), 7.46(d, /=7.2 Hz, 2H), 7.36(m, IH), 7.25(m, 2H), 7.18(m, IH), 6.81-6.71(m, 3H), 5.94(s, 2H), 5.89(br, IH), 4.71 (d, /=5.7 Hz, 2H), 4.20(s, 2H)
Compound No. 219: (2-Benzylquinazolino-4-yl)-(3-fluorobenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.0 Hz, IH), 7.69(t, /=7.3 Hz, 2H), 7.40(m, 3H), 7.23(m, 4H), 7.03(m, 3H), 6.15(br, IH), 4.81(d, /=5.7 Hz, 2H), 4.18(s, 2H)
Compound No. 220: (2-Benzylquinazolino-4-yl)-[2-(3-fluorophenyl)-ethyl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.82(d, /=8.4 Hz, IH), 7.68(d, /=7.5 Hz, IH), 7.49(m, 3H), 7.34(m, 5H), 6.92(m, 3H), 5.69(br, IH), 4.21 (s, 2H), 3.84(q, /=6.6 Hz, 2H), 2.92(t, /=7.2 Hz, 2H)
Compound No. 221: 2-[2-(2-Benzylquinazolino-4-ylamino)-ethoxy]-ethanol iH NMR(CDCl3, 300 MHz) δ 7.80(d, /=8.4 Hz, IH), 7.66(d, /=8.4 Hz, 2H), 7.45(d, /=7.2 Hz, 2H), 7.36(d, J=7.7 Hz, IH), 7.28(m, 3H), 6.12(br, IH), 4.17(s, 2H), 3.78(m, 6H), 3.59(t, /=4.5 Hz, 2H), 2.13(br s, IH),
Compound No. 222: 2-(2-Benzylquinazolino-4-ylamino)-ethanol
Η NMR(CDCl3, 300 MHz) δ 7.80(d, /=8.3 Hz, IH), 7.67(m, 2H), 7.40(m, 3H), 7.23(m, 4H), 6.22(br, IH), 4.15(s, 2H), 3.83(t, /=4.5 Hz, 2H), 3.76(m, 2H)
Compound No. 223: Benzyl-(2-pyridino-2-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.80(d, /=3.9 Hz, IH), 8.55(d, /=7.9 Hz, IH), 8.08(d, /=8.4 Hz, IH), 7.84(m, 2H), 7.71(t, J=7.7 Hz, IH), 7.42(m, 3H), 7.34(m, 4H), 6.65(br, IH), 4.99(s, 2H)
Compound No. 224: (3-Methoxybenzyl)-(2-pyridino-2-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.81(d, /=4.2 Hz, IH), 8.56(d, /=7.8 Hz, IH), 8.08(d, /=8.4 Hz, IH), 7.92-7.72(m, 3H), 7.44(t, /=7.6 Hz, IH), 7.36(t, /=6.1 Hz, IH), 7.24(m, 2H), 7.02(m, IH), 6.83(m,lH), 6.80(br, IH), 4.97(s, 2H), 3.75(s, 3H)
Compound No. 225: (4-Methoxybenzyl)-(2-pyridino-2-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.82(d, /=4.2 Hz, IH), 8.59(d, /=7.9 Hz, IH), 8.08(d, /=8.3 Hz, IH), 7.84(m, 2H), 7.71(t, /=7.3 Hz, IH), 7.43(m, 4H), 6.86(d, /=8.6 Hz, 2H), 6.61(br, IH), 4.93(s, 2H), 3.78(s, 3H)
Compound No. 226:
(2-Pyridino-2-ylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.78(d, /=4.4 Hz, IH), 8.44(d, /=7.9 Hz, IH), 8.04(m, 2H), 7.74(m, IH), 7.65(m, 2H), 7.48(m, IH), 7.44-7.34(m, 4H), 6.12(br, IH), 5.03(s, 2H)
Compound No. 227: Phenethyl-(2-pyridino-2-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.84(d, /=4.0 Hz, IH), 8.62(d, /=7.9 Hz, IH), 8.08(d, /=8.3 Hz, IH), 7.86(t, /=3.8 Hz, IH), 7.73(m, 2H), 7.45-7.24(m, 7H), 6.54(br, IH), 4.07(t, /=6.7 Hz, 2H), 3.10(t, /=7.1 Hz, 2H)
Compound No. 228: (4-Phenylbutyl)-(2-pyridino-2-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.83(d, /=4.2 Hz, IH), 8.55(d, /=7.9 Hz, IH), 8.06(d, /=8.3 H, IHz), 7.84(m, 2H), 7.71(t, /=7.5 Hz, IH), 7.44(t, /=7.5 Hz, IH), 7.37(t, /=6.0 Hz, IH), 7.28-7.16(m, 5H), 6.44(br, IH), 3.83(m, 2H), 2.70(t, /=6.3 Hz, 2H), 1.81(m, 4H)
Compound No. 229:
Naphthaleno-l-ylmethyl-(2-pyridino-2-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.83(d, /=4.0 Hz, IH), 8.60(d, /=7.9 Hz, IH), 8.10(d, /=8.3 Hz, IH), 8.05(m, IH), 7.83(m, 4H), 7,71(m, IH), 7.63(m, IH), 7.50-7.36(m, 5H), 6.78(br, IH), 5.43(s, 2H)
Compound No. 230:
Benzo[l,3]dioxol-5-ylmethyl-(2-pyridino-2-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.83(d, /=4.1 Hz, IH), 8.58(d, /=8.0 Hz, IH), 8.08(d,
/=8.3 Hz, IH), 7.84(m, 2H), 7.73(d, /=7.2 Hz, IH), 7.45(m, IH), 7.36(m, IH), 6.90(m, 2H), 6.76(d, /=7.8 Hz, IH), 6.61(br, IH), 5.92(s, 2H), 4.90(s, 2H) Compound No. 231: (3-Fluorobenzyl)-(2-pyridino-2-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.80(Clx /=4.1 Hz, IH), 8.49(d, /=8.1 Hz, IH), 8.05(m, 2H), 7.83(m, IH), 7.73(t, J=7.7 Hz, IH), 7.47(m, IH), 7.37(m, IH), 7.28(m, 2H), 7.18(m, IH), 6.94(m, IH), 6.43(br, IH), 5.00(s, 2H)
Compound No. 232:
[2-(3-Fluorophenyl)-ethyl]-(2-pyridino-2-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.83(d, /=4.1 Hz, IH), 8.59(d, /=8.2 Hz, IH), 8.07(d, /=8.3 Hz, IH), 7.86(t, ]=7.7 Hz, IH), 7.73(m, 2H), 7.39(m, 2H), 7.25(m, IH), 7.00(m, 3H), 6.45(br, IH), 4.03(m, 2H), 3.08(t, /=6.6 Hz, 2H)
Compound No. 233: 2-[2-(2-Pyridino-2-ylquinazolino-4-ylamino)-ethoxy]-ethanol
1H NMR(CDCl3, 300 MHz) δ 8.89(t, /=6.8 Hz, 2H), 8.46(d, /=8.0 Hz, IH), 8.00(m, 2H), 7.58(d, /=7.5 Hz, 2H), 7.41(, /=7.2 Hzt, IH), 6.63(br, IH), 4.08(m, 4H), 8.83(m, 4H)
Compound No. 234: 2-(2-Pyridino-2-ylquinazolino-4-ylamino)-ethanol 1H NMR(CDCl3, 300 MHz) δ 8.80(d, /=4.6 Hz, IH), 8.56(d, /=8.1 Hz, IH), 8.01(d, /=8.3 Hz, IH), 7.84(m, 2H), 7.74(t, J=7.7 Hz, IH), 7.40(m, IH), 7.36(m, IH), 6.81(br, IH), 3.97(m, 4H)
Compound No. 235: Benzyl-(2-pyridino-3-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 9.72(s, IH), 8.67(d, /=4.5 Hz, IH), 8.54(m, IH), 7.96(d,
/=8.3 Hz, IH), 7.79(m, 2H), 7.46-7.29(m, 6H), 6.52(br, IH), 4.99(d, /=5.4 Hz, 2H)
Compound No. 236: (3-Methoxybenzyl)-(2-pyridino-3-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 9.72(s, IH), 8.86(d, / = 7.9 Hz, IH), 8.68(d, /=3.8 Hz, IH), 8.01 (d, /=8.3 Hz, IH), 7.85(d, /=8.1 Hz, IH), 7.83(m, IH), 7.43(m, 2H), 7.26(m, IH), 7.01(t, /=5.9 Hz, 2H), 6.84(t, /=4.13 Hz, IH), 6.68(br, IH), 4.97(d, /=5.4 Hz, 2H), 3.77(s, 3H)
Compound No. 237: (4-Methoxybenzyl)-(2-pyridino-3-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 9.74(S, IH), 8.83(d, /=7.9 Hz, IH), 8.66(d, /=3.6 Hz, IH), 7.95(d, /=8.3 Hz, IH), 7.75(m, 2H), 7.38(m, 4H), 6.87(d, /=8.8 Hz, 2H), 6.38(br, IH), 4.90(d, /=5.4 Hz, 2H), 3.78(s, 3H)
Compound No. 238:
(2-Pyridino-3-ylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine
Η NMR(CDCl3, 300 MHz) δ 9.89(s, IH), 8.74(m, 2H), 7.96(d, /=8.3 Hz, IH), 7.78(m, 4H), 7.47(m, 4H), 6.39(br, IH), 5.05(d, /=5.4 Hz, 2H)
Compound No. 239: Phenethyl-(2-pyridino-3-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 9.77(s, IH), 8.85(s, /=8.0 Hz, IH), 7.95(d, /=8.5 Hz, IH), 7.73(m, IH), 7.41(m, 7H), 6.17(br, IH), 4.05(m, 2H), 3.10(t, /=6.9 Hz, 2H)
Compound No. 240: (4-Phenylbutyl)-(2-pyridino-3-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 9.74(s, IH), 8.82(d, /=8.0 Hz, IH), 8.68(d, /=3.9 Hz, IH), 7.95(d, /=8.1 Hz, IH), 7.72(t, /=7.6 Hz, 2H), 7.41(m, 2H), 7.24(m, 5H), 6.12(br, IH), 3.80(t, /=5.9 Hz, 2H), 2.71(t, /=6.7 Hz, 2H), 1.81(t, /=3.4 Hz, 4H)
Compound No. 241: Naphthaleno-l-ylmethyl-(2-pyridino-3-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz)) δ 9.82(s, IH), 8.88(d, /=7.9 Hz, IH), 8.69(m, IH), 8.12(m, IH), 7.92(m, 3H), 7.80(m, IH), 7.61(m, 2H), 7.50(m, 5H), 6.05(br, IH), 5.43(d, /=4.8 Hz, 2H)
Compound No. 242:
Benzo[l,3]dioxol-5-ylmethyl-(2-pyridino-3-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 9.72(s, IH), 8.89(d, /=8.0 Hz, IH), 8.69(d, /=4.5 Hz, IH), 8.03(d, /=8.5 Hz, IH), 7.86(d, /=8.1 Hz, IH), 7.73(t, /=7.3 Hz, IH), 7.43(t, /=6.5 Hz, 2H), 6.92(d, /=7.8 Hz, 2H), 7.77(d, J=7.7 Hz, 2H), 5.92(s, 2H), 4.90(d, / = 5.4 Hz, 2H)
Compound No. 243: (3-Fluorobenzyl)-(2-pyridino-3-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 9.69(s, IH), 8.81(4 /=8.0 Hz, IH), 8.68(d, /=3.8 Hz, IH), 8.00(d, /=8.3 Hz, IH), 7.87(d, /=8.1 Hz, IH), 7.75(m, IH), 7.44(m, 2H), 7.29(m, 2H), 7.14(m, IH), 6.96(m, IH), 6.72(br, IH), 5.00(d, /=5.6 Hz, 2H)
Compound No. 244:
[2-(3-Fluorophenyl)-ethyl]-(2-pyridino-3-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 9.75(s, IH), 8.86(d, /=8.0 Hz, IH), 8.69(d, /=4. Hz, IH), 7.97(d, /=8.4 Hz, IH), 7.70(m, 2H), 7.43(m, 2H), 7.27(m, 2H), 6.99(m, 3H), 6.28(br, IH), 4.05(m, 2H), 3.11 (t, /=6.9 H, 2Hz)
Compound No. 245: 2-[2-(2-Pyridino-3-ylquinazolino-4-ylamino)-ethoxy]-ethanol Η NMR(CDCl3, 300 MHz) δ 9.66(s, IH), 8.73(d, /=7.2 Hz, IH), 8.63(d, /=2.8 Hz, IH), 7.86(d, /=8.3 H, IHz), 7.79(d, /=8.2 Hz, IH), 7.65(m, IH), 7.35(m, 2H), 6.81(br, IH), 3.97(m, 2H), 3.83(m, 4H), 3.67(m, 2H)
Compound No. 246: 2-(2-Pyridino-3-ylquinazolino-4-ylamino)-ethanol
1H NMR(CDCl3, 300 MHz) δ 9.67(s, IH), 8.76(d, /=8.03 Hz, IH), 8.66(d, /=3.4 Hz, IH),
7.94(t, J=7.7 Hz, 2H), 7.72(t, /=7.6 Hz, IH), 7.42(m, 2H), 6.94(br, IH), 4.00(m, 4H)
Compound No. 247: Benzyl-(2-pyridino-4-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.74(m, 2H),8.43(d, /=5.5 Hz, 2H), 7.98(d, /=8.3 Hz, IH), 7.75(t, /=4.4 Hz, 2H), 7.48(m, 3H), 7.36(m, 3H), 6.21(br, IH), 5.01(d, /=5.4 Hz, 2H)
Compound No. 248: (3-Methoxybenzyl)-(2-pyridino-4-ylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 8.73(d, /=5.0 Hz, 2H), 8.43(d, /=5.5 Hz, 2H), 9.98(d, /=8.2 Hz, IH), 7.77(t, J=7.7 Hz, 2H), 7.49(d, /=7.2 Hz, IH), 7.26(m, 2H), 6.84(m, IH), 6.35(br, IH), 4.98(d, /=5.3 Hz, 2H)
Compound No. 249: (4-Methoxybenzyl)-(2-pyridino-4-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.74(d, /=5.5 Hz, 2H), 8.46(d, /=5.5 Hz, 2H), 7.98(d, /=8.2 Hz, IH), 7.76(t, /=7.6 Hz, 2H), 7.47(t, /=7.6 Hz, IH), 7.38(d, /=8.5 Hz, 2H), 6.90(d, /=8.5 Hz, 2H), 6.29(br, IH), 4.93(d, /=5.4 Hz, 2H), 3.80(s, 3H)
Compound No. 250: (2-Pyridino-4-ylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.72(m, 2H), 8.40(d, /=4.71 Hz, 2H), 8.02(d, /=8.3 Hz, IH), 7.84(m, 2H), 7.75(m, IH), 7.65(m, IH), 7.52(m, 3H), 6.57(br, IH), 5.02(d, /=5.3 Hz, 2H)
Compound No. 251: Phenethyl-(2-pyτidino-4-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.74(d, /=5.5 Hz, 2H), 8.45(d, /=5.5 Hz, 2H), 7.96(d, /=8.3 Hz, IH), 7.76(t, /=7.4 Hz, IH), 7.67(dH, /=8.2 Hz, 1), 7.46(d, /=7.2 Hz, IH), 7.33(m, 5H), 6.09(br, IH), 4.06(m, 2H), 3.11(t, /=6.9 Hz, 2H)
Compound No. 252: (4-Phenylbutyl)-(2-pyridino-4-ylquinazolino-4-yl)-amine 1H NMR(300MHz, CDC13, 300 MHz) δ 8.76(d, /=5.4 Hz, 2H), 8.42(d, /=5.5 Hz, 2H), 7.97(d, /=8.3 Hz, IH), 7.75(t, /=7.5 Hz, 2H), 7.47(t, }=7.5 Hz, IH), 7.25(m, 6H), 6.10(br, IH), 3.82(d, /=5.6 Hz, 2H), 2.73(t, /=6.6 Hz, 2H), 1.84(m, 4H)
Compound No. 253: Naphthaleno-l-ylmethyl-(2-pyridino-4-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.76(d, /=5.4 Hz, 2H), 8.46(d, /=5.3 Hz, 2H), 8.12(d, /=8.4 Hz, IH), 7.95(m, 3H), 7.77(m, IH), 7.62(t, /=5.8 Hz, 2H), 7.50(m, 4H), 5.99(br, IH), 5.44(d, /=4.9 Hz, 2H)
Compound No. 254:
Benzo[l,3]dioxol-5-ylmethyl-(2-pyridino-4-ylquinazolino-4-yl)-amine iH NMR(CDCl3, 300 MHz) δ 8.74(d, /=5.4 Hz, 2H), 8.40(d, /=6.06 Hz, 2H), 7.96(d, /=8.4 Hz, IH), 7.76(m, 2H), 7.48(t, /=7.6 Hz, IH), 6.92(d, /=7.97 Hz, 2H), 6.80(d, J=77 Hz, IH), 6.07(br, IH), 5.96(s, 2H), 4.91(d, /=5.3 Hz, 2H)
Compound No. 255: (3-Fluorobenzyl)-(2-pyridino-4-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.74(d, /=5.4 Hz, 2H)x 8.38(d, /=5.1 Hz, 2H), 7.98(4 /=8.4 H, IHz), 7.79(t, /=7.8 Hz, 2H), 7.51(t, /=3.9 Hz, IH), 7.35(t, /=3.9 Hz, IH), 7.25(m, IH), 7.17(m, IH), 7.01(m, IH), 6.24(br, IH), 5.01(d, /=5.5 Hz, 2H)
Compound No. 256:
[2-(3-Fluorophenyl)-ethyl]-(2-pyridino-4-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.76(d, /=5.5 Hz, 2H), 8.44(d, /=5.3 Hz, 2H), 7.98(d, /=8.4 Hz, IH), 7.67(d, /=8.0 Hz, IH), 7.48(d, /=7.3 Hz, IH), 7.28(m, IH), 7.03(m, 3H), 6.14(br, IH), 4.05(m, 2H), 3.11(t, /=6.9 Hz, 2H)
Compound No. 257: 2-[2-(2-Pyridino-4-ylquinazolino-4-ylamino)-ethoxy]-ethanol Η NMR(CDCl3, 300 MHz) δ 8.72(d, /=4.8 Hz, 2H), 8.36(d, /=5.8 Hz, 2H), 7.92(d, /=8.3 Hz, IH), 7.83(d, /=8.2 Hz, IH), 7.73(t, /=7.6 Hz, IH), 7.45(t, /=7.6 Hz, IH), 6.64(br, IH), 4.02(m, 2H), 3.81(m, 4H), 3.69(m, 2H)
Compound No. 258: 2-(2-Pyτidino-4-ylquinazolino-4-ylamino)-ethanol Η NMR(CDCl3, 300 MHz) δ 8.71(d, /=4.8 Hz, 2H), 8.35(d, /=5.5 Hz, 2H), 8.13(d, /=8.4 Hz, IH), 7.90(d, /=8.2 Hz, IH), 7.73(t, /=8.3 Hz, IH), 7.47(t, /=7.6 Hz, IH), 7.18(br, IH), 3.99(m, 4H)
Compound No. 259: Benzyl-[2-(4-chlorophenyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 8.52(d, /=8.6 Hz, 2H), 7.92(d, /=8.2 Hz, IH), 7.71(m, 2H),
7.40(m, 8H), 5.97(br, IH), 5.00(d, /=5.5 Hz, 2H)
Compound No. 260:
[2-(4-chlorophenyl)-quinazolino-4-yl]-(3-methoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.52(d, /=8.5 Hz, 2H), 7.92(d, /=8.3 Hz, IH), 7.72(m, 2H), 7.42(m, 3H), 7.28(m, IH), 7.03(d, /=8.0 Hz, 2H), 6.87(t, /=4.2 Hz, IH), 5.98(br, IH), 4.98(d, /=5.5 Hz, 2H), 3.78(s, 3H)
Compound No. 261: [2-(4-Chlorophenyl)-quinazolino-4-yl]-(4-methoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.53(d, /=8.5 Hz, 2H), 7.96(d, /=8.55 Hz, IH), 7.72(m, 2H), 7.38(m, 5H), 6.90(d, /=8.6 Hz, 2H), 4.92(d, /=5.3 Hz, 2H), 3.80(s, 3H)
Compound No. 262:
[2-(4-Chlorophenyl)-quinazolino-4-yl]-(3-trifluoromethylbenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.45(d, /=8.6 Hz, 2H), 7.95(d,, /=8.5 Hz IH), 7.75(m, 3H), 7.65(d, J=7.7 Hz, IH), 7.56(d, J=7.7 Hz, IH), 7.45(m, 4H), 6.12(br, IH), 5.05(d, /=5.5 Hz, 2H)
Compound No. 263: [2-(4-Chlorophenyl)-quinazolino-4-yl]-phenethylamine 1H NMR(CDCl3, 300 MHz) δ 8.54(d, /=8.4 Hz, 2H), 7.94(d, /=8.5 Hz, IH), 7.70(t, /=7.5 Hz, IH), 7.60(d, /=8.1 Hz, IH), 7.46(d, /=8.6 Hz, 2H), 7.35(m, 6H), 6.04(br, IH), 4.05(m, 2H), 3.10(t, /=7.0 Hz, 2H)
Compound No. 264: [2-(4-Chlorophenyl)-quinazolino-4-yl]-(4-phenylbutyl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.50(d, /=8.5 Hz, 2H), 7.93(d, /=8.6 Hz, IH), 7.70(m, 2H), 7.41(m, 3H), 7.25(m, 5H), 6.09(br, IH), 3.80(d, /=5.5 Hz, 2H), 2.72(m, 2H), 1.82(m, 4H)
Compound No. 265:
[2-(4-Chlorophenyl)-quinazolino-4-yl]-naphthaleno-l-ylmethylamine
1H NMR(CDCl3, 300 MHz) δ 8.58(d, /=8.5 Hz, 2H), 8.17(m, IH), 7.91(m, 3H), 7.63(m, IH), 7.51(m, 7H), 7.36(m, IH), 5.87(br, IH), 5.42(d, /=4.8 Hz, 2H)
Compound No. 266:
Benzo[l,3]dioxol-5-ylmethyl-[2-(4-chlorophenyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 8.52(d, /=8.6 Hz, 2H), 7.92(d, /=8.3 Hz, IH), 7.71 (m, 2H), 7.43(m, 3H), 6.93(d, /=11.4 Hz, 2H), 6.80(d, /=10.2 Hz, IH), 5.95(s, 2H), 5.94(br, IH), 4.89(d, /=4.9 Hz, 2H)
Compound No. 267: [2-(4-Chlorophenyl)-quinazolino-4-yl]-(3-fluorobenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.48(4 /=8.5 Hz, 2H), 7.92(d, /=8.5 Hz, IH), 7.74(m, 2H, 7.77(m, 3H), 7.23(m, 3H), 7.00(m, IH), 6.07(br, IH), 4.98(d, /=5.5 Hz, 2H)
Compound No. 268:
[2-(4-Chlorophenyl)-quinazolino-4-yl]-[2-(3-fluorophenyl)-ethyl]-amine
1H NMR(CDCl3, 300 MHz) δ 8.52(d, /=8.6 Hz, 2H), 7.94(d, /=8.6 Hz, IH), 7.72(d,
/=7.2 Hz, IH), 7.63(d, /=8.1 Hz, IH), 7.43(m, 3H), 7.28(m, IH), 7.02(m, 3H), 6.08(br,
IH), 4.03(m, 2H), 3.10(t, /=7.0 Hz, 2H)
Compound No. 269:
2-{2-[2-(4-Chlorophenyl)-quinazolino-4-ylamino]-ethoxy}-ethanol
1H NMR(CDCl3, 300 MHz) δ 8.47(d, /=8.4 Hz, 2H), 7.90(d, /=8.3 Hz, IH), 7.72(m, 2H),
7.41(m, 3H), 6.52(br, IH), 4.00(m, 2H), 3.81(m, 4H), 3.67(m, 2H)
Compound No. 270: 2-[2-(4-Chlorophenyl)-quinazolino-4-ylamino]-ethanol
1H NMR(CDCl3, 300 MHz) δ 8.46(4 /=8.5 Hz, 2H), 7.90(d, /=8.4 Hz, IH), 7.75(m, 2H),
7.46(m, 3H), 6.21 (br, IH), 3.00(m, 4H)
Compound No. 271: (2,4-Dimethoxybenzyl)-(2-isopropylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.1 Hz, IH), 7.68-7.60(m, 2H), 7.38-7.33(m, 2H), 6.50-6.42(m, 2H), 6.24(br, IH), 4.83(d, /=5.7 Hz, 2H), 3.88(s, 3H), 3.80(s, 3H), 3.17(m, IH), 1.40(d, /=6.9 Hz, 6H)
Compound No. 272: (2-Benzylquinazolino-4-yl)-(2,4-dimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.77(4 /=8.4 Hz, IH), 7.64(t, /=7.7Hz, IH), 7.56(d, /=8.1 Hz, IH), 7.48(d, /=6.9 Hz, 2H), 7.30(m, 4H), 7.09(d, /=8.4 Hz, IH), 6.45(d, /=2.4Hz, IH), 6.32(dd, /3=8.4 Hz, /2=2.4Hz, IH), 6.17(br, IH), 4.73(d, /=6.0 Hz, 2H), 4.20(s, 2H), 3.85(s, 3H), 3.78(s, 3H)
Compound No. 273: 4-(2,4-Dimethoxybenzyloxy)-2-phenylquinazoline 1H NMR(CDCl3, 300 MHz) δ 8.63(m, 2H), 8.17(d, IH, /=7.8 Hz), 7.98(d, /=8.1 Hz, IH), 7.79(m, IH), 7.53(m, 5H), 6.53(m, 2H), 5.75(s, 2H), 3.87(s, 3H), 3.83(s, 3H)
Compound No. 274: 4-(2,4-Dimethoxybenzylsulf anyl)-2-phenylquinazoline 1H NMR(CDCl3, 300 MHz) δ 8.68(dd, /3=7.5 Hz, /2=2.1Hz, 2H), 8.05(d, /=8.4Hz, IH), 7.98(d, /=8.4 Hz, IH), 7.80(t, /=7.5 Hz, IH), 7.45(m, 5H), 6.50(d, /=2.4 Hz, IH), 6.41(dd, Hz, /2=2.3Hz, IH), 4.80(s, 2H), 3.88(s, 3H), 3.78(s, 3H)
Compound No. 275: (2-Methoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.48-7.38(m, 4H), 7.26(m, IH), 6.99(m, IH), 6.92(m, 2H), 6.02(br, IH), 4.82(d, /=5.7 Hz, 2H), 3.91(s, 3H), 3.70(t, /=6.6 Hz, 4H), 1.98(m, 4H)
Compound No. 276: (2-Methoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.50-7.46(m, 4H), 7.30-7.26(m, IH), 7.00(t, /=7.5 Hz, IH), 6.92(m, 2H), 5.96(br, IH), 4.80(d, /=5.4 Hz, 2H), 3.91(s, 7H), 1.62(m, 6H)
Compound No. 277: (2-Methoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 7.53-7.44(m, 3H), 7.36-7.26(m, 2H), 7.06(td, /3=6.6 Hz, /2=1.5 Hz, IH), 6.93(m, 2H), 6.04(br, IH), 4.80(d, /=5.7 Hz, 2H), 3.90(m, 7H), 3.79(m, 4H)
Compound No. 278: (2-Methoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine
Η NMR(CDCl3, 300 MHz) δ 7.52-7.43(m, 3H), 7.36(d, /=7.5 Hz, IH), 7.28(m, IH), 7.04(t, /=8.1 Hz, IH), 6.93(m, 2H), 6.01(br, IH), 4.80(d, /=5.4 Hz, 2H), 3.97(t, /=4.8 Hz, 4H), 3.91(s, 3H), 2.50(t, /=4.8 Hz, 4H), 2.35(s, 3H)
Compound No. 279:
(3-Methoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.50-7.44(m, 3H), 7.27(m, IH), 7.03-6.96(m, 3H), 6.83(dd,
Figure imgf000077_0001
Hz, IH), 5.73(br, IH), 4.80(d, /=5.1 Hz, 2H), 3.80(s, 3H), 3.67(t, /=6.6 Hz, 4H), 1.96(m, 4H)
Compound No. 280: (3-Methoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.52-7.43(m, 3H), 7.27(m, IH), 7.04-6.96(m, IH), 6.84(dd, Hz, /2=2.1 Hz, IH), 5.69(br, IH), 4.77(d, /=5.4 Hz, 2H), 3.87(m, 4H), 3.80(s, 3H), 1.62(m, 6H)
Compound No. 281:
(3-Methoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.57-7.47(m, 3H), 7.28(m, IH), 7.08(t, /=7.8 Hz, IH), 7.00-6.94(m, 2H), 6.85(dd,
Figure imgf000077_0002
Hz, IH), 5.76(br, IH), 4.77(d, /=5.4 Hz, 2H), 3.89(m, 4H), 3.80-3.75(m, 7H)
Compound No. 282:
(3-Methoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.54-7.45(m, 3H), 7.27(m, IH), 7.05(m, IH), 6.97(m, 2H),
6.84(dd, Hz, /2=2.1 Hz, IH), 5.74(br, IH), 4.77(d, /=5.4 Hz, 2H), 3.93(t, /=4.8 Hz, 4H), 3.80(s, 3H), 2.47(t, /=4.8 Hz, 4H), 2.34(s, 3H)
Compound No. 283: (4-Methoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.49(d, /=3.6 Hz, 2H), 7.44(d, /=8.1 Hz, IH), 7.33(d, /=8.7 Hz, 2H), 6.99(m, IH), 6.88(d, /=8.7 Hz, 2H), 5.68(br, IH), 4.75(d, /=5.4 Hz, 2H), 3.81(s, 3H), 3.68(t, /=6.9 Hz, 4H), 1.96(m, 4H)
Compound No. 284: (4-Methoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.51-7.41 (m, 3H), 7.33(d, /=8.7 Hz, 2H), 7.00(m, IH), 6.89(d, /=8.4 Hz, 2H), 5.62(br, IH), 4.73(d, /=5.4 Hz, 2H), 3.88(m, 4H), 3.81(s, 3H), 1.27(m, 6H) Compound No. 285: (4-Methoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.53-7.44(m, 3H), 7.32(d, /=8.7 Hz, 2H), 7.06(m, IH), 6.89(d, /=8.7 Hz, 2H), 5.69(br, IH), 4.72(d, /=5.1 Hz, 2H), 3.88(m, 4H), 3.81(s, 3H), 3.77(m, 4H)
Compound No. 286: (4-Methoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine 1H NMR(CDCl3, 300 MHz) δ 7.54-7.42(m, 3H), 7.33(d, /=8.7 Hz, 2H), 7.03(m, IH), 6.89(d, /=8.7 Hz, 2H), 5.65(br, IH), 4.73(d, /=5.4 Hz, 2H), 3.95(t, /=4.8 Hz, 4H), 3.81(s, 3H), 2.48(t, /=4.8 Hz, 4H), 2.34(s, 3H)
Compound No. 287: (2,3-Dimethoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.47(m, 3H), 7.00(m, 3H), 6.88(dd,
Figure imgf000078_0001
Hz, /2=3.6 Hz, IH), 6.01(br, IH), 4.84(d, J=6.0 Hz, 2H), 3.92(s, 3H), 3.88(s, 3H), 3.69(t, 4H), 1.97(m, 4H)
Compound No. 288:
(2,3-Dimethoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.50-7.41(m, 3H), 7.00(m, 3H), 6.88(dd, /2=7.2 Hz, /2=2.7 Hz, IH), 5.97(br, IH), 4.82(d, /=5.7 Hz, 2H), 3.92(s, 3H), 3.88(s, 7H), 1.65(m, 6H)
Compound No. 289:
(2,3-Dimethoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.51-7.44(m, 3H), 7.08-6.94(m, 3H), 6.89(dd, /i=8.1 Hz, /2=1.5 Hz, IH), 6.05(br, IH), 4.81(d, /=5.7 Hz, 2H), 3.93-3.89(m, 10H), 3.79(t, /=4.8 Hz, 4H)
Compound No. 290: (2,3-Dimethoxybenzyl)-[2-(4-inethylpiperazino-l-yl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.49-7.44(m, 3H), 7.05-6.96(m, 3H), 6.89(dd,
Figure imgf000079_0001
Hz, /2=1.5 Hz, IH), 6.00(br, IH), 4.82(d, /=5.7 Hz, 2H), 3.96(t, /=4.8 Hz, 4H), 3.92(s, 3H), 3.89(S, 3H), 2.50(t, /=4.8 Hz, 4H), 2.35(s, 3H)
Compound No. 291:
(2,4-Dimethoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.46(d, /=3.9 Hz, 2H), 7.42(d, /=8.1 Hz, IH), 7.31(d, /=8.4 Hz, IH), 6.98(s, IH), 6.49(d, /=2.4 Hz, IH), 6.44(dd, /3=8.1 Hz, J2=IA Hz, IH), 5.94(br, IH), 4.74(d, /=6.0 Hz, 2H), 3.87(s, 3H), 3.80(s, 3H), 3.71(t, /=6.6 Hz, 4H), 1.98(m, 4H)
Compound No. 292: (2,4-Dimethoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.49-7.39(m, 3H), 7.27(m, IH), 6.99(t, /=6.6 Hz, IH), 6.49(d, /=2.4 Hz, IH), 6.44(dd, /3=8.1 Hz, /2=2.1 Hz, IH), 5.88(br, IH), 4.72(d, /=5.4 Hz, 2H), 3.97(m, 4H), 3.87(s, 3H), 3.80(s, 3H), 1.66(m, 6H)
Compound No. 293: (2,4-Dimethoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.53-7.43(m, 3H), 7.26(m, 2H), 7.05(m, IH), 6.50(d, /=2.1 Hz, IH), 6.45(dd, /3=8.1 Hz, /2=2.1 Hz, IH), 5.94(br, IH), 4.72(d, /=5.7 Hz, 2H), 3.94-3.78(m, 14H)
Compound No. 294:
(2,4-Dimethoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.50(m, 2H), 7.43(d, IH, /=8.1 Hz), 7.26(m, IH), 7.06(m, IH), 6.50(d, /=2.1 Hz, IH), 6.45(dd, /2=8.1 Hz, /2=2.1 Hz, IH), 6.00(br, IH), 4.72(d, /=5.4 Hz, 2H), 4.01(m, 4H), 3.87(s, 3H), 3.81(s, 3H), 2.54(t, /=4.8 Hz, 4H), 2.37(s, 3H)
Compound No. 295: (2,5-Dimethoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.45(m, 3H), 6.99(m, 2H)x 6.79(m, 2H), 6.02(br s, IH), 4.79(d, /=5.7Hz, 2H), 3.86(s, 3H), 3.75(s, 3H), 3.71(br t, /=6.8Hz, 4H), 1.97(br t, /=6.8Hz, 4H)
Compound No. 296:
(2,5-Dimethoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.44(m, 3H), 6.97(m, 2H), 6.79(m, 2H), 5.99(br s, IH),
4.77(d, /=5.7Hz, 2H), 3.91(br s, 4H), 3.87(s, 3H), 3.75(s, 3H), 1.65(br s, 6H)
Compound No. 297:
(2,5-Dimethoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.48(m, 3H), 7.06(br t, /=7.5Hz, IH), 6.94(d, /=2.7Hz, IH),
6.80(m, 2H), 6.05(br s, IH), 4.76(d, /=5.7Hz, 2H), 3.92(m, 4H), 3.90(s, 3H), 3.79(m, 4H), 3.75(s, 3H)
Compound No. 298: (2,5-Dimethoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine
Η NMR(CDCl3, 300 MHz) δ 7.46(m, 3H), 7.06(br t, /=7.8Hz, IH), 6.95(d, /=3.0Hz, IH), 6.80(m, 2H), 6.02(br s, IH), 4.77(d, /=5.7Hz, 2H), 3.97(br t, /-5.8Hz, 4H), 3.86(s, 3H), 3.75(s, 3H), 2.50(br t, /=5.8Hz, 4H), 2.35(s, 3H)
Compound No. 299: (3,4-Dimethoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.49(d, /=3.9Hz, 2H), 7.46(d, /=8.4Hz, IH), 7.00(m, 3H), 6.84(m, IH), 5.71(br s, IH), 4.75(d, /=5.4Hz, 2H), 3.89(s, 3H), 3.86(s, 3H), 3.69(br t, /=6.6Hz, 4H), 1.97(br t, /=6.6Hz, 4H)
Compound No. 300: (3,4-Dimethoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.45(m, 3H), 6.99(m, 3H), 6.85(d, /=8.4Hz, IH) , 5.64(br s, IH), 4.73(d, /=5.7Hz, 2H), 3.89(In, 10H), 1.65(m, 6H),
Compound No. 301: (3,4-Dimethoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.52(m, 3H), 7.08(t, /=7.8Hz, IH), 6.94(m, 2H), 6.85(d, /=8.4Hz, IH), 5.71(br s, IH), 4.72(d, /=4.8Hz, 2H), 3.91(m, 4H), 3.89(s, 3H), 3.86(s, 3H), 3.78(m, 4H)
Compound No. 302: (3,4-Dimethoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.49(m, 3H), 7.05(t, /=7.8Hz, IH), 6.95(m, 2H), 6.84(m, IH), 5.66(br s, IH), 4.73(d, /=5.4Hz, 2H), 3.96(br t, /=5.0Hz, 4H), 3.89(s, 3H), 3.86(s, 3H), 2.49(brvt, /=5.0Hz, 4H), 2.35(s, 3H)
Compound No. 303:
(3,5-Dimethoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.50(m, 3H), 7.01(m, IH), 6.56(d, /=1.8Hz, 2H), 6.39(br t, /=2.3Hz, IH), 5.82(br s, IH), 4.75(d, /=5.4Hz, 2H), 3.77(s, 6H), 3.67(br t, /=6.6 Hz, 4H), 1.95(br t, /=6.6 Hz, 4H)
Compound No. 304:
(3,5-Dimethoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.46(m, 3H), 7.02(t, /=8.1Hz, IH), 6.56(br d, J=IAHz, 2H),
6.40(br t, /=1.8Hz, IH), 5.71 (br s, IH), 4.73(d /=5.4 Hz, 2H), 3.88(m, 4H), 3.78(s, 6H), 1.62(s, 6H)
Compound No. 305: (3,5-Dimethoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.52(m, 3H), 7.09(br t, /=7.8Hz, IH), 6.55(br d, /=2.1Hz, 2H), 6.40(br t, /=2.1Hz, IH), 5.75(br s, IH), 4.73(d /=5.4 Hz, 2H), 3.91(m, 4H), 3.78(m, 10H) Compound No. 306: (3,5-Dimethoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.50(m, 3H), 7.06(t, /-7.8Hz, IH), 6.56(d, /=2.4Hz, 2H), 6.40(br t, /=2.1Hz, IH), 5.72(br s, IH), 4.73(d /=5.4 Hz, 2H), 3.94(br t, /=4.2Hz, 4H), 3.78(s, 6H), 2.48(br t, /=5.0Hz, 4H), 2.34(s, 3H)
Compound No. 307: Benzo[l,3]dioxol-5-ylmethyl-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.48(br d, /=3.9 Hz, 2H), 7.45(d, /=8.1Hz, IH), 6.99(quartet, /=4.1 Hz, IH), 6.92(s, IH), 6.86(d, /=7.8 Hz, IH), 6.76(d, /=7.8 Hz, IH), 5.95(s, 2H), 5.70(br s, IH), 4.72(d, J=5.7 Hz, 2H), 3.68(br t, /=6.6 Hz, 4H), 1.97(m, 4H)
Compound No. 308: Benzo[l,3]dioxol-5-ylmethyl-(2-piperidino-l-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.48(m, 3H), 7.03(m, IH), 6.85(m, 3H), 5.95(s, 2H), 5.64(br s, IH), 4.69(t, /=5.4 Hz, 2H), 3.89(m, 4H), 1.64(m, 6H)
Compound No. 309: Benzo[l,3]dioxol-5-ylmethyl-(2-morpholino-4-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.51 (m, 3H), 7.07(t, /=7.4 Hz, IH), 6.89(s, IH), 6.85(d, /=7.8Hz, IH), 6.78(d, /=7.8 Hz, IH), 5.96(s, 2H), 5.69(br s, IH), 4.70(d, /=5.4 Hz, 2H), 3.89(m, 4H), 3.78(m, 4H)
Compound No. 310:
Benzo[l,3]dioxol-5-ylmethyl-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amin e
1H NMR(CDCl3, 300 MHz) δ 7.48(m, 3H), 7.05(t, /=8.1Hz, IH), 6.89(s, IH), 6.85(d, /=7.8Hz, IH), 6.78(d, /=7.8 Hz, IH), 5.96(s, 2H), 5.68(br s, IH), 4.70(d, /=5.4 Hz, 2H), 3.95(br t, /=4.8 Hz, 4H), 2.48(br t, /=4.8 Hz, 4H), 2.35(s, 3H) Compound No. 311: (2-Pyrrolidino-l-ylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-ainine
1H NMR(CDCl3, 300 MHz) δ 7.57(br t, /=7.8 Hz, 2H), 7.48(t, /=7.7Hz, IH), 7.02(t, /=8.0 Hz, IH), 6.66(s, 2H), 6.11(br s, IH), 4.74(d, /=5.4 Hz, 2H), 3.84(s, 9H), 3.71(br t, /=6.2 Hz, 4H), 1.98(br t, /=6.9 Hz, 4H)
Compound No. 312: (2-Piperidino-l-ylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.50(m, 3H), 7.03(br t, /=8.0 Hz, IH), 6.65(s, 2H), 5.71(br s, IH), 4.72(d, /=5.1 Hz, 2H), 3.91(m, 4H), 3.84(s, 9H), 1.65(m, 6H)
Compound No. 313: (2-Morpholino-4-ylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.53(m, 3H), 7.11(br t, /=8.4 Hz, IH), 6.63(s, 2H), 5.74(br s, IH), 4.72(d, /=5.4 Hz, 2H), 3.85(m, 16H)
Compound No. 314: [2-(4-Methylpiperazino-l-yl)-quinazolino-4-yl]-(3,4,5-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.53(m, 3H), 7.06(m, IH), 6.64(s, 2H), 5.77(br s, IH), 4.72(d, /=5.1 Hz, 2H), 3.97(br t, /=4.5 Hz, 4H), 3.85(s, 9H), 2.50(br t, /=5.0 Hz, 4H), 2.36(s, 3H)
Compound No. 315: (2-Pyrrolidino-l-ylquinazolino-4-yl)-(2,4,6-trimethoxybenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.46(m, 2H), 7.38(d, /=8.1 Hz, IH), 6.98(m, IH), 6.17(s, 2H), 5.84(br s, IH), 4.81(d, /=5.1 Hz, 2H), 3.85(s, 6H), 3.83(s, 3H), 3.74(br t, /=6.5 Hz, 4H), 1.98(m, 4H)
Compound No. 316: (2-Piperidino-l-ylquinazolino-4-yl)-(2,4,6-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.41(m, 3H), 6.98(m, IH), 616(s, 2H), 5.86(br s, IH), 4.80(d, /=5.1 Hz, 2H), 3.97(m, 4H), 3.85(s, 6H), 3.83(s, 3H), 1.65(m, 6H)
Compound No. 317: (2-Morpholino-4-ylquinazolino-4-yl)-(2,4,6-trimethoxybenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.47(m, 3H), 7.02(m, IH), 6.17(s, 2H), 5.93(br s, IH), 4.79(d, /=5.1 Hz, 2H), 3.99(m, 4H), 3.86(m, 13H)
Compound No. 318: [2-(4-Methylpiperazino-l-yl)-quinazolino-4-yl]-(2,4,6-trimethoxybenzyl)-amine Η NMR(CDCl3, 300 MHz) δ 7.45(m, 3H), 6.98(m, IH), 6.16(s, 2H), 5.91(br s, IH), 4.80(d, /=5.1 Hz, 2H), 4.01(br t, /=4.7 Hz, 4H), 3.83(s, 6H), 3.79(s, 3H), 2.52(br t, /=5.0 Hz, 4H), 2.04(s, 3H)
Compound No. 319: (2,4-Dimethoxybenzyl)-(2-ethoxyquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.60(m, 2H), 7.52(d, /=8.1 Hz, IH), 7.23(m, 2H), 6.48(m, 2H), 6.11(br s, IH), 4.78(d, /=5.4 Hz, 2H), 4.51(quartet, /=7.2 Hz, 2H), 3.88(s, 3H), 3.81(s, 3H), 1.47(t, /=7.2 Hz, 3H)
Compound No. 320: Benzo[l,3]dioxol-5-ylmethyl-(2-ethoxyquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.63(m, 3H), 7.24(m, IH), 6.82(m, 3H), 5.96(s, 2H), 5.79(br s, IH), 4.75(d, /=5.4 Hz, 2H), 4.50(quartet, /=7.2 Hz, 2H), 1.46(t, /=7.2 Hz, 3H)
Compound No. 321: (2-Isopropylquinazolino-4-yl)~(2-methoxybenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.01(d, / = 8.1 Hz, IH), 7.81(d, / = 8.1 Hz, IH), 7.69(t, / = 7.3 Hz, IH), 7.43(t, / = 7.4 Hz, 2H), 7.31(m, IH), 6.93(t, / = 7.0 Hz, 2H), 4.95(d, / = 5.8 Hz, 2H), 3.93(s, 3H), 3,31(m, IH), 1.41(d, / = 6.8 Hz, 6H)
Compound No. 322: (2,3-Dimethoxybenzyl)-(2-isopropylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 7.97(d, /=8.2 Hz, IH), 7.82(d, /=8.3 Hz, IH), 7.69(t, /=7.3 Hz, IH), 7.41(t, /=7.6 Hz, IH), 7.03(m, 2H), 6.89(m, IH), 4.96(d, /=5.8 Hz, 2H), 3.96(s, 3H), 3.89(3, 3H), 3.30(t, /=7.1 Hz, IH), 1.79(d, /=6.8 Hz, 6H)
Compound No. 323: (3,5-Dimethoxybenzyl)-(2-isopropylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.21(d, /=6.3 Hz, IH), 8.02(d, /=8.4 Hz, IH), 7.63(t, J=7.7 Hz, IH), 7.37(t, /=7.5 Hz, IH), 6.65(d, /=2.1 Hz, 2H), 6.36(d, /=2.0 Hz, IH), 4.90(d, /=5.5 Hz, 2H), 3.75(s, 6H), 3.34(t, /=7.0 Hz, IH), 1.38(d, /=6.7 Hz, 6H)
Compound No.324: (3,4-Dimethoxybenzyl)-(2-isopropylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.17(d, /=6.2 Hz, IH), 7.97(d, /=8.5 Hz, IH), 7.62(t, J=7.7 Hz, IH), 7.34(t, /=7.5 Hz, IH), 7.12(s, IH), 7.05(d, /=8.1 Hz, IH), 6.82(d, /=8.2 Hz, IH), 4.90(d, /=5.5 Hz, 2H), 3.86(s, 6H), 3.33(t, /=7.1 Hz, IH), 1.40(d, /=6.7 Hz, 6H)
Compound No. 325: (2-Isopropylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.22(d, /=6.2 Hz, IH), 8.00(d, /=8.5 Hz, IH), 7.64(t, J=7.7 Hz, IH), 7.36(t, /=7.4 Hz, IH), 6.79(s, 2H), 4.90(d, /=5.5 Hz, 2H), 3.84(s, 9H), 3.34(t, /=7.2 Hz, IH), 1.39(d, /=6.7 Hz, 6H)
Compound No. 326: (2,5-Dimethoxybenzyl)-(2-isopropylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.06(d, /=8.1 Hz, IH), 7.86(d, /=8.0 Hz, IH), 7.70(t, /=7.3 Hz, IH), 7.43(t, /=7.4 Hz, IH), 7.01(s, IH), 6.80(m, 2H), 4.93(d, /=5.6 Hz, 2H), 3.89(s, 3H), 3.75(s, 3H), 3.36(t, /=7.4 Hz, IH), 1.40(d, /=6.9 Hz, 6H)
Compound No. 327: (2-Isopropylquinazolino-4-yl)-(2,4,6-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.09(d, /=8.0 Hz, IH), 7.73(d, /=8.1 Hz, IH), 7.65(t, /=7.2 Hz, IH), 7.41(t, /=7.3 Hz, IH), 6.31(br, IH), 6.18(s, 2H), 4.97(d, /=5.3 Hz, 2H), 3.88(s, 9H), 3.34(t, /=7.3 Hz, IH), 1.42(d, /=6.5 Hz, 6H)
Compound No. 328: (2-Benzylquinazolino-4-yl)-(2-methoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.78(d, /=8.1 Hz, IH), 7.65(m, IH), 7.58(d, /=8.1 Hz, IH), 7.37-7.18(m, 6H), 6.87(d, /=8.4 Hz, IH), 6.83(t, /=7.2 Hz, IH), 6.21(br, IH), 4.81(d, /=5.7 Hz, 2H), 4.20(s, 2H), 3.88(s, 3H) Compound No. 329: (2-Benzylquinazolino-4-yl)-(2,3-dimethoxybenzyl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.78(Ci, /=8.1 Hz, IH), 7.67(dd,
Figure imgf000086_0001
Hz, IH), 7.60(d, /=8.4 Hz, IH), 7.46(d, /=6.9 Hz, 2H), 7.36-7.17(m, 4H), 6.93(t, /=8.1 Hz, IH), 6.83(m, 2H), 6.22(br, IH), 4.83(d, /=5.7 Hz, 2H), 4.20(s, 2H), 3.90(s, 3H), 3.86(s, 3H)
Compound No. 330: (2-Benzylquinazolino-4-yl)-(3,5-dimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.89(t, /=9.0 Hz, 2H), 7.62(t, J=7.7 Hz, IH), 7.48(d, /=7.1 Hz, 2H), 7.31(m, 4H), 6.55(d, /=1.9 Hz, 2H), 6.37(s, IH), 4.81(d, /=5.3 Hz, 2H), 4.22(s, 2H), 3.73(s, 6H)
Compound No. 331: (2-Benzylquinazolino-4-yl)-(3,4-dimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.11(d, /=6.1 Hz, IH), 7.91(d, /=8.2 Hz, IH), 7.52(m, 3H), 7.23(m, 4H), 7.02(s, IH), 6.92(m, IH), 6.75(d, /=8.2 Hz, IH), 4.83(d, /=5.2 Hz, 2H), 4.27(s, 2H), 3.86(s, 3H), 3.69(s, 3H)
Compound No. 332: (2-Benzylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.03(d, /=7.6 Hz, IH), 7.91 (d, /=8.4 Hz, IH), 7.61 (t, J=7.7 Hz, IH), 7.50(d, /=6.8 Hz, 2H), 7.32(t, /=7.6 Hz, IH), 7.23(m, 3H), 6.66(s, 2H), 4.81 (d, /=5.2 Hz, 2H), 4.25(s, 2H), 3.86(s, 9H)
Compound No. 333: (2-Benzylquinazolino-4-yl)-(2,4-dimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.95(d, /=8.1 Hz, IH), 7.68(m, 2H), 7.54(m, 2H), 7.40-7.24(m, 4H), 7.10(d, /=8.3 Hz, IH), 6.45(d, /=2.23 Hz, IH), 6.35(m, IH), 4.79(d, /=5.5 Hz, 2H), 4.28(s, 2H), 3.86(s, 3H), 3.81 (s, 3H)
Compound No. 334: (2-Benzylquinazolino-4-yl)-(2,5-dimethoxybenzyl)-amine
1H NMRCDCl3, 300 MHz) δ 8.26(d, /=8.3 Hz, IH), 8.13(d, /=8.2 Hz, IH), 7.61(m, 3H), 7.40(t, ]=7.7 Hz, IH), 7.24(m, 4H), 7.79(m, 3H), 4.94(d, /=5.4 Hz, 2H), 4.38(s, 2H), 3.85(s, 3H), 3.68(s, 3H) Compound No. 335: (2-Benzylquinazolino-4-yl)-(2,4,6-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.12(d, /=8.1 Hz, IH), 7.63(m, 4H), 7.35(m, 4H), 6.17(s, 2H), 4.96(d, /=5.4 Hz, 2H), 4.40(s, 2H), 3.85(s, 9H)
Compound No. 336: (2-Phenylquinazolino-4-yl)-(3,4,5-triinethoxybenzyl)-amine
Compound No. 337: (2-Phenylquinazolino-4-yl)-(2,4/6-trimethoxybenzyl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.76(d, /=5.4 Hz, 2H), 7.69(m, 2H), 7.54(m, 3H), 7.41(t, /=7.6 Hz, IH), 7.28(s, IH), 6.19(s, 2H), 5.00(d, 2H, /=5.1 Hz), 3.90(s, 9H)
Compound No. 338: (2-Furano-2-ylquinazolino-4-yl)-(2-methoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.01(d, /=8.4 Hz, IH), 7.70(m, 3H), 7.48(d, /=6.6 Hz, 2H), 7.39(t, /=7.5 Hz, IH), 7.29(d, /=7.8 Hz, IH), 6.95(t, /=7.4 Hz, 2H), 6.60(m, IH), 6.87(br, IH), 4.97(d, /=5.3 Hz, 2H), 3.93(s, 3H)
Compound No. 339: (2-Furano-2-ylquinazolino-4-yl)-(3-methoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.01 (d, /=8.4 Hz, IH), 7.78(d, /=8.1 Hz, IH), 7.67(m, 2H), 7.42(m, 2H), 7.27(m, 2H), 6.87(d, /=2.0 Hz, IH), 6.58(m, IH), 6.50(br, IH), 4.94(d, /=5.2 Hz, 2H), 3.80(s, 3H)
Compound No. 340: (2-Furano-2-ylquinazolino-4-yl)-(4-methoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.01(d, /=8.3 Hz, IH), 7.77(d, /=8.1 Hz, IH), 7.67(t, /=7.2 Hz, 2H), 7.41(m, 4H), 6.90(d, /=8.6 Hz, 2H), 6.59(m, IH), 6.50(br, IH), 4.89(d, /=5.5 Hz, 2H), 3.82(s, 3H)
Compound No. 341: Benzo[l,3]dioxol-5-ylmethyl-(2-furano-2-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.99(d, /=8.3 Hz, IH), 7.78(d, /=8.1 Hz, IH), 7.65(m, 2H), 7.41(t, /=5.6 Hz, 2H), 6.94(t, /=7.6 Hz, 2H), 6.78(d, /=7.9 Hz, IH), 6.57(m, IH), 6.41(br, IH), 5.95(s, 2H), 4.85(d, /=5.4 Hz, 2H) Compound No. 342: (2,3-Dimethoxybenzyl)-(2-furano-2-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.02(d, /=8.2 Hz, IH), 7.71(m, 3H), 7.52(d, /=2.3 Hz, IH), 7.39(m, IH), 7.07(t, /=4.9 Hz, 2H), 6.90(m, IH), 6.67(br, IH), 6.60(m, IH), 4.49(d, /=5.5 Hz, 2H)
Compound No. 343: (3,5-Dimethoxybenzyl)-(2-furano-2-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.02(d, /=8.3 Hz, IH), 7.84(d, /=8.2 Hz, IH), 7.68(m, 2H), 7.45(d, /=3.1 Hz, IH), 7.38(m, IH), 6.65(m, 2H), 6.64(br, IH), 6.57(m, IH), 6.40(t, /=2.1 Hz, IH), 4.90(d, /=5.3 Hz, 2H), 3.77(s, 6H)
Compound No. 344: (3,4-Dimethoxybenzyl)-(2-furano-2-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.00(d, /=8.3 Hz, IH), 7.79(d, /=8.1 Hz, IH), 7.66(t, /=2.3 Hz, 2H), 7.47(d, /=3.2 Hz, IH), 7.36(m, IH), 7.09(s, IH), 7.01 (m, IH), 6.86(d, /=8.2 Hz, IH), 6.59(m, IH), 6.46(br, IH), 4.99(d, /=5.3 Hz, 2H), 3.88(s, 3H), 3.85(s, 3H)
Compound No. 345: (2-Furano-2-ylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.01(d, /=8.3 Hz, IH), 7.86(d, /=8.3 Hz, IH), 7.65(t, /=6.2 Hz, 2H), 7.54(d, /=3.1 Hz, IH), 7.34(t, /=7.5 Hz, IH), 6.80(br, IH), 6.77(s, 2H), 6.60(m, IH), 4.99(d, /=5.4 Hz, 2H), 3.87(s, 9H) Compound No. 346: (2,4-Dimethoxybenzyl)-(2-furano-2-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.01(d, /=8.2 Hz, IH), 7.69(m, 3H),7.51(d, /=4.6 Hz, IH), 7.38(t, /=7.4 Hz, 2H), 6.60(m, IH), 6.48(m, 3H), 4.88(d, /=5.4 Hz, 2H), 3.89(s, 3H), 3.81(s, 3H)
Compound No. 347: (2,5-Dimethoxybenzyl)-(2-furano-2-ylquinazolino-4-yl)-amine iH NMR(CDCl3, 300 MHz) δ 8.01 (d, /=8.3 Hz, IH), 7.70(m, 3H), 7.50(d, /=2.9 Hz, IH), 7.41 (d, /=7.3 Hz, IH), 7.10(d, /=2.8 Hz, IH), 6.84(m, 2H), 6.58(m, IH), 4.94(d, /=5.4 Hz, 2H), 3.89(s, 3H), 3.74(s, 3H) Compound No. 348: (2-Furano-2-ylquinazolino-4-yl)-(2,4,6-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.01(Cl, /=8.2 Hz, IH), 7.67(m, 4H), 7.37(t, /=7.5 Hz, IH), 6.60(m, IH), 6.21(br, IH), 6.17(s, 2H), 4.96(d, /=5.4 Hz, 2H), 3.87(s, 9H)
Compound No. 349: (2-Methoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.21 (d, /=3.3 Hz, IH), 7.91 (d, /=8.3 Hz, IH), 7.68(m, 2H), 7.52(m, 2H), 7.37(t, /=7.6 Hz, 2H), 7.29(d, }=7.7 Hz, IH), 7.19(t, /=4.2 Hz, IH), 6.95(t, J=7.7 Hz, 2H), 6.49(br,lH), 4.98(d, /=5.3 Hz, 2H), 3.95(s, 3H)
Compound No. 350: (3-Methoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 8.17(d, /=3.2 Hz, IH), 7.91(d, /=8.3 Hz, IH), 7.71(m, 2H), 7.47(m, IH), 7.37(m, IH), 7.28(m, IH), 7.16(m, IH), 7.06(d, /=7.4 Hz, 2H), 6.84(m, IH), 6.30(br, IH), 4.94(d, /=5.5 Hz, 2H), 3.79(s, 3H)
Compound No. 351: (4-Methoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine Η NMR(CDCl3, 300 MHz) δ 8.17(d, /=3.1 Hz, IH), 7.90(d, /=8.5 Hz, IH), 7.70(m, 2H), 7.46(m, 3H), 7.36(m, IH), 7.17(t, /=4.3 Hz, IH), 6.91 (d, /=8.5 Hz, 2H), 6.23(br, IH), 4.90(d, /=5.3 Hz, 2H), 3.82(s, 3H)
Compound No. 352:
Benzo[l,3]dioxol-5-ylmethyl-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.10(d, /=3.1 Hz, IH), 7.88(d, /=8.5 Hz, IH), 7.69(m, 2H),
7.46(t, /=2.5 Hz, IH), 7.38(m, IH), 7.17(m, IH), 6.96(t, /=7.5 Hz, 2H), 6.80(d, /=7.9 Hz, IH), 6.11(br, IH), 5.96(s, 2H), 4.87(d, /=5.3 Hz, 2H)
Compound No. 353: (2,3-Dimethoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.21(d, /=3.2 Hz, IH), 7.91(d, /=8.2 Hz, IH), 7.69(m, 2H), 7.49(d, /=4.8 Hz, IH), 7.36(m, IH), 7.17(m, 2H), 7.04(m, IH), 6.90(d, /=7.2 Hz, IH), 6.45(br, IH), 5.00(d, /=5.4 Hz, 2H), 3.98(s, 3H), 3.90(s, 3H) Compound No. 354: (3,5-Dimethoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.20(4 /=3.3 Hzx IH), 7.92(4 /=8.4 Hz, IH), 7.76(4 /=10.9 Hz, IH), 7.68(t, J=7.7 Hz, IH), 7.48(4 /=4.9 Hz, IH), 7.36(t, /=7.6Hz, IH), 7.16(m, IH), 6.66(s7 2H), 6.41(s, IH), 4.90(4 /=5.4 Hz, 2H), 3.78(s, 3H)
Compound No. 355: (3,4-Dimethoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 8.19(4 /=3.0 Hz, IH), 7.91(4 /=8.5 Hz, IH), 7.67(m, 2H), 7.49(t, /=2.5 Hz, IH), 7.35(m, IH), 7.17(m, IH), 7.09(m, IH), 7.01 (m, IH), 6.85(4 /=8.1 Hz, IH), 6.38(br, IH), 4.89(4 /=5.3 Hz, 2H), 3.88(s, 3H), 3.84(s, 3H)
Compound No. 356: (2-Thiopenyl-2-ylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.19(d, /=3.1 Hz, IH), 7.91(d, /=8.4 Hz, IH), 7.79(d,
7=8.1 Hz, IH), 7.68(t, /=7.6 Hz, IH), 7.48(4 /=5.0 Hz, IH), 7.36(t, /=7.6 Hz, IH), 7.17(t, /=4.3 Hz, IH), 6.75(s, 2H), 6.43(br, IH), 4.88(4 /=5.4 Hz, 2H), 3.85(s, 9H)
Compound No. 357:
(2,4-Dimethoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.23(4 /=3.0 Hz, IH), 7.91(4 /=8.2 Hz, IH), 7.65(m, 2H), 7.48(t, /=7.6 Hz, 2H), 7.38(4 /=7.9Hz, IH), 7.19(m, IH), 6.48(m, 3H), 4.90(4 /=5.4 Hz, 2H), 3.93(s, 3H), 3.80(s, 3H)
Compound No. 358:
(2,5-Dimethoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.22(4 /=3.1 Hz, IH), 7.91(4 /=8.5 Hz, IH), 7.69(m, 2H),
7.49(t, /=3.5 Hz, IH), 7.37(m, IH), 7.18(m, 2H), 6.81(t, /=4.8 Hz, 2H), 6.52(br, IH), 4.95(4 /=5.3 Hz, 2H), 3.90(s, 3H), 3.74(s, 3H) Compound No. 359: (2-Thiopenyl-2-ylquinazolino-4-yl)-(2,4/6-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 8.28(d, /=3.2 Hz, IH), 7.93(d, /=8.4 Hz, IH), 7.65(m, 2H), 7.49(d, /=4.8 Hz, IH), 7.35(t, /=7.6 Hz, IH), 7.19(t, /=4.3 Hz, IH), 6.20(br, IH), 6.18(S, 2H), 5.00(d, /=5.3 Hz, 2H), 3.88(s, 9H)
Compound No. 360: (2-Methoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.90(d, /=8.4 Hz, IH), 7.68-7.55(m, 4H), 7.38-7.20(m, 6H), 6.85(m, 2H), 6.24(br, IH), 5.41(s, IH), 4.84(d, /=6.0 Hz, 2H), 3.87(s, 3H), 3.50(s, 3H)
Compound No. 361: (3-Methoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.95(d, /=8.3 Hz, IH), 7.75(d, /=8.1 Hz, IH), 7.64(m, 3H), 7.28(m, 5H), 6.94(s, 2H), 6.83(d, /=8.1 Hz, IH), 6.59(br, IH), 5.42(s, IH), 4.83(d, /=4.9 Hz, 2H), 3.76(S, 3H), 3.49(s, 3H)
Compound No. 362: (4-Methoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine Η NMR(CDCl3, 300 MHz) δ 7.93(d, /=8.4 Hz, IH), 7.70-7.57(m, 4H), 7.39-7.22(m, 6H), 6.81(d, /=8.4 Hz, 2H), 5.89(br, IH), 5.42(s, IH), 4.76(d, /=5.4 Hz, 2H), 3.79(s, 3H), 3.50(s, 3H)
Compound No. 363: Benzo[l,3]dioxol-5-ylmethyl-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine Η NMR(CDCl3, 300 MHz) δ 7.95(d, /=8.3 Hz, IH), 7.81(d, /=8.1 Hz, IH), 7.64(m, 2H), 7.35(m, 5H), 6.83(m, 2H), 6.70(d, /=7.9 Hz, IH), 5.93(s, 2H), 5.46(s, IH), 4.76(d, /=5.1 Hz, 2H), 3.51(s, 3H)
Compound No. 364:
(2,3-Dimethoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine 1H NMR(CDCl3, 300 MHz) δ 8.00(d, /=8.3 Hz, IH), 7.69(m, 3H), 7.32(m, 5H), 6.89(m, 3H), 5.50(s, IH), 4.90(d, /=5.2 Hz, 2H), 3.93(s, 3H), 3.88(s, 3H), 3.51(s, 3H)
Compound No. 365: (3,5-Dimethoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.95(d, /=8.3 Hz, IH), 7.77(d, IH, /=8.1 Hz), 7.65(m, 3H), 7.31(m, 5H), 6.60(br, IH), 6.55(s, 2H), 6.39(d, /=2.0 Hz, IH), 5.44(s, IH), 4.81(d, /=5.1 Hz, 2H), 3.75(s, 6H), 3.49(s, 3H)
Compound No. 366:
(3,4-Dimethoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine
Η NMR(CDCl3, 300 MHz) δ 7.94(d, /=8.4 Hz, IH), 7.78(d, /=8.1 Hz, IH), 7.68(d, /=6.9 Hz, 2H), 7.58(t, /=7.6 Hz, IH), 7.33(m, 5H), 6.96(s, IH), 6.91(t, /=4.1 Hz, IH), 5.45(s, IH), 4.80(d, /=5.2 Hz, 2H), 3.88(s, 3H), 3.80(s, 3H), 3.50(s, 3H)
Compound No. 367:
[2-(Methoxyρhenylmethyl)-quinazolino-4-yl]-(3,4/5-trimethoxybenzyl)-amine Η NMR(CDCl3, 300 MHz) δ 7.95(d, /=8.3 Hz, IH), 7.83(d, /=8.2 Hz, IH), 7.63(m, 3H), 7.30(m, 5H), 6.75(br, IH), 6.64(s, 2H), 5.45(s, IH), 4.80(d, /=5.2 Hz, 2H), 3.78(s, 9H), 3.48(s, 3H)
Compound No. 368: (2,4-Dimethoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.97(d, /=8.3 Hz, IH), 7.67(m, 4H), 7.33(m, 5H), 7.18(d, /=8.3 Hz, IH), 6.48(br, IH), 6.45(s, IH), 6.35(m, IH), 5.50(s, IH), 4.79(d, /=5.1 Hz, 2H), 8.85(s, 3H), 3.79(s, 3H), 3.52(s, 3H)
Compound No. 369: (2,5-Dimethoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine Η NMR(CDCl3, 300 MHz) δ 7.96(d, /=8.3 Hz, IH), 7.66(m, 4H), 7.34(m, 5H), 6.97(s, IH), 6.80(t, /=3.8 Hz, IH), 6.54(br, IH), 5.47(s, IH), 4.86(d, /=5.0 Hz, 2H), 3.86(s, 3H), 3.72(s, 3H), 3.50(S, 3H)
Compound No. 370: [2-(Methoxyphenylmethyl)-quinazolino-4-yl]-(2,4,6-trimethoxybenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.89(d, /=8.1 Hz, IH), 7.75(dd, J1 =8.4 Hz, J2=Ll Hz, 2H), 7.63(td, Hz, /2=1.2 Hz, IH), 7.51(d, /=7.2 Hz, IH), 7.35-7.21(m, 4H), 6.16(s, 2H), 5.98(br, IH), 5.43(s, IH), 4.87(d, /=5.4 Hz, 2H), 3.82(s, 3H), 3.80(s, 6H), 3.52(s, 3H)
Compound No. 371: (2-Methoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.85(d, /=8.6 Hz, IH), 7.64(m, 2H), 7.56(d, /=7.4 Hz, 2H), 7.30(m, 6H), 6.90(t, /=7.9 Hz, 2H), 6.55(br, IH), 4.90(d, /=5.4 Hz, 2H), 4.40(d, /=7.0 Hz, IH), 3.92(s, 3H), 1.79(d, /=7.1 Hz, 3H)
Compound No. 372:
(3-Methoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.85(d, /=8.6 Hz, IH), 7.74(d, /=8.1 Hz, IH), 7.63(m, IH), 7.51(d, /=7.2 Hz, 2H), 7.25(m, 5H), 6.97(d, /=7.9 Hz, 2H), 6.86(d, /=2.0 Hz, IH), 4.88(d, /=5.4 Hz, 2H), 4.36(m, IH), 3.77(s, 3H), 1.75(d, /=7.1 Hz, 3H)
Compound No. 373:
(4-Methoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.84(d, /=8.5 Hz, IH), 7.73(4 /=8.1 Hz, IH), 7.62(t, /=7.6
Hz, IH), 7.53(d, /=7.6 Hz, 2H), 7.27(m, 6H), 6.85(d, /=7.6 Hz, 2H), 6.38(br, IH), 4.81(d, /=5.5 Hz, 2H), 4.40(m, IH), 3.81 (s, 3H), 1.78(d, /=7.3 Hz, 3H)
Compound No. 374: Benzo[l,3]dioxol-5-ylmethyl-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.85(d, /=8.4 Hz, IH), 7.75(d, /=8.5 Hz, IH), 7.63(m, IH), 5.52(d, /=7.5 Hz, 2H), 7.28(m, 4H), 6.85(t, /=6.7 Hz, 2H), 6.73(d, /=7.8 Hz, IH), 6.49(br, IH), 5.94(s, 2H), 4.78(d, /=5.4 Hz, 2H), 4.40(m, IH), 1.78(d, /=7.2 Hz, 3H) Compound No. 375: (2,3-Dimethoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.85(d, /=8.0 Hz, IH), 7.65(m, 2H), 7.55(d, /=7.5 Hz, 2H), 7.28(m, 5H), 6.91 (m, 3H), 6.54(br, IH), 4.91 (d, /=5.4 Hz, 2H), 4.41 (m, IH), 3.94(s, 3H), 3.89(s, 3H), 1.78(d, /=7.4 Hz, 3H)
Compound No. 376: (3,5-Dimethoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine 1H NMR(CDCl3, 300 MHz) δ 7.84(d, /=8.3 Hz, IH), 7.74(d, /=8.1 Hz, IH), 7.63(m, IH), 7.52(d, /=7.3 Hz, 2H), 7.24(m, 4H), 6.56(s, 2H), 6.41 (s, IH), 4.48(d, /=5.3 Hz, 2H), 4.38(m, IH), 3.75(s, 6H), 1.78(d, /=7.1 Hz, 3H)
Compound No. 377: (3,4-Dimethoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.3 Hz, IH), 7.75(d, /=8.2 Hz, IH), 7.62(d, /=7.4 Hz, IH), 7.53(d, /=7.2 Hz, 2H), 7.25(m, 5H), 6.94(d, /=5.6 Hz, 2H), 6.82(d, /=8.6 Hz, IH), 6.32(br, IH), 4.84(d, /=5.4 Hz, 2H), 4.38(m, IH), 3.89(s, 3H), 3.79(s, 3H), 1.78(d, /=7.1 Hz, 3H)
Compound No. 378: [2-(l-Phenylethyl)-quinazolino-4-yl]-(3,4,5-tπmethoxybenzyl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.82(t, /=9.2 Hz, 2H), 7.54(m, 2H), 7.27(m, 5H), 6.65(s, 2H), 4.86(d, /=5.4 Hz, 2H), 4.40(m, IH), 3.79(s, 9H), 1.78(d, /=7.1 Hz, 3H)
Compound No. 379:
(2,4-Dimethoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.85(d, /=8.4 Hz, IH), 7.60(m, 4H), 7.32(m, 3H), 7.21 (t,
/=6.9 Hz, 2H), 6.48(d, /=2.0 Hz, IH), 6.39(br, IH), 6.36(d, /=8.1 Hz, IH), 4.48(d, /=5.3 Hz, 2H), 4.40(m, IH), 3.88(s, 3H), 3.82(s, 3H), l,80(d, /=7.1 Hz, 3H) Compound No. 380: (2,5-Dimethoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
1H NMR(CDCl3, 300 MHz) δ 7.83(d, /=8.2 Hz, IH), 7.63(m, 2H), 7.56(d, /=7.4 Hz, 2H), 7.35(m, IH), 7.28(m, 2H), 7.19(d, /=7.3 Hz, IH), 6.98(d, /=2.8 Hz, IH), 6.82(m, 2H), 6.28(br, IH), 4.88(d, /=5.4 Hz, 2H), 4.38(m, 2H), 3.88(s, 3H), 3.79(s, 3H), 1.79(d, /=7.1 Hz, 3H)
Compound No. 381: [2-(l-Phenylethyl)-quinazolino-4-yl]-(2,4,6-trimethoxybenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.76(d, /=8.4 Hz, IH), 7.64-7.50(m, 4H), 7.31-7.24(m, 3H), 7.16(t, /=7.2 Hz, IH), 6.17(s, 2H), 6.03(br, IH), 5.02-4.83(m, 2H), 4.31(q, /=7.2 Hz, IH), 3.83(s, 9H), 1.80(d, /=7.2 Hz, 3H)
Compound No. 382: (2-Cyclopropylquinazolino-4-yl)-(2-methoxybenzyl)-amine iH NMR(CDCl3, 300 MHz) δ 7.75(d, /=8.0 Hz, IH), 7.62(m, 2H), 7.35(m, 3H), 6.93(m, 2H), 6.32(br, IH), 4.81(d, /=5.4 Hz, 2H), 3.98(s, 3H), 2.19(m, IH), 1.25(m, 2H), 1.01(m, 2H)
Compound No. 383: (2-Cyclopropylquinazolino-4-yl)-(3-methoxybenzyl)-amine Η NMR(CDCl3, 300 MHz) δ 7.77-7.61 (m, 3H), 7.35-7.24(m, 2H), 6.94(m, 2H), 6.84(dd, /j=8.4 Hz, /2=2.7 Hz, IH), 5.93(br, IH), 4.78(d, /=5.7 Hz, 2H), 3.79(s, 3H), 2.17(m, IH), 1.17(m, 2H), 0.95(m, 2H)
Compound No. 384: (2-Cyclopropylquinazolino-4-yl)-(4-methoxybenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.78(d, /=7.9 Hz, IH), 7.70(m, 2H), 7.35(m, 3H), 6.90(d, /=7.8 Hz, 2H), 5.98(br, IH), 4.74(d, /=5.4 Hz, 2H), 3.82(s, 3H), 2.20(m, IH), 1.21(m, 2H), 1.01 (m, 2H)
Compound No. 385: Benzo[l,3]dioxol-5-ylmethyl-(2-cyclopropylquinazolino-4-yl)-amine
Η NMR(CDCl3, 300 MHz) δ 7.76(d, /=8.0 Hz, IH), 7.66(m, 2H), 7.43(m, IH), 6.84(m, 3H), 5.96(s, 2H), 4.71 (d, /=5.4 Hz, 2H), 2.19(m, IH), 1.20(m, 2H), 1.01(m, 2H)
Compound No. 386: (2-Cyclopropylquinazolino-4-yl)-(2,3-dimethoxybenzyl)-amine Η NMR(CDCl3, 300 MHz) δ 7.74(d, /=7.9 Hz, IH), 7.64(m, 2H), 7.32(d, /=8.4 Hz, IH), 6.99(m, 2H), 6.89(m, IH), 6.32(br, IH), 4.83(d, /=5.4 Hz, 2H), 3.94(s, 3H), 3.89(s, 3H), 2.18(m, IH), 1.22(m, 2H), 1.01(m, 2H)
Compound No. 387: (2-Cyclopropylquinazolino-4-yl)-(3,5-dimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.76(d, /=7.8 Hz, IH), 7.66(m, 2H), 7.35(m, IH), 6.54(s, 2H), 6.39(s, IH), 6.23(br, IH), 4.74(d, /=5.4 Hz, 2H), 3.79(s, 6H), 2.18(m, IH), 1.19(m, 2H), 0.99(m, 2H)
Compound No. 388:
(2-Cyclopropylquinazolino-4-yl)-(3,4-dimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.76(d, /=7.8 Hz, IH), 7.67(t, /=7.4 Hz, 2H), 7.31(t, /=3.8 Hz, IH), 6.94(d, /=5.0 Hz, 2H), 6.84(t, /=4.3 Hz, IH), 6.07 (br, IH), 4.74(d, /=5.4 Hz, 2H), 3.89(s, 3H), 3.87(s, 3H), 2.20(m, IH), 1.22(m, 2H), 1.00(m, 2H)
Compound No. 389: (2-Cyclopropylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine iH NMR(CDCl3, 300 MHz) δ 7.77-7.64(m, 3H), 7.33(t, /=7.2 Hz, IH), 6.61 (s, IH), 6.00(br, IH), 4.72(d, /=5.4 Hz, 2H), 3.84(s, 9H), 2.19(m, IH), 1.19(m, 2H), 0.98(m, 2H)
Compound No. 390:
(2-Cyclopropylquinazolino-4-yl)-(2,4-dimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.73(d, /=8.3 Hz, IH), 7.62(m, 2H), 7.32(d, /=9.3 Hz, 2H),
6.48(m, 2H), 6.14(br, IH), 4.73(d, /=5.4 Hz, 2H), 3.89(s, 3H), 3.81(s, 3H), 2.19(m, IH), 1.25(m, 2H), 1.01(m, 2H) Compound No. 391: (2-Cyclopropylquinazolino-4-yl)-(2,5-dimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.74(d, /=8.5 Hz, IH), 7.63(m, 2H), 7.33(t, /=7.5 Hz, IH), 6.98(d, /=2.1 Hz, IH), 6.81(m, 2H), 6.25(br, IH), 3.88(s, 3H), 3.78(s, 3H), 2.18(m, IH), 1.25(m, 2H), 1.01(m, 2H)
Compound No. 392: (2-Cyclopropylquinazolino-4-yl)-(2,4,6-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.73(d, /=8.3 Hz, IH), 7.64(m, IH), 7.53(d, /=6.2 Hz, IH), 7.29(m, IH), 2.17(s, 2H), 6.06(br, IH), 4.82(d, /=5.3 Hz, 2H), 3.87(s, 6H), 3.84(s, 3H), 2.18(m, IH), 1.30(m, 2H), 1.00(m, 2H)
Compound No. 393: (2-Methoxybenzyl)-(2-propylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.78(d, /=8.2 Hz, IH), 7.68(m, 2H), 7.44(d, /=7.3 Hz, IH), 7.38(d, / = 7.0 Hz, IH), 7.34(m, IH), 6.95(t, /=7.8 Hz, 2H), 6.24(br, IH), 4.91 (d, /=5.7 Hz, 2H), 3.93(s, 3H), 2.87(t, J=7.7 Hz, 2H), 1.93(m, 2H), 1.04(t, /=7.4 Hz, 3H)
Compound No. 394: (3-Methoxybenzyl)-(2-propylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.80(d, /=8.4 Hz, IH), 7.68(m, 2H), 7.35(m, 2H), 6.99(m, 2H), 6.85(m, IH), 5.83(br s, IH), 4.86(d, /=5.1 Hz, 2H), 3.80(s, 3H), 2.86(t, J=7.7 Hz, 2H), 1.90(sextet, J^7.5 Hz, 2H), 1.02(t, /=7.4 Hz, 3H)
Compound No. 395: (4-Methoxybenzyl)-(2-propylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.79(d, /=8.4Hz, IH), 7.65(m, 2H), 7.38(m, 3H), 6.88(d, /=8.4Hz, 2H), 5.81(br s, IH), 4.80(d, /=5.1 Hz, 2H), 3.81(s, 3H), 2.86(t, /=7.8 Hz, 2H), 1.91 (sextet, /=7.5 Hz, 2H), 1.03(t, /=7.5 Hz, 3H)
Compound No. 396: Benzo[l,3]dioxol-5-ylmethyl-(2-propylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.80(d, /=7.8Hz, IH), 7.68(m, 2H), 7.37(t, /=7.5 Hz, IH), 6.89(m, 2H), 6.78(d, /=7.8 Hz, IH), 5.95(s, 2H), 5.80(br s, IH), 4.78(d, /=5.4 Hz, 2H), 2.86(t, /=7.8 Hz, 2H), 1.91 (sextet, /=7.5 Hz, 2H), 1.03(t, /=7.5 Hz, 3H)
Compound No. 397: (2,3-Dimethoxybenzyl)-(2-propylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.76(d, /=8.4Hz, IH), 7.64(m, 2H), 7.37(t, /=7.2 Hz, IH), 7.03(d, /=4.8 Hz, 2H), 6.88(t, /=4.8 Hz, IH), 6.17(br s, IH), 4.90(d, /=5.7 Hz, 2H), 3.94(s, 3H), 3.89(s, 3H), 2.86(t, /=7.8 Hz, 2H), 1.91(sextet, /=7.5 Hz, 2H), 1.03(t, /=7.5 Hz, 3H)
Compound No. 398: (3,5-Dimethoxybenzyl)-(2-propylquinazolino-4-yl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.80(d, /=8.1Hz, IH), 7.70(m, 2H), 7.38(t, /=7.2 Hz, IH), 6.57(d, /=2.1 Hz, 2H), 6.41(m, IH), 5.83(br s, IH), 4.82(d, /=5.4 Hz, 2H), 3.78(s, 6H), 2.86(t, /=7.8 Hz, 2H), 1.91 (sextet, /=7.5 Hz, 2H), 1.03(t, /=7.5 Hz, 3H)
Compound No. 399: (3,4-Dimethoxybenzyl)-(2-propylquinazolino-4-yl)-amine iH NMR(CDCl3, 300 MHz) δ 7.80(d, /=8.1Hz, IH), 7.69(m, 2H), 7.37(t, /=7.5 Hz, IH), 6.97(d, /=7.2 Hz, 2H), 6.85(d, /=8.4 Hz, IH), 5.81 (br s, IH), 4.81 (d, /=5.4 Hz, 2H), 3.88(s, 3H), 3.86(s, 3H), 2.86(t, /=7.8 Hz, 2H), 1.91(sextet, /=7.5 Hz, 2H), 1.03(t, J=7.5 Hz, 3H)
Compound No. 400: (2-Propylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.81 (d, /=8.3 Hz, 3H), 7.71 (m, 2H), 4.40(m, IH), 6.68(s, 2H), 6.07(br, IH), 4.82(d, /=5.5 Hz, 2H), 3.86(s, 9H), 2.88(t, J=7.7 Hz, 2H), 1.94(m, 2H), 1.03(t, /=7.4 Hz, 2H)
Compound No. 401: (2,4-Dimethoxybenzyl)-(2-propylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.78(d, /=8.5 Hz, IH), 7.64(m, 2H), 7.36(m, 2H), 7.47(m, 2H), 6.14(br, IH), 4.82(d, /=5.4 Hz, 2H), 3.90(s, 3H), 3.82(s, 3H), 2.87(t, /=7.8 Hz, 2H), 1.96(m, 2H), 1.05(t, /=7.3 Hz, 2H)
Compound No.402: (2,5-Dimethoxybenzyl)-(2-propylquinazolino-4-yl)-amine 1H NMR(CDCl3, 300 MHz) δ 7.78(d, /=8.1 Hz, IH), 7.66(m, 2H), 7.37(m, IH), 7.05(s, IH), 6.82(m, 2H), 6.29(br, IH), 4.87(d, /=5.4 Hz, 2H), 3.88(s, 3H), 3.76(s, 3H), 2.86(t, /=7.6 Hz, 2H), 1.95(m, 2H), 1.05(t, /=7.5 Hz, 2H)
Compound No. 403: (2-Propylquinazolino-4-yl)-(2,4,6-trimethoxybenzyl)-amine
1H NMR(CDCl3, 300 MHz) δ 7.76(d, /=8.3 Hz, IH), 7.60(m, 2H), 7.35(m, IH), 6.18(s, 2H), 5.98(br, IH), 4.88(d, /=5.4 Hz, 2H), 3.87(s, 6H), 3.85(3, 3H), 2.88(t, /=7.5 Hz, 2H), 1.98(m, 2H), 1.07(t, /=7.4 Hz, 2H)
Compound No. 404: (2-Methoxybenzyl)-quinazolino-4-ylamine
1H NMR(CDCl3, 300 MHz) δ 8.74(s, IH), 7.88(d, /=8.2 Hz, IH), 7.70(m, 2H), 7.47(m, 2H), 7.32(m, IH), 6.97(d, /=7.8 Hz, 2H), 6.25(br, IH), 4.88(d, /=5.5 Hz, 2H), 3.93(s, 3H)
Compound No. 405: (3-Methoxybenzyl)-quinazolino-4-ylamine
IH NMR(CDCl3, 300 MHz) δ 8.73(s, IH), 7.86(d, /=8.3 Hz, IH), 7.73(t, /=9.0 Hz, 2H), 7.47(m, IH), 7.31(m, IH), 6.99(t, /=7.4 Hz, 2H), 6.87(d, J=8.1 Hz, IH), 6.01(br, IH), 4.87(d, /=5.4 Hz, 2H), 3.82(s, 3H)
Compound No. 406: (4-Methoxybenzyl)-quinazolino-4-ylamine
1H NMR(CDCl3, 300 MHz) δ 8.71(s, IH), 7.85(d, /=8.1Hz, IH), 7.71(m, 2H), 7.45(t, /=7.5 Hz, IH), 7.34(d, /=8.7 Hz, 2H), 6.90(d, /=8.7 Hz, IH), 5.88(br s, IH), 4.80(d, /=5.1 Hz, 2H), 3.82(s, 3H)
Compound No. 407: Benzo[l,3]dioxol-5-ylmethylquinazolino-4-ylamine
1H NMR(CDCl3, 300 MHz) δ 8.72(s, IH), 7.88(d, /=8.4 Hz, IH), 7.40(m, 2H), 7.48(d, /=7.2 Hz, IH), 6.90(m, 2H), 6.81 (d, /=7.4 Hz, IH), 5.98(s, 2H), 5.96(br, IH), 4.78(d, /=5.4 Hz, 2H)
Compound No. 408: (2,3-Dimethoxybenzyl)-quinazolino-4-ylamine
1H NMR(CDCl3, 300 MHz) δ 8.70(s, IH), 7.73(m, 3H), 7.43(m, IH), 7.04(m, 2H), 6.93(m, IH), 6.32(br, IH), 4.89(d, /=5.4 Hz, 2H), 3.95(s, 3H), 3.90(s, 3H)
Compound No. 409: (3,5-Dimethoxybenzyl)-quinazolino-4-ylamine 1H NMR(CDCl3, 300 MHz) δ 8.71(s, IH), 7.87(d, /=8.4Hz, IH), 7.73(m, 2H), 7.47(t, /=7.2 Hz, IH), 6.40(d, /=2.4 Hz, 2H), 6.41 (t, /=2.1 Hz, IH), 5.93(br s, IH), 4.81(d, /=5.1 Hz, 2H), 3.79(s, 6H)
Compound No. 410: (3,4-Dimethoxybenzyl)~quinazolino-4-ylamine
1H NMR(CDCl3, 300 MHz) δ 8.73(s, IH), 7.87(d, /=8.2 Hz, IH), 7.75(t, /=7.4 Hz, 2H), 7.47(t, /=7.6 Hz, IH), 6.97(d, /=7.8 Hz, 2H), 6.86(d, /=8.0 Hz, IH), 6.08(br, IH), 4.81(d, /=5.2 Hz, 2H), 3.89(s, 3H), 3.87(s, 3H)
Compound No. 411: Quinazolino-4-yl-(3,4,5-trimethoxybenzyl)-amine
Η NMR(CDCl3, 300 MHz) δ 8.73(s, IH), 7.84(m, IH), 7.78(m, IH), 7.50(m, IH), 6.63(d, /=7.8 Hz, 2H), 6.23(br, IH), 4.80(d, /=5.3 Hz, 2H), 3.85(s, 9H)
Compound No.412: (2,4-Dimethoxybenzyl)-quinazolino-4-ylamine 1H NMR(CDCl3, 300 MHz) δ 8.70(s, IH), 7.83(d, /=8.3 Hz, IH), 7.72(m, 2H), 7.44(t, /=7.6 Hz, IH), 7.32(d, /=8.2 Hz, IH), 6.48(m, 2H), 6.26(br, IH), 4.80(d, /=5.4 Hz, 2H), 3.89(s, 3H), 3.82(s, 3H)
Compound No. 413: (2,5-Dimethoxybenzyl)-quinazolino-4-ylamine 1H NMR(CDCl3, 300 MHz) δ 8.69(s, IH), 7.84(d, /=8.4Hz, IH), 7.69(m, 2H), 7.44(t, /=7.2 Hz, IH), 6.99(d, /=3.0 Hz, IH), 6.83(m, 2H), 6.29(br s, IH), 4.85(d, /=5.4 Hz, 2H), 3.88(s, 3H), 3.76(s, 3H)
Compound No.414: Quinazolino-4-yl-(2,4,6-trimethoxybenzyl)-amine Η NMR(CDCl3, 300 MHz) δ 8.72(s, IH), 7.81(d, /=8.1Hz, IH), 7.69(t, /=7.5 Hz, IH), 7.60(d, /=8.1Hz, IH), 7.40(t, /=7.5 Hz, IH), 6.19(s, 2H), 6.03(br s, IH), 4.83(d, /=5.1 Hz, 2H), 3.86(s, 6H), 3.84(s, 3H)
Compound No. 415: 4-Benzyloxy-2-isopropylquinazoline Η NMR(CDCl3, 300 MHz) δ 8.16(d, /=8.1 Hz, IH), 7.87(s, /=8.4 Hz, IH), 7.77(m, IH), 7.54(d, /=7.5 Hz, 2H), 7.49-7.34(m, 4H), 5.66(s, 2H), 3.22(m, IH), 1.40(d, /=6.9 Hz, 6H) Compound No. 416: 4-Benzylsulf anyl-2-isopropylquinazoline
1H NMR(CDCl3, 300 MHz) δ 8.01((Ix /=8.4 Hzx IH), 7.89(d, /=8.4 Hz, IH), 7.78(m, IH), 7.48(m, 3H), 7.35-7.23(m, 3H), 4.67(s, 2H), 3.29(m, IH), 1.43(d, /=6.9 MHz, 6H)
The compound represented by the formula 1 may be prepared into a variety of preparation forms depending on the purpose. The following are non-limiting examples of some preparation forms comprising the compound represented by the formula 1 as an active ingredient.
Preparation Example 1: Preparation of tablets
A tablet for oral administration was prepared by wet granulation and dry granulation.
[Composition] Active ingredient 200 mg, hard silicic anhydride 10 mg, magnesium stearate
2 mg, mycrocrystalline cellulose 50 mg, sodium starch glycolate 25 mg, corn starch 113 mg, anhydrous ethanol proper quantity.
Preparation Example 2: Preparation of ointments An ointment with the following composition was prepared.
[Composition]
Active ingredient 5 g, cetyl palmitate 20 g, cetanol 40 g, stearyl alcohol 40 g, isopropyl myristrate 80 g, sorbitan monostearate 20 g, polysorbate 60 g, propyl p-oxybenzoate 1 g, methyl p-oxybenzoate 1 g, phosphoric acid and purified water proper quantity.
Preparation Example 3: Preparation of injections
An injection with the following composition was prepared. [Composition] Active ingredient 100 mg, mannitol 180 mg, dibasic sodium phosphate 25 mg, water for injection 2974 mg. Experimental Example 1. Analysis of glucose absorption
C2C12 muscle cells were cultured in DMEM (Dulbecco's modified Eagle's medium) containing 10 % bovine calf serum. When the cell density increased to about 85 to 90 %, the culture medium was replaced with 1 % bovine calf serum and cell differentiation was induced for 6 days. Completely differentiated cells were cultured for 3 hours with Krebs-Ringer buffer (KRB) containing 5 mM glucose. The test materials were added at a concentration of 10 μM. 30 minutes later, 0.2 μCi 2-deoxyglucose was added. KRB was removed 20 minutes later and the cells were washed for 3 times with cold PBS. The cells were lysed with 0.5N NaOH and counted using a radioactive counter.
As seen in Table 2 below, the group treated with the compound represented by the formula 1 showed glucose absorption 2.8 times as large as the control group.
Table 2
Figure imgf000102_0001
Figure imgf000103_0001
Figure imgf000104_0001
Figure imgf000105_0001
Experimental Example 2. Measurement of AMPK activity by Western blot
C2C12 cells were cultured and differentiated in the same manner as in Experimental Example 1. Treatment with the test materials was also performed in the same manner as in Experimental Example 1 (10 μM for 50 minutes). The culture medium was removed and the cells were washed for 2 times with PBS and protein extracts were obtained using a lysis buffer (50 mM tris-HCl, pH 7.4, 1 % NP-40, 0.25 % sodium deoxycholate, 150 mM NaCl, 1 mM EDTA, 1 mM PMSF, 1 mM sodium o-vanadate, 1 mM NaF, 1 μg/ mL apronitin, 1 μg/mL leu-peptin, 1 μg/mL pepstatin). The AMPK activity was determined from Western blot analysis of the degree of phosphorylation of serine-79 by acetyl CoA carboxylase and the degree of phosphorylation of threonine-172. The amount of ERK
(extracellular signal regulated protein kinase) was confirmed by Western blot in order to quantify the proteins.
The result of Western blot analysis is given in Table 3 below, wherein "strong" means that the degree of phosphorylation of threonine-172 increased by 3 times or more, "mild" means that the degree of phosphorylation of threonine-172 increased by 1 to 3 times and "weak" means that the degree of phosphorylation of threonine-172 increased by less than 1 time.
Table 3
Figure imgf000107_0001
Figure imgf000108_0001
As seen in Table 3, FIG. 1 and FIG. 2a to FIG. 2g, increase of AMPK activity was observed when the muscle cells were treated with the compound represented by the formula 1. Experimental Example 3. Preventive and therapeutic effect for diabetes/obesity in db/db mice
8- to 9-week-old male db/db mice (C57BL/Ks) were tested. 0.5 % carboxylmethylcellulose (CMC), rosiglitazone dissolved in 0.5 % carboxylmethylcellulose (CMC) and the test material were administered orally or abdominally every afternoon to the negative control group, the positive control group and the test group, respectively. Blood glucose level measurement was made just before the administration, at an interval of 3-4 days, by incising the tail vein. Body weight and the amount of feed were measured every day just before the administration.
After 10 days of administration, blood glucose level measurement and body weight measurement, serum was separated from blood for measuring the biochemical parameters related with liver function, kidney function and lipid level.
As seen in FIGs. 3a and 3b, FIGs. 4a and 4b, FIGs. 5a, 5b and 5c and FIGs. 6a, 6b and 6c, the test group to which the compound represented by the formula 1 had been administered abdominally or orally showed significant decrease in blood glucose level and body weight compared with the control group, which implies the preventive and therapeutic effect for diabetes and obesity.
Experimental Example 4. Preventive and therapeutic effect for diabetes/obesity in ob/ob mice Experimental Example 4-1
6- week old male ob/ob mice (Harlan) were accustomed to the environment of the animal breeding facility of SK for a week. During the period, the mice were freely given feed and water. The mice were grouped based on the body weight. The mice were grouped into the control group, the positive control group (sibutramine) and the test group. The administration dosage was 15 mg/kg for the positive control group and 200 mg/kg/10 mL for the test group. Administration was given abdominally using an insulin syringe. Administration was given once a day at 5 p.m. over a 4-week period. The control group was administered with 0.5 % carboxymethyl cellulose (CMC), at kg/ 1O mL.
Body weight was measured over the 4-week period. The difference in the body weight of the control group and the body weight of the test group (g) and the increase of the body weight (%) were calculated to evaluate the inhibitive effect against body weight increase. Also, the amount of feed intake was measured in order to evaluate the inhibitive effect against feed intake.
Experimental Example 4-2
Oral administration test was performed for the materials that showed effectiveness in Experimental Example 1. Grouping of the mice, administration dosage, administration period, etc. were the same as in Experimental Example 3-1. Forced oral administration was performed using a bouige.
As seen in FIGs. 7a and 7b, FIGs. 8a and 8b and FIG. 9, the test group to which the compound represented by the formula 1 had been administered abdominally or orally showed significant decrease in blood glucose level and body weight compared with the control group, which implies the preventive and therapeutic effect for diabetes and obesity.
Industrial Applicability As apparent from the above description, the compounds of the present invention are effective in lowering blood glucose level and body weight and can be used for treatment of diabetes and/ or obesity.
While the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art will appreciate that various modifications and substitutions can be made thereto without departing from the spirit and scope of the invention as set forth in the appended claims.

Claims

Claims
1. A quinazoline derivative represented by the formula 1 below or a pharmaceutically available salt thereof:
Figure imgf000111_0001
wherein
Ra is a substituent selected from hydrogen, (Ci-Ci8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, halogeno-(Ci-C6)alkyl, hydroxy-(C1-C6)alkyl,
(Ci-C6)alkoxy-(Ci-C6)alkyl/ cyano-(C1-Cό)alkyl/ amino-(Ci-C6)alkyl,
(Ci-C6)alkylamino-(Ci-C6)alkyl, di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl, (Ci-C6)alkylthio-(Ci-C6)alkyl, (Ci-C6)alkylsulfinyl-(Ci-C6)alkyl and
(Ci-C6)alkylsulfonyl-(Ci-C6)alkyl/ or -X1-Q1 [wherein X1 is a direct bond or selected from Ox S, SO, SO2, N(R4), CO, CO2, CH(OR4), CON(R4), N(R4)CO, SO2N(R4), N(R4)SO2, C(R4)2O, C(R4)2S, N(R4)C(R4)2, N(R4)CON(R4) and N(R4)CSN(R4), wherein R4 is a hydrogen atom, (Ci-C6)alkyl, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)Cy cloalkyl-(Ci-C6)alkyl, (C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(C1-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(C1-C6)alkyl, and Q1 and R4 may be identical or different], wherein the neighboring carbon atoms of (C2-C6)alkylene of Ra may be separated by a group selected from O, S, SO, SO2 , N(R5), CO, CH(OR5), CON(R5), N(R5)CO, SO2N(R5), N(R5)SO2, C(R5)=C(R5) and C≡C, wherein R5 is a hydrogen atom or (Ci-C6)alkyl, any CH2=CH- or HC≡C- of Ra may have a substituent, at the terminal or CH2= or HC≡, selected from halogeno, carboxyl, carbamoyl, (Ci-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, amino-(C1-Cό)alkyl, (C1-C6)alkylamino-(C1-C6)alkyl and di-[(C1-C6)alkyl]amino-(Ci-C6)alkyl or -Q2-X2 [wherein X2 is a direct bond or selected from CO and N(R6)CO, wherein R6 is a hydrogen atom or (C1-Cό)alkyl, and Q2 is aryl, aryl-(C1-C6)alkyl, heteroaryl, heteroaryl-(Q-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl], any CH2 or CH3 of Ra may have at least one substituent selected from halogeno,
Figure imgf000112_0001
hydroxy, cyano, amino, carboxyl, carbamoyl, (C1-Cό)alkoxy, (Ci-C6)alkylthio, (C1-C6)alkylsulfinyl, (Ci-C6)alkylsulfonyl, (Ci-C6)alkylamino, di-[(Ci-C6)alkyl]amino, (Ci-C6)alkoxycarbonyl, N-(Ci-Cό)alkylcarbamoyl,
N, N-di- [(Ci -Ce) alky 1] carbamoyl, (C2-C6)alkanoyl, (C2-C6)alkanoyloxy, (C2-C6)alkanoylamino, N-(C1-C6)alkyl-(C2-C6)alkanoylamino,
N-(C1-C6)alkylsulfamoyl, N,N-di-[(Ci-C6)alkyl]sulfamoyl,
(C1-C6)alkanesulfonylamino and N-(Ci-C6)alkyl-(Ci-C6)alkanesulfonylamino, or -X3-Q3 [wherein X3 is a direct bond or selected from O, S, SO, SO2, N(R7), CO, CH(OR7), CON(R7), N(R7)CO, SO2N(R7), N(R7)SO2, C(R7)2O, C(R7)2S, N(R7)C(R7)2, N(R7)CON(R7) and N(R7)CSN(R7), wherein R7 is a hydrogen atom, (Ci-C6)alkyl, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl,
(C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl, and Q3 and R7 may be identical or different], any aryl, heteroaryl or heterocyclyl of Ra may have 0 to 3 identical or different substituents selected from halogeno, trifluoromethyl, cyano, nitro, hydroxy, amino, carboxyl, carbamoyl, (Ci-C6)alkyl, (C2-Cs) alkenyl, (C2-Cs) alky nyl, (Ci-C6)alkoxy, (C2-C6)alkenyloxy, (C2-C6)alkynyloxy, (Ci-C6)alkylthio, (Ci-C6)alkylsulfinyl, (Ci-C6)alkylsulfonyl, (Ci-C6)alkylamino, di-[(Ci-C6)alkyl]amino, (Ci-C6)alkoxycarbonyl, N-(Ci-Cό)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, (C2-C6)alkanoyl, (C2-C6)alkanoyloxy, (C2-C6)alkanoylamino,
N-(Ci-C6)alkyl-(C2-C6)alkanoylamino, N-(Ci-C6)alkylsulfamoyl,
N,N-di-[(Ci-C6)alkyl]sulfamoyl, (Ci-C6)alkanesulfonylamino and
N-(Ci-C6)alkyl-(Ci-C6)alkanesulfonylamino, or -X4-R8 [wherein X4 is a direct bond or selected from O and N(R9), wherein R9 is a hydrogen atom or (Ci-C6)alkyl, and R8 is halogeno-(Ci-C6)alkyl, hydroxy-(Ci-C6)alkyl, (Ci-C6)alkoxy-(Ci-C6)alkyl, cyano-(C1-Cό)alkyl, amino-(Ci-C6)alkyl, (Ci-C6)alkylamino-(Ci-C6)alkyl, di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl, (C2-Cό)alkanoylamino-(Ci-C6)alkyl or
(Ci-C6)alkoxycarbonylamino-(C1-C6)alkyl], or -X5-Q4 [wherein X5 is a direct bond or selected from O, CO and N(R10), wherein R10 is a hydrogen atom or (Ci-C6)alkyl, and
Q4 is aryl, aryl-(Ci-Cό)alkyl, heteroaryl, heteroaryl-(C1-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl, which may have 1 or 2 identical or different substituents selected from halogeno, (Ci-C6)alkyl and (C1-C6)alkoxy] and heterocyclyl of Ra may have 1 or 2 oxo or thioxo substituents;
Rb is a substituent selected from hydrogen, (Ci-Ciβjalkyl, (C2-Cs)alkenyl, (C2-Cβ)alkynyl, halogeno-(C1-C6)alkyl/ hydroxy-(Ci-C6)alkyl/
(Ci-C6)alkoxy-(C1-C6)alkyl/ cyano-(C1-C6)alkyl/ amino-(Ci-C6)alkyl/
(C1-C6)alkylamino-(C1-C6)alkyl/ di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl/
(Ci-C6)alkylthio-(Ci-C6)alkyl, (C1-C6)alkylsulfinyl-(Ci-C6)alkyl and
(C1-C6)alkylsulfonyl-(C1-C6)alkyl/ or -X1-Q1 [wherein X1 is a direct bond or selected from O, S, SO, SO2, N(R4), CO, CO2(R4), CH(OR4), CON(R4), N(R4)CO, SO2N(R4), N(R4)SO2, C(R4)2O, C(R4)2S, N(R4)C(R4)2, N(R4)CON(R4) and N(R4)CSN(R4), wherein R4 is a hydrogen atom, (Ci-Ce)alkyl, aryl, aryl-(C1-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(C1-C6)alkyl, (C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(C1-C6)alkyl, heterocyclyl or heterocyclyl-(C1-C6)alkyl, and Q1 and R4 may be identical or different], wherein the neighboring carbon atoms of (C2-C6)alkylene of Rb may be separated by a group selected from O, S, SO, SO2, N(R5), CO, CH(OR5), CON(R5), N(R5)CO, SO2N(R5), N(RS)SO2, CH=CH and C≡C, wherein R5 is a hydrogen atom or (Ci-C6)alkyl, any CH2=CH- or HC≡C- of Rb may have a substituent, at the terminal or at
CH2= or HC=, selected from halogeno, carboxyl, carbamoyl, (Ci-C6)alkoxycarbonyl, N-(C1-Cό)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, amino-(C1-C6)alkyl, (Ci-C6)alkylamino-(C1-C6)alkyl and di-[(C1-C6)alkyl]amino-(Ci-C6)alkyl, or -Q2-X2 [wherein X2 is a direct bond or selected from CO and N(R6)CO, wherein R6 is a hydrogen atom or (C1-C6)alkyl, and Q2 is aryl, aryl-(C1-C6)alkyl, heteroaryl, heteroaryl-(C-ι-C6)alkyl, heterocyclyl or heterocyclyl-(C-ι-C6)alkyl], any CH2 or CH3 of Rb may have at least one substituent selected from halogeno, (C1-Cό)alkyl, hydroxy, cyano, amino, carboxyl, carbamoyl, (Ci-C6)alkoxy, (Ci-C6)alkylthio, (Ci-C6)alkylsulfinyl, (Ci-C6)alkylsulfonyl, (Ci-C6)alkylamino, di-[(C1-C6)alkyl]amino, (C1-Cό)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl,
N,N-di-[(Ci-C6)alkyl]carbamoyl, (C2-Ce)alkanoyl, (C2-C6) alkanoyloxy, (C2-C6) alkanoylamino, N-(Cι-C6)alkyl-(C2-C6)alkanoylamino,
N-(CΛ)alkylsulfamoyl,
Figure imgf000114_0001
(Ci-C6)alkanesulfonylamino and N-(C1-C6)alkyl-(Ci-C6)alkanesulfonylamino or -X3-Q3 [wherein X3 is a direct bond or selected from O, S, SOx SO2, N(R7), CO, CH(OR7), CON(R7), N(R7)CO, SO2N(R7), N(R7)SO2, C(R7)2O, C(R7)2S, N(R7)C(R7)2, N(R7)CON(R7) and N(R7)CSN(R7), wherein R7 is a hydrogen atom, (Ci-C6)alkyl, aryl, aryl-(C1-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl,
(C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(C-ι-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl, and Q3 and R7 may be identical or different], any aryl, heteroaryl or heterocyclyl of Rb may have 1, 2 or 3 identical or different substituents selected from hydrogen, halogeno, trifluoromethyl, cyano, nitro, hydroxy, amino, carboxyl, carbamoyl, (Ci-C6)alkyl, (C2-C8) alkenyl, (C2-C8)alkynyl, (Ci-Cό)alkoxy, (C2-C6)alkenyloxy, (C2-C6)alkynyloxy, (Ci-C6)alkylthio, (C1 -C6) alky lsulfinyl, (C;i-C6)alkylsulfonyl, (Ci-C6)alkylamino, di-[(Ci-C6)alkyl]amino, (C1 -C6) alkoxy carbony 1, N-(C1 -C6)alky lcarbamoy 1, N, N-di- [(C1 -C6) alky 1] carbamoyl, (C2-C6)alkanoyl, (C2-C6)alkanoyloxy, (C2-C6)alkanoylamino,
N-(Ci-C6)alkyl-(C2-Cό)alkanoylamino, (C3-C6)alkenoylamino,
N-(C1 -C6)alkyl-(C3-C6)alkenoylamino, (C3-C6)alkynoylamino, N-(C1-C6)alkyl-(C3-C6)alkynoylamino, N-(C1-C6)alkylsulfamoyl,
N,N-di-[(C1-C6)alkyl]sulfamoyl, (C1-C6)alkanesulfonylamino and
N-(C1-C6)alkyl-(Ci-C6)alkanesulfonylamino, or -X4-R8 [wherein X4 is a direct bond or selected from O and N(R9), wherein R9 is a hydrogen atom or (Ci-C6)alkyl, and R8 is halogeno-(Ci-C6)alkyl, hydroxy-(C1-Cό)alkyl, (Ci-C6)alkoxy-(Ci-C6)alkyl, cyano-(Ci-C6)alkyl, amino-(Ci-C6)alkyl, (C1-C6)alkylamino-(C1-C6)alkyl or di-[(C1-C6)alkyl]amino-(Ci-C6)alkyl], or -X^Q4 [wherein X5 is a direct bond or selected from O, CO and N(R10), wherein R10 is a hydrogen atom or (Ci-C6)alkyl, and Q4 is aryl, aryl-(C1-C6)alkyl, heteroaryl, heteroaryl-(C1-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl, which may have 1 or 2 identical or different substituents selected from halogeno, (Ci-C6)alkyl and (Gι-C6)alkoxy], heterocyclyl of Rb may have 1 or 2 oxo or thioxo substituents and any identical or different substituents of aryl, heteroaryl or heterocyclyl of Rb may bond with each other to form -CH=CH-CH=CH-, -N=CH-CH=CH-, -CH=N-CH=CH-, -CH=CH-N=CH-, CH=CH-CH=N-, -N=CH-N=CH-, -CH=N-CH=N-, -N=CH-CH=N-, -N=N-CH=CH-, -CH=CH-N=N-, -CH=CH-O-, -0-CH=CH-, -CH=CH-S-, -S-CH=CH-, -C(RH)2-C(RH)2-O-, -0-C(RH)2-C(RH)2-, -C(RH)2-C(RH)2-S-, -S-C(R^)2-C(RH)2-, -0-C(RH)2-O-, -0-C(RH)2-C(RH)2-O-, -S-C(RH)2-S-, -S-C(RH)2-C(RH)2-S-, -CH=CH-NH-, -NH-CH=CH-,
-C(RH)2-C(RH)2-NH-, -NH-C(RH)2-C(RH)2-, -N=CH-NH-, -NH-CH=N-, -NH-C(RH)2-NH-, -0-CH=N-, -N=CH-O-, -S-CH=N-, -N=CH-S-, -0-C(RH)2-NH-, -NH-C(RH)2-O-, -S-C(RH)2-NH-, -NH-C(RH)2-S-, -0-N=CH-, -CH=N-O-, -S-N=CH-, -CH=N-S-, -0-NH-C(RH)2-, -C(RH)2-NH-O-, -S-NH-C(RH)2-, -C(RH)2-NH-S-, -NH-N=CH-, -CH=N-NH-, -NH-NH-C(RH)2-, -C(RH)2-NH-NH, -N=N-NH- or -NH-N=N- [wherein R11 is a hydrogen atom or (Ci-C6)alkyl]; m is 0, 1, 2, 3 or 4; and each Rc may be identical or different and is selected from hydrogen, halogeno, trifluoromethyl, cyano, isocyano, nitro, hydroxy, mercapto, amino, formyl, carboxyl, carbamoyl, (Ci-C6)alkyl, (C2-Cs)alkenyl, (C2-Cs)alkynyl,
Figure imgf000115_0001
(C2-Cό)alkenyloxy, (C2-Cό)alkynyloxy, (C1-C6)alkylthio, (Ci-C6)alkylsulfinyl, (Ci-C6)alkylsulfonyl, (Ci-C6)alkylamino, di-[(C1-C6)alkyl]amino, (Cα-Cό)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, (C2-C6) alkanoyl, (C2-C6) alkanoyloxy, (C2-C6)alkanoylamino,
N-(Ci-C6)alkyl-(C2-C6)alkanoylamino, (C3-Cό)alkenoylamino,
N-(Ci -C6)alkyl-(C3-C6)alkenoylamino, (C3-C6)alkynoylamino,
N-(Ci -C6)alkyl-(C3-C6)alkynoylamino, N-(Ci-C6)alkylsulfamoyl, N,N-di-[(Ci-C6)alkyl]sulfamoyl, (Ci-C6)alkanesulfonylamino,
N-(Ci-C6)alkyl-(Ci-C6)alkanesulfonylamino, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl, (C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl and heterocyclyl-(Ci-C6)alkyl, wherein the neighboring carbon atoms of any (C2-Cό)alkylene of Rc may be separated by a group selected from O, S, SO, SO2, N(R12), CO, CH(OR12), CON(R12),
N(R12)CO, SO2N(R12), N(R12)SO2, CH=CH and C≡C, wherein R12 is a hydrogen atom or (Ci-Cό)alkyl/ any CH2=CH- or HC≡C- of Rc may have a substituent, at the terminal or at CH2= or HC≡, selected from halogeno, carboxyl, carbamoyl, (C1-Ce)alkoxycarbonyl/ N-(Ci-C6)alkylcarbamoyl, N/N-di-[(C1-C6)alkyl]carbamoyl/ amino-(Ci-C6)alkyl, (Ci-C6)alkylamino-(Ci-C6)alkyl and di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl, or -Q5-X6 [wherein X6 is a direct bond or selected from CO and N(R13)CO, wherein R13 is a hydrogen atom or (C1-C6)alkyl/ and Q5 is aryl, aryl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(Gι-C6)alkyl], any CH2 or CH3 of Rc may have at least one substituent selected from halogeno, (Ci-C6)alkyl, hydroxy, cyano, amino, carboxyl, carbamoyl, (Ci-Cό)alkoxy, (Ci-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C6)alkylsulfonyl, (C1 -C6) alky lamino, di-[(Ci-C6)alkyl]amino, (Ci-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl,
N,N-di-[(Ci-C6)alkyl]carbamoyl, (C2-C6) alkanoyl, (C2-C6)alkanoyloxy,
(C2-C6)alkanoylamino, N-(Ci-C6)alkyl-(C2-C6)alkanoylamino, N-(C1-C6)alkylsulfamoyl, N,N-di-[(Ci-C6)alkyl]sulfamoyl,
(Ci-Cό)alkanesulfonylamino and N-(Ci-C6)alkyl-(Ci-C6)alkanesulfonylamino, or -X7-Q6 [wherein X? is a direct bond or selected from O, S, SO, SO2, N(R14), CO, CH(OR14), CON(R14), N(R14)CO, SO2N(R14), N(R14)SO2, C(R14)2O, C(R14)2S and N(R14)C(R14)2, wherein R14 is a hydrogen atom or (Ci-Cό)alkyl, and Q6 is aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl,
(C3-C7)cycloalkenyl, (C3-C7)cycloalkenyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(C1-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl], any aryl, heteroaryl or heterocyclyl of Rc may have 1, 2 or 3 identical or different substituents selected from hydrogen, halogeno, trifluoromethyl, cyano, nitro, hydroxy, amino, carboxyl, carbamoyl, (C1-C6)alkyl, (C2-Cs) alkenyl, (C2-C8)alkynyl, (C1-C6)alkoxy, (C2-C6)alkenyloxy, (C2-C6)alkynyloxy, (Ci-C6)alkylthio, (C1-C6)alkylsulfinyl, (Ci-C6)alkylsulfonyl, (Ci-Cό)alkylamino, di-[(Q-C6)alkyl]amino, (Ci-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, (C2-C6)alkanoyl, (C2-C6)alkanoyloxy, (C2-C6)alkanoylamino, N-(Ci-C6)alkyl-(C2-C6)alkanoylamino, (C3-C6)alkenoy lamino,
N-(C1-C6)alkyl-(C3-C6)alkenoylamino, (C3-C6)alkynoylamino, N-(Q-C6)alkyl-(C3-C6)alkynoylamino, N-(Ci-C6)alkylsulfamoyl/
N/N-di-[(Ci-C6)alkyl]sulfamoyl/ (Ci-C6)alkanesulfonylamino and
N-(Ci-C6)alkyl-(Ci-C6)alkanesulfonylamino, or -X8-R15 [wherein X8 is a direct bond or selected from O and N(R16), wherein R16 is a hydrogen atom or (C1-C6)alkyl, and R15 is halogeno-(C1-Cό)alkyl/ hydroxy-(Ci-C6)alkyl, (Ci-C6)alkoxy-(C1-C6)alkyl/ cyano-(Ci-C6)alkyl, amino-(Ci-C6)alkyl/ (C1-C6)alkylamino-(Ci-C6)alkyl or di-[(Ci-C6)alkyl]amino-(Ci-C6)alkyl]/ or -X9-Q7 [wherein X9 is a direct bond or selected from O, CO and N(R17), wherein R17 is a hydrogen atom or (Ci-C6)alkyl, Q7 is aryl, aryl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocy CIyI-(C1 -C6)alkyl, which may have 1 or 2 identical or different substituents selected from halogeno, (Ci-Cό)alkyl and (Ci-C6)alkoxy, and any heterocyclyl of Q7 may have 1 or 2 oxo or thioxo substituents], heterocyclyl of Rc may have 1 or 2 oxo or thioxo substituents and any identical or different substituents of aryl, heteroaryl or heterocyclyl of Rc may bond with each other to form -CH=CH-CH=CH-, -N=CH-CH=CH-, -CH=N-CH=CH-, -CH=CH-N=CH-, CH=CH-CH=N-, -N=CH-N=CH-, -CH=N-CH=N-, -N=CH-CH=N-, -N=N-CH=CH-, -CH=CH-N=N-, -CH=CH-O-, -0-CH=CH-, -CH=CH-S-, -S-CH=CH-, -C(R18)2-C(R18)2-O-, -0-C(R1S)2-C(R1S)2-, -C(R1S)2-C(R1S)2-S-, -S-C(R1S)2-C(R1S)2-, -0-C(R1S)2-O-, -0-C(R1S)2-C(R1S)2-O-, -S-C(R1S)2-S-, -S-C(R1S)2-C(R1S)2-S-, -CH=CH-NH-, -NH-CH=CH-,
-C(R18)2-C(R18)2-NH-, -NH-C(R1S)2-C(R1S)2-, -N=CH-NH-, -NH-CH=N-, -NH-C(R18)2-NH-, -0-CH=N-, -N=CH-O-, -S-CH=N-, -N=CH-S-, -0-C(R1S)2-NH-, -NH-C(R1S)2-O-, -S-C(R18)2-NH-, -NH-C(R18)2-S-, -0-N=CH-, -CH=N-O-, -S-N=CH-, -CH=N-S-, -O-NH-C(R18)2-, -C(R18)2-NH-O-, -S-NH-C(R18)2-, -C(R1 S)2-NH-S-, -NH-N=CH-, -CH=N-NH-, -NH-NH-C(R18)2-, -C(R18)2-NH-NH, -N=N-NH- or -NH-N=N- [wherein R18 is a hydrogen atom or (Ci-C6)alkyl].
2. The compound of Claim 1, which is represented by the formula 1-1 below:
Figure imgf000118_0001
wherein
X is a direct bond or selected from O, S, SO, SO2 and NR5, wherein R5 is a hydrogen atom, (Ci-C6)alkyl, aryl, aryl-(C1 -C6) alky 1,
Figure imgf000118_0002
(C3-C7)cycloalkyl-(Ci-Cό)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl or heterocyclyl-(Ci-C6)alkyl;
Ri is a substituent selected from hydrogen, (Ci-C8)alkyl, halogeno-(C1-C6)alkyl, hydroxy-(C1-C6)alkyl, (Ci-C6)alkoxy-(Ci-C6)alkyl, amino-(Ci-C6)alkyl, (Ci-C6)alkylamino-(Ci-C6)alkyl, di-[(Ci-C6)alkyl]amino-(C1-C6)alkyl and (Ci-C6)alkylsulfinyl, or -Xl-Q? [wherein X1 is a direct bond or selected from O, S and NR5, and Q1 and R5 may be identical or different], wherein the neighboring carbon atoms of (C2-C6)alkylene of Ri may be separated by a group selected from O, S and N(R5), any CH2 or CH3 of Ri may have at least one substituent selected from halogeno, (C1-Cό)alkyl, hydroxy, amino, (Ci-Cό)alkoxy
Figure imgf000118_0003
(Ci-C6)alkylsulfinyl, (C1-Cό)alkylamino and di-[(Ci-C6)alkyl]amino, any aryl, heteroaryl or heterocyclyl of Ri may have 0 to 3 identical or different substituents selected from halogeno, hydroxy, amino, (Ci-Cό)alkyl, aryl, aryl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl, heterocyclyl-(Ci-C6)alkyl, (Ci-C6)alkoxy, (Ci-Cό)alkylthio and (Ci-C6)alkylsulfinyl and heterocyclyl of Ri may have 1 or 2 oxo or thioxo substituents;
R2 is a substituent selected from hydrogen, (Ci-Ci8)alkyl, (C2-C8)alkenyl, halogeno-(Ci-C8)alkyl, hydroxy-(Ci-Ce)alkyl, (Ci-C8)alkoxy-(Ci-C8)alkyl, amino-(Ci-C8)alkyl, (Ci-C8)alkylamino-(d-C8)alkyl, di-[(Ci-C8)alkyl]amino-(Ci-C8)alkyl, (Ci-C8)alkylsulfinyl, aryl, aryl-(Ci-C8)alkyl,
(C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(d-C8)alkyl, heteroaryl, heteroaryl-(Ci-Cs)alkyl, heterocyclyl and heterocyclyl-(C1-C8)alkyl/ wherein the neighboring carbon atoms of (C2-C6)alkylene of R2 may be separated by a group selected from O7 S, N(R5), CO, CH(OR5), CON(R5), N(R5)CO, SO2N(R5), N(RS)SO2 and CH=CH, any CH2 or CH3 of R2 may have at least one substituent selected from halogeno, (C1-C6)alkyl substituent, hydroxy, cyano, amino, carboxyl, carbamoyl, (Ci-C6)alkoxy (Q-C6)alkylthio, (Ci-C6)alkylsulfinyl, (Ci-C6)alkylamino, di-[(Ci-C6)alkyl]amino, (d-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl,
N,N-di-[(Ci-C6)alkyl]carbamoyl, aryl, aryl-(C1-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(C1-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl and heterocyclyl-(Ci-C6)alkyl, any aryl, heteroaryl or heterocyclyl of R2 may have 0 to 3 identical or different substituents selected from halogeno, trifluoromethyl, cyano, nitro, hydroxy, amino, carboxyl, carbamoyl, (C1-C6)alkyl, aryl, aryl-(C1-Cβ)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl, heterocyclyl-(Ci-C6)alkyl, (C2-Cs)alkenyl, (C2-C8)alkynyl, (Ci-C6)alkoxy, (C1-C6)alkylthio, (Ci-C6)alkylsulfinyl,
(Ci-C6)alkylamino, di-[(Ci-C6)alkyl]amino, (C1-C6)alkoxycarbonyl,
N-(C1-Cό)alkylcarbamoyl and N,N-di-[(Ci-C6)alkyl]carbamoyl, heterocyclyl of R2 may have 1 or 2 oxo or thioxo substituents and any identical or different substituents of aryl, heteroaryl or heterocyclyl of R2 may bond with each other to form -CH=CH-CH=CH-, -N=CH-CH=CH-, -CH=N-CH=CH-, -CH=CH-N=CH-, CH=CH-CH=N-, -N=CH-N=CH-, -CH=N-CH=N-, -N=CH-CH=N-, -CH=CH-O-, -0-CH=CH-, -CH=CH-S-, -S-CH=CH-, -C(R6)2-C(R6)2-O-, -O-C(R6)2-C(R6)2-, -C(R6)2-C(R6)2-S-, -S-C(R6)2-C(R6)2-, -O-C(R6)2-O-, -O-C(R6)2-C(R6)2-O-, -S-C(R6)2-S-, -S-C(R6)2-C(R6)2-S-, -CH=CH-NH-, -NH-CH=CH-, -C(R6)2-C(R6)2-NH-, -NH-C(R6)2-C(R6)2-, -N=CH-NH-, -NH-CH=N-, -NH-C(R6)2-NH-, -0-CH=N-, -N=CH-O-, -S-CH=N-, -N=CH-S-, -O-C(R6)2-NH-, -NH-C(RO)2-O-, -S-C(R6)2-NH-, -NH-C(R6)2-S-, -N=N-NH- or -NH-N=N- [wherein R6 is a hydrogen atom or (O-C^alkyl]; and each of R3 and R4 may be identical or different, and each may be independently a substituent selected from hydrogen, halogeno, trifluoromethyl, cyano, nitro, hydroxy, mercapto, amino, formyl, carboxyl, carbamoyl,(C1-C6)alkyl, (C2-C8)alkenyl, (C2-C6)alkoxy, (C1-C6)alkylthio, (Ci-C6)alkylsulfinyl,
(Ci-C6)alkylamino, di-[(C1-C6)alkyl]amino, (Ci-C6)alkoxycarbonyl,
N-(Ci-C6)alkylcarbamoyl, N,N-di-[(C1-C6)alkyl]carbamoyl, aryl, aryl-(C1-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl and heterocyclyl-(C1-C6)alkyl, any CH2 or CH3 of R3 and R4 may have at least one substituent selected from halogeno, hydroxy, amino, carboxyl, carbamoyl, (Ci-C6)alkoxy, (C1-C6)alkylthio, (Ci-Cό)alkylsulfinyl, (Ci-C6)alkylamino, di-[(Ci-C6)alkyl]amino, (Ci-C6)alkoxycarbonyl, N-(Ci-C6)alkylcarbamoyl, N,N-di-[(Ci-C6)alkyl]carbamoyl, aryl, aryl-(Ci-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(Ci-C6)alkyl, heteroaryl, heteroaryl-(Ci-C6)alkyl, heterocyclyl and heterocyclyl-(Ci-C6)alkyl, any aryl, heteroaryl or heterocyclyl of R3 and R4 may have 1, 2 or 3 identical or different substituents selected from halogeno, trifluoromethyl, nitro, hydroxy, amino, (Ci-C6)alkoxy, (Ci-C6)alkylthio, (O-C^alkylamino, di-[(Ci-C6)alkyl] amino,
(Ci-C6)alkoxycarbonyl, N-(C1-C6)alkylcarbamoyl and
N, N-di- [(C1 -Cό)alky 1] carbamoyl and heterocyclyl of R3 and R4 may have 1 or 2 oxo or thioxo substituents.
3. The compound of Claim 2, wherein
X is O, S or NR5;
Ri is a hydrogen atom, C1-Ce alkyl, Ci-C4 haloalkyl, C1-C6 alkylhydroxy, Ci-C6 alkylsulfanyl, phenyl, phenyl Ci-C8 alkyl, pyridino, furano, thiopheno, C3-C7 cycloalkyl, pyrrolidino, piperidino, morpholino or N-(C1-Cό)alkylpiperazino; R2 is Ci-Cis alkyl, C2-C8 haloalkyl, C3-C7 cycloalkyl, (C3-C7)cycloalkyl Ci-C8 alkyl, C2-C8 alkenyl, (C3-C7)cycloalkenyl Ci-C8 alkyl, (Ci-Cs)alkyl C1-C8 alkoxyalkyl, Ci-C8 hydroxyalkyl, hydroxy-(Ci-C8)alkyl-(C1-C8)alkoxy alkyl, phenyl, phenyl Ci-C8 alkyl, di-phenyl Ci-C8 alkyl, phenyl Ci-C8 alkylhydroxy, phenyl Ci-C8 alkenyl, piperidine Ci-C8 alkyl, N-[phenyl-(Ci-C6)alkyl]piperidino, N-(Ci-C6)alkylpiperidine Ci-C8 alkyl, pyrrolidinone N-(Ci-C8)alkyl, naphthalene Ci-C8 alkyl, morpholine
Ci-C8 alkyl, piperazine Ci-C8 alkyl, N-(Ci-C6)alkylpiperazine Ci-C8 alkyl, pyridine Ci-Ce alkyl, pyrrolidine Ci-Cs alkyl, N-(C1-C6)alkylpyrrolidine Ci-Cs alkyl, thiopene Ci-Ce alkyl or benzodioxol Ci-C8 alkyl; each of R3 and R4 is a hydrogen atom, nitro or Ci-C8 alkoxy; and R5 is a hydrogen atom, Ci-C4 alkyl or Ci-C8 hydroxyalkyl, wherein the aforementioned cyclic substituent selected from C3-C7 cycloalkyl, phenyl, piperidine, naphthalene, morpholine, pyridine, pyrrolidine, pyrrolidinone, piperazine, thiopene, and benzodioxol may have 1 to 3 substituents selected from Ci-C8 alkyl, halogeno, hydroxy, Ci-C8 alkoxy, nitro and trifluoromethyl.
4. The compound of Claim 1, which is selected from the following compounds:
Compound No. 1: 2-[2-(2-phenylquinazolino-4-ylamino)-ethoxy]-ethanol Compound No. 2: isopropyl-(2-trichloromethylquinazolino-4-yl)-amine Compound No. 3: cyclopropyl-(2-trichloromethylquinazolino-4-yl)-amine Compound No. 4:
(2-piperidino-l-ylethyl)-(2-trichloromethylquinazolino-4-yl)-amine Compound No. 5: (l-phenylethyl)-(2-trichloromethylquinazolino-4-yl)-amine Compound No. 6: (4-phenylbutyl)-(2-trichloromethylquinazolino-4-yl)-amine Compound No. 7: propyl-(2-trichloromethylquinazolino-4-yl)-amine
Compound No. 8: (2-ethylsulfanylquinazolino-4-yl)-isopropylamine Compound No. 9: (2-ethylsulfanylquinazolino-4-yl)-(3-fluorobenzyl)-amine Compound No. 10: (2-ethylsulfanylquinazolino-4-yl)-[2-(3-fluorophenyl)-ethyl]-amine Compound No. 11:
(2-ethylsulfanylquinazolino-4-yl)-(2-morpholino-4-ylethyl)-amine Compound No. 12:
(2-ethylsulfanylquinazolino-4-yl)-[2-(3-trifluoromethyl-phenyl)ethyl]-amine Compound No. 13: (6-nitro-quinazolino-4-yl)-phenylamine Compound No. 14:
(6,7-diethoxyquinazolino-4-yl)-naphthaleno-l-ylmethylamine Compound No. 15: (6,7-diethoxyquinazolino-4-yl)-(3-morpholino-4-ylpropyl)-amine
Compound No. 16: allyl-(6,7-diethoxyquinazolino-4-yl)-amine Compound No. 17: (6/7-diethoxyquinazolino-4-yl)-(2-pyridino-2-ylethyl)-amine
Compound No. 18: (4-chlorobenzyl)-(6/7-diethoxyquinazolino-4-yl)-amine Compound No. 19: butyl-(2-ethylsulfanylquinazolino-4-yl)-amine Compound No. 20: sec-butyl-(2-ethylsulfanylquinazolino-4-yl)-amine Compound No. 21: (2-ethylsulfanylquinazolino-4-yl)-isobutylamine Compound No. 22: benzyl-(2-ethylsulfanylquinazolino-4-yl)-amine
Compound No. 23: (2-ethylsulfanylquinazolino-4-yl)-(l-phenylethyl)-amine Compound No. 24:
(2-ethylsulfanylquinazolino-4-yl)-(3-methoxybenzyl)-amine Compound No. 25: (2-ethylsulf anylquinazolino-4-yl)-(4-methoxybenzyl)-amine Compound No. 26:
(2-ethylsulf anylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine Compound No. 27: cyclohexyl-(2-ethylsulfanylquinazolino-4-yl)-amine Compound No. 28: cyclopentyl-(2-ethylsulfanylquinazolino-4-yl)-amine Compound No. 29: (2-ethylsulfanylquinazolino-4-yl)-phenethylamine
Compound No. 30: (2-ethylsulfanylquinazolino-4-yl)-(4-phenylbutyl)-amine Compound No. 31: (2-ethylsulf anylquinazolino-4-yl)-propylamine Compound No. 32: (2-ethylsulfanylquinazoline4-yl)-(3-phenylpropyl)-amine Compound No. 33: (2-ethylsulfanylquinazolino-4-yl)-(3-isopropoxypropyl)-amine
Compound No. 34: (2-ethylsulfanylquinazolino-4-yl)-(2-methoxy-ethyl)-amine
Compound No. 35: (2-ethylsulf anylquinazolino-4-yl)-naphthaleno-l-ylmethylamine Compound No. 36:
(2-ethylsulf anylquinazolino-4-yl)-(3-morpholino-4-ylpropyl)-amine Compound No. 37: benzo[l,3]dioxol-5-ylmethyl-(2-ethylsulfanylquinazolino-4-yl)-amine
Compound No. 38:
(3,5-dimethoxybenzyl)-(2-ethylsulfanylquinazolino-4-yl)-amine Compound No. 39: (2-ethylsulfanylquinazolino-4-yl)-(2-fluorobenzyl)-amine
Compound No. 40:
(2-ethylsulfanylquinazolino-4-yl)-(l-methoxymethylpropyl)-amine
Compound No. 41:
(l-benzyl-piperidino-4-yl)-(2-ethylsulfanylquinazolino-4-yl)-amine Compound No. 42: allyl-(2-ethylsulfanylquinazolino-4-yl)-amine
Compound No. 43: (2-ethylsulfanylquinazolino-4-yl)-hexadecylamine
Compound No. 44: (2-ethylsulfanylquinazolino-4-yl)-(2-piperidino-l-ylethyl)-amine
Compound No. 45: (2-ethylsulfanylquinazolino-4-yl)-(2-pyrrolidino-l-ylethyl)-amine
Compound No. 46: (2-ethylsulfanylquinazolino-4-yl)-(2-pyridino-2-ylethyl)-amine
Compound No. 47: 2-(2-ethylsulfanylquinazolino-4-ylamino)-ethanol
Compound No. 48: (2-ethylsulfanylquinazolino-4-yl)-[3-(2-methyl-piperidino-l-yl)-propyl]-amine
Compound No. 49:
(2-chloro-6-fluorobenzyl)-(2-ethylsulfanylquinazolino-4-yl)-amine
Compound No. 50:
2-[2-(2-ethylsulfanylquinazolino-4-ylamino)-ethoxy]-ethanol Compound No. 51: cyclohexyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 52: (4-phenylbutyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 53: (5-phenyl-pentyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 54: (4-methylbenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 55: isobutyl-(2-phenylquinazolino-4-yl)-amine Compound No. 56: butyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 57: naphthaleno-l-ylmethyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 58: (2-phenylquinazolino-4-yl)-pyridino-2-ylmethylamine Compound No. 59: (l-phenylquinazolino-4-yl)-thiopenyl-2-ylmethylamine Compound No. 60: isopropyl-(2-phenylquinazolino-4-yl)-amine Compound No. 61: (2-phenylquinazolino-4-yl)-propylamine
Compound No. 62: (3-isopropoxypropyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 63: (3-fluorobenzyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 64: (2-phenylquinazolino-4-yl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amine Compound No. 65: benzo[l/3]dioxol-5-ylmethyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 66: (2-phenylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine
Compound No. 67: (2-methoxy-ethyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 68: phenethyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 69: phenyl-(2-phenylquinazolino-4-yl)-amine Compound No. 70: (4-methoxyphenyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 71: (2-phenylquinazolino-4-yl)-o-tollylamine Compound No. 72: (4-isopropyl-phenyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 73: (2/4-dimethyl-phenyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 74: (2-phenylquinazolino-4-yl)-(4-undecyl-phenyl)-amine Compound No. 75: (4-ethyl-phenyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 76: (4-fluorophenyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 77: (2-methoxyphenyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 78:
(2-phenylquinazolino-4-yl)-(2,4/6-trimethyl-phenyl)-amine
CompoundNo.79: (4-butyl-phenyl)-(2-phenylquinazolino-4-yl)-amine CompoundNo.80:(2-phenoxy-phenyl)-(2-phenylquinazolino-4-yl)-amine CompoundNo.81: (3-phenoxy-phenyl)-(2-phenylquinazolino-4-yl)-amine CompoundNo.82:(4-phenoxy-phenyl)-(2-phenylquinazolino-4-yl)-amine CompoundNo.83:(3-bromophenyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 84: 2-methoxy-5-(2-phenylquinazolino-4-ylamino)phenol Compound No. 85: 5-(2-phenylquinazolino-4-ylamino)-pentane-l-ol Compound No. 86: benzyl-(2-phenylquinazolino-4-yl)-amine Compound No. 87: (l-phenylethyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 88: (4-chlorobenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 89: (3,4-dichlorobenzyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 90: (3-methoxybenzyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 91: (2-methoxybenzyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 92: (3,5-dimethoxybenzyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 93: (2,3-dimethoxybenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 94: (2-fluorobenzyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 95: cyclopentyl-(2-phenylquinazolino-4-yl)-amine Compound No. 96: sec-butyl-(2-phenylquinazolino-4-yl)-amine Compound No. 97: allyl-(2-phenylquinazolino-4-yl)-amine Compound No. 98:
(2-phenylquinazolino-4-yl)-(2-trifluoromethylbenzyl)-amine
Compound No. 99: hexadecyl-(2-phenylquinazolino-4-yl)-amine Compound No. 100:
(2-phenylquinazolino-4-yl)-(2-pyrrolidino-l-ylethyl)-amine Compound No. 101:
(2-phenylquinazolino-4-yl)-(2-piperidino-l-ylethyl)-amine
Compound No. 102: (2-phenylquinazolino-4-yl)-(2-pyridino-2-ylethyl)-amine Compound No. 103:
[2-(3-fluorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine Compound No. 104:
(l-methoxymethylpropyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 105: (l-benzyl-piperidino-4-yl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 106: (2-morpholino-4-ylethyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 107: [2-(3,4-dimethoxyphenyl)-ethyl]-(2-phenylquinazolino-4-yl)-ainine
Compound No. 108: (2,4-dichlorobenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 109: (2-chlorobenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 110: cyclopropyl-(2-phenylquinazolino-4-yl)-amine Compound No. Ill: (2-phenylquinazolino-4-yl)-pyridino-3-ylmethylamine
Compound No. 112: 2-(2-phenylquinazolino-4-ylamino)-propane-l-ol
Compound No. 113: 2-methoxy-4-[(2-phenylquinazolino-4-ylamino)-methyl]-phenol
Compound No. 114: (2-fluoro-ethyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 115: (2,3-dichlorobenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 116: (3-nitrobenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 117:
(l-ethyl-pyrrolidino-2-ylmethyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 118: (3/4-dimethoxybenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 119: (2-phenylquinazolino-4-yl)-(2-/?-tollylethyl)-amine
Compound No. 120: [2-(3-methoxyphenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
Compound No. 121: (l-ethylpropyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 122:
[2-(2/5-dimethoxyphenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
Compound No. 123: [2-(4-chlorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
Compound No. 124: [2-(4-methoxyphenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
Compound No. 125: (l,3-dimethylbutyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 126: [2-(3-chlorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
Compound No. 127: [2-(2/4-dichlorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
Compound No. 128: [2-(3/4-difluorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine Compound No. 129: (2-phenylquinazolino-4-yl)-(3/4/5-trimethoxybenzyl)-amine
Compound No. 130: (3-methylbutyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 131:
(2-cyclohex-l-enylethyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 132: cyclohexylmethyl-(2-phenylquinazolino-4-yl)-amine Compound No. 133: (2/2-diphenylethyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 134: (2,4-difluorobenzyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 135: (2,5-difluorobenzyl)-(2~phenylquinazolino-4-yl)-amine
Compound No. 136: (3,3-diρhenylpropyl)-(2-phenylquinazolino-4~yl)-amine Compound No. 137: [2-(4-bromophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
Compound No. 138: butylmethyl-(2-phenylquinazolino-4-yl)-amine Compound No. 139:
(2-phenylquinazolino-4-yl)-(4-trifluoromethylbenzyl)-amine
Compound No. 140: [2-(2-fluorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine
Compound No. 141: (2-phenylquinazolino-4-yl)-pyridino-4-ylmethylamine Compound No. 142: (2-phenylquinazolino-4-yl)-pyridino-2-ylmethylamine
Compound No. 143: (2/3-dimethylcyclohexyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 144:
(2/4-dimethoxybenzyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 145: (3-chlorobenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 146: l-phenyl-2-(2-phenylquinazolino-4-ylamino)-ethanol Compound No. 147: (2/5-dimethoxybenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 148: (4-bromobenzyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 149:
[2-(3,4-dichlorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine Compound No. 150: l-[3-(2-phenylquinazolino-4-ylamino)-propyl]-pyrrolidino-2-one
Compound No. 151:
[2-(2-chlorophenyl)-ethyl]-(2-phenylquinazolino-4-yl)-amine Compound No. 152: 2-[2-(2-phenylquinazolino-4-ylamino)-ethyl]-phenol
Compound No. 153: (3-bromobenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 154: (2,6-dimethoxybenzyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 155: (2-bromobenzyl)-(2-phenylquinazolino-4-yl)-amine Compound No. 156:
(3-morpholino-4-ylpropyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 157: 2-[butyl-(2-phenylquinazolino-4-yl)-amino]-ethanol
Compound No. 158:
[2-(4-methylpiperazino-l-yl)-ethyl]-(2-phenylquinazolino-4-yl)-amine Compound No. 159: cyclopentylmethyl-(2-phenylquinazolino-4-yl)-amine
Compound No. 160: (2-phenylquinazolino-4-yl)-(2-piperazino-l-ylethyl)-amine
Compound No. 161:
0-(4-nitrobenzyl)-N-(2-phenylquinazolino-4-yl)-hydroxylamine Compound No. 162: (4-chlorophenyl)-(2-phenylquinazolino-4-yl)-amine
Compound No. 163: benzyl-(2-methylquinazolino-4-yl)-amine
Compound No. 164: (3-methoxybenzyl)-(2-methylquinazolino-4-yl)-amine
Compound No. 165: (4-methoxybenzyl)-(2-methylquinazolino-4-yl)-amine
Compound No. 166: (2-methy lquinazolino-4-yl)-(3-trif luoromethy lbenzy l)-amine
Compound No. 167: (2-methylquinazolino-4-yl)-phenethylamine
Compound No. 168: (2-methylquinazolino-4-yl)-(4-phenylbutyl)-amine
Compound No. 169:
(2-methylquinazolino-4-yl)-naphthaleno-l-ylmethylamine Compound No. 170: benzo [1 ,3] dioxol-5-ylmethy l-(2-methy lquinazolino-4-yl)-amine Compound No. 171: (3-fluorobenzyl)-(2-methylquinazolino-4-yl)-amine
Compound No. 172: [2-(3-fluorophenyl)-ethyl]-(2-methylquinazolino-4-yl)-amine
Compound No. 173: 2-[2-(2-methylquinazolino-4-ylamino)-ethoxy]-ethanol Compound No. 174: 2-(2-methylquinazolino-4-ylamino)-ethanol
Compound No. 175: benzyl-(2-isopropylquinazolino-4-yl)-amine
Compound No. 176: (2-isopropylquinazolino-4-yl)-(3-methoxybenzyl)-amine
Compound No. 177: (2-isopropylquinazolino-4-yl)-(4-methoxybenzyl)-amine
Compound No. 178: (2-isopropylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine
Compound No. 179: (2-isopropylquinazolino-4-yl)-phenethylamine
Compound No. 180: (2-isopropylquinazolino-4-yl)-(4-phenylbutyl)-amine
Compound No. 181:
(2-isopropylquinazolino-4-yl)-naphthaleno-l-ylmethylamine Compound No. 182: benzo[l,3]dioxol-5-ylmethyl-(2-isopropylquinazolino-4-yl)-amine
Compound No. 183: (3-fluorobenzyl)-(2-isopropylquinazolino-4-yl)-amine
Compound No. 184:
[2-(3-fluorophenyl)-ethyl]-(2-isopropylquinazolino-4-yl)-amine Compound No. 185:
2-[2-(2-isopropylquinazolino-4-ylamino)-ethoxy]-ethanol
Compound No. 186: 2-(2-isopropylquinazolino-4-ylamino)-ethanol
Compound No. 187: benzyl-(2-tert-butylquinazolino-4-yl)-amine
Compound No. 188: (2-terf-butylquinazolino-4-yl)-(3-methoxybenzyl)-amine Compound No. 189: (2-fer£-butylquinazolino-4-yl)-(4-methoxybenzyl)-amine
Compound No. 189: (2-fer£-butylquinazolino-4-yl)-(4-methoxybenzyl)-amine
Compound No. 190: (2-fer£-butylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine
Compound No. 191: (2-terf-butylquinazolino-4-yl)-phenethylamine Compound No. 192: (2-terf-butylquinazolino-4-yl)-(4-phenylbutyl)-amine
Compound No. 193: (2-tert-butylquinazolino-4-yl)-naphthaleno-l-ylmethylamine
Compound No. 194: benzo[l/3]dioxol-5-ylmethyl-(2-teri-butylquinazolino-4-yl)-amine
Compound No. 195: (2-terf-butylquinazolino-4-yl)-(3-fluorobenzyl)-amine Compound No. 196:
(2-ter£-butylquinazolino-4-yl)-[2-(3-fluorophenyl)-ethyl]-amine
Compound No. 197: 2- [2-(2-terf-buty lquinazolino-4-ylamino)-ethoxy] -ethanol
Compound No. 198: 2-(2-feri-butylquinazolino-4-ylamino)-ethanol Compound No. 199: benzyl-(2-cyclohexylquinazolino-4-yl)-amine
Compound No. 200: (2-cyclohexylquinazolino-4-yl)-(3-methoxybenzyl)-amine
Compound No. 201:
(2-cyclohexylquinazolino-4-yl)-(4-methoxybenzyl)-amine Compound No. 202:
(2-cyclohexylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine
Compound No. 203: (2-cyclohexylquinazolino-4-yl)-phenethylamine
Compound No. 204: (2-cyclohexylquinazolino-4-yl)-(4-phenylbutyl)-amine
Compound No. 205: (2-cyclohexylquinazolino-4-yl)-naphthaleno-l-ylmethylamine
Compound No. 206: benzo[l,3]dioxol-5-ylmethyl-(2-cyclohexylquinazolino-4-yl)-amine
Compound No. 207: (2-cyclohexylquinazolino-4-yl)-(3-fluorobenzyl)-amine
Compound No. 208: (2-cyclohexylquinazolino-4-yl)-[2-(3-fluorophenyl)-ethyl]-amine
Compound No. 209: 2-[2-(2-cyclohexylquinazolino-4-ylamino)-ethoxy]-ethanol
Compound No. 210: 2-(2-cyclohexylquinazolino-4-ylamino)-ethanol
Compound No. 211: benzyl-(2-benzylquinazolino-4-yl)-amine Compound No. 212: (2-benzylquinazolino-4-yl)-(3-methoxybenzyl)-amine
Compound No. 213: (2-benzylquinazolino-4-yl)-(4-methoxybenzyl)-amine Compound No. 214: (2-benzylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine
Compound No. 215: (2-benzylquinazolino-4-yl)-phenethylamine
Compound No. 216: (2-benzylquinazolino-4-yl)-(4-phenylbutyl)-amine Compound No. 217:
(2-benzylquinazolino-4-yl)-naphthaleno-l-ylmethylamine
Compound No. 218: benzo[l/3]dioxol-5-ylmethyl-(2-benzylquinazolino-4-yl)-amine
Compound No. 219: (2-benzylquinazolino-4-yl)-(3-fluorobenzyl)-amine Compound No. 220:
(2-benzylquinazolino-4-yl)-[2-(3-fluorophenyl)-ethyl]-amine
Compound No. 221: 2-[2-(2-benzylquinazolino-4-ylamino)-ethoxy]-ethanol
Compound No. 222: 2-(2-benzylquinazolino-4-ylamino)-ethanol
Compound No. 223: benzyl-(2-pyridino-2-ylquinazolino-4-yl)-amine Compound No. 224:
(3-methoxybenzyl)-(2-pyridino-2-ylquinazolino-4-yl)-amine
Compound No. 225: (4-methoxybenzyl)-(2-pyridino-2-ylquinazolino-4-yl)-amine
Compound No. 226: (2-pyridino-2-ylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine
Compound No. 227: phenethyl-(2-pyridino-2-ylquinazolino-4-yl)-amine
Compound No. 228: (4-phenylbutyl)-(2-pyridino-2-ylquinazolino-4-yl)-amine
Compound No. 229: naphthaleno-l-ylmethyl-(2-pyridino-2-ylquinazolino-4-yl)-amine Compound No. 230: benzo[l,3]dioxol-5-ylmethyl-(2-pyridino-2-ylquinazolino-4-yl)-amine
Compound No. 231: (3-fluorobenzyl)-(2-pyridino-2-ylquinazolino-4-yl)-amine
Compound No. 232: [2-(3-fluorophenyl)-ethyl]-(2-pyridino-2-ylquinazolino-4-yl)-amine
Compound No. 233: 2-[2-(2-pyridino-2-ylquinazolino-4-ylamino)-ethoxy]-ethanol
Compound No. 234: 2-(2-pyridino-2-ylquinazolino-4-ylamino)-ethanol
Compound No. 235: benzyl-(2-pyridino-3-ylquinazolino-4-yl)-amine
Compound No. 236: (3-methoxybenzyl)-(2-pyridino-3-ylquinazolino-4-yl)-amine
Compound No. 237: (4-methoxybenzyl)-(2-pyridino-3-ylquinazolino-4-yl)-amine
Compound No. 238:
(2-pyridino-3-ylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine Compound No. 239: phenethyl-(2-pyridino-3-ylquinazolino-4-yl)-amine
Compound No. 240: (4-phenylbutyl)-(2-pyridino-3-ylquinazolino-4-yl)-amine
Compound No. 241: naphthaleno-l-ylmethyl-(2-pyridino-3-ylquinazolino-4-yl)-amine
Compound No. 242: benzo[l,3]dioxol-5-ylmethyl-(2-pyridino-3-ylquinazolino-4-yl)-amine
Compound No. 243: (3-fluorobenzyl)-(2-pyridino-3-ylquinazolino-4-yl)-amine
Compound No. 244:
[2-(3-fluorophenyl)-ethyl]-(2-pyridino-3-ylquinazolino-4-yl)-amine Compound No. 245:
2-[2-(2-pyridino-3-ylquinazolino-4-ylamino)-ethoxy]-ethanol
Compound No. 246: 2-(2-pyridino-3-ylquinazolino-4-ylamino)-ethanol
Compound No. 247: benzyl-(2-pyridino-4-ylquinazolino-4-yl)-amine
Compound No. 248: (3-methoxybenzy l)-(2-py ridino-4-ylquinazolino-4-yl)-amine
Compound No. 249: (4-methoxybenzyl)-(2-pyridino-4-ylquinazolino-4-yl)-amine
Compound No. 250:
(2-pyridino-4-ylquinazolino-4-yl)-(3-trifluoromethylbenzyl)-amine Compound No. 251: phenethyl-(2-pyridino-4-ylquinazolino-4-yl)-amine
Compound No. 252: (4-phenylbutyl)-(2-pyridino-4-ylquinazolino-4-yl)-amine Compound No. 253: naphthaleno-l-ylmethyl-(2-pyridino-4-ylquinazolino-4-yl)-amine
Compound No. 254: benzo[l/3]dioxol-5-ylmethyl-(2-pyridino-4-ylquinazolino-4-yl)-amine Compound No. 255:
(3-fluorobenzyl)-(2-pyridino-4-ylquinazolino-4-yl)-amine
Compound No. 256:
[2-(3-fluorophenyl)-ethyl]-(2-pyridino-4-ylquinazolino-4-yl)-amine
Compound No. 257: 2-[2-(2-pyridino-4-ylquinazolino-4-ylamino)-ethoxy]-ethanol
Compound No. 258: 2-(2-pyridino-4-ylquinazolino-4-ylamino)-ethanol
Compound No. 259: benzyl-[2-(4-chlorophenyl)-quinazolino-4-yl]-amine
Compound No. 260:
[2-(4-chlorophenyl)-quinazolino-4-yl]-(3-methoxybenzyl)-amine Compound No. 261:
[2-(4-chlorophenyl)-quinazolino-4-yl]-(4-methoxybenzyl)-amine
Compound No. 262:
[2-(4-chlorophenyl)-quinazolino-4-yl]-(3-trifluoromethylbenzyl)-amine
Compound No. 263: [2-(4-chlorophenyl)-quinazolino-4-yl]-phenethylamine Compound No. 264:
[2-(4-chlorophenyl)-quinazolino-4-yl]-(4-phenylbutyl)-amine
Compound No. 265:
[2-(4-chlorophenyl)-quinazolino-4-yl]-naphthaleno-l-ylmethylamine
Compound No. 266: benzo[l,3]dioxol-5-ylmethyl-[2-(4-chlorophenyl)-quinazolino-4-yl]-amine
Compound No. 267: [2-(4-chlorophenyl)-quinazolino-4-yl]-(3-fluorobenzyl)-amine
Compound No. 268:
[2-(4-chloropheny l)-quinazolino-4-y 1] - [2-(3-fluorophenyl)-ethy 1] -amine Compound No. 269:
2-{2-[2-(4-chlorophenyl)-quinazolino-4-ylamino]-ethoxy}-ethanol Compound No. 270: 2-[2-(4-chlorophenyl)-quinazolino-4-ylamino]-ethanol Compound No. 271: (2/4-dimethoxybenzyl)-(2-isopropylquinazolino-4-yl)-amine
Compound No. 272: (2-benzylquinazolino-4-yl)-(2/4-dimethoxybenzyl)-amine
Compound No. 273: 4-(2,4-dimethoxybenzyloxy)-2-phenylquinazoline Compound No. 274: 4-(2,4-dimethoxybenzylsulfanyl)-2-phenylquinazoline Compound No. 275:
(2-methoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine Compound No. 276:
(2-methoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine
Compound No. 277: (2-methoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine
Compound No. 278: (2-methoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine
Compound No. 279: (3-methoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
Compound No. 280:
(3-methoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine Compound No. 281:
(3-methoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine Compound No. 282:
(3-methoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine Compound No. 283: (4-methoxybenzy l)-(2-py rrolidino-1 -y lquinazolino-4-yl)-amine
Compound No. 284: (4-methoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine
Compound No. 285:
(4-methoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine Compound No. 286:
(4-methoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine Compound No. 287:
(2/3-diiϊiethoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
Compound No. 288:
(2/3-dimethoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine Compound No. 289:
(2/3-dimethoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine
Compound No. 290:
(2/3-dimethoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine
Compound No. 291: (2,4-dimethoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
Compound No. 292:
(2,4-dimethoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine
Compound No. 293:
(2/4-dimethoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine Compound No. 294:
(2/4-dimethoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine
Compound No. 295:
(2/5-dimethoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
Compound No. 296: (2/5-dimethoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine
Compound No. 297:
(2,5-dimethoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine
Compound No. 298:
(2,5-dimethoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine Compound No. 299:
(3/4-dimethoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
Compound No. 300:
(3,4-dimethoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine
Compound No. 301: (3,4-dimethoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine
Compound No. 302: (3,4-dimethoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine
Compound No. 303:
(3/5-dimethoxybenzyl)-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
Compound No. 304: (3/5-dimethoxybenzyl)-(2-piperidino-l-ylquinazolino-4-yl)-amine
Compound No. 305:
(3,5-dimethoxybenzyl)-(2-morpholino-4-ylquinazolino-4-yl)-amine
Compound No. 306:
(3,5-dimethoxybenzyl)-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-amine Compound No. 307: benzo[l/3]dioxol-5-ylmethyl-(2-pyrrolidino-l-ylquinazolino-4-yl)-amine
Compound No. 308: benzo[l/3]dioxol-5-ylmethyl-(2-piperidino-l-ylquinazolino-4-yl)-amine
Compound No. 309: benzo [1,3] dioxol-5-y lmethy l-(2-morpholino-4-y lquinazolino-4-yl)-amine
Compound No. 310: benzo[l,3]dioxol-5-ylmethyl-[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]- amine
Compound No. 311: (2-pyrrolidino-l-ylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine
Compound No. 312:
(2-piperidino-l-ylquinazolino-4-yl)-(3,4/5-trimethoxybenzyl)-amine
Compound No. 313:
(2-morpholino-4-ylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine Compound No. 314:
[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-(3,4/5-trimethoxybenzyl)-ami ne
Compound No. 315:
(2-pyrrolidino-l-ylquinazolino-4-yl)-(2/4/6-trimethoxybenzyl)-amine Compound No. 316:
(2-piperidino-l-ylquinazolino-4-yl)-(2/4/6-trimethoxybenzyl)-amine Compound No. 317:
(2-morpholino-4-ylquinazolino-4-yl)-(2/4/6-trimethoxybenzyl)-amine
Compound No. 318:
[2-(4-methylpiperazino-l-yl)-quinazolino-4-yl]-(2,4/6-trimethoxybenzyl)-ami ne
Compound No. 319: (2,4-dimethoxybenzyl)-(2-ethoxyquinazolino-4-yl)-amine
Compound No. 320: benzo[l,3]dioxol-5-ylmethyl-(2-ethoxyquinazolino-4-yl)-amine Compound No. 321: (2-isopropylquinazolino-4-yl)-(2-methoxybenzyl)-amine
Compound No. 322: (2,3-dimethoxybenzyl)-(2-isopropylquinazolino-4-yl)-amine
Compound No. 323:
(3/5-dimethoxybenzyl)-(2-isopropylquinazolino-4-yl)-amine Compound No. 324:
(3/4-dimethoxybenzyl)-(2-isopropylquinazolino-4-yl)-amine
Compound No. 325: (2-isopropylquinazolino-4-yl)-(3,4/5-trimethoxybenzyl)-amine
Compound No. 326: (2/5-dimethoxybenzyl)-(2-isopropylquinazolino-4-yl)-amine
Compound No. 327: (2-isopropylquinazolino-4-yl)-(2,4/6-trimethoxybenzyl)-amine
Compound No. 328: (2-benzylquinazolino-4-yl)-(2-methoxybenzyl)-amine
Compound No. 329: (2-benzylquinazolino-4-y l)-(2,3-dimethoxybenzyl)-amine
Compound No. 330: (2-benzylquinazolino-4-yl)-(3,5-dimethoxybenzyl)-amine
Compound No. 331:
(2-benzylquinazolino-4-yl)-(3/4-dimethoxybenzyl)-amine Compound No. 332:
(2-benzylquinazolino-4-yl)-(3,4/5-trimethoxybenzyl)-amine Compound No. 333: (2-benzylquinazolino-4-yl)-(2/4-dimethoxybenzyl)-amine
Compound No. 334:
(2-benzylquinazolino-4-yl)-(2,5-dimethoxybenzyl)-amine Compound No. 335:
(2-benzylquinazolino-4-yl)-(2,4/6-trimethoxybenzyl)-amine
Compound No. 336: (2-phenylquinazolino-4-yl)-(3,4/5-trimethoxybenzyl)-amine
Compound No. 337: (2-pheny lquinazolino-4-yl)-(2/4/6-trimethoxybenzy l)-amine
Compound No. 338: (2-furano-2-ylquinazolino-4-yl)-(2-methoxybenzyl)-amine
Compound No. 339:
(2-furano-2-ylquinazolino-4-yl)-(3-methoxybenzyl)-amine Compound No. 340:
(2-furano-2-ylquinazolino-4-yl)-(4-methoxybenzyl)-amine Compound No. 341: benzo[l/3]dioxol-5-ylmethyl-(2-furano-2-ylquinazolino-4-yl)-amine Compound No. 342: (2/3-dimethoxybenzyl)-(2-furano-2-ylquinazolino-4-yl)-amine
Compound No. 343: (3/5-dimethoxybenzyl)-(2-furano-2-ylquinazolino-4-yl)-amine
Compound No. 344:
(3/4-dimethoxybenzyl)-(2-furano-2-ylquinazolino-4-yl)-amine Compound No. 345:
(2-furano-2-ylquinazolino-4-yl)-(3/4/5-trimethoxybenzyl)-amine
Compound No. 346: (2/4-dimethoxybenzyl)-(2-furano-2-ylquinazolino-4-yl)-amine
Compound No. 347: (2,5-dimethoxybenzyl)-(2-furano-2-ylquinazolino-4-yl)-amine Compound No. 348: (2-furano-2-ylquinazolino-4-yl)-(2,4,6-trimethoxybenzyl)-amine
Compound No. 349: (2-methoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
Compound No. 350: (3-methoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
Compound No. 351: (4-methoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
Compound No. 352: benzo[l/3]dioxol-5-ylmethyl-(2-thiopenyl-2-ylquinazolino-4-yl)-amine Compound No. 353:
(2,3-dimethoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
Compound No. 354:
(3/5-dimethoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
Compound No. 355: (3,4-dimethoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
Compound No. 356:
(2-thiopenyl-2-ylquinazolino-4-yl)-(3,4,5-trimethoxybenzyl)-amine
Compound No. 357:
(2/4-dimethoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine Compound No. 358:
(2/5-dimethoxybenzyl)-(2-thiopenyl-2-ylquinazolino-4-yl)-amine
Compound No. 359:
(2-thiopenyl-2-ylquinazolino-4-yl)-(2,4/6-trimethoxybenzyl)-amine
Compound No. 360: (2-methoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine
Compound No. 361:
(3-methoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine
Compound No. 362:
(4-methoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine Compound No. 363: benzo[l/3]dioxol-5-ylmethyl-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-a mine
Compound No. 364:
(2,3-dimethoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine
Compound No. 365: (3,5-dimethoxybenzy I)- [2-(methoxyphenylmethyl)-quinazolino-4-yl] -amine
Compound No. 366:
(3,4-dimethoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine
Compound No. 367:
[2-(methoxyphenylmethyl)-quinazolino-4-yl]-(3,4/5-trimethoxybenzyl)-amine Compound No. 368:
(2/4-dimethoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine
Compound No. 369:
(2/5-dimethoxybenzyl)-[2-(methoxyphenylmethyl)-quinazolino-4-yl]-amine
Compound No. 370: [2-(methoxyphenylmethyl)-quinazolino-4-yl]-(2,4/6-trimethoxybenzyl)-amine
Compound No. 371: (2-methoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
Compound No. 372:
(3-methoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine Compound No. 373:
(4-methoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
Compound No. 374: benzo[l,3]dioxol-5-ylmethyl-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
Compound No. 375: (2,3-dimethoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
Compound No. 376:
(3,5-dimethoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
Compound No. 377:
(3,4-dimethoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine Compound No. 378:
[2-(l-phenylethyl)-quinazolino-4-yl]-(3/4/5-trimethoxybenzyl)-amine Compound No. 379:
(2/4-dimethoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine
Compound No. 380:
(2/5-dimethoxybenzyl)-[2-(l-phenylethyl)-quinazolino-4-yl]-amine Compound No. 381:
[2-(l-phenylethyl)-quinazolino-4-yl]-(2,4/6-trimethoxybenzyl)-amine
Compound No. 382: (2-cyclopropylquinazolino-4-yl)-(2-methoxybenzyl)-amine
Compound No. 383: (2-cy clopropylquinazolino-4-yl)-(3-methoxybenzy l)-amine
Compound No. 384: (2-cyclopropylquinazolino-4-yl)-(4-methoxybenzyl)-amine
Compound No. 385: benzo[l,3]dioxol-5-ylmethyl-(2-cyclopropylquinazolino-4-yl)-amine Compound No. 386:
(2-cyclopropylquinazolino-4-yl)-(2,3-dimethoxybenzyl)-amine
Compound No. 387: (2-cyclopropylquinazolino-4-yl)-(3,5-dimethoxybenzyl)-amine
Compound No. 388: (2-cyclopropylquinazolino-4-yl)-(3,4-dimethoxybenzyl)-amine
Compound No. 389:
(2-cyclopropylquinazolino-4-yl)-(3/4/5-trimethoxybenzyl)-amine
Compound No. 390:
(2-cyclopropylquinazolino-4-yl)-(2,4-dimethoxybenzyl)-amine Compound No. 391:
(2-cyclopropylquinazolino-4-yl)-(2/5-dimethoxybenzyl)-amine
Compound No. 392:
(2-cyclopropylquinazolino-4-yl)-(2/4/6-trimethoxybenzyl)-amine
Compound No. 393: (2-methoxybenzyl)-(2-propylquinazolino-4-yl)-amine Compound No. 394: (3-methoxybenzyl)-(2-propylquinazolino-4-yl)-amine
Compound No. 395: (4-methoxybenzyl)-(2-propylquinazolino-4-yl)-amine Compound No. 396: benzo[l,3]dioxol-5-ylmethyl-(2-propylquinazolino-4-yl)-amine Compound No. 397:
(2,3-dimethoxybenzyl)-(2-propylquinazolino-4-yl)-amine Compound No. 398:
(3,5-dimethoxybenzyl)-(2-propylquinazolino-4-yl)-amine Compound No. 399:
(3,4-dimethoxybenzyl)-(2-propylquinazolino-4-yl)-amine
Compound No. 400: (2-propy lquinazolino-4-yl)-(3/4/5-trimethoxybenzyl)-amine Compound No. 401:
(2/4-dimethoxybenzyl)-(2-propylquinazolino-4-yl)-amine Compound No. 402:
(2/5-dimethoxybenzyl)-(2-propylquinazolino-4-yl)-amine Compound No. 403:
(2-propylquinazolino-4-yl)-(2/4,6-trimethoxybenzyl)-amine
Compound No. 404: (2-methoxybenzyl)-quinazolino-4-ylamine Compound No. 405: (3-methoxybenzyl)-quinazolino-4-ylamine Compound No. 406: (4-methoxybenzyl)-quinazolino-4-ylamine Compound No. 407: benzo[l,3]dioxol-5-ylmethylquinazolino-4-ylamine
Compound No. 408: (2,3-dimethoxybenzyl)-quinazolino-4-ylamine Compound No. 409: (3,5-dimethoxybenzyl)-quinazolino-4-ylamine Compound No. 410: (3,4-dimethoxybenzyl)-quinazolino-4-ylamine Compound No. 411. quinazolino-4-yl-(3,4/5-trimethoxybenzyl)-amine Compound No. 412: (2,4-dimethoxybenzyl)-quinazolino-4-ylamine
Compound No. 413: (2,5-dimethoxybenzyl)-quinazolino-4-ylamine Compound No. 414: quinazolino-4-yl-(2/4,6-trimethoxybenzyl)-amine Compound No. 415: 4-benzyloxy-2-isopropylquinazoline Compound No. 416: 4-benzylsulfanyl-2-isopropylquinazoline.
5. A pharmaceutical composition comprising the quinazoline derivatives represented by the formula 1 below or a pharmaceutically available salt or prodrug thereof:
Figure imgf000143_0001
wherein Ra, Rb, Rc and m are the same as defined in Claim 1.
6. A medicine for treatment and prevention of diabetes comprising the quinazoline derivatives represented by the formula 1 below or a pharmaceutically available salt or prodrug thereof:
Figure imgf000143_0002
wherein Ra, Rb, Rc and m are the same as defined in Claim 1.
7. A medicine for treatment and prevention of obesity comprising the quinazoline derivatives represented by the formula 1 below or a pharmaceutically available salt or prodrug thereof:
Figure imgf000143_0003
wherein Ra, Rb, Rc and m are the same as defined in Claim 1.
PCT/KR2005/004664 2004-12-31 2005-12-30 Quinazoline derivatives for the treatment and prevention of diabetes and obesity WO2006071095A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP05823851A EP1844023A1 (en) 2004-12-31 2005-12-30 Quinazoline derivatives for the treatment and prevention of diabetes and obesity
JP2007549270A JP2008526734A (en) 2004-12-31 2005-12-30 Quinazoline derivatives effective in preventing diabetes and obesity

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR20040117708 2004-12-31
KR10-2004-0117708 2004-12-31

Publications (1)

Publication Number Publication Date
WO2006071095A1 true WO2006071095A1 (en) 2006-07-06

Family

ID=36615173

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2005/004664 WO2006071095A1 (en) 2004-12-31 2005-12-30 Quinazoline derivatives for the treatment and prevention of diabetes and obesity

Country Status (4)

Country Link
EP (1) EP1844023A1 (en)
JP (1) JP2008526734A (en)
KR (1) KR20060079121A (en)
WO (1) WO2006071095A1 (en)

Cited By (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007042669A2 (en) * 2005-10-12 2007-04-19 Sanofis-Aventis Derivatives of 4-amino-quinazoline, preparation method thereof and use of same in therapeutics
WO2007071632A3 (en) * 2005-12-20 2007-08-30 Neurosearch As 2-pyridin-2-yl-quinazoline derivatives as potassium channel modulating agents for the treatment of respiratory diseases
WO2008157500A1 (en) * 2007-06-17 2008-12-24 Kalypsys, Inc. Aminoquinazoline cannabinoid receptor modulators for treatment of disease
WO2009000085A1 (en) * 2007-06-27 2008-12-31 Painceptor Pharma Corporation Quinoline and quinazoline derivatives useful as modulators of gated ion channels
WO2009131173A1 (en) 2008-04-23 2009-10-29 協和発酵キリン株式会社 2-aminoquinazoline derivative
US7846915B2 (en) 2004-10-20 2010-12-07 Resverlogix Corporation Stilbenes and chalcones for the prevention and treatment of cardiovascular diseases
JP2011506480A (en) * 2007-12-12 2011-03-03 ライジェル ファーマシューティカルズ， インコーポレイテッド Carboxamide, sulfonamide, and amine compounds for metabolic disorders
US8053440B2 (en) 2007-02-01 2011-11-08 Resverlogix Corporation Compounds for the prevention and treatment of cardiovascular diseases
US8114995B2 (en) 2008-06-26 2012-02-14 Resverlogix Corp. Methods of preparing quinazolinone derivatives
US8212045B2 (en) 2007-09-21 2012-07-03 Array Biopharma, Inc. Pyridin-2-yl-amino-1, 2, 4-thiadiazole derivatives as glucokinase activators for the treatment of diabetes mellitus
US8252806B2 (en) 2005-03-14 2012-08-28 Neurosearch A/S Potassium channel modulating agents and their medical use
US8410109B2 (en) 2005-07-29 2013-04-02 Resverlogix Corp. Pharmaceutical compositions for the prevention and treatment of complex diseases and their delivery by insertable medical devices
US8575184B2 (en) 2009-09-03 2013-11-05 Bristol-Myers Squibb Company Quinazolines as potassium ion channel inhibitors
US8889730B2 (en) 2012-04-10 2014-11-18 Pfizer Inc. Indole and indazole compounds that activate AMPK
US8952021B2 (en) 2009-01-08 2015-02-10 Resverlogix Corp. Compounds for the prevention and treatment of cardiovascular disease
US9073878B2 (en) 2012-11-21 2015-07-07 Zenith Epigenetics Corp. Cyclic amines as bromodomain inhibitors
US9238640B2 (en) 2009-03-18 2016-01-19 Resverlogix Corp. Anti-inflammatory agents
US9271978B2 (en) 2012-12-21 2016-03-01 Zenith Epigenetics Corp. Heterocyclic compounds as bromodomain inhibitors
US20160159751A1 (en) * 2014-12-05 2016-06-09 Subramaniam Ananthan Novel quinazolines as biogenic amine transport modulators
US9394285B2 (en) 2013-03-15 2016-07-19 Pfizer Inc. Indole and indazole compounds that activate AMPK
CN106045924A (en) * 2016-07-28 2016-10-26 黑龙江八农垦大学 Synthesis method of aryl-substituted quinazoline amine derivative
US9610251B2 (en) 2011-11-01 2017-04-04 Resverlogix Corp. Pharmaceutical compositions for substituted quinazolinones
US9624195B2 (en) 2014-12-24 2017-04-18 Gilead Sciences, Inc. Isoquinoline compounds
US9701677B2 (en) 2014-12-24 2017-07-11 Gilead Sciences, Inc. Fused pyrimidine compounds
US9730936B2 (en) 2014-12-24 2017-08-15 Gilead Sciences, Inc. Quinazoline compounds
US9757368B2 (en) 2009-04-22 2017-09-12 Resverlogix Corp. Anti-inflammatory agents
US9765039B2 (en) 2012-11-21 2017-09-19 Zenith Epigenetics Ltd. Biaryl derivatives as bromodomain inhibitors
US9802904B2 (en) 2012-12-28 2017-10-31 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Inhibitors of the USP1/UAF1 deubiquitinase complex and uses thereof
US9828373B2 (en) 2014-07-26 2017-11-28 Sunshine Lake Pharma Co., Ltd. 2-amino-pyrido[2,3-D]pyrimidin-7(8H)-one derivatives as CDK inhibitors and uses thereof
US9873702B2 (en) 2014-12-05 2018-01-23 Southern Research Institute Heterocyclic compounds as biogenic amine transport modulators
US9949979B2 (en) 2011-12-15 2018-04-24 Novartis Ag Use of inhibitors of the activity or function of PI3K
US10111885B2 (en) 2015-03-13 2018-10-30 Resverlogix Corp. Compositions and therapeutic methods for the treatment of complement-associated diseases
WO2020021064A1 (en) 2018-07-26 2020-01-30 Domain Therapeutics Substituted quinazolinone derivatives and their use as positive allosteric modulators of mglur4
US10934284B2 (en) 2013-02-01 2021-03-02 Wellstat Therapeutics Corporation Aminoquinazoline compounds having anti-inflammatory, antifungal, antiparasitic, and anticancer activity
CN112608302A (en) * 2020-12-28 2021-04-06 郑州大学第一附属医院 Quinazoline derivative for activating targeted ubiquitination degradation of EGFR protein through low oxygen reduction and application thereof
US11279702B2 (en) 2020-05-19 2022-03-22 Kallyope, Inc. AMPK activators
CN114315802A (en) * 2021-12-14 2022-04-12 西安医学院 Quinazoline nitrogen-containing heterocyclic derivative and preparation method and application thereof
WO2022091029A1 (en) * 2020-10-30 2022-05-05 Resverlogix Corp. Methods for lowering hba1c level with a combination of a bet bromodomain inhibitor and a sodium dependent glucose transport 2 inhibitor
US11407768B2 (en) 2020-06-26 2022-08-09 Kallyope, Inc. AMPK activators
CZ309449B6 (en) * 2020-12-24 2023-01-25 Ústav experimentální botaniky AV ČR, v. v. i. Quinazoline derivatives as selective cyclooxygenase-1 inhibitors

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2009268547A1 (en) * 2008-07-11 2010-01-14 Myrexis, Inc. Pharmaceutical compounds as cytotoxic agents and the use thereof
PH12012500097A1 (en) * 2009-07-21 2011-01-27 Shanghai Inst Organic Chem Potent small molecule inhibitors of autophagy, and methods of use thereof
KR101467996B1 (en) * 2010-04-30 2014-12-11 전북대학교산학협력단 The qhinazoline derivatives which are inhibitor of ADP-ribosyl cyclases

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998013354A1 (en) * 1996-09-25 1998-04-02 Zeneca Limited Quinazoline derivatives and pharmaceutical compositions containing them
WO2000010981A1 (en) * 1998-08-21 2000-03-02 Parker Hughes Institute Quinazoline derivatives
WO2000012497A2 (en) * 1998-08-28 2000-03-09 Scios Inc. Quinazoline derivatives as medicaments
WO2004087680A1 (en) * 2003-03-31 2004-10-14 Taisho Pharmaceutical Co., Ltd. Novel quinazoline derivatives and methods of treatment related to the use thereof

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3340260A (en) * 1962-12-03 1967-09-05 Ciba Geigy Corp 4-amino-pyrimidines
JPS542325A (en) * 1977-06-07 1979-01-09 Sankyo Co Ltd Agricultural and horticultural pesticide
IL89027A (en) * 1988-01-29 1993-01-31 Lilly Co Eli Quinazoline derivatives, process for their preparation and fungicidal, insecticidal and miticidal compositions containing them
PT100905A (en) * 1991-09-30 1994-02-28 Eisai Co Ltd BICYCLE HYGIENEOUS HETEROCYCLIC COMPOUNDS CONTAINING BENZENE, CYCLOHEXAN OR PYRIDINE AND PYRIMIDINE, PYRIDINE OR IMIDAZOLE SUBSTITUTES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
JP2657760B2 (en) * 1992-07-15 1997-09-24 小野薬品工業株式会社 4-aminoquinazoline derivatives and pharmaceuticals containing them
GB2295387A (en) * 1994-11-23 1996-05-29 Glaxo Inc Quinazoline antagonists of alpha 1c adrenergic receptors
US6046206A (en) * 1995-06-07 2000-04-04 Cell Pathways, Inc. Method of treating a patient having a precancerous lesions with amide quinazoline derivatives
DE19756388A1 (en) * 1997-12-18 1999-06-24 Hoechst Marion Roussel De Gmbh New 2-aryl-4-amino-6,7-di:methoxy-quinazoline derivatives useful as guanylate cyclase activators for treating cardiovascular diseases, etc.
WO2002062767A1 (en) * 2001-02-07 2002-08-15 Sumitomo Pharmaceuticals Company, Limited Novel quinazoline derivatives
DE10224462A1 (en) * 2002-06-03 2003-12-11 Bayer Ag Use of cGMP stimulating compounds
WO2004092196A2 (en) * 2003-04-09 2004-10-28 Exelixis, Inc. Tie-2 modulators and methods of use
CA2531327A1 (en) * 2003-07-03 2005-01-13 Myriad Genetics, Inc. Compounds and therapeutical use thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998013354A1 (en) * 1996-09-25 1998-04-02 Zeneca Limited Quinazoline derivatives and pharmaceutical compositions containing them
WO2000010981A1 (en) * 1998-08-21 2000-03-02 Parker Hughes Institute Quinazoline derivatives
WO2000012497A2 (en) * 1998-08-28 2000-03-09 Scios Inc. Quinazoline derivatives as medicaments
WO2004087680A1 (en) * 2003-03-31 2004-10-14 Taisho Pharmaceutical Co., Ltd. Novel quinazoline derivatives and methods of treatment related to the use thereof

Cited By (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8093273B2 (en) 2004-10-20 2012-01-10 Resverlogix Corp. Flavanoids and isoflavanoids for the prevention and treatment of cardiovascular diseases
US8242130B2 (en) 2004-10-20 2012-08-14 Resverlogix Corp. Flavanoids and isoflavanoids for the prevention and treatment of cardiovascular diseases
US7846915B2 (en) 2004-10-20 2010-12-07 Resverlogix Corporation Stilbenes and chalcones for the prevention and treatment of cardiovascular diseases
US8252806B2 (en) 2005-03-14 2012-08-28 Neurosearch A/S Potassium channel modulating agents and their medical use
US8410109B2 (en) 2005-07-29 2013-04-02 Resverlogix Corp. Pharmaceutical compositions for the prevention and treatment of complex diseases and their delivery by insertable medical devices
WO2007042669A2 (en) * 2005-10-12 2007-04-19 Sanofis-Aventis Derivatives of 4-amino-quinazoline, preparation method thereof and use of same in therapeutics
WO2007042669A3 (en) * 2005-10-12 2007-05-31 Sanofis Aventis Derivatives of 4-amino-quinazoline, preparation method thereof and use of same in therapeutics
WO2007071632A3 (en) * 2005-12-20 2007-08-30 Neurosearch As 2-pyridin-2-yl-quinazoline derivatives as potassium channel modulating agents for the treatment of respiratory diseases
US8053440B2 (en) 2007-02-01 2011-11-08 Resverlogix Corporation Compounds for the prevention and treatment of cardiovascular diseases
US8889698B2 (en) 2007-02-01 2014-11-18 Resverlogix Corp. Compounds for the prevention and treatment of cardiovascular diseases
US9199990B2 (en) 2007-02-01 2015-12-01 Resverlogix Corp. Compounds for the prevention and treatment of cardiovascular diseases
US10532054B2 (en) 2007-02-01 2020-01-14 Resverlogix Corp. Compounds for the prevention and treatment of cardiovascular diseases
WO2008157500A1 (en) * 2007-06-17 2008-12-24 Kalypsys, Inc. Aminoquinazoline cannabinoid receptor modulators for treatment of disease
WO2009000085A1 (en) * 2007-06-27 2008-12-31 Painceptor Pharma Corporation Quinoline and quinazoline derivatives useful as modulators of gated ion channels
US8212045B2 (en) 2007-09-21 2012-07-03 Array Biopharma, Inc. Pyridin-2-yl-amino-1, 2, 4-thiadiazole derivatives as glucokinase activators for the treatment of diabetes mellitus
US8853409B2 (en) 2007-09-21 2014-10-07 Array Biopharma Inc. Pyridin-2yl-amino-1, 2, 4-thiadiazole derivatives as glucokinase activators for the treatment of diabetes mellitus
US9079890B2 (en) 2007-09-21 2015-07-14 Array Biopharma Inc. Intermediates for the preparation of pyridin-2-yl-amino-1,2,4-thiadiazole derivatives
JP2011506480A (en) * 2007-12-12 2011-03-03 ライジェル ファーマシューティカルズ， インコーポレイテッド Carboxamide, sulfonamide, and amine compounds for metabolic disorders
WO2009131173A1 (en) 2008-04-23 2009-10-29 協和発酵キリン株式会社 2-aminoquinazoline derivative
US8114995B2 (en) 2008-06-26 2012-02-14 Resverlogix Corp. Methods of preparing quinazolinone derivatives
US8952021B2 (en) 2009-01-08 2015-02-10 Resverlogix Corp. Compounds for the prevention and treatment of cardiovascular disease
US11407719B2 (en) 2009-03-18 2022-08-09 Resverlogix Corp. Anti-inflammatory agents
US10131640B2 (en) 2009-03-18 2018-11-20 Resverlogix Corp. Anti-inflammatory agents
US10882828B2 (en) 2009-03-18 2021-01-05 Resverlogix Corp. Anti-inflammatory agents
US9238640B2 (en) 2009-03-18 2016-01-19 Resverlogix Corp. Anti-inflammatory agents
US9757368B2 (en) 2009-04-22 2017-09-12 Resverlogix Corp. Anti-inflammatory agents
US11008306B2 (en) 2009-09-03 2021-05-18 Bristol-Myers Squibb Company Quinazolines as potassium ion channel inhibitors
US9822096B2 (en) 2009-09-03 2017-11-21 Bristol-Myers Squibb Company Quinazolines as potassium ion channel inhibitors
US9458114B2 (en) 2009-09-03 2016-10-04 Bristol-Myers Squibb Company Quinazolines as potassium ion channel inhibitors
US10214511B2 (en) 2009-09-03 2019-02-26 Bristol-Myers Squibb Company Quinazolines as potassium ion channel inhibitors
US8575184B2 (en) 2009-09-03 2013-11-05 Bristol-Myers Squibb Company Quinazolines as potassium ion channel inhibitors
US10676460B2 (en) 2009-09-03 2020-06-09 Bristol-Myers Squibb Company Quinazolines as potassium ion channel inhibitors
US9610251B2 (en) 2011-11-01 2017-04-04 Resverlogix Corp. Pharmaceutical compositions for substituted quinazolinones
US10016426B2 (en) 2011-11-01 2018-07-10 Resverlogix Corp. Pharmaceutical compositions for substituted quinazolinones
US9949979B2 (en) 2011-12-15 2018-04-24 Novartis Ag Use of inhibitors of the activity or function of PI3K
US8889730B2 (en) 2012-04-10 2014-11-18 Pfizer Inc. Indole and indazole compounds that activate AMPK
US9278940B2 (en) 2012-11-21 2016-03-08 Zenith Epigenetics Corp. Cyclic amines as bromodomain inhibitors
US9765039B2 (en) 2012-11-21 2017-09-19 Zenith Epigenetics Ltd. Biaryl derivatives as bromodomain inhibitors
US9073878B2 (en) 2012-11-21 2015-07-07 Zenith Epigenetics Corp. Cyclic amines as bromodomain inhibitors
US9271978B2 (en) 2012-12-21 2016-03-01 Zenith Epigenetics Corp. Heterocyclic compounds as bromodomain inhibitors
US9802904B2 (en) 2012-12-28 2017-10-31 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Inhibitors of the USP1/UAF1 deubiquitinase complex and uses thereof
US10934284B2 (en) 2013-02-01 2021-03-02 Wellstat Therapeutics Corporation Aminoquinazoline compounds having anti-inflammatory, antifungal, antiparasitic, and anticancer activity
US9394285B2 (en) 2013-03-15 2016-07-19 Pfizer Inc. Indole and indazole compounds that activate AMPK
US9828373B2 (en) 2014-07-26 2017-11-28 Sunshine Lake Pharma Co., Ltd. 2-amino-pyrido[2,3-D]pyrimidin-7(8H)-one derivatives as CDK inhibitors and uses thereof
US9873702B2 (en) 2014-12-05 2018-01-23 Southern Research Institute Heterocyclic compounds as biogenic amine transport modulators
US10087148B2 (en) * 2014-12-05 2018-10-02 The United States Of America As Represented By The Secretary, Department Of Health And Human Services Office Of Technology Transfer, National Institute Of Health Quinazolines as biogenic amine transport modulators
US20160159751A1 (en) * 2014-12-05 2016-06-09 Subramaniam Ananthan Novel quinazolines as biogenic amine transport modulators
US9701677B2 (en) 2014-12-24 2017-07-11 Gilead Sciences, Inc. Fused pyrimidine compounds
US11304948B2 (en) 2014-12-24 2022-04-19 Gilead Sciences, Inc. Quinazoline compounds
US10548898B2 (en) 2014-12-24 2020-02-04 Gilead Sciences Inc. Quinazoline compounds
US10206926B2 (en) 2014-12-24 2019-02-19 Gilead Sciences, Inc. Quinazoline compounds
US9730936B2 (en) 2014-12-24 2017-08-15 Gilead Sciences, Inc. Quinazoline compounds
US9624195B2 (en) 2014-12-24 2017-04-18 Gilead Sciences, Inc. Isoquinoline compounds
US10772894B2 (en) 2015-03-13 2020-09-15 Resverlogix Corp. Compositions and therapeutic methods for the treatment of complement-associated diseases
US10111885B2 (en) 2015-03-13 2018-10-30 Resverlogix Corp. Compositions and therapeutic methods for the treatment of complement-associated diseases
CN106045924A (en) * 2016-07-28 2016-10-26 黑龙江八农垦大学 Synthesis method of aryl-substituted quinazoline amine derivative
WO2020021064A1 (en) 2018-07-26 2020-01-30 Domain Therapeutics Substituted quinazolinone derivatives and their use as positive allosteric modulators of mglur4
US11279702B2 (en) 2020-05-19 2022-03-22 Kallyope, Inc. AMPK activators
US11851429B2 (en) 2020-05-19 2023-12-26 Kallyope, Inc. AMPK activators
US11407768B2 (en) 2020-06-26 2022-08-09 Kallyope, Inc. AMPK activators
WO2022091029A1 (en) * 2020-10-30 2022-05-05 Resverlogix Corp. Methods for lowering hba1c level with a combination of a bet bromodomain inhibitor and a sodium dependent glucose transport 2 inhibitor
CZ309449B6 (en) * 2020-12-24 2023-01-25 Ústav experimentální botaniky AV ČR, v. v. i. Quinazoline derivatives as selective cyclooxygenase-1 inhibitors
CN112608302A (en) * 2020-12-28 2021-04-06 郑州大学第一附属医院 Quinazoline derivative for activating targeted ubiquitination degradation of EGFR protein through low oxygen reduction and application thereof
CN114315802A (en) * 2021-12-14 2022-04-12 西安医学院 Quinazoline nitrogen-containing heterocyclic derivative and preparation method and application thereof

Also Published As

Publication number Publication date
JP2008526734A (en) 2008-07-24
KR20060079121A (en) 2006-07-05
EP1844023A1 (en) 2007-10-17

Similar Documents

Publication Publication Date Title
WO2006071095A1 (en) Quinazoline derivatives for the treatment and prevention of diabetes and obesity
CN102548983B (en) Heteroaromatic and aromatic piperazinyl azetidinyl amides as monoacylglycerol lipase inhibitor
US20080207614A1 (en) Quinazoline derivatives for the treatment and prevention of diabetes and obesity
CN101466714B (en) Purinone derivatives as HM74A agonists
CN102596923B (en) 1, 2, 4-thiazolidin-3-one derivatives and their use in the treatment of cancer
CN101531638B (en) Compound used as a regulator of estrogen-related receptor and applications thereof
CN101679365A (en) As the new pyrrole-2-carboxamides derivatives of glucokinase activators, their manufacture method and pharmaceutical application
JP5897566B2 (en) Cyclic N, N'-diarylthiourea and N, N'-diarylurea-androgen receptor antagonists, anticancer agents, methods for their preparation and uses
MXPA06007715A (en) (3-oxo-3, 4-dihydro-quinoxalin-2-yl-amino) -benzamide derivatives and related compound as glycogen phosphorylase inhibitors for the treatment of diabetes and obesity.
CA2437409C (en) Azoles as malonyl-coa decarboxylase inhibitors useful as metabolic modulators
DE602004009582T2 (en) CYANOAMIDE COMPOUNDS AS USEFUL MALONYL COA DECARBOXYLASE HEMMER
EA024703B1 (en) Combination of olanzapine and taar1 agonist
TW201313708A (en) Monoacylglycerol lipase inhibitors for the treatment of metabolic diseases and related disorders
CN114014796A (en) Epstein salt and preparation method and application thereof
US20090176780A1 (en) Nitrogenous heterocyclic compounds
CN101827595B (en) Substituted piperazines and piperidines as modulators of the neuropeptide Y2 receptor
KR20030085005A (en) Antipruritics
CN105367565B (en) Piperazine (pyridine) cyclohexyl derivatives and its application for treating Mental disease
KR101676889B1 (en) Phenylimidazole compounds
KR20020067919A (en) Novel Compounds
KR101123071B1 (en) Novel imidazole derivatives or pharmaceutically acceptable salts thereof, preparation method thereof and pharmaceutical composition for the prevention and treatment of melanoma containing the same as an active ingredient
US20220281817A1 (en) Benzamide derivative, preparation method therefor, and pharmaceutical composition comprising same as active ingredient for prevention or treatment of cancer
CN105111151A (en) Aminopyrimidine derivative used as PPAR-gamma regulator
US5116839A (en) Use of isoxazolin-3-one derivatives as antidepressants
US20130252992A1 (en) Cyclic n,n'-diarylthiourea - androgen receptor antagonist, anti breast cancer composition and use thereof

Legal Events

Date Code Title Description
DPE2 Request for preliminary examination filed before expiration of 19th month from priority date (pct application filed from 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2007549270

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2005823851

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2005823851

Country of ref document: EP