DE10064823A1 - New (hetero)aryl-substituted aliphatic carboxylic acid derivatives, useful as integrin receptor ligands for treating, e.g. atherosclerosis, restenosis, rheumatoid arthritis, cancer, osteoporosis or hypertension - Google Patents
New (hetero)aryl-substituted aliphatic carboxylic acid derivatives, useful as integrin receptor ligands for treating, e.g. atherosclerosis, restenosis, rheumatoid arthritis, cancer, osteoporosis or hypertensionInfo
- Publication number
- DE10064823A1 DE10064823A1 DE10064823A DE10064823A DE10064823A1 DE 10064823 A1 DE10064823 A1 DE 10064823A1 DE 10064823 A DE10064823 A DE 10064823A DE 10064823 A DE10064823 A DE 10064823A DE 10064823 A1 DE10064823 A1 DE 10064823A1
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- aryl
- cycloalkyl
- aralkyl
- alkynyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
- 125000005842 heteroatom Chemical group 0.000 title abstract 7
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 title abstract 3
- 201000001320 Atherosclerosis Diseases 0.000 title 1
- 206010020772 Hypertension Diseases 0.000 title 1
- 206010028980 Neoplasm Diseases 0.000 title 1
- 208000001132 Osteoporosis Diseases 0.000 title 1
- 201000011510 cancer Diseases 0.000 title 1
- 102000006495 integrins Human genes 0.000 title 1
- 108010044426 integrins Proteins 0.000 title 1
- 239000003446 ligand Substances 0.000 title 1
- 208000037803 restenosis Diseases 0.000 title 1
- 206010039073 rheumatoid arthritis Diseases 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 abstract 15
- 125000003118 aryl group Chemical group 0.000 abstract 10
- 229910052760 oxygen Inorganic materials 0.000 abstract 9
- 125000003342 alkenyl group Chemical group 0.000 abstract 6
- 125000000304 alkynyl group Chemical group 0.000 abstract 6
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 6
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 6
- 125000001072 heteroaryl group Chemical group 0.000 abstract 6
- 229910052717 sulfur Inorganic materials 0.000 abstract 6
- 125000004475 heteroaralkyl group Chemical group 0.000 abstract 5
- 229910052757 nitrogen Inorganic materials 0.000 abstract 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 3
- 125000002950 monocyclic group Chemical group 0.000 abstract 3
- 125000004945 acylaminoalkyl group Chemical group 0.000 abstract 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract 2
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 abstract 2
- 125000004366 heterocycloalkenyl group Chemical group 0.000 abstract 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 2
- 125000003367 polycyclic group Chemical group 0.000 abstract 2
- 229920006395 saturated elastomer Polymers 0.000 abstract 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 abstract 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract 1
- -1 aralkoxycarbonyl Chemical group 0.000 abstract 1
- 125000005140 aralkylsulfonyl group Chemical group 0.000 abstract 1
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 abstract 1
- 125000005129 aryl carbonyl group Chemical group 0.000 abstract 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 abstract 1
- 125000002619 bicyclic group Chemical group 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 abstract 1
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 229940002612 prodrug Drugs 0.000 abstract 1
- 239000000651 prodrug Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000006850 spacer group Chemical group 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/40—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
-
- 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
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
(Hetero)aryl-substituted aliphatic carboxylic acid derivatives (I) are new. (Hetero)aryl-substituted aliphatic carboxylic acid derivatives of formula (I) and their salts, prodrugs, pure enantiomers or diastereomers and tautomers are new. T = COOH, a group hydrolyzable to COOH or bioisostere of COOH; U = -(Xu)a-(CR1R2)b-(CH2)c-, -(Xu)a-(CR1R2)b-C(R1)=C(R2)c- or -(Xu)a-(CR1R2)b-CC-; a = 0 or 1; Xu = -(CR3R4)d-, O or S; b, c, d = 0 - 2; R1 - R4 = H, T, OH or halo; or 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 3-7C cycloalkyl, mono- or di-(1-6C alkyl)-aminoalkyl, 1-2C alkylene-T, 2C alkenylene-T, 2C alkynylene-T, aryl or aralkyl (all optionally substituted (os)); or R1 + R2, R3 + R4 or R1 + R3 = group (completing an os 3-7 membered ring containing 0-3 of O, S and N as heteroatom(s)); G = mono- or bicyclic 6-10C aryl (os) or 5-10C heteroaryl residue (substituted by U and X in adjacent positions); X = CO, CONR'1, NR'1CO, NR'1, S, SO, SO2, SO2NR'1, NR'1SO2, CS, NR'1CS, CS-O, O-CS, CO-O, O-CO, O, CC, CR'2-O-CR'3, CR'2R'3, CR'2R'3-NR'3, C(=CR'2R'3), CR'2=CR'3, CR'2(OR'4)-CR'3, CR'2CR'3(OR'4) or 4-11 membered, mono- or polycyclic cycloaliphatic or aromatic ring (os and containing 0-6 double bonds and 0-6 of O, S and N as heteroatom(s)); R'1 = H or 1-8C alkyl, 2-8C alkenyl, 2-8C alkynyl, OR'5, 3-7C cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, (1-6C) alkylcarbonyl, (1-6C) alkoxycarbonyl, 1-6C alkylsulfonyl, aralkoxycarbonyl, aralkylcarbonyl, arylcarbonyl, arylsulfonyl, heteroarylcarbonyl, aralkylsulfonyl, heteroarylsulfonyl or heteroaralkylsulfonyl (all os); R'2, R'3 = H, OH or (1-6C alkyl, 1-4C alkoxy, 2-6C alkenyl, 2-6C alkynyl, cycloalkylalkyl, 3-7C cycloalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl (all os); R'4, R'5 = H or 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, cycloalkylalkyl, 3-7C cycloalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl (all os); A = 4-8 membered, monocyclic, saturated, unsaturated or aromatic ring (os and containing 1-4 of O, S and N as heteroatom(s)), 9-14 membered, polycyclic, saturated, unsaturated or aromatic ring (os and containing 1-6 of O, S and N as heteroatom(s) or -C(=Z)-Z'; Z, Z' = O, S or N (os); R18, R 19 = H or 1-8C alkyl, 2-6C alkenyl, 2-6C alkynyl, (1-4C) alkoxy-(1-5C) alkyl, mono- or dialkylaminoalkyl, acylaminoalkyl, aryl, heterocycloalkyl, heterocycloalkenyl, heteroaryl, 3-7C cycloalkyl, 3-7C cycloalkyl-(1-4C) alkyl, aralkyl, heterocycloalkyl-(1-4C) alkyl, heterocycloalkenyl-(1-4C) alkyl, heteroaralkyl, SO2R20, COOR20, CONR20R21 or COR20 (all os); R20, R21 = H or 1-8C alkyl, 2-6C alkenyl, 2-6C alkynyl, (1-4C) alkoxy-(1-5C) alkyl, mono- or dialkylaminoalkyl, acylaminoalkyl, aryl, heterocycloalkyl, heterocycloalkenyl, heteroaryl, 3-7C cycloalkyl, 3-7C cycloalkyl-(1-4C) alkyl, aralkyl, heterocycloalkyl-(1-4C) alkyl, heterocycloalkenyl-(1-4C) alkyl or heteroaralkyl (all os); and E = spacer element covalently linking A with G, such that the number of atomic bonds along the shortest possible route through E is 2-15.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10064823A DE10064823A1 (en) | 2000-12-22 | 2000-12-22 | New (hetero)aryl-substituted aliphatic carboxylic acid derivatives, useful as integrin receptor ligands for treating, e.g. atherosclerosis, restenosis, rheumatoid arthritis, cancer, osteoporosis or hypertension |
PCT/EP2001/014924 WO2002051810A2 (en) | 2000-12-22 | 2001-12-18 | Integrin receptor ligands |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10064823A DE10064823A1 (en) | 2000-12-22 | 2000-12-22 | New (hetero)aryl-substituted aliphatic carboxylic acid derivatives, useful as integrin receptor ligands for treating, e.g. atherosclerosis, restenosis, rheumatoid arthritis, cancer, osteoporosis or hypertension |
Publications (1)
Publication Number | Publication Date |
---|---|
DE10064823A1 true DE10064823A1 (en) | 2002-06-27 |
Family
ID=7668842
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE10064823A Withdrawn DE10064823A1 (en) | 2000-12-22 | 2000-12-22 | New (hetero)aryl-substituted aliphatic carboxylic acid derivatives, useful as integrin receptor ligands for treating, e.g. atherosclerosis, restenosis, rheumatoid arthritis, cancer, osteoporosis or hypertension |
Country Status (2)
Country | Link |
---|---|
DE (1) | DE10064823A1 (en) |
WO (1) | WO2002051810A2 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7521473B2 (en) | 2004-02-25 | 2009-04-21 | Wyeth | Inhibitors of protein tyrosine phosphatase 1B |
US11697666B2 (en) | 2021-04-16 | 2023-07-11 | Gilead Sciences, Inc. | Methods of preparing carbanucleosides using amides |
US11767337B2 (en) | 2020-02-18 | 2023-09-26 | Gilead Sciences, Inc. | Antiviral compounds |
US12030903B2 (en) | 2020-02-18 | 2024-07-09 | Gilead Sciences, Inc. | Antiviral compounds |
US12054507B2 (en) | 2020-02-18 | 2024-08-06 | Gilead Sciences, Inc. | Antiviral compounds |
US12116380B2 (en) | 2022-08-16 | 2024-10-15 | Gilead Sciences, Inc. | Phospholipid compounds and methods of making and using the same |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BRPI0412259B1 (en) | 2003-07-22 | 2019-08-20 | Astex Therapeutics Limited | 3,4-Disubstituted 1H-pyrazole compounds as cyclin-dependent kinase (CDK) modulators, their uses, process for their preparation and pharmaceutical composition |
AR054425A1 (en) | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | PIPERIDIN ADDITION SALTS 4-IL-ACID AMID 4- (2,6-DICLORO-BENZOILAMINO) 1H-PIRAZOL-3-CARBOXILICO. |
US8404718B2 (en) | 2005-01-21 | 2013-03-26 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors |
US8329703B2 (en) | 2005-02-15 | 2012-12-11 | Xtl Biopharmaceuticals Ltd. | Pyrazole compounds |
WO2008048589A2 (en) | 2006-10-13 | 2008-04-24 | Xtl Biopharmaceuticals Ltd | Compounds and methods for treatment of hcv |
CN110446708B (en) | 2017-07-21 | 2022-12-02 | 安塔比奥公司 | Chemical compound |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0889877B1 (en) * | 1996-03-29 | 2001-08-29 | G.D. Searle & Co. | META-SUBSTITUTED PHENYLENE DERIVATIVES AND THEIR USE AS ALPHAvBETA3 INTEGRIN ANTAGONISTS OR INHIBITORS |
AU748621B2 (en) * | 1998-08-13 | 2002-06-06 | Merck & Co., Inc. | Integrin receptor antagonists |
-
2000
- 2000-12-22 DE DE10064823A patent/DE10064823A1/en not_active Withdrawn
-
2001
- 2001-12-18 WO PCT/EP2001/014924 patent/WO2002051810A2/en not_active Application Discontinuation
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7521473B2 (en) | 2004-02-25 | 2009-04-21 | Wyeth | Inhibitors of protein tyrosine phosphatase 1B |
US11767337B2 (en) | 2020-02-18 | 2023-09-26 | Gilead Sciences, Inc. | Antiviral compounds |
US12030903B2 (en) | 2020-02-18 | 2024-07-09 | Gilead Sciences, Inc. | Antiviral compounds |
US12054507B2 (en) | 2020-02-18 | 2024-08-06 | Gilead Sciences, Inc. | Antiviral compounds |
US11697666B2 (en) | 2021-04-16 | 2023-07-11 | Gilead Sciences, Inc. | Methods of preparing carbanucleosides using amides |
US12116380B2 (en) | 2022-08-16 | 2024-10-15 | Gilead Sciences, Inc. | Phospholipid compounds and methods of making and using the same |
Also Published As
Publication number | Publication date |
---|---|
WO2002051810A3 (en) | 2003-03-20 |
WO2002051810A2 (en) | 2002-07-04 |
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Legal Events
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8139 | Disposal/non-payment of the annual fee |