CN1358191A - N-吡唑a2a受体激动剂 - Google Patents
N-吡唑a2a受体激动剂 Download PDFInfo
- Publication number
- CN1358191A CN1358191A CN00809459A CN00809459A CN1358191A CN 1358191 A CN1358191 A CN 1358191A CN 00809459 A CN00809459 A CN 00809459A CN 00809459 A CN00809459 A CN 00809459A CN 1358191 A CN1358191 A CN 1358191A
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- Prior art keywords
- alkyl
- aryl
- heteroaryl
- randomly
- halogen
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
Abstract
Description
化合物号 | A2aKi,nM | n |
12 | +++ | 2 |
13 | ++ | 3 |
14 | ++ | 1 |
15 | ++ | 3 |
16 | ++ | 2 |
17 | - | 1 |
18 | +++ | 3 |
19 | +++ | 3 |
20 | +++ | 3 |
21 | +++ | 3 |
22 | +++ | 3 |
HEK-hA2AAR细胞 | CHO-hA1AR | |||
结合亲和力 | n | 结合亲和力 | n | |
WRC-0470 | 272(6.55±0.04)[0.83±0.07] | 6 | 7278(5.16±0.09)[1.13±0.21] | 3 |
化合物16 | 1269(5.90±0.03)[0.73±0.04] | 7 | >16460(4.59±0.35)[0.92±0.04] | 3 |
CGS21680 | 609(6.22±0.06){0.65±0.07) | 3 | >3540(5.47±0.20) | 3 |
NECA | 360(6.45±0.06)[0.83±0.08] | 3 | 328(6.49±0.06)[0.88±0.03] | 3 |
R-PIA | 1656(5.78±0.02)[1.05±0.02) | 3 | 477(6.35±0.11)[1.03±0.08] | 3 |
交叉力(EC50) | |||
激动剂 | n | 大鼠 | 脬鼠 |
Compound 16 | 4 | 6.4±1.2 | 18.6±6.0 |
腺苷 | 4 | 59.2±6.4 | 86.0±0.5 |
CGS21680 | 4 | 0.5±0.1 | 1.7±0.4 |
WRC0470 | 3 | 0.6±0.2 | 2.4±1.1 |
激动剂 | t0.5(min) | t0.9(min) | n |
腺苷 | 1.06±0.1 | 5.6±0.8 | 11 |
HENECA | 28.6±1.1 | 32.8±3.1 | 3 |
R-PIA | 7.9±0.1 | 12.6±0.8 | 3 |
CGS21680 | 14.5±0.9 | 19.5±0.9 | 3 |
YT-146 | 17.7±1.0 | 28.5±4.0 | 3 |
化合物12 | 14.83±2.1 | 15.0±0.8 | 3 |
化合物13 | 14.4±1.9 | 21.3±3.9 | 4 |
化合物16 | 5.2±0.2 | 11.3±1.1 | 5 |
激动剂 | CBF("成倍增加") | n |
化合物16(10μg/kg/min) | 3.40±0.04 | 3 |
化合物16(310μg/kg/min) | 3.83±0.39 | 6 |
WRC-470(1μg/kg/min) | 3.14±0.24 | 6 |
GSC21680(2μg/kg/min) | 3.54±0.093 | 3 |
YT-146(1μg/kg/min) | 3.44±0.47 | 3 |
激动剂 | t0.5(min) | t0.9(min) | n |
化合物16(10μg/kg/min) | 1.9±0.2 | 10.1±0.7 | 3 |
化合物16(310μg/kg/min) | 2.6±0.4 | 12.3±1.1 | 6 |
WRC-470(1μg/kg/min) | 9.5±0.8 | 22.5±1.6 | 6 |
GSC21680(2μg/kg/min) | 9.7±0.8 | 21.4±0.8 | 3 |
YT-146(1μg/kg/min) | 17.8.±3.4 | 32.9±5.6 | 3 |
Claims (25)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/338,185 US6403567B1 (en) | 1999-06-22 | 1999-06-22 | N-pyrazole A2A adenosine receptor agonists |
US09/338,185 | 1999-06-22 |
Publications (2)
Publication Number | Publication Date |
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CN1358191A true CN1358191A (zh) | 2002-07-10 |
CN1167709C CN1167709C (zh) | 2004-09-22 |
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CNB008094594A Expired - Lifetime CN1167709C (zh) | 1999-06-22 | 2000-06-21 | N-吡唑a2a受体激动剂 |
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US (9) | US6403567B1 (zh) |
EP (1) | EP1189916B1 (zh) |
JP (1) | JP4727880B2 (zh) |
KR (1) | KR100463300B1 (zh) |
CN (1) | CN1167709C (zh) |
AR (1) | AR024441A1 (zh) |
AT (1) | ATE256141T1 (zh) |
AU (1) | AU760806B2 (zh) |
BE (1) | BE2011C004I2 (zh) |
BR (1) | BRPI0011856B8 (zh) |
CA (1) | CA2377746C (zh) |
CY (1) | CY2011002I1 (zh) |
DE (2) | DE60007127T2 (zh) |
DK (1) | DK1189916T3 (zh) |
ES (1) | ES2209974T3 (zh) |
FR (1) | FR11C0004I2 (zh) |
HK (1) | HK1044952B (zh) |
IL (2) | IL147198A0 (zh) |
LU (1) | LU91785I2 (zh) |
MX (1) | MXPA01013325A (zh) |
NO (2) | NO322457B1 (zh) |
NZ (1) | NZ516334A (zh) |
PT (1) | PT1189916E (zh) |
TR (1) | TR200200588T2 (zh) |
TW (1) | TWI230161B (zh) |
WO (1) | WO2000078779A2 (zh) |
ZA (1) | ZA200200301B (zh) |
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CN101668768B (zh) * | 2007-05-17 | 2012-08-29 | 吉利德帕洛阿尔托股份有限公司 | 制备a2a-腺苷受体激动剂及其多晶型物的方法 |
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