JP2003522189A - ケモカインレセプター活性のモジュレーターとしてのピリミジン化合物およびそれらの使用 - Google Patents
ケモカインレセプター活性のモジュレーターとしてのピリミジン化合物およびそれらの使用Info
- Publication number
- JP2003522189A JP2003522189A JP2001558051A JP2001558051A JP2003522189A JP 2003522189 A JP2003522189 A JP 2003522189A JP 2001558051 A JP2001558051 A JP 2001558051A JP 2001558051 A JP2001558051 A JP 2001558051A JP 2003522189 A JP2003522189 A JP 2003522189A
- Authority
- JP
- Japan
- Prior art keywords
- amino
- formula
- compound
- thio
- methyl
- 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.)
- Pending
Links
- 102000009410 Chemokine receptor Human genes 0.000 title claims description 8
- 108050000299 Chemokine receptor Proteins 0.000 title claims description 8
- 230000000694 effects Effects 0.000 title description 4
- 150000003230 pyrimidines Chemical class 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 33
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 140
- 238000011282 treatment Methods 0.000 claims description 43
- 239000000126 substance Substances 0.000 claims description 40
- 239000002904 solvent Substances 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 239000012453 solvate Substances 0.000 claims description 19
- -1 2,3-difluorophenyl Chemical group 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 102000019034 Chemokines Human genes 0.000 claims description 13
- 108010012236 Chemokines Proteins 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 102000002791 Interleukin-8B Receptors Human genes 0.000 claims description 8
- 108010018951 Interleukin-8B Receptors Proteins 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- FYJXTHIJKZOBDD-MRVPVSSYSA-N (2r)-2-[[8-amino-2-[(3-chlorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(Cl)=C1 FYJXTHIJKZOBDD-MRVPVSSYSA-N 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- MCBMLPDEXRAKDO-MRVPVSSYSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one Chemical compound N=1C=2NC(=O)CC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F MCBMLPDEXRAKDO-MRVPVSSYSA-N 0.000 claims description 4
- KSTLGFMLCSREDG-UHFFFAOYSA-N 2-[[8-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]propane-1,3-diol Chemical compound N1=C2NC(N)=NC2=C(NC(CO)CO)N=C1SCC1=CC=CC(F)=C1F KSTLGFMLCSREDG-UHFFFAOYSA-N 0.000 claims description 4
- RURRPCNSHIMRGD-SECBINFHSA-N 2-benzylsulfanyl-6-[[(2r)-1-hydroxypropan-2-yl]amino]-7,9-dihydropurin-8-one Chemical compound N=1C=2NC(=O)NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC=C1 RURRPCNSHIMRGD-SECBINFHSA-N 0.000 claims description 4
- UUQYSXBFJGFLKV-UHFFFAOYSA-N 4-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one Chemical compound N=1C=2NC(=O)CC=2C(N)=NC=1SCC1=CC=CC(F)=C1F UUQYSXBFJGFLKV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- HNISIXROLNYCDM-SECBINFHSA-N (2r)-2-[(8-amino-2-benzylsulfanyl-7h-purin-6-yl)amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC=C1 HNISIXROLNYCDM-SECBINFHSA-N 0.000 claims description 3
- PKZKDRUQEOVESZ-MRVPVSSYSA-N (2r)-2-[[8-amino-2-[(2-fluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC=C1F PKZKDRUQEOVESZ-MRVPVSSYSA-N 0.000 claims description 3
- NYPVTAVIUQXVBD-SNVBAGLBSA-N (2r)-2-[[8-amino-2-[(2-methylphenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC=C1C NYPVTAVIUQXVBD-SNVBAGLBSA-N 0.000 claims description 3
- ROEMIMZCSNFQTP-SSDOTTSWSA-N (2r)-2-[[8-amino-2-[(3-chloro-2-fluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(Cl)=C1F ROEMIMZCSNFQTP-SSDOTTSWSA-N 0.000 claims description 3
- YWPYWSARFFOWGB-MRVPVSSYSA-N (2r)-2-[[8-amino-2-[(3-chloro-4-methoxyphenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound C1=C(Cl)C(OC)=CC=C1CSC1=NC(N[C@H](C)CO)=C(N=C(N)N2)C2=N1 YWPYWSARFFOWGB-MRVPVSSYSA-N 0.000 claims description 3
- TUZBVXBBJUMRKH-SNVBAGLBSA-N (2r)-2-[[8-amino-2-[(3-methylphenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(C)=C1 TUZBVXBBJUMRKH-SNVBAGLBSA-N 0.000 claims description 3
- UHMAUIOYRZTETM-SNVBAGLBSA-N (2r)-2-[[8-amino-2-[(4-methylphenyl)methylsulfanyl]-7h-purin-6-yl]amino]propan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=C(C)C=C1 UHMAUIOYRZTETM-SNVBAGLBSA-N 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N 1-butanol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 3
- JKVINFJVZJHNLK-UHFFFAOYSA-N 2-[[8-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]-2-methylpropan-1-ol Chemical compound N=1C=2NC(N)=NC=2C(NC(C)(CO)C)=NC=1SCC1=CC=CC(F)=C1F JKVINFJVZJHNLK-UHFFFAOYSA-N 0.000 claims description 3
- PYMFWZQOVMSEJK-UHFFFAOYSA-N 2-[[8-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]-2-methylpropane-1,3-diol Chemical compound N=1C=2NC(N)=NC=2C(NC(CO)(CO)C)=NC=1SCC1=CC=CC(F)=C1F PYMFWZQOVMSEJK-UHFFFAOYSA-N 0.000 claims description 3
- VOUCOPWIMWCBPG-UHFFFAOYSA-N 2-[[8-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-7h-purin-6-yl]amino]ethanol Chemical compound N1=C2NC(N)=NC2=C(NCCO)N=C1SCC1=CC=CC(F)=C1F VOUCOPWIMWCBPG-UHFFFAOYSA-N 0.000 claims description 3
- 230000033115 angiogenesis Effects 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
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- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- 108091008928 CXC chemokine receptors Proteins 0.000 claims description 2
- 102000054900 CXCR Receptors Human genes 0.000 claims description 2
- 241001553014 Myrsine salicina Species 0.000 claims description 2
- 150000001350 alkyl halides Chemical class 0.000 claims description 2
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- 238000002360 preparation method Methods 0.000 abstract description 11
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- 150000002391 heterocyclic compounds Chemical class 0.000 abstract description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 101
- 238000004949 mass spectrometry Methods 0.000 description 51
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Landscapes
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Applications Claiming Priority (3)
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| GB0003019.7 | 2000-02-11 | ||
| GB0003019A GB2359078A (en) | 2000-02-11 | 2000-02-11 | Pharmaceutically active pyrimidine derivatives |
| PCT/SE2001/000245 WO2001058902A1 (en) | 2000-02-11 | 2001-02-07 | Pyrimidine compounds and their use as modulators of chemokine receptor activity |
Publications (2)
| Publication Number | Publication Date |
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| JP2003522189A true JP2003522189A (ja) | 2003-07-22 |
| JP2003522189A5 JP2003522189A5 (cg-RX-API-DMAC7.html) | 2008-03-27 |
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| JP2001558051A Pending JP2003522189A (ja) | 2000-02-11 | 2001-02-07 | ケモカインレセプター活性のモジュレーターとしてのピリミジン化合物およびそれらの使用 |
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| WO (1) | WO2001058902A1 (cg-RX-API-DMAC7.html) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003522191A (ja) * | 2000-02-11 | 2003-07-22 | アストラゼネカ・アクチエボラーグ | ケモカイン受容体活性のモジュレーターとしてのピリミジン化合物およびそれらの使用 |
| JP2005526857A (ja) * | 2002-05-24 | 2005-09-08 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | Ｃｃｒ９インヒビターおよびその使用方法 |
| JP2012509877A (ja) * | 2008-11-25 | 2012-04-26 | メルク・シャープ・エンド・ドーム・コーポレイション | 可溶性グアニレートシクラーゼ活性化剤 |
Families Citing this family (18)
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| SE9903544D0 (sv) | 1999-10-01 | 1999-10-01 | Astra Pharma Prod | Novel compounds |
| GB2359081A (en) | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
| GB2359551A (en) * | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| SE0003828D0 (sv) * | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Novel compounds |
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| SE0102716D0 (sv) * | 2001-08-14 | 2001-08-14 | Astrazeneca Ab | Novel compounds |
| GB0217431D0 (en) | 2002-07-27 | 2002-09-04 | Astrazeneca Ab | Novel compounds |
| AU2003255819A1 (en) * | 2002-08-24 | 2004-03-11 | Astrazeneca Ab | Pyrimidine derivatives as modulators of chemokine receptor activity |
| GB0221828D0 (en) * | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| GB0221829D0 (en) * | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| GB0328243D0 (en) * | 2003-12-05 | 2004-01-07 | Astrazeneca Ab | Methods |
| GB0401269D0 (en) * | 2004-01-21 | 2004-02-25 | Astrazeneca Ab | Compounds |
| EP1612210B1 (en) * | 2004-06-29 | 2007-09-26 | Grünenthal GmbH | New analogs of nitrobenzylthioinosine |
| MX2007002240A (es) | 2004-08-28 | 2007-04-20 | Astrazeneca Ab | Derivados de pirimidinosulfonamida como moduladores del receptor quimiocina. |
| BRPI0817318A2 (pt) | 2007-09-25 | 2015-03-17 | Actimis Pharmaceuticals Inc | Composto, composição farmacêutica, e, método para tratar uma doença, ou uma condição, ou sintoma da mesma. |
| TW200922587A (en) | 2007-09-25 | 2009-06-01 | Actimis Pharmaceuticals Inc | Alkylthio pyrimidines as CRTH2 antagonists |
| NZ609204A (en) * | 2010-09-14 | 2015-05-29 | Inst Biochemii I Biofizyki Pan | Compounds as modulators of a mutant cftr protein and their use for treating diseases associated with cftr protein malfunction |
| CN109020882A (zh) * | 2018-08-09 | 2018-12-18 | 杭州华东医药集团浙江华义制药有限公司 | 3,5-二氯-2-氰基吡啶的合成方法 |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3318900A (en) | 1964-05-06 | 1967-05-09 | Janssen Pharmaceutica Nv | Derivatives of benzimidazolinyl piperidine |
| DE2331223C2 (de) | 1972-06-19 | 1984-11-22 | Kohjin Co., Ltd., Tokio / Tokyo | S-substituierte-2-Thioadenosine, deren 5'-Monophosphate, Verfahren zu deren Herstellung und Arzneimittel, welche diese enthalten |
| JPS5188994A (en) * | 1975-02-04 | 1976-08-04 | Shinkijichikan 88 aminoadeninjudotainoseizoho | |
| EG12406A (en) | 1976-08-12 | 1979-03-31 | Janssen Pharmaceutica Nv | Process for preparing of novel n-aryl-n-(1-l-4-piperidinyl)-arylacetamides |
| FR2421899A1 (fr) | 1978-01-16 | 1979-11-02 | Roussel Uclaf | Nouveaux derives du tetrahydropyridinyl-indole et leurs sels, le procede de preparation et l'application a titre de medicaments de ces nouveaux produits |
| US4410528A (en) | 1980-05-16 | 1983-10-18 | Kyowa Hakko Kogyo Co., Ltd. | Hypotensive piperidine derivatives |
| CA1338012C (en) | 1987-04-27 | 1996-01-30 | John Michael Mccall | Pharmaceutically active amines |
| FR2659656B1 (fr) | 1990-03-15 | 1994-09-09 | Sanofi Sa | Derives de pyrimidinedione-2,4 et medicaments les contenant. |
| DE4119767A1 (de) | 1991-06-15 | 1992-12-17 | Dresden Arzneimittel | Verfahren zur herstellung von (pyrimid-2-yl-thio- bzw. seleno)-essigsaeurederivaten |
| US5521197A (en) | 1994-12-01 | 1996-05-28 | Eli Lilly And Company | 3-<1-alkylenearyl>-4-<1,2,3,6-tetrahydropyridinyl>-and 3-<1-alkylenearyl>-4-piperidinyl-1h-indoles: new 5-HT1F agonists |
| PT778277E (pt) * | 1995-12-08 | 2003-11-28 | Pfizer | Derivados heterociclicos substituidos como antagonistas do crf |
| WO1997040035A1 (en) | 1996-04-19 | 1997-10-30 | Neurosearch A/S | 1-(4-piperidyl)-benzimidazoles having neurotrophic activity |
| ES2273369T3 (es) * | 1996-08-28 | 2007-05-01 | Pfizer Inc. | Derivados 6,5 heterobiciclicos sustituidos. |
| AU5522498A (en) * | 1996-12-13 | 1998-07-03 | Merck & Co., Inc. | Substituted aryl piperazines as modulators of chemokine receptor activity |
| WO1999004794A1 (en) | 1997-07-25 | 1999-02-04 | Merck & Co., Inc. | Cyclic amine modulators of chemokine receptor activity |
| AR013669A1 (es) | 1997-10-07 | 2001-01-10 | Smithkline Beecham Corp | Compuestos y metodos |
| DE69817393T2 (de) * | 1997-11-28 | 2004-06-17 | Sumitomo Pharmaceuticals Co., Ltd. | Neue heterozyklische verbindungen |
| DK1049689T3 (da) | 1998-01-19 | 2002-07-22 | Pfizer | 4-(2-keto-1-benzimidazolinyl)piperidinderivater som ORL1-receptoragonister |
| WO1999047515A1 (en) | 1998-03-19 | 1999-09-23 | Nihon Nohyaku Co., Ltd. | Arylpiperidine derivatives and use thereof |
| WO1999051608A1 (en) * | 1998-04-03 | 1999-10-14 | Du Pont Pharmaceuticals Company | THIAZOLO[4,5-d]PYRIMIDINES AND PYRIDINES AS CORTICOTROPIN RELEASING FACTOR (CRF) ANTAGONISTS |
| MA26659A1 (fr) | 1998-08-06 | 2004-12-20 | Pfizer | Dérivés de benzimidazole nouveaux, compositions pharmaceutiques les contenant et procédé pour leur préparation. |
| SE9802729D0 (sv) * | 1998-08-13 | 1998-08-13 | Astra Pharma Prod | Novel Compounds |
| PE20001420A1 (es) | 1998-12-23 | 2000-12-18 | Pfizer | Moduladores de ccr5 |
| JP2002533464A (ja) | 1998-12-28 | 2002-10-08 | カー・イュー・ルーベン・リサーチ・アンド・ディベロップメント | プテリジン誘導体の免疫抑制作用 |
| CA2361561A1 (en) | 1999-02-02 | 2000-08-10 | K.U. Leuven Research & Development | Immunosurpressive effects of pteridine derivatives |
| US6248755B1 (en) | 1999-04-06 | 2001-06-19 | Merck & Co., Inc. | Pyrrolidine modulators of chemokine receptor activity |
| US6432981B1 (en) | 1999-06-11 | 2002-08-13 | Merck & Co., Inc. | Cyclopentyl modulators of chemokine receptor activity |
| US6340681B1 (en) | 1999-07-16 | 2002-01-22 | Pfizer Inc | 2-benzimidazolylamine compounds as ORL-1-receptor agonists |
| JP2003509425A (ja) | 1999-09-15 | 2003-03-11 | ワーナー−ランバート・カンパニー | キナーゼ阻害剤としてのプテリジノン |
| PE20010628A1 (es) | 1999-10-01 | 2001-06-18 | Takeda Chemical Industries Ltd | Compuestos de amina ciclica, su produccion y su uso |
| SE9903544D0 (sv) | 1999-10-01 | 1999-10-01 | Astra Pharma Prod | Novel compounds |
| ES2249237T3 (es) | 2000-01-05 | 2006-04-01 | Pfizer Inc. | Compuestos de bencimidazol como antagonistas del receptor orl1. |
| WO2001058906A1 (en) * | 2000-02-11 | 2001-08-16 | Astrazeneca Ab | Pyrimidine compounds and their use as modulators of chemokine receptor activity |
| GB2359081A (en) * | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
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| GB2359551A (en) | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB0005642D0 (en) * | 2000-03-10 | 2000-05-03 | Astrazeneca Uk Ltd | Chemical compounds |
| SE0101322D0 (sv) * | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Novel compounds |
| SE0102716D0 (sv) | 2001-08-14 | 2001-08-14 | Astrazeneca Ab | Novel compounds |
-
2000
- 2000-02-11 GB GB0003019A patent/GB2359078A/en not_active Withdrawn
-
2001
- 2001-02-07 US US10/203,584 patent/US6958344B2/en not_active Expired - Fee Related
- 2001-02-07 AU AU2001230704A patent/AU2001230704A1/en not_active Abandoned
- 2001-02-07 WO PCT/SE2001/000245 patent/WO2001058902A1/en not_active Ceased
- 2001-02-07 JP JP2001558051A patent/JP2003522189A/ja active Pending
- 2001-02-07 EP EP01902950A patent/EP1265899A1/en not_active Withdrawn
-
2005
- 2005-01-14 US US11/036,682 patent/US20050234077A1/en not_active Abandoned
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003522191A (ja) * | 2000-02-11 | 2003-07-22 | アストラゼネカ・アクチエボラーグ | ケモカイン受容体活性のモジュレーターとしてのピリミジン化合物およびそれらの使用 |
| JP2005526857A (ja) * | 2002-05-24 | 2005-09-08 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | Ｃｃｒ９インヒビターおよびその使用方法 |
| JP2006265259A (ja) * | 2002-05-24 | 2006-10-05 | Millennium Pharmaceuticals Inc | Ｃｃｒ９インヒビターおよびその使用方法 |
| JP4828822B2 (ja) * | 2002-05-24 | 2011-11-30 | ミレニアム ファーマシューティカルズ， インコーポレイテッド | Ｃｃｒ９インヒビターおよびその使用方法 |
| JP2012509877A (ja) * | 2008-11-25 | 2012-04-26 | メルク・シャープ・エンド・ドーム・コーポレイション | 可溶性グアニレートシクラーゼ活性化剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2001230704A1 (en) | 2001-08-20 |
| EP1265899A1 (en) | 2002-12-18 |
| WO2001058902A1 (en) | 2001-08-16 |
| US6958344B2 (en) | 2005-10-25 |
| GB0003019D0 (en) | 2000-03-29 |
| US20030040523A1 (en) | 2003-02-27 |
| GB2359078A (en) | 2001-08-15 |
| US20050234077A1 (en) | 2005-10-20 |
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