CN102414207B - 氟化氨基三唑衍生物 - Google Patents
氟化氨基三唑衍生物 Download PDFInfo
- Publication number
- CN102414207B CN102414207B CN201080018293.6A CN201080018293A CN102414207B CN 102414207 B CN102414207 B CN 102414207B CN 201080018293 A CN201080018293 A CN 201080018293A CN 102414207 B CN102414207 B CN 102414207B
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- CN
- China
- Prior art keywords
- methyl
- oxazole
- ethyl
- triazole
- difluoro
- 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.)
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- JSIAIROWMJGMQZ-UHFFFAOYSA-N 2h-triazol-4-amine Chemical class NC1=CNN=N1 JSIAIROWMJGMQZ-UHFFFAOYSA-N 0.000 title abstract description 35
- 150000001875 compounds Chemical class 0.000 claims abstract description 200
- 150000003839 salts Chemical class 0.000 claims description 118
- -1 methoxyl group Chemical group 0.000 claims description 102
- 239000000203 mixture Substances 0.000 claims description 79
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 62
- 201000010099 disease Diseases 0.000 claims description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 229910052731 fluorine Inorganic materials 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- 239000011737 fluorine Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 239000001301 oxygen Substances 0.000 claims description 26
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 25
- 101000818546 Homo sapiens N-formyl peptide receptor 2 Proteins 0.000 claims description 24
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- 208000027866 inflammatory disease Diseases 0.000 claims description 22
- 108090000623 proteins and genes Proteins 0.000 claims description 22
- 102000004169 proteins and genes Human genes 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 230000004913 activation Effects 0.000 claims description 17
- 208000006673 asthma Diseases 0.000 claims description 17
- 230000004044 response Effects 0.000 claims description 17
- OMCWOZYMSYZUTD-UHFFFAOYSA-N 2-methyl-5-(3-methylphenyl)-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC=CC(C)=C1 OMCWOZYMSYZUTD-UHFFFAOYSA-N 0.000 claims description 15
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- GEAPKHXZFUKEDK-UHFFFAOYSA-N 2-methyl-5-phenyl-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC=CC=C1 GEAPKHXZFUKEDK-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- BOOHMTNMZRZLIK-UHFFFAOYSA-N 5-[3-(dimethylamino)phenyl]-1,3-oxazole-4-carboxylic acid Chemical compound CN(C)C1=CC=CC(C2=C(N=CO2)C(O)=O)=C1 BOOHMTNMZRZLIK-UHFFFAOYSA-N 0.000 claims description 11
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- NDFZHVTZGZRQMP-UHFFFAOYSA-N 2-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC=CC(C(F)(F)F)=C1 NDFZHVTZGZRQMP-UHFFFAOYSA-N 0.000 claims description 10
- MOFHRDAQQJGDIT-UHFFFAOYSA-N 5-(3-chlorophenyl)-2-methyl-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC=CC(Cl)=C1 MOFHRDAQQJGDIT-UHFFFAOYSA-N 0.000 claims description 10
- WUBHAXRXECUOML-UHFFFAOYSA-N 2-methyl-5-[3-(trifluoromethoxy)phenyl]-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC=CC(OC(F)(F)F)=C1 WUBHAXRXECUOML-UHFFFAOYSA-N 0.000 claims description 9
- ZHOCERQZGTWUBY-UHFFFAOYSA-N 5-(3,5-difluorophenyl)-2-methyl-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC(F)=CC(F)=C1 ZHOCERQZGTWUBY-UHFFFAOYSA-N 0.000 claims description 9
- UHZDXZWJFQEEFP-UHFFFAOYSA-N 5-(3-chlorophenyl)-1,3-oxazole-4-carboxylic acid Chemical compound N1=COC(C=2C=C(Cl)C=CC=2)=C1C(=O)O UHZDXZWJFQEEFP-UHFFFAOYSA-N 0.000 claims description 9
- PLKBCEKRBXOTJA-UHFFFAOYSA-N 5-(3-fluorophenyl)-1,3-oxazole-4-carboxylic acid Chemical compound N1=COC(C=2C=C(F)C=CC=2)=C1C(=O)O PLKBCEKRBXOTJA-UHFFFAOYSA-N 0.000 claims description 9
- FBYNJPSNTIETJB-UHFFFAOYSA-N 5-(3-methylphenyl)-1,3-oxazole-4-carboxylic acid Chemical compound CC1=CC=CC(C2=C(N=CO2)C(O)=O)=C1 FBYNJPSNTIETJB-UHFFFAOYSA-N 0.000 claims description 9
- VXGVPBUIHUSJID-UHFFFAOYSA-N 5-(4-fluorophenyl)-1,3-oxazole-4-carboxylic acid Chemical compound N1=COC(C=2C=CC(F)=CC=2)=C1C(=O)O VXGVPBUIHUSJID-UHFFFAOYSA-N 0.000 claims description 9
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 9
- RUKDIKJSGDVSIF-UHFFFAOYSA-N 5-phenyl-1,3-oxazole-4-carboxylic acid Chemical compound N1=COC(C=2C=CC=CC=2)=C1C(=O)O RUKDIKJSGDVSIF-UHFFFAOYSA-N 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 7
- 206010013774 Dry eye Diseases 0.000 claims description 7
- 208000009319 Keratoconjunctivitis Sicca Diseases 0.000 claims description 7
- 241000700605 Viruses Species 0.000 claims description 7
- 206010069351 acute lung injury Diseases 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
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- 125000002541 furyl group Chemical group 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- GWIAKFVUPNZBQG-UHFFFAOYSA-N 2-cyclopropyl-5-phenyl-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C=1N=C(C2CC2)OC=1C1=CC=CC=C1 GWIAKFVUPNZBQG-UHFFFAOYSA-N 0.000 claims description 5
- AGVNKFAFPDWEAR-UHFFFAOYSA-N 2-ethyl-5-phenyl-1,3-oxazole-4-carboxylic acid Chemical compound O1C(CC)=NC(C(O)=O)=C1C1=CC=CC=C1 AGVNKFAFPDWEAR-UHFFFAOYSA-N 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 230000036039 immunity Effects 0.000 claims description 4
- 206010038997 Retroviral infections Diseases 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 7
- 239000002904 solvent Substances 0.000 description 173
- 239000002585 base Substances 0.000 description 166
- 238000000034 method Methods 0.000 description 139
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 97
- 230000002829 reductive effect Effects 0.000 description 96
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 94
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 91
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- 239000007789 gas Substances 0.000 description 57
- 238000003760 magnetic stirring Methods 0.000 description 53
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 51
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 43
- 230000008569 process Effects 0.000 description 41
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 40
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 33
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
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- MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical group C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 description 18
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IB2009052445 | 2009-06-09 | ||
| IBPCT/IB2009/052445 | 2009-06-09 | ||
| PCT/IB2010/052509 WO2010143116A1 (en) | 2009-06-09 | 2010-06-07 | Fluorinated aminotriazole derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102414207A CN102414207A (zh) | 2012-04-11 |
| CN102414207B true CN102414207B (zh) | 2015-09-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201080018293.6A Expired - Fee Related CN102414207B (zh) | 2009-06-09 | 2010-06-07 | 氟化氨基三唑衍生物 |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US8580831B2 (enExample) |
| EP (1) | EP2440555B1 (enExample) |
| JP (2) | JP5095035B2 (enExample) |
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| CN (1) | CN102414207B (enExample) |
| AR (1) | AR077032A1 (enExample) |
| AU (1) | AU2010258334B2 (enExample) |
| BR (1) | BRPI1010738A8 (enExample) |
| CA (1) | CA2760588C (enExample) |
| CL (1) | CL2011003097A1 (enExample) |
| ES (1) | ES2587139T3 (enExample) |
| IL (1) | IL216792A (enExample) |
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|---|---|---|---|---|
| AR069650A1 (es) | 2007-12-14 | 2010-02-10 | Actelion Pharmaceuticals Ltd | Derivados de aminopirazol como agonistas no peptidicos del receptor alx humano |
| KR101213007B1 (ko) | 2007-12-18 | 2012-12-20 | 액테리온 파마슈티칼 리미티드 | Ａｌｘ 작용제로서의 아미노트리아졸 유도체 |
| CN102414168B (zh) | 2009-05-18 | 2014-05-21 | 埃科特莱茵药品有限公司 | 用作为alx受体和/或fprl2激动剂的桥联螺[2.4]庚烷衍生物 |
| KR20120046159A (ko) | 2009-06-12 | 2012-05-09 | 액테리온 파마슈티칼 리미티드 | Ａｌｘ 수용체 아고니스트로서의 옥사졸 및 티아졸 유도체 |
| CA2814826C (en) | 2010-11-17 | 2019-02-12 | Actelion Pharmaceuticals Ltd | Bridged spiro[2.4]heptane ester derivatives |
| MX2013006420A (es) * | 2010-12-07 | 2013-07-29 | Actelion Pharmaceuticals Ltd | Derivados de aminotriazol hidrolixado como agonistas del receptor de alx. |
| US8846733B2 (en) * | 2010-12-07 | 2014-09-30 | Actelion Pharmaceuticals Ltd. | Oxazolyl-methylether derivatives as ALX receptor agonists |
| MA37618B1 (fr) | 2012-05-16 | 2017-08-31 | Actelion Pharmaceuticals Ltd | Dérivés pontés fluorés de spiro[2.4]heptane en tant qu'agonistes de récepteur alx |
| TW201348219A (zh) | 2012-05-16 | 2013-12-01 | Actelion Pharmaceuticals Ltd | 作爲ａｌｘ受體激動劑之經１－（對－甲苯基）環丙基取代橋聯螺［２．４］庚烷衍生物 |
| LT2855453T (lt) | 2012-06-04 | 2017-02-27 | Actelion Pharmaceuticals Ltd. | Benzimidazolo prolino dariniai |
| US9493446B2 (en) | 2012-10-10 | 2016-11-15 | Actelion Pharmaceuticals Ltd. | Orexin receptor antagonists which are [ortho bi-(hetero-)aryl]-[2-(meta bi-(hetero-)aryl)-pyrrolidin-1-yl]-methanone derivatives |
| EP2970241A1 (en) | 2013-03-12 | 2016-01-20 | Actelion Pharmaceuticals Ltd. | Azetidine amide derivatives as orexin receptor antagonists |
| EP2990419B1 (en) | 2013-04-22 | 2019-09-18 | The University of Tokyo | Preventive or therapeutic agent for inflammatory disease |
| AR096686A1 (es) | 2013-06-25 | 2016-01-27 | Actelion Pharmaceuticals Ltd | Derivados de espiro[2.4]heptano puenteados sustituidos con difluoroetil-oxazol como agonistas del receptor de alx |
| MX360699B (es) | 2013-07-18 | 2018-11-14 | Idorsia Pharmaceuticals Ltd | Derivados de espiro [2.4] heptano puenteado substituidos por piperazina, utilizados como agonistas del receptor alx. |
| AR097279A1 (es) | 2013-08-09 | 2016-03-02 | Actelion Pharmaceuticals Ltd | Derivados de benzimidazolil-metil urea como agonistas del receptor de alx |
| SI3077391T1 (sl) | 2013-12-04 | 2018-11-30 | Idorsia Pharmaceuticals Ltd | Uporaba benzimidazol-prolinskih derivatov |
| MX2023014205A (es) | 2021-06-01 | 2024-01-18 | Azcuris Co Ltd | Derivado de oxazol novedoso y composicion farmaceutica para prevenir o tratar enfermedades alergicas que comprende el mismo. |
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| JPS62234018A (ja) | 1986-04-02 | 1987-10-14 | Rooto Seiyaku Kk | 糖尿病併発症治療剤 |
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