NZ620208A - Substituted n-[1-cyano-2-(phenyl)ethyl]-2-azabicyclo[2,2,1]heptane-3-carboxamide inhibitors of cathepsin c - Google Patents
Substituted n-[1-cyano-2-(phenyl)ethyl]-2-azabicyclo[2,2,1]heptane-3-carboxamide inhibitors of cathepsin c Download PDFInfo
- Publication number
- NZ620208A NZ620208A NZ620208A NZ62020812A NZ620208A NZ 620208 A NZ620208 A NZ 620208A NZ 620208 A NZ620208 A NZ 620208A NZ 62020812 A NZ62020812 A NZ 62020812A NZ 620208 A NZ620208 A NZ 620208A
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- NZ
- New Zealand
- Prior art keywords
- alkyl
- acid
- mmol
- group
- optionally substituted
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title abstract description 13
- 102000005600 Cathepsins Human genes 0.000 title description 4
- 108010084457 Cathepsins Proteins 0.000 title description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 abstract description 51
- 102000003902 Cathepsin C Human genes 0.000 abstract description 22
- 108090000267 Cathepsin C Proteins 0.000 abstract description 22
- 238000011282 treatment Methods 0.000 abstract description 13
- 125000001424 substituent group Chemical group 0.000 abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- 230000002265 prevention Effects 0.000 abstract description 3
- 208000023504 respiratory system disease Diseases 0.000 abstract description 2
- -1 peptidyl nitrile Chemical class 0.000 description 149
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- 238000000034 method Methods 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
- 239000000543 intermediate Substances 0.000 description 51
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 230000015572 biosynthetic process Effects 0.000 description 36
- 229910001868 water Inorganic materials 0.000 description 36
- 238000003786 synthesis reaction Methods 0.000 description 35
- 125000004432 carbon atom Chemical group C* 0.000 description 34
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- 125000005842 heteroatom Chemical group 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 28
- 239000002904 solvent Substances 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
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- 239000012317 TBTU Substances 0.000 description 6
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 6
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- 125000006413 ring segment Chemical group 0.000 description 5
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 4
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- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
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| AR100743A1 (es) | 2014-06-06 | 2016-10-26 | Basf Se | Compuestos de [1,2,4]triazol sustituido |
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| US10479781B2 (en) | 2015-03-05 | 2019-11-19 | Neuprozyme Therapeutics ApS | Peptidyl nitril compounds as dipeptidyl peptidase I inhibitors |
| HRP20250115T1 (hr) | 2018-03-01 | 2025-05-23 | Astrazeneca Ab | Farmaceutski pripravci koji sadrže (2s)-{(1s)-1-cijano-2-[4-(3-metil-2-okso-2,3-dihidro-1,3-benzoksazol-5-il)fenil]etil} -1,4-oksazepan-2-karboksamid |
| EP3817822A4 (en) | 2018-07-06 | 2022-07-27 | Kymera Therapeutics, Inc. | PROTEIN DEGRADANTS AND USES THEREOF |
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| WO2020251972A1 (en) * | 2019-06-10 | 2020-12-17 | Kymera Therapeutics, Inc. | Smarca degraders and uses thereof |
| IL294150A (en) | 2019-12-23 | 2022-08-01 | Kymera Therapeutics Inc | Smarca joints and their uses |
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| KR20230084134A (ko) | 2020-08-26 | 2023-06-12 | 하이스코 파마수티컬즈 피티이. 엘티디. | 디펩티딜 펩티다제 1의 저해제로서 작용하는 니트릴 유도체 및 이의 용도 |
| CN114106005B (zh) * | 2020-08-26 | 2025-08-01 | 西藏海思科制药有限公司 | 一种作为二肽基肽酶1抑制剂的腈衍生物及其用途 |
| CA3199568A1 (en) * | 2020-12-04 | 2022-06-09 | Reistone Biopharma Company Limited | Small molecule inhibitor of cathepsin c and medicinal use thereof |
| US12479854B2 (en) | 2021-07-29 | 2025-11-25 | Enanta Pharmaceuticals, Inc. | Spiropyrrolidine derived antiviral agents |
| CN119156391A (zh) | 2022-06-07 | 2024-12-17 | 瑞石生物医药有限公司 | 苯并[c]色满化合物的可药用盐、其多晶型及用途 |
| CA3258114A1 (en) | 2022-06-07 | 2025-03-20 | Reistone Biopharma Company Ltd | BENZO[C]CHROMANE COMPOUND POLYMORPH, ITS PREPARATION PROCESS AND ITS USE |
| CN120112535A (zh) * | 2022-11-04 | 2025-06-06 | 南京明德新药研发有限公司 | 含氰基取代的杂环类衍生物及其制备方法 |
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| US6960597B2 (en) | 2000-06-30 | 2005-11-01 | Orth-Mcneil Pharmaceutical, Inc. | Aza-bridged-bicyclic amino acid derivatives as α4 integrin antagonists |
| WO2002069901A2 (en) * | 2001-03-02 | 2002-09-12 | Merck Frosst Canada & Co. | Cathepsin cysteine protease inhibitors |
| JP2006527704A (ja) * | 2003-06-18 | 2006-12-07 | プロザイメックス・アクティーゼルスカブ | プロテアーゼ阻害剤 |
| TW200528440A (en) * | 2003-10-31 | 2005-09-01 | Fujisawa Pharmaceutical Co | 2-cyanopyrrolidinecarboxamide compound |
| US20060223846A1 (en) * | 2005-03-08 | 2006-10-05 | Dyatkin Alexey B | Aza-bridged-bicyclic amino acid derivatives as alpha4 integrin antagonists |
| WO2009074829A1 (en) * | 2007-12-12 | 2009-06-18 | Astrazeneca Ab | Peptidyl nitriles and use thereof as dipeptidyl peptidase i inhibitors |
| WO2010142985A1 (en) | 2009-06-10 | 2010-12-16 | Astrazeneca Ab | Substituted n-[1-cyano-2-(phenyl)ethyl]piperidin-2-ylcarboxmide compounds 761 |
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| AU2012311656B2 (en) | 2016-10-06 |
| CN103814028A (zh) | 2014-05-21 |
| PH12014500529A1 (en) | 2014-04-21 |
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| CA2848929A1 (en) | 2013-03-28 |
| JP2014526492A (ja) | 2014-10-06 |
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| EA024817B1 (ru) | 2016-10-31 |
| EA201400358A1 (ru) | 2014-09-30 |
| KR20140078626A (ko) | 2014-06-25 |
| CN103814028B (zh) | 2016-02-17 |
| US8999975B2 (en) | 2015-04-07 |
| WO2013041497A1 (en) | 2013-03-28 |
| US20130172327A1 (en) | 2013-07-04 |
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