HRP20030995A2 - Novel compounds and compositions as cathepsin inhibitors - Google Patents
Novel compounds and compositions as cathepsin inhibitors Download PDFInfo
- Publication number
- HRP20030995A2 HRP20030995A2 HR20030995A HRP20030995A HRP20030995A2 HR P20030995 A2 HRP20030995 A2 HR P20030995A2 HR 20030995 A HR20030995 A HR 20030995A HR P20030995 A HRP20030995 A HR P20030995A HR P20030995 A2 HRP20030995 A2 HR P20030995A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- x5nr12c
- phenylmethanesulfonyl
- methyl
- propionamide
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 188
- 239000000203 mixture Substances 0.000 title claims description 176
- 102000005600 Cathepsins Human genes 0.000 title description 3
- 108010084457 Cathepsins Proteins 0.000 title description 3
- 239000003112 inhibitor Substances 0.000 title description 2
- -1 -X4 Chemical group 0.000 claims description 672
- 125000000217 alkyl group Chemical group 0.000 claims description 352
- 125000005842 heteroatom Chemical group 0.000 claims description 198
- 239000001257 hydrogen Substances 0.000 claims description 168
- 229910052739 hydrogen Inorganic materials 0.000 claims description 168
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 155
- 125000003118 aryl group Chemical group 0.000 claims description 134
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 125
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 97
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 88
- 229940080818 propionamide Drugs 0.000 claims description 86
- 150000003254 radicals Chemical class 0.000 claims description 82
- 125000005843 halogen group Chemical group 0.000 claims description 71
- 238000000034 method Methods 0.000 claims description 57
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 51
- 150000001204 N-oxides Chemical class 0.000 claims description 49
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 49
- 150000003839 salts Chemical class 0.000 claims description 44
- 239000000651 prodrug Substances 0.000 claims description 43
- 229940002612 prodrug Drugs 0.000 claims description 43
- 125000001153 fluoro group Chemical group F* 0.000 claims description 38
- 125000004429 atom Chemical group 0.000 claims description 37
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 36
- 125000001118 alkylidene group Chemical group 0.000 claims description 33
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 31
- 125000006588 heterocycloalkylene group Chemical group 0.000 claims description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 29
- 201000010099 disease Diseases 0.000 claims description 28
- 125000002723 alicyclic group Chemical group 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- STUHQDIOZQUPGP-UHFFFAOYSA-N morpholin-4-ium-4-carboxylate Chemical compound OC(=O)N1CCOCC1 STUHQDIOZQUPGP-UHFFFAOYSA-N 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 239000012453 solvate Substances 0.000 claims description 21
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 19
- 125000000172 C5-C10 aryl group Chemical group 0.000 claims description 18
- 125000006413 ring segment Chemical group 0.000 claims description 18
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 15
- 125000002619 bicyclic group Chemical group 0.000 claims description 14
- SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical class SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- PVQHCTFSERQJAR-NSHDSACASA-N (2r)-3-benzylsulfonyl-n-(cyanomethyl)-2-hydroxypropanamide Chemical compound N#CCNC(=O)[C@@H](O)CS(=O)(=O)CC1=CC=CC=C1 PVQHCTFSERQJAR-NSHDSACASA-N 0.000 claims description 13
- 108090000613 Cathepsin S Proteins 0.000 claims description 13
- 125000001931 aliphatic group Chemical group 0.000 claims description 13
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 13
- MLOUIFCSRKBQMN-REQUTJCGSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-(oxan-4-ylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)NC1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 MLOUIFCSRKBQMN-REQUTJCGSA-N 0.000 claims description 12
- 241001465754 Metazoa Species 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- TXJYKYKFSMXUKR-HNNXBMFYSA-N [(2r)-3-benzylsulfonyl-1-(cyanomethylamino)-1-oxopropan-2-yl] morpholine-4-carboxylate Chemical compound C([C@@H](C(NCC#N)=O)OC(=O)N1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 TXJYKYKFSMXUKR-HNNXBMFYSA-N 0.000 claims description 11
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 11
- MCMIQNCAMAMQNI-KJXWVISYSA-N (2r)-n-[1-(1,3-benzothiazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-(oxan-4-ylamino)propanamide Chemical compound C([C@@H](C(=O)NC(CCC)C(O)C=1SC2=CC=CC=C2N=1)NC1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 MCMIQNCAMAMQNI-KJXWVISYSA-N 0.000 claims description 10
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 10
- OSGOUNPIVAKAME-PXNSSMCTSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]-3-benzylsulfonyl-2-(methoxymethoxy)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)OCOC)S(=O)(=O)CC1=CC=CC=C1 OSGOUNPIVAKAME-PXNSSMCTSA-N 0.000 claims description 9
- 102100035654 Cathepsin S Human genes 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- LMGKUMPEAQVASX-GOTSBHOMSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-(oxan-4-ylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)NC1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 LMGKUMPEAQVASX-GOTSBHOMSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- JRRPRBDCSKIJBI-IJXZTRCJSA-N tert-butyl n-[(2r)-1-[[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]amino]-3-(cyclopropylmethylsulfonyl)-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)NC(=O)OC(C)(C)C)S(=O)(=O)CC1CC1 JRRPRBDCSKIJBI-IJXZTRCJSA-N 0.000 claims description 8
- KECOZLVLHKYYLU-MMBKUXRPSA-N tert-butyl n-[(2r)-1-[[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]amino]-3-benzylsulfonyl-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)NC(=O)OC(C)(C)C)S(=O)(=O)CC1=CC=CC=C1 KECOZLVLHKYYLU-MMBKUXRPSA-N 0.000 claims description 8
- KECOZLVLHKYYLU-QKDPSFTKSA-N tert-butyl n-[(2r)-1-[[1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]amino]-3-benzylsulfonyl-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)NC(CCC)C(O)C=1OC2=CC=CC=C2N=1)NC(=O)OC(C)(C)C)S(=O)(=O)CC1=CC=CC=C1 KECOZLVLHKYYLU-QKDPSFTKSA-N 0.000 claims description 8
- FYWNGHYIQMXOOI-KZUDCZAMSA-N (2r)-3-benzylsulfonyl-n-[cyano(thiophen-2-yl)methyl]-2-hydroxypropanamide Chemical compound C([C@H](O)C(=O)NC(C#N)C=1SC=CC=1)S(=O)(=O)CC1=CC=CC=C1 FYWNGHYIQMXOOI-KZUDCZAMSA-N 0.000 claims description 7
- VFJLNPKVRZYJKL-AZUAARDMSA-N [(2s)-3-benzylsulfonyl-1-[[(2s)-1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl] morpholine-4-carboxylate Chemical compound C([C@H](C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CN=C2N=1)OC(=O)N1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 VFJLNPKVRZYJKL-AZUAARDMSA-N 0.000 claims description 7
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 7
- 125000003431 oxalo group Chemical group 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- CELKLXRGCOTINM-REQUTJCGSA-N tert-butyl n-[(2r)-1-[[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxy-4-phenylbutan-2-yl]amino]-3-(cyclopropylmethylsulfonyl)-1-oxopropan-2-yl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](CCC=1C=CC=CC=1)C(O)C=1OC2=CC=CC=C2N=1)S(=O)(=O)CC1CC1 CELKLXRGCOTINM-REQUTJCGSA-N 0.000 claims description 7
- KBJIVPOCNCFCEG-QKDPSFTKSA-N tert-butyl n-[(2r)-1-[[1-(1,3-benzothiazol-2-yl)-1-hydroxypentan-2-yl]amino]-3-benzylsulfonyl-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)NC(CCC)C(O)C=1SC2=CC=CC=C2N=1)NC(=O)OC(C)(C)C)S(=O)(=O)CC1=CC=CC=C1 KBJIVPOCNCFCEG-QKDPSFTKSA-N 0.000 claims description 7
- SYJTYOPAKNHYIT-NTZARQNWSA-N tert-butyl n-[(2r)-3-benzylsulfonyl-1-[[(2s)-1-hydroxy-4-phenyl-1-(1,3-thiazol-2-yl)butan-2-yl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](CCC=1C=CC=CC=1)C(O)C=1SC=CN=1)S(=O)(=O)CC1=CC=CC=C1 SYJTYOPAKNHYIT-NTZARQNWSA-N 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- SEMGQBHBOHGXDJ-RYUDHWBXSA-N (2r)-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-2-hydroxy-n-[(2s)-1-oxobutan-2-yl]propanamide Chemical compound CC[C@@H](C=O)NC(=O)[C@@H](O)CS(=O)(=O)CC1=CC=CC=C1OC(F)F SEMGQBHBOHGXDJ-RYUDHWBXSA-N 0.000 claims description 6
- VGPYQDIPGAIEOD-RBUKOAKNSA-N (2r)-n-[(1s)-1-cyano-3-phenylpropyl]-2-hydroxy-4-phenylbutanamide Chemical compound C([C@@H](O)C(=O)N[C@@H](CCC=1C=CC=CC=1)C#N)CC1=CC=CC=C1 VGPYQDIPGAIEOD-RBUKOAKNSA-N 0.000 claims description 6
- DMIKDDSFWBKUAG-OALUTQOASA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-[(5-nitro-1,3-thiazol-2-yl)amino]propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)NC=1SC(=CN=1)[N+]([O-])=O)S(=O)(=O)CC1=CC=CC=C1 DMIKDDSFWBKUAG-OALUTQOASA-N 0.000 claims description 6
- SWBGIFKSDLOABR-AIJCFQAPSA-N (2r)-n-[1-(1,3-benzothiazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-(dibenzylamino)propanamide Chemical compound C([C@@H](C(=O)NC(CCC)C(O)C=1SC2=CC=CC=C2N=1)N(CC=1C=CC=CC=1)CC=1C=CC=CC=1)S(=O)(=O)CC1=CC=CC=C1 SWBGIFKSDLOABR-AIJCFQAPSA-N 0.000 claims description 6
- DBKZXSXBLRLWKH-QKDPSFTKSA-N (2r)-n-[1-(1,3-benzothiazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-(propan-2-ylamino)propanamide Chemical compound C([C@@H](C(=O)NC(CCC)C(O)C=1SC2=CC=CC=C2N=1)NC(C)C)S(=O)(=O)CC1=CC=CC=C1 DBKZXSXBLRLWKH-QKDPSFTKSA-N 0.000 claims description 6
- CJPPIVIRLVFXPB-WCSIJFPASA-N (2r)-n-[1-(1,3-benzothiazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-(oxan-4-ylamino)propanamide Chemical compound C([C@@H](C(=O)NC(CCC)C(=O)C=1SC2=CC=CC=C2N=1)NC1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 CJPPIVIRLVFXPB-WCSIJFPASA-N 0.000 claims description 6
- JLFAQCLGVPWBQB-IJXZTRCJSA-N (2s)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-2-(propan-2-ylamino)-3-thiophen-2-ylpropanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)NC(C)C)C1=CC=CS1 JLFAQCLGVPWBQB-IJXZTRCJSA-N 0.000 claims description 6
- AJGATIKLZBKBPZ-ZWKOTPCHSA-N C([C@H](C(=O)N[C@@H](CC)C(=O)C=1OC(CC)=NN=1)OC(=O)N1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 Chemical compound C([C@H](C(=O)N[C@@H](CC)C(=O)C=1OC(CC)=NN=1)OC(=O)N1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 AJGATIKLZBKBPZ-ZWKOTPCHSA-N 0.000 claims description 6
- 230000004927 fusion Effects 0.000 claims description 6
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 claims description 6
- YKWHKILAGONYKL-HNNXBMFYSA-N (1r)-2-[(cyanomethyl)amino]-1-({[2-(difluoromethoxy)benzyl]sulfonyl}methyl)-2-oxoethyl morpholine-4-carboxylate Chemical compound FC(F)OC1=CC=CC=C1CS(=O)(=O)C[C@@H](C(=O)NCC#N)OC(=O)N1CCOCC1 YKWHKILAGONYKL-HNNXBMFYSA-N 0.000 claims description 5
- AIZRFRRBPNCLDE-JTQLQIEISA-N (2r)-n-(cyanomethyl)-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-2-hydroxypropanamide Chemical compound N#CCNC(=O)[C@@H](O)CS(=O)(=O)CC1=CC=CC=C1OC(F)F AIZRFRRBPNCLDE-JTQLQIEISA-N 0.000 claims description 5
- OJCORVXMEWEAFG-OKHNBNEASA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-(cyclohexylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)NC1CCCCC1)S(=O)(=O)CC1=CC=CC=C1 OJCORVXMEWEAFG-OKHNBNEASA-N 0.000 claims description 5
- JGYMLNNBSYASDC-QKZQDKRESA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-(dibenzylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)N(CC=1C=CC=CC=1)CC=1C=CC=CC=1)S(=O)(=O)CC1=CC=CC=C1 JGYMLNNBSYASDC-QKZQDKRESA-N 0.000 claims description 5
- GZKHCMKTFJOJTJ-SRBHEWTHSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-[bis(thiophen-2-ylmethyl)amino]propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)N(CC=1SC=CC=1)CC=1SC=CC=1)S(=O)(=O)CC1=CC=CC=C1 GZKHCMKTFJOJTJ-SRBHEWTHSA-N 0.000 claims description 5
- TWNNQCRTIJQSRR-IGKIAQTJSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]-3-benzylsulfonyl-2-tri(propan-2-yl)silyloxypropanamide Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)O[Si](C(C)C)(C(C)C)C(C)C)S(=O)(=O)CC1=CC=CC=C1 TWNNQCRTIJQSRR-IGKIAQTJSA-N 0.000 claims description 5
- NBCSQKUQOPZPMI-SFTDATJTSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-(propan-2-ylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)NC(C)C)S(=O)(=O)CC1=CC=CC=C1 NBCSQKUQOPZPMI-SFTDATJTSA-N 0.000 claims description 5
- FSOZRRMCWKYFCJ-UIOOFZCWSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-[2-methoxyethyl(oxan-4-yl)amino]propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)N(CCOC)C1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 FSOZRRMCWKYFCJ-UIOOFZCWSA-N 0.000 claims description 5
- LSOPNGVXJKBJNV-FUHYEJFZSA-N (2r)-n-[1-(1,3-benzothiazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-(dimethylamino)propanamide Chemical compound C([C@@H](C(=O)NC(CCC)C(O)C=1SC2=CC=CC=C2N=1)N(C)C)S(=O)(=O)CC1=CC=CC=C1 LSOPNGVXJKBJNV-FUHYEJFZSA-N 0.000 claims description 5
- QSHRTMFXFVXKDR-LBAQZLPGSA-N (2r)-n-[1-(1,3-benzothiazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-(propan-2-ylamino)propanamide Chemical compound C([C@@H](C(=O)NC(CCC)C(=O)C=1SC2=CC=CC=C2N=1)NC(C)C)S(=O)(=O)CC1=CC=CC=C1 QSHRTMFXFVXKDR-LBAQZLPGSA-N 0.000 claims description 5
- VDBXPPTWLHZFIH-ABLWVSNPSA-N (2r)-n-[cyano(thiophen-2-yl)methyl]-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-2-hydroxypropanamide Chemical compound C([C@H](O)C(=O)NC(C#N)C=1SC=CC=1)S(=O)(=O)CC1=CC=CC=C1OC(F)F VDBXPPTWLHZFIH-ABLWVSNPSA-N 0.000 claims description 5
- PLZOJOMMRPOWBH-STQMWFEESA-N (2s)-2-[[(2r)-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-2-hydroxypropanoyl]amino]-n-methoxy-n-methylbutanamide Chemical compound CON(C)C(=O)[C@H](CC)NC(=O)[C@@H](O)CS(=O)(=O)CC1=CC=CC=C1OC(F)F PLZOJOMMRPOWBH-STQMWFEESA-N 0.000 claims description 5
- QAQBNESGJGKRGM-OALUTQOASA-N (2s)-n-[(1s)-1-cyano-3-phenylpropyl]-2-fluoro-4-phenylbutanamide Chemical compound C([C@H](F)C(=O)N[C@@H](CCC=1C=CC=CC=1)C#N)CC1=CC=CC=C1 QAQBNESGJGKRGM-OALUTQOASA-N 0.000 claims description 5
- ARPWDWXNMXRUEZ-ZDOMSUIMSA-N (2s)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-2-(oxan-4-ylamino)-3-thiophen-2-ylpropanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)NC1CCOCC1)C1=CC=CS1 ARPWDWXNMXRUEZ-ZDOMSUIMSA-N 0.000 claims description 5
- CNMAGQNGXWHLIN-SFHVURJKSA-N (3s)-n-benzyl-3-[3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanoylamino]-2-oxopentanamide Chemical compound N([C@@H](CC)C(=O)C(=O)NCC=1C=CC=CC=1)C(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F CNMAGQNGXWHLIN-SFHVURJKSA-N 0.000 claims description 5
- FQTWFPDFUXCIRR-RXVVDRJESA-N [(2r)-1-[[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxobutan-2-yl]amino]-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-1-oxopropan-2-yl] morpholine-4-carboxylate Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1SC2=CC=CC=C2N=1)OC(=O)N1CCOCC1)S(=O)(=O)CC1=CC=CC=C1OC(F)F FQTWFPDFUXCIRR-RXVVDRJESA-N 0.000 claims description 5
- RENVUVSNIKMBQL-AVRDEDQJSA-N [(2r)-1-[[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]amino]-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-1-oxopropan-2-yl] morpholine-4-carboxylate Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)OC(=O)N1CCOCC1)S(=O)(=O)CC1=CC=CC=C1OC(F)F RENVUVSNIKMBQL-AVRDEDQJSA-N 0.000 claims description 5
- LWNNLSDXCAFEMI-AWEZNQCLSA-N [(2r)-3-benzylsulfonyl-1-(cyanomethylamino)-1-oxopropan-2-yl] n-(2-methoxyethyl)carbamate Chemical compound COCCNC(=O)O[C@H](C(=O)NCC#N)CS(=O)(=O)CC1=CC=CC=C1 LWNNLSDXCAFEMI-AWEZNQCLSA-N 0.000 claims description 5
- MLLLTAPEDRVQNR-HKUYNNGSSA-N [(2s)-3-cyclohexyl-1-[[(2s)-1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl] morpholine-4-carboxylate Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CN=C2N=1)OC(=O)N1CCOCC1)C1CCCCC1 MLLLTAPEDRVQNR-HKUYNNGSSA-N 0.000 claims description 5
- HDBKKUCMWJXJHF-UHFFFAOYSA-N [4,4-dimethyl-1-oxo-1-[(3-oxo-1-phenylmethoxycarbonylazepan-4-yl)amino]pentan-2-yl] morpholine-4-carboxylate Chemical compound C1CCN(C(=O)OCC=2C=CC=CC=2)CC(=O)C1NC(=O)C(CC(C)(C)C)OC(=O)N1CCOCC1 HDBKKUCMWJXJHF-UHFFFAOYSA-N 0.000 claims description 5
- 150000007824 aliphatic compounds Chemical class 0.000 claims description 5
- DWLVWMUCHSLGSU-UHFFFAOYSA-N dimethylcarbamic acid Chemical compound CN(C)C(O)=O DWLVWMUCHSLGSU-UHFFFAOYSA-N 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- JWEIPHMUKZSLTR-IBGZPJMESA-N n-[(1s)-1-cyano-3-phenylpropyl]-4-phenylbutanamide Chemical compound N([C@@H](CCC=1C=CC=CC=1)C#N)C(=O)CCCC1=CC=CC=C1 JWEIPHMUKZSLTR-IBGZPJMESA-N 0.000 claims description 5
- 230000007170 pathology Effects 0.000 claims description 5
- JUQXHQHGCKAAOA-LYKKTTPLSA-N (2r)-3-(cyclopropylmethylsulfonyl)-n-[1-(5-ethyl-1,2,4-oxadiazol-3-yl)-1-oxobutan-2-yl]-2-(oxan-4-ylamino)propanamide Chemical compound C([C@@H](C(=O)NC(CC)C(=O)C=1N=C(CC)ON=1)NC1CCOCC1)S(=O)(=O)CC1CC1 JUQXHQHGCKAAOA-LYKKTTPLSA-N 0.000 claims description 4
- JQCAPUONYUKMHK-RDJZCZTQSA-N (2r)-3-benzylsulfonyl-2-hydroxy-n-[(2s)-1-oxo-1-pyridazin-3-ylpentan-2-yl]propanamide Chemical compound C([C@H](O)C(=O)N[C@@H](CCC)C(=O)C=1N=NC=CC=1)S(=O)(=O)CC1=CC=CC=C1 JQCAPUONYUKMHK-RDJZCZTQSA-N 0.000 claims description 4
- ZJACADWPDLENNQ-RDJZCZTQSA-N (2r)-n-[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxobutan-2-yl]-3-benzylsulfonyl-2-hydroxypropanamide Chemical compound C([C@H](O)C(=O)N[C@@H](CC)C(=O)C=1SC2=CC=CC=C2N=1)S(=O)(=O)CC1=CC=CC=C1 ZJACADWPDLENNQ-RDJZCZTQSA-N 0.000 claims description 4
- PIBITRCGIBGVSU-MMBKUXRPSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-(propan-2-ylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)NC(C)C)S(=O)(=O)CC1=CC=CC=C1 PIBITRCGIBGVSU-MMBKUXRPSA-N 0.000 claims description 4
- QUWLGQGIESCFMI-OKHNBNEASA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-[(1-methylpiperidin-4-yl)amino]propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)NC1CCN(C)CC1)S(=O)(=O)CC1=CC=CC=C1 QUWLGQGIESCFMI-OKHNBNEASA-N 0.000 claims description 4
- ODWQEMCLDQYEDA-PMACEKPBSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-3-(cyclopropylmethylsulfonyl)-2-(oxan-4-ylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)NC1CCOCC1)S(=O)(=O)CC1CC1 ODWQEMCLDQYEDA-PMACEKPBSA-N 0.000 claims description 4
- AXIHNVQGIBUFTQ-ZEQRLZLVSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-(cyclohexylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)NC1CCCCC1)S(=O)(=O)CC1=CC=CC=C1 AXIHNVQGIBUFTQ-ZEQRLZLVSA-N 0.000 claims description 4
- CYFPDAQKQHKDHS-PMACEKPBSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-(dimethylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)N(C)C)S(=O)(=O)CC1=CC=CC=C1 CYFPDAQKQHKDHS-PMACEKPBSA-N 0.000 claims description 4
- SBVLGQBIJPONKQ-ZEQRLZLVSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-[(1-methylpiperidin-4-yl)amino]propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)NC1CCN(C)CC1)S(=O)(=O)CC1=CC=CC=C1 SBVLGQBIJPONKQ-ZEQRLZLVSA-N 0.000 claims description 4
- VAIVIMZHMPZOEP-AHWVRZQESA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-phenylmethoxypropanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)OCC=1C=CC=CC=1)S(=O)(=O)CC1=CC=CC=C1 VAIVIMZHMPZOEP-AHWVRZQESA-N 0.000 claims description 4
- KPSPSMBJJCEFMA-JYUUXGOASA-N (2r)-n-[1-(1,3-benzothiazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-(dibenzylamino)propanamide Chemical compound C([C@@H](C(=O)NC(CCC)C(=O)C=1SC2=CC=CC=C2N=1)N(CC=1C=CC=CC=1)CC=1C=CC=CC=1)S(=O)(=O)CC1=CC=CC=C1 KPSPSMBJJCEFMA-JYUUXGOASA-N 0.000 claims description 4
- CYNUPJYXWLLSCP-ANYOKISRSA-N (2r)-n-[1-(1,3-benzothiazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-(dimethylamino)propanamide Chemical compound C([C@@H](C(=O)NC(CCC)C(=O)C=1SC2=CC=CC=C2N=1)N(C)C)S(=O)(=O)CC1=CC=CC=C1 CYNUPJYXWLLSCP-ANYOKISRSA-N 0.000 claims description 4
- MFSMUSJBCXXWAF-LBAQZLPGSA-N (2r)-n-[1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-2-(cyclohexylamino)-3-(cyclopropylmethylsulfonyl)propanamide Chemical compound C([C@@H](C(=O)NC(CCC)C(=O)C=1OC2=CC=CC=C2N=1)NC1CCCCC1)S(=O)(=O)CC1CC1 MFSMUSJBCXXWAF-LBAQZLPGSA-N 0.000 claims description 4
- CSDZSCKUEBXGQP-ZEQRLZLVSA-N (2s)-n-[(1s)-1-cyano-3-phenylpropyl]-2-(2-morpholin-4-yl-2-oxoethoxy)-4-phenylbutanamide Chemical compound C([C@H](OCC(=O)N1CCOCC1)C(=O)N[C@@H](CCC=1C=CC=CC=1)C#N)CC1=CC=CC=C1 CSDZSCKUEBXGQP-ZEQRLZLVSA-N 0.000 claims description 4
- ITDLVDJKSMUMOU-ROUUACIJSA-N (2s)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-2-(propan-2-ylamino)-3-thiophen-2-ylpropanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)NC(C)C)C1=CC=CS1 ITDLVDJKSMUMOU-ROUUACIJSA-N 0.000 claims description 4
- NHGPIGPNLVLJOX-IRXDYDNUSA-N (2s)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-2-hydroxy-3-phenylpropanamide Chemical compound C([C@H](O)C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)C1=CC=CC=C1 NHGPIGPNLVLJOX-IRXDYDNUSA-N 0.000 claims description 4
- MYEWRAUDTYFNTH-OALUTQOASA-N (3s)-n-benzyl-3-[[(2r)-3-benzylsulfonyl-2-hydroxypropanoyl]amino]-2-oxopentanamide Chemical compound C([C@H](O)C(=O)N[C@@H](CC)C(=O)C(=O)NCC=1C=CC=CC=1)S(=O)(=O)CC1=CC=CC=C1 MYEWRAUDTYFNTH-OALUTQOASA-N 0.000 claims description 4
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 4
- UUPVMNFYLCNSEQ-UHFFFAOYSA-N 3-[3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanoylamino]-n-(oxan-4-yl)-2-oxopentanamide Chemical compound C1COCCC1NC(=O)C(=O)C(CC)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F UUPVMNFYLCNSEQ-UHFFFAOYSA-N 0.000 claims description 4
- HQBAMJMLDZWMMD-UHFFFAOYSA-N 3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-n-(1,2-dioxo-1-pyrrolidin-1-ylpentan-3-yl)propanamide Chemical compound C1CCCN1C(=O)C(=O)C(CC)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F HQBAMJMLDZWMMD-UHFFFAOYSA-N 0.000 claims description 4
- XEYMGNNFYXIIHN-UHFFFAOYSA-N 3-cyclohexyl-n-(1-oxo-4-phenylbutan-2-yl)propanamide Chemical compound C1CCCCC1CCC(=O)NC(C=O)CCC1=CC=CC=C1 XEYMGNNFYXIIHN-UHFFFAOYSA-N 0.000 claims description 4
- HIMHFLLWWDHBIY-OYKVQYDMSA-N N([C@@H](CCC=1C=CC=CC=1)C#N)C(=O)C(O)CC(F)(F)CC1=CC=CC=C1 Chemical compound N([C@@H](CCC=1C=CC=CC=1)C#N)C(=O)C(O)CC(F)(F)CC1=CC=CC=C1 HIMHFLLWWDHBIY-OYKVQYDMSA-N 0.000 claims description 4
- ZFTWFALVSVFTAP-SFHVURJKSA-N [(2r)-3-benzylsulfonyl-1-[(4-cyanooxan-4-yl)amino]-1-oxopropan-2-yl] morpholine-4-carboxylate Chemical compound O=C([C@H](CS(=O)(=O)CC=1C=CC=CC=1)OC(=O)N1CCOCC1)NC1(C#N)CCOCC1 ZFTWFALVSVFTAP-SFHVURJKSA-N 0.000 claims description 4
- FNJASIJNMHFRFB-KGLIPLIRSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] (3r)-3-hydroxypyrrolidine-1-carboxylate Chemical compound C1[C@H](O)CCN1C(=O)O[C@H](C(=O)NCC#N)CC1CCCCC1 FNJASIJNMHFRFB-KGLIPLIRSA-N 0.000 claims description 4
- FNJASIJNMHFRFB-KBPBESRZSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] (3s)-3-hydroxypyrrolidine-1-carboxylate Chemical compound C1[C@@H](O)CCN1C(=O)O[C@H](C(=O)NCC#N)CC1CCCCC1 FNJASIJNMHFRFB-KBPBESRZSA-N 0.000 claims description 4
- ANOVETNMJYVZOY-INIZCTEOSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] 4-ethylpiperazine-1-carboxylate Chemical compound C1CN(CC)CCN1C(=O)O[C@H](C(=O)NCC#N)CC1CCCCC1 ANOVETNMJYVZOY-INIZCTEOSA-N 0.000 claims description 4
- OJFMVVJTBJMCAF-ZDUSSCGKSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] azetidine-1-carboxylate Chemical compound C([C@@H](C(NCC#N)=O)OC(=O)N1CCC1)C1CCCCC1 OJFMVVJTBJMCAF-ZDUSSCGKSA-N 0.000 claims description 4
- QCNQQJBBRIBCOS-AWEZNQCLSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] morpholine-4-carboxylate Chemical compound C([C@@H](C(NCC#N)=O)OC(=O)N1CCOCC1)C1CCCCC1 QCNQQJBBRIBCOS-AWEZNQCLSA-N 0.000 claims description 4
- NZUQEPQXEKZZSW-NSHDSACASA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] n-(2,2,2-trifluoroethyl)carbamate Chemical compound FC(F)(F)CNC(=O)O[C@H](C(=O)NCC#N)CC1CCCCC1 NZUQEPQXEKZZSW-NSHDSACASA-N 0.000 claims description 4
- SYIFLOLEMMHBEZ-LBPRGKRZSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] n-(2-hydroxyethyl)carbamate Chemical compound OCCNC(=O)O[C@H](C(=O)NCC#N)CC1CCCCC1 SYIFLOLEMMHBEZ-LBPRGKRZSA-N 0.000 claims description 4
- HKWGJQMQFXBOCN-LOACHALJSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] n-(oxolan-2-ylmethyl)carbamate Chemical compound O([C@@H](CC1CCCCC1)C(=O)NCC#N)C(=O)NCC1CCCO1 HKWGJQMQFXBOCN-LOACHALJSA-N 0.000 claims description 4
- VRIHSJYQMYVOSO-HNNXBMFYSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] piperidine-1-carboxylate Chemical compound C([C@@H](C(NCC#N)=O)OC(=O)N1CCCCC1)C1CCCCC1 VRIHSJYQMYVOSO-HNNXBMFYSA-N 0.000 claims description 4
- XRFHDQTZEZBJMF-HNNXBMFYSA-N [(2s)-1-(cyanomethylamino)-4-cyclohexyl-1-oxobutan-2-yl] morpholine-4-carboxylate Chemical compound C([C@@H](C(NCC#N)=O)OC(=O)N1CCOCC1)CC1CCCCC1 XRFHDQTZEZBJMF-HNNXBMFYSA-N 0.000 claims description 4
- GZCKWLDLKQQJHS-UGKGYDQZSA-N [(2s)-1-[[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]amino]-4-cyclohexyl-1-oxobutan-2-yl] morpholine-4-carboxylate Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)OC(=O)N1CCOCC1)CC1CCCCC1 GZCKWLDLKQQJHS-UGKGYDQZSA-N 0.000 claims description 4
- XBNLRBQBZMPOIZ-IRXDYDNUSA-N [(2s)-3-cyclohexyl-1-[[(2s)-1-(5-ethyl-1,3,4-oxadiazol-2-yl)-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl] morpholine-4-carboxylate Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1OC(CC)=NN=1)OC(=O)N1CCOCC1)C1CCCCC1 XBNLRBQBZMPOIZ-IRXDYDNUSA-N 0.000 claims description 4
- 150000004677 hydrates Chemical class 0.000 claims description 4
- ZWAYYIWOBRSSNU-UHFFFAOYSA-N n-(1-cyanocyclopropyl)-2,2-difluoro-5-phenylpentanamide Chemical compound C1CC1(C#N)NC(=O)C(F)(F)CCCC1=CC=CC=C1 ZWAYYIWOBRSSNU-UHFFFAOYSA-N 0.000 claims description 4
- AXVWCSDAVJGQNL-UHFFFAOYSA-N n-(cyanomethyl)-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanamide Chemical compound FC(F)OC1=CC=CC=C1CS(=O)(=O)CCC(=O)NCC#N AXVWCSDAVJGQNL-UHFFFAOYSA-N 0.000 claims description 4
- JPYZKTSVMMQCJY-UHFFFAOYSA-N n-(cyanomethyl)-3-cyclohexyl-2-phenylmethoxypropanamide Chemical compound C=1C=CC=CC=1COC(C(NCC#N)=O)CC1CCCCC1 JPYZKTSVMMQCJY-UHFFFAOYSA-N 0.000 claims description 4
- TVRADSFMTXVZLV-SFHVURJKSA-N n-[(1s)-1-cyano-3-phenylpropyl]-2,2-difluoro-4-phenylbutanamide Chemical compound N([C@@H](CCC=1C=CC=CC=1)C#N)C(=O)C(F)(F)CCC1=CC=CC=C1 TVRADSFMTXVZLV-SFHVURJKSA-N 0.000 claims description 4
- BQBHATJABIXBFM-IBGZPJMESA-N n-[(1s)-1-cyano-3-phenylpropyl]-2,2-difluoro-5-phenylpentanamide Chemical compound N([C@@H](CCC=1C=CC=CC=1)C#N)C(=O)C(F)(F)CCCC1=CC=CC=C1 BQBHATJABIXBFM-IBGZPJMESA-N 0.000 claims description 4
- JQBJMAUNNFWPCL-DEOSSOPVSA-N n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxo-4-phenylbutan-2-yl]-3-[(4-methylphenyl)methylsulfonyl]propanamide Chemical compound C1=CC(C)=CC=C1CS(=O)(=O)CCC(=O)N[C@H](C(=O)C=1OC2=CC=CC=C2N=1)CCC1=CC=CC=C1 JQBJMAUNNFWPCL-DEOSSOPVSA-N 0.000 claims description 4
- VBSYARIBGUCUOS-UHFFFAOYSA-N n-[1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]-3-benzylsulfonyl-2-(pyrimidin-2-ylamino)propanamide Chemical compound N=1C2=CC=CC=C2OC=1C(=O)C(CC)NC(=O)C(NC=1N=CC=CN=1)CS(=O)(=O)CC1=CC=CC=C1 VBSYARIBGUCUOS-UHFFFAOYSA-N 0.000 claims description 4
- ISZVZVWCIXKDGG-UHFFFAOYSA-N n-cyclopentyl-3-[3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanoylamino]-n-ethyl-2-oxopentanamide Chemical compound C1CCCC1N(CC)C(=O)C(=O)C(CC)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F ISZVZVWCIXKDGG-UHFFFAOYSA-N 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims description 3
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims description 3
- YFLCIXFSLVOVCJ-DQEYMECFSA-N (2r)-3-benzylsulfonyl-2-(oxan-4-ylamino)-n-[(2s)-1-oxo-4-phenyl-1-(1,3-thiazol-2-yl)butan-2-yl]propanamide Chemical compound C([C@H](NC(=O)[C@H](CS(=O)(=O)CC=1C=CC=CC=1)NC1CCOCC1)C(=O)C=1SC=CN=1)CC1=CC=CC=C1 YFLCIXFSLVOVCJ-DQEYMECFSA-N 0.000 claims description 3
- VGPJFWYCPHDUHT-WCSIJFPASA-N (2r)-3-benzylsulfonyl-2-(oxan-4-ylamino)-n-[1-oxo-1-(3-phenyl-1,2,4-oxadiazol-5-yl)butan-2-yl]propanamide Chemical compound C([C@@H](C(=O)NC(CC)C(=O)C=1ON=C(N=1)C=1C=CC=CC=1)NC1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 VGPJFWYCPHDUHT-WCSIJFPASA-N 0.000 claims description 3
- GCVSIYKLIWOINY-ANYOKISRSA-N (2r)-3-benzylsulfonyl-n-[1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-oxobutan-2-yl]-2-(oxan-4-ylamino)propanamide Chemical compound C([C@@H](C(=O)NC(CC)C(=O)C=1ON=C(N=1)C1CC1)NC1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 GCVSIYKLIWOINY-ANYOKISRSA-N 0.000 claims description 3
- YBOGDEORUDCYJV-VQTJNVASSA-N (2r)-n-[(1s)-1-cyano-3-phenylpropyl]-2-methoxy-4-phenylbutanamide Chemical compound C([C@@H](OC)C(=O)N[C@@H](CCC=1C=CC=CC=1)C#N)CC1=CC=CC=C1 YBOGDEORUDCYJV-VQTJNVASSA-N 0.000 claims description 3
- RLMPAUWDFDUPMO-QIELNMHASA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-[2-methoxyethyl(oxan-4-yl)amino]propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)N(CCOC)C1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 RLMPAUWDFDUPMO-QIELNMHASA-N 0.000 claims description 3
- QFMURCFOQSSUAK-HOCLYGCPSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-2-hydroxypropanamide Chemical compound C([C@H](O)C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)S(=O)(=O)CC1=CC=CC=C1OC(F)F QFMURCFOQSSUAK-HOCLYGCPSA-N 0.000 claims description 3
- XAEDXEPLOBJLII-UGKGYDQZSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]-3-benzylsulfonyl-2-(2-nitroanilino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)NC=1C(=CC=CC=1)[N+]([O-])=O)S(=O)(=O)CC1=CC=CC=C1 XAEDXEPLOBJLII-UGKGYDQZSA-N 0.000 claims description 3
- IRKUPQKURRYTDO-ACHIHNKUSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-(dibenzylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)N(CC=1C=CC=CC=1)CC=1C=CC=CC=1)S(=O)(=O)CC1=CC=CC=C1 IRKUPQKURRYTDO-ACHIHNKUSA-N 0.000 claims description 3
- LRZFDEVIGZSTFM-NSOVKSMOSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-3-benzylsulfonyl-2-[bis(thiophen-2-ylmethyl)amino]propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)N(CC=1SC=CC=1)CC=1SC=CC=1)S(=O)(=O)CC1=CC=CC=C1 LRZFDEVIGZSTFM-NSOVKSMOSA-N 0.000 claims description 3
- LCQHMJSLVVXOSB-GKPPEQDDSA-N (2r,5s)-2-[[2-(difluoromethoxy)phenyl]methylsulfonylmethyl]-6-ethoxy-5-ethylmorpholin-3-one Chemical compound O=C1N[C@@H](CC)C(OCC)O[C@H]1CS(=O)(=O)CC1=CC=CC=C1OC(F)F LCQHMJSLVVXOSB-GKPPEQDDSA-N 0.000 claims description 3
- VGPYQDIPGAIEOD-OALUTQOASA-N (2s)-n-[(1s)-1-cyano-3-phenylpropyl]-2-hydroxy-4-phenylbutanamide Chemical compound C([C@H](O)C(=O)N[C@@H](CCC=1C=CC=CC=1)C#N)CC1=CC=CC=C1 VGPYQDIPGAIEOD-OALUTQOASA-N 0.000 claims description 3
- QPFWBOMRNZXVOG-WMZOPIPTSA-N (2s)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-2-fluoro-4-phenylbutanamide Chemical compound C([C@H](F)C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)CC1=CC=CC=C1 QPFWBOMRNZXVOG-WMZOPIPTSA-N 0.000 claims description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 3
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims description 3
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims description 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 claims description 3
- CBKUDXXRBQXXSS-UHFFFAOYSA-N 3-[3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanoylamino]-2-oxo-n-phenylpentanamide Chemical compound C=1C=CC=CC=1NC(=O)C(=O)C(CC)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F CBKUDXXRBQXXSS-UHFFFAOYSA-N 0.000 claims description 3
- TXNPQAIPLUYZGZ-UHFFFAOYSA-N 3-[3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanoylamino]-n,n-dimethyl-2-oxopentanamide Chemical compound CN(C)C(=O)C(=O)C(CC)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F TXNPQAIPLUYZGZ-UHFFFAOYSA-N 0.000 claims description 3
- YORZRUUOTRYRFJ-UHFFFAOYSA-N 3-[3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanoylamino]-n-(2-morpholin-4-ylethyl)-2-oxopentanamide Chemical compound C1COCCN1CCNC(=O)C(=O)C(CC)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F YORZRUUOTRYRFJ-UHFFFAOYSA-N 0.000 claims description 3
- XNVSINGACFAUMO-UHFFFAOYSA-N 3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-n-(1,2-dioxo-1-piperazin-1-ylpentan-3-yl)propanamide Chemical compound C1CNCCN1C(=O)C(=O)C(CC)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F XNVSINGACFAUMO-UHFFFAOYSA-N 0.000 claims description 3
- NPXHGTPNKHDDMZ-UHFFFAOYSA-N 3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-n-(1-morpholin-4-yl-1,2-dioxopentan-3-yl)propanamide Chemical compound C1COCCN1C(=O)C(=O)C(CC)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F NPXHGTPNKHDDMZ-UHFFFAOYSA-N 0.000 claims description 3
- BSXLGRQGALFDNC-ZDUSSCGKSA-N 3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-n-[(2s)-1-(5-ethyl-1,3,4-oxadiazol-2-yl)-1-oxobutan-2-yl]propanamide Chemical compound N([C@@H](CC)C(=O)C=1OC(CC)=NN=1)C(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F BSXLGRQGALFDNC-ZDUSSCGKSA-N 0.000 claims description 3
- OVAKHFSFQXKDEM-UHFFFAOYSA-N 3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-n-[1-(4-methylsulfonylpiperazin-1-yl)-1,2-dioxopentan-3-yl]propanamide Chemical compound C1CN(S(C)(=O)=O)CCN1C(=O)C(=O)C(CC)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F OVAKHFSFQXKDEM-UHFFFAOYSA-N 0.000 claims description 3
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- XLOGMDVJCSIMQF-NSHDSACASA-N [(2r)-1-(cyanomethylamino)-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-1-oxopropan-2-yl] carbamate Chemical compound N#CCNC(=O)[C@@H](OC(=O)N)CS(=O)(=O)CC1=CC=CC=C1OC(F)F XLOGMDVJCSIMQF-NSHDSACASA-N 0.000 claims description 3
- IYHBDGOVGCLDPH-INIZCTEOSA-N [(2r)-3-benzylsulfonyl-1-[(1-cyanocyclopropyl)amino]-1-oxopropan-2-yl] morpholine-4-carboxylate Chemical compound O=C([C@H](CS(=O)(=O)CC=1C=CC=CC=1)OC(=O)N1CCOCC1)NC1(C#N)CC1 IYHBDGOVGCLDPH-INIZCTEOSA-N 0.000 claims description 3
- RZWFEFBOXRMZNA-GJZGRUSLSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] (2s)-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound OC[C@@H]1CCCN1C(=O)O[C@H](C(=O)NCC#N)CC1CCCCC1 RZWFEFBOXRMZNA-GJZGRUSLSA-N 0.000 claims description 3
- MTJFRXRGUYMLBJ-JTQLQIEISA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] carbamate Chemical compound N#CCNC(=O)[C@@H](OC(=O)N)CC1CCCCC1 MTJFRXRGUYMLBJ-JTQLQIEISA-N 0.000 claims description 3
- GAJQBQADNNWXGU-AWEZNQCLSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] n,n-diethylcarbamate Chemical compound CCN(CC)C(=O)O[C@H](C(=O)NCC#N)CC1CCCCC1 GAJQBQADNNWXGU-AWEZNQCLSA-N 0.000 claims description 3
- DDQYAEHHMNTGKM-ZDUSSCGKSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] n-cyclopropylcarbamate Chemical compound O([C@@H](CC1CCCCC1)C(=O)NCC#N)C(=O)NC1CC1 DDQYAEHHMNTGKM-ZDUSSCGKSA-N 0.000 claims description 3
- HDTKYTBZRXXITH-ZDUSSCGKSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] n-tert-butylcarbamate Chemical compound CC(C)(C)NC(=O)O[C@H](C(=O)NCC#N)CC1CCCCC1 HDTKYTBZRXXITH-ZDUSSCGKSA-N 0.000 claims description 3
- RVGIWGHSQIAAEM-AWEZNQCLSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] pyrrolidine-1-carboxylate Chemical compound C([C@@H](C(NCC#N)=O)OC(=O)N1CCCC1)C1CCCCC1 RVGIWGHSQIAAEM-AWEZNQCLSA-N 0.000 claims description 3
- ZEGQSNAGYMQKQM-SFTDATJTSA-N [(2s)-3-cyclohexyl-1-oxo-1-[[(2s)-1-oxo-1-(5-phenyl-1,3,4-oxadiazol-2-yl)butan-2-yl]amino]propan-2-yl] morpholine-4-carboxylate Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1OC(=NN=1)C=1C=CC=CC=1)OC(=O)N1CCOCC1)C1CCCCC1 ZEGQSNAGYMQKQM-SFTDATJTSA-N 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 229940126543 compound 14 Drugs 0.000 claims description 3
- 229940125758 compound 15 Drugs 0.000 claims description 3
- 229940125810 compound 20 Drugs 0.000 claims description 3
- 229940125846 compound 25 Drugs 0.000 claims description 3
- 229940125877 compound 31 Drugs 0.000 claims description 3
- GKFWTJZBNTWHOD-UHFFFAOYSA-N n-(1-benzoylpiperidin-4-yl)-3-[3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanoylamino]-2-oxopentanamide Chemical compound C1CN(C(=O)C=2C=CC=CC=2)CCC1NC(=O)C(=O)C(CC)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F GKFWTJZBNTWHOD-UHFFFAOYSA-N 0.000 claims description 3
- WXZLLISUWHNCAM-UHFFFAOYSA-N n-(4-cyano-1-ethylpiperidin-4-yl)-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanamide Chemical compound C1CN(CC)CCC1(C#N)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F WXZLLISUWHNCAM-UHFFFAOYSA-N 0.000 claims description 3
- RYSUBCOTGMKOQP-UHFFFAOYSA-N n-(4-cyano-1-ethylpiperidin-4-yl)-3-cyclohexylpropanamide Chemical compound C1CN(CC)CCC1(C#N)NC(=O)CCC1CCCCC1 RYSUBCOTGMKOQP-UHFFFAOYSA-N 0.000 claims description 3
- AQBBWKHACYNRDU-UHFFFAOYSA-N n-(cyanomethyl)-3-cyclohexyl-2-(4-methoxyphenoxy)propanamide Chemical compound C1=CC(OC)=CC=C1OC(C(=O)NCC#N)CC1CCCCC1 AQBBWKHACYNRDU-UHFFFAOYSA-N 0.000 claims description 3
- JINQCEXQOSFVFN-AJZOCDQUSA-N n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]-2-(2-cyanoanilino)-3-cyclohexylpropanamide Chemical compound N([C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)C(=O)C(NC=1C(=CC=CC=1)C#N)CC1CCCCC1 JINQCEXQOSFVFN-AJZOCDQUSA-N 0.000 claims description 3
- GCAZPVCJGXFXFX-SFHVURJKSA-N n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-2,2-difluoro-5-phenylpentanamide Chemical compound N([C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)C(=O)C(F)(F)CCCC1=CC=CC=C1 GCAZPVCJGXFXFX-SFHVURJKSA-N 0.000 claims description 3
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 3
- PMSFDXOIVCQGHK-YCRPNKLZSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]-2-hydroxy-2-methylsulfonyl-3-phenylpropanamide Chemical compound C([C@](O)(C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)S(C)(=O)=O)C1=CC=CC=C1 PMSFDXOIVCQGHK-YCRPNKLZSA-N 0.000 claims description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 101100240520 Caenorhabditis elegans nhr-14 gene Proteins 0.000 claims description 2
- MLVOSDLCPIAFNB-UGKGYDQZSA-N [(2r)-1-[[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]amino]-3-benzylsulfonyl-1-oxopropan-2-yl] pyrrolidine-1-carboxylate Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)OC(=O)N1CCCC1)S(=O)(=O)CC1=CC=CC=C1 MLVOSDLCPIAFNB-UGKGYDQZSA-N 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- DUEZCIWUQMDEPV-HNNXBMFYSA-N n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanamide Chemical compound N([C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)C(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F DUEZCIWUQMDEPV-HNNXBMFYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 21
- FATAVLOOLIRUNA-UHFFFAOYSA-N formylmethyl Chemical group [CH2]C=O FATAVLOOLIRUNA-UHFFFAOYSA-N 0.000 claims 3
- POUBRJMTXIEUQH-DQEYMECFSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxo-4-phenylbutan-2-yl]-3-(cyclopropylmethylsulfonyl)-2-(oxan-4-ylamino)propanamide Chemical compound C([C@H](NC(=O)[C@H](CS(=O)(=O)CC1CC1)NC1CCOCC1)C(=O)C=1OC2=CC=CC=C2N=1)CC1=CC=CC=C1 POUBRJMTXIEUQH-DQEYMECFSA-N 0.000 claims 2
- GFPXPRQSYUPGGU-KEKNWZKVSA-N (2r)-n-[1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-2-(cycloheptylamino)-3-(cyclopropylmethylsulfonyl)propanamide Chemical compound C([C@@H](C(=O)NC(CCC)C(=O)C=1OC2=CC=CC=C2N=1)NC1CCCCCC1)S(=O)(=O)CC1CC1 GFPXPRQSYUPGGU-KEKNWZKVSA-N 0.000 claims 2
- 208000031295 Animal disease Diseases 0.000 claims 2
- FEDRUOFUCGAOHK-ZDUSSCGKSA-N [(2s)-1-(cyanomethylamino)-3-cyclohexyl-1-oxopropan-2-yl] n-(2-methoxyethyl)carbamate Chemical compound COCCNC(=O)O[C@H](C(=O)NCC#N)CC1CCCCC1 FEDRUOFUCGAOHK-ZDUSSCGKSA-N 0.000 claims 2
- GUDMTEGDXVJZEE-UHFFFAOYSA-N n-benzyl-2-hydroxyacetamide Chemical compound OCC(=O)NCC1=CC=CC=C1 GUDMTEGDXVJZEE-UHFFFAOYSA-N 0.000 claims 2
- YMJRDZSVSJUACX-UHFFFAOYSA-N (4-aminopiperidin-1-yl)-phenylmethanone Chemical compound C1CC(N)CCN1C(=O)C1=CC=CC=C1 YMJRDZSVSJUACX-UHFFFAOYSA-N 0.000 claims 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims 1
- 239000000835 fiber Substances 0.000 claims 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 267
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 184
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 120
- 239000000243 solution Substances 0.000 description 120
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 101
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 98
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 91
- 235000019439 ethyl acetate Nutrition 0.000 description 90
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 80
- 238000005160 1H NMR spectroscopy Methods 0.000 description 79
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 76
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 69
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 60
- 235000019341 magnesium sulphate Nutrition 0.000 description 60
- 239000002904 solvent Substances 0.000 description 59
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 50
- 239000011541 reaction mixture Substances 0.000 description 50
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- 239000011780 sodium chloride Substances 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 35
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 32
- 238000003756 stirring Methods 0.000 description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- 229920006395 saturated elastomer Polymers 0.000 description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
- 239000007787 solid Substances 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 25
- 239000012044 organic layer Substances 0.000 description 23
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 22
- 239000000047 product Substances 0.000 description 22
- 230000002829 reductive effect Effects 0.000 description 22
- 239000000741 silica gel Substances 0.000 description 22
- 229910002027 silica gel Inorganic materials 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 18
- 125000006239 protecting group Chemical group 0.000 description 18
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
- DJNNKOSWQYSRTL-SNVBAGLBSA-N (2r)-n-(cyanomethyl)-3-cyclohexyl-2-hydroxypropanamide Chemical compound N#CCNC(=O)[C@H](O)CC1CCCCC1 DJNNKOSWQYSRTL-SNVBAGLBSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 239000012043 crude product Substances 0.000 description 14
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000008186 active pharmaceutical agent Substances 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- 230000014759 maintenance of location Effects 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 11
- 239000011347 resin Substances 0.000 description 11
- 229920005989 resin Polymers 0.000 description 11
- LJIBIZWTMYDZKL-NSHDSACASA-N (2s)-2-[benzylsulfonyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoic acid Chemical compound CC(C)(C)OC(=O)N([C@@H](C)C(O)=O)S(=O)(=O)CC1=CC=CC=C1 LJIBIZWTMYDZKL-NSHDSACASA-N 0.000 description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 150000001721 carbon Chemical group 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 239000012131 assay buffer Substances 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 9
- CNKXAONHMAXJPX-QMMMGPOBSA-N (2r)-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-2-hydroxypropanoic acid Chemical compound OC(=O)[C@@H](O)CS(=O)(=O)CC1=CC=CC=C1OC(F)F CNKXAONHMAXJPX-QMMMGPOBSA-N 0.000 description 8
- COOMAYNPLIMRGM-PPHPATTJSA-N (2s)-2-amino-4-phenylbutanenitrile;hydrochloride Chemical compound Cl.N#C[C@@H](N)CCC1=CC=CC=C1 COOMAYNPLIMRGM-PPHPATTJSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 238000010828 elution Methods 0.000 description 8
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000012085 test solution Substances 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- ULOFZFJIJPPXMM-VQSBYGRUSA-N (2r)-2-amino-n-[1-(1,3-benzothiazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonylpropanamide Chemical compound C([C@H](N)C(=O)NC(CCC)C(O)C=1SC2=CC=CC=C2N=1)S(=O)(=O)CC1=CC=CC=C1 ULOFZFJIJPPXMM-VQSBYGRUSA-N 0.000 description 6
- JIFPVWKYFODQNZ-UHFFFAOYSA-N 2,2-difluoro-5-phenylpentanoic acid Chemical compound OC(=O)C(F)(F)CCCC1=CC=CC=C1 JIFPVWKYFODQNZ-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 238000000105 evaporative light scattering detection Methods 0.000 description 6
- 230000001575 pathological effect Effects 0.000 description 6
- DYFLWZLTQLEOIZ-LYNSQETBSA-N (1s)-2-amino-1-(1,3-benzoxazol-2-yl)pentan-1-ol Chemical compound C1=CC=C2OC([C@@H](O)C(N)CCC)=NC2=C1 DYFLWZLTQLEOIZ-LYNSQETBSA-N 0.000 description 5
- MCKVHMPSBPHRDD-WWKKGYIRSA-N (2r)-2-amino-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonylpropanamide Chemical compound C([C@H](N)C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)S(=O)(=O)CC1=CC=CC=C1 MCKVHMPSBPHRDD-WWKKGYIRSA-N 0.000 description 5
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- 102000005927 Cysteine Proteases Human genes 0.000 description 5
- 108010005843 Cysteine Proteases Proteins 0.000 description 5
- OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical class N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 5
- 229950009215 phenylbutanoic acid Drugs 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 235000019345 sodium thiosulphate Nutrition 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 5
- DBAZNOUSKXILRL-AXDSSHIGSA-N (1s)-2-amino-1-(3-phenyl-1,2,4-oxadiazol-5-yl)butan-1-ol Chemical compound O1C([C@@H](O)C(N)CC)=NC(C=2C=CC=CC=2)=N1 DBAZNOUSKXILRL-AXDSSHIGSA-N 0.000 description 4
- ULAWACKYHXHXIE-VIFPVBQESA-N (2r)-3-(cyclopropylmethylsulfonyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CS(=O)(=O)CC1CC1 ULAWACKYHXHXIE-VIFPVBQESA-N 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- CZGUDAFCRRPGPG-UHFFFAOYSA-N 3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanoic acid Chemical compound OC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F CZGUDAFCRRPGPG-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 4
- 229910000071 diazene Inorganic materials 0.000 description 4
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 238000013178 mathematical model Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- BSSFXKBERWKTDS-UHFFFAOYSA-N tert-butyl n-[1-(5-ethyl-1,3,4-oxadiazol-2-yl)-1-hydroxybutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC(CC)C(O)C1=NN=C(CC)O1 BSSFXKBERWKTDS-UHFFFAOYSA-N 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- PRMXLQQEFUKYLE-MLWJPKLSSA-N (1s)-2-amino-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)butan-1-ol Chemical compound O1C([C@@H](O)C(N)CC)=NC(C2CC2)=N1 PRMXLQQEFUKYLE-MLWJPKLSSA-N 0.000 description 3
- LQMLKVZKWQBSEC-SNVBAGLBSA-N (2r)-2-methoxy-4-phenylbutanoic acid Chemical compound CO[C@@H](C(O)=O)CCC1=CC=CC=C1 LQMLKVZKWQBSEC-SNVBAGLBSA-N 0.000 description 3
- DEQMOMVDLREURK-JTQLQIEISA-N (2r)-3-benzylsulfanyl-2-[(5-nitro-1,3-thiazol-2-yl)amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC=1SC(=CN=1)[N+]([O-])=O)SCC1=CC=CC=C1 DEQMOMVDLREURK-JTQLQIEISA-N 0.000 description 3
- OWQPBYNBKQPXIC-VIFPVBQESA-N (2r)-3-benzylsulfonyl-2-hydroxypropanoic acid Chemical compound OC(=O)[C@@H](O)CS(=O)(=O)CC1=CC=CC=C1 OWQPBYNBKQPXIC-VIFPVBQESA-N 0.000 description 3
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
- VGGPKFXGWLUJJC-UHFFFAOYSA-N 2-amino-1-(1,3-benzothiazol-2-yl)pentan-1-ol Chemical compound C1=CC=C2SC(C(O)C(N)CCC)=NC2=C1 VGGPKFXGWLUJJC-UHFFFAOYSA-N 0.000 description 3
- DHNLWBALDJWTTH-UHFFFAOYSA-N 2-ethyl-1,3,4-oxadiazole Chemical compound CCC1=NN=CO1 DHNLWBALDJWTTH-UHFFFAOYSA-N 0.000 description 3
- MJUJAQLUQXCSRD-UHFFFAOYSA-N 2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound OC(=O)C(O)C(CC)NC(=O)OC(C)(C)C MJUJAQLUQXCSRD-UHFFFAOYSA-N 0.000 description 3
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 3
- IEUCCVZHHPPESY-UHFFFAOYSA-N 3-benzylsulfanyl-2-(2-nitroanilino)propanoic acid Chemical compound C=1C=CC=C([N+]([O-])=O)C=1NC(C(=O)O)CSCC1=CC=CC=C1 IEUCCVZHHPPESY-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241001024304 Mino Species 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- SCPOXVMCOGFNIX-RXVVDRJESA-N [(2s)-1-[[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl] morpholine-4-carboxylate Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)OC(=O)N1CCOCC1)C1CCCCC1 SCPOXVMCOGFNIX-RXVVDRJESA-N 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 235000019419 proteases Nutrition 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- NBDAUFXJXMBQRC-ZETCQYMHSA-N tert-butyl n-[(2s)-1-oxobutan-2-yl]carbamate Chemical compound CC[C@@H](C=O)NC(=O)OC(C)(C)C NBDAUFXJXMBQRC-ZETCQYMHSA-N 0.000 description 3
- RSMRLGVUDZWPMH-UHFFFAOYSA-N tert-butyl n-[1-hydroxy-1-([1,3]oxazolo[4,5-b]pyridin-2-yl)butan-2-yl]carbamate Chemical compound C1=CC=C2OC(C(O)C(NC(=O)OC(C)(C)C)CC)=NC2=N1 RSMRLGVUDZWPMH-UHFFFAOYSA-N 0.000 description 3
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- PCEIEQLJYDMRFZ-UHFFFAOYSA-N (1-cyanocyclopropyl)azanium;chloride Chemical compound Cl.N#CC1(N)CC1 PCEIEQLJYDMRFZ-UHFFFAOYSA-N 0.000 description 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 2
- MZEKOAKWBBNMBO-MHPPCMCBSA-N (1s)-2-amino-1-(1,3-benzoxazol-2-yl)butan-1-ol Chemical compound C1=CC=C2OC([C@@H](O)C(N)CC)=NC2=C1 MZEKOAKWBBNMBO-MHPPCMCBSA-N 0.000 description 2
- POQGCDJWNWOFAM-MSZQBOFLSA-N (1s)-2-amino-1-(5-ethyl-1,2,4-oxadiazol-3-yl)butan-1-ol Chemical class CCC(N)[C@H](O)C1=NOC(CC)=N1 POQGCDJWNWOFAM-MSZQBOFLSA-N 0.000 description 2
- YOBRUVQXEJBWIW-WAQLSPKVSA-N (2r)-2-amino-3-(cyclopropylmethylsulfonyl)-n-[(2s)-1-(5-ethyl-1,2,4-oxadiazol-3-yl)-1-hydroxybutan-2-yl]propanamide Chemical compound C([C@H](N)C(=O)N[C@@H](CC)C(O)C=1N=C(CC)ON=1)S(=O)(=O)CC1CC1 YOBRUVQXEJBWIW-WAQLSPKVSA-N 0.000 description 2
- WADTUTNNIIQRER-KSCSMHSMSA-N (2r)-2-amino-3-benzylsulfonyl-n-[(2s)-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-hydroxybutan-2-yl]propanamide Chemical compound C([C@H](N)C(=O)N[C@@H](CC)C(O)C=1ON=C(N=1)C1CC1)S(=O)(=O)CC1=CC=CC=C1 WADTUTNNIIQRER-KSCSMHSMSA-N 0.000 description 2
- CNPZJSDXOSSHRU-JENVPCQVSA-N (2r)-2-amino-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-(cyclopropylmethylsulfonyl)propanamide Chemical compound C([C@H](N)C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)S(=O)(=O)CC1CC1 CNPZJSDXOSSHRU-JENVPCQVSA-N 0.000 description 2
- MCKVHMPSBPHRDD-VQSBYGRUSA-N (2r)-2-amino-n-[1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonylpropanamide Chemical compound C([C@H](N)C(=O)NC(CCC)C(O)C=1OC2=CC=CC=C2N=1)S(=O)(=O)CC1=CC=CC=C1 MCKVHMPSBPHRDD-VQSBYGRUSA-N 0.000 description 2
- RNVYOZMPPCJCPH-SFHVURJKSA-N (2r)-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-2-tri(propan-2-yl)silyloxypropanoic acid Chemical compound CC(C)[Si](C(C)C)(C(C)C)O[C@H](C(O)=O)CS(=O)(=O)CC1=CC=CC=C1OC(F)F RNVYOZMPPCJCPH-SFHVURJKSA-N 0.000 description 2
- ZSEHYLRKLPSCBR-ZDUSSCGKSA-N (2r)-3-benzylsulfonyl-2-(morpholine-4-carbonyloxy)propanoic acid Chemical compound C([C@@H](C(=O)O)OC(=O)N1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 ZSEHYLRKLPSCBR-ZDUSSCGKSA-N 0.000 description 2
- FXDQSBOGQYWXKA-SFHVURJKSA-N (2r)-3-benzylsulfonyl-2-tri(propan-2-yl)silyloxypropanoic acid Chemical compound CC(C)[Si](C(C)C)(C(C)C)O[C@H](C(O)=O)CS(=O)(=O)CC1=CC=CC=C1 FXDQSBOGQYWXKA-SFHVURJKSA-N 0.000 description 2
- JKQXURXTJNVELI-ZDOMSUIMSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-(cyclopropylmethylsulfonyl)-2-(oxan-4-ylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)NC1CCOCC1)S(=O)(=O)CC1CC1 JKQXURXTJNVELI-ZDOMSUIMSA-N 0.000 description 2
- MJKYAHWDIWCPFN-NVPCEHRXSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfanyl-2-[(5-nitro-1,3-thiazol-2-yl)amino]propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)NC=1SC(=CN=1)[N+]([O-])=O)SCC1=CC=CC=C1 MJKYAHWDIWCPFN-NVPCEHRXSA-N 0.000 description 2
- MSXPOYVDHPKDPT-ZDOMSUIMSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-benzylsulfonyl-2-(dimethylamino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)N(C)C)S(=O)(=O)CC1=CC=CC=C1 MSXPOYVDHPKDPT-ZDOMSUIMSA-N 0.000 description 2
- DHILXLDATKGGIF-AWEZNQCLSA-N (2s)-2-(2-morpholin-4-yl-2-oxoethoxy)-4-phenylbutanoic acid Chemical compound C([C@@H](C(=O)O)OCC(=O)N1CCOCC1)CC1=CC=CC=C1 DHILXLDATKGGIF-AWEZNQCLSA-N 0.000 description 2
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 2
- VHNRDWWEOVUQRA-JENVPCQVSA-N (2s)-2-amino-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-3-thiophen-2-ylpropanamide Chemical compound C([C@H](N)C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)C1=CC=CS1 VHNRDWWEOVUQRA-JENVPCQVSA-N 0.000 description 2
- GXPWLXURDGFCCN-VIFPVBQESA-N (2s)-2-fluoro-4-phenylbutanoic acid Chemical compound OC(=O)[C@@H](F)CCC1=CC=CC=C1 GXPWLXURDGFCCN-VIFPVBQESA-N 0.000 description 2
- VHSLNJMKOAJSPK-DTIOYNMSSA-N (2s)-3-amino-n-benzyl-2-hydroxypentanamide Chemical compound CCC(N)[C@H](O)C(=O)NCC1=CC=CC=C1 VHSLNJMKOAJSPK-DTIOYNMSSA-N 0.000 description 2
- NIGLNFQRLXLABO-PMACEKPBSA-N (2s)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxopentan-2-yl]-2-(oxan-4-ylamino)-3-thiophen-2-ylpropanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(=O)C=1OC2=CC=CC=C2N=1)NC1CCOCC1)C1=CC=CS1 NIGLNFQRLXLABO-PMACEKPBSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 125000006017 1-propenyl group Chemical group 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- AJTVSSFTXWNIRG-UHFFFAOYSA-N 2-[bis(2-hydroxyethyl)amino]ethanesulfonic acid Chemical compound OCC[NH+](CCO)CCS([O-])(=O)=O AJTVSSFTXWNIRG-UHFFFAOYSA-N 0.000 description 2
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 2
- XFKYKTBPRBZDFG-UHFFFAOYSA-N 2-aminoacetonitrile;hydrochloride Chemical compound Cl.NCC#N XFKYKTBPRBZDFG-UHFFFAOYSA-N 0.000 description 2
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- GXKDVJFJBRCPPZ-UHFFFAOYSA-N 3-(cyclopropylmethylsulfanyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CSCC1CC1 GXKDVJFJBRCPPZ-UHFFFAOYSA-N 0.000 description 2
- GKUNHIBXFWZKOG-UHFFFAOYSA-N 3-benzylsulfonyl-2-(2-nitroanilino)propanoic acid Chemical compound C=1C=CC=C([N+]([O-])=O)C=1NC(C(=O)O)CS(=O)(=O)CC1=CC=CC=C1 GKUNHIBXFWZKOG-UHFFFAOYSA-N 0.000 description 2
- LIEPOZURJKCPRB-UHFFFAOYSA-N 3-cyclohexyl-2-hydroxy-n-[1-([1,3]oxazolo[4,5-b]pyridin-2-yl)-1-oxobutan-2-yl]propanamide Chemical compound N=1C2=NC=CC=C2OC=1C(=O)C(CC)NC(=O)C(O)CC1CCCCC1 LIEPOZURJKCPRB-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- OSKHEBDRYLYZPN-UHFFFAOYSA-N 4-amino-1-ethylpiperidine-4-carbonitrile Chemical compound CCN1CCC(N)(C#N)CC1 OSKHEBDRYLYZPN-UHFFFAOYSA-N 0.000 description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 2
- 108090000625 Cathepsin K Proteins 0.000 description 2
- 102000004171 Cathepsin K Human genes 0.000 description 2
- 229940122805 Cathepsin S inhibitor Drugs 0.000 description 2
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 2
- LXHNDYSVBOVADI-UGKGYDQZSA-N [(2r)-1-[[(2s)-1-(1,3-benzoxazol-2-yl)-1-oxobutan-2-yl]amino]-3-benzylsulfonyl-1-oxopropan-2-yl] morpholine-4-carboxylate Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C=1OC2=CC=CC=C2N=1)OC(=O)N1CCOCC1)S(=O)(=O)CC1=CC=CC=C1 LXHNDYSVBOVADI-UGKGYDQZSA-N 0.000 description 2
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 2
- CBQYDTGHHZVQTO-KRWDZBQOSA-N [(2s)-1-ethoxy-1-oxo-4-phenylbutan-2-yl] 4-nitrobenzoate Chemical compound C([C@@H](C(=O)OCC)OC(=O)C=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 CBQYDTGHHZVQTO-KRWDZBQOSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 2
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 description 2
- KOMDBNXFZQHCIS-UHFFFAOYSA-N benzyl 2,3,4,7-tetrahydroazepine-1-carboxylate Chemical compound C1CCC=CCN1C(=O)OCC1=CC=CC=C1 KOMDBNXFZQHCIS-UHFFFAOYSA-N 0.000 description 2
- MLOQDSPTAWUYJP-UHFFFAOYSA-N benzyl 4-azido-3-hydroxyazepane-1-carboxylate Chemical compound C1CCC(N=[N+]=[N-])C(O)CN1C(=O)OCC1=CC=CC=C1 MLOQDSPTAWUYJP-UHFFFAOYSA-N 0.000 description 2
- YIQIYQACMGRMHN-UHFFFAOYSA-N benzyl n-pent-4-enyl-n-prop-2-enylcarbamate Chemical compound C=CCCCN(CC=C)C(=O)OCC1=CC=CC=C1 YIQIYQACMGRMHN-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 108010085937 benzyloxycarbonyl-phenylalanylarginine-4-methylcoumaryl-7-amide Proteins 0.000 description 2
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 229960002303 citric acid monohydrate Drugs 0.000 description 2
- 229940126086 compound 21 Drugs 0.000 description 2
- 229940125833 compound 23 Drugs 0.000 description 2
- 229940125851 compound 27 Drugs 0.000 description 2
- 229940127204 compound 29 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- ZJYKSSGYDPNKQS-LLVKDONJSA-N ethyl (2r)-2-hydroxy-4-phenylbutanoate Chemical compound CCOC(=O)[C@H](O)CCC1=CC=CC=C1 ZJYKSSGYDPNKQS-LLVKDONJSA-N 0.000 description 2
- DMSUUOVMAXTZEF-GFCCVEGCSA-N ethyl (2r)-2-methoxy-4-phenylbutanoate Chemical compound CCOC(=O)[C@H](OC)CCC1=CC=CC=C1 DMSUUOVMAXTZEF-GFCCVEGCSA-N 0.000 description 2
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- YYSWIOVOKHEOCZ-UHFFFAOYSA-N methoxymethyl 3-benzylsulfonyl-2-hydroxypropanoate Chemical compound COCOC(=O)C(O)CS(=O)(=O)CC1=CC=CC=C1 YYSWIOVOKHEOCZ-UHFFFAOYSA-N 0.000 description 2
- LQQGOBWFRAFWEJ-HNNXBMFYSA-N methyl (2s)-2-(2-morpholin-4-yl-2-oxoethoxy)-4-phenylbutanoate Chemical compound C([C@@H](C(=O)OC)OCC(=O)N1CCOCC1)CC1=CC=CC=C1 LQQGOBWFRAFWEJ-HNNXBMFYSA-N 0.000 description 2
- VBYOZNMHXQWSJY-JTQLQIEISA-N methyl (2s)-2-hydroxy-4-phenylbutanoate Chemical compound COC(=O)[C@@H](O)CCC1=CC=CC=C1 VBYOZNMHXQWSJY-JTQLQIEISA-N 0.000 description 2
- DQWADVKQCYOJTK-VIFPVBQESA-N methyl (2s)-3-cyclohexyl-2-hydroxypropanoate Chemical compound COC(=O)[C@@H](O)CC1CCCCC1 DQWADVKQCYOJTK-VIFPVBQESA-N 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 102200025791 rs179363876 Human genes 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- NAEOBYXQIPVGKZ-UHFFFAOYSA-N tert-butyl 2-[amino-hydroxy-(5-pyridin-2-yl-1,3-oxazol-2-yl)methyl]butanoate Chemical compound O1C(C(N)(O)C(C(=O)OC(C)(C)C)CC)=NC=C1C1=CC=CC=N1 NAEOBYXQIPVGKZ-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- CFGUUKMNYCDMIQ-IJXZTRCJSA-N tert-butyl n-[(2s)-1-[[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]amino]-1-oxo-3-thiophen-2-ylpropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N[C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)NC(=O)OC(C)(C)C)C1=CC=CS1 CFGUUKMNYCDMIQ-IJXZTRCJSA-N 0.000 description 2
- NLOXUGUEIAKRJL-MLCCFXAWSA-N tert-butyl n-[(2s)-1-hydroxy-4-phenyl-1-(1,3-thiazol-2-yl)butan-2-yl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)C(O)C=1SC=CN=1)CC1=CC=CC=C1 NLOXUGUEIAKRJL-MLCCFXAWSA-N 0.000 description 2
- UVWYYZKVWACGSO-AWEZNQCLSA-N tert-butyl n-[(2s)-1-oxo-4-phenyl-1-(1,3-thiazol-2-yl)butan-2-yl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)C(=O)C=1SC=CN=1)CC1=CC=CC=C1 UVWYYZKVWACGSO-AWEZNQCLSA-N 0.000 description 2
- POQXUDBUMCSVHF-QMMMGPOBSA-N tert-butyl n-[(2s)-1-oxopentan-2-yl]carbamate Chemical compound CCC[C@@H](C=O)NC(=O)OC(C)(C)C POQXUDBUMCSVHF-QMMMGPOBSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 229960000281 trometamol Drugs 0.000 description 2
- QYYZXEPEVBXNNA-QGZVFWFLSA-N (1R)-2-acetyl-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-methylsulfonyl-1,3-dihydroisoindole-1-carboxamide Chemical compound C(C)(=O)N1[C@H](C2=CC=C(C=C2C1)S(=O)(=O)C)C(=O)NC1=CC=C(C=C1)C(C(F)(F)F)(C(F)(F)F)O QYYZXEPEVBXNNA-QGZVFWFLSA-N 0.000 description 1
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
- IKTCVHBXJPYAPP-MHPPCMCBSA-N (1s)-2-amino-1-(1,3-benzothiazol-2-yl)butan-1-ol Chemical compound C1=CC=C2SC([C@@H](O)C(N)CC)=NC2=C1 IKTCVHBXJPYAPP-MHPPCMCBSA-N 0.000 description 1
- ADKDTZDHGNAFAD-CRSWKAPQSA-N (1s)-2-amino-1-(5-ethyl-1,2,4-oxadiazol-3-yl)butan-1-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCC(N)[C@H](O)C1=NOC(CC)=N1 ADKDTZDHGNAFAD-CRSWKAPQSA-N 0.000 description 1
- VGFUWKUEUFAMNM-XDKWHASVSA-N (1s)-2-amino-1-([1,3]oxazolo[4,5-b]pyridin-2-yl)butan-1-ol Chemical compound C1=CC=C2OC([C@@H](O)C(N)CC)=NC2=N1 VGFUWKUEUFAMNM-XDKWHASVSA-N 0.000 description 1
- VAJDTCWANLDTPY-KIYNQFGBSA-N (1s)-2-amino-4-phenyl-1-(1,3-thiazol-2-yl)butan-1-ol Chemical compound NC([C@H](O)C=1SC=CN=1)CCC1=CC=CC=C1 VAJDTCWANLDTPY-KIYNQFGBSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- LCQHMJSLVVXOSB-NOLJZWGESA-N (2R,5S,6S)-2-[[2-(difluoromethoxy)phenyl]methylsulfonylmethyl]-6-ethoxy-5-ethylmorpholin-3-one Chemical compound O=C1N[C@@H](CC)[C@@H](OCC)O[C@H]1CS(=O)(=O)CC1=CC=CC=C1OC(F)F LCQHMJSLVVXOSB-NOLJZWGESA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- ATVFTGTXIUDKIZ-YFKPBYRVSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-sulfanylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CS)C(O)=O ATVFTGTXIUDKIZ-YFKPBYRVSA-N 0.000 description 1
- FBDPHMXPELRJAM-AHTKWCMKSA-N (2r)-2-amino-3-benzylsulfonyl-n-[(2s)-1-hydroxy-4-phenyl-1-(1,3-thiazol-2-yl)butan-2-yl]propanamide Chemical compound C([C@H](N)C(=O)N[C@@H](CCC=1C=CC=CC=1)C(O)C=1SC=CN=1)S(=O)(=O)CC1=CC=CC=C1 FBDPHMXPELRJAM-AHTKWCMKSA-N 0.000 description 1
- NAYMVQDFSGPBBZ-VIQWUECVSA-N (2r)-2-amino-3-benzylsulfonyl-n-[1-hydroxy-1-(3-phenyl-1,2,4-oxadiazol-5-yl)butan-2-yl]propanamide Chemical compound C([C@H](N)C(=O)NC(CC)C(O)C=1ON=C(N=1)C=1C=CC=CC=1)S(=O)(=O)CC1=CC=CC=C1 NAYMVQDFSGPBBZ-VIQWUECVSA-N 0.000 description 1
- BLZOSHBZDVNUDY-RXMQYKEDSA-N (2r)-2-amino-n-methoxy-n-methylbutanamide Chemical compound CC[C@@H](N)C(=O)N(C)OC BLZOSHBZDVNUDY-RXMQYKEDSA-N 0.000 description 1
- JNJCEALGCZSIGB-SECBINFHSA-N (2r)-2-hydroxy-4-phenylbutanoic acid Chemical compound OC(=O)[C@H](O)CCC1=CC=CC=C1 JNJCEALGCZSIGB-SECBINFHSA-N 0.000 description 1
- UIKRLQWERZKQNI-NSHDSACASA-N (2r)-3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CS(=O)(=O)CC1=CC=CC=C1OC(F)F UIKRLQWERZKQNI-NSHDSACASA-N 0.000 description 1
- MKWMCIYAWFUTKR-LBPRGKRZSA-N (2r)-3-benzylsulfonyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CS(=O)(=O)CC1=CC=CC=C1 MKWMCIYAWFUTKR-LBPRGKRZSA-N 0.000 description 1
- ZJACADWPDLENNQ-WBVHZDCISA-N (2r)-n-[(2r)-1-(1,3-benzothiazol-2-yl)-1-oxobutan-2-yl]-3-benzylsulfonyl-2-hydroxypropanamide Chemical compound C([C@H](O)C(=O)N[C@H](CC)C(=O)C=1SC2=CC=CC=C2N=1)S(=O)(=O)CC1=CC=CC=C1 ZJACADWPDLENNQ-WBVHZDCISA-N 0.000 description 1
- CNEYINWZGXRPQN-HKJCUSPOSA-N (2r)-n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxybutan-2-yl]-3-benzylsulfonyl-2-(2-nitroanilino)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(O)C=1OC2=CC=CC=C2N=1)NC=1C(=CC=CC=1)[N+]([O-])=O)S(=O)(=O)CC1=CC=CC=C1 CNEYINWZGXRPQN-HKJCUSPOSA-N 0.000 description 1
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
- SPFMQWBKVUQXJV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;hydrate Chemical compound O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O SPFMQWBKVUQXJV-BTVCFUMJSA-N 0.000 description 1
- CAAQAOPBTSEEPE-YFKPBYRVSA-N (2s)-2-(hydroxymethyl)pyrrolidine-1-carboxylic acid Chemical compound OC[C@@H]1CCCN1C(O)=O CAAQAOPBTSEEPE-YFKPBYRVSA-N 0.000 description 1
- OJLISTAWQHSIHL-VIFPVBQESA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-thiophen-2-ylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=CS1 OJLISTAWQHSIHL-VIFPVBQESA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- IKTCVHBXJPYAPP-BYDSUWOYSA-N (2s)-2-amino-1-(1,3-benzothiazol-2-yl)butan-1-ol Chemical compound C1=CC=C2SC(C(O)[C@@H](N)CC)=NC2=C1 IKTCVHBXJPYAPP-BYDSUWOYSA-N 0.000 description 1
- GZVQTYMOEXXNHA-KNVGNIICSA-N (2s)-2-amino-1-(1,3-benzoxazol-2-yl)-4-phenylbutan-1-ol Chemical compound C([C@H](N)C(O)C=1OC2=CC=CC=C2N=1)CC1=CC=CC=C1 GZVQTYMOEXXNHA-KNVGNIICSA-N 0.000 description 1
- DYFLWZLTQLEOIZ-YMNIQAILSA-N (2s)-2-amino-1-(1,3-benzoxazol-2-yl)pentan-1-ol Chemical compound C1=CC=C2OC(C(O)[C@@H](N)CCC)=NC2=C1 DYFLWZLTQLEOIZ-YMNIQAILSA-N 0.000 description 1
- SGUZJMYNTCMEOG-VIFPVBQESA-N (2s)-2-amino-4,4-difluoro-5-phenylpentanoic acid Chemical compound OC(=O)[C@@H](N)CC(F)(F)CC1=CC=CC=C1 SGUZJMYNTCMEOG-VIFPVBQESA-N 0.000 description 1
- JCBPETKZIGVZRE-BYPYZUCNSA-N (2s)-2-aminobutan-1-ol Chemical compound CC[C@H](N)CO JCBPETKZIGVZRE-BYPYZUCNSA-N 0.000 description 1
- ULAXUFGARZZKTK-YFKPBYRVSA-N (2s)-2-aminopentan-1-ol Chemical compound CCC[C@H](N)CO ULAXUFGARZZKTK-YFKPBYRVSA-N 0.000 description 1
- FTUNKDBKIAAXTR-LBPRGKRZSA-N (2s)-3-cyclohexyl-2-(morpholine-4-carbonyloxy)propanoic acid Chemical compound C([C@@H](C(=O)O)OC(=O)N1CCOCC1)C1CCCCC1 FTUNKDBKIAAXTR-LBPRGKRZSA-N 0.000 description 1
- ZXSHWDDJZJZNSH-VIFPVBQESA-N (2s)-4,4-difluoro-2-hydroxy-5-phenylpentanoic acid Chemical compound OC(=O)[C@@H](O)CC(F)(F)CC1=CC=CC=C1 ZXSHWDDJZJZNSH-VIFPVBQESA-N 0.000 description 1
- DJNNKOSWQYSRTL-JTQLQIEISA-N (2s)-n-(cyanomethyl)-3-cyclohexyl-2-hydroxypropanamide Chemical compound N#CCNC(=O)[C@@H](O)CC1CCCCC1 DJNNKOSWQYSRTL-JTQLQIEISA-N 0.000 description 1
- ZJACADWPDLENNQ-DOTOQJQBSA-N (2s)-n-[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxobutan-2-yl]-3-benzylsulfonyl-2-hydroxypropanamide Chemical compound C([C@@H](O)C(=O)N[C@@H](CC)C(=O)C=1SC2=CC=CC=C2N=1)S(=O)(=O)CC1=CC=CC=C1 ZJACADWPDLENNQ-DOTOQJQBSA-N 0.000 description 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
- GNQLTCVBSGVGHC-UHFFFAOYSA-N (3,4-difluorophenyl)methanol Chemical compound OCC1=CC=C(F)C(F)=C1 GNQLTCVBSGVGHC-UHFFFAOYSA-N 0.000 description 1
- OEGPRYNGFWGMMV-UHFFFAOYSA-N (3,4-dimethoxyphenyl)methanol Chemical compound COC1=CC=C(CO)C=C1OC OEGPRYNGFWGMMV-UHFFFAOYSA-N 0.000 description 1
- HHWYYUUOGAUCKX-UHFFFAOYSA-N (3-fluoro-4-methoxyphenyl)methanol Chemical compound COC1=CC=C(CO)C=C1F HHWYYUUOGAUCKX-UHFFFAOYSA-N 0.000 description 1
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
- JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 1
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical class O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
- JHHZLHWJQPUNKB-BYPYZUCNSA-N (3s)-pyrrolidin-3-ol Chemical compound O[C@H]1CCNC1 JHHZLHWJQPUNKB-BYPYZUCNSA-N 0.000 description 1
- GEZMEIHVFSWOCA-UHFFFAOYSA-N (4-fluorophenyl)methanol Chemical compound OCC1=CC=C(F)C=C1 GEZMEIHVFSWOCA-UHFFFAOYSA-N 0.000 description 1
- FEOMFFKZOZMBKD-UHFFFAOYSA-N (4-phenoxyphenyl)methanol Chemical compound C1=CC(CO)=CC=C1OC1=CC=CC=C1 FEOMFFKZOZMBKD-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- DZKRDHLYQRTDBU-UPHRSURJSA-N (z)-but-2-enediperoxoic acid Chemical compound OOC(=O)\C=C/C(=O)OO DZKRDHLYQRTDBU-UPHRSURJSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- FGWYWKIOMUZSQF-UHFFFAOYSA-N 1,1,1-triethoxypropane Chemical compound CCOC(CC)(OCC)OCC FGWYWKIOMUZSQF-UHFFFAOYSA-N 0.000 description 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- UIVATUPCWVUVIM-UHFFFAOYSA-N 1-aminocyclopropane-1-carbonitrile Chemical compound N#CC1(N)CC1 UIVATUPCWVUVIM-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 1
- PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 1
- AMMPLVWPWSYRDR-UHFFFAOYSA-N 1-methylbicyclo[2.2.2]oct-2-ene-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(C)C=C2 AMMPLVWPWSYRDR-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- GRNOZCCBOFGDCL-UHFFFAOYSA-N 2,2,2-trichloroacetyl isocyanate Chemical compound ClC(Cl)(Cl)C(=O)N=C=O GRNOZCCBOFGDCL-UHFFFAOYSA-N 0.000 description 1
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- RNXIVWTWKFJRGM-UHFFFAOYSA-N 2,2-difluoro-4-phenylbutanoic acid Chemical compound OC(=O)C(F)(F)CCC1=CC=CC=C1 RNXIVWTWKFJRGM-UHFFFAOYSA-N 0.000 description 1
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical class OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- BMTSZVZQNMNPCT-UHFFFAOYSA-N 2-aminopyridin-3-ol Chemical compound NC1=NC=CC=C1O BMTSZVZQNMNPCT-UHFFFAOYSA-N 0.000 description 1
- LBORPQYMABOVPW-UHFFFAOYSA-N 2-benzoyl-3-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC(O)=C1C(=O)C1=CC=CC=C1 LBORPQYMABOVPW-UHFFFAOYSA-N 0.000 description 1
- RXNZFHIEDZEUQM-UHFFFAOYSA-N 2-bromo-1,3-thiazole Chemical compound BrC1=NC=CS1 RXNZFHIEDZEUQM-UHFFFAOYSA-N 0.000 description 1
- ANIJFZVZXZQFDH-UHFFFAOYSA-N 2-bromo-5-nitro-1,3-thiazole Chemical compound [O-][N+](=O)C1=CN=C(Br)S1 ANIJFZVZXZQFDH-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- YMQRPXBBBOXHNZ-UHFFFAOYSA-N 2-chloro-1-morpholin-4-ylethanone Chemical compound ClCC(=O)N1CCOCC1 YMQRPXBBBOXHNZ-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- ZWVHTXAYIKBMEE-UHFFFAOYSA-N 2-hydroxyacetophenone Chemical compound OCC(=O)C1=CC=CC=C1 ZWVHTXAYIKBMEE-UHFFFAOYSA-N 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 description 1
- MGOLNIXAPIAKFM-UHFFFAOYSA-N 2-isocyanato-2-methylpropane Chemical compound CC(C)(C)N=C=O MGOLNIXAPIAKFM-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- KXRQQPIHUMSJSS-UHFFFAOYSA-N 2-piperidin-2-ylpyridine Chemical group N1CCCCC1C1=CC=CC=N1 KXRQQPIHUMSJSS-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- BNBQQYFXBLBYJK-UHFFFAOYSA-N 2-pyridin-2-yl-1,3-oxazole Chemical compound C1=COC(C=2N=CC=CC=2)=N1 BNBQQYFXBLBYJK-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
- HQURMOWWAFAJBN-UHFFFAOYSA-N 3-[3-[[2-(difluoromethoxy)phenyl]methylsulfonyl]propanoylamino]-2-oxo-n-pyridin-3-ylpentanamide Chemical compound C=1C=CN=CC=1NC(=O)C(=O)C(CC)NC(=O)CCS(=O)(=O)CC1=CC=CC=C1OC(F)F HQURMOWWAFAJBN-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OWQPBYNBKQPXIC-UHFFFAOYSA-N 3-benzylsulfonyl-2-hydroxypropanoic acid Chemical compound OC(=O)C(O)CS(=O)(=O)CC1=CC=CC=C1 OWQPBYNBKQPXIC-UHFFFAOYSA-N 0.000 description 1
- BMBCBBLMHJNKQR-UHFFFAOYSA-N 3-benzylsulfonylpropanamide Chemical compound NC(=O)CCS(=O)(=O)CC1=CC=CC=C1 BMBCBBLMHJNKQR-UHFFFAOYSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- YJKWVYDYBPQFEG-UHFFFAOYSA-N 3-cyclohexyl-2-hydroxy-n-[1-hydroxy-1-([1,3]oxazolo[4,5-b]pyridin-2-yl)butan-2-yl]propanamide Chemical compound N=1C2=NC=CC=C2OC=1C(O)C(CC)NC(=O)C(O)CC1CCCCC1 YJKWVYDYBPQFEG-UHFFFAOYSA-N 0.000 description 1
- WMHUKKRNWMPXKB-UHFFFAOYSA-N 3-cyclohexyl-2-hydroxypropanoic acid Chemical compound OC(=O)C(O)CC1CCCCC1 WMHUKKRNWMPXKB-UHFFFAOYSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- ZXSHWDDJZJZNSH-UHFFFAOYSA-N 4,4-difluoro-2-hydroxy-5-phenylpentanoic acid Chemical compound OC(=O)C(O)CC(F)(F)CC1=CC=CC=C1 ZXSHWDDJZJZNSH-UHFFFAOYSA-N 0.000 description 1
- QYBXZYYECZFQRX-UHFFFAOYSA-N 4-(morpholin-4-ylmethyl)benzoic acid Chemical class C1=CC(C(=O)O)=CC=C1CN1CCOCC1 QYBXZYYECZFQRX-UHFFFAOYSA-N 0.000 description 1
- CHZMEOYZCMOGKK-UHFFFAOYSA-N 4-amino-1-ethylpiperidine-4-carbonitrile;hydrochloride Chemical compound Cl.CCN1CCC(N)(C#N)CC1 CHZMEOYZCMOGKK-UHFFFAOYSA-N 0.000 description 1
- PIXPZAQNJHLAPB-UHFFFAOYSA-N 4-aminooxane-4-carbonitrile;hydrochloride Chemical compound Cl.N#CC1(N)CCOCC1 PIXPZAQNJHLAPB-UHFFFAOYSA-N 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 1
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
- AWQSAIIDOMEEOD-UHFFFAOYSA-N 5,5-Dimethyl-4-(3-oxobutyl)dihydro-2(3H)-furanone Chemical compound CC(=O)CCC1CC(=O)OC1(C)C AWQSAIIDOMEEOD-UHFFFAOYSA-N 0.000 description 1
- LPNANKDXVBMDKE-UHFFFAOYSA-N 5-bromopent-1-ene Chemical compound BrCCCC=C LPNANKDXVBMDKE-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006448 Bronchiolitis Diseases 0.000 description 1
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 108090000624 Cathepsin L Proteins 0.000 description 1
- 102000004172 Cathepsin L Human genes 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229940126639 Compound 33 Drugs 0.000 description 1
- 229940127007 Compound 39 Drugs 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000898449 Homo sapiens Cathepsin B Proteins 0.000 description 1
- 101000761509 Homo sapiens Cathepsin K Proteins 0.000 description 1
- 101000983583 Homo sapiens Procathepsin L Proteins 0.000 description 1
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
- 240000005125 Myrtus communis Species 0.000 description 1
- 235000013418 Myrtus communis Nutrition 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010035742 Pneumonitis Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- GHBAYRBVXCRIHT-VIFPVBQESA-N S-benzyl-L-cysteine zwitterion Chemical compound OC(=O)[C@@H](N)CSCC1=CC=CC=C1 GHBAYRBVXCRIHT-VIFPVBQESA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- FNYLWPVRPXGIIP-UHFFFAOYSA-N Triamterene Chemical group NC1=NC2=NC(N)=NC(N)=C2N=C1C1=CC=CC=C1 FNYLWPVRPXGIIP-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- HLFHCCVHNQCXLZ-YFKPBYRVSA-N [(2s)-1-oxopentan-2-yl]carbamic acid Chemical compound CCC[C@@H](C=O)NC(O)=O HLFHCCVHNQCXLZ-YFKPBYRVSA-N 0.000 description 1
- HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 1
- WDQHNOPSSYGXKB-UHFFFAOYSA-N [2-(difluoromethoxy)phenyl]methanethiol Chemical compound FC(F)OC1=CC=CC=C1CS WDQHNOPSSYGXKB-UHFFFAOYSA-N 0.000 description 1
- GPIBKUJXKCEZOH-UHFFFAOYSA-M [Cl-].CC(C)[Mg+] Chemical compound [Cl-].CC(C)[Mg+] GPIBKUJXKCEZOH-UHFFFAOYSA-M 0.000 description 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- VNEMVKOXLBIWTB-UHFFFAOYSA-N aminomethyl benzoate Chemical class NCOC(=O)C1=CC=CC=C1 VNEMVKOXLBIWTB-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- MXOQNVMDKHLYCZ-UHFFFAOYSA-N benzamidoxime Chemical compound ON=C(N)C1=CC=CC=C1 MXOQNVMDKHLYCZ-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- AQIHMSVIAGNIDM-UHFFFAOYSA-N benzoyl bromide Chemical compound BrC(=O)C1=CC=CC=C1 AQIHMSVIAGNIDM-UHFFFAOYSA-N 0.000 description 1
- DWKDPFXZJQTJHM-UHFFFAOYSA-N benzyl 4-amino-3-hydroxyazepane-1-carboxylate Chemical compound C1C(O)C(N)CCCN1C(=O)OCC1=CC=CC=C1 DWKDPFXZJQTJHM-UHFFFAOYSA-N 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- VCOVUYXJMHMVNV-FMYROPPKSA-N benzyl n-[(2s)-1-[[(2s)-1-[[(2s)-5-(diaminomethylideneamino)-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound N([C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NC=1C=C2OC(=O)C=C(C)C2=CC=1)C(=O)OCC1=CC=CC=C1 VCOVUYXJMHMVNV-FMYROPPKSA-N 0.000 description 1
- OSLGKRDOEMLAJV-UHFFFAOYSA-N benzyl n-prop-2-enylcarbamate Chemical compound C=CCNC(=O)OCC1=CC=CC=C1 OSLGKRDOEMLAJV-UHFFFAOYSA-N 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- PNPBGYBHLCEVMK-UHFFFAOYSA-L benzylidene(dichloro)ruthenium;tricyclohexylphosphane Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1P(C1CCCCC1)C1CCCCC1.C1CCCCC1P(C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-L 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 description 1
- OGODKNYCTJYXFF-UHFFFAOYSA-N bis(4-methylbenzoyl) 2,3-dihydroxybutanedioate Chemical class C1=CC(C)=CC=C1C(=O)OC(=O)C(O)C(O)C(=O)OC(=O)C1=CC=C(C)C=C1 OGODKNYCTJYXFF-UHFFFAOYSA-N 0.000 description 1
- SIOVKLKJSOKLIF-UHFFFAOYSA-N bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)OC(C)=N[Si](C)(C)C SIOVKLKJSOKLIF-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125878 compound 36 Drugs 0.000 description 1
- 229940125807 compound 37 Drugs 0.000 description 1
- 229940127573 compound 38 Drugs 0.000 description 1
- 229940126540 compound 41 Drugs 0.000 description 1
- 229940125936 compound 42 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 201000010251 cutis laxa Diseases 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- CGZZMOTZOONQIA-UHFFFAOYSA-N cycloheptanone Chemical compound O=C1CCCCCC1 CGZZMOTZOONQIA-UHFFFAOYSA-N 0.000 description 1
- HJZLEGIHUQOJBA-UHFFFAOYSA-N cyclohexane propionic acid Chemical compound OC(=O)CCC1CCCCC1 HJZLEGIHUQOJBA-UHFFFAOYSA-N 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical class OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004980 cyclopropylene group Chemical group 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 229960000673 dextrose monohydrate Drugs 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000004982 dihaloalkyl group Chemical group 0.000 description 1
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 150000004662 dithiols Chemical class 0.000 description 1
- ZOKYTRIEIDWYSG-UHFFFAOYSA-N dodec-5-ene Chemical group CCCCCCC=CCCCC ZOKYTRIEIDWYSG-UHFFFAOYSA-N 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 102000053907 human CTSB Human genes 0.000 description 1
- 102000049698 human CTSK Human genes 0.000 description 1
- 102000050937 human CTSL Human genes 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000000752 ionisation method Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000004500 isothiazol-4-yl group Chemical group S1N=CC(=C1)* 0.000 description 1
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000036546 leukodystrophy Diseases 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 229910052751 metal Chemical group 0.000 description 1
- 239000002184 metal Chemical group 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- VBYOZNMHXQWSJY-SNVBAGLBSA-N methyl (2r)-2-hydroxy-4-phenylbutanoate Chemical compound COC(=O)[C@H](O)CCC1=CC=CC=C1 VBYOZNMHXQWSJY-SNVBAGLBSA-N 0.000 description 1
- OSDXSOSJRPQCHJ-XVNBXDOJSA-N methyl 3-(3,4-dihydroxyphenyl)-3-[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxypropanoate Chemical compound C=1C=C(O)C(O)=CC=1C(CC(=O)OC)OC(=O)\C=C\C1=CC=C(O)C(O)=C1 OSDXSOSJRPQCHJ-XVNBXDOJSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- LPWAKYISHIZIPO-UHFFFAOYSA-N morpholin-4-ylmethyl benzoate Chemical class C=1C=CC=CC=1C(=O)OCN1CCOCC1 LPWAKYISHIZIPO-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- OMCUPXRCMTUDHI-UHFFFAOYSA-N n'-hydroxycyclopropanecarboximidamide Chemical compound ON=C(N)C1CC1 OMCUPXRCMTUDHI-UHFFFAOYSA-N 0.000 description 1
- HKTDZWWXGAQVIL-UHFFFAOYSA-N n-(cyanomethyl)-3-cyclohexylpropanamide Chemical compound N#CCNC(=O)CCC1CCCCC1 HKTDZWWXGAQVIL-UHFFFAOYSA-N 0.000 description 1
- ZJACADWPDLENNQ-MYJWUSKBSA-N n-[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxobutan-2-yl]-3-benzylsulfonyl-2-hydroxypropanamide Chemical compound N([C@@H](CC)C(=O)C=1SC2=CC=CC=C2N=1)C(=O)C(O)CS(=O)(=O)CC1=CC=CC=C1 ZJACADWPDLENNQ-MYJWUSKBSA-N 0.000 description 1
- HJBILRKEBVFKRN-LROBGIAVSA-N n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxypentan-2-yl]-2,2-difluoro-5-phenylpentanamide Chemical compound N([C@@H](CCC)C(O)C=1OC2=CC=CC=C2N=1)C(=O)C(F)(F)CCCC1=CC=CC=C1 HJBILRKEBVFKRN-LROBGIAVSA-N 0.000 description 1
- ZJACADWPDLENNQ-UHFFFAOYSA-N n-[1-(1,3-benzothiazol-2-yl)-1-oxobutan-2-yl]-3-benzylsulfonyl-2-hydroxypropanamide Chemical compound N=1C2=CC=CC=C2SC=1C(=O)C(CC)NC(=O)C(O)CS(=O)(=O)CC1=CC=CC=C1 ZJACADWPDLENNQ-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- ZHCAAFJSYLFLPX-UHFFFAOYSA-N nitrocyclohexatriene Chemical group [O-][N+](=O)C1=CC=C=C[CH]1 ZHCAAFJSYLFLPX-UHFFFAOYSA-N 0.000 description 1
- 150000002829 nitrogen Chemical group 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- CXLGNJCMPWUZKM-UHFFFAOYSA-N oxane-4-carbaldehyde Chemical compound O=CC1CCOCC1 CXLGNJCMPWUZKM-UHFFFAOYSA-N 0.000 description 1
- 125000005188 oxoalkyl group Chemical group 0.000 description 1
- YNOGYQAEJGADFJ-UHFFFAOYSA-N oxolan-2-ylmethanamine Chemical compound NCC1CCCO1 YNOGYQAEJGADFJ-UHFFFAOYSA-N 0.000 description 1
- MEBLRZKPLXIWCO-UHFFFAOYSA-N oxolan-2-ylmethylcarbamic acid Chemical compound OC(=O)NCC1CCCO1 MEBLRZKPLXIWCO-UHFFFAOYSA-N 0.000 description 1
- XEEVLJKYYUVTRC-UHFFFAOYSA-N oxomalonic acid Chemical compound OC(=O)C(=O)C(O)=O XEEVLJKYYUVTRC-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 208000022256 primary systemic amyloidosis Diseases 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical compound [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical class [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- CLWCTACKHJFWBV-MLWJPKLSSA-N tert-butyl 2-[(s)-amino(hydroxy)methyl]butanoate Chemical compound CCC([C@@H](N)O)C(=O)OC(C)(C)C CLWCTACKHJFWBV-MLWJPKLSSA-N 0.000 description 1
- PEQGOTIXJMEPEH-FHWLQOOXSA-N tert-butyl N-[(2R)-3-benzylsulfonyl-1-[[(1S,2S)-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-hydroxybutan-2-yl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C(C)(C)(C)OC(N[C@@H](CS(=O)(=O)CC1=CC=CC=C1)C(N[C@@H](CC)[C@H](O)C1=NC(=NO1)C1CC1)=O)=O PEQGOTIXJMEPEH-FHWLQOOXSA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- AMWBULKKLCAABK-UHFFFAOYSA-N tert-butyl n-(1-cyano-1-hydroxybutan-2-yl)carbamate Chemical compound N#CC(O)C(CC)NC(=O)OC(C)(C)C AMWBULKKLCAABK-UHFFFAOYSA-N 0.000 description 1
- UETSWVCUPQBUGT-MRVPVSSYSA-N tert-butyl n-[(2r)-1-[methoxy(methyl)amino]-1-oxobutan-2-yl]carbamate Chemical compound CON(C)C(=O)[C@@H](CC)NC(=O)OC(C)(C)C UETSWVCUPQBUGT-MRVPVSSYSA-N 0.000 description 1
- ZXTDUIJJUKOALU-NKUHCKNESA-N tert-butyl n-[(2s)-1-(1,3-benzoxazol-2-yl)-1-hydroxybutan-2-yl]carbamate Chemical compound C1=CC=C2OC(C(O)[C@@H](NC(=O)OC(C)(C)C)CC)=NC2=C1 ZXTDUIJJUKOALU-NKUHCKNESA-N 0.000 description 1
- UFEIHLFBTRLWSQ-PEHGTWAWSA-N tert-butyl n-[(2s)-1-(5-ethyl-1,2,4-oxadiazol-3-yl)-1-hydroxybutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](CC)C(O)C1=NOC(CC)=N1 UFEIHLFBTRLWSQ-PEHGTWAWSA-N 0.000 description 1
- XCNAWAXVHWFUSF-AWEZNQCLSA-N tert-butyl n-[(2s)-1-[methoxy(methyl)amino]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)N(C)OC)CCC1=CC=CC=C1 XCNAWAXVHWFUSF-AWEZNQCLSA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- LHJCZOXMCGQVDQ-UHFFFAOYSA-N tri(propan-2-yl)silyl trifluoromethanesulfonate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OS(=O)(=O)C(F)(F)F LHJCZOXMCGQVDQ-UHFFFAOYSA-N 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/30—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms
- C07C233/31—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
- C07C255/29—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton containing cyano groups and acylated amino groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
- C07C255/44—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms at least one of the singly-bound nitrogen atoms being acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C255/46—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of non-condensed rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/12—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/24—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
- C07C317/46—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
- C07D211/66—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having a hetero atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/08—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/12—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/28—Radicals substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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
- C07D277/82—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members 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
- C07D309/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Tropical Medicine & Parasitology (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Furan Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrane Compounds (AREA)
- Pyrrole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US29530101P | 2001-06-01 | 2001-06-01 | |
PCT/US2002/017411 WO2002098850A2 (en) | 2001-06-01 | 2002-06-03 | Chemical compounds and pharmaceutical compositions as cathepsin s inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20030995A2 true HRP20030995A2 (en) | 2005-08-31 |
Family
ID=23137113
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20030995A HRP20030995A2 (en) | 2001-06-01 | 2003-11-28 | Novel compounds and compositions as cathepsin inhibitors |
Country Status (18)
Country | Link |
---|---|
US (1) | US20040142999A1 (ja) |
EP (1) | EP1397340A2 (ja) |
JP (1) | JP2004535422A (ja) |
KR (1) | KR20040015725A (ja) |
CN (1) | CN1512983A (ja) |
AU (1) | AU2002305790B2 (ja) |
BR (1) | BR0210912A (ja) |
CA (1) | CA2448418A1 (ja) |
EA (1) | EA007335B1 (ja) |
HR (1) | HRP20030995A2 (ja) |
IL (1) | IL159125A0 (ja) |
MX (1) | MXPA03010766A (ja) |
NO (1) | NO20035328D0 (ja) |
NZ (1) | NZ528944A (ja) |
PL (1) | PL367128A1 (ja) |
RS (1) | RS94603A (ja) |
WO (1) | WO2002098850A2 (ja) |
ZA (1) | ZA200308392B (ja) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2433520A1 (en) * | 2000-12-22 | 2002-07-04 | Axys Pharmaceuticals, Inc. | Novel compounds and compositions as cathepsin inhibitors |
US6982263B2 (en) | 2001-06-08 | 2006-01-03 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nitriles useful as reversible inhibitors of cysteine proteases |
YU34604A (sh) * | 2001-11-14 | 2006-08-17 | Aventis Pharmaceuticals Inc. | Oligopeptidi kao inhibitori katepsina s i kompozicije koje ih sadrže |
EP1491537B1 (en) * | 2002-03-29 | 2010-07-07 | Senju Pharmaceutical Co., Ltd. | Hydroxymorpholinone derivative and medicinal use thereof |
US7091360B2 (en) * | 2002-04-16 | 2006-08-15 | Aventis Pharma S.A. | Process for preparing heteroaryl and unsaturated heterocycloalkylmagnesium reagents and uses thereof |
WO2004000838A1 (en) * | 2002-06-24 | 2003-12-31 | Axys Pharmaceuticals, Inc. | Peptidic compounds as cysteine protease inhibitors |
WO2004022526A1 (en) * | 2002-09-04 | 2004-03-18 | Merck Frosst Canada & Co. | Cathepsin cysteine protease inhibitors |
WO2005028429A2 (en) | 2003-09-18 | 2005-03-31 | Axys Pharmaceuticals, Inc. | Haloalkyl containing compounds as cysteine protease inhibitors |
AU2004284089B2 (en) * | 2003-10-24 | 2009-11-26 | Aventis Pharmaceuticals Inc. | Novel keto-oxadiazole derivatives as cathepsin inhibitors |
EP1697355A2 (en) * | 2003-12-23 | 2006-09-06 | Axys Pharmaceuticals, Inc. | Amidino compounds as cysteine protease inhibitors |
WO2006060810A1 (en) | 2004-12-02 | 2006-06-08 | Schering Aktiengesellschaft | Sulfonamide compounds as cysteine protease inhibitors |
ES2400582T3 (es) | 2005-03-21 | 2013-04-10 | Virobay, Inc. | Compuestos de alfa cetoamida como inhibidores de cisteína proteasa |
WO2006102535A2 (en) | 2005-03-22 | 2006-09-28 | Celera Genomics | Sulfonyl containing compounds as cysteine protease inhibitors |
ES2535603T3 (es) | 2006-10-04 | 2015-05-13 | Virobay, Inc. | Compuestos que contienen di-fluoro como inhibidores de la cisteína proteasa |
US7893112B2 (en) | 2006-10-04 | 2011-02-22 | Virobay, Inc. | Di-fluoro containing compounds as cysteine protease inhibitors |
US8324417B2 (en) | 2009-08-19 | 2012-12-04 | Virobay, Inc. | Process for the preparation of (S)-2-amino-5-cyclopropyl-4,4-difluoropentanoic acid and alkyl esters and acid salts thereof |
CA2782292A1 (en) * | 2009-12-10 | 2011-06-16 | Medivir Uk Limited | Cysteine protease inhibitors |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5874424A (en) * | 1995-12-20 | 1999-02-23 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1β converting enzyme |
DE3606480A1 (de) * | 1986-02-28 | 1987-09-03 | Behringwerke Ag | Oligopeptidylnitrilderivate, diese enthaltende mittel, verfahren zu ihrer herstellung und ihre verwendung |
CA2111930A1 (en) * | 1992-12-25 | 1994-06-26 | Ryoichi Ando | Aminoketone derivatives |
US5486623A (en) * | 1993-12-08 | 1996-01-23 | Prototek, Inc. | Cysteine protease inhibitors containing heterocyclic leaving groups |
US5847135A (en) * | 1994-06-17 | 1998-12-08 | Vertex Pharmaceuticals, Incorporated | Inhibitors of interleukin-1β converting enzyme |
US5498616A (en) * | 1994-11-04 | 1996-03-12 | Cephalon, Inc. | Cysteine protease and serine protease inhibitors |
US6022861A (en) * | 1995-06-07 | 2000-02-08 | Cor Therapeutics, Inc. | Ketoheterocyclic inhibitors of factor Xa |
US6124333A (en) * | 1995-06-22 | 2000-09-26 | British Biotech Pharmaceuticals Limited | Metalloproteinase inhibitors |
CA2238175A1 (en) * | 1995-11-28 | 1997-06-19 | Cephalon, Inc. | D-amino acid derived inhibitors of cysteine and serine proteases |
US6004933A (en) * | 1997-04-25 | 1999-12-21 | Cortech Inc. | Cysteine protease inhibitors |
GB9723407D0 (en) * | 1997-11-05 | 1998-01-07 | Ciba Geigy Ag | Organic compounds |
US6114310A (en) * | 1998-01-23 | 2000-09-05 | Microcide Pharmaceuticals, Inc. | Efflux pump inhibitors |
US5942640A (en) * | 1998-04-20 | 1999-08-24 | American Cyanamid Company | Process for the manufacture of N-(1-cyanoalkyl)-2-phenoxypropionamide derivatives |
AU4415899A (en) * | 1998-06-03 | 1999-12-20 | Cortech, Inc. | Alpha-keto oxadiazoles as serine protease inhibitors |
US5998390A (en) * | 1998-09-28 | 1999-12-07 | The Research Foundation Of State University Of New York | Combination of bisphosphonate and tetracycline |
TW200404789A (en) * | 1999-03-15 | 2004-04-01 | Axys Pharm Inc | Novel compounds and compositions as protease inhibitors |
CA2367348A1 (en) * | 1999-03-15 | 2000-09-21 | Axys Pharmaceuticals, Inc. | Novel compounds and compositions as protease inhibitors |
TR200201874T2 (tr) * | 1999-03-15 | 2002-10-21 | Axys Pharmaceuticals, Inc. | Proteaz inhibitörleri olarak yeni bileşikler ve bileşimler. |
WO2001019796A1 (en) * | 1999-09-16 | 2001-03-22 | Axys Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions as cathepsin s inhibitors |
-
2002
- 2002-06-03 NZ NZ528944A patent/NZ528944A/en unknown
- 2002-06-03 MX MXPA03010766A patent/MXPA03010766A/es not_active Application Discontinuation
- 2002-06-03 AU AU2002305790A patent/AU2002305790B2/en not_active Expired - Fee Related
- 2002-06-03 WO PCT/US2002/017411 patent/WO2002098850A2/en active Application Filing
- 2002-06-03 KR KR10-2003-7015739A patent/KR20040015725A/ko not_active Application Discontinuation
- 2002-06-03 RS YUP-946/03A patent/RS94603A/sr unknown
- 2002-06-03 EA EA200301203A patent/EA007335B1/ru not_active IP Right Cessation
- 2002-06-03 CN CNA028111524A patent/CN1512983A/zh active Pending
- 2002-06-03 JP JP2003501840A patent/JP2004535422A/ja active Pending
- 2002-06-03 IL IL15912502A patent/IL159125A0/xx unknown
- 2002-06-03 EP EP02734640A patent/EP1397340A2/en not_active Withdrawn
- 2002-06-03 BR BR0210912-3A patent/BR0210912A/pt not_active IP Right Cessation
- 2002-06-03 CA CA002448418A patent/CA2448418A1/en not_active Abandoned
- 2002-06-03 PL PL02367128A patent/PL367128A1/xx unknown
-
2003
- 2003-10-28 ZA ZA200308392A patent/ZA200308392B/en unknown
- 2003-11-21 US US10/719,080 patent/US20040142999A1/en not_active Abandoned
- 2003-11-28 HR HR20030995A patent/HRP20030995A2/hr not_active Application Discontinuation
- 2003-11-28 NO NO20035328A patent/NO20035328D0/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
JP2004535422A (ja) | 2004-11-25 |
BR0210912A (pt) | 2004-08-31 |
EP1397340A2 (en) | 2004-03-17 |
WO2002098850A2 (en) | 2002-12-12 |
IL159125A0 (en) | 2004-05-12 |
RS94603A (en) | 2007-02-05 |
MXPA03010766A (es) | 2005-03-07 |
EA007335B1 (ru) | 2006-08-25 |
PL367128A1 (en) | 2005-02-21 |
NO20035328D0 (no) | 2003-11-28 |
CA2448418A1 (en) | 2002-12-12 |
ZA200308392B (en) | 2005-01-28 |
EA200301203A1 (ru) | 2004-04-29 |
AU2002305790B2 (en) | 2008-01-31 |
KR20040015725A (ko) | 2004-02-19 |
NZ528944A (en) | 2007-09-28 |
WO2002098850A3 (en) | 2003-04-24 |
CN1512983A (zh) | 2004-07-14 |
US20040142999A1 (en) | 2004-07-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP20030995A2 (en) | Novel compounds and compositions as cathepsin inhibitors | |
JP2002539201A (ja) | プロテアーゼインヒビターとしてのアミン誘導体 | |
US20070049594A1 (en) | Novel compounds and compositions as cathepsin inhibitors | |
HRP20010737A2 (en) | N-cyanomethylamides as protease inhibitors | |
US20070135386A1 (en) | Novel Compounds and Compositions as Cathepsin Inhibitors | |
AU2004261366A1 (en) | Novel cyano thiazolides, methods for the production thereof, and use thereof as a medicament | |
AU2002305790A1 (en) | Chemical compounds and pharmaceutical compositions as cathepsin S inhibitors | |
RU2346943C2 (ru) | Новые соединения и композиции в качестве ингибиторов катепсина | |
US7101880B2 (en) | Peptidic compounds as cysteine protease inhibitors | |
US7226921B2 (en) | Compounds and compositions as cathepsin S inhibitors | |
RU2424239C2 (ru) | Гетероциклические соединения и фармацевтические композиции как ингибиторы катепсина s | |
WO2022133069A1 (en) | Peptidomimetic matriptase 2 inhibitors and uses thereof | |
EP1516877A1 (en) | Amine derivatives as protease inhibitors | |
JP2005500275A (ja) | カテプシンインヒビターとしての新規な化合物および組成物 | |
AU2002357716A1 (en) | Oligopeptides and compositions containing them as cathepsin S inhibitors | |
MXPA01009240A (en) | Amine derivatives as protease inhibitors | |
AU2002241728A1 (en) | Novel compounds and compositions as cathepsin inhibitors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A1OB | Publication of a patent application | ||
ARAI | Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application | ||
ODRP | Renewal fee for the maintenance of a patent |
Payment date: 20060519 Year of fee payment: 5 |
|
OBST | Application withdrawn |