CA2781614A1

CA2781614A1 - 5-alkynyl-thiophene-2-carboxylic acid derivatives and their use for the treatment or prevention of flavivirus infections

5-alkynyl-thiophene-2-carboxylic acid derivatives and their use for the treatment or prevention of flavivirus infections Download PDF

Info

Publication number: CA2781614A1
Authority: CA; Canada
Prior art keywords: amino; thiophene; dimethyl; carboxylic acid; ynyl
Prior art date: 2009-11-25
Legal status : Abandoned

Application number

CA2781614A

Other languages

English (en)

French (fr)

Inventor

Laval Chan Chun Kong

Sanjoy Kumar Das

Carl Poisson

Current Assignee

Vertex Pharmaceuticals Inc

Original Assignee

Vertex Pharmaceuticals Inc

Priority date

2009-11-25

Filing date

2010-11-23

Publication date

2011-06-09

2010-11-23 Application filed by Vertex Pharmaceuticals Inc filed Critical Vertex Pharmaceuticals Inc

2011-06-09 Publication of CA2781614A1 publication Critical patent/CA2781614A1/en

Status Abandoned legal-status Critical Current

Links

238000011282 treatment Methods 0.000 title description 9
206010054261 Flavivirus infection Diseases 0.000 title description 7
230000002265 prevention Effects 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 226
150000003839 salts Chemical class 0.000 claims abstract description 43
208000036142 Viral infection Diseases 0.000 claims abstract description 12
230000009385 viral infection Effects 0.000 claims abstract description 12
241000710781 Flaviviridae Species 0.000 claims abstract description 8
125000000217 alkyl group Chemical group 0.000 claims description 135
-1 carboxy, hydroxyl Chemical group 0.000 claims description 123
229910052736 halogen Inorganic materials 0.000 claims description 50
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 49
150000002367 halogens Chemical class 0.000 claims description 43
239000003795 chemical substances by application Substances 0.000 claims description 35
239000003814 drug Substances 0.000 claims description 33
108010050904 Interferons Proteins 0.000 claims description 32
102000014150 Interferons Human genes 0.000 claims description 32
125000000623 heterocyclic group Chemical group 0.000 claims description 32
238000000034 method Methods 0.000 claims description 24
230000003612 virological effect Effects 0.000 claims description 24
229940079322 interferon Drugs 0.000 claims description 23
125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 18
125000004093 cyano group Chemical group *C#N 0.000 claims description 18
239000003112 inhibitor Substances 0.000 claims description 18
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
208000015181 infectious disease Diseases 0.000 claims description 14
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
108060004795 Methyltransferase Proteins 0.000 claims description 12
230000000694 effects Effects 0.000 claims description 12
125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 11
239000008194 pharmaceutical composition Substances 0.000 claims description 11
125000001424 substituent group Chemical group 0.000 claims description 11
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 10
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
125000001425 triazolyl group Chemical group 0.000 claims description 10
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 9
125000003277 amino group Chemical group 0.000 claims description 9
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
108020004684 Internal Ribosome Entry Sites Proteins 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 8
230000002401 inhibitory effect Effects 0.000 claims description 8
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
230000017105 transposition Effects 0.000 claims description 8
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
125000001153 fluoro group Chemical group F* 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
SGQLPEMPVMPRNR-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-propan-2-ylamino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1=C(C#CC(C)(C)C)SC(C(O)=O)=C1N(C(C)C)C(=O)C1=CC=C(Cl)C=C1Cl SGQLPEMPVMPRNR-UHFFFAOYSA-N 0.000 claims description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
125000004043 oxo group Chemical group O=* 0.000 claims description 6
IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
229960000329 ribavirin Drugs 0.000 claims description 5
HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 5
239000003001 serine protease inhibitor Substances 0.000 claims description 5
125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
229940065638 intron a Drugs 0.000 claims description 4
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
229940002988 pegasys Drugs 0.000 claims description 4
108010092853 peginterferon alfa-2a Proteins 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
229940021747 therapeutic vaccine Drugs 0.000 claims description 4
125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 3
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 3
125000005915 C6-C14 aryl group Chemical group 0.000 claims description 3
FWKQNCXZGNBPFD-UHFFFAOYSA-N Guaiazulene Chemical compound CC(C)C1=CC=C(C)C2=CC=C(C)C2=C1 FWKQNCXZGNBPFD-UHFFFAOYSA-N 0.000 claims description 3
239000003242 anti bacterial agent Substances 0.000 claims description 3
230000000692 anti-sense effect Effects 0.000 claims description 3
239000003963 antioxidant agent Substances 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical group C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 2
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 2
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 2
NBWWZQBKAJYUSU-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(2-methoxyethyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1=C(C#CC(C)(C)C)SC(C(O)=O)=C1N(CCOC)C(=O)C1=CC=C(Cl)C=C1Cl NBWWZQBKAJYUSU-UHFFFAOYSA-N 0.000 claims description 2
DVKAZZAFTYBIBP-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(oxan-4-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCOCC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O DVKAZZAFTYBIBP-UHFFFAOYSA-N 0.000 claims description 2
CXJVWFOGCVHFKQ-UHFFFAOYSA-N 3-[(2,4-dimethylbenzoyl)-(4-hydroxycyclohexyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound CC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C1CCC(O)CC1 CXJVWFOGCVHFKQ-UHFFFAOYSA-N 0.000 claims description 2
DKOJRDPYSCBWQX-UHFFFAOYSA-N 3-[(2-chloro-4-methylbenzoyl)-(4-hydroxycyclohexyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound ClC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C1CCC(O)CC1 DKOJRDPYSCBWQX-UHFFFAOYSA-N 0.000 claims description 2
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
HAGOOSUDXBHSMT-IYARVYRRSA-N S1C(C#CC(C)(C)C)=CC(N([C@@H]2CC[C@@H](O)CC2)C(=O)C=2C=CC(Cl)=CC=2)=C1C(O)=O Chemical compound S1C(C#CC(C)(C)C)=CC(N([C@@H]2CC[C@@H](O)CC2)C(=O)C=2C=CC(Cl)=CC=2)=C1C(O)=O HAGOOSUDXBHSMT-IYARVYRRSA-N 0.000 claims 2
108010092851 peginterferon alfa-2b Proteins 0.000 claims 2
229940106366 pegintron Drugs 0.000 claims 2
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
KWKCSVSLEKTKLY-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1,3-dimethoxypropan-2-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1=C(C#CC(C)(C)C)SC(C(O)=O)=C1N(C(COC)COC)C(=O)C1=CC=C(Cl)C=C1Cl KWKCSVSLEKTKLY-UHFFFAOYSA-N 0.000 claims 1
PBLLBBNJLUNGQA-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1,3-dioxan-5-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2COCOC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O PBLLBBNJLUNGQA-UHFFFAOYSA-N 0.000 claims 1
KBILOKJMFYGVEL-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1,4-dioxaspiro[4.5]decan-8-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCC3(CC2)OCCO3)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O KBILOKJMFYGVEL-UHFFFAOYSA-N 0.000 claims 1
VYMARQHNGPZNCI-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1-methoxypropan-2-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1=C(C#CC(C)(C)C)SC(C(O)=O)=C1N(C(C)COC)C(=O)C1=CC=C(Cl)C=C1Cl VYMARQHNGPZNCI-UHFFFAOYSA-N 0.000 claims 1
MKRZVIZUUCWRDB-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1-methylsulfonylpiperidin-4-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCN(CC2)S(C)(=O)=O)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O MKRZVIZUUCWRDB-UHFFFAOYSA-N 0.000 claims 1
NTGGXFHJTLLUPU-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(1-pyrimidin-2-ylpiperidin-4-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCN(CC2)C=2N=CC=CN=2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O NTGGXFHJTLLUPU-UHFFFAOYSA-N 0.000 claims 1
KXPYCFRMQXOHKU-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(2,2,2-trifluoroethyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(CC(F)(F)F)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O KXPYCFRMQXOHKU-UHFFFAOYSA-N 0.000 claims 1
UQWJKFWBWFQVAB-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(2-methyl-3-oxo-2-azaspiro[4.5]decan-8-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1C(=O)N(C)CC21CCC(N(C(=O)C=1C(=CC(Cl)=CC=1)Cl)C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)CC2 UQWJKFWBWFQVAB-UHFFFAOYSA-N 0.000 claims 1
MYUZGWMZZRDKQA-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(3-oxo-2-azaspiro[4.5]decan-8-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCC3(CC(=O)NC3)CC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O MYUZGWMZZRDKQA-UHFFFAOYSA-N 0.000 claims 1
LPWNNRFFJGOEKN-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(4,4-difluorocyclohexyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCC(F)(F)CC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O LPWNNRFFJGOEKN-UHFFFAOYSA-N 0.000 claims 1
RBXCYJQSDQDLTI-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-(oxolan-3-yl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2COCC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O RBXCYJQSDQDLTI-UHFFFAOYSA-N 0.000 claims 1
JUFWROUHJJOECC-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-[1-(2,2-difluoroethyl)piperidin-4-yl]amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCN(CC(F)F)CC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O JUFWROUHJJOECC-UHFFFAOYSA-N 0.000 claims 1
VZCXCIOTUWVZLX-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-[1-(2-fluoroethyl)piperidin-4-yl]amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCN(CCF)CC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O VZCXCIOTUWVZLX-UHFFFAOYSA-N 0.000 claims 1
NVWUPEMFXAHJEL-UHFFFAOYSA-N 3-[(2,4-dichlorobenzoyl)-[1-(2-methylpropanoyl)piperidin-4-yl]amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1CN(C(=O)C(C)C)CCC1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)C1=CC=C(Cl)C=C1Cl NVWUPEMFXAHJEL-UHFFFAOYSA-N 0.000 claims 1
AOWPCMNNWKHMEE-UHFFFAOYSA-N 3-[(2-amino-4-chlorobenzoyl)-[4-[methyl(2-methylpropanoyl)amino]cyclohexyl]amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound C1CC(N(C)C(=O)C(C)C)CCC1N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C(=O)C1=CC=C(Cl)C=C1N AOWPCMNNWKHMEE-UHFFFAOYSA-N 0.000 claims 1
FXUMYKGLQZKAEV-UHFFFAOYSA-N 3-[(4-chloro-3-fluorobenzoyl)-(4-hydroxycyclohexyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCC(O)CC2)C(=O)C=2C=C(F)C(Cl)=CC=2)=C1C(O)=O FXUMYKGLQZKAEV-UHFFFAOYSA-N 0.000 claims 1
VQBGEWVEDKRADV-UHFFFAOYSA-N 3-[cyclobutyl-(2,4-dichlorobenzoyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O VQBGEWVEDKRADV-UHFFFAOYSA-N 0.000 claims 1
CCPFITPFDGSRRP-UHFFFAOYSA-N 3-[cyclopentyl-(2,4-dichlorobenzoyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCCC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O CCPFITPFDGSRRP-UHFFFAOYSA-N 0.000 claims 1
CGJZZXWOHGIDKN-UHFFFAOYSA-N 3-[cyclopropyl-(2,4-dichlorobenzoyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CC2)C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1C(O)=O CGJZZXWOHGIDKN-UHFFFAOYSA-N 0.000 claims 1
PKEAKMDQXCCAPM-UHFFFAOYSA-N 3-[tert-butyl-(2,4-dichlorobenzoyl)amino]-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C(=O)C=2C(=CC(Cl)=CC=2)Cl)C(C)(C)C)=C1C(O)=O PKEAKMDQXCCAPM-UHFFFAOYSA-N 0.000 claims 1
JARYWUSNBQQCLK-UHFFFAOYSA-N 5-(3,3-dimethylbut-1-ynyl)-3-[(2-fluoro-4-methylbenzoyl)-(4-hydroxycyclohexyl)amino]thiophene-2-carboxylic acid Chemical compound FC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C1CCC(O)CC1 JARYWUSNBQQCLK-UHFFFAOYSA-N 0.000 claims 1
RGOKCNBSFCCMJH-UHFFFAOYSA-N 5-(3,3-dimethylbut-1-ynyl)-3-[(4-fluorobenzoyl)-(4-hydroxycyclohexyl)amino]thiophene-2-carboxylic acid Chemical compound S1C(C#CC(C)(C)C)=CC(N(C2CCC(O)CC2)C(=O)C=2C=CC(F)=CC=2)=C1C(O)=O RGOKCNBSFCCMJH-UHFFFAOYSA-N 0.000 claims 1
CPXYBXFTEYLSEH-QAQDUYKDSA-N BrC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 Chemical compound BrC1=CC(C)=CC=C1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 CPXYBXFTEYLSEH-QAQDUYKDSA-N 0.000 claims 1
JMIAHFRTUPKEHZ-UHFFFAOYSA-N C1(CC1)CN(C1=C(SC(=C1)C#CC(C)(C)C)C(=O)O)C(C1=C(C=C(C=C1)Cl)Cl)=O.ClC1=C(C(=O)N(C2=C(SC(=C2)C#CC(C)(C)C)C(=O)O)CC)C=CC(=C1)Cl Chemical compound C1(CC1)CN(C1=C(SC(=C1)C#CC(C)(C)C)C(=O)O)C(C1=C(C=C(C=C1)Cl)Cl)=O.ClC1=C(C(=O)N(C2=C(SC(=C2)C#CC(C)(C)C)C(=O)O)CC)C=CC(=C1)Cl JMIAHFRTUPKEHZ-UHFFFAOYSA-N 0.000 claims 1
ZPJCHQRIANSREL-UHFFFAOYSA-N C1(CCCCC1)N(C1=C(SC(=C1)C#CC(C)(C)C)C(=O)O)C(C1=C(C=C(C=C1)Cl)Cl)=O.ClC1=C(C(=O)N(C2=C(SC(=C2)C#CC(C)(C)C)C(=O)O)C)C=CC(=C1)Cl Chemical compound C1(CCCCC1)N(C1=C(SC(=C1)C#CC(C)(C)C)C(=O)O)C(C1=C(C=C(C=C1)Cl)Cl)=O.ClC1=C(C(=O)N(C2=C(SC(=C2)C#CC(C)(C)C)C(=O)O)C)C=CC(=C1)Cl ZPJCHQRIANSREL-UHFFFAOYSA-N 0.000 claims 1
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