AU2008206702A1 - Thiazolidine derivatives and methods for the preparation thereof - Google Patents

Info

Publication number

AU2008206702A1

AU2008206702A1 AU2008206702A AU2008206702A AU2008206702A1 AU 2008206702 A1 AU2008206702 A1 AU 2008206702A1 AU 2008206702 A AU2008206702 A AU 2008206702A AU 2008206702 A AU2008206702 A AU 2008206702A AU 2008206702 A1 AU2008206702 A1 AU 2008206702A1

Authority

AU

Australia

Prior art keywords

trifluorophenyl

thiazolidine

amino

butanoyl

methyl

Prior art date

2007-01-16

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims description 129
• 150000003548 thiazolidines Chemical class 0.000 title claims 6
• 238000002360 preparation method Methods 0.000 title description 116
• 150000001875 compounds Chemical class 0.000 claims description 333
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 178
• -1 morpholin-4-ylethyl Chemical group 0.000 claims description 129
• 125000005518 carboxamido group Chemical group 0.000 claims description 85
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 81
• 239000000203 mixture Substances 0.000 claims description 68
• 229910052739 hydrogen Inorganic materials 0.000 claims description 65
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 60
• 150000003839 salts Chemical group 0.000 claims description 55
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 54
• 239000001257 hydrogen Substances 0.000 claims description 54
• 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 claims description 52
• 125000000217 alkyl group Chemical group 0.000 claims description 49
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 43
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 30
• 125000004360 trifluorophenyl group Chemical group 0.000 claims description 30
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 29
• 238000006482 condensation reaction Methods 0.000 claims description 29
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 27
• 239000002253 acid Substances 0.000 claims description 26
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 26
• 241000124008 Mammalia Species 0.000 claims description 22
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 22
• YDGXLVKDGGLWPF-UHFFFAOYSA-N 1,3-thiazolidine-2-carboxamide Chemical compound NC(=O)C1NCCS1 YDGXLVKDGGLWPF-UHFFFAOYSA-N 0.000 claims description 21
• 239000003795 chemical substances by application Substances 0.000 claims description 20
• 201000010099 disease Diseases 0.000 claims description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
• YMHAVNUJTQOHLO-UOGPZTOASA-N 3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carboxylic acid Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1C(O)=O YMHAVNUJTQOHLO-UOGPZTOASA-N 0.000 claims description 19
• ZFARZBFCWQXUEO-QNAPOOHRSA-N methyl 3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1SCCN1C(=O)C[C@H](N)CC1=CC(F)=C(F)C=C1F ZFARZBFCWQXUEO-QNAPOOHRSA-N 0.000 claims description 19
• 230000001404 mediated effect Effects 0.000 claims description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims description 18
• 229910052701 rubidium Inorganic materials 0.000 claims description 17
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
• UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 claims description 16
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 16
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 16
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 15
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 15
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
• GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 14
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 14
• 206010012601 diabetes mellitus Diseases 0.000 claims description 14
• 239000000651 prodrug Chemical group 0.000 claims description 14
• 229940002612 prodrug Drugs 0.000 claims description 14
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 13
• 150000002367 halogens Chemical class 0.000 claims description 13
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 13
• 230000002401 inhibitory effect Effects 0.000 claims description 13
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
• 150000001413 amino acids Chemical class 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 230000003301 hydrolyzing effect Effects 0.000 claims description 12
• 125000006239 protecting group Chemical group 0.000 claims description 12
• 102000004877 Insulin Human genes 0.000 claims description 11
• 108090001061 Insulin Proteins 0.000 claims description 11
• 208000008589 Obesity Diseases 0.000 claims description 11
• 208000001132 Osteoporosis Diseases 0.000 claims description 11
• 206010003246 arthritis Diseases 0.000 claims description 11
• TYYMLFVDYGZKHF-SMFUYQKNSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 TYYMLFVDYGZKHF-SMFUYQKNSA-N 0.000 claims description 11
• 229940125396 insulin Drugs 0.000 claims description 11
• 235000020824 obesity Nutrition 0.000 claims description 11
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
• 125000001424 substituent group Chemical group 0.000 claims description 11
• 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims description 11
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 10
• 208000002705 Glucose Intolerance Diseases 0.000 claims description 10
• 125000003545 alkoxy group Chemical group 0.000 claims description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
• 230000005764 inhibitory process Effects 0.000 claims description 10
• 201000009104 prediabetes syndrome Diseases 0.000 claims description 10
• FRXUECPZDRGFBP-BXWDTWGJSA-N 2-[4-[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]phenoxy]acetic acid Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1C(=O)NC1=CC=C(OCC(O)=O)C=C1 FRXUECPZDRGFBP-BXWDTWGJSA-N 0.000 claims description 9
• 230000000269 nucleophilic effect Effects 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
• 229910052702 rhenium Inorganic materials 0.000 claims description 8
• INUDFZPOCPXRIM-SECBINFHSA-N (3r)-3-amino-1-(1,3-thiazolidin-3-yl)-4-(2,4,5-trifluorophenyl)butan-1-one Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1 INUDFZPOCPXRIM-SECBINFHSA-N 0.000 claims description 7
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 7
• IRBRJRYDYQPOHI-UHFFFAOYSA-N C(=O)=C1SCCN1 Chemical compound C(=O)=C1SCCN1 IRBRJRYDYQPOHI-UHFFFAOYSA-N 0.000 claims description 7
• 125000002252 acyl group Chemical group 0.000 claims description 7
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
• ZLKLIPZIHIGNIB-WSNNEZGNSA-N (2s)-2-[4-[[[(2r)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-methylbutanoic acid Chemical compound C1=CC(O[C@@H](C(C)C)C(O)=O)=CC=C1CNC(=O)[C@@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZLKLIPZIHIGNIB-WSNNEZGNSA-N 0.000 claims description 6
• OFYPGMVLIRMOKY-BSOCMFCZSA-N 1-[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]piperidine-4-carboxylic acid Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1C(=O)N1CCC(C(O)=O)CC1 OFYPGMVLIRMOKY-BSOCMFCZSA-N 0.000 claims description 6
• ZLKLIPZIHIGNIB-PAQRCMFQSA-N 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-methylbutanoic acid Chemical compound C1=CC(OC(C(C)C)C(O)=O)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZLKLIPZIHIGNIB-PAQRCMFQSA-N 0.000 claims description 6
• GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 claims description 6
• YVONDORDYHTIHH-RLVCRIBASA-N 6-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2,3-dihydro-1,4-benzodioxine-2-carboxylic acid Chemical compound C([C@H](CC(=O)N1C(SCC1)C(=O)NCC=1C=C2OCC(OC2=CC=1)C(O)=O)N)C1=CC(F)=C(F)C=C1F YVONDORDYHTIHH-RLVCRIBASA-N 0.000 claims description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 6
• 125000003277 amino group Chemical group 0.000 claims description 6
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 6
• 229910000024 caesium carbonate Inorganic materials 0.000 claims description 6
• 235000015497 potassium bicarbonate Nutrition 0.000 claims description 6
• 239000011736 potassium bicarbonate Substances 0.000 claims description 6
• 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 6
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 6
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
• ZLKLIPZIHIGNIB-WQWSHVPRSA-N (2r)-2-[4-[[[(2r)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-methylbutanoic acid Chemical compound C1=CC(O[C@H](C(C)C)C(O)=O)=CC=C1CNC(=O)[C@@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZLKLIPZIHIGNIB-WQWSHVPRSA-N 0.000 claims description 5
• YMHAVNUJTQOHLO-OQPBUACISA-N (2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carboxylic acid Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCS[C@H]1C(O)=O YMHAVNUJTQOHLO-OQPBUACISA-N 0.000 claims description 5
• FJJPDSRSWDECJJ-ADRQNKRLSA-N 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenyl]acetic acid Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1C(=O)NCC1=CC=C(CC(O)=O)C=C1 FJJPDSRSWDECJJ-ADRQNKRLSA-N 0.000 claims description 5
• BKCZVCXBHBKIJK-ISGGMURCSA-N 3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-n-[2-(1h-imidazol-5-yl)ethyl]-1,3-thiazolidine-2-carboxamide Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1C(=O)NCCC1=CNC=N1 BKCZVCXBHBKIJK-ISGGMURCSA-N 0.000 claims description 5
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 5
• ZIKFLNMVMAFLQI-RBFZIWAESA-N ethyl 1-[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZIKFLNMVMAFLQI-RBFZIWAESA-N 0.000 claims description 5
• OIBQLQNXRUNJHJ-SZYCOLMRSA-N ethyl 2-[4-[[[3-[(3r)-3-(1-acetyloxyethoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-methylbutanoate Chemical compound C1=CC(OC(C(=O)OCC)C(C)C)=CC=C1CNC(=O)C1N(C(=O)C[C@@H](CC=2C(=CC(F)=C(F)C=2)F)NC(=O)OC(C)OC(C)=O)CCS1 OIBQLQNXRUNJHJ-SZYCOLMRSA-N 0.000 claims description 5
• RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 5
• 229910052727 yttrium Inorganic materials 0.000 claims description 5
• CIFMKLKCUSSHMN-KITIHOALSA-N (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-3-fluoroanilino]-3-methylbutanoic acid Chemical compound FC1=CC(N[C@H](C(C)C)C(O)=O)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 CIFMKLKCUSSHMN-KITIHOALSA-N 0.000 claims description 4
• ZLKLIPZIHIGNIB-LAMXGVLKSA-N (2s)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-methylbutanoic acid Chemical compound C1=CC(O[C@@H](C(C)C)C(O)=O)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZLKLIPZIHIGNIB-LAMXGVLKSA-N 0.000 claims description 4
• YBYKIRVSSYQWRY-UGSZZNERSA-N 2,2-dimethylpropanoyloxymethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-methylbutanoate Chemical compound C1=CC(OC(C(C)C)C(=O)OCOC(=O)C(C)(C)C)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 YBYKIRVSSYQWRY-UGSZZNERSA-N 0.000 claims description 4
• IIWKMMFEKKPJQI-NKTHEXPSSA-N 2-[3-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]acetic acid Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1C(=O)NCC1=CC=CC(OCC(O)=O)=C1 IIWKMMFEKKPJQI-NKTHEXPSSA-N 0.000 claims description 4
• QPVQUZRUJDJEIX-FQEBHOFPSA-N 2-[[2-[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]-3,4-dihydro-1h-isoquinolin-7-yl]oxy]-3-methylbutanoic acid Chemical compound C([C@@H](N)CC(=O)N1CCSC1C(=O)N1CCC2=CC=C(C=C2C1)OC(C(C)C)C(O)=O)C1=CC(F)=C(F)C=C1F QPVQUZRUJDJEIX-FQEBHOFPSA-N 0.000 claims description 4
• YUBFYXVNUWPQFT-MGFKIWBESA-N 2-[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]acetic acid Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1C(=O)NCC(O)=O YUBFYXVNUWPQFT-MGFKIWBESA-N 0.000 claims description 4
• AAGWKHSEAIXNGH-RBFZIWAESA-N 3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-n-benzyl-1,3-thiazolidine-2-carboxamide Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1C(=O)NCC1=CC=CC=C1 AAGWKHSEAIXNGH-RBFZIWAESA-N 0.000 claims description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
• 125000005605 benzo group Chemical group 0.000 claims description 4
• 150000003857 carboxamides Chemical class 0.000 claims description 4
• YXBDCYDMXMSFAK-JRLVAEJTSA-N ethyl (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoate Chemical compound C1=CC(N[C@@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 YXBDCYDMXMSFAK-JRLVAEJTSA-N 0.000 claims description 4
• ZISAPBBDTDALHX-GZAIGYLVSA-N ethyl 2-[4-[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1NC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZISAPBBDTDALHX-GZAIGYLVSA-N 0.000 claims description 4
• ZSRFLOUIEKJRKW-FQEBHOFPSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-methylbutanoate Chemical compound C1=CC(OC(C(=O)OCC)C(C)C)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZSRFLOUIEKJRKW-FQEBHOFPSA-N 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• 125000002757 morpholinyl group Chemical group 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• ZUNWVBNRQTWJFD-WQWSHVPRSA-N (2r)-2-[4-[[[(2r)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoic acid Chemical compound C1=CC(N[C@H](C(C)C)C(O)=O)=CC=C1CNC(=O)[C@@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZUNWVBNRQTWJFD-WQWSHVPRSA-N 0.000 claims description 3
• ZIPBLKFAKRBQKW-OZWXPUTRSA-N (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-methylbutanoic acid;hydrochloride Chemical compound Cl.C1=CC(O[C@H](C(C)C)C(O)=O)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZIPBLKFAKRBQKW-OZWXPUTRSA-N 0.000 claims description 3
• RUMXITRGPIEVEF-LAMXGVLKSA-N (2s)-2-[2-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-5-bromoanilino]-3-methylbutanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC1=CC(Br)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 RUMXITRGPIEVEF-LAMXGVLKSA-N 0.000 claims description 3
• ZUNWVBNRQTWJFD-LAMXGVLKSA-N (2s)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoic acid Chemical compound C1=CC(N[C@@H](C(C)C)C(O)=O)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZUNWVBNRQTWJFD-LAMXGVLKSA-N 0.000 claims description 3
• GRNVZZOVEXCLQE-MTICYMICSA-N (2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-n-[[4-[[(2r)-1-(dimethylamino)-3-methyl-1-oxobutan-2-yl]amino]phenyl]methyl]-1,3-thiazolidine-2-carboxamide Chemical compound C1=CC(N[C@H](C(C)C)C(=O)N(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 GRNVZZOVEXCLQE-MTICYMICSA-N 0.000 claims description 3
• MZZKUJJBVSAJPV-MTICYMICSA-N (2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-n-[[4-[[(2r)-1-(ethylamino)-3-methyl-1-oxobutan-2-yl]amino]phenyl]methyl]-1,3-thiazolidine-2-carboxamide Chemical compound C1=CC(N[C@@H](C(=O)NCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 MZZKUJJBVSAJPV-MTICYMICSA-N 0.000 claims description 3
• RXKLHSBTWQITOC-KJQJYJGISA-N (2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-n-[[4-[[(2r)-3-methyl-1-[2-(methylamino)ethylamino]-1-oxobutan-2-yl]amino]phenyl]methyl]-1,3-thiazolidine-2-carboxamide Chemical compound C1=CC(N[C@@H](C(=O)NCCNC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 RXKLHSBTWQITOC-KJQJYJGISA-N 0.000 claims description 3
• KAWLDYAXTVSEOF-CPDRSWAVSA-N (2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-n-[[4-[[(2r)-3-methyl-1-oxo-1-(piperidin-4-ylamino)butan-2-yl]amino]phenyl]methyl]-1,3-thiazolidine-2-carboxamide Chemical compound C([C@@H](N)CC(=O)N1CCS[C@H]1C(=O)NCC1=CC=C(C=C1)N[C@H](C(C)C)C(=O)NC1CCNCC1)C1=CC(F)=C(F)C=C1F KAWLDYAXTVSEOF-CPDRSWAVSA-N 0.000 claims description 3
• FIKHVLBRAHJUSI-VFSZNHPQSA-N (2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-n-[[4-[[(2r)-3-methyl-1-oxo-1-piperazin-1-ylbutan-2-yl]amino]phenyl]methyl]-1,3-thiazolidine-2-carboxamide Chemical compound C([C@@H](N)CC(=O)N1CCS[C@H]1C(=O)NCC1=CC=C(C=C1)N[C@H](C(C)C)C(=O)N1CCNCC1)C1=CC(F)=C(F)C=C1F FIKHVLBRAHJUSI-VFSZNHPQSA-N 0.000 claims description 3
• XERTYVXARDIBRI-GHHKSXATSA-N (2s,3s)-2-[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]-3-methylpentanoic acid Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)C1SCCN1C(=O)C[C@H](N)CC1=CC(F)=C(F)C=C1F XERTYVXARDIBRI-GHHKSXATSA-N 0.000 claims description 3
• BTMYROPUHHEMJB-BSOCMFCZSA-N (3r)-3-amino-1-[2-(4-methylpiperazine-1-carbonyl)-1,3-thiazolidin-3-yl]-4-(2,4,5-trifluorophenyl)butan-1-one Chemical compound C1CN(C)CCN1C(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 BTMYROPUHHEMJB-BSOCMFCZSA-N 0.000 claims description 3
• NXKWJBXNSVGUHO-UWFASSMRSA-N 2-[4-[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]piperidin-1-yl]-3-methylbutanoic acid Chemical compound C1CN(C(C(C)C)C(O)=O)CCC1NC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 NXKWJBXNSVGUHO-UWFASSMRSA-N 0.000 claims description 3
• QUWBPUIJKJQLDT-NKTHEXPSSA-N 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-3-fluorophenoxy]-2-methylpropanoic acid Chemical compound FC1=CC(OC(C)(C)C(O)=O)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 QUWBPUIJKJQLDT-NKTHEXPSSA-N 0.000 claims description 3
• OXTGCEAIOCOHOO-UQEGFRFESA-N 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-3-fluorophenoxy]butanoic acid Chemical compound FC1=CC(OC(CC)C(O)=O)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 OXTGCEAIOCOHOO-UQEGFRFESA-N 0.000 claims description 3
• PKZVUKVLIUQYQI-UEXBFKPASA-N 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-n-methylanilino]-3-methylbutanoic acid Chemical compound C1=CC(N(C)C(C(C)C)C(O)=O)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 PKZVUKVLIUQYQI-UEXBFKPASA-N 0.000 claims description 3
• ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 claims description 3
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 3
• 125000006242 amine protecting group Chemical group 0.000 claims description 3
• 125000004432 carbon atom Chemical group C* 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• YXBDCYDMXMSFAK-DSSGHVNRSA-N ethyl (2r)-2-[4-[[[(2r)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoate Chemical compound C1=CC(N[C@@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 YXBDCYDMXMSFAK-DSSGHVNRSA-N 0.000 claims description 3
• YXBDCYDMXMSFAK-KAZGAHJFSA-N ethyl (2s)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoate Chemical compound C1=CC(N[C@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 YXBDCYDMXMSFAK-KAZGAHJFSA-N 0.000 claims description 3
• ABUPXTPOOOSPII-AVJJPXIXSA-N ethyl (2s,3s)-2-[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]-3-methylpentanoate Chemical compound CCOC(=O)[C@H]([C@@H](C)CC)NC(=O)C1SCCN1C(=O)C[C@H](N)CC1=CC(F)=C(F)C=C1F ABUPXTPOOOSPII-AVJJPXIXSA-N 0.000 claims description 3
• AKFDKXQYMSXKAU-UPMSZNRZSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-3-fluorophenoxy]-3-methylbutanoate Chemical compound FC1=CC(OC(C(=O)OCC)C(C)C)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 AKFDKXQYMSXKAU-UPMSZNRZSA-N 0.000 claims description 3
• RYEFYQXDRFJZFN-ZFAMYZPZSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-3-fluorophenoxy]butanoate Chemical compound FC1=CC(OC(CC)C(=O)OCC)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 RYEFYQXDRFJZFN-ZFAMYZPZSA-N 0.000 claims description 3
• NLWGNYWZJHVFHZ-JRHFUVFWSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-n-methylanilino]-3-methylbutanoate Chemical compound C1=CC(N(C)C(C(C)C)C(=O)OCC)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 NLWGNYWZJHVFHZ-JRHFUVFWSA-N 0.000 claims description 3
• ARLIQBRYLXYYRV-DRJRLWMOSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-methylbutanoate;hydrochloride Chemical compound Cl.C1=CC(OC(C(=O)OCC)C(C)C)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ARLIQBRYLXYYRV-DRJRLWMOSA-N 0.000 claims description 3
• SOOMSOFJGXDQPT-PKZZPTEUSA-N ethyl 6-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2,3-dihydro-1,4-benzodioxine-2-carboxylate Chemical compound C([C@@H](N)CC(=O)N1CCSC1C(=O)NCC=1C=C2OCC(OC2=CC=1)C(=O)OCC)C1=CC(F)=C(F)C=C1F SOOMSOFJGXDQPT-PKZZPTEUSA-N 0.000 claims description 3
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 3
• 235000014655 lactic acid Nutrition 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• WYSJJWJCQAJTQU-UCWRFOARSA-N methyl 3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carboxylate Chemical compound COC(=O)C1SCCN1C(=O)C[C@H](N)CC1=CC(F)=C(F)C=C1F WYSJJWJCQAJTQU-UCWRFOARSA-N 0.000 claims description 3
• ZESMCYXZKZIVNF-HNNQXCQYSA-N methyl 4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZESMCYXZKZIVNF-HNNQXCQYSA-N 0.000 claims description 3
• 229910052760 oxygen Inorganic materials 0.000 claims description 3
• FBCBSWNLSNUXJV-LVPRMVSMSA-N propan-2-yl (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoate Chemical compound C1=CC(N[C@@H](C(=O)OC(C)C)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 FBCBSWNLSNUXJV-LVPRMVSMSA-N 0.000 claims description 3
• VXSAERDPLACFRK-KITIHOALSA-N (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2-(trifluoromethyl)anilino]-3-methylbutanoic acid Chemical compound C1=C(C(F)(F)F)C(N[C@H](C(C)C)C(O)=O)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 VXSAERDPLACFRK-KITIHOALSA-N 0.000 claims description 2
• NSAJENMOXNDHEX-KITIHOALSA-N (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2-fluoroanilino]-3-methylbutanoic acid Chemical compound C1=C(F)C(N[C@H](C(C)C)C(O)=O)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 NSAJENMOXNDHEX-KITIHOALSA-N 0.000 claims description 2
• ZUNWVBNRQTWJFD-HGMMTPDKSA-N (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoic acid Chemical compound C1=CC(N[C@H](C(C)C)C(O)=O)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZUNWVBNRQTWJFD-HGMMTPDKSA-N 0.000 claims description 2
• IDMQQXXSDWAOHU-PRESPHQNSA-N (2r)-2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=CC=C(C=C1)CNC(=O)C1SCCN1C(=O)C[C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(O)=O)C1=CC=CC=C1 IDMQQXXSDWAOHU-PRESPHQNSA-N 0.000 claims description 2
• PRYWJNAVBFXOIE-HJHRRKNKSA-N (2s)-2-[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]-3-methylbutanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)C1SCCN1C(=O)C[C@H](N)CC1=CC(F)=C(F)C=C1F PRYWJNAVBFXOIE-HJHRRKNKSA-N 0.000 claims description 2
• LAUMNKKRZUPITH-GKOGFXNCSA-N (3r)-3-amino-1-[2-(piperazine-1-carbonyl)-1,3-thiazolidin-3-yl]-4-(2,4,5-trifluorophenyl)butan-1-one Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1C(=O)N1CCNCC1 LAUMNKKRZUPITH-GKOGFXNCSA-N 0.000 claims description 2
• QZGHBIUQNWNHOG-JRLVAEJTSA-N 2-[(2,2,2-trifluoroacetyl)amino]ethyl (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoate Chemical compound C1=CC(N[C@H](C(C)C)C(=O)OCCNC(=O)C(F)(F)F)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 QZGHBIUQNWNHOG-JRLVAEJTSA-N 0.000 claims description 2
• STZGCLGKCFFUBH-NKTHEXPSSA-N 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2-fluorophenoxy]-2-methylpropanoic acid Chemical compound C1=C(F)C(OC(C)(C)C(O)=O)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 STZGCLGKCFFUBH-NKTHEXPSSA-N 0.000 claims description 2
• ZIXCRNJNDWBOCW-ADRQNKRLSA-N 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-2-methylpropanoic acid Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZIXCRNJNDWBOCW-ADRQNKRLSA-N 0.000 claims description 2
• NNCLQAWPULZMKY-IUCRNYMKSA-N 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-2-methylpropanoic acid;hydrochloride Chemical compound Cl.C1=CC(OC(C)(C)C(O)=O)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 NNCLQAWPULZMKY-IUCRNYMKSA-N 0.000 claims description 2
• NCEDLMUAOLHRAJ-BXWDTWGJSA-N 3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-n-(1h-benzimidazol-2-ylmethyl)-1,3-thiazolidine-2-carboxamide Chemical compound C([C@H](CC(=O)N1C(SCC1)C(=O)NCC=1NC2=CC=CC=C2N=1)N)C1=CC(F)=C(F)C=C1F NCEDLMUAOLHRAJ-BXWDTWGJSA-N 0.000 claims description 2
• CJSHFPGMMMDUQX-QMRFKDRMSA-N 3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-n-(pyridin-4-ylmethyl)-1,3-thiazolidine-2-carboxamide Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1C(=O)NCC1=CC=NC=C1 CJSHFPGMMMDUQX-QMRFKDRMSA-N 0.000 claims description 2
• DDHAQEUNSBGCCJ-YAOANENCSA-N 3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-n-[2-(1h-indol-3-yl)ethyl]-1,3-thiazolidine-2-carboxamide Chemical compound C([C@H](CC(=O)N1C(SCC1)C(=O)NCCC=1C2=CC=CC=C2NC=1)N)C1=CC(F)=C(F)C=C1F DDHAQEUNSBGCCJ-YAOANENCSA-N 0.000 claims description 2
• QBWONUGOJGPKIR-VYTXHYLQSA-N 5-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-1,3-benzodioxole-2-carboxylic acid Chemical compound C([C@H](CC(=O)N1C(SCC1)C(=O)NCC=1C=C2OC(OC2=CC=1)C(O)=O)N)C1=CC(F)=C(F)C=C1F QBWONUGOJGPKIR-VYTXHYLQSA-N 0.000 claims description 2
• 239000005711 Benzoic acid Substances 0.000 claims description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 2
• GSRVXHSKVWTGMM-ADRQNKRLSA-N [4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenyl] acetate Chemical compound C1=CC(OC(=O)C)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 GSRVXHSKVWTGMM-ADRQNKRLSA-N 0.000 claims description 2
• 235000010233 benzoic acid Nutrition 0.000 claims description 2
• WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 claims description 2
• PCDHSSHKDZYLLI-UHFFFAOYSA-N butan-1-one Chemical compound CCC[C]=O PCDHSSHKDZYLLI-UHFFFAOYSA-N 0.000 claims description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
• 239000003814 drug Substances 0.000 claims description 2
• XRHMVMSHESRPEM-BPAMGIGYSA-N ethyl (2S)-2-[[3-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]-3-methylbutanoate Chemical compound CCOC(=O)[C@@H](NC(=O)C1SCCN1C(=O)C[C@H](N)Cc1cc(F)c(F)cc1F)C(C)C XRHMVMSHESRPEM-BPAMGIGYSA-N 0.000 claims description 2
• MXAOKLOXVBOKEW-ADCSMLMYSA-N ethyl (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2-(trifluoromethyl)anilino]-3-methylbutanoate Chemical compound C1=C(C(F)(F)F)C(N[C@@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 MXAOKLOXVBOKEW-ADCSMLMYSA-N 0.000 claims description 2
• WQSWFGROKIRGSF-IIEMKKSWSA-N ethyl (2s)-2-[[6-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]pyridin-3-yl]amino]-3-methylbutanoate;hydrochloride Chemical compound Cl.N1=CC(N[C@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 WQSWFGROKIRGSF-IIEMKKSWSA-N 0.000 claims description 2
• UPAPYMORAMNESW-GZAIGYLVSA-N ethyl 2-[3-[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=CC(NC(=O)C2N(CCS2)C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)=C1 UPAPYMORAMNESW-GZAIGYLVSA-N 0.000 claims description 2
• MYIVWHAJXYALMZ-SMFUYQKNSA-N ethyl 2-[3-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=CC(CNC(=O)C2N(CCS2)C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)=C1 MYIVWHAJXYALMZ-SMFUYQKNSA-N 0.000 claims description 2
• YXBDCYDMXMSFAK-FQEBHOFPSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoate Chemical compound C1=CC(NC(C(=O)OCC)C(C)C)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 YXBDCYDMXMSFAK-FQEBHOFPSA-N 0.000 claims description 2
• IRCGPLRKGXDPQB-UGSZZNERSA-N ethyl 2-[[2-[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]-3,4-dihydro-1h-isoquinolin-6-yl]oxy]-3-methylbutanoate Chemical compound C([C@@H](N)CC(=O)N1CCSC1C(=O)N1CC2=CC=C(C=C2CC1)OC(C(=O)OCC)C(C)C)C1=CC(F)=C(F)C=C1F IRCGPLRKGXDPQB-UGSZZNERSA-N 0.000 claims description 2
• ATLYXUSEFJBBCU-YZJYNBPASA-N ethyl 5-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-1,3-benzodioxole-2-carboxylate Chemical compound C([C@@H](N)CC(=O)N1CCSC1C(=O)NCC1=CC=C2OC(OC2=C1)C(=O)OCC)C1=CC(F)=C(F)C=C1F ATLYXUSEFJBBCU-YZJYNBPASA-N 0.000 claims description 2
• 238000001953 recrystallisation Methods 0.000 claims description 2
• 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 claims 9
• UBAYFZVPLUBJHX-UHFFFAOYSA-N 1,3-thiazolidine-2-carboxamide;hydrochloride Chemical compound Cl.NC(=O)C1NCCS1 UBAYFZVPLUBJHX-UHFFFAOYSA-N 0.000 claims 3
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 2
• XIPLQXNQDFBPSX-CVPCNNORSA-N ethyl 2-[[2-[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]-3,4-dihydro-1h-isoquinolin-7-yl]oxy]-3-methylbutanoate;hydrochloride Chemical compound Cl.C([C@@H](N)CC(=O)N1CCSC1C(=O)N1CCC2=CC=C(C=C2C1)OC(C(=O)OCC)C(C)C)C1=CC(F)=C(F)C=C1F XIPLQXNQDFBPSX-CVPCNNORSA-N 0.000 claims 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 claims 1
• QYYRKMWJQQAQSV-MWTRTKDXSA-N 2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-2-methylpropanoic acid Chemical compound C1=CC(NC(C)(C)C(O)=O)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 QYYRKMWJQQAQSV-MWTRTKDXSA-N 0.000 claims 1
• ZUNWVBNRQTWJFD-PAQRCMFQSA-N 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoic acid Chemical compound C1=CC(NC(C(C)C)C(O)=O)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZUNWVBNRQTWJFD-PAQRCMFQSA-N 0.000 claims 1
• WFHWZMSRGHXHES-JRLVAEJTSA-N 2-hydroxyethyl (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoate Chemical compound C1=CC(N[C@H](C(C)C)C(=O)OCCO)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 WFHWZMSRGHXHES-JRLVAEJTSA-N 0.000 claims 1
• WNLAZJAMLUNUCR-ILRUXTBWSA-N 4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2-hydroxybenzoic acid Chemical compound C([C@H](N)CC=1C(=CC(F)=C(F)C=1)F)C(=O)N1CCSC1C(=O)NCC1=CC=C(C(O)=O)C(O)=C1 WNLAZJAMLUNUCR-ILRUXTBWSA-N 0.000 claims 1
• JONWIIXAHBVXNW-UHFFFAOYSA-N Cl.O1C(=COC=C1)C(=O)O Chemical compound Cl.O1C(=COC=C1)C(=O)O JONWIIXAHBVXNW-UHFFFAOYSA-N 0.000 claims 1
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• MCJHRDLFDPIUGY-FPRIQVAYSA-N ethyl (2r)-2-[4-[[8-[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]-1,4-dioxo-6,7,9,9a-tetrahydro-3h-pyrazino[1,2-a]pyrazin-2-yl]methyl]phenoxy]-3-methylbutanoate Chemical compound C1=CC(O[C@@H](C(=O)OCC)C(C)C)=CC=C1CN1C(=O)C2CN(C(=O)C3N(CCS3)C(=O)C[C@H](N)CC=3C(=CC(F)=C(F)C=3)F)CCN2C(=O)C1 MCJHRDLFDPIUGY-FPRIQVAYSA-N 0.000 claims 1
• YXBDCYDMXMSFAK-WMTVXVAQSA-N ethyl (2s)-2-[4-[[[(2r)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-3-methylbutanoate Chemical compound C1=CC(N[C@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 YXBDCYDMXMSFAK-WMTVXVAQSA-N 0.000 claims 1
• FRISPUCLLZSEBV-ANLYYEBFSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-3-fluorophenoxy]-3-methylbutanoate;hydrochloride Chemical compound Cl.FC1=CC(OC(C(=O)OCC)C(C)C)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 FRISPUCLLZSEBV-ANLYYEBFSA-N 0.000 claims 1
• DUEXFHBNSRGHCO-UGSZZNERSA-N ethyl 2-[[2-[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]-3,4-dihydro-1h-isoquinolin-7-yl]oxy]-3-methylbutanoate Chemical compound C([C@@H](N)CC(=O)N1CCSC1C(=O)N1CCC2=CC=C(C=C2C1)OC(C(=O)OCC)C(C)C)C1=CC(F)=C(F)C=C1F DUEXFHBNSRGHCO-UGSZZNERSA-N 0.000 claims 1
• BYCNNESRBOCZLP-XDTYDRSUSA-N ethyl 5-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-1,3-benzodioxole-2-carboxylate;hydrochloride Chemical compound Cl.C([C@@H](N)CC(=O)N1CCSC1C(=O)NCC1=CC=C2OC(OC2=C1)C(=O)OCC)C1=CC(F)=C(F)C=C1F BYCNNESRBOCZLP-XDTYDRSUSA-N 0.000 claims 1
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• ISMLHSAZLRACOR-NREPNLDQSA-N ethyl (2s)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2-fluoroanilino]-3-methylbutanoate Chemical compound C1=C(F)C(N[C@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ISMLHSAZLRACOR-NREPNLDQSA-N 0.000 description 2
• ZSRFLOUIEKJRKW-KAZGAHJFSA-N ethyl (2s)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-methylbutanoate Chemical compound C1=CC(O[C@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ZSRFLOUIEKJRKW-KAZGAHJFSA-N 0.000 description 2
• JJWTWYHCWFFNHK-LGTHEAAHSA-N ethyl (2s)-3-methyl-2-[4-[[[(2r)-3-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]butanoate Chemical compound C1=CC(O[C@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@@H]1N(C(=O)C[C@@H](CC=2C(=CC(F)=C(F)C=2)F)NC(=O)OC(C)(C)C)CCS1 JJWTWYHCWFFNHK-LGTHEAAHSA-N 0.000 description 2
• RJLWFEPHNRKFQU-SLTKKEMYSA-N ethyl (2s)-3-methyl-2-[4-[[[(2s)-3-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]butanoate Chemical compound C1=CC(N[C@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@@H](CC=2C(=CC(F)=C(F)C=2)F)NC(=O)OC(C)(C)C)CCS1 RJLWFEPHNRKFQU-SLTKKEMYSA-N 0.000 description 2
• JJWTWYHCWFFNHK-JPDBUEETSA-N ethyl (2s)-3-methyl-2-[4-[[[(2s)-3-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]butanoate Chemical compound C1=CC(O[C@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@@H](CC=2C(=CC(F)=C(F)C=2)F)NC(=O)OC(C)(C)C)CCS1 JJWTWYHCWFFNHK-JPDBUEETSA-N 0.000 description 2
• AUBPEEOHUNULEG-UHFFFAOYSA-N ethyl 2-[4-(aminomethyl)phenoxy]acetate;hydrochloride Chemical compound Cl.CCOC(=O)COC1=CC=C(CN)C=C1 AUBPEEOHUNULEG-UHFFFAOYSA-N 0.000 description 2
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• SAQDEFPRJWRBTE-QPJICYPMSA-N (2r)-2-[[5-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]pyrimidin-2-yl]amino]-3-methylbutanoic acid Chemical compound C1=NC(N[C@H](C(C)C)C(O)=O)=NC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 SAQDEFPRJWRBTE-QPJICYPMSA-N 0.000 description 1
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• LXFMHRJCQKEPPH-UFFYZIETSA-N ethyl (2S)-2-[4-[[[(2S)-3-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2-fluoroanilino]-3-methylbutanoate hydrochloride Chemical compound Cl.CCOC(=O)[C@@H](NC1=C(F)C=C(CNC(=O)[C@@H]2SCCN2C(=O)C[C@H](N)CC2=C(F)C=C(F)C(F)=C2)C=C1)C(C)C LXFMHRJCQKEPPH-UFFYZIETSA-N 0.000 description 1
• ARLIQBRYLXYYRV-KKEFPKGYSA-N ethyl (2S)-2-[4-[[[(2S)-3-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]-3-methylbutanoate hydrochloride Chemical compound Cl.CCOC(=O)[C@@H](OC1=CC=C(CNC(=O)[C@@H]2SCCN2C(=O)C[C@H](N)CC2=C(F)C=C(F)C(F)=C2)C=C1)C(C)C ARLIQBRYLXYYRV-KKEFPKGYSA-N 0.000 description 1
• JCFIIBLEDPCVAS-CYBMUJFWSA-N ethyl (2r)-2-[4-(aminomethyl)anilino]-3-methylbutanoate Chemical compound CCOC(=O)[C@@H](C(C)C)NC1=CC=C(CN)C=C1 JCFIIBLEDPCVAS-CYBMUJFWSA-N 0.000 description 1
• BOTWGEUVJWFHLQ-CYBMUJFWSA-N ethyl (2r)-2-[4-(aminomethyl)phenoxy]-3-methylbutanoate Chemical compound CCOC(=O)[C@@H](C(C)C)OC1=CC=C(CN)C=C1 BOTWGEUVJWFHLQ-CYBMUJFWSA-N 0.000 description 1
• ISMLHSAZLRACOR-ADCSMLMYSA-N ethyl (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2-fluoroanilino]-3-methylbutanoate Chemical compound C1=C(F)C(N[C@@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 ISMLHSAZLRACOR-ADCSMLMYSA-N 0.000 description 1
• CZPGXQKLLWMFJL-ADCSMLMYSA-N ethyl (2r)-2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-3-fluoroanilino]-3-methylbutanoate Chemical compound FC1=CC(N[C@@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 CZPGXQKLLWMFJL-ADCSMLMYSA-N 0.000 description 1
• HJQATGWHLSJCHD-UFKXBGGNSA-N ethyl (2r)-2-[5-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]pyridin-2-yl]oxy-3-methylbutanoate Chemical compound C1=NC(O[C@@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 HJQATGWHLSJCHD-UFKXBGGNSA-N 0.000 description 1
• HJRWXPPHBSGOQU-UFKXBGGNSA-N ethyl (2r)-2-[[5-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]pyridin-2-yl]amino]-3-methylbutanoate Chemical compound C1=NC(N[C@@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 HJRWXPPHBSGOQU-UFKXBGGNSA-N 0.000 description 1
• RJLWFEPHNRKFQU-OIUQCLNLSA-N ethyl (2r)-3-methyl-2-[4-[[[(2s)-3-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]butanoate Chemical compound C1=CC(N[C@@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@@H](CC=2C(=CC(F)=C(F)C=2)F)NC(=O)OC(C)(C)C)CCS1 RJLWFEPHNRKFQU-OIUQCLNLSA-N 0.000 description 1
• JJWTWYHCWFFNHK-BOGJOCPPSA-N ethyl (2r)-3-methyl-2-[4-[[[(2s)-3-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]butanoate Chemical compound C1=CC(O[C@@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@@H](CC=2C(=CC(F)=C(F)C=2)F)NC(=O)OC(C)(C)C)CCS1 JJWTWYHCWFFNHK-BOGJOCPPSA-N 0.000 description 1
• JCFIIBLEDPCVAS-ZDUSSCGKSA-N ethyl (2s)-2-[4-(aminomethyl)anilino]-3-methylbutanoate Chemical compound CCOC(=O)[C@H](C(C)C)NC1=CC=C(CN)C=C1 JCFIIBLEDPCVAS-ZDUSSCGKSA-N 0.000 description 1
• HJRWXPPHBSGOQU-VAQLEPBLSA-N ethyl (2s)-2-[[5-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]pyridin-2-yl]amino]-3-methylbutanoate Chemical compound C1=NC(N[C@H](C(=O)OCC)C(C)C)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 HJRWXPPHBSGOQU-VAQLEPBLSA-N 0.000 description 1
• JRFIQNMUPHAVQJ-INIZCTEOSA-N ethyl (2s)-3-methyl-2-[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]anilino]butanoate Chemical compound CCOC(=O)[C@H](C(C)C)NC1=CC=C(CNC(=O)OC(C)(C)C)C=C1 JRFIQNMUPHAVQJ-INIZCTEOSA-N 0.000 description 1
• STIPQAUQYAPPPL-UHFFFAOYSA-N ethyl 1,3-thiazolidine-2-carboxylate Chemical compound CCOC(=O)C1NCCS1 STIPQAUQYAPPPL-UHFFFAOYSA-N 0.000 description 1
• LMARPZPLPBLWGD-QFADGXAASA-N ethyl 1-[3-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)C1N(C(=O)C[C@@H](CC=2C(=CC(F)=C(F)C=2)F)NC(=O)OC(C)(C)C)CCS1 LMARPZPLPBLWGD-QFADGXAASA-N 0.000 description 1
• IBGBOGKPIMZRRU-UHFFFAOYSA-N ethyl 2-(4-aminophenoxy)acetate Chemical compound CCOC(=O)COC1=CC=C(N)C=C1 IBGBOGKPIMZRRU-UHFFFAOYSA-N 0.000 description 1
• UFENDJKWVPGHGY-UHFFFAOYSA-N ethyl 2-(4-aminophenoxy)acetate;hydrochloride Chemical compound Cl.CCOC(=O)COC1=CC=C(N)C=C1 UFENDJKWVPGHGY-UHFFFAOYSA-N 0.000 description 1
• AHZPCHIMDHLWOY-FPDMAROZSA-N ethyl 2-[3-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]acetate;hydrochloride Chemical compound Cl.CCOC(=O)COC1=CC=CC(CNC(=O)C2N(CCS2)C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)=C1 AHZPCHIMDHLWOY-FPDMAROZSA-N 0.000 description 1
• WWGTZWCTIBWXQT-VLEDXSGQSA-N ethyl 2-[4-[[[(2r)-3-[3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1CNC(=O)[C@@H]1N(C(=O)CC(CC=2C(=CC(F)=C(F)C=2)F)NC(=O)OC(C)(C)C)CCS1 WWGTZWCTIBWXQT-VLEDXSGQSA-N 0.000 description 1
• NFMXJIQAIOKIIO-CJAUYULYSA-N ethyl 2-[4-[[[(2s)-3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]anilino]-2-methylpropanoate Chemical compound C1=CC(NC(C)(C)C(=O)OCC)=CC=C1CNC(=O)[C@H]1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 NFMXJIQAIOKIIO-CJAUYULYSA-N 0.000 description 1
• WWGTZWCTIBWXQT-HFLPEKOISA-N ethyl 2-[4-[[[3-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1CNC(=O)C1N(C(=O)C[C@@H](CC=2C(=CC(F)=C(F)C=2)F)NC(=O)OC(C)(C)C)CCS1 WWGTZWCTIBWXQT-HFLPEKOISA-N 0.000 description 1
• PVZMHJRAEADONR-IHKRANBOSA-N ethyl 2-[4-[[[3-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1CNC(=O)C1N(C(=O)C[C@@H](CC=2C(=CC(F)=C(F)C=2)F)NC(=O)OC(C)(C)C)CCS1 PVZMHJRAEADONR-IHKRANBOSA-N 0.000 description 1
• IGVOZGSEBUCZGF-FPDMAROZSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2-fluorophenoxy]-2-methylpropanoate;hydrochloride Chemical compound Cl.C1=C(F)C(OC(C)(C)C(=O)OCC)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 IGVOZGSEBUCZGF-FPDMAROZSA-N 0.000 description 1
• MBAUOGFCFIWPPL-FPDMAROZSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-3-fluorophenoxy]-2-methylpropanoate;hydrochloride Chemical compound Cl.FC1=CC(OC(C)(C)C(=O)OCC)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 MBAUOGFCFIWPPL-FPDMAROZSA-N 0.000 description 1
• NFAHWEUEOAAQSM-FPDMAROZSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]acetate;hydrochloride Chemical compound Cl.C1=CC(OCC(=O)OCC)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 NFAHWEUEOAAQSM-FPDMAROZSA-N 0.000 description 1
• YNYBGKCOJWHSCS-CQTDTLOKSA-N ethyl 2-[4-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]propanoate Chemical compound C1=CC(OC(C)C(=O)OCC)=CC=C1CNC(=O)C1N(C(=O)C[C@H](N)CC=2C(=CC(F)=C(F)C=2)F)CCS1 YNYBGKCOJWHSCS-CQTDTLOKSA-N 0.000 description 1
• ZIQKBWIYPJFXRC-CVPCNNORSA-N ethyl 2-[[2-[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]-3,4-dihydro-1h-isoquinolin-6-yl]oxy]-3-methylbutanoate;hydrochloride Chemical compound Cl.C([C@@H](N)CC(=O)N1CCSC1C(=O)N1CC2=CC=C(C=C2CC1)OC(C(=O)OCC)C(C)C)C1=CC(F)=C(F)C=C1F ZIQKBWIYPJFXRC-CVPCNNORSA-N 0.000 description 1
• JJWTWYHCWFFNHK-UGOCBOTJSA-N ethyl 3-methyl-2-[4-[[[3-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]phenoxy]butanoate Chemical compound C1=CC(OC(C(=O)OCC)C(C)C)=CC=C1CNC(=O)C1N(C(=O)C[C@@H](CC=2C(=CC(F)=C(F)C=2)F)NC(=O)OC(C)(C)C)CCS1 JJWTWYHCWFFNHK-UGOCBOTJSA-N 0.000 description 1
• PGZGLXMUEJMKJW-BXXBBJPTSA-N ethyl 6-[[[3-[(3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2,3-dihydro-1,4-benzodioxine-2-carboxylate Chemical compound C([C@H](CC(=O)N1CCSC1C(=O)NCC=1C=C2OCC(OC2=CC=1)C(=O)OCC)NC(=O)OC(C)(C)C)C1=CC(F)=C(F)C=C1F PGZGLXMUEJMKJW-BXXBBJPTSA-N 0.000 description 1
• SPSJYTVMNHHFNU-MKTXYTBSSA-N ethyl 6-[[[3-[(3r)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-1,3-thiazolidine-2-carbonyl]amino]methyl]-2,3-dihydro-1,4-benzodioxine-2-carboxylate;hydrochloride Chemical compound Cl.C([C@@H](N)CC(=O)N1CCSC1C(=O)NCC=1C=C2OCC(OC2=CC=1)C(=O)OCC)C1=CC(F)=C(F)C=C1F SPSJYTVMNHHFNU-MKTXYTBSSA-N 0.000 description 1
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