JP4959569B2 - 新規なジペプチジルペプチダーゼiv阻害剤、それらを含む医薬品組成物、およびそれらを調製するためのプロセス - Google Patents
新規なジペプチジルペプチダーゼiv阻害剤、それらを含む医薬品組成物、およびそれらを調製するためのプロセス Download PDFInfo
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- JP4959569B2 JP4959569B2 JP2007536276A JP2007536276A JP4959569B2 JP 4959569 B2 JP4959569 B2 JP 4959569B2 JP 2007536276 A JP2007536276 A JP 2007536276A JP 2007536276 A JP2007536276 A JP 2007536276A JP 4959569 B2 JP4959569 B2 JP 4959569B2
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- Prior art keywords
- mmol
- acetyl
- carbonitrile
- cyclopentylamino
- ylmethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 34
- 238000000034 method Methods 0.000 title description 75
- 230000008569 process Effects 0.000 title description 2
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 title 1
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 154
- -1 2,5-dimethyl-1H-1-pyrrolylmethyl Chemical group 0.000 claims description 79
- 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 53
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 35
- 229940125396 insulin Drugs 0.000 claims description 27
- 102000004877 Insulin Human genes 0.000 claims description 26
- 108090001061 Insulin Proteins 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 claims description 5
- VLJNHYLEOZPXFW-UHFFFAOYSA-N pyrrolidine-2-carboxamide Chemical compound NC(=O)C1CCCN1 VLJNHYLEOZPXFW-UHFFFAOYSA-N 0.000 claims description 5
- QGNRKZMCGJBYSD-ILXRZTDVSA-N (2s)-1-[2-[[(1s,3r)-3-(pyrazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C([C@@H]1CC[C@@H](C1)NCC(=O)N1[C@@H](CCC1)C#N)N1C=CC=N1 QGNRKZMCGJBYSD-ILXRZTDVSA-N 0.000 claims description 4
- XFYHCMFFNFVTDO-RFGFWPKPSA-N (2s,4s)-4-fluoro-1-[2-[[(1s,3r)-3-(triazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1[C@@H](F)C[C@@H](C#N)N1C(=O)CN[C@@H]1C[C@H](CN2N=NC=C2)CC1 XFYHCMFFNFVTDO-RFGFWPKPSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
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- PPGDORKIIFXPNU-DBVUQKKJSA-N (2s)-1-[2-[[(1r,3s)-3-(1,3-dihydroisoindol-2-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N([C@H]1C[C@@H](CN2CC3=CC=CC=C3C2)CC1)CC(=O)N1CCC[C@H]1C#N PPGDORKIIFXPNU-DBVUQKKJSA-N 0.000 claims description 3
- NWOQBZHQGOHVFO-XHSDSOJGSA-N (2s)-1-[2-[[(1r,3s)-3-(2,3-dihydrobenzotriazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N([C@H]1C[C@@H](CN2C3=CC=CC=C3NN2)CC1)CC(=O)N1CCC[C@H]1C#N NWOQBZHQGOHVFO-XHSDSOJGSA-N 0.000 claims description 3
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- VMYUSJJAIOYGFX-XHSDSOJGSA-N (2s)-1-[2-[[(1r,3s)-3-(benzotriazol-2-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N([C@H]1C[C@@H](CN2N=C3C=CC=CC3=N2)CC1)CC(=O)N1CCC[C@H]1C#N VMYUSJJAIOYGFX-XHSDSOJGSA-N 0.000 claims description 3
- WTSADRPXCPMCAW-ZNMIVQPWSA-N (2s)-1-[2-[[(1r,3s)-3-(imidazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C([C@H]1CC[C@H](C1)NCC(=O)N1[C@@H](CCC1)C#N)N1C=CN=C1 WTSADRPXCPMCAW-ZNMIVQPWSA-N 0.000 claims description 3
- KIHLKFPJLZFBGT-XHSDSOJGSA-N (2s)-1-[2-[[(1r,3s)-3-(morpholin-4-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C([C@H]1CC[C@H](C1)NCC(=O)N1[C@@H](CCC1)C#N)N1CCOCC1 KIHLKFPJLZFBGT-XHSDSOJGSA-N 0.000 claims description 3
- KLOWNBULXQPQHF-ZNMIVQPWSA-N (2s)-1-[2-[[(1r,3s)-3-[(1,1-dioxo-1,2-thiazolidin-2-yl)methyl]cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C([C@H]1CC[C@H](C1)NCC(=O)N1[C@@H](CCC1)C#N)N1CCCS1(=O)=O KLOWNBULXQPQHF-ZNMIVQPWSA-N 0.000 claims description 3
- YMTDMNKORGPJSB-QGTPRVQTSA-N (2s)-1-[2-[[(1r,3s)-3-[[5-(4-fluorophenyl)tetrazol-2-yl]methyl]cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1=CC(F)=CC=C1C1=NN(C[C@@H]2C[C@@H](CC2)NCC(=O)N2[C@@H](CCC2)C#N)N=N1 YMTDMNKORGPJSB-QGTPRVQTSA-N 0.000 claims description 3
- NZHRKBKTKWQHRW-RDBSUJKOSA-N (2s)-1-[2-[[(1s,3r)-3-(1,2,4-triazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C([C@@H]1CC[C@@H](C1)NCC(=O)N1[C@@H](CCC1)C#N)N1C=NC=N1 NZHRKBKTKWQHRW-RDBSUJKOSA-N 0.000 claims description 3
- SJHWGKPRJMQRHX-NJAFHUGGSA-N (2s)-1-[2-[[(1s,3r)-3-(indazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N([C@@H]1C[C@H](CN2C3=CC=CC=C3C=N2)CC1)CC(=O)N1CCC[C@H]1C#N SJHWGKPRJMQRHX-NJAFHUGGSA-N 0.000 claims description 3
- BRPQMFNSYFZPLR-RDBSUJKOSA-N (2s)-1-[2-[[(1s,3r)-3-(triazol-2-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C([C@@H]1CC[C@@H](C1)NCC(=O)N1[C@@H](CCC1)C#N)N1N=CC=N1 BRPQMFNSYFZPLR-RDBSUJKOSA-N 0.000 claims description 3
- HQDWBFMTDPWUFE-URVUXULASA-N (2s)-1-[2-[[(1s,3r)-3-[(4-phenylpiperazin-1-yl)methyl]cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C([C@@H]1CC[C@@H](C1)NCC(=O)N1[C@@H](CCC1)C#N)N(CC1)CCN1C1=CC=CC=C1 HQDWBFMTDPWUFE-URVUXULASA-N 0.000 claims description 3
- NZHRKBKTKWQHRW-RUXDESIVSA-N (2s)-1-[2-[[3-(1,2,4-triazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CCC1)C#N)C(=O)CNC(C1)CCC1CN1C=NC=N1 NZHRKBKTKWQHRW-RUXDESIVSA-N 0.000 claims description 3
- NICVLZBRCPWCAC-NRXISQOPSA-N (2s)-1-[2-[[3-(1,3-thiazolidin-3-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CCC1)C#N)C(=O)CNC(C1)CCC1CN1CCSC1 NICVLZBRCPWCAC-NRXISQOPSA-N 0.000 claims description 3
- YKQBPZCZJJHCEZ-VNXZQDSDSA-N (2s)-1-[2-[[3-[(4-benzylpiperazin-1-yl)methyl]cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CCC1)C#N)C(=O)CNC(C1)CCC1CN(CC1)CCN1CC1=CC=CC=C1 YKQBPZCZJJHCEZ-VNXZQDSDSA-N 0.000 claims description 3
- QULDJKFBPRFVJU-JCYILVPMSA-N (2s)-1-[2-[[3-[(4-methylpiperazin-1-yl)methyl]cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1CN(C)CCN1CC1CC(NCC(=O)N2[C@@H](CCC2)C#N)CC1 QULDJKFBPRFVJU-JCYILVPMSA-N 0.000 claims description 3
- UUACHWJZZYHNDN-JCYILVPMSA-N (2s)-1-[2-[[3-[[2-butyl-4-chloro-5-(hydroxymethyl)imidazol-1-yl]methyl]cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1CC(NCC(=O)N2[C@@H](CCC2)C#N)CC1 UUACHWJZZYHNDN-JCYILVPMSA-N 0.000 claims description 3
- UUCQSOXCUYPYQY-DVWBAYGPSA-N (2s,4s)-1-[2-[[(1r,3s)-3-(3,4-dihydro-1h-isoquinolin-2-ylmethyl)cyclopentyl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile Chemical compound C1[C@@H](F)C[C@@H](C#N)N1C(=O)CN[C@H]1C[C@@H](CN2CC3=CC=CC=C3CC2)CC1 UUCQSOXCUYPYQY-DVWBAYGPSA-N 0.000 claims description 3
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- JSYGLDMGERSRPC-RQJABVFESA-N (2s,4s)-4-fluoro-1-[2-[[(1r,3r)-3-(1,2,4-triazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1[C@@H](F)C[C@@H](C#N)N1C(=O)CN[C@H]1C[C@H](CN2N=CN=C2)CC1 JSYGLDMGERSRPC-RQJABVFESA-N 0.000 claims description 3
- JSYGLDMGERSRPC-FQUUOJAGSA-N (2s,4s)-4-fluoro-1-[2-[[(1r,3s)-3-(1,2,4-triazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1[C@@H](F)C[C@@H](C#N)N1C(=O)CN[C@H]1C[C@@H](CN2N=CN=C2)CC1 JSYGLDMGERSRPC-FQUUOJAGSA-N 0.000 claims description 3
- POHFRNVKGQVFQA-QVYXHAGSSA-N (2s,4s)-4-fluoro-1-[2-[[(1r,3s)-3-(1,2,4-triazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile;2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1O.C1[C@@H](F)C[C@@H](C#N)N1C(=O)CN[C@H]1C[C@@H](CN2N=CN=C2)CC1 POHFRNVKGQVFQA-QVYXHAGSSA-N 0.000 claims description 3
- IRNUBPKZFZIPQB-QVYXHAGSSA-N (2s,4s)-4-fluoro-1-[2-[[(1r,3s)-3-(1,2,4-triazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile;2-oxopentanedioic acid Chemical compound OC(=O)CCC(=O)C(O)=O.C1[C@@H](F)C[C@@H](C#N)N1C(=O)CN[C@H]1C[C@@H](CN2N=CN=C2)CC1 IRNUBPKZFZIPQB-QVYXHAGSSA-N 0.000 claims description 3
- STCKGUTYUCRBAW-QVYXHAGSSA-N (2s,4s)-4-fluoro-1-[2-[[(1r,3s)-3-(1,2,4-triazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.C1[C@@H](F)C[C@@H](C#N)N1C(=O)CN[C@H]1C[C@@H](CN2N=CN=C2)CC1 STCKGUTYUCRBAW-QVYXHAGSSA-N 0.000 claims description 3
- IAWFHPXSNMKWIL-QVYXHAGSSA-N (2s,4s)-4-fluoro-1-[2-[[(1r,3s)-3-(1,2,4-triazol-1-ylmethyl)cyclopentyl]amino]acetyl]pyrrolidine-2-carbonitrile;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1[C@@H](F)C[C@@H](C#N)N1C(=O)CN[C@H]1C[C@@H](CN2N=CN=C2)CC1 IAWFHPXSNMKWIL-QVYXHAGSSA-N 0.000 claims description 3
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- HNPOHJCNUGAMBX-XQQFMLRXSA-N (4s)-3-[2-[[(1r,3s)-3-(1,2,4-triazol-1-ylmethyl)cyclopentyl]amino]acetyl]-1,3-thiazolidine-4-carbonitrile Chemical compound C([C@H]1CC[C@H](C1)NCC(=O)N1[C@H](CSC1)C#N)N1C=NC=N1 HNPOHJCNUGAMBX-XQQFMLRXSA-N 0.000 claims description 3
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- VOWUTEFBRHOLNE-ABHNRTSZSA-N 1-[[3-[[2-[(2s)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]cyclopentyl]methyl]piperidine-4-carbonitrile Chemical compound N1([C@@H](CCC1)C#N)C(=O)CNC(C1)CCC1CN1CCC(C#N)CC1 VOWUTEFBRHOLNE-ABHNRTSZSA-N 0.000 claims description 3
- OHCQGILMLJDBSB-JCYILVPMSA-N 2-butyl-5-chloro-3-[[3-[[2-[(2s)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]cyclopentyl]methyl]imidazole-4-carbonitrile Chemical compound CCCCC1=NC(Cl)=C(C#N)N1CC1CC(NCC(=O)N2[C@@H](CCC2)C#N)CC1 OHCQGILMLJDBSB-JCYILVPMSA-N 0.000 claims description 3
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- YKXYBILTTSDSQL-HIFRSBDPSA-N tert-butyl n-[(1s,3r)-3-(2,3-dihydroindazol-1-ylmethyl)cyclopentyl]carbamate Chemical compound C1[C@@H](NC(=O)OC(C)(C)C)CC[C@H]1CN1C2=CC=CC=C2CN1 YKXYBILTTSDSQL-HIFRSBDPSA-N 0.000 description 1
- UFKKBPOMWYMQAX-NEPJUHHUSA-N tert-butyl n-[(1s,3r)-3-(pyrazol-1-ylmethyl)cyclopentyl]carbamate Chemical compound C1[C@@H](NC(=O)OC(C)(C)C)CC[C@H]1CN1N=CC=C1 UFKKBPOMWYMQAX-NEPJUHHUSA-N 0.000 description 1
- MCAQYCJCJFBDAE-MSOLQXFVSA-N tert-butyl n-[(1s,3r)-3-[(4-phenylpiperazin-1-yl)methyl]cyclopentyl]carbamate Chemical compound C1[C@@H](NC(=O)OC(C)(C)C)CC[C@H]1CN1CCN(C=2C=CC=CC=2)CC1 MCAQYCJCJFBDAE-MSOLQXFVSA-N 0.000 description 1
- FTHSVVZIFSSENA-WDEREUQCSA-N tert-butyl n-[(1s,4r)-4-(1,2,4-triazol-1-ylmethyl)cyclopent-2-en-1-yl]carbamate Chemical compound C1=C[C@@H](NC(=O)OC(C)(C)C)C[C@H]1CN1N=CN=C1 FTHSVVZIFSSENA-WDEREUQCSA-N 0.000 description 1
- IADYKWQLWYXWCK-BQBZGAKWSA-N tert-butyl n-[(2s,4s)-4-fluoropyrrolidine-2-carbonyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(=O)[C@@H]1C[C@H](F)CN1 IADYKWQLWYXWCK-BQBZGAKWSA-N 0.000 description 1
- GTKKTQURDHPDOT-ZCFIWIBFSA-N tert-butyl n-[(4s)-1,3-thiazolidine-4-carbonyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(=O)[C@H]1CSCN1 GTKKTQURDHPDOT-ZCFIWIBFSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- DDUFYKNOXPZZIW-CRCLSJGQSA-N vince lactam Chemical compound C1[C@H]2C(=O)N[C@@H]1C=C2 DDUFYKNOXPZZIW-CRCLSJGQSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
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- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
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- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
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- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
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- 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
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- 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
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- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
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- C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
- C07C309/66—Methanesulfonates
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- C07D207/325—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 two 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 with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
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- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
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- C07D295/12—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
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Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
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| US61810204P | 2004-10-12 | 2004-10-12 | |
| US60/618,102 | 2004-10-12 | ||
| IN1096/MUM/2004 | 2004-10-14 | ||
| IN1096MU2004 | 2004-10-14 | ||
| US63526604P | 2004-12-10 | 2004-12-10 | |
| US60/635,266 | 2004-12-10 | ||
| IN1332MU2004 | 2004-12-14 | ||
| IN1332/MUM/2004 | 2004-12-14 | ||
| PCT/IB2005/002204 WO2006040625A1 (en) | 2004-10-12 | 2005-07-26 | Novel dipeptidyl peptidase iv inhibitors, pharmaceutical compositions containing them, and process for their preparation |
Publications (3)
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| JP2008515962A JP2008515962A (ja) | 2008-05-15 |
| JP2008515962A5 JP2008515962A5 (https=) | 2008-09-11 |
| JP4959569B2 true JP4959569B2 (ja) | 2012-06-27 |
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| JP2007536276A Expired - Fee Related JP4959569B2 (ja) | 2004-10-12 | 2005-07-26 | 新規なジペプチジルペプチダーゼiv阻害剤、それらを含む医薬品組成物、およびそれらを調製するためのプロセス |
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| JP (1) | JP4959569B2 (https=) |
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- 2005-07-26 CA CA2583457A patent/CA2583457C/en not_active Expired - Fee Related
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- 2005-07-26 JP JP2007536276A patent/JP4959569B2/ja not_active Expired - Fee Related
- 2005-07-26 KR KR1020077010262A patent/KR20070073887A/ko not_active Ceased
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- 2005-07-26 EA EA200700720A patent/EA013463B1/ru not_active IP Right Cessation
- 2005-07-26 WO PCT/IB2005/002204 patent/WO2006040625A1/en not_active Ceased
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- 2005-07-26 MX MX2007004305A patent/MX2007004305A/es active IP Right Grant
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Also Published As
| Publication number | Publication date |
|---|---|
| MY142423A (en) | 2010-11-30 |
| BRPI0516340A (pt) | 2008-09-16 |
| EP1799639A1 (en) | 2007-06-27 |
| EA013463B1 (ru) | 2010-04-30 |
| EA200700720A1 (ru) | 2007-08-31 |
| IL182444A0 (en) | 2007-07-24 |
| WO2006040625A1 (en) | 2006-04-20 |
| MX2007004305A (es) | 2007-06-18 |
| AP2007003973A0 (en) | 2007-07-30 |
| US7205323B2 (en) | 2007-04-17 |
| AU2005293266B2 (en) | 2011-09-29 |
| US7538128B2 (en) | 2009-05-26 |
| US20060142585A1 (en) | 2006-06-29 |
| KR20070073887A (ko) | 2007-07-10 |
| AR053415A1 (es) | 2007-05-09 |
| EP1799639B1 (en) | 2013-09-04 |
| US20070238728A1 (en) | 2007-10-11 |
| JP2008515962A (ja) | 2008-05-15 |
| CA2583457C (en) | 2013-01-29 |
| US20070232608A1 (en) | 2007-10-04 |
| NZ554515A (en) | 2009-12-24 |
| CA2583457A1 (en) | 2006-04-20 |
| US7524844B2 (en) | 2009-04-28 |
| AU2005293266A1 (en) | 2006-04-20 |
| TW200614988A (en) | 2006-05-16 |
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