BG107327A - Инхибитори на протеаза - Google Patents

Инхибитори на протеаза Download PDF

Info

Publication number: BG107327A
Authority: BG; Bulgaria
Prior art keywords: methyl; azepan; amide; carboxylic acid; oxo
Prior art date: 2000-06-14

Application number

BG107327A

Other languages

Bulgarian (bg)

English (en)

Inventor

Robert Marquis

Yu Ru

Daniel VEBER

Maxwell CUMMINGS

Scott Thompson

Dennis Yamashita

Original Assignee

Smithkline Beecham Corporation

Priority date (The priority date 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 date listed.)

2000-06-14

Filing date

2002-11-28

Publication date

2003-07-31

2002-11-28 Application filed by Smithkline Beecham Corporation filed Critical Smithkline Beecham Corporation

2003-07-31 Publication of BG107327A publication Critical patent/BG107327A/bg

Links

239000000137 peptide hydrolase inhibitor Substances 0.000 title claims abstract description 10
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title abstract description 9
150000001875 compounds Chemical class 0.000 claims abstract description 694
238000000034 method Methods 0.000 claims abstract description 289
201000010099 disease Diseases 0.000 claims abstract description 38
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 38
108090000625 Cathepsin K Proteins 0.000 claims abstract description 26
239000004365 Protease Substances 0.000 claims abstract description 18
102000035195 Peptidases Human genes 0.000 claims abstract description 16
108091005804 Peptidases Proteins 0.000 claims abstract description 16
150000003839 salts Chemical class 0.000 claims abstract description 15
239000011159 matrix material Substances 0.000 claims abstract description 14
208000001132 Osteoporosis Diseases 0.000 claims abstract description 10
206010065687 Bone loss Diseases 0.000 claims abstract description 9
210000000845 cartilage Anatomy 0.000 claims abstract description 9
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
208000007565 gingivitis Diseases 0.000 claims abstract description 8
150000004677 hydrates Chemical class 0.000 claims abstract description 8
239000012453 solvate Substances 0.000 claims abstract description 8
201000008482 osteoarthritis Diseases 0.000 claims abstract description 7
206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 7
230000015556 catabolic process Effects 0.000 claims abstract description 6
238000006731 degradation reaction Methods 0.000 claims abstract description 6
230000002401 inhibitory effect Effects 0.000 claims abstract description 6
102000004171 Cathepsin K Human genes 0.000 claims abstract 3
-1 piperidinyl-ethyl Chemical group 0.000 claims description 554
OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 claims description 338
125000000217 alkyl group Chemical group 0.000 claims description 305
238000002360 preparation method Methods 0.000 claims description 190
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 177
238000004128 high performance liquid chromatography Methods 0.000 claims description 113
239000000203 mixture Substances 0.000 claims description 81
125000000484 butyl group Chemical class [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 79
150000001408 amides Chemical class 0.000 claims description 57
DYSJMQABFPKAQM-UHFFFAOYSA-N 1-benzothiophene-2-carboxylic acid Chemical compound C1=CC=C2SC(C(=O)O)=CC2=C1 DYSJMQABFPKAQM-UHFFFAOYSA-N 0.000 claims description 52
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 51
229910052739 hydrogen Inorganic materials 0.000 claims description 49
229910052799 carbon Inorganic materials 0.000 claims description 45
125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
102000005927 Cysteine Proteases Human genes 0.000 claims description 35
108010005843 Cysteine Proteases Proteins 0.000 claims description 35
XZELWEMGWISCTP-UHFFFAOYSA-N 5-methoxy-1-benzofuran-2-carboxylic acid Chemical compound COC1=CC=C2OC(C(O)=O)=CC2=C1 XZELWEMGWISCTP-UHFFFAOYSA-N 0.000 claims description 34
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
YMZTUCZCQMQFMK-UHFFFAOYSA-N 3-methyl-1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2C(C)=C(C(O)=O)OC2=C1 YMZTUCZCQMQFMK-UHFFFAOYSA-N 0.000 claims description 30
125000000499 benzofuranyl group Chemical class O1C(=CC2=C1C=CC=C2)* 0.000 claims description 26
125000003342 alkenyl group Chemical group 0.000 claims description 25
125000002541 furyl group Chemical group 0.000 claims description 25
125000000304 alkynyl group Chemical group 0.000 claims description 23
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
125000001544 thienyl group Chemical group 0.000 claims description 21
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 19
125000001972 isopentyl group Chemical class [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 18
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 17
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 16
JBVXXGSEMNXAMH-LSLKUGRBSA-N (2s)-2-amino-4-methyl-n-(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)pentanamide Chemical compound C1C(=O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC=N1 JBVXXGSEMNXAMH-LSLKUGRBSA-N 0.000 claims description 15
125000000842 isoxazolyl group Chemical group 0.000 claims description 15
125000004076 pyridyl group Chemical group 0.000 claims description 15
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 14
ADRFTNFHVKVATK-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenyl]furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1C1=CC=CC(C(F)(F)F)=C1 ADRFTNFHVKVATK-UHFFFAOYSA-N 0.000 claims description 13
230000015572 biosynthetic process Effects 0.000 claims description 12
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 claims description 12
238000003786 synthesis reaction Methods 0.000 claims description 12
QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 12
239000003814 drug Substances 0.000 claims description 11
239000007800 oxidant agent Substances 0.000 claims description 11
125000005605 benzo group Chemical group 0.000 claims description 10
230000005764 inhibitory process Effects 0.000 claims description 10
230000001590 oxidative effect Effects 0.000 claims description 10
UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 claims description 10
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
102000012479 Serine Proteases Human genes 0.000 claims description 8
108010022999 Serine Proteases Proteins 0.000 claims description 8
VDVJGIYXDVPQLP-UHFFFAOYSA-N piperonylic acid Chemical compound OC(=O)C1=CC=C2OCOC2=C1 VDVJGIYXDVPQLP-UHFFFAOYSA-N 0.000 claims description 8
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 8
125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 8
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 7
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 7
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 7
201000001245 periodontitis Diseases 0.000 claims description 7
239000000546 pharmaceutical excipient Substances 0.000 claims description 6
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 6
238000000926 separation method Methods 0.000 claims description 6
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 5
125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 5
241000222716 Crithidia Species 0.000 claims description 5
241000233872 Pneumocystis carinii Species 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
208000015181 infectious disease Diseases 0.000 claims description 5
201000004792 malaria Diseases 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
125000001436 propyl group Chemical class [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
201000004409 schistosomiasis Diseases 0.000 claims description 5
229940079593 drug Drugs 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
HITUZQPFDWNUHA-UHFFFAOYSA-N 5-fluoro-1-benzofuran-2-carboxylic acid Chemical compound FC1=CC=C2OC(C(=O)O)=CC2=C1 HITUZQPFDWNUHA-UHFFFAOYSA-N 0.000 claims description 3
HKDJXQQOMYETKO-LYKKTTPLSA-N O=C1CN(S(=O)(=O)CCC)CCCC1NC(=O)[C@H](CC(C)C)NC(=O)C1=CC=CS1 Chemical compound O=C1CN(S(=O)(=O)CCC)CCCC1NC(=O)[C@H](CC(C)C)NC(=O)C1=CC=CS1 HKDJXQQOMYETKO-LYKKTTPLSA-N 0.000 claims description 3
NRKKLJOOPCBMLZ-UEWDXFNNSA-N (2S)-2-amino-4-methyl-N-(3-oxo-1-propylsulfonylazepan-4-yl)pentanamide Chemical compound CCCS(=O)(=O)N1CCCC(NC(=O)[C@@H](N)CC(C)C)C(=O)C1 NRKKLJOOPCBMLZ-UEWDXFNNSA-N 0.000 claims description 2
APYFKVNVFGCYJO-LBAQZLPGSA-N (2s)-4-methyl-n-(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)-2-(3-piperidin-1-ylpropanoylamino)pentanamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)CCN1CCCCC1 APYFKVNVFGCYJO-LBAQZLPGSA-N 0.000 claims description 2
PSJMNAIMOCVKGC-UHFFFAOYSA-N 3-ethyl-1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2C(CC)=C(C(O)=O)OC2=C1 PSJMNAIMOCVKGC-UHFFFAOYSA-N 0.000 claims description 2
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IPPUBOMFHJXYTO-UHFFFAOYSA-N 3-methyl-n-[1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)carbamoyl]cyclopentyl]-1-benzofuran-2-carboxamide Chemical compound O1C2=CC=CC=C2C(C)=C1C(=O)NC1(C(=O)NC2C(CN(CCC2)S(=O)(=O)C=2N=CC=CC=2)=O)CCCC1 IPPUBOMFHJXYTO-UHFFFAOYSA-N 0.000 claims description 2
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MBJKFAUPYMUFOV-UHFFFAOYSA-N 4-methoxy-3-methyl-1-benzofuran-2-carboxylic acid Chemical compound COC1=CC=CC2=C1C(C)=C(C(O)=O)O2 MBJKFAUPYMUFOV-UHFFFAOYSA-N 0.000 claims description 2
GMIDGDXRCTUPNM-UHFFFAOYSA-N 5-fluoro-3-methyl-1-benzofuran-2-carboxylic acid Chemical compound C1=C(F)C=C2C(C)=C(C(O)=O)OC2=C1 GMIDGDXRCTUPNM-UHFFFAOYSA-N 0.000 claims description 2
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239000011347 resin Substances 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
229910052707 ruthenium Inorganic materials 0.000 description 1
230000007017 scission Effects 0.000 description 1
XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000012289 standard assay Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
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239000011550 stock solution Substances 0.000 description 1
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125000000565 sulfonamide group Chemical group 0.000 description 1
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150000003462 sulfoxides Chemical class 0.000 description 1
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239000000829 suppository Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
JYYSRYZQQVAEFL-UHFFFAOYSA-N tert-butyl 2,3,4,7-tetrahydroazepine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC=CC1 JYYSRYZQQVAEFL-UHFFFAOYSA-N 0.000 description 1
AGWMEEDCHKOTNZ-UHFFFAOYSA-N tert-butyl 3-hydroxy-4-(4-methylpentanoylamino)azepane-1-carboxylate Chemical compound CC(C)CCC(=O)NC1CCCN(C(=O)OC(C)(C)C)CC1O AGWMEEDCHKOTNZ-UHFFFAOYSA-N 0.000 description 1
UYRPECRSIWXLMK-GBYJYRDPSA-N tert-butyl 4-[2-[[2-[[(2S)-1-[(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]-1-benzofuran-5-yl]oxy]ethyl]piperazine-1-carboxylate Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCN1CCN(C(=O)OC(C)(C)C)CC1 UYRPECRSIWXLMK-GBYJYRDPSA-N 0.000 description 1
ARIXSJWFRFSRTP-XIJSCUBXSA-N tert-butyl 4-[2-[[2-[[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]carbamoyl]-1-benzofuran-5-yl]oxy]ethyl]piperazine-1-carboxylate Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCN1CCN(C(=O)OC(C)(C)C)CC1 ARIXSJWFRFSRTP-XIJSCUBXSA-N 0.000 description 1
NUHXKEOHSGKGDR-HSBZDZAISA-N tert-butyl 4-[[(2s)-2-amino-4-methylpentanoyl]amino]-3-hydroxyazepane-1-carboxylate Chemical compound CC(C)C[C@H](N)C(=O)NC1CCCN(C(=O)OC(C)(C)C)CC1O NUHXKEOHSGKGDR-HSBZDZAISA-N 0.000 description 1
YLLLNYLAZHPCNH-UHFFFAOYSA-N tert-butyl 4-amino-3-hydroxyazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(N)C(O)C1 YLLLNYLAZHPCNH-UHFFFAOYSA-N 0.000 description 1
FHSJLGJEGJGFDG-UHFFFAOYSA-N tert-butyl 4-azido-3-hydroxyazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(N=[N+]=[N-])C(O)C1 FHSJLGJEGJGFDG-UHFFFAOYSA-N 0.000 description 1
DJCGFLINOSWAOV-UHFFFAOYSA-N tert-butyl 8-oxa-5-azabicyclo[5.1.0]octane-5-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC2OC21 DJCGFLINOSWAOV-UHFFFAOYSA-N 0.000 description 1
UTOLHTDJTLAQHJ-GPJFCIFZSA-N tert-butyl N-[(2S)-1-[(1-benzoyl-3-hydroxyazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCCN1C(=O)C1=CC=CC=C1 UTOLHTDJTLAQHJ-GPJFCIFZSA-N 0.000 description 1
LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
QIRGSPUWJKPBLG-XBMUEBEBSA-N tert-butyl n-[(2s)-1-[(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-n-methylcarbamate Chemical compound C1C(O)C(NC(=O)[C@@H](N(C)C(=O)OC(C)(C)C)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC=N1 QIRGSPUWJKPBLG-XBMUEBEBSA-N 0.000 description 1
HRAKBUBNYAGJMU-VIQWUECVSA-N tert-butyl n-[(2s)-1-[(3-hydroxy-6,6-dimethyl-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CC(C)(C)CN1S(=O)(=O)C1=CC=CC=N1 HRAKBUBNYAGJMU-VIQWUECVSA-N 0.000 description 1
SYNUZGXGRZTRSR-XBMUEBEBSA-N tert-butyl n-[(2s)-1-[[1-(2-fluorophenyl)sulfonyl-3-hydroxyazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC=C1F SYNUZGXGRZTRSR-XBMUEBEBSA-N 0.000 description 1
PIUMNZJRAJCDLP-GPJFCIFZSA-N tert-butyl n-[(2s)-1-[[1-(3-chlorophenyl)sulfonyl-3-hydroxyazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC(Cl)=C1 PIUMNZJRAJCDLP-GPJFCIFZSA-N 0.000 description 1
WOHVMJJLQPVEJY-KBWCOIMZSA-N tert-butyl n-[(2s)-1-[[3-hydroxy-1-(3-methoxyphenyl)sulfonylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC1=CC=CC(S(=O)(=O)N2CC(O)C(NC(=O)[C@H](CC(C)C)NC(=O)OC(C)(C)C)CCC2)=C1 WOHVMJJLQPVEJY-KBWCOIMZSA-N 0.000 description 1
MIMRTPZXRUVGRK-KBWCOIMZSA-N tert-butyl n-[(2s)-1-[[3-hydroxy-1-(4-methoxyphenyl)sulfonylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1CC(O)C(NC(=O)[C@H](CC(C)C)NC(=O)OC(C)(C)C)CCC1 MIMRTPZXRUVGRK-KBWCOIMZSA-N 0.000 description 1
NGQNFRPEXIIKAF-AVAKVYKDSA-N tert-butyl n-[(2s)-1-[[3-hydroxy-1-(pyridine-2-carbonyl)azepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCCN1C(=O)C1=CC=CC=N1 NGQNFRPEXIIKAF-AVAKVYKDSA-N 0.000 description 1
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
PPATWCQATRATAM-UHFFFAOYSA-N tert-butyl n-pent-4-enyl-n-prop-2-enylcarbamate Chemical compound CC(C)(C)OC(=O)N(CC=C)CCCC=C PPATWCQATRATAM-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
UJJLJRQIPMGXEZ-UHFFFAOYSA-N tetrahydro-2-furoic acid Chemical compound OC(=O)C1CCCO1 UJJLJRQIPMGXEZ-UHFFFAOYSA-N 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000009210 therapy by ultrasound Methods 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000002769 thiazolinyl group Chemical group 0.000 description 1
JXHSGSLIUHNKRC-UHFFFAOYSA-N thieno[2,3-b]thiophene-5-carboxylic acid Chemical compound C1=CSC2=C1C=C(C(=O)O)S2 JXHSGSLIUHNKRC-UHFFFAOYSA-N 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical group ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
229960002898 threonine Drugs 0.000 description 1
230000036962 time dependent Effects 0.000 description 1
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
230000008733 trauma Effects 0.000 description 1
WORJEOGGNQDSOE-ASTXPPQBSA-N trichloro(deuterio)methane;trideuterio(deuteriooxy)methane Chemical compound [2H]C(Cl)(Cl)Cl.[2H]OC([2H])([2H])[2H] WORJEOGGNQDSOE-ASTXPPQBSA-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
239000004474 valine Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1

Classifications

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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A—HUMAN NECESSITIES
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
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- A61P33/08—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis for Pneumocystis carinii
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- A61P35/04—Antineoplastic agents specific for metastasis
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D223/12—Nitrogen atoms not forming part of a nitro radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Physical Education & Sports Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Tropical Medicine & Parasitology (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Oncology (AREA)
Pain & Pain Management (AREA)
Communicable Diseases (AREA)
Biomedical Technology (AREA)
Immunology (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Epoxy Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

BG107327A 2000-06-14 2002-11-28 Инхибитори на протеаза BG107327A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US59384500A	2000-06-14	2000-06-14
PCT/US2001/019062 WO2001095911A1 (fr)	2000-06-14	2001-06-14	Inhibiteurs de proteases

Publications (1)

Publication Number	Publication Date
BG107327A true BG107327A (bg)	2003-07-31

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Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG107327A BG107327A (bg)	2000-06-14	2002-11-28	Инхибитори на протеаза

Country Status (25)

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EP (1)	EP1307204A4 (fr)
JP (1)	JP2004503502A (fr)
KR (1)	KR20030008220A (fr)
CN (1)	CN1444481A (fr)
AP (1)	AP2002002671A0 (fr)
AR (1)	AR032622A1 (fr)
AU (1)	AU2001268407A1 (fr)
BG (1)	BG107327A (fr)
BR (1)	BR0111693A (fr)
CA (1)	CA2412353A1 (fr)
CZ (1)	CZ20024086A3 (fr)
EA (1)	EA200300018A1 (fr)
EC (1)	ECSP024388A (fr)
HU (1)	HUP0301231A2 (fr)
IL (1)	IL153421A0 (fr)
MA (1)	MA25758A1 (fr)
MX (1)	MXPA02012442A (fr)
NO (1)	NO20025786L (fr)
NZ (1)	NZ522965A (fr)
OA (1)	OA12288A (fr)
PE (1)	PE20011374A1 (fr)
PL (1)	PL360508A1 (fr)
SK (1)	SK17592002A3 (fr)
WO (1)	WO2001095911A1 (fr)
ZA (1)	ZA200209808B (fr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2001034159A1 (fr) *	1999-11-10	2001-05-17	Smithkline Beecham Corporation	Inhibiteurs de protease
EP1231921A4 (fr) *	1999-11-10	2004-06-23	Smithkline Beecham Corp	Inhibiteurs de proteases
CN1635903A (zh) *	2000-11-22	2005-07-06	史密丝克莱恩比彻姆公司	蛋白酶抑制剂
NZ526883A (en)	2001-02-20	2005-11-25	Chugai Pharmaceutical Co Ltd	Azoles as malonyl-coa decarboxylase inhibitors useful as metabolic modulators
US7709510B2 (en)	2001-02-20	2010-05-04	Chugai Seiyaku Kabushiki Kaisha	Azoles as malonyl-CoA decarboxylase inhibitors useful as metabolic modulators
AU2002342682A1 (en) *	2001-05-17	2002-11-25	Smithkline Beecham Corporation	Protease inhibitors
GB0220187D0 (en) *	2002-08-30	2002-10-09	Novartis Ag	Organic compounds
CA2533749C (fr)	2003-08-01	2012-07-10	Chugai Seiyaku Kabushiki Kaisha	Composes de piperidine utiles en tant qu'inhibiteurs de malonyl-coa decarboxylase
JP4727578B2 (ja)	2003-08-01	2011-07-20	中外製薬株式会社	マロニル−ＣｏＡデカルボキシラーゼ阻害剤として有用な複素環式化合物
EP2208495B1 (fr)	2003-08-01	2011-12-14	Chugai Seiyaku Kabushiki Kaisha	Composes azole a base de cyanoguanidine-utilises comme inhibiteurs de malonyl-coa decarboxylase
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2001
- 2001-06-14 NZ NZ522965A patent/NZ522965A/en unknown
- 2001-06-14 IL IL15342101A patent/IL153421A0/xx unknown
- 2001-06-14 AR ARP010102840A patent/AR032622A1/es not_active Application Discontinuation
- 2001-06-14 PE PE2001000566A patent/PE20011374A1/es not_active Application Discontinuation
- 2001-06-14 PL PL36050801A patent/PL360508A1/xx not_active Application Discontinuation
- 2001-06-14 AP APAP/P/2002/002671A patent/AP2002002671A0/en unknown
- 2001-06-14 HU HU0301231A patent/HUP0301231A2/hu unknown
- 2001-06-14 JP JP2002510089A patent/JP2004503502A/ja active Pending
- 2001-06-14 BR BR0111693-2A patent/BR0111693A/pt not_active IP Right Cessation
- 2001-06-14 EP EP01946344A patent/EP1307204A4/fr not_active Withdrawn
- 2001-06-14 SK SK1759-2002A patent/SK17592002A3/sk not_active Application Discontinuation
- 2001-06-14 CA CA002412353A patent/CA2412353A1/fr not_active Abandoned
- 2001-06-14 OA OA1200200377A patent/OA12288A/en unknown
- 2001-06-14 AU AU2001268407A patent/AU2001268407A1/en not_active Abandoned
- 2001-06-14 CZ CZ20024086A patent/CZ20024086A3/cs unknown
- 2001-06-14 CN CN01813500A patent/CN1444481A/zh active Pending
- 2001-06-14 MX MXPA02012442A patent/MXPA02012442A/es unknown
- 2001-06-14 WO PCT/US2001/019062 patent/WO2001095911A1/fr not_active Ceased
- 2001-06-14 EA EA200300018A patent/EA200300018A1/ru unknown
- 2001-06-14 KR KR1020027017045A patent/KR20030008220A/ko not_active Withdrawn
2002
- 2002-11-28 BG BG107327A patent/BG107327A/bg unknown
- 2002-12-02 NO NO20025786A patent/NO20025786L/no not_active Application Discontinuation
- 2002-12-03 ZA ZA200209808A patent/ZA200209808B/en unknown
- 2002-12-12 EC EC2002004388A patent/ECSP024388A/es unknown
- 2002-12-13 MA MA26952A patent/MA25758A1/fr unknown

Also Published As

Publication number	Publication date
PE20011374A1 (es)	2002-04-07
SK17592002A3 (sk)	2003-05-02
WO2001095911A1 (fr)	2001-12-20
NO20025786D0 (no)	2002-12-02
CA2412353A1 (fr)	2001-12-20
BR0111693A (pt)	2004-04-06
EP1307204A4 (fr)	2004-06-02
PL360508A1 (en)	2004-09-06
OA12288A (en)	2003-12-12
JP2004503502A (ja)	2004-02-05
EA200300018A1 (ru)	2003-06-26
AP2002002671A0 (en)	2002-12-31
NZ522965A (en)	2004-06-25
EP1307204A1 (fr)	2003-05-07
AR032622A1 (es)	2003-11-19
NO20025786L (no)	2003-02-12
MA25758A1 (fr)	2003-04-01
MXPA02012442A (es)	2003-04-25
IL153421A0 (en)	2003-07-06
ZA200209808B (en)	2004-07-09
CN1444481A (zh)	2003-09-24
KR20030008220A (ko)	2003-01-24
AU2001268407A1 (en)	2001-12-24
CZ20024086A3 (cs)	2003-05-14
HUP0301231A2 (hu)	2003-08-28
ECSP024388A (es)	2003-02-06

Publication	Publication Date	Title
KR100630986B1 (ko)	2006-10-09	프로테아제 억제제
AU2001243441B2 (en)	2004-11-25	Protease inhibitors
AU2001243441A1 (en)	2001-12-13	Protease inhibitors
BG107327A (bg)	2003-07-31	Инхибитори на протеаза
US7405209B2 (en)	2008-07-29	Protease inhibitors
EP1384713A1 (fr)	2004-01-28	Derives de 4-amino-azepan-3-one comme inhibiteurs de protease
KR20040004445A (ko)	2004-01-13	프로테아제 억제제
AU2003261482B2 (en)	2007-01-25	Protease inhibitors
MXPA01006613A (en)	2002-03-26	Protease inhibitors
HK1063051A (en)	2004-12-10	4-amino-azepan-3-one derivatives as protease inhibitors