NO323354B1 - Nye spiroheterocykliske forbindelser nyttige som inhibitorer av cystein proteaser samt anvendelse og fremstilling derav og farmasoytisk preparat. - Google Patents
Nye spiroheterocykliske forbindelser nyttige som inhibitorer av cystein proteaser samt anvendelse og fremstilling derav og farmasoytisk preparat. Download PDFInfo
- Publication number
- NO323354B1 NO323354B1 NO20021207A NO20021207A NO323354B1 NO 323354 B1 NO323354 B1 NO 323354B1 NO 20021207 A NO20021207 A NO 20021207A NO 20021207 A NO20021207 A NO 20021207A NO 323354 B1 NO323354 B1 NO 323354B1
- Authority
- NO
- Norway
- Prior art keywords
- cyano
- ylcarbamoyl
- carboxylic acid
- amide
- ethyl
- Prior art date
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- -1 spiro heterocyclic compounds Chemical class 0.000 title claims description 100
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 14
- 102000005927 Cysteine Proteases Human genes 0.000 title description 21
- 108010005843 Cysteine Proteases Proteins 0.000 title description 21
- 239000003112 inhibitor Substances 0.000 title description 19
- 238000002360 preparation method Methods 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 201
- STUHQDIOZQUPGP-UHFFFAOYSA-N morpholin-4-ium-4-carboxylate Chemical compound OC(=O)N1CCOCC1 STUHQDIOZQUPGP-UHFFFAOYSA-N 0.000 claims description 73
- 239000000460 chlorine Substances 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 38
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000003386 piperidinyl group Chemical group 0.000 claims description 22
- 125000006239 protecting group Chemical group 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- 238000010168 coupling process Methods 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 230000008878 coupling Effects 0.000 claims description 14
- 238000005859 coupling reaction Methods 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 13
- 125000005219 aminonitrile group Chemical group 0.000 claims description 13
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
- 150000001413 amino acids Chemical class 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 229910021529 ammonia Inorganic materials 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 150000002825 nitriles Chemical class 0.000 claims description 9
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 208000023275 Autoimmune disease Diseases 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 230000018044 dehydration Effects 0.000 claims description 6
- 238000006297 dehydration reaction Methods 0.000 claims description 6
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 208000001132 Osteoporosis Diseases 0.000 claims description 5
- 125000001589 carboacyl group Chemical group 0.000 claims description 5
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 3
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 3
- 208000003807 Graves Disease Diseases 0.000 claims description 3
- 208000015023 Graves' disease Diseases 0.000 claims description 3
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 3
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 206010039710 Scleroderma Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 201000008937 atopic dermatitis Diseases 0.000 claims description 3
- 125000003725 azepanyl group Chemical group 0.000 claims description 3
- 125000002393 azetidinyl group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 206010028417 myasthenia gravis Diseases 0.000 claims description 3
- MPQGVCZLBWGGCZ-UHFFFAOYSA-N n-[1-[(1-benzyl-3-cyanoazetidin-3-yl)amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1CCCCC1CC(NC(=O)N1CCOCC1)C(=O)NC(C1)(C#N)CN1CC1=CC=CC=C1 MPQGVCZLBWGGCZ-UHFFFAOYSA-N 0.000 claims description 3
- RFMAMOXGFSKWPV-UHFFFAOYSA-N n-[1-[(1-benzyl-4-cyanopiperidin-4-yl)amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1CCCCC1CC(NC(=O)N1CCOCC1)C(=O)NC(CC1)(C#N)CCN1CC1=CC=CC=C1 RFMAMOXGFSKWPV-UHFFFAOYSA-N 0.000 claims description 3
- UIVPCIQLAQMYPY-UHFFFAOYSA-N n-[1-[(3-cyano-1-methylpiperidin-3-yl)amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1N(C)CCCC1(C#N)NC(=O)C(NC(=O)N1CCOCC1)CC1CCCCC1 UIVPCIQLAQMYPY-UHFFFAOYSA-N 0.000 claims description 3
- IQCKXZJSZFWFQH-UHFFFAOYSA-N n-[1-[(3-cyano-1-pentan-3-ylpyrrolidin-3-yl)amino]-4,4-dimethyl-1-oxopentan-2-yl]morpholine-4-carboxamide Chemical compound C1N(C(CC)CC)CCC1(C#N)NC(=O)C(CC(C)(C)C)NC(=O)N1CCOCC1 IQCKXZJSZFWFQH-UHFFFAOYSA-N 0.000 claims description 3
- GRWCWNBGKIZOGM-UHFFFAOYSA-N n-[1-[(4-cyano-1,2-dimethylpiperidin-4-yl)amino]-4,4-dimethyl-1-oxopentan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(C)C(C)CC1(C#N)NC(=O)C(CC(C)(C)C)NC(=O)N1CCOCC1 GRWCWNBGKIZOGM-UHFFFAOYSA-N 0.000 claims description 3
- IRSOCWQJNYLTDD-UHFFFAOYSA-N n-[1-[(4-cyano-1-methylpiperidin-4-yl)amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(C)CCC1(C#N)NC(=O)C(NC(=O)N1CCOCC1)CC1CCCCC1 IRSOCWQJNYLTDD-UHFFFAOYSA-N 0.000 claims description 3
- QKDPOLJIBGOWFA-UHFFFAOYSA-N n-[1-[(4-cyano-1-propylpiperidin-4-yl)amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(CCC)CCC1(C#N)NC(=O)C(NC(=O)N1CCOCC1)CC1CCCCC1 QKDPOLJIBGOWFA-UHFFFAOYSA-N 0.000 claims description 3
- XSKPZPRUGOTUTE-UHFFFAOYSA-N n-[1-[[3-cyano-1-(cyclohexylmethyl)pyrrolidin-3-yl]amino]-4,4-dimethyl-1-oxopentan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(CC2CCCCC2)CC1(C#N)NC(=O)C(CC(C)(C)C)NC(=O)N1CCOCC1 XSKPZPRUGOTUTE-UHFFFAOYSA-N 0.000 claims description 3
- AKWRDYPNFXZINM-UHFFFAOYSA-N n-[1-[[3-cyano-1-[(3-methylphenyl)methyl]pyrrolidin-3-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound CC1=CC=CC(CN2CC(CC2)(NC(=O)C(CC2CCCCC2)NC(=O)N2CCOCC2)C#N)=C1 AKWRDYPNFXZINM-UHFFFAOYSA-N 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
- BGXAGLKPJAXBIQ-UHFFFAOYSA-N 5-chloro-n-[1-[(4-cyano-1-methylpiperidin-4-yl)amino]-3-cyclohexyl-1-oxopropan-2-yl]thiophene-2-carboxamide Chemical compound C1CN(C)CCC1(C#N)NC(=O)C(NC(=O)C=1SC(Cl)=CC=1)CC1CCCCC1 BGXAGLKPJAXBIQ-UHFFFAOYSA-N 0.000 claims description 2
- SENDJJXBZDNXDM-UHFFFAOYSA-N C1CN(C(C)C)CCC1(C#N)NC(=O)C(N)CC1CCCCC1 Chemical compound C1CN(C(C)C)CCC1(C#N)NC(=O)C(N)CC1CCCCC1 SENDJJXBZDNXDM-UHFFFAOYSA-N 0.000 claims description 2
- HILOMLHTDJGNRH-UHFFFAOYSA-N C1N(CCC)CCC1(C#N)NC(=O)C(N)CC1CCCCC1 Chemical compound C1N(CCC)CCC1(C#N)NC(=O)C(N)CC1CCCCC1 HILOMLHTDJGNRH-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- VIRVFGOUFHKKPU-UHFFFAOYSA-N N-[1-[(4-cyanopiperidin-4-yl)-(1-phenylethyl)amino]-4,4-dimethyl-1-oxopentan-2-yl]morpholine-4-carboxamide Chemical compound C=1C=CC=CC=1C(C)N(C1(CCNCC1)C#N)C(=O)C(CC(C)(C)C)NC(=O)N1CCOCC1 VIRVFGOUFHKKPU-UHFFFAOYSA-N 0.000 claims description 2
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 claims description 2
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- VDSRGDJGKKJISR-UHFFFAOYSA-N n-(4-cyano-1-propylpiperidin-4-yl)-4,4-dimethyl-2-[(2-thiophen-2-ylacetyl)amino]pentanamide Chemical compound C1CN(CCC)CCC1(C#N)NC(=O)C(CC(C)(C)C)NC(=O)CC1=CC=CS1 VDSRGDJGKKJISR-UHFFFAOYSA-N 0.000 claims description 2
- BICDQDLWODWVMD-UHFFFAOYSA-N n-[1-[(1-benzyl-3-cyanopyrrolidin-3-yl)amino]-3-(4-chlorophenyl)-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1=CC(Cl)=CC=C1CC(C(=O)NC1(CN(CC=2C=CC=CC=2)CC1)C#N)NC(=O)N1CCOCC1 BICDQDLWODWVMD-UHFFFAOYSA-N 0.000 claims description 2
- LKUZESSPIVOPMW-UHFFFAOYSA-N n-[1-[(1-benzyl-3-cyanopyrrolidin-3-yl)amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C=1C=C2C=CC=CC2=CC=1CC(NC(=O)N1CCOCC1)C(=O)NC(C1)(C#N)CCN1CC1=CC=CC=C1 LKUZESSPIVOPMW-UHFFFAOYSA-N 0.000 claims description 2
- GAWSSVFUEYCHIE-UHFFFAOYSA-N n-[1-[(1-benzyl-3-cyanopyrrolidin-3-yl)amino]-4-methyl-1-oxopent-4-en-2-yl]morpholine-4-carboxamide Chemical compound C1CN(CC=2C=CC=CC=2)CC1(C#N)NC(=O)C(CC(=C)C)NC(=O)N1CCOCC1 GAWSSVFUEYCHIE-UHFFFAOYSA-N 0.000 claims description 2
- UXTLPZQSDLKIPA-UHFFFAOYSA-N n-[1-[(1-benzyl-4-cyanopiperidin-4-yl)amino]-4,4-dimethyl-1-oxopentan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(CC=2C=CC=CC=2)CCC1(C#N)NC(=O)C(CC(C)(C)C)NC(=O)N1CCOCC1 UXTLPZQSDLKIPA-UHFFFAOYSA-N 0.000 claims description 2
- ANUKOPFIGVJEJB-UHFFFAOYSA-N n-[1-[(3-cyano-1-cyclopentylpyrrolidin-3-yl)amino]-4,4-dimethyl-1-oxopentan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(C2CCCC2)CC1(C#N)NC(=O)C(CC(C)(C)C)NC(=O)N1CCOCC1 ANUKOPFIGVJEJB-UHFFFAOYSA-N 0.000 claims description 2
- BKJJSIQISAJXJT-UHFFFAOYSA-N n-[1-[(3-cyano-1-propylpyrrolidin-3-yl)amino]-4,4-dimethyl-1-oxopentan-2-yl]morpholine-4-carboxamide Chemical compound C1N(CCC)CCC1(C#N)NC(=O)C(CC(C)(C)C)NC(=O)N1CCOCC1 BKJJSIQISAJXJT-UHFFFAOYSA-N 0.000 claims description 2
- QFYLALQVSSZTGX-UHFFFAOYSA-N n-[1-[(4-cyano-1-propan-2-ylpiperidin-4-yl)amino]-4,4-dimethyl-1-oxopentan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(C(C)C)CCC1(C#N)NC(=O)C(CC(C)(C)C)NC(=O)N1CCOCC1 QFYLALQVSSZTGX-UHFFFAOYSA-N 0.000 claims description 2
- KFLRFXOJSWLCPS-UHFFFAOYSA-N n-[1-[(4-cyano-1-propylpiperidin-4-yl)amino]-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(CCC)CCC1(C#N)NC(=O)C(NC(=O)N1CCOCC1)CC1=CC=C(Cl)C(Cl)=C1 KFLRFXOJSWLCPS-UHFFFAOYSA-N 0.000 claims description 2
- SZHFBLNVHHHCRB-UHFFFAOYSA-N n-[1-[(4-cyano-1-propylpiperidin-4-yl)amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(CCC)CCC1(C#N)NC(=O)C(NC(=O)N1CCOCC1)CC1=CC=C(C=CC=C2)C2=C1 SZHFBLNVHHHCRB-UHFFFAOYSA-N 0.000 claims description 2
- MLJLTOGPAKLYJE-UHFFFAOYSA-N n-[1-[(4-cyano-1-propylpiperidin-4-yl)amino]-4,4-dimethyl-1-oxopentan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(CCC)CCC1(C#N)NC(=O)C(CC(C)(C)C)NC(=O)N1CCOCC1 MLJLTOGPAKLYJE-UHFFFAOYSA-N 0.000 claims description 2
- RCTOBPRCGHONCY-UHFFFAOYSA-N n-[1-[[3-cyano-1-(1h-indol-3-ylmethyl)pyrrolidin-3-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(CC=2C3=CC=CC=C3NC=2)CC1(C#N)NC(=O)C(NC(=O)N1CCOCC1)CC1CCCCC1 RCTOBPRCGHONCY-UHFFFAOYSA-N 0.000 claims description 2
- WXNYFYULNSKWQR-UHFFFAOYSA-N n-[1-[[3-cyano-1-(2-methylpent-2-enyl)pyrrolidin-3-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1N(CC(C)=CCC)CCC1(C#N)NC(=O)C(NC(=O)N1CCOCC1)CC1CCCCC1 WXNYFYULNSKWQR-UHFFFAOYSA-N 0.000 claims description 2
- XYGHCJFBSRZPQF-UHFFFAOYSA-N n-[1-[[3-cyano-1-(2-methylpropyl)piperidin-3-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1N(CC(C)C)CCCC1(C#N)NC(=O)C(NC(=O)N1CCOCC1)CC1CCCCC1 XYGHCJFBSRZPQF-UHFFFAOYSA-N 0.000 claims description 2
- BKPDUNCXYWFCER-UHFFFAOYSA-N n-[1-[[3-cyano-1-(2-methylpropyl)pyrrolidin-3-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1N(CC(C)C)CCC1(C#N)NC(=O)C(NC(=O)N1CCOCC1)CC1CCCCC1 BKPDUNCXYWFCER-UHFFFAOYSA-N 0.000 claims description 2
- RDVFWLFNAPLGJG-UHFFFAOYSA-N n-[1-[[3-cyano-1-(cyclohexylmethyl)pyrrolidin-3-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound C1CCCCC1CC(NC(=O)N1CCOCC1)C(=O)NC(C1)(C#N)CCN1CC1CCCCC1 RDVFWLFNAPLGJG-UHFFFAOYSA-N 0.000 claims description 2
- DLHRAXGANAYHNQ-UHFFFAOYSA-N n-[1-[[3-cyano-1-(cyclohexylmethyl)pyrrolidin-3-yl]amino]-4-methyl-1-oxopentan-2-yl]morpholine-4-carboxamide Chemical compound C1CN(CC2CCCCC2)CC1(C#N)NC(=O)C(CC(C)C)NC(=O)N1CCOCC1 DLHRAXGANAYHNQ-UHFFFAOYSA-N 0.000 claims description 2
- WIOAKLGGTTXIQC-UHFFFAOYSA-N n-[1-[[3-cyano-1-[(5-methylthiophen-2-yl)methyl]pyrrolidin-3-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound S1C(C)=CC=C1CN1CC(C#N)(NC(=O)C(CC2CCCCC2)NC(=O)N2CCOCC2)CC1 WIOAKLGGTTXIQC-UHFFFAOYSA-N 0.000 claims description 2
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- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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Applications Claiming Priority (3)
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US15373899P | 1999-09-13 | 1999-09-13 | |
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PCT/US2000/023584 WO2001019816A1 (en) | 1999-09-13 | 2000-08-28 | Novel spiroheterocyclic compounds useful as reversible inhibitors of cysteine proteases |
Publications (3)
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NO20021207L NO20021207L (no) | 2002-03-12 |
NO20021207D0 NO20021207D0 (no) | 2002-03-12 |
NO323354B1 true NO323354B1 (no) | 2007-04-10 |
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NO20021207A NO323354B1 (no) | 1999-09-13 | 2002-03-12 | Nye spiroheterocykliske forbindelser nyttige som inhibitorer av cystein proteaser samt anvendelse og fremstilling derav og farmasoytisk preparat. |
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EP (1) | EP1218372B1 (pl) |
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CN (1) | CN100410250C (pl) |
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TW (1) | TWI230159B (pl) |
WO (1) | WO2001019816A1 (pl) |
YU (1) | YU17402A (pl) |
Families Citing this family (47)
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WO2000055125A2 (en) | 1999-03-15 | 2000-09-21 | Axys Pharmaceuticals, Inc. | N-cyanomethyl amides as protease inhibitors |
US6420364B1 (en) | 1999-09-13 | 2002-07-16 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compound useful as reversible inhibitors of cysteine proteases |
US7030116B2 (en) | 2000-12-22 | 2006-04-18 | Aventis Pharmaceuticals Inc. | Compounds and compositions as cathepsin inhibitors |
AR036375A1 (es) | 2001-08-30 | 2004-09-01 | Novartis Ag | Compuestos pirrolo [2,3-d] pirimidina -2- carbonitrilo, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos compuestos para la preparacion de medicamentos |
WO2003024924A1 (en) | 2001-09-14 | 2003-03-27 | Aventis Pharmaceuticals Inc. | Novel compounds and compositions as cathepsin inhibitors |
CA2459825A1 (en) | 2001-10-02 | 2003-04-10 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compounds useful as reversible inhibitors of cysteine proteases |
WO2003037892A1 (en) * | 2001-10-29 | 2003-05-08 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compounds useful as reversible inhibitors of cysteine proteases |
HUP0401906A3 (en) | 2001-11-14 | 2008-07-28 | Aventis Pharma Inc | Novel cathepsin s inhibitors, process for their preparation and pharmaceutical compositions containing them |
US7087604B2 (en) | 2002-03-08 | 2006-08-08 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
WO2004000838A1 (en) * | 2002-06-24 | 2003-12-31 | Axys Pharmaceuticals, Inc. | Peptidic compounds as cysteine protease inhibitors |
WO2004050024A2 (en) | 2002-11-27 | 2004-06-17 | Incyte Corporation | 3-aminopyrrolidine derivatives as modulators of chemokine receptors |
US20060122184A1 (en) * | 2002-12-05 | 2006-06-08 | Axys Pharmaceuticals, Inc. | Cyanomethyl derivatives as cysteine protease inhibitors |
US7109243B2 (en) | 2003-03-24 | 2006-09-19 | Irm Llc | Inhibitors of cathepsin S |
US7384970B2 (en) | 2003-03-24 | 2008-06-10 | Irm Llc | Inhibitors of cathepsin S |
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US7173051B2 (en) | 2003-06-13 | 2007-02-06 | Irm, Llc | Inhibitors of cathepsin S |
US7256207B2 (en) | 2003-08-20 | 2007-08-14 | Irm Llc | Inhibitors of cathepsin S |
KR20060079143A (ko) | 2003-09-18 | 2006-07-05 | 액시스 파마슈티컬스 인코포레이티드 | 시스테인 프로테아제 억제제로서의 할로알킬 함유 화합물 |
US7297714B2 (en) * | 2003-10-21 | 2007-11-20 | Irm Llc | Inhibitors of cathepsin S |
WO2006060810A1 (en) | 2004-12-02 | 2006-06-08 | Schering Aktiengesellschaft | Sulfonamide compounds as cysteine protease inhibitors |
NZ561681A (en) | 2005-03-21 | 2011-01-28 | Virobay Inc | Alpha ketoamide compounds as cysteine protease inhibitors |
CA2602112A1 (en) | 2005-03-22 | 2006-09-28 | Celera Genomics | Sulfonyl containing compounds as cysteine protease inhibitors |
AU2006259573A1 (en) * | 2005-06-14 | 2006-12-28 | Pharmacopeia, Inc. | Heterocyclic aspartyl protease inhibitors, preparation and use thereof |
WO2007053498A1 (en) | 2005-11-01 | 2007-05-10 | Millennium Pharmaceuticals, Inc. | Compounds useful as antagonists of ccr2 |
US8067415B2 (en) | 2005-11-01 | 2011-11-29 | Millennium Pharmaceuticals, Inc. | Compounds useful as antagonists of CCR2 |
AR059035A1 (es) * | 2006-01-16 | 2008-03-12 | Syngenta Participations Ag | Insecticidas derivados de antranilamida |
CA2653662C (en) | 2006-06-01 | 2015-02-10 | Sanofi-Aventis | Spirocyclic nitriles as protease inhibitors |
US7893112B2 (en) | 2006-10-04 | 2011-02-22 | Virobay, Inc. | Di-fluoro containing compounds as cysteine protease inhibitors |
KR101555931B1 (ko) | 2006-10-04 | 2015-09-30 | 비로베이, 인코포레이티드 | 시스테인 프로테아제 억제제로서의 디플루오로 함유 화합물 |
DE102006057036A1 (de) * | 2006-12-04 | 2008-06-05 | Bayer Cropscience Ag | Biphenylsubstituierte spirocyclische Ketoenole |
WO2009087379A2 (en) | 2008-01-09 | 2009-07-16 | Amura Therapeutics Limited | Tetrahydrofuro (3, 2 -b) pyrrol- 3 -one derivatives as inhibitors of cysteine proteinases |
EP2198879A1 (en) | 2008-12-11 | 2010-06-23 | Institut Curie | CD74 modulator agent for regulating dendritic cell migration and device for studying the motility capacity of a cell |
US8324417B2 (en) | 2009-08-19 | 2012-12-04 | Virobay, Inc. | Process for the preparation of (S)-2-amino-5-cyclopropyl-4,4-difluoropentanoic acid and alkyl esters and acid salts thereof |
WO2012151319A1 (en) | 2011-05-02 | 2012-11-08 | Virobay, Inc. | Cathepsin inhibitors for the treatment of bone cancer and bone cancer pain |
CN104744409A (zh) * | 2011-06-07 | 2015-07-01 | 株式会社吴羽 | 氧杂环丁烷化合物的制造方法、唑甲基环戊醇化合物的制造方法、以及中间体化合物 |
EP2537532A1 (en) | 2011-06-22 | 2012-12-26 | J. Stefan Institute | Cathepsin-binding compounds bound to a nanodevice and their diagnostic and therapeutic use |
WO2013072705A1 (en) | 2011-11-18 | 2013-05-23 | Heptares Therapeutics Limited | Muscarinic m1 receptor agonists |
GB201513743D0 (en) | 2015-08-03 | 2015-09-16 | Heptares Therapeutics Ltd | Muscarinic agonists |
GB201617454D0 (en) * | 2016-10-14 | 2016-11-30 | Heptares Therapeutics Limited | Pharmaceutical compounds |
GB201810239D0 (en) | 2018-06-22 | 2018-08-08 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
GB201819960D0 (en) | 2018-12-07 | 2019-01-23 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
GB202020191D0 (en) | 2020-12-18 | 2021-02-03 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
US11124497B1 (en) | 2020-04-17 | 2021-09-21 | Pardes Biosciences, Inc. | Inhibitors of cysteine proteases and methods of use thereof |
WO2021252644A1 (en) * | 2020-06-09 | 2021-12-16 | Pardes Biosciences, Inc. | Inhibitors of cysteine proteases and methods of use thereof |
US11174231B1 (en) | 2020-06-09 | 2021-11-16 | Pardes Biosciences, Inc. | Inhibitors of cysteine proteases and methods of use thereof |
CN117836270A (zh) * | 2021-03-10 | 2024-04-05 | 文森雷生物科学股份有限公司 | Usp30抑制剂及其用途 |
WO2023044171A1 (en) * | 2021-09-20 | 2023-03-23 | Pardes Biosciences, Inc. | Inhibitors of cysteine proteases and methods of use thereof |
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US5776718A (en) * | 1995-03-24 | 1998-07-07 | Arris Pharmaceutical Corporation | Reversible protease inhibitors |
KR19980703261A (ko) * | 1995-03-24 | 1998-10-15 | 다니엘 이이치. 페트리 | 가역성 프로테아제 억제제 |
TW438591B (en) * | 1995-06-07 | 2001-06-07 | Arris Pharm Corp | Reversible cysteine protease inhibitors |
WO2000055125A2 (en) * | 1999-03-15 | 2000-09-21 | Axys Pharmaceuticals, Inc. | N-cyanomethyl amides as protease inhibitors |
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- 2000-08-28 ES ES00959506T patent/ES2199856T3/es not_active Expired - Lifetime
- 2000-08-28 DE DE60003702T patent/DE60003702T2/de not_active Expired - Lifetime
- 2000-08-28 JP JP2001523393A patent/JP2003529546A/ja active Pending
- 2000-08-28 PL PL00364045A patent/PL364045A1/pl unknown
- 2000-08-28 IL IL14818400A patent/IL148184A0/xx active IP Right Grant
- 2000-09-11 MY MYPI20004216A patent/MY122696A/en unknown
- 2000-09-11 TW TW089118587A patent/TWI230159B/zh not_active IP Right Cessation
- 2000-09-13 AR ARP000104795A patent/AR032136A1/es not_active Suspension/Interruption
- 2000-10-17 SA SA00210456A patent/SA00210456B1/ar unknown
-
2002
- 2002-02-14 IL IL148184A patent/IL148184A/en not_active IP Right Cessation
- 2002-03-05 BG BG106483A patent/BG106483A/bg active Pending
- 2002-03-12 HR HR20020221A patent/HRP20020221A2/hr not_active IP Right Cessation
- 2002-03-12 NO NO20021207A patent/NO323354B1/no unknown
-
2003
- 2003-02-06 HK HK03100843.6A patent/HK1048807A1/zh unknown
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