CA2356313A1 - Alkynyl containing hydroxamic acid derivatives, their preparation and their use as matrix metalloproteinase (mmp) inhibitors/tnf-alpha converting enzyme (tace) inhibitors - Google Patents
Alkynyl containing hydroxamic acid derivatives, their preparation and their use as matrix metalloproteinase (mmp) inhibitors/tnf-alpha converting enzyme (tace) inhibitors Download PDFInfo
- Publication number
- CA2356313A1 CA2356313A1 CA002356313A CA2356313A CA2356313A1 CA 2356313 A1 CA2356313 A1 CA 2356313A1 CA 002356313 A CA002356313 A CA 002356313A CA 2356313 A CA2356313 A CA 2356313A CA 2356313 A1 CA2356313 A1 CA 2356313A1
- Authority
- CA
- Canada
- Prior art keywords
- sulfonyl
- phenyl
- methyl
- ynyloxy
- hydroxy
- 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.)
- Abandoned
Links
- 125000000304 alkynyl group Chemical group 0.000 title claims abstract description 14
- 239000002253 acid Substances 0.000 title claims description 41
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 title description 25
- 102000002274 Matrix Metalloproteinases Human genes 0.000 title description 19
- 108010000684 Matrix Metalloproteinases Proteins 0.000 title description 19
- 239000003112 inhibitor Substances 0.000 title description 14
- 102000043279 ADAM17 Human genes 0.000 title description 2
- 108091007505 ADAM17 Proteins 0.000 title description 2
- 238000002360 preparation method Methods 0.000 title description 2
- BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 88
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 64
- 125000003118 aryl group Chemical group 0.000 claims abstract description 28
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 25
- 239000001257 hydrogen Substances 0.000 claims abstract description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 15
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
- 125000004429 atom Chemical group 0.000 claims abstract description 7
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 6
- 208000037357 HIV infectious disease Diseases 0.000 claims abstract description 6
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 6
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims abstract description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 94
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 93
- 238000000034 method Methods 0.000 claims description 66
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 65
- -1 4-({[4-(But-2-ynyloxy)phenyl]sulfonyl}methyl)-1-ethyl-N-hydroxypiperidine-4- carboxamide triflouroacetic acid salt Chemical class 0.000 claims description 58
- 239000000203 mixture Substances 0.000 claims description 57
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 27
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 102000004190 Enzymes Human genes 0.000 claims description 17
- 108090000790 Enzymes Proteins 0.000 claims description 17
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- KXAUOPCRPRDTTJ-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-1-(4-methoxybenzoyl)piperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(=O)N1CCC(S(=O)(=O)C=2C=CC(OCC#CC)=CC=2)(C(O)=O)CC1 KXAUOPCRPRDTTJ-UHFFFAOYSA-N 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- FTUZKTMZGQDLFF-UHFFFAOYSA-N 1-acetyl-4-(4-but-2-ynoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(C(C)=O)CC1 FTUZKTMZGQDLFF-UHFFFAOYSA-N 0.000 claims description 6
- XGTMGHQYSZYWOQ-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-1-[(4-cyanophenyl)methyl]piperidine-4-carboxylic acid Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC(=CC=2)C#N)CC1 XGTMGHQYSZYWOQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 6
- NMMMNOVWJHIFHB-UHFFFAOYSA-N tert-butyl 4-[(4-but-2-ynoxyphenyl)sulfanylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate Chemical compound C1=CC(OCC#CC)=CC=C1SCC1(C(=O)NO)CCN(C(=O)OC(C)(C)C)CC1 NMMMNOVWJHIFHB-UHFFFAOYSA-N 0.000 claims description 6
- XOBSNYRLSVUYKY-UHFFFAOYSA-N tert-butyl 4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)CC1(C(=O)NO)CCN(C(=O)OC(C)(C)C)CC1 XOBSNYRLSVUYKY-UHFFFAOYSA-N 0.000 claims description 6
- QZQPVHJCQNJHAK-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-1-[(3,4-dichlorophenyl)methyl]piperidine-4-carboxylic acid Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 QZQPVHJCQNJHAK-UHFFFAOYSA-N 0.000 claims description 5
- GVMOFIZLRIIJNO-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-1-[(4-chlorophenyl)methyl]piperidine-4-carboxylic acid Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC(Cl)=CC=2)CC1 GVMOFIZLRIIJNO-UHFFFAOYSA-N 0.000 claims description 5
- BAANPGNVLMXHFB-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-1-[(4-methylphenyl)methyl]piperidine-4-carboxylic acid Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC(C)=CC=2)CC1 BAANPGNVLMXHFB-UHFFFAOYSA-N 0.000 claims description 5
- DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 claims description 5
- LELMFJKEAGQMMN-UHFFFAOYSA-N 4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-n-hydroxy-1-(2,2,5-trimethyl-1,3-dioxane-5-carbonyl)piperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)CC1(C(=O)NO)CCN(C(=O)C2(C)COC(C)(C)OC2)CC1 LELMFJKEAGQMMN-UHFFFAOYSA-N 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- WGANCLOVDGTTMN-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]-n-hydroxy-4-(4-oct-2-ynoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1=CC(OCC#CCCCCC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(Br)=CC=2)CC1 WGANCLOVDGTTMN-UHFFFAOYSA-N 0.000 claims description 4
- XMAZUULAIZPAJR-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]-n-hydroxy-4-(4-pent-2-ynoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1=CC(OCC#CCC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(Br)=CC=2)CC1 XMAZUULAIZPAJR-UHFFFAOYSA-N 0.000 claims description 4
- AATWHYMDJNDPRO-UHFFFAOYSA-N 1-benzoyl-4-(4-but-2-ynoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(C(=O)C=2C=CC=CC=2)CC1 AATWHYMDJNDPRO-UHFFFAOYSA-N 0.000 claims description 4
- KZRYIPSHAPSGMG-UHFFFAOYSA-N 2-[[4-(4-but-2-ynoxyphenyl)sulfonyl-4-(hydroxycarbamoyl)piperidin-1-yl]methyl]-3-methylbenzoic acid;hydrochloride Chemical compound Cl.C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C(=CC=CC=2C)C(O)=O)CC1 KZRYIPSHAPSGMG-UHFFFAOYSA-N 0.000 claims description 4
- RSCINQLGTCOLIH-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-n-hydroxy-1-(pyrrolidine-1-carbonyl)piperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(C(=O)N2CCCC2)CC1 RSCINQLGTCOLIH-UHFFFAOYSA-N 0.000 claims description 4
- ITNHZRQBKQAHAQ-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-n-hydroxy-1-(trifluoromethylsulfonyl)piperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(S(=O)(=O)C(F)(F)F)CC1 ITNHZRQBKQAHAQ-UHFFFAOYSA-N 0.000 claims description 4
- QFAMXNMLWJDJPV-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-n-hydroxy-1-[(4-methoxyphenyl)methyl]piperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1CN1CCC(S(=O)(=O)C=2C=CC(OCC#CC)=CC=2)(C(=O)NO)CC1 QFAMXNMLWJDJPV-UHFFFAOYSA-N 0.000 claims description 4
- BQFOLVGRADWVHE-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-n-hydroxypiperidine-4-carboxamide;hydrochloride Chemical compound Cl.C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCNCC1 BQFOLVGRADWVHE-UHFFFAOYSA-N 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 206010052779 Transplant rejections Diseases 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 claims description 4
- OLDVZKVEHWUWRL-UHFFFAOYSA-N ethyl 4-(4-but-2-ynoxyphenyl)sulfonyl-4-(hydroxycarbamoyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1(C(=O)NO)S(=O)(=O)C1=CC=C(OCC#CC)C=C1 OLDVZKVEHWUWRL-UHFFFAOYSA-N 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- GUKXYZOXYJXJKW-UHFFFAOYSA-N methyl 4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC)CCC1(C(=O)NO)CS(=O)(=O)C1=CC=C(OCC#CC)C=C1 GUKXYZOXYJXJKW-UHFFFAOYSA-N 0.000 claims description 4
- OAYSBBNCSYNXFX-UHFFFAOYSA-N n-hydroxy-1-[(4-methoxyphenyl)methyl]-4-(4-prop-2-ynoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1CN1CCC(S(=O)(=O)C=2C=CC(OCC#C)=CC=2)(C(=O)NO)CC1 OAYSBBNCSYNXFX-UHFFFAOYSA-N 0.000 claims description 4
- DNSZKZUFQIXHCV-UHFFFAOYSA-N tert-butyl 4-(4-but-2-ynoxyphenyl)sulfanyl-4-(hydroxycarbamoyl)piperidine-1-carboxylate Chemical compound C1=CC(OCC#CC)=CC=C1SC1(C(=O)NO)CCN(C(=O)OC(C)(C)C)CC1 DNSZKZUFQIXHCV-UHFFFAOYSA-N 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- UISLAVXNDUNVEW-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]-4-(4-but-2-ynoxyphenyl)sulfanyl-n-hydroxypiperidine-4-carboxamide;4-(4-but-2-ynoxyphenyl)sulfanyl-n-hydroxypiperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1SC1(C(=O)NO)CCNCC1.C1=CC(OCC#CC)=CC=C1SC1(C(=O)NO)CCN(CC=2C=CC(Br)=CC=2)CC1 UISLAVXNDUNVEW-UHFFFAOYSA-N 0.000 claims description 3
- DFCLXDHFDSKKBC-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]-4-(4-but-2-ynoxyphenyl)sulfinylpiperidine-4-carboxylic acid Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)C1(C(O)=O)CCN(CC=2C=CC(Br)=CC=2)CC1 DFCLXDHFDSKKBC-UHFFFAOYSA-N 0.000 claims description 3
- SEFCVQRMTNTWJO-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]-n-hydroxy-4-(4-prop-2-ynoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1CC(C(=O)NO)(S(=O)(=O)C=2C=CC(OCC#C)=CC=2)CCN1CC1=CC=C(Br)C=C1 SEFCVQRMTNTWJO-UHFFFAOYSA-N 0.000 claims description 3
- MAHYPKDQXXPNOJ-UHFFFAOYSA-N 1-benzyl-4-(4-but-2-ynoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC=CC=2)CC1 MAHYPKDQXXPNOJ-UHFFFAOYSA-N 0.000 claims description 3
- UOZWZUJPVCEUDL-UHFFFAOYSA-N 3-(4-but-2-ynoxyphenyl)sulfonyl-1-[(4-chlorophenyl)methyl]-n-hydroxypiperidine-3-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CN(CC=2C=CC(Cl)=CC=2)CCC1 UOZWZUJPVCEUDL-UHFFFAOYSA-N 0.000 claims description 3
- UCTVQSRWPLZYBU-UHFFFAOYSA-N 3-(4-but-2-ynoxyphenyl)sulfonyl-1-ethyl-n-hydroxypiperidine-3-carboxamide Chemical compound C1N(CC)CCCC1(C(=O)NO)S(=O)(=O)C1=CC=C(OCC#CC)C=C1 UCTVQSRWPLZYBU-UHFFFAOYSA-N 0.000 claims description 3
- DKOGZWXYBDUGGO-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-1-[(4-carbamoylphenyl)methyl]-n-hydroxypiperidine-4-carboxamide;hydrochloride Chemical compound Cl.C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(=CC=2)C(N)=O)CC1 DKOGZWXYBDUGGO-UHFFFAOYSA-N 0.000 claims description 3
- XOHRBGNAGARONC-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-n-hydroxy-1-(2,2,5-trimethyl-1,3-dioxane-5-carbonyl)piperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(C(=O)C2(C)COC(C)(C)OC2)CC1 XOHRBGNAGARONC-UHFFFAOYSA-N 0.000 claims description 3
- MQVSUVRJFZGXCO-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-n-hydroxy-1-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1CCC(S(=O)(=O)C=2C=CC(OCC#CC)=CC=2)(C(=O)NO)CC1 MQVSUVRJFZGXCO-UHFFFAOYSA-N 0.000 claims description 3
- XEVTYXFEXRJMNO-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-n-hydroxy-1-(pyridine-3-carbonyl)piperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(C(=O)C=2C=NC=CC=2)CC1 XEVTYXFEXRJMNO-UHFFFAOYSA-N 0.000 claims description 3
- ZOVPTYWIZPVNBM-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-n-hydroxy-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]piperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(OCCN3CCCCC3)=CC=2)CC1 ZOVPTYWIZPVNBM-UHFFFAOYSA-N 0.000 claims description 3
- LNKUSJOCKSXGPT-UHFFFAOYSA-N 4-(4-but-2-ynoxyphenyl)sulfonyl-n-hydroxyoxane-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCOCC1 LNKUSJOCKSXGPT-UHFFFAOYSA-N 0.000 claims description 3
- OEZDAJHXHWVOEQ-UHFFFAOYSA-N 4-[(4-but-2-ynoxyphenyl)sulfanylmethyl]-n-hydroxyoxane-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1SCC1(C(=O)NO)CCOCC1 OEZDAJHXHWVOEQ-UHFFFAOYSA-N 0.000 claims description 3
- FSRJQXYJWIBDKG-UHFFFAOYSA-N 4-[(4-but-2-ynoxyphenyl)sulfanylmethyl]-n-hydroxypiperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1SCC1(C(=O)NO)CCNCC1 FSRJQXYJWIBDKG-UHFFFAOYSA-N 0.000 claims description 3
- BKWMETWYCKMSOM-UHFFFAOYSA-N 4-[(4-but-2-ynoxyphenyl)sulfinylmethyl]-n-hydroxyoxane-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)CC1(C(=O)NO)CCOCC1 BKWMETWYCKMSOM-UHFFFAOYSA-N 0.000 claims description 3
- XYPIHDZTKUQVLO-UHFFFAOYSA-N 4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-1-but-2-ynyl-n-hydroxypiperidine-4-carboxamide;hydrochloride Chemical compound Cl.C1=CC(OCC#CC)=CC=C1S(=O)(=O)CC1(C(=O)NO)CCN(CC#CC)CC1 XYPIHDZTKUQVLO-UHFFFAOYSA-N 0.000 claims description 3
- NILIMKWDWHKQOZ-UHFFFAOYSA-N 4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-n-hydroxy-1-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoyl]piperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)CC1(C(=O)NO)CCN(C(=O)C(C)(CO)CO)CC1 NILIMKWDWHKQOZ-UHFFFAOYSA-N 0.000 claims description 3
- IIYKIYALGFZKHC-UHFFFAOYSA-N 4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-n-hydroxyoxane-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)CC1(C(=O)NO)CCOCC1 IIYKIYALGFZKHC-UHFFFAOYSA-N 0.000 claims description 3
- MNIICWKMSWNHRM-UHFFFAOYSA-N 4-[[4-(4-but-2-ynoxyphenyl)sulfonyl-4-(hydroxycarbamoyl)piperidin-1-yl]methyl]benzoic acid;hydrochloride Chemical compound Cl.C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(=CC=2)C(O)=O)CC1 MNIICWKMSWNHRM-UHFFFAOYSA-N 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- QSEXAVVAPDJHHB-UHFFFAOYSA-N benzyl 4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)CC1(C(=O)NO)CCN(C(=O)OCC=2C=CC=CC=2)CC1 QSEXAVVAPDJHHB-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 239000011347 resin Substances 0.000 claims description 3
- 229920005989 resin Polymers 0.000 claims description 3
- VJDQBINUEBWNCB-UHFFFAOYSA-N tert-butyl 4-[(4-but-2-ynoxyphenyl)sulfinylmethyl]-4-(hydroxycarbamoyl)piperidine-1-carboxylate Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)CC1(C(=O)NO)CCN(C(=O)OC(C)(C)C)CC1 VJDQBINUEBWNCB-UHFFFAOYSA-N 0.000 claims description 3
- MNQFMKHWJNOSIX-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]-4-(4-but-2-ynoxyphenyl)sulfonyl-n-hydroxypiperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(Br)=CC=2)CC1 MNQFMKHWJNOSIX-UHFFFAOYSA-N 0.000 claims description 2
- KGOVOYVELNVBED-UHFFFAOYSA-N 1-[2-(benzylamino)acetyl]-4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-n-hydroxypiperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)CC1(C(=O)NO)CCN(C(=O)CNCC=2C=CC=CC=2)CC1 KGOVOYVELNVBED-UHFFFAOYSA-N 0.000 claims description 2
- NPWNPFHGYNOBOO-UHFFFAOYSA-N 1-acetyl-4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-n-hydroxypiperidine-4-carboxamide Chemical compound C1=CC(OCC#CC)=CC=C1S(=O)(=O)CC1(C(=O)NO)CCN(C(C)=O)CC1 NPWNPFHGYNOBOO-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004407 fluoroaryl group Chemical group 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
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- 150000002334 glycols Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- MSYBLBLAMDYKKZ-UHFFFAOYSA-N hydron;pyridine-3-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=CN=C1 MSYBLBLAMDYKKZ-UHFFFAOYSA-N 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 description 1
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- QXWKFAXQZKRDCC-UHFFFAOYSA-N methyl 1-acetyl-4-(4-but-2-ynoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C=1C=C(OCC#CC)C=CC=1S(=O)(=O)C1(C(=O)OC)CCN(C(C)=O)CC1 QXWKFAXQZKRDCC-UHFFFAOYSA-N 0.000 description 1
- AIAYHILDRDALSZ-UHFFFAOYSA-N methyl 4-(4-but-2-ynoxyphenyl)sulfonyl-1-(4-methoxybenzoyl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OC)(S(=O)(=O)C=2C=CC(OCC#CC)=CC=2)CCN1C(=O)C1=CC=C(OC)C=C1 AIAYHILDRDALSZ-UHFFFAOYSA-N 0.000 description 1
- UAXYFHDMBBAQOY-UHFFFAOYSA-N methyl 4-(4-but-2-ynoxyphenyl)sulfonyl-1-(pyridine-3-carbonyl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OC)(S(=O)(=O)C=2C=CC(OCC#CC)=CC=2)CCN1C(=O)C1=CC=CN=C1 UAXYFHDMBBAQOY-UHFFFAOYSA-N 0.000 description 1
- CSQWQTBRMARMAP-UHFFFAOYSA-N methyl 4-(4-but-2-ynoxyphenyl)sulfonyl-1-(thiophene-2-carbonyl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OC)(S(=O)(=O)C=2C=CC(OCC#CC)=CC=2)CCN1C(=O)C1=CC=CS1 CSQWQTBRMARMAP-UHFFFAOYSA-N 0.000 description 1
- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- RZVWBASHHLFBJF-UHFFFAOYSA-N methyl piperidine-4-carboxylate Chemical compound COC(=O)C1CCNCC1 RZVWBASHHLFBJF-UHFFFAOYSA-N 0.000 description 1
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- 230000002297 mitogenic effect Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- JFYIOIVDXGEDDW-UHFFFAOYSA-N n,n-bis(2-chloroethyl)pentan-3-amine;dihydrochloride Chemical compound Cl.Cl.CCC(CC)N(CCCl)CCCl JFYIOIVDXGEDDW-UHFFFAOYSA-N 0.000 description 1
- MRNUOMIAYMSZOS-UHFFFAOYSA-N n,n-bis(2-chloroethyl)propan-2-amine;hydrochloride Chemical compound [Cl-].ClCC[NH+](C(C)C)CCCl MRNUOMIAYMSZOS-UHFFFAOYSA-N 0.000 description 1
- OFCCYDUUBNUJIB-UHFFFAOYSA-N n,n-diethylcarbamoyl chloride Chemical compound CCN(CC)C(Cl)=O OFCCYDUUBNUJIB-UHFFFAOYSA-N 0.000 description 1
- JMFWSMLIKYACHO-UHFFFAOYSA-M n-(4-chlorobut-2-ynyl)-n-(3-chlorophenyl)carbamate Chemical compound ClCC#CCN(C(=O)[O-])C1=CC=CC(Cl)=C1 JMFWSMLIKYACHO-UHFFFAOYSA-M 0.000 description 1
- DYGBNAYFDZEYBA-UHFFFAOYSA-N n-(cyclopropylmethyl)-2-[4-(4-methoxybenzoyl)piperidin-1-yl]-n-[(4-oxo-1,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]acetamide Chemical compound C1=CC(OC)=CC=C1C(=O)C1CCN(CC(=O)N(CC2CC2)CC=2NC(=O)C=3COCCC=3N=2)CC1 DYGBNAYFDZEYBA-UHFFFAOYSA-N 0.000 description 1
- QUKJNGDEQKDQGY-UHFFFAOYSA-N n-hydroxy-2-sulfonylacetamide Chemical class ONC(=O)C=S(=O)=O QUKJNGDEQKDQGY-UHFFFAOYSA-N 0.000 description 1
- CPGWSLFYXMRNDV-UHFFFAOYSA-N n-methyl-n-phenylcarbamoyl chloride Chemical compound ClC(=O)N(C)C1=CC=CC=C1 CPGWSLFYXMRNDV-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- VFXVAXFIFHSGNR-UHFFFAOYSA-N octyl carbonochloridate Chemical compound CCCCCCCCOC(Cl)=O VFXVAXFIFHSGNR-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000004880 oxines Chemical class 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- CGJURZHXCYKANX-UHFFFAOYSA-N ozone;tetrabutylazanium Chemical compound [O-][O+]=O.CCCC[N+](CCCC)(CCCC)CCCC CGJURZHXCYKANX-UHFFFAOYSA-N 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001151 peptidyl group Chemical group 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- SEHDKKMNXXAYLS-UHFFFAOYSA-N piperidine-1-carboxamide;hydrochloride Chemical compound Cl.NC(=O)N1CCCCC1 SEHDKKMNXXAYLS-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- XACWJIQLDLUFSR-UHFFFAOYSA-N pyrrolidine-1-carbonyl chloride Chemical compound ClC(=O)N1CCCC1 XACWJIQLDLUFSR-UHFFFAOYSA-N 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 239000002447 tumor necrosis factor alpha converting enzyme inhibitor Substances 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000005186 women's health Effects 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
- C07D211/66—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having a hetero atom as the second substituent in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US23803899A | 1999-01-27 | 1999-01-27 | |
US09/238,038 | 1999-01-27 | ||
PCT/US2000/001864 WO2000044723A1 (en) | 1999-01-27 | 2000-01-27 | Alkynyl containing hydroxamic acid derivatives, their preparation and their use as matrix metalloproteinase (mmp) inhibitors/tnf-alpha converting enzyme (tace) inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2356313A1 true CA2356313A1 (en) | 2000-08-03 |
Family
ID=22896246
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002356313A Abandoned CA2356313A1 (en) | 1999-01-27 | 2000-01-27 | Alkynyl containing hydroxamic acid derivatives, their preparation and their use as matrix metalloproteinase (mmp) inhibitors/tnf-alpha converting enzyme (tace) inhibitors |
Country Status (13)
Country | Link |
---|---|
JP (1) | JP2002535390A (cs) |
KR (1) | KR20010101732A (cs) |
AR (1) | AR035312A1 (cs) |
AT (1) | ATE309986T1 (cs) |
AU (1) | AU769418B2 (cs) |
CA (1) | CA2356313A1 (cs) |
CZ (1) | CZ20012711A3 (cs) |
DE (1) | DE60024056D1 (cs) |
EA (1) | EA200100806A1 (cs) |
HU (1) | HUP0200223A3 (cs) |
IL (1) | IL144345A0 (cs) |
NZ (1) | NZ512566A (cs) |
ZA (1) | ZA200105222B (cs) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004060875A1 (ja) * | 2002-12-26 | 2004-07-22 | Carna Biosciences Inc. | アルキニル基置換アザ糖誘導体およびそれを有効成分とする薬剤 |
KR20090042779A (ko) * | 2006-06-30 | 2009-04-30 | 쉐링 코포레이션 | P53 활성을 증가시키는 치환된 피페리딘 및 이의 사용 |
CA2724887A1 (en) * | 2008-06-02 | 2009-12-10 | Cipla Limited | Processes for the synthesis of levocetirizine and intermediates for use therein |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20000075809A (ko) * | 1997-02-27 | 2000-12-26 | 윌리암 에이취 캘넌, 에곤 이 버그 | 매트릭스 메탈로프로테이나제 억제제로서의 n-하이드록시-2-(알킬, 아릴 또는 헤테로아릴 설파닐, 설피닐 또는 설포닐)-3-치환된 알킬, 아릴 또는 헤테로아릴아미드 |
IL137566A0 (en) * | 1998-02-19 | 2001-07-24 | American Cyanamid Co | N-hydroxy-2-(alkyl, aryl or heteroaryl sulfanyl, sulfinyl or sulfonyl)-3-substituted-alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors |
-
2000
- 2000-01-26 AR ARP000100327A patent/AR035312A1/es not_active Application Discontinuation
- 2000-01-27 AU AU26305/00A patent/AU769418B2/en not_active Ceased
- 2000-01-27 JP JP2000595979A patent/JP2002535390A/ja active Pending
- 2000-01-27 IL IL14434500A patent/IL144345A0/xx unknown
- 2000-01-27 AT AT00904569T patent/ATE309986T1/de not_active IP Right Cessation
- 2000-01-27 DE DE60024056T patent/DE60024056D1/de not_active Expired - Lifetime
- 2000-01-27 HU HU0200223A patent/HUP0200223A3/hu unknown
- 2000-01-27 KR KR1020017009432A patent/KR20010101732A/ko not_active Application Discontinuation
- 2000-01-27 EA EA200100806A patent/EA200100806A1/ru unknown
- 2000-01-27 NZ NZ512566A patent/NZ512566A/xx unknown
- 2000-01-27 CA CA002356313A patent/CA2356313A1/en not_active Abandoned
- 2000-01-27 CZ CZ20012711A patent/CZ20012711A3/cs unknown
-
2001
- 2001-06-25 ZA ZA200105222A patent/ZA200105222B/en unknown
Also Published As
Publication number | Publication date |
---|---|
HUP0200223A3 (en) | 2002-12-28 |
HUP0200223A2 (en) | 2002-06-29 |
EA200100806A1 (ru) | 2002-08-29 |
AU769418B2 (en) | 2004-01-29 |
ZA200105222B (en) | 2002-09-25 |
AR035312A1 (es) | 2004-05-12 |
JP2002535390A (ja) | 2002-10-22 |
KR20010101732A (ko) | 2001-11-14 |
NZ512566A (en) | 2004-02-27 |
ATE309986T1 (de) | 2005-12-15 |
CZ20012711A3 (cs) | 2002-05-15 |
DE60024056D1 (de) | 2005-12-22 |
IL144345A0 (en) | 2002-05-23 |
AU2630500A (en) | 2000-08-18 |
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EEER | Examination request | ||
FZDE | Discontinued |