OA10621A - Thienyl-, furyl-, pyrrolyl- and biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin - Google Patents

Info

Publication number

OA10621A

OA10621A OA70095A OA70095A OA10621A OA 10621 A OA10621 A OA 10621A OA 70095 A OA70095 A OA 70095A OA 70095 A OA70095 A OA 70095A OA 10621 A OA10621 A OA 10621A

Authority

OA

OAPI

Prior art keywords

methyl

isoxazolyl

thiophene

sulfonamide

chloro

Prior art date

1995-04-04

Links

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• Global Dossier
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• 108050009340 Endothelin Proteins 0.000 title claims abstract description 144
• 102000002045 Endothelin Human genes 0.000 title claims abstract description 125
• ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 title claims abstract description 114
• 230000000694 effects Effects 0.000 title claims abstract description 70
• 125000002541 furyl group Chemical group 0.000 title claims description 16
• 125000001544 thienyl group Chemical group 0.000 title claims description 13
• SBXDENYROQKXBE-UHFFFAOYSA-N 2-phenylbenzenesulfonamide Chemical class NS(=O)(=O)C1=CC=CC=C1C1=CC=CC=C1 SBXDENYROQKXBE-UHFFFAOYSA-N 0.000 title description 4
• 229940124530 sulfonamide Drugs 0.000 claims abstract description 248
• 238000000034 method Methods 0.000 claims abstract description 111
• 102000005962 receptors Human genes 0.000 claims abstract description 68
• 108020003175 receptors Proteins 0.000 claims abstract description 68
• 150000003456 sulfonamides Chemical class 0.000 claims abstract description 51
• 102000010180 Endothelin receptor Human genes 0.000 claims abstract description 18
• 108050001739 Endothelin receptor Proteins 0.000 claims abstract description 18
• 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 18
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 13
• 150000002148 esters Chemical class 0.000 claims abstract description 4
• 150000001875 compounds Chemical class 0.000 claims description 249
• BWJZHYWAXLWLTB-UHFFFAOYSA-N thiophene-3-sulfonamide Chemical compound NS(=O)(=O)C=1C=CSC=1 BWJZHYWAXLWLTB-UHFFFAOYSA-N 0.000 claims description 159
• -1 3lkenyl Chemical group 0.000 claims description 150
• 125000003118 aryl group Chemical group 0.000 claims description 135
• 125000000217 alkyl group Chemical group 0.000 claims description 110
• 239000001257 hydrogen Substances 0.000 claims description 87
• 229910052739 hydrogen Inorganic materials 0.000 claims description 87
• 125000003342 alkenyl group Chemical group 0.000 claims description 70
• 125000000304 alkynyl group Chemical group 0.000 claims description 70
• KTFDYVNEGTXQCV-UHFFFAOYSA-N 2-Thiophenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CS1 KTFDYVNEGTXQCV-UHFFFAOYSA-N 0.000 claims description 69
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 65
• 125000000623 heterocyclic group Chemical group 0.000 claims description 63
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 61
• 150000002431 hydrogen Chemical group 0.000 claims description 60
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 55
• 125000003545 alkoxy group Chemical group 0.000 claims description 54
• 150000004820 halides Chemical class 0.000 claims description 53
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 46
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 45
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 42
• 125000001424 substituent group Chemical group 0.000 claims description 41
• 201000010099 disease Diseases 0.000 claims description 38
• 230000001404 mediated effect Effects 0.000 claims description 37
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 35
• 125000005605 benzo group Chemical group 0.000 claims description 30
• 125000001188 haloalkyl group Chemical group 0.000 claims description 29
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
• 229910052799 carbon Inorganic materials 0.000 claims description 27
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
• 208000035475 disorder Diseases 0.000 claims description 23
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 22
• 125000004104 aryloxy group Chemical group 0.000 claims description 20
• 238000011282 treatment Methods 0.000 claims description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 206010020772 Hypertension Diseases 0.000 claims description 17
• 229910052760 oxygen Inorganic materials 0.000 claims description 17
• 125000002577 pseudohalo group Chemical group 0.000 claims description 17
• 206010047139 Vasoconstriction Diseases 0.000 claims description 16
• 125000004432 carbon atom Chemical group C* 0.000 claims description 16
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 16
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
• 208000024891 symptom Diseases 0.000 claims description 16
• 230000025033 vasoconstriction Effects 0.000 claims description 16
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
• 125000004429 atom Chemical group 0.000 claims description 13
• 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 claims description 13
• 125000004122 cyclic group Chemical group 0.000 claims description 13
• 125000005843 halogen group Chemical group 0.000 claims description 13
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 12
• 229910052717 sulfur Inorganic materials 0.000 claims description 12
• 208000006673 asthma Diseases 0.000 claims description 11
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
• QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
• 150000001408 amides Chemical class 0.000 claims description 9
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 9
• 230000035939 shock Effects 0.000 claims description 9
• 230000003042 antagnostic effect Effects 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 150000002367 halogens Chemical class 0.000 claims description 8
• 239000005022 packaging material Substances 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 7
• 125000004414 alkyl thio group Chemical group 0.000 claims description 7
• 125000001769 aryl amino group Chemical group 0.000 claims description 7
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
• 206010040070 Septic Shock Diseases 0.000 claims description 6
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
• 125000005110 aryl thio group Chemical group 0.000 claims description 6
• 229910052794 bromium Inorganic materials 0.000 claims description 6
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 6
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
• 125000001041 indolyl group Chemical group 0.000 claims description 6
• 208000027866 inflammatory disease Diseases 0.000 claims description 6
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
• BJVAENLIIOACPY-UHFFFAOYSA-N 1-benzothiophene-3-sulfonamide Chemical compound C1=CC=C2C(S(=O)(=O)N)=CSC2=C1 BJVAENLIIOACPY-UHFFFAOYSA-N 0.000 claims description 5
• OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 claims description 5
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 5
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
• 229910052801 chlorine Inorganic materials 0.000 claims description 5
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 5
• 125000005842 heteroatom Chemical group 0.000 claims description 5
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
• 229920006395 saturated elastomer Polymers 0.000 claims description 5
• 206010002199 Anaphylactic shock Diseases 0.000 claims description 4
• 102000003951 Erythropoietin Human genes 0.000 claims description 4
• 108090000394 Erythropoietin Proteins 0.000 claims description 4
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
• 125000003282 alkyl amino group Chemical group 0.000 claims description 4
• 125000005037 alkyl phenyl group Chemical group 0.000 claims description 4
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
• 150000001412 amines Chemical class 0.000 claims description 4
• 208000003455 anaphylaxis Diseases 0.000 claims description 4
• 229940105423 erythropoietin Drugs 0.000 claims description 4
• 125000003106 haloaryl group Chemical group 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 4
• 125000003368 amide group Chemical group 0.000 claims description 3
• 125000002837 carbocyclic group Chemical group 0.000 claims description 3
• XNTWONAICPPJDM-UHFFFAOYSA-N furan-3-sulfonamide Chemical compound NS(=O)(=O)C=1C=COC=1 XNTWONAICPPJDM-UHFFFAOYSA-N 0.000 claims description 3
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
• 125000005504 styryl group Chemical group 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
• RPGLFLADGRRVLZ-UHFFFAOYSA-N 1-(furan-2-yl)-2-phenylethanone Chemical compound C=1C=COC=1C(=O)CC1=CC=CC=C1 RPGLFLADGRRVLZ-UHFFFAOYSA-N 0.000 claims description 2
• HXMVINSKZVYIDI-UHFFFAOYSA-N 2-phenyl-1-thiophen-2-ylethanone Chemical compound C=1C=CSC=1C(=O)CC1=CC=CC=C1 HXMVINSKZVYIDI-UHFFFAOYSA-N 0.000 claims description 2
• 206010052428 Wound Diseases 0.000 claims description 2
• 208000027418 Wounds and injury Diseases 0.000 claims description 2
• ILZXWYADEVOZKS-UHFFFAOYSA-N [2-(2-phenylethenyl)furan-3-yl] acetate Chemical compound C1=COC(C=CC=2C=CC=CC=2)=C1OC(=O)C ILZXWYADEVOZKS-UHFFFAOYSA-N 0.000 claims description 2
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
• 125000002619 bicyclic group Chemical group 0.000 claims description 2
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
• 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 2
• SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 6
• 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims 1
• SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 claims 1
• USQCUKQZXOWUDF-YWZLYKJASA-N 6-chloro-n-[(3s)-1-[(2s)-1-(4-methyl-5-oxo-1,4-diazepan-1-yl)-1-oxopropan-2-yl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound O=C([C@@H](N1C([C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1)=O)C)N1CCN(C)C(=O)CC1 USQCUKQZXOWUDF-YWZLYKJASA-N 0.000 claims 1
• 241001280643 Halice Species 0.000 claims 1
• 101000636811 Homo sapiens Neudesin Proteins 0.000 claims 1
• SRBFZHDQGSBBOR-HWQSCIPKSA-N L-arabinopyranose Chemical compound O[C@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-HWQSCIPKSA-N 0.000 claims 1
• 101000956900 Mesobuthus martensii HMG-CoA reductase inhibitor bumarsin Proteins 0.000 claims 1
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• 240000006939 Pachycereus weberi Species 0.000 claims 1
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• 125000003302 alkenyloxy group Chemical group 0.000 claims 1
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• HKIOYBQGHSTUDB-UHFFFAOYSA-N folpet Chemical group C1=CC=C2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C2=C1 HKIOYBQGHSTUDB-UHFFFAOYSA-N 0.000 claims 1
• 229960003444 immunosuppressant agent Drugs 0.000 claims 1
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