OA11167A - Sulfonamides for treatment of endothelin-mediated disorders - Google Patents

Info

Publication number

OA11167A

OA11167A OA9900233A OA9900233A OA11167A OA 11167 A OA11167 A OA 11167A OA 9900233 A OA9900233 A OA 9900233A OA 9900233 A OA9900233 A OA 9900233A OA 11167 A OA11167 A OA 11167A

Authority

OA

OAPI

Prior art keywords

methyl

isoxazolyl

chloro

amino

sulfonyl

Prior art date

1997-04-28

Links

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• Global Dossier
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• 229940124530 sulfonamide Drugs 0.000 title claims abstract description 223
• 108050009340 Endothelin Proteins 0.000 title claims abstract description 120
• 102000002045 Endothelin Human genes 0.000 title claims abstract description 110
• 150000003456 sulfonamides Chemical class 0.000 title claims abstract description 105
• 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 101
• 230000001404 mediated effect Effects 0.000 title claims description 30
• -1 alkali metal salt Chemical class 0.000 claims abstract description 379
• 239000000203 mixture Chemical class 0.000 claims abstract description 180
• 238000000034 method Methods 0.000 claims abstract description 99
• 238000009472 formulation Methods 0.000 claims abstract description 95
• 150000003839 salts Chemical class 0.000 claims abstract description 95
• 230000000694 effects Effects 0.000 claims abstract description 86
• 230000008569 process Effects 0.000 claims abstract description 35
• 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 20
• 239000003960 organic solvent Substances 0.000 claims abstract description 17
• 125000001544 thienyl group Chemical group 0.000 claims abstract description 17
• 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 9
• 229920006395 saturated elastomer Polymers 0.000 claims abstract description 9
• 150000001340 alkali metals Chemical class 0.000 claims abstract description 7
• 150000001875 compounds Chemical class 0.000 claims description 282
• 125000000217 alkyl group Chemical group 0.000 claims description 138
• 125000003118 aryl group Chemical group 0.000 claims description 136
• 239000001257 hydrogen Substances 0.000 claims description 116
• 229910052739 hydrogen Inorganic materials 0.000 claims description 116
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 109
• 239000011734 sodium Substances 0.000 claims description 104
• 229910052708 sodium Inorganic materials 0.000 claims description 104
• BWJZHYWAXLWLTB-UHFFFAOYSA-N thiophene-3-sulfonamide Chemical compound NS(=O)(=O)C=1C=CSC=1 BWJZHYWAXLWLTB-UHFFFAOYSA-N 0.000 claims description 98
• 239000000243 solution Substances 0.000 claims description 80
• 125000003342 alkenyl group Chemical group 0.000 claims description 78
• 125000000304 alkynyl group Chemical group 0.000 claims description 72
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 72
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 66
• 102000005962 receptors Human genes 0.000 claims description 66
• 108020003175 receptors Proteins 0.000 claims description 66
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 65
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 61
• 125000003545 alkoxy group Chemical group 0.000 claims description 60
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 59
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 58
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 56
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 54
• 125000000623 heterocyclic group Chemical group 0.000 claims description 50
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 50
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 48
• 150000004820 halides Chemical class 0.000 claims description 47
• 125000001424 substituent group Chemical group 0.000 claims description 46
• 229910001868 water Inorganic materials 0.000 claims description 44
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 35
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 35
• 239000003513 alkali Substances 0.000 claims description 33
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 33
• 208000035475 disorder Diseases 0.000 claims description 33
• 125000002577 pseudohalo group Chemical group 0.000 claims description 33
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 29
• 239000002253 acid Substances 0.000 claims description 29
• 125000001188 haloalkyl group Chemical group 0.000 claims description 29
• 125000005843 halogen group Chemical group 0.000 claims description 29
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 27
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
• 201000010099 disease Diseases 0.000 claims description 26
• 239000000843 powder Substances 0.000 claims description 26
• 229910000397 disodium phosphate Inorganic materials 0.000 claims description 25
• 235000019800 disodium phosphate Nutrition 0.000 claims description 25
• 125000001072 heteroaryl group Chemical group 0.000 claims description 25
• 125000004104 aryloxy group Chemical group 0.000 claims description 23
• 239000002775 capsule Substances 0.000 claims description 23
• 229910052799 carbon Inorganic materials 0.000 claims description 22
• 239000002904 solvent Substances 0.000 claims description 22
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 19
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
• 125000002541 furyl group Chemical group 0.000 claims description 18
• 102000010180 Endothelin receptor Human genes 0.000 claims description 17
• 108050001739 Endothelin receptor Proteins 0.000 claims description 17
• 206010020772 Hypertension Diseases 0.000 claims description 17
• 125000004432 carbon atom Chemical group C* 0.000 claims description 17
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 17
• 206010047139 Vasoconstriction Diseases 0.000 claims description 16
• 229910052760 oxygen Inorganic materials 0.000 claims description 16
• 230000025033 vasoconstriction Effects 0.000 claims description 16
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 15
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 15
• 208000024891 symptom Diseases 0.000 claims description 15
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 14
• 125000004122 cyclic group Chemical group 0.000 claims description 14
• 238000001914 filtration Methods 0.000 claims description 14
• 239000008176 lyophilized powder Substances 0.000 claims description 14
• 238000004519 manufacturing process Methods 0.000 claims description 14
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 13
• 125000003282 alkyl amino group Chemical group 0.000 claims description 13
• 239000011575 calcium Substances 0.000 claims description 13
• 229910052791 calcium Inorganic materials 0.000 claims description 13
• 239000010410 layer Substances 0.000 claims description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims description 13
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 12
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
• 239000012044 organic layer Substances 0.000 claims description 12
• 235000000346 sugar Nutrition 0.000 claims description 12
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 11
• GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 11
• 239000005022 packaging material Substances 0.000 claims description 11
• 239000000600 sorbitol Substances 0.000 claims description 11
• 235000010356 sorbitol Nutrition 0.000 claims description 11
• 125000001769 aryl amino group Chemical group 0.000 claims description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
• 239000003085 diluting agent Substances 0.000 claims description 10
• 125000001041 indolyl group Chemical group 0.000 claims description 10
• 239000008101 lactose Substances 0.000 claims description 10
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 10
• PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 claims description 10
• 239000001488 sodium phosphate Substances 0.000 claims description 10
• 208000006673 asthma Diseases 0.000 claims description 9
• 230000002401 inhibitory effect Effects 0.000 claims description 9
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 8
• 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 8
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 8
• 230000003042 antagnostic effect Effects 0.000 claims description 8
• 239000011230 binding agent Substances 0.000 claims description 8
• 239000007884 disintegrant Substances 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 claims description 8
• 229910052700 potassium Inorganic materials 0.000 claims description 8
• 239000011591 potassium Substances 0.000 claims description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 7
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
• 208000027866 inflammatory disease Diseases 0.000 claims description 7
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 7
• 239000000314 lubricant Substances 0.000 claims description 7
• 238000002156 mixing Methods 0.000 claims description 7
• 229910052717 sulfur Inorganic materials 0.000 claims description 7
• 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 6
• 206010040070 Septic Shock Diseases 0.000 claims description 6
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
• 125000004414 alkyl thio group Chemical group 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 229940016286 microcrystalline cellulose Drugs 0.000 claims description 6
• 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 6
• 239000008108 microcrystalline cellulose Substances 0.000 claims description 6
• 238000011084 recovery Methods 0.000 claims description 6
• 230000035939 shock Effects 0.000 claims description 6
• 235000015424 sodium Nutrition 0.000 claims description 6
• 239000008109 sodium starch glycolate Substances 0.000 claims description 6
• 229920003109 sodium starch glycolate Polymers 0.000 claims description 6
• 229940079832 sodium starch glycolate Drugs 0.000 claims description 6
• KMHLVJAMVJZVMR-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-[3-(cyanomethyl)-2,4,6-trimethylphenyl]thiophene-2-carboxamide Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)NC=2C(=C(CC#N)C(C)=CC=2C)C)=C1Cl KMHLVJAMVJZVMR-UHFFFAOYSA-N 0.000 claims description 5
• POLAVUVVBKLQNP-UHFFFAOYSA-N 5-(chloromethyl)-6-methyl-1,3-benzodioxole Chemical compound C1=C(CCl)C(C)=CC2=C1OCO2 POLAVUVVBKLQNP-UHFFFAOYSA-N 0.000 claims description 5
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
• 206010053317 Hydrophobia Diseases 0.000 claims description 5
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
• 125000002947 alkylene group Chemical group 0.000 claims description 5
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-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
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
• 125000004986 diarylamino group Chemical group 0.000 claims description 5
• 238000001035 drying Methods 0.000 claims description 5
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 5
• YFJUSGDKCDQMNE-UHFFFAOYSA-N n-(2-acetyl-4,6-dimethylphenyl)-3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]thiophene-2-carboxamide Chemical compound CC(=O)C1=CC(C)=CC(C)=C1NC(=O)C1=C(S(=O)(=O)NC2=C(C(C)=NO2)Cl)C=CS1 YFJUSGDKCDQMNE-UHFFFAOYSA-N 0.000 claims description 5
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
• 239000012047 saturated solution Substances 0.000 claims description 5
• 238000005406 washing Methods 0.000 claims description 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 4
• 208000019255 Menstrual disease Diseases 0.000 claims description 4
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
• AJDYXXCWHDGBML-UHFFFAOYSA-N [3-[[3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]thiophene-2-carbonyl]amino]-2,4,6-trimethylphenyl]methyl acetate Chemical compound CC(=O)OCC1=C(C)C=C(C)C(NC(=O)C2=C(C=CS2)S(=O)(=O)NC2=C(C(C)=NO2)Cl)=C1C AJDYXXCWHDGBML-UHFFFAOYSA-N 0.000 claims description 4
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 4
• 239000003708 ampul Substances 0.000 claims description 4
• 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 4
• 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 4
• 125000005110 aryl thio group Chemical group 0.000 claims description 4
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 4
• 125000003106 haloaryl group Chemical group 0.000 claims description 4
• 125000001475 halogen functional group Chemical group 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
• 229910052744 lithium Inorganic materials 0.000 claims description 4
• 150000007524 organic acids Chemical class 0.000 claims description 4
• 235000005985 organic acids Nutrition 0.000 claims description 4
• 235000007686 potassium Nutrition 0.000 claims description 4
• 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
• 125000000335 thiazolyl group Chemical group 0.000 claims description 4
• 229910052725 zinc Inorganic materials 0.000 claims description 4
• 239000011701 zinc Substances 0.000 claims description 4
• WRQZFIKPBQESAY-UHFFFAOYSA-N (2,4,6-trimethylphenyl) 3-[(4-bromo-3-methyl-1,2-oxazol-5-yl)sulfamoyl]thiophene-2-carboxylate Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)OC=2C(=CC(C)=CC=2C)C)=C1Br WRQZFIKPBQESAY-UHFFFAOYSA-N 0.000 claims description 3
• LUZPZMXRVHRPFI-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-[2-(cyclohexanecarbonyl)-4,6-dimethylphenyl]thiophene-2-carboxamide Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)NC=2C(=CC(C)=CC=2C)C(=O)C2CCCCC2)=C1Cl LUZPZMXRVHRPFI-UHFFFAOYSA-N 0.000 claims description 3
• YRPFAUGLERVXFY-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-[2-(cyclopropanecarbonyl)-4,6-dimethylphenyl]thiophene-2-carboxamide Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)NC=2C(=CC(C)=CC=2C)C(=O)C2CC2)=C1Cl YRPFAUGLERVXFY-UHFFFAOYSA-N 0.000 claims description 3
• UXNJXSWMWFYCEM-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-[3-(hydroxymethyl)-2,4,6-trimethylphenyl]thiophene-2-carboxamide Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)NC=2C(=C(CO)C(C)=CC=2C)C)=C1Cl UXNJXSWMWFYCEM-UHFFFAOYSA-N 0.000 claims description 3
• 229920002785 Croscarmellose sodium Polymers 0.000 claims description 3
• 206010052428 Wound Diseases 0.000 claims description 3
• 208000027418 Wounds and injury Diseases 0.000 claims description 3
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 3
• 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
• 150000001342 alkaline earth metals Chemical class 0.000 claims description 3
• 239000012736 aqueous medium Substances 0.000 claims description 3
• 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 3
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 3
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 3
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
• XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical group [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 claims description 3
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 125000005504 styryl group Chemical group 0.000 claims description 3
• 239000008215 water for injection Substances 0.000 claims description 3
• 235000016804 zinc Nutrition 0.000 claims description 3
• VMRGBLIETYGKNV-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-(2,4,6-trimethylphenyl)thiophene-2-carboxamide Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)NC=2C(=CC(C)=CC=2C)C)=C1Cl VMRGBLIETYGKNV-UHFFFAOYSA-N 0.000 claims description 2
• PXJLTFSEDOQPST-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-[2,4-dimethyl-6-(2-methylpropanoyl)phenyl]-4,5-dimethylthiophene-2-carboxamide Chemical compound CC(C)C(=O)C1=CC(C)=CC(C)=C1NC(=O)C1=C(S(=O)(=O)NC2=C(C(C)=NO2)Cl)C(C)=C(C)S1 PXJLTFSEDOQPST-UHFFFAOYSA-N 0.000 claims description 2
• QPOBBZPLOYXBDB-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-[2-(1-hydroxypropan-2-yl)-4,6-dimethylphenyl]thiophene-2-carboxamide Chemical compound OCC(C)C1=CC(C)=CC(C)=C1NC(=O)C1=C(S(=O)(=O)NC2=C(C(C)=NO2)Cl)C=CS1 QPOBBZPLOYXBDB-UHFFFAOYSA-N 0.000 claims description 2
• UJZHLVAXBHAVFY-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-[2-(2-methoxyacetyl)-4,6-dimethylphenyl]-5-methylthiophene-2-carboxamide Chemical compound COCC(=O)C1=CC(C)=CC(C)=C1NC(=O)C1=C(S(=O)(=O)NC2=C(C(C)=NO2)Cl)C=C(C)S1 UJZHLVAXBHAVFY-UHFFFAOYSA-N 0.000 claims description 2
• RZIFIFAUKQMMES-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-[2-(cyclohexanecarbonyl)-4,6-dimethylphenyl]-4-methylthiophene-2-carboxamide Chemical compound O1N=C(C)C(Cl)=C1NS(=O)(=O)C=1C(C)=CSC=1C(=O)NC1=C(C)C=C(C)C=C1C(=O)C1CCCCC1 RZIFIFAUKQMMES-UHFFFAOYSA-N 0.000 claims description 2
• PBBDPCDFMNKCAE-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-[2-(cyclopropanecarbonyl)-4,6-dimethylphenyl]-4-methylthiophene-2-carboxamide Chemical compound O1N=C(C)C(Cl)=C1NS(=O)(=O)C=1C(C)=CSC=1C(=O)NC1=C(C)C=C(C)C=C1C(=O)C1CC1 PBBDPCDFMNKCAE-UHFFFAOYSA-N 0.000 claims description 2
• VRGYYWMUTXDXKN-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-methoxy-n-methylthiophene-2-carboxamide Chemical compound S1C=CC(S(=O)(=O)NC2=C(C(C)=NO2)Cl)=C1C(=O)N(C)OC VRGYYWMUTXDXKN-UHFFFAOYSA-N 0.000 claims description 2
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