SK143399A3 - Sulfonamides for treatment of endothelin-mediated disorders - Google Patents

Sulfonamides for treatment of endothelin-mediated disorders Download PDF

Info

Publication number: SK143399A3
Authority: SK; Slovakia
Prior art keywords: methyl; isoxazolyl; chloro; amino; sulfonyl
Prior art date: 1997-04-28

Application number

SK1433-99A

Other languages

English (en)

Slovak (sk)

Inventor

Chengde Wu

Natalie Blok

Timothy P Kogan

Karin Keller

Patricia Woodard

Original Assignee

Texas Biotechnology Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-04-28

Filing date

1998-04-02

Publication date

2000-05-16

1997-04-28 Priority claimed from US08/847,797 external-priority patent/US5783705A/en

1998-04-02 Application filed by Texas Biotechnology Corp filed Critical Texas Biotechnology Corp

2000-05-16 Publication of SK143399A3 publication Critical patent/SK143399A3/sk

Links

108050009340 Endothelin Proteins 0.000 title claims abstract description 231
102000002045 Endothelin Human genes 0.000 title claims abstract description 217
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 209
229940124530 sulfonamide Drugs 0.000 title claims abstract description 188
150000003456 sulfonamides Chemical class 0.000 title claims abstract description 100
238000011282 treatment Methods 0.000 title claims description 29
230000001404 mediated effect Effects 0.000 title claims description 24
-1 alkali metal salt Chemical class 0.000 claims abstract description 767
150000003839 salts Chemical class 0.000 claims abstract description 141
239000000203 mixture Chemical class 0.000 claims abstract description 113
238000000034 method Methods 0.000 claims abstract description 87
230000000694 effects Effects 0.000 claims abstract description 76
159000000000 sodium salts Chemical class 0.000 claims abstract description 63
229910052783 alkali metal Inorganic materials 0.000 claims abstract description 42
230000008569 process Effects 0.000 claims abstract description 29
125000001544 thienyl group Chemical group 0.000 claims abstract description 28
238000009472 formulation Methods 0.000 claims abstract description 21
239000003960 organic solvent Substances 0.000 claims abstract description 21
150000001340 alkali metals Chemical class 0.000 claims abstract description 19
229920006395 saturated elastomer Polymers 0.000 claims abstract description 12
239000012266 salt solution Substances 0.000 claims abstract description 11
150000001875 compounds Chemical class 0.000 claims description 266
125000000217 alkyl group Chemical group 0.000 claims description 221
125000003118 aryl group Chemical group 0.000 claims description 137
239000001257 hydrogen Substances 0.000 claims description 105
229910052739 hydrogen Inorganic materials 0.000 claims description 105
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 104
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 89
125000000753 cycloalkyl group Chemical group 0.000 claims description 88
125000000392 cycloalkenyl group Chemical group 0.000 claims description 85
125000003342 alkenyl group Chemical group 0.000 claims description 81
125000003545 alkoxy group Chemical group 0.000 claims description 76
125000000304 alkynyl group Chemical group 0.000 claims description 75
BWJZHYWAXLWLTB-UHFFFAOYSA-N thiophene-3-sulfonamide Chemical compound NS(=O)(=O)C=1C=CSC=1 BWJZHYWAXLWLTB-UHFFFAOYSA-N 0.000 claims description 74
102000005962 receptors Human genes 0.000 claims description 71
108020003175 receptors Proteins 0.000 claims description 71
125000003710 aryl alkyl group Chemical group 0.000 claims description 63
125000000623 heterocyclic group Chemical group 0.000 claims description 62
125000004432 carbon atom Chemical group C* 0.000 claims description 60
208000037265 diseases, disorders, signs and symptoms Diseases 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 50
125000001424 substituent group Chemical group 0.000 claims description 47
229910052736 halogen Inorganic materials 0.000 claims description 46
150000002367 halogens Chemical class 0.000 claims description 44
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
239000008194 pharmaceutical composition Substances 0.000 claims description 42
239000000243 solution Substances 0.000 claims description 41
125000002877 alkyl aryl group Chemical group 0.000 claims description 38
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 37
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
125000001188 haloalkyl group Chemical group 0.000 claims description 35
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 33
201000010099 disease Diseases 0.000 claims description 32
239000004480 active ingredient Substances 0.000 claims description 31
125000005843 halogen group Chemical group 0.000 claims description 31
NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 claims description 30
125000002577 pseudohalo group Chemical group 0.000 claims description 29
239000002904 solvent Substances 0.000 claims description 29
125000004104 aryloxy group Chemical group 0.000 claims description 27
125000001072 heteroaryl group Chemical group 0.000 claims description 26
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 24
239000011734 sodium Substances 0.000 claims description 24
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
230000027455 binding Effects 0.000 claims description 23
125000002541 furyl group Chemical group 0.000 claims description 23
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
239000002775 capsule Substances 0.000 claims description 22
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 22
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 21
239000002253 acid Substances 0.000 claims description 21
125000004093 cyano group Chemical group *C#N 0.000 claims description 21
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 20
125000005605 benzo group Chemical group 0.000 claims description 20
229910052708 sodium Inorganic materials 0.000 claims description 20
206010047139 Vasoconstriction Diseases 0.000 claims description 19
125000001769 aryl amino group Chemical group 0.000 claims description 19
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 19
239000000843 powder Substances 0.000 claims description 19
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 19
230000025033 vasoconstriction Effects 0.000 claims description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
125000005530 alkylenedioxy group Chemical group 0.000 claims description 18
239000005557 antagonist Substances 0.000 claims description 17
125000004122 cyclic group Chemical group 0.000 claims description 17
208000024891 symptom Diseases 0.000 claims description 17
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 16
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 16
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 15
206010020772 Hypertension Diseases 0.000 claims description 15
125000004663 dialkyl amino group Chemical group 0.000 claims description 15
229910052717 sulfur Inorganic materials 0.000 claims description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical group OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 14
125000000168 pyrrolyl group Chemical group 0.000 claims description 14
239000011575 calcium Substances 0.000 claims description 13
229910000397 disodium phosphate Inorganic materials 0.000 claims description 13
235000019800 disodium phosphate Nutrition 0.000 claims description 13
239000003937 drug carrier Substances 0.000 claims description 13
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
125000000842 isoxazolyl group Chemical group 0.000 claims description 13
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 13
229910052760 oxygen Inorganic materials 0.000 claims description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 12
208000001647 Renal Insufficiency Diseases 0.000 claims description 12
125000003282 alkyl amino group Chemical group 0.000 claims description 12
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 12
239000011230 binding agent Substances 0.000 claims description 12
229910052791 calcium Inorganic materials 0.000 claims description 12
201000006370 kidney failure Diseases 0.000 claims description 12
125000005129 aryl carbonyl group Chemical group 0.000 claims description 11
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
229910052799 carbon Inorganic materials 0.000 claims description 11
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
229910052801 chlorine Inorganic materials 0.000 claims description 11
150000004820 halides Chemical class 0.000 claims description 11
208000002815 pulmonary hypertension Diseases 0.000 claims description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
102000010180 Endothelin receptor Human genes 0.000 claims description 10
108050001739 Endothelin receptor Proteins 0.000 claims description 10
125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 10
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 10
239000008121 dextrose Substances 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
239000008176 lyophilized powder Substances 0.000 claims description 10
238000004519 manufacturing process Methods 0.000 claims description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 9
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 9
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 9
125000005110 aryl thio group Chemical group 0.000 claims description 9
208000006673 asthma Diseases 0.000 claims description 9
229910052794 bromium Inorganic materials 0.000 claims description 9
239000008101 lactose Substances 0.000 claims description 9
229910052744 lithium Inorganic materials 0.000 claims description 9
239000000314 lubricant Substances 0.000 claims description 9
JVLWFOCFTARHQQ-UHFFFAOYSA-N n-(2-acetyl-4,6-dimethylphenyl)-3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-5-methylthiophene-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=C(C)S1 JVLWFOCFTARHQQ-UHFFFAOYSA-N 0.000 claims description 9
238000007911 parenteral administration Methods 0.000 claims description 9
239000011591 potassium Substances 0.000 claims description 9
229910052700 potassium Inorganic materials 0.000 claims description 9
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 8
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 8
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 8
125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 8
125000006639 cyclohexyl carbonyl group Chemical group 0.000 claims description 8
125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims description 8
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
229910052749 magnesium Inorganic materials 0.000 claims description 8
125000004430 oxygen atom Chemical group O* 0.000 claims description 8
239000005022 packaging material Substances 0.000 claims description 8
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
229920002785 Croscarmellose sodium Polymers 0.000 claims description 7
229920002472 Starch Polymers 0.000 claims description 7
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 7
BTIIGNUPPKUQAP-UHFFFAOYSA-N [1-[2,3-dihydroxy-4-[4-(oxoazaniumylmethylidene)pyridin-1-yl]butyl]pyridin-4-ylidene]methyl-oxoazanium;diperchlorate Chemical compound [O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O.C1=CC(=C[NH+]=O)C=CN1CC(O)C(O)CN1C=CC(=C[NH+]=O)C=C1 BTIIGNUPPKUQAP-UHFFFAOYSA-N 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 7
238000001914 filtration Methods 0.000 claims description 7
125000001841 imino group Chemical group [H]N=* 0.000 claims description 7
239000011777 magnesium Substances 0.000 claims description 7
235000019359 magnesium stearate Nutrition 0.000 claims description 7
238000002156 mixing Methods 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
239000001301 oxygen Chemical group 0.000 claims description 7
239000001488 sodium phosphate Substances 0.000 claims description 7
239000008107 starch Substances 0.000 claims description 7
235000019698 starch Nutrition 0.000 claims description 7
235000000346 sugar Nutrition 0.000 claims description 7
239000011593 sulfur Substances 0.000 claims description 7
229910052725 zinc Inorganic materials 0.000 claims description 7
239000011701 zinc Substances 0.000 claims description 7
208000024172 Cardiovascular disease Diseases 0.000 claims description 6
BEGKPPZBSJFKMI-UHFFFAOYSA-N [Na].O1N=CC=C1 Chemical compound [Na].O1N=CC=C1 BEGKPPZBSJFKMI-UHFFFAOYSA-N 0.000 claims description 6
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 6
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
125000004414 alkyl thio group Chemical group 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
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 6
239000012044 organic layer Substances 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
229920000168 Microcrystalline cellulose Polymers 0.000 claims description 5
206010049771 Shock haemorrhagic Diseases 0.000 claims description 5
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
125000002947 alkylene group Chemical group 0.000 claims description 5
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
125000004986 diarylamino group Chemical group 0.000 claims description 5
125000004475 heteroaralkyl group Chemical group 0.000 claims description 5
125000001041 indolyl group Chemical group 0.000 claims description 5
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 5
235000019813 microcrystalline cellulose Nutrition 0.000 claims description 5
239000008108 microcrystalline cellulose Substances 0.000 claims description 5
229940016286 microcrystalline cellulose Drugs 0.000 claims description 5
206010002199 Anaphylactic shock Diseases 0.000 claims description 4
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 4
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 4
208000032456 Hemorrhagic Shock Diseases 0.000 claims description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
208000003455 anaphylaxis Diseases 0.000 claims description 4
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
238000001035 drying Methods 0.000 claims description 4
125000003106 haloaryl 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
230000002401 inhibitory effect Effects 0.000 claims description 4
239000000600 sorbitol Substances 0.000 claims description 4
235000010356 sorbitol Nutrition 0.000 claims description 4
125000000335 thiazolyl group Chemical group 0.000 claims description 4
OEDKACDUUGHIHJ-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-2-methoxy-N-methyl-3H-thiophene-2-carboxamide Chemical compound COC1(SC=CC1S(NC1=C(C(=NO1)C)Cl)(=O)=O)C(=O)NC OEDKACDUUGHIHJ-UHFFFAOYSA-N 0.000 claims description 3
NQVASRWCYTWTEU-UHFFFAOYSA-N 4,5-dimethylthiophene-2-carboxamide Chemical compound CC=1C=C(C(N)=O)SC=1C NQVASRWCYTWTEU-UHFFFAOYSA-N 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
125000003368 amide group Chemical group 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
125000005135 aryl sulfinyl group Chemical group 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
125000002619 bicyclic group Chemical group 0.000 claims description 3
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 3
125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims description 3
229960001681 croscarmellose sodium Drugs 0.000 claims description 3
239000002270 dispersing agent Substances 0.000 claims description 3
239000003018 immunosuppressive agent Substances 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
230000035939 shock Effects 0.000 claims description 3
PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical group 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 3
229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
229940023144 sodium glycolate Drugs 0.000 claims description 3
JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 claims description 3
KNTSDSCGWPXOEN-UHFFFAOYSA-N (2,4,6-trimethylphenyl)carbamic acid Chemical compound CC1=CC(C)=C(NC(O)=O)C(C)=C1 KNTSDSCGWPXOEN-UHFFFAOYSA-N 0.000 claims description 2
WIGHJRMMMPJLKR-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-2-[3-(cyanomethyl)-2,4,6-trimethylphenyl]-3H-thiophene-2-carboxamide Chemical compound C(#N)CC=1C(=C(C(=CC1C)C)C1(SC=CC1S(NC1=C(C(=NO1)C)Cl)(=O)=O)C(=O)N)C WIGHJRMMMPJLKR-UHFFFAOYSA-N 0.000 claims description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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SK1433-99A 1997-04-28 1998-04-02 Sulfonamides for treatment of endothelin-mediated disorders SK143399A3 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US08/847,797 US5783705A (en)	1997-04-28	1997-04-28	Process of preparing alkali metal salys of hydrophobic sulfonamides
US08/938,444 US6248767B1 (en)	1997-04-28	1997-09-26	Formulation of sulfonamides for treatment of endothelin-mediated disorders
PCT/US1998/006680 WO1998049162A1 (en)	1997-04-28	1998-04-02	Sulfonamides for treatment of endothelin-mediated disorders

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EP (1)	EP0980369B1 (cs)
JP (3)	JP3455233B2 (cs)
CN (2)	CN1179961C (cs)
AP (1)	AP9901643A0 (cs)
AT (1)	ATE292129T1 (cs)
AU (1)	AU749167B2 (cs)
BR (1)	BR9812258A (cs)
CA (2)	CA2281090C (cs)
CZ (1)	CZ301452B6 (cs)
DE (2)	DE69839534D1 (cs)
EA (1)	EA003993B1 (cs)
EE (1)	EE04156B1 (cs)
ES (1)	ES2241133T3 (cs)
HU (1)	HU227183B1 (cs)
ID (1)	ID25921A (cs)
IL (2)	IL156977A (cs)
NO (1)	NO995221L (cs)
NZ (1)	NZ336898A (cs)
OA (1)	OA11167A (cs)
PL (1)	PL197843B1 (cs)
SG (2)	SG100767A1 (cs)
SK (1)	SK143399A3 (cs)
TR (3)	TR200101905T2 (cs)
WO (1)	WO1998049162A1 (cs)

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1998
- 1998-04-02 JP JP54098298A patent/JP3455233B2/ja not_active Expired - Fee Related
- 1998-04-02 ES ES98915281T patent/ES2241133T3/es not_active Expired - Lifetime
- 1998-04-02 NZ NZ336898A patent/NZ336898A/en unknown
- 1998-04-02 CN CNB988046148A patent/CN1179961C/zh not_active Expired - Fee Related
- 1998-04-02 EE EEP199900469A patent/EE04156B1/xx not_active IP Right Cessation
- 1998-04-02 SG SG200106591A patent/SG100767A1/en unknown
- 1998-04-02 PL PL336290A patent/PL197843B1/pl not_active IP Right Cessation
- 1998-04-02 BR BR9812258-4A patent/BR9812258A/pt not_active Application Discontinuation
- 1998-04-02 IL IL15697798A patent/IL156977A/xx not_active IP Right Cessation
- 1998-04-02 TR TR2001/01905T patent/TR200101905T2/xx unknown
- 1998-04-02 CN CN2004100923126A patent/CN1636994B/zh not_active Expired - Fee Related
- 1998-04-02 WO PCT/US1998/006680 patent/WO1998049162A1/en not_active Ceased
- 1998-04-02 EP EP98915281A patent/EP0980369B1/en not_active Expired - Lifetime
- 1998-04-02 SG SG200106590A patent/SG100766A1/en unknown
- 1998-04-02 CA CA002281090A patent/CA2281090C/en not_active Expired - Fee Related
- 1998-04-02 EA EA199900966A patent/EA003993B1/ru not_active IP Right Cessation
- 1998-04-02 US US09/403,599 patent/US6432994B1/en not_active Expired - Lifetime
- 1998-04-02 TR TR1999/02401T patent/TR199902401T2/xx unknown
- 1998-04-02 DE DE69839534T patent/DE69839534D1/de not_active Expired - Lifetime
- 1998-04-02 SK SK1433-99A patent/SK143399A3/sk unknown
- 1998-04-02 ID IDW991119A patent/ID25921A/id unknown
- 1998-04-02 CA CA002496680A patent/CA2496680A1/en not_active Abandoned
- 1998-04-02 DE DE69829558T patent/DE69829558T2/de not_active Expired - Lifetime
- 1998-04-02 HU HU0001442A patent/HU227183B1/hu not_active IP Right Cessation
- 1998-04-02 AU AU69504/98A patent/AU749167B2/en not_active Ceased
- 1998-04-02 IL IL13131898A patent/IL131318A/en not_active IP Right Cessation
- 1998-04-02 AT AT98915281T patent/ATE292129T1/de not_active IP Right Cessation
- 1998-04-02 CZ CZ0367599A patent/CZ301452B6/cs not_active IP Right Cessation
- 1998-04-02 AP APAP/P/1999/001643A patent/AP9901643A0/en unknown
- 1998-04-02 TR TR2002/02738T patent/TR200202738T2/xx unknown
1999
- 1999-10-22 OA OA9900233A patent/OA11167A/en unknown
- 1999-10-26 NO NO995221A patent/NO995221L/no unknown
2001
- 2001-02-23 US US09/792,237 patent/US6458805B2/en not_active Expired - Fee Related
- 2001-12-20 US US10/029,561 patent/US6683103B2/en not_active Expired - Fee Related
2002
- 2002-12-04 JP JP2002352236A patent/JP4256150B2/ja not_active Expired - Fee Related
2007
- 2007-12-12 JP JP2007320895A patent/JP2008074875A/ja active Pending

Also Published As

Publication number	Publication date
US6458805B2 (en)	2002-10-01
HUP0001442A3 (en)	2001-12-28
OA11167A (en)	2003-04-29
IL131318A (en)	2004-08-31
US20010039289A1 (en)	2001-11-08
EA003993B1 (ru)	2003-12-25
US20020091270A1 (en)	2002-07-11
EP0980369B1 (en)	2005-03-30
HU227183B1 (en)	2010-09-28
CZ367599A3 (cs)	2000-02-16
CN1179961C (zh)	2004-12-15
NO995221L (no)	1999-12-28
JP4256150B2 (ja)	2009-04-22
ATE292129T1 (de)	2005-04-15
US6683103B2 (en)	2004-01-27
HK1028033A1 (en)	2001-03-02
EE04156B1 (et)	2003-10-15
IL156977A (en)	2005-03-20
DE69829558T2 (de)	2006-02-16
IL156977A0 (en)	2004-02-08
NZ336898A (en)	2001-10-26
ES2241133T3 (es)	2005-10-16
SG100767A1 (en)	2003-12-26
DE69829558D1 (de)	2005-05-04
DE69839534D1 (de)	2008-07-03
CN1253560A (zh)	2000-05-17
JP2001520643A (ja)	2001-10-30
CA2281090A1 (en)	1998-11-05
EE9900469A (et)	2000-06-15
WO1998049162A1 (en)	1998-11-05
EP0980369A1 (en)	2000-02-23
CA2496680A1 (en)	1998-11-05
TR200101905T2 (tr)	2002-06-21
CZ301452B6 (cs)	2010-03-10
AP9901643A0 (en)	1999-10-02
ID25921A (id)	2000-11-09
JP3455233B2 (ja)	2003-10-14
US6432994B1 (en)	2002-08-13
CA2281090C (en)	2005-06-07
NO995221D0 (no)	1999-10-26
CN1636994B (zh)	2010-05-12
JP2003176288A (ja)	2003-06-24
HUP0001442A2 (hu)	2001-11-28
TR200202738T2 (tr)	2003-03-21
CN1636994A (zh)	2005-07-13
IL131318A0 (en)	2001-01-28
BR9812258A (pt)	2000-07-25
TR199902401T2 (xx)	2000-08-21
EA199900966A1 (ru)	2000-08-28
PL197843B1 (pl)	2008-05-30
PL336290A1 (en)	2000-06-19
JP2008074875A (ja)	2008-04-03
SG100766A1 (en)	2003-12-26
AU6950498A (en)	1998-11-24
AU749167B2 (en)	2002-06-20

Publication	Publication Date	Title
SK143399A3 (en)	2000-05-16	Sulfonamides for treatment of endothelin-mediated disorders
KR100400795B1 (ko)	2003-10-08	엔도텔린-매개된 질환 치료용 설폰아미드 및 약제학적으로 허용되는 이의 염
EP0946552B1 (en)	2004-07-07	Sulfonamides and derivatives thereof that modulate the activity of endothelin
ES2201181T3 (es)	2004-03-16	Tienil-, furil-, pirrolil- y bifenilsulfonamidas y derivados de los mismos que modulan la actividad de endotelina.
CA2395684C (en)	2012-01-03	Sulfonamides and derivatives thereof that modulate the activity of endothelin
US6613804B2 (en)	2003-09-02	Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin
US6342610B2 (en)	2002-01-29	N-aryl thienyl-, furyl-, and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin
HK1072606A (en)	2005-09-02	Sulfonamides for treatment of endothelin-mediated disorders
HK1072607A (en)	2005-09-02	Process for preparing alkali metal salts of hydrophobic sulfonamides
EP1533311A1 (en)	2005-05-25	Sulfonamides and derivatives thereof that modulate the activity of endothelin