SK36599A3 - Sulfonamides and derivatives thereof that modulate the activity of endothelin - Google Patents

Sulfonamides and derivatives thereof that modulate the activity of endothelin Download PDF

Info

Publication number: SK36599A3
Authority: SK; Slovakia
Prior art keywords: methyl; sulfonamide; chloro; isoxazolyl; thiophene
Prior art date: 1996-09-27

Application number

SK365-99A

Other languages

English (en)

Slovak (sk)

Inventor

Chengde Wu

Bore Gowda Raju

Timothy P Kogan

Natalie Blok

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.)

1996-09-27

Filing date

1997-09-26

Publication date

2000-02-14

1997-09-26 Application filed by Texas Biotechnology Corp filed Critical Texas Biotechnology Corp

2000-02-14 Publication of SK36599A3 publication Critical patent/SK36599A3/sk

Links

108050009340 Endothelin Proteins 0.000 title claims abstract description 248
102000002045 Endothelin Human genes 0.000 title claims abstract description 230
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 219
229940124530 sulfonamide Drugs 0.000 title claims abstract description 136
230000000694 effects Effects 0.000 title claims abstract description 71
150000003456 sulfonamides Chemical class 0.000 title claims abstract description 64
150000003839 salts Chemical class 0.000 claims abstract description 119
239000000203 mixture Substances 0.000 claims abstract description 93
102000005962 receptors Human genes 0.000 claims abstract description 67
108020003175 receptors Proteins 0.000 claims abstract description 67
238000000034 method Methods 0.000 claims abstract description 59
230000001404 mediated effect Effects 0.000 claims abstract description 39
230000027455 binding Effects 0.000 claims abstract description 25
102000010180 Endothelin receptor Human genes 0.000 claims abstract description 24
108050001739 Endothelin receptor Proteins 0.000 claims abstract description 24
230000002401 inhibitory effect Effects 0.000 claims abstract description 8
-1 -NH 2 Inorganic materials 0.000 claims description 924
BWJZHYWAXLWLTB-UHFFFAOYSA-N thiophene-3-sulfonamide Chemical compound NS(=O)(=O)C=1C=CSC=1 BWJZHYWAXLWLTB-UHFFFAOYSA-N 0.000 claims description 243
150000001875 compounds Chemical class 0.000 claims description 236
125000000217 alkyl group Chemical group 0.000 claims description 204
125000003118 aryl group Chemical group 0.000 claims description 138
239000002253 acid Substances 0.000 claims description 79
229910052739 hydrogen Inorganic materials 0.000 claims description 74
239000001257 hydrogen Substances 0.000 claims description 73
150000002148 esters Chemical class 0.000 claims description 71
HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 claims description 67
125000003342 alkenyl group Chemical group 0.000 claims description 67
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 67
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 64
125000000304 alkynyl group Chemical group 0.000 claims description 61
125000001072 heteroaryl group Chemical group 0.000 claims description 61
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 55
150000002431 hydrogen Chemical class 0.000 claims description 51
239000000243 solution Substances 0.000 claims description 50
150000007513 acids Chemical class 0.000 claims description 47
125000003710 aryl alkyl group Chemical group 0.000 claims description 47
239000008194 pharmaceutical composition Substances 0.000 claims description 46
159000000000 sodium salts Chemical class 0.000 claims description 46
125000003545 alkoxy group Chemical group 0.000 claims description 45
201000010099 disease Diseases 0.000 claims description 45
229910052736 halogen Inorganic materials 0.000 claims description 43
150000002367 halogens Chemical class 0.000 claims description 43
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 41
125000004093 cyano group Chemical group *C#N 0.000 claims description 40
125000002877 alkyl aryl group Chemical group 0.000 claims description 36
125000004432 carbon atom Chemical group C* 0.000 claims description 36
125000001188 haloalkyl group Chemical group 0.000 claims description 36
125000000623 heterocyclic group Chemical group 0.000 claims description 36
125000001424 substituent group Chemical group 0.000 claims description 35
125000000392 cycloalkenyl group Chemical group 0.000 claims description 34
125000000753 cycloalkyl group Chemical group 0.000 claims description 33
125000005843 halogen group Chemical group 0.000 claims description 32
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 31
125000002577 pseudohalo group Chemical group 0.000 claims description 30
238000011282 treatment Methods 0.000 claims description 27
239000002775 capsule Substances 0.000 claims description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 24
208000024891 symptom Diseases 0.000 claims description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
208000035475 disorder Diseases 0.000 claims description 22
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
150000002402 hexoses Chemical class 0.000 claims description 20
229910052717 sulfur Inorganic materials 0.000 claims description 20
ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 claims description 19
206010020772 Hypertension Diseases 0.000 claims description 19
206010047139 Vasoconstriction Diseases 0.000 claims description 19
230000025033 vasoconstriction Effects 0.000 claims description 19
125000004104 aryloxy group Chemical group 0.000 claims description 18
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 17
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 17
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
229910052757 nitrogen Inorganic materials 0.000 claims description 17
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 16
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 16
125000004414 alkyl thio group Chemical group 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
239000000843 powder Substances 0.000 claims description 16
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims description 15
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims description 15
150000001413 amino acids Chemical class 0.000 claims description 15
125000001769 aryl amino group Chemical group 0.000 claims description 15
125000005110 aryl thio group Chemical group 0.000 claims description 15
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 15
125000004122 cyclic group Chemical group 0.000 claims description 15
239000008176 lyophilized powder Substances 0.000 claims description 15
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 15
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 14
150000008444 O-glycosides Chemical class 0.000 claims description 14
125000003282 alkyl amino group Chemical group 0.000 claims description 14
125000005129 aryl carbonyl group Chemical group 0.000 claims description 14
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 14
125000003106 haloaryl group Chemical group 0.000 claims description 14
229930182473 O-glycoside Natural products 0.000 claims description 13
235000001014 amino acid Nutrition 0.000 claims description 13
239000003937 drug carrier Substances 0.000 claims description 13
125000002950 monocyclic group Chemical group 0.000 claims description 13
239000008121 dextrose Substances 0.000 claims description 12
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 12
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 11
208000001647 Renal Insufficiency Diseases 0.000 claims description 11
230000009471 action Effects 0.000 claims description 11
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 11
208000006673 asthma Diseases 0.000 claims description 11
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 11
201000006370 kidney failure Diseases 0.000 claims description 11
208000002815 pulmonary hypertension Diseases 0.000 claims description 11
239000011734 sodium Substances 0.000 claims description 11
125000004434 sulfur atom Chemical group 0.000 claims description 11
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 10
229910052708 sodium Inorganic materials 0.000 claims description 10
235000000346 sugar Nutrition 0.000 claims description 10
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 9
125000000842 isoxazolyl group Chemical group 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 9
239000005022 packaging material Substances 0.000 claims description 9
125000005530 alkylenedioxy group Chemical group 0.000 claims description 8
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 7
229910052783 alkali metal Inorganic materials 0.000 claims description 7
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
125000003368 amide group Chemical group 0.000 claims description 7
125000003277 amino group Chemical group 0.000 claims description 7
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 7
208000024172 Cardiovascular disease Diseases 0.000 claims description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 6
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
125000005017 substituted alkenyl group Chemical group 0.000 claims description 6
125000000335 thiazolyl group Chemical group 0.000 claims description 6
206010002199 Anaphylactic shock Diseases 0.000 claims description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 5
102000003951 Erythropoietin Human genes 0.000 claims description 5
108090000394 Erythropoietin Proteins 0.000 claims description 5
239000002202 Polyethylene glycol Substances 0.000 claims description 5
206010040070 Septic Shock Diseases 0.000 claims description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
208000003455 anaphylaxis Diseases 0.000 claims description 5
125000004181 carboxyalkyl group Chemical group 0.000 claims description 5
229940105423 erythropoietin Drugs 0.000 claims description 5
208000027866 inflammatory disease Diseases 0.000 claims description 5
125000004430 oxygen atom Chemical group O* 0.000 claims description 5
229920001223 polyethylene glycol Polymers 0.000 claims description 5
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 5
150000003140 primary amides Chemical class 0.000 claims description 5
150000003334 secondary amides Chemical class 0.000 claims description 5
125000000547 substituted alkyl group Chemical group 0.000 claims description 5
239000011593 sulfur Substances 0.000 claims description 5
125000001425 triazolyl group Chemical group 0.000 claims description 5
BNMNQUBPZZSXQU-UHFFFAOYSA-N 1,3-dioxole-4-carboxylic acid Chemical compound OC(=O)C1=COCO1 BNMNQUBPZZSXQU-UHFFFAOYSA-N 0.000 claims description 4
229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 4
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 4
206010052428 Wound Diseases 0.000 claims description 4
208000027418 Wounds and injury Diseases 0.000 claims description 4
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
235000003704 aspartic acid Nutrition 0.000 claims description 4
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
235000013922 glutamic acid Nutrition 0.000 claims description 4
239000004220 glutamic acid Substances 0.000 claims description 4
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
ZQBAKBUEJOMQEX-UHFFFAOYSA-N phenyl salicylate Chemical compound OC1=CC=CC=C1C(=O)OC1=CC=CC=C1 ZQBAKBUEJOMQEX-UHFFFAOYSA-N 0.000 claims description 4
125000002098 pyridazinyl group Chemical group 0.000 claims description 4
238000006467 substitution reaction Methods 0.000 claims description 4
208000032456 Hemorrhagic Shock Diseases 0.000 claims description 3
206010049771 Shock haemorrhagic Diseases 0.000 claims description 3
125000000539 amino acid group Chemical group 0.000 claims description 3
230000003042 antagnostic effect Effects 0.000 claims description 3
150000001720 carbohydrates Chemical class 0.000 claims description 3
235000014633 carbohydrates Nutrition 0.000 claims description 3
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
229940081734 cellulose acetate phthalate Drugs 0.000 claims description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
238000009505 enteric coating Methods 0.000 claims description 3
239000002702 enteric coating Substances 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
102000014187 peptide receptors Human genes 0.000 claims description 3
108010011903 peptide receptors Proteins 0.000 claims description 3
125000006684 polyhaloalkyl group Polymers 0.000 claims description 3
239000012064 sodium phosphate buffer Substances 0.000 claims description 3
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
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 2
UBGVFFQTVMYJMH-UHFFFAOYSA-N NCC=1C(=C(C(=CC1C)C)C1(SC=CC1S(NC1=C(C(=NO1)C)Cl)(=O)=O)C(=O)N)C Chemical compound NCC=1C(=C(C(=CC1C)C)C1(SC=CC1S(NC1=C(C(=NO1)C)Cl)(=O)=O)C(=O)N)C UBGVFFQTVMYJMH-UHFFFAOYSA-N 0.000 claims description 2
235000021355 Stearic acid Nutrition 0.000 claims description 2
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
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 2
125000006323 alkenyl amino group Chemical group 0.000 claims description 2
125000003302 alkenyloxy group Chemical group 0.000 claims description 2
125000005136 alkenylsulfinyl group Chemical group 0.000 claims description 2
125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 2
125000005108 alkenylthio group Chemical group 0.000 claims description 2
125000005154 alkyl sulfonyl amino alkyl group Chemical group 0.000 claims description 2
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 2
239000007853 buffer solution Substances 0.000 claims description 2
125000005019 carboxyalkenyl group Chemical group 0.000 claims description 2
125000004966 cyanoalkyl group Chemical group 0.000 claims description 2
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
229960000969 phenyl salicylate Drugs 0.000 claims description 2
239000008117 stearic acid Substances 0.000 claims description 2
238000011146 sterile filtration Methods 0.000 claims description 2
125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
125000005135 aryl sulfinyl group Chemical group 0.000 claims 5
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims 3
CRJFLGHZBYIKES-UHFFFAOYSA-N 1-[3-(cyanomethyl)-2,4,6-trimethylphenyl]-3-thiophen-3-ylsulfonylurea Chemical compound Cc1cc(C)c(NC(=O)NS(=O)(=O)c2ccsc2)c(C)c1CC#N CRJFLGHZBYIKES-UHFFFAOYSA-N 0.000 claims 1
125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 1
VCQULTIBQFNMQW-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-2-[3-(hydroxymethyl)-2,4,6-trimethylphenyl]-3h-thiophene-2-carboxamide Chemical compound CC1=NOC(NS(=O)(=O)C2C(SC=C2)(C(N)=O)C=2C(=C(CO)C(C)=CC=2C)C)=C1Cl VCQULTIBQFNMQW-UHFFFAOYSA-N 0.000 claims 1
FTIBGHOWVJVQPO-UHFFFAOYSA-N 5-[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]thiophene-2-sulfonyl chloride Chemical compound CN1N=C(C(F)(F)F)C=C1C1=CC=C(S(Cl)(=O)=O)S1 FTIBGHOWVJVQPO-UHFFFAOYSA-N 0.000 claims 1
QCSUKRIEWPSRKV-KCOMHQNASA-N CC1=CC(=C(C(=C1CO[C@@H]2[C@H]([C@H]([C@@H]([C@H](O2)CO)O)O)O)C)C3(C(C=CS3)S(=O)(=O)NC4=C(C(=NO4)C)Cl)C(=O)N)C Chemical compound CC1=CC(=C(C(=C1CO[C@@H]2[C@H]([C@H]([C@@H]([C@H](O2)CO)O)O)O)C)C3(C(C=CS3)S(=O)(=O)NC4=C(C(=NO4)C)Cl)C(=O)N)C QCSUKRIEWPSRKV-KCOMHQNASA-N 0.000 claims 1
YXUIMCDBZCFYFX-UHFFFAOYSA-N CC1=NOC(NS(C2C=CSC2(C(N)=O)C2=C(C)C(O)=C(C)C=C2C)(=O)=O)=C1Cl Chemical compound CC1=NOC(NS(C2C=CSC2(C(N)=O)C2=C(C)C(O)=C(C)C=C2C)(=O)=O)=C1Cl YXUIMCDBZCFYFX-UHFFFAOYSA-N 0.000 claims 1
239000001856 Ethyl cellulose Substances 0.000 claims 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims 1
FCPDAEIQSSAIJC-UHFFFAOYSA-N N1N=NN=C1CC=1C(=C(C(=CC1C)C)C1(SC=CC1S(NC1=C(C(=NO1)C)Cl)(=O)=O)C(=O)N)C Chemical compound N1N=NN=C1CC=1C(=C(C(=CC1C)C)C1(SC=CC1S(NC1=C(C(=NO1)C)Cl)(=O)=O)C(=O)N)C FCPDAEIQSSAIJC-UHFFFAOYSA-N 0.000 claims 1
BTIYYMLKVODXLC-UHFFFAOYSA-N NS([S+]1C=CC=C1)(=O)=O Chemical compound NS([S+]1C=CC=C1)(=O)=O BTIYYMLKVODXLC-UHFFFAOYSA-N 0.000 claims 1
229920001214 Polysorbate 60 Polymers 0.000 claims 1
HLHVVGYKNJBNLP-UHFFFAOYSA-N S(N)(=O)(=O)C=1C(=C(C(=CC1C)C)C1(SC=CC1S(NC1=C(C(=NO1)C)Cl)(=O)=O)C(=O)N)C Chemical compound S(N)(=O)(=O)C=1C(=C(C(=CC1C)C)C1(SC=CC1S(NC1=C(C(=NO1)C)Cl)(=O)=O)C(=O)N)C HLHVVGYKNJBNLP-UHFFFAOYSA-N 0.000 claims 1
125000006350 alkyl thio alkyl group Chemical group 0.000 claims 1
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125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
210000001835 viscera Anatomy 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1

Classifications

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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D419/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms
- C07D419/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D419/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/08—Bronchodilators
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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SK365-99A 1996-09-27 1997-09-26 Sulfonamides and derivatives thereof that modulate the activity of endothelin SK36599A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US08/721,183 US5962490A (en)	1987-09-25	1996-09-27	Thienyl-, furyl- and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin
PCT/US1997/017402 WO1998013366A1 (en)	1996-09-27	1997-09-26	Sulfonamides and derivatives thereof that modulate the activity of endothelin

Publications (1)

Publication Number	Publication Date
SK36599A3 true SK36599A3 (en)	2000-02-14

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ID=24896894

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK365-99A SK36599A3 (en)	1996-09-27	1997-09-26	Sulfonamides and derivatives thereof that modulate the activity of endothelin

Country Status (23)

Country	Link
US (5)	US5962490A (de)
EP (2)	EP1342721A1 (de)
JP (2)	JP3743520B2 (de)
KR (1)	KR100372195B1 (de)
CN (2)	CN100558724C (de)
AP (1)	AP9901471A0 (de)
AT (1)	ATE270669T1 (de)
AU (1)	AU736269B2 (de)
BR (1)	BR9711550A (de)
CA (1)	CA2261760C (de)
CZ (1)	CZ85499A3 (de)
DE (1)	DE69729803T2 (de)
EA (2)	EA004146B1 (de)
ES (1)	ES2224271T3 (de)
IL (1)	IL128145A0 (de)
NO (1)	NO991388L (de)
NZ (1)	NZ334797A (de)
OA (1)	OA11024A (de)
PL (1)	PL332323A1 (de)
PT (1)	PT946552E (de)
SK (1)	SK36599A3 (de)
TR (1)	TR199900705T2 (de)
WO (1)	WO1998013366A1 (de)

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1996
- 1996-09-27 US US08/721,183 patent/US5962490A/en not_active Expired - Lifetime
1997
- 1997-09-26 EA EA199900294A patent/EA004146B1/ru not_active IP Right Cessation
- 1997-09-26 ES ES97943629T patent/ES2224271T3/es not_active Expired - Lifetime
- 1997-09-26 PT PT97943629T patent/PT946552E/pt unknown
- 1997-09-26 US US08/938,325 patent/US6420567B1/en not_active Expired - Fee Related
- 1997-09-26 EA EA200300824A patent/EA200300824A1/ru unknown
- 1997-09-26 IL IL12814597A patent/IL128145A0/xx unknown
- 1997-09-26 AP APAP/P/1999/001471A patent/AP9901471A0/en unknown
- 1997-09-26 KR KR10-1999-7002629A patent/KR100372195B1/ko not_active Expired - Lifetime
- 1997-09-26 NZ NZ334797A patent/NZ334797A/en unknown
- 1997-09-26 PL PL97332323A patent/PL332323A1/xx unknown
- 1997-09-26 AU AU45059/97A patent/AU736269B2/en not_active Ceased
- 1997-09-26 WO PCT/US1997/017402 patent/WO1998013366A1/en not_active Ceased
- 1997-09-26 TR TR1999/00705T patent/TR199900705T2/xx unknown
- 1997-09-26 EP EP03007240A patent/EP1342721A1/de not_active Withdrawn
- 1997-09-26 BR BR9711550-9A patent/BR9711550A/pt not_active IP Right Cessation
- 1997-09-26 EP EP97943629A patent/EP0946552B1/de not_active Expired - Lifetime
- 1997-09-26 CZ CZ99854A patent/CZ85499A3/cs unknown
- 1997-09-26 JP JP51597998A patent/JP3743520B2/ja not_active Expired - Lifetime
- 1997-09-26 CA CA002261760A patent/CA2261760C/en not_active Expired - Lifetime
- 1997-09-26 CN CNB031584780A patent/CN100558724C/zh not_active Expired - Lifetime
- 1997-09-26 CN CNB971983437A patent/CN1215069C/zh not_active Expired - Lifetime
- 1997-09-26 SK SK365-99A patent/SK36599A3/sk unknown
- 1997-09-26 DE DE69729803T patent/DE69729803T2/de not_active Expired - Lifetime
- 1997-09-26 AT AT97943629T patent/ATE270669T1/de not_active IP Right Cessation
1999
- 1999-03-12 OA OA9900058A patent/OA11024A/en unknown
- 1999-03-22 NO NO991388A patent/NO991388L/no unknown
- 1999-03-22 US US09/274,280 patent/US6331637B1/en not_active Expired - Fee Related
2001
- 2001-11-05 US US10/011,610 patent/US6632829B2/en not_active Expired - Fee Related
2002
- 2002-04-03 JP JP2002101613A patent/JP2002308875A/ja active Pending
2003
- 2003-05-28 US US10/447,763 patent/US20030208084A1/en not_active Abandoned

Also Published As

Publication number	Publication date
KR100372195B1 (ko)	2003-02-14
NO991388L (no)	1999-05-27
BR9711550A (pt)	2000-01-18
US6420567B1 (en)	2002-07-16
NZ334797A (en)	2001-02-23
JP3743520B2 (ja)	2006-02-08
EA199900294A1 (ru)	2000-02-28
CN1215069C (zh)	2005-08-17
AU736269B2 (en)	2001-07-26
CA2261760A1 (en)	1998-04-02
ATE270669T1 (de)	2004-07-15
DE69729803T2 (de)	2005-07-14
US20020091272A1 (en)	2002-07-11
CN1231664A (zh)	1999-10-13
US6632829B2 (en)	2003-10-14
DE69729803D1 (de)	2004-08-12
CA2261760C (en)	2005-03-29
AP9901471A0 (en)	1999-03-31
EA004146B1 (ru)	2004-02-26
AU4505997A (en)	1998-04-17
OA11024A (en)	2001-11-06
KR20000048681A (ko)	2000-07-25
ES2224271T3 (es)	2005-03-01
US6331637B1 (en)	2001-12-18
TR199900705T2 (xx)	1999-07-21
CZ85499A3 (cs)	1999-06-16
PT946552E (pt)	2004-10-29
NO991388D0 (no)	1999-03-22
EA200300824A1 (ru)	2003-12-25
IL128145A0 (en)	1999-11-30
EP0946552B1 (de)	2004-07-07
WO1998013366A1 (en)	1998-04-02
JP2002308875A (ja)	2002-10-23
US5962490A (en)	1999-10-05
EP1342721A1 (de)	2003-09-10
PL332323A1 (en)	1999-08-30
US20030208084A1 (en)	2003-11-06
JP2000507607A (ja)	2000-06-20
CN100558724C (zh)	2009-11-11
EP0946552A1 (de)	1999-10-06
CN1530366A (zh)	2004-09-22

Publication	Publication Date	Title
US6632829B2 (en)	2003-10-14	Sulfonamides and derivatives thereof that modulate the activity of endothelin
US6683103B2 (en)	2004-01-27	Sulfonamides for treatment of endothelin-mediated disorders
US6248767B1 (en)	2001-06-19	Formulation of sulfonamides for treatment of endothelin-mediated disorders
CA2395684C (en)	2012-01-03	Sulfonamides and derivatives thereof that modulate the activity of endothelin
EP1533311B1 (de)	2007-04-25	Sulfonamide und deren Derivate als Modulatoren der Endothelin-Aktivität
HK1059079A (en)	2004-06-18	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