NO20023168L - Sulfonamider og derivater derav som modulerer aktiviteten av endotelin - Google Patents

Sulfonamider og derivater derav som modulerer aktiviteten av endotelin Download PDF

Info

Publication number: NO20023168L
Authority: NO; Norway
Prior art keywords: endothelin; stated; compound; alkyl; lower alkyl
Prior art date: 1999-12-31

Application number

NO20023168A

Other languages

English (en)

Norwegian (no)

Other versions

NO20023168D0 (no

Inventor

Chengde Wu

George W Holland

Natalie Blok

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.)

1999-12-31

Filing date

2002-06-28

Publication date

2002-08-30

2002-06-28 Application filed by Texas Biotechnology Corp filed Critical Texas Biotechnology Corp

2002-06-28 Publication of NO20023168D0 publication Critical patent/NO20023168D0/no

2002-08-30 Publication of NO20023168L publication Critical patent/NO20023168L/no

Links

108050009340 Endothelin Proteins 0.000 title claims abstract description 185
102000002045 Endothelin Human genes 0.000 title claims abstract description 158
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 148
230000000694 effects Effects 0.000 title claims abstract description 88
229940124530 sulfonamide Drugs 0.000 title claims abstract description 72
150000003456 sulfonamides Chemical class 0.000 title claims abstract description 45
238000000034 method Methods 0.000 claims abstract description 98
102000005962 receptors Human genes 0.000 claims abstract description 69
108020003175 receptors Proteins 0.000 claims abstract description 69
230000001404 mediated effect Effects 0.000 claims abstract description 49
230000027455 binding Effects 0.000 claims abstract description 40
102000010180 Endothelin receptor Human genes 0.000 claims abstract description 26
108050001739 Endothelin receptor Proteins 0.000 claims abstract description 26
230000002401 inhibitory effect Effects 0.000 claims abstract description 12
150000001875 compounds Chemical class 0.000 claims description 330
125000000217 alkyl group Chemical group 0.000 claims description 252
-1 2-oxazolyl Chemical group 0.000 claims description 165
125000003118 aryl group Chemical group 0.000 claims description 102
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 94
238000002360 preparation method Methods 0.000 claims description 94
229910052739 hydrogen Inorganic materials 0.000 claims description 89
125000003545 alkoxy group Chemical group 0.000 claims description 88
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 87
239000001257 hydrogen Substances 0.000 claims description 84
125000003342 alkenyl group Chemical group 0.000 claims description 71
125000001072 heteroaryl group Chemical group 0.000 claims description 71
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 68
150000003839 salts Chemical class 0.000 claims description 67
125000003710 aryl alkyl group Chemical group 0.000 claims description 65
239000000243 solution Substances 0.000 claims description 65
125000000304 alkynyl group Chemical group 0.000 claims description 62
150000004820 halides Chemical class 0.000 claims description 59
125000000623 heterocyclic group Chemical group 0.000 claims description 51
159000000000 sodium salts Chemical group 0.000 claims description 49
201000010099 disease Diseases 0.000 claims description 48
125000001188 haloalkyl group Chemical group 0.000 claims description 48
229910052799 carbon Inorganic materials 0.000 claims description 47
208000035475 disorder Diseases 0.000 claims description 46
125000000753 cycloalkyl group Chemical group 0.000 claims description 45
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 43
125000002577 pseudohalo group Chemical group 0.000 claims description 41
125000002877 alkyl aryl group Chemical group 0.000 claims description 39
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 39
229910052757 nitrogen Inorganic materials 0.000 claims description 36
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 35
125000000392 cycloalkenyl group Chemical group 0.000 claims description 34
125000004432 carbon atom Chemical group C* 0.000 claims description 33
125000004122 cyclic group Chemical group 0.000 claims description 32
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
239000000843 powder Substances 0.000 claims description 29
125000001424 substituent group Chemical group 0.000 claims description 27
239000002775 capsule Substances 0.000 claims description 26
208000024891 symptom Diseases 0.000 claims description 26
150000001413 amino acids Chemical class 0.000 claims description 25
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 23
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 21
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
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 20
125000003282 alkyl amino group Chemical group 0.000 claims description 20
125000004104 aryloxy group Chemical group 0.000 claims description 20
239000003937 drug carrier Substances 0.000 claims description 20
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 20
239000005022 packaging material Substances 0.000 claims description 19
206010020772 Hypertension Diseases 0.000 claims description 18
206010047139 Vasoconstriction Diseases 0.000 claims description 18
125000005530 alkylenedioxy group Chemical group 0.000 claims description 18
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 18
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 18
230000025033 vasoconstriction Effects 0.000 claims description 18
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 17
239000000825 pharmaceutical preparation Substances 0.000 claims description 17
229910052727 yttrium Inorganic materials 0.000 claims description 17
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 16
239000000460 chlorine Substances 0.000 claims description 16
150000002402 hexoses Chemical class 0.000 claims description 16
208000002815 pulmonary hypertension Diseases 0.000 claims description 15
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 14
125000004414 alkyl thio group Chemical group 0.000 claims description 14
125000004093 cyano group Chemical group *C#N 0.000 claims description 14
239000008121 dextrose Substances 0.000 claims description 14
229930182473 O-glycoside Natural products 0.000 claims description 13
150000008444 O-glycosides Chemical class 0.000 claims description 13
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 13
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 13
208000006673 asthma Diseases 0.000 claims description 13
125000004966 cyanoalkyl group Chemical group 0.000 claims description 13
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 13
125000001769 aryl amino group Chemical group 0.000 claims description 12
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 12
235000000346 sugar Nutrition 0.000 claims description 12
208000024172 Cardiovascular disease Diseases 0.000 claims description 11
125000004429 atom Chemical group 0.000 claims description 11
238000004519 manufacturing process Methods 0.000 claims description 11
208000001647 Renal Insufficiency Diseases 0.000 claims description 10
125000002947 alkylene group Chemical group 0.000 claims description 10
208000027866 inflammatory disease Diseases 0.000 claims description 10
201000006370 kidney failure Diseases 0.000 claims description 10
150000003334 secondary amides Chemical class 0.000 claims description 10
208000010412 Glaucoma Diseases 0.000 claims description 9
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 9
229910052801 chlorine Inorganic materials 0.000 claims description 9
CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 claims description 9
150000003291 riboses Chemical class 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
125000004475 heteroaralkyl group Chemical group 0.000 claims description 8
208000010125 myocardial infarction Diseases 0.000 claims description 8
IAYNHDZSSDUYHY-UHFFFAOYSA-N n-(2-acetyl-4,6-dimethylphenyl)-3-[(3,4-dimethyl-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)C)C=CS1 IAYNHDZSSDUYHY-UHFFFAOYSA-N 0.000 claims description 8
239000012064 sodium phosphate buffer Substances 0.000 claims description 8
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 7
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 7
206010040070 Septic Shock Diseases 0.000 claims description 7
229910052783 alkali metal Inorganic materials 0.000 claims description 7
125000006323 alkenyl amino group Chemical group 0.000 claims description 7
125000003302 alkenyloxy group Chemical group 0.000 claims description 7
125000005136 alkenylsulfinyl group Chemical group 0.000 claims description 7
125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 7
125000005108 alkenylthio group Chemical group 0.000 claims description 7
125000005154 alkyl sulfonyl amino alkyl group Chemical group 0.000 claims description 7
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims description 7
125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 7
125000005019 carboxyalkenyl group Chemical group 0.000 claims description 7
125000004181 carboxyalkyl group Chemical group 0.000 claims description 7
229920001223 polyethylene glycol Polymers 0.000 claims description 7
125000001749 primary amide group Chemical group 0.000 claims description 7
206010002199 Anaphylactic shock Diseases 0.000 claims description 6
102000003951 Erythropoietin Human genes 0.000 claims description 6
108090000394 Erythropoietin Proteins 0.000 claims description 6
208000032456 Hemorrhagic Shock Diseases 0.000 claims description 6
239000002202 Polyethylene glycol Substances 0.000 claims description 6
206010049771 Shock haemorrhagic Diseases 0.000 claims description 6
230000002159 abnormal effect Effects 0.000 claims description 6
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 6
125000004450 alkenylene group Chemical group 0.000 claims description 6
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 6
125000003368 amide group Chemical group 0.000 claims description 6
208000003455 anaphylaxis Diseases 0.000 claims description 6
125000005135 aryl sulfinyl group Chemical group 0.000 claims description 6
125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 6
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
125000005110 aryl thio group Chemical group 0.000 claims description 6
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 6
238000000576 coating method Methods 0.000 claims description 6
125000004663 dialkyl amino group Chemical group 0.000 claims description 6
125000004986 diarylamino group Chemical group 0.000 claims description 6
229940105423 erythropoietin Drugs 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
125000003106 haloaryl group Chemical group 0.000 claims description 6
208000019622 heart disease Diseases 0.000 claims description 6
239000003550 marker Substances 0.000 claims description 6
230000010412 perfusion Effects 0.000 claims description 6
ZQBAKBUEJOMQEX-UHFFFAOYSA-N phenyl salicylate Chemical compound OC1=CC=CC=C1C(=O)OC1=CC=CC=C1 ZQBAKBUEJOMQEX-UHFFFAOYSA-N 0.000 claims description 6
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 6
230000002207 retinal effect Effects 0.000 claims description 6
206010006482 Bronchospasm Diseases 0.000 claims description 5
229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 5
208000010228 Erectile Dysfunction Diseases 0.000 claims description 5
208000033830 Hot Flashes Diseases 0.000 claims description 5
206010060800 Hot flush Diseases 0.000 claims description 5
208000017657 Menopausal disease Diseases 0.000 claims description 5
208000019255 Menstrual disease Diseases 0.000 claims description 5
208000029725 Metabolic bone disease Diseases 0.000 claims description 5
208000001132 Osteoporosis Diseases 0.000 claims description 5
230000003042 antagnostic effect Effects 0.000 claims description 5
125000005129 aryl carbonyl group Chemical group 0.000 claims description 5
230000007885 bronchoconstriction Effects 0.000 claims description 5
150000001720 carbohydrates Chemical class 0.000 claims description 5
235000014633 carbohydrates Nutrition 0.000 claims description 5
230000015271 coagulation Effects 0.000 claims description 5
238000005345 coagulation Methods 0.000 claims description 5
238000001914 filtration Methods 0.000 claims description 5
201000001881 impotence Diseases 0.000 claims description 5
230000009245 menopause Effects 0.000 claims description 5
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
230000002611 ovarian Effects 0.000 claims description 5
201000011461 pre-eclampsia Diseases 0.000 claims description 5
230000035935 pregnancy Effects 0.000 claims description 5
208000023504 respiratory system disease Diseases 0.000 claims description 5
208000025865 Ulcer Diseases 0.000 claims description 4
229940081734 cellulose acetate phthalate Drugs 0.000 claims description 4
239000011248 coating agent Substances 0.000 claims description 4
238000004108 freeze drying Methods 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
YMSLHGRGMAOKEC-UHFFFAOYSA-N n-(2-cyano-3,4,6-trimethylphenyl)-3-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]thiophene-2-carboxamide Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)NC=2C(=C(C)C(C)=CC=2C)C#N)=C1C YMSLHGRGMAOKEC-UHFFFAOYSA-N 0.000 claims description 4
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
231100000397 ulcer Toxicity 0.000 claims description 4
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 3
235000021355 Stearic acid Nutrition 0.000 claims description 3
238000009505 enteric coating Methods 0.000 claims description 3
239000002702 enteric coating Substances 0.000 claims description 3
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
229960000969 phenyl salicylate Drugs 0.000 claims description 3
239000008117 stearic acid Substances 0.000 claims description 3
239000008227 sterile water for injection Substances 0.000 claims description 3
FRZNJFWQVYAVCE-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)phenyl]urea Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C=CC(OCCN3CCOCC3)=CC=2)=CC(C(C)(C)C)=N1 FRZNJFWQVYAVCE-UHFFFAOYSA-N 0.000 claims description 2
206010062016 Immunosuppression Diseases 0.000 claims description 2
230000001506 immunosuppresive effect Effects 0.000 claims description 2
RELNXHXBXUQAQS-UHFFFAOYSA-N n-(2-acetyl-4,6-dimethylphenyl)-2-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]benzamide Chemical group CC(=O)C1=CC(C)=CC(C)=C1NC(=O)C1=CC=CC=C1S(=O)(=O)NC1=C(Cl)C(C)=NO1 RELNXHXBXUQAQS-UHFFFAOYSA-N 0.000 claims description 2
YHOCCQUMOCSPRT-UHFFFAOYSA-N n-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-[(2,4,6-trimethylphenyl)methyl]-1-benzothiophene-3-sulfonamide Chemical compound CC1=NOC(NS(=O)(=O)C=2C3=CC=CC=C3SC=2CC=2C(=CC(C)=CC=2C)C)=C1Cl YHOCCQUMOCSPRT-UHFFFAOYSA-N 0.000 claims description 2
238000011146 sterile filtration Methods 0.000 claims description 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 8
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 3
125000001475 halogen functional group Chemical group 0.000 claims 3
239000001856 Ethyl cellulose Substances 0.000 claims 2
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 2
229920001214 Polysorbate 60 Polymers 0.000 claims 2
125000005083 alkoxyalkoxy group Chemical group 0.000 claims 2
ULBTUVJTXULMLP-UHFFFAOYSA-N butyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCC ULBTUVJTXULMLP-UHFFFAOYSA-N 0.000 claims 2
239000004203 carnauba wax Substances 0.000 claims 2
235000013869 carnauba wax Nutrition 0.000 claims 2
239000004359 castor oil Substances 0.000 claims 2
235000019438 castor oil Nutrition 0.000 claims 2
230000003247 decreasing effect Effects 0.000 claims 2
229920001249 ethyl cellulose Polymers 0.000 claims 2
235000019325 ethyl cellulose Nutrition 0.000 claims 2
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims 2
230000008629 immune suppression Effects 0.000 claims 1
XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 127
238000009472 formulation Methods 0.000 abstract description 75
108090000765 processed proteins & peptides Proteins 0.000 abstract description 15
102000004196 processed proteins & peptides Human genes 0.000 abstract description 9
125000002541 furyl group Chemical group 0.000 abstract description 5
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical class NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 abstract description 4
125000001544 thienyl group Chemical group 0.000 abstract description 4
REPFEAIBUZAYOL-UHFFFAOYSA-N n-(1,2-oxazol-3-yl)thiophene-2-sulfonamide Chemical class C=1C=CSC=1S(=O)(=O)NC=1C=CON=1 REPFEAIBUZAYOL-UHFFFAOYSA-N 0.000 abstract description 2
HLBCDKJOMBEQMZ-UHFFFAOYSA-N n-(1,2-oxazol-3-yl)-1h-pyrrole-2-sulfonamide Chemical class C=1C=CNC=1S(=O)(=O)NC=1C=CON=1 HLBCDKJOMBEQMZ-UHFFFAOYSA-N 0.000 abstract 1
NRNITHABNQZDAT-UHFFFAOYSA-N n-(1,2-oxazol-3-yl)benzenesulfonamide Chemical class C=1C=CC=CC=1S(=O)(=O)NC=1C=CON=1 NRNITHABNQZDAT-UHFFFAOYSA-N 0.000 abstract 1
WDPJORZQTNVWPF-UHFFFAOYSA-N n-(1,2-oxazol-3-yl)furan-2-sulfonamide Chemical class C=1C=COC=1S(=O)(=O)NC=1C=CON=1 WDPJORZQTNVWPF-UHFFFAOYSA-N 0.000 abstract 1
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101000967299 Homo sapiens Endothelin receptor type B Proteins 0.000 description 42
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102100040611 Endothelin receptor type B Human genes 0.000 description 40
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238000001727 in vivo Methods 0.000 description 40
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YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
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NPBAJZVIRSZENG-UHFFFAOYSA-N 1-(2-amino-3,5-dimethylphenyl)ethanone Chemical compound CC(=O)C1=CC(C)=CC(C)=C1N NPBAJZVIRSZENG-UHFFFAOYSA-N 0.000 description 22
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
239000000556 agonist Substances 0.000 description 20
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239000002552 dosage form Substances 0.000 description 19
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
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239000000872 buffer Substances 0.000 description 18
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- C07D261/16—Benzene-sulfonamido isoxazoles
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- C07—ORGANIC CHEMISTRY
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- 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
- 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
- C07D417/14—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 three or more hetero rings

Landscapes

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Gynecology & Obstetrics (AREA)
Orthopedic Medicine & Surgery (AREA)
Diabetes (AREA)
Hematology (AREA)
Vascular Medicine (AREA)
Pregnancy & Childbirth (AREA)
Pain & Pain Management (AREA)
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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NO20023168A 1999-12-31 2002-06-28 Sulfonamider og derivater derav som modulerer aktiviteten av endotelin NO20023168L (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US17410499P	1999-12-31	1999-12-31
PCT/US2000/035599 WO2001049685A2 (en)	1999-12-31	2000-12-29	Sulfonamides and derivatives thereof that modulate the activity of endothelin

Publications (2)

Publication Number	Publication Date
NO20023168D0 NO20023168D0 (no)	2002-06-28
NO20023168L true NO20023168L (no)	2002-08-30

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NO20023168A NO20023168L (no)	1999-12-31	2002-06-28	Sulfonamider og derivater derav som modulerer aktiviteten av endotelin

Country Status (24)

Country	Link
US (1)	US6686382B2 (cs)
EP (1)	EP1244657B1 (cs)
JP (1)	JP4202649B2 (cs)
KR (1)	KR20020072285A (cs)
CN (1)	CN1414965A (cs)
AT (2)	ATE360628T1 (cs)
AU (1)	AU2464301A (cs)
BR (1)	BR0016821A (cs)
CA (1)	CA2395684C (cs)
CZ (1)	CZ20022293A3 (cs)
DE (2)	DE60017195T2 (cs)
DK (1)	DK1533311T3 (cs)
EA (1)	EA004735B1 (cs)
EE (1)	EE200200363A (cs)
ES (2)	ES2285334T3 (cs)
HU (1)	HUP0203935A3 (cs)
IL (1)	IL150311A0 (cs)
MX (1)	MXPA02006461A (cs)
NO (1)	NO20023168L (cs)
NZ (1)	NZ519717A (cs)
PL (1)	PL197782B1 (cs)
PT (1)	PT1533311E (cs)
SK (1)	SK9532002A3 (cs)
WO (1)	WO2001049685A2 (cs)

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2000
- 2000-12-29 DE DE60017195T patent/DE60017195T2/de not_active Expired - Lifetime
- 2000-12-29 PL PL355951A patent/PL197782B1/pl not_active IP Right Cessation
- 2000-12-29 NZ NZ519717A patent/NZ519717A/xx unknown
- 2000-12-29 US US09/751,825 patent/US6686382B2/en not_active Expired - Fee Related
- 2000-12-29 DK DK04025616T patent/DK1533311T3/da active
- 2000-12-29 ES ES04025616T patent/ES2285334T3/es not_active Expired - Lifetime
- 2000-12-29 JP JP2001550225A patent/JP4202649B2/ja not_active Expired - Lifetime
- 2000-12-29 SK SK953-2002A patent/SK9532002A3/sk unknown
- 2000-12-29 AU AU24643/01A patent/AU2464301A/en not_active Abandoned
- 2000-12-29 HU HU0203935A patent/HUP0203935A3/hu unknown
- 2000-12-29 AT AT04025616T patent/ATE360628T1/de active
- 2000-12-29 CA CA2395684A patent/CA2395684C/en not_active Expired - Lifetime
- 2000-12-29 BR BR0016821-1A patent/BR0016821A/pt active Search and Examination
- 2000-12-29 DE DE60034605T patent/DE60034605T2/de not_active Expired - Lifetime
- 2000-12-29 KR KR1020027008513A patent/KR20020072285A/ko not_active Application Discontinuation
- 2000-12-29 EE EEP200200363A patent/EE200200363A/xx unknown
- 2000-12-29 WO PCT/US2000/035599 patent/WO2001049685A2/en active IP Right Grant
- 2000-12-29 EP EP00988434A patent/EP1244657B1/en not_active Expired - Lifetime
- 2000-12-29 AT AT00988434T patent/ATE286051T1/de not_active IP Right Cessation
- 2000-12-29 IL IL15031100A patent/IL150311A0/xx unknown
- 2000-12-29 ES ES00988434T patent/ES2236028T3/es not_active Expired - Lifetime
- 2000-12-29 CN CN00818061A patent/CN1414965A/zh active Pending
- 2000-12-29 EA EA200200713A patent/EA004735B1/ru not_active IP Right Cessation
- 2000-12-29 CZ CZ20022293A patent/CZ20022293A3/cs unknown
- 2000-12-29 PT PT04025616T patent/PT1533311E/pt unknown
- 2000-12-29 MX MXPA02006461A patent/MXPA02006461A/es active IP Right Grant
2002
- 2002-06-28 NO NO20023168A patent/NO20023168L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
NZ519717A (en)	2003-06-30
MXPA02006461A (es)	2003-09-05
PL197782B1 (pl)	2008-04-30
HUP0203935A3 (en)	2006-02-28
BR0016821A (pt)	2002-12-10
DE60017195D1 (de)	2005-02-03
EA004735B1 (ru)	2004-08-26
DK1533311T3 (da)	2007-09-17
DE60017195T2 (de)	2005-12-22
US6686382B2 (en)	2004-02-03
JP4202649B2 (ja)	2008-12-24
EA200200713A1 (ru)	2002-12-26
JP2003519230A (ja)	2003-06-17
EE200200363A (et)	2003-08-15
CA2395684A1 (en)	2001-07-12
DE60034605T2 (de)	2007-09-06
CA2395684C (en)	2012-01-03
ATE360628T1 (de)	2007-05-15
WO2001049685A3 (en)	2002-02-14
IL150311A0 (en)	2002-12-01
PL355951A1 (en)	2004-05-31
CZ20022293A3 (cs)	2003-04-16
WO2001049685A2 (en)	2001-07-12
ATE286051T1 (de)	2005-01-15
KR20020072285A (ko)	2002-09-14
US20010056183A1 (en)	2001-12-27
ES2236028T3 (es)	2005-07-16
EP1244657B1 (en)	2004-12-29
CN1414965A (zh)	2003-04-30
SK9532002A3 (en)	2003-06-03
PT1533311E (pt)	2007-06-14
AU2464301A (en)	2001-07-16
DE60034605D1 (de)	2007-06-06
HUP0203935A2 (hu)	2003-04-28
NO20023168D0 (no)	2002-06-28
EP1244657A2 (en)	2002-10-02
ES2285334T3 (es)	2007-11-16

Publication	Publication Date	Title
EP0946552B1 (en)	2004-07-07	Sulfonamides and derivatives thereof that modulate the activity of endothelin
NO20023168L (no)	2002-08-30	Sulfonamider og derivater derav som modulerer aktiviteten av endotelin
EP0980369B1 (en)	2005-03-30	Sulfonamides for treatment of endothelin-mediated disorders
EP1498418B1 (en)	2008-05-21	Sulfonamides for treatment of endothelin-mediated disorders
EP1533311B1 (en)	2007-04-25	Sulfonamides and derivatives thereof that modulate the activity of endothelin

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2004-11-29	FC2A	Withdrawal, rejection or dismissal of laid open patent application