IL130660A - History of benzothiophenecarboxamide and PGD2 antibodies containing them - Google Patents
History of benzothiophenecarboxamide and PGD2 antibodies containing themInfo
- Publication number
- IL130660A IL130660A IL13066097A IL13066097A IL130660A IL 130660 A IL130660 A IL 130660A IL 13066097 A IL13066097 A IL 13066097A IL 13066097 A IL13066097 A IL 13066097A IL 130660 A IL130660 A IL 130660A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- hydrate
- acceptable salt
- pharmaceutically acceptable
- configuration
- Prior art date
Links
- 239000005557 antagonist Substances 0.000 title claims description 19
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical class C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 110
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 150000002367 halogens Chemical group 0.000 claims abstract description 7
- 150000002431 hydrogen Chemical group 0.000 claims abstract 5
- BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 claims description 22
- BHMBVRSPMRCCGG-UHFFFAOYSA-N prostaglandine D2 Natural products CCCCCC(O)C=CC1C(CC=CCCCC(O)=O)C(O)CC1=O BHMBVRSPMRCCGG-UHFFFAOYSA-N 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 17
- 229940079593 drug Drugs 0.000 claims description 16
- 206010028748 Nasal obstruction Diseases 0.000 claims description 11
- 210000003979 eosinophil Anatomy 0.000 claims description 10
- 230000008595 infiltration Effects 0.000 claims description 9
- 238000001764 infiltration Methods 0.000 claims description 9
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 210000004969 inflammatory cell Anatomy 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 claims 2
- 101000988802 Homo sapiens Hematopoietic prostaglandin D synthase Proteins 0.000 claims 2
- 101150020741 Hpgds gene Proteins 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 26
- -1 bicyclic amide Chemical class 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- 238000000034 method Methods 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- ZAZIPEFQVRYIGU-UHFFFAOYSA-N 5-hydroxy-1-benzothiophene-3-carboxylic acid Chemical compound C1=C(O)C=C2C(C(=O)O)=CSC2=C1 ZAZIPEFQVRYIGU-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 102000009389 Prostaglandin D receptors Human genes 0.000 description 10
- 108050000258 Prostaglandin D receptors Proteins 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- 108010058846 Ovalbumin Proteins 0.000 description 9
- 239000000427 antigen Substances 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 238000009739 binding Methods 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 229940092253 ovalbumin Drugs 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 8
- 210000003928 nasal cavity Anatomy 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 238000001816 cooling Methods 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000000921 elemental analysis Methods 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 210000003630 histaminocyte Anatomy 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 210000004623 platelet-rich plasma Anatomy 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 229940086542 triethylamine Drugs 0.000 description 5
- 241000700199 Cavia porcellus Species 0.000 description 4
- 241000282414 Homo sapiens Species 0.000 description 4
- 206010039085 Rhinitis allergic Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 201000010105 allergic rhinitis Diseases 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 230000009284 tracheal contraction Effects 0.000 description 4
- SREMGAABESHPOH-UHFFFAOYSA-N (3-carbonochloridoyl-1-benzothiophen-5-yl) acetate Chemical compound CC(=O)OC1=CC=C2SC=C(C(Cl)=O)C2=C1 SREMGAABESHPOH-UHFFFAOYSA-N 0.000 description 3
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 3
- BDJKRWGHGBKNEZ-UHFFFAOYSA-N 5-(benzenesulfonyloxy)-1-benzothiophene-3-carboxylic acid Chemical compound C1=C2C(C(=O)O)=CSC2=CC=C1OS(=O)(=O)C1=CC=CC=C1 BDJKRWGHGBKNEZ-UHFFFAOYSA-N 0.000 description 3
- PKNZOCWPMMEQCH-UHFFFAOYSA-N 5-acetyloxy-1-benzothiophene-3-carboxylic acid Chemical compound CC(=O)OC1=CC=C2SC=C(C(O)=O)C2=C1 PKNZOCWPMMEQCH-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 3
- 206010012438 Dermatitis atopic Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 206010063837 Reperfusion injury Diseases 0.000 description 3
- 206010070834 Sensitisation Diseases 0.000 description 3
- 201000008736 Systemic mastocytosis Diseases 0.000 description 3
- 208000024780 Urticaria Diseases 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 208000002205 allergic conjunctivitis Diseases 0.000 description 3
- 208000024998 atopic conjunctivitis Diseases 0.000 description 3
- 201000008937 atopic dermatitis Diseases 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 230000020411 cell activation Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000008313 sensitization Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- QCOGKXLOEWLIDC-UHFFFAOYSA-N N-methylbutylamine Chemical compound CCCCNC QCOGKXLOEWLIDC-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 150000001559 benzoic acids Chemical class 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
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- 230000002685 pulmonary effect Effects 0.000 description 2
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
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- 210000003437 trachea Anatomy 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- WCLJJXZYFZQDSV-UHFFFAOYSA-N (3-carbonochloridoyl-1-benzothiophen-5-yl) benzenesulfonate Chemical compound C1=C2C(C(=O)Cl)=CSC2=CC=C1OS(=O)(=O)C1=CC=CC=C1 WCLJJXZYFZQDSV-UHFFFAOYSA-N 0.000 description 1
- ZXBHFWFKSIYJEK-MFJOXFORSA-N (z)-7-[(1s,3s,4r,5r)-4-[(5-hydroxy-1-benzothiophene-3-carbonyl)amino]-6,6-dimethyl-3-bicyclo[3.1.1]heptanyl]hept-5-enoic acid Chemical compound C1=C(O)C=C2C(C(=O)N[C@H]3[C@@]4(C[C@](C[C@@H]3C\C=C/CCCC(O)=O)(C4(C)C)[H])[H])=CSC2=C1 ZXBHFWFKSIYJEK-MFJOXFORSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MNCMBBIFTVWHIP-UHFFFAOYSA-N 1-anthracen-9-yl-2,2,2-trifluoroethanone Chemical group C1=CC=C2C(C(=O)C(F)(F)F)=C(C=CC=C3)C3=CC2=C1 MNCMBBIFTVWHIP-UHFFFAOYSA-N 0.000 description 1
- DRBLTQNCQJXSNU-UHFFFAOYSA-N 1-benzothiophene-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CSC2=C1 DRBLTQNCQJXSNU-UHFFFAOYSA-N 0.000 description 1
- FOTIRCKWBGLFNQ-UHFFFAOYSA-N 1-methyl-5-[(1-methyltetrazol-5-yl)disulfanyl]tetrazole Chemical compound CN1N=NN=C1SSC1=NN=NN1C FOTIRCKWBGLFNQ-UHFFFAOYSA-N 0.000 description 1
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- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- QTWBEVAYYDZLQL-UHFFFAOYSA-N thiophene-3-carbonyl chloride Chemical compound ClC(=O)C=1C=CSC=1 QTWBEVAYYDZLQL-UHFFFAOYSA-N 0.000 description 1
- ODHXBMXNKOYIBV-UHFFFAOYSA-N triphenylamine Chemical compound C1=CC=CC=C1N(C=1C=CC=CC=1)C1=CC=CC=C1 ODHXBMXNKOYIBV-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL14586497A IL145864A (en) | 1996-12-13 | 1997-12-10 | Benzothiophenecarboxyamide derivatives |
| IL14586397A IL145863A (en) | 1996-12-13 | 1997-12-10 | Benzothiophenecarboxamide derivatives |
| IL14586597A IL145865A (en) | 1996-12-13 | 1997-12-10 | Benzothiophene derivatives |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33349596 | 1996-12-13 | ||
| JP25400197 | 1997-09-19 | ||
| PCT/JP1997/004527 WO1998025919A1 (en) | 1996-12-13 | 1997-12-10 | Benzothiophenecarboxamide derivatives and pgd2 antagonists comprising them |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL130660A0 IL130660A0 (en) | 2000-06-01 |
| IL130660A true IL130660A (en) | 2002-03-10 |
Family
ID=26541496
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL13066097A IL130660A (en) | 1996-12-13 | 1997-12-10 | History of benzothiophenecarboxamide and PGD2 antibodies containing them |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US6083974A (cs) |
| EP (1) | EP0944614B1 (cs) |
| JP (1) | JP3215441B2 (cs) |
| KR (1) | KR100433568B1 (cs) |
| CN (2) | CN1105112C (cs) |
| AR (1) | AR008939A1 (cs) |
| AT (1) | ATE223911T1 (cs) |
| AU (1) | AU718958B2 (cs) |
| BR (1) | BR9714016A (cs) |
| CA (1) | CA2274591C (cs) |
| CZ (1) | CZ297324B6 (cs) |
| DE (1) | DE69715448T2 (cs) |
| DK (1) | DK0944614T3 (cs) |
| ES (1) | ES2181039T3 (cs) |
| HU (1) | HU226458B1 (cs) |
| ID (1) | ID22753A (cs) |
| IL (1) | IL130660A (cs) |
| NO (1) | NO992838L (cs) |
| NZ (1) | NZ336143A (cs) |
| PL (1) | PL191760B1 (cs) |
| PT (1) | PT944614E (cs) |
| RU (1) | RU2161617C1 (cs) |
| TR (1) | TR199901280T2 (cs) |
| TW (1) | TW438790B (cs) |
| WO (1) | WO1998025919A1 (cs) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3340428B2 (ja) | 1998-03-31 | 2002-11-05 | 塩野義製薬株式会社 | ベンゾチオフェンカルボン酸アミド誘導体の製造法 |
| BR9909290A (pt) * | 1998-03-31 | 2000-12-05 | Shinogi Co | Processo para preparar derivados de ácido 5-hidroxibenzo [b] tiofeno-3-carboxìlico |
| KR100422920B1 (ko) * | 1998-06-03 | 2004-03-12 | 시오노기세이야쿠가부시키가이샤 | Ｐｇｄ2 길항제를 포함하는 소양증을 위한 치료제 |
| AU5430100A (en) * | 1999-07-02 | 2001-01-22 | Shionogi & Co., Ltd. | Novel process for producing bicyclic amino alcohol |
| AU2001241068A1 (en) | 2000-03-09 | 2001-09-17 | Ono Pharmaceutical Co., Ltd. | Indole derivatives, process for preparation of the same and use thereof |
| US20030055077A1 (en) * | 2000-04-12 | 2003-03-20 | Jones Thomas R. | Method and compositions for the treatment of allergic conditions using pgd2 receptor antagonists |
| US6410583B1 (en) * | 2000-07-25 | 2002-06-25 | Merck Frosst Canada & Co. | Cyclopentanoindoles, compositions containing such compounds and methods of treatment |
| US7217725B2 (en) | 2000-09-14 | 2007-05-15 | Allergan, Inc. | Prostaglandin D2 antagonist |
| US7273883B2 (en) | 2000-09-14 | 2007-09-25 | Allergan, Inc. | Prostaglandin EP4 antagonist |
| JP4017978B2 (ja) * | 2000-10-17 | 2007-12-05 | 塩野義製薬株式会社 | Ｐｇｄ２アンタゴニストの製造方法 |
| EP1338594A4 (en) * | 2000-11-01 | 2004-06-16 | Shionogi & Co | PGD2 RECEPTOR ANTAGONIST PHARMACEUTICAL COMPOSITIONS |
| AR038136A1 (es) | 2002-01-24 | 2004-12-29 | Merck Frosst Canada Inc | Cicloalcanindoles con sustitucion con fluor composiciones que contienen estos compuestos y metodos de tratamiento |
| AU2003221325A1 (en) * | 2002-03-19 | 2003-09-29 | Ono Pharmaceutical Co., Ltd. | Carboxyoic acid compounds and drugs containing the compounds as the acive ingredient |
| EP1598065A2 (en) * | 2002-07-12 | 2005-11-23 | Japan Science and Technology Agency | Drugs for improving prognosis of brain injury |
| WO2004030674A1 (ja) * | 2002-09-30 | 2004-04-15 | Shionogi & Co., Ltd. | プロスタグランジンｄ２、プロスタグランジンｄ２アゴニストおよびプロスタグランジンｄ２アンタゴニストの新規用途 |
| AU2003275868B2 (en) | 2002-10-30 | 2009-07-09 | Merck Frosst Canada Ltd | Pyridopyrrolizine and pyridoindolizine derivatives |
| ATE394399T1 (de) | 2004-03-11 | 2008-05-15 | Actelion Pharmaceuticals Ltd | Tetrahydropyridoindolderivate |
| JPWO2006068162A1 (ja) * | 2004-12-24 | 2008-06-12 | 塩野義製薬株式会社 | 慢性閉塞性肺疾患の治療剤 |
| TW200716093A (en) * | 2005-04-28 | 2007-05-01 | Shionogi & Co | An antiasthmatic agent containing PGD2 receptor antagonist and leukotriene receptor antagonist |
| TWI410410B (zh) | 2007-08-10 | 2013-10-01 | Ono Pharmaceutical Co | Phenylacetic acid compounds |
| KR20120098908A (ko) | 2009-12-23 | 2012-09-05 | 아이언우드 파마슈티컬스, 인코포레이티드 | Ｃｒｔｈ２ 조절제 |
| US20130178475A1 (en) | 2010-03-17 | 2013-07-11 | Ironwood Pharmaceuticals, Inc. | sGC STIMULATORS |
| MX2012015252A (es) | 2010-06-30 | 2013-05-30 | Ironwood Pharmaceuticals Inc | Estimuladores de sgc. |
| US20130259830A1 (en) | 2010-07-12 | 2013-10-03 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
| WO2012009137A1 (en) | 2010-07-12 | 2012-01-19 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
| WO2012064559A1 (en) | 2010-11-09 | 2012-05-18 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
| US9139564B2 (en) | 2011-12-27 | 2015-09-22 | Ironwood Pharmaceuticals, Inc. | 2-benzyl, 3-(pyrimidin-2-yl) substituted pyrazoles useful as sGC stimulators |
| WO2014047111A1 (en) | 2012-09-18 | 2014-03-27 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
| US9487508B2 (en) | 2012-09-19 | 2016-11-08 | Ironwood Pharmaceuticals, Inc. | SGC stimulators |
| US9481689B2 (en) | 2013-03-15 | 2016-11-01 | Ironwood Pharmaceuticals, Inc. | sGC stimulators |
| CN106304835A (zh) | 2013-12-11 | 2017-01-04 | 铁木医药有限公司 | sGC刺激剂 |
| EP3094327A1 (en) | 2014-01-13 | 2016-11-23 | Ironwood Pharmaceuticals, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF NEUROMUSCULAR DISORDERS |
| EP3194382B1 (en) | 2014-09-17 | 2021-09-08 | Cyclerion Therapeutics, Inc. | Pyrazole derivatives as sgc stimulators |
| CA2961489A1 (en) | 2014-09-17 | 2016-03-24 | Glen Robert RENNIE | Sgc stimulators |
| WO2016044445A2 (en) | 2014-09-17 | 2016-03-24 | Ironwood Pharmaceuticals, Inc. | sGC STIMULATORS |
| WO2016128565A1 (en) | 2015-02-13 | 2016-08-18 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Ptgdr-1 and/or ptgdr-2 antagonists for preventing and/or treating systemic lupus erythematosus |
| US10889577B2 (en) | 2016-07-07 | 2021-01-12 | Cyclerion Therapeutics, Inc. | Solid forms of an sGC stimulator |
| CN114736240A (zh) | 2016-07-07 | 2022-07-12 | 赛克里翁治疗有限公司 | sGC刺激剂的磷前药 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8406906D0 (en) * | 1984-03-16 | 1984-04-18 | Akzo Nv | Benzo-thiazole and benzothiophene derivatives |
| US4560343A (en) * | 1984-06-11 | 1985-12-24 | Honeywell Inc. | Functional check for a hot surface ignitor element |
| JPS6149A (ja) * | 1984-06-12 | 1986-01-06 | Ono Pharmaceut Co Ltd | 新規な１３―アザ―１４―オキソ―ＴｘＡ２類似化合物およびそれらを有効成分として含有するトロンボキサン起因疾患治療剤 |
| NZ218115A (en) * | 1985-11-18 | 1990-02-26 | Shionogi & Co | Bicyclic sulphonamides and pharmaceutical compositions |
| CA1294974C (en) * | 1987-05-08 | 1992-01-28 | Sanji Hagishita | Bicyclic sulfonamide derivatives and process therefor |
| US5356926A (en) * | 1992-02-24 | 1994-10-18 | Warner-Lambert Company | 3-alkyloxy-, aryloxy-, or arylalkyloxy-benzo [β]thiophene-2-carboxamides as inhibitors of cell adhesion |
| CA2113787A1 (en) * | 1993-01-29 | 1994-07-30 | Nobuyuki Hamanaka | Carbocyclic sulfonamides |
| DE4317076A1 (de) * | 1993-05-21 | 1994-11-24 | Bayer Ag | Benzthiophencarbonsäureamid-S-oxide |
| US5863936A (en) * | 1995-04-18 | 1999-01-26 | Geron Corporation | Telomerase inhibitors |
| CA2225250C (en) * | 1995-06-21 | 2005-03-22 | Shionogi & Co., Ltd. | Bicyclic amino derivatives and pgd2 antagonist containing the same |
| WO1998015545A1 (en) * | 1996-10-08 | 1998-04-16 | Eli Lilly And Company | New serotonin 5-ht1f agonists |
-
1997
- 1997-12-10 AU AU54097/98A patent/AU718958B2/en not_active Ceased
- 1997-12-10 AT AT97947866T patent/ATE223911T1/de not_active IP Right Cessation
- 1997-12-10 DE DE69715448T patent/DE69715448T2/de not_active Expired - Lifetime
- 1997-12-10 HU HU0002869A patent/HU226458B1/hu not_active IP Right Cessation
- 1997-12-10 IL IL13066097A patent/IL130660A/en not_active IP Right Cessation
- 1997-12-10 WO PCT/JP1997/004527 patent/WO1998025919A1/en active IP Right Grant
- 1997-12-10 CA CA002274591A patent/CA2274591C/en not_active Expired - Fee Related
- 1997-12-10 PT PT97947866T patent/PT944614E/pt unknown
- 1997-12-10 CN CN97180628A patent/CN1105112C/zh not_active Expired - Fee Related
- 1997-12-10 PL PL334072A patent/PL191760B1/pl not_active IP Right Cessation
- 1997-12-10 US US09/308,176 patent/US6083974A/en not_active Expired - Lifetime
- 1997-12-10 RU RU99115766/04A patent/RU2161617C1/ru not_active IP Right Cessation
- 1997-12-10 ES ES97947866T patent/ES2181039T3/es not_active Expired - Lifetime
- 1997-12-10 NZ NZ336143A patent/NZ336143A/en unknown
- 1997-12-10 ID IDW990472A patent/ID22753A/id unknown
- 1997-12-10 TR TR1999/01280T patent/TR199901280T2/xx unknown
- 1997-12-10 DK DK97947866T patent/DK0944614T3/da active
- 1997-12-10 EP EP97947866A patent/EP0944614B1/en not_active Expired - Lifetime
- 1997-12-10 BR BR9714016-3A patent/BR9714016A/pt active Search and Examination
- 1997-12-10 KR KR10-1999-7005154A patent/KR100433568B1/ko not_active Expired - Fee Related
- 1997-12-10 CZ CZ0206599A patent/CZ297324B6/cs not_active IP Right Cessation
- 1997-12-10 JP JP52649298A patent/JP3215441B2/ja not_active Expired - Fee Related
- 1997-12-11 TW TW086118667A patent/TW438790B/zh not_active IP Right Cessation
- 1997-12-12 AR ARP970105862A patent/AR008939A1/es active IP Right Grant
-
1999
- 1999-06-10 NO NO992838A patent/NO992838L/no unknown
-
2002
- 2002-06-11 CN CNB021227608A patent/CN1185226C/zh not_active Expired - Fee Related
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| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
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| MM9K | Patent not in force due to non-payment of renewal fees |