IL116405A - Hexahydrobenz [E] Transformed Tricyclic Isoindole, Alpha 1 - an antagonistic adrenergic composition containing it and its uses - Google Patents
Hexahydrobenz [E] Transformed Tricyclic Isoindole, Alpha 1 - an antagonistic adrenergic composition containing it and its usesInfo
- Publication number
- IL116405A IL116405A IL11640595A IL11640595A IL116405A IL 116405 A IL116405 A IL 116405A IL 11640595 A IL11640595 A IL 11640595A IL 11640595 A IL11640595 A IL 11640595A IL 116405 A IL116405 A IL 116405A
- Authority
- IL
- Israel
- Prior art keywords
- methoxy
- dione
- hexahydro
- benz
- ethyl
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title abstract description 68
- 230000003042 antagnostic effect Effects 0.000 title abstract description 5
- 230000001800 adrenalinergic effect Effects 0.000 title description 7
- AFUKREKRACCNKC-UHFFFAOYSA-N 2,3,3a,4,5,9b-hexahydro-1h-benzo[e]isoindole Chemical class C1=CC=C2C3CNCC3CCC2=C1 AFUKREKRACCNKC-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 430
- 150000003839 salts Chemical class 0.000 claims abstract description 60
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 200
- -1 methoxyethyl Chemical group 0.000 claims description 96
- 125000000217 alkyl group Chemical group 0.000 claims description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 42
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 31
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 25
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 24
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000004252 isoindol-1-yl group Chemical group [H]N1C([H])=C2C([H])=C([H])C([H])=C([H])C2=C1* 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 16
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- QKDLQFSLLCQTOH-UHFFFAOYSA-N Trichodonin Natural products C1C(O)C2C3(COC(=O)C)C(C=O)C(C)(C)CCC3OC(=O)C22C(=O)C(=C)C1C2 QKDLQFSLLCQTOH-UHFFFAOYSA-N 0.000 claims description 3
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 125000005518 carboxamido group Chemical group 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 claims 2
- QAFVXBQPQCSSLI-UHFFFAOYSA-N 1h-thieno[3,2-d]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)NC2=C1SC=C2 QAFVXBQPQCSSLI-UHFFFAOYSA-N 0.000 claims 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- PZMKGWRBZNOIPQ-UHFFFAOYSA-N 1h-thieno[3,2-d]pyrimidin-4-one Chemical compound OC1=NC=NC2=C1SC=C2 PZMKGWRBZNOIPQ-UHFFFAOYSA-N 0.000 claims 1
- 101100179596 Caenorhabditis elegans ins-3 gene Proteins 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 176
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 30
- 239000000951 adrenergic alpha-1 receptor antagonist Substances 0.000 abstract 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 377
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 274
- 238000005481 NMR spectroscopy Methods 0.000 description 207
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 201
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 192
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 190
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 171
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 159
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 155
- 239000007787 solid Substances 0.000 description 155
- 239000000047 product Substances 0.000 description 129
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 126
- 229910001868 water Inorganic materials 0.000 description 122
- 239000000243 solution Substances 0.000 description 114
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 112
- 235000019439 ethyl acetate Nutrition 0.000 description 110
- 239000012948 isocyanate Substances 0.000 description 72
- 238000006243 chemical reaction Methods 0.000 description 70
- 150000002513 isocyanates Chemical class 0.000 description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 69
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 68
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 63
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 53
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 51
- 238000004458 analytical method Methods 0.000 description 51
- 238000010992 reflux Methods 0.000 description 51
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 50
- 229940093499 ethyl acetate Drugs 0.000 description 47
- 239000000741 silica gel Substances 0.000 description 46
- 229910002027 silica gel Inorganic materials 0.000 description 46
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
- 239000012458 free base Substances 0.000 description 44
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
- 238000004440 column chromatography Methods 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 38
- 239000002904 solvent Substances 0.000 description 37
- 239000012267 brine Substances 0.000 description 35
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 239000010410 layer Substances 0.000 description 32
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical class OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 31
- 235000019441 ethanol Nutrition 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 26
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 26
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 101150041968 CDC13 gene Proteins 0.000 description 22
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- 238000001914 filtration Methods 0.000 description 20
- 108060003345 Adrenergic Receptor Proteins 0.000 description 19
- 102000017910 Adrenergic receptor Human genes 0.000 description 19
- PVBRSNZAOAJRKO-UHFFFAOYSA-N ethyl 2-sulfanylacetate Chemical compound CCOC(=O)CS PVBRSNZAOAJRKO-UHFFFAOYSA-N 0.000 description 19
- 238000003756 stirring Methods 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- 239000004202 carbamide Substances 0.000 description 17
- 239000000284 extract Substances 0.000 description 17
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 16
- 229910000027 potassium carbonate Inorganic materials 0.000 description 16
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- 239000012230 colorless oil Substances 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- 235000019253 formic acid Nutrition 0.000 description 13
- 150000002431 hydrogen Chemical class 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 12
- 239000012043 crude product Substances 0.000 description 12
- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- 210000002307 prostate Anatomy 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 235000015320 potassium carbonate Nutrition 0.000 description 10
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 229910000029 sodium carbonate Inorganic materials 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 239000005557 antagonist Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 150000003840 hydrochlorides Chemical class 0.000 description 9
- 229960001289 prazosin Drugs 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- NIPZZXUFJPQHNH-UHFFFAOYSA-M pyrazine-2-carboxylate Chemical compound [O-]C(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-M 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
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- 239000002502 liposome Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 7
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 6
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 6
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 230000008485 antagonism Effects 0.000 description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 6
- 229960001389 doxazosin Drugs 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 6
- 229960001693 terazosin Drugs 0.000 description 6
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- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
- 241000282465 Canis Species 0.000 description 5
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- HQVFCQRVQFYGRJ-UHFFFAOYSA-N formic acid;hydrate Chemical compound O.OC=O HQVFCQRVQFYGRJ-UHFFFAOYSA-N 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 5
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- 238000011699 spontaneously hypertensive rat Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
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- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 5
- 238000001665 trituration Methods 0.000 description 5
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
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- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
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- RNMMKNZSITXHEZ-UHFFFAOYSA-N ethyl 3-amino-1h-indole-2-carboxylate;hydrochloride Chemical compound Cl.C1=CC=C2C(N)=C(C(=O)OCC)NC2=C1 RNMMKNZSITXHEZ-UHFFFAOYSA-N 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
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- 239000003380 propellant Substances 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- UFBAKNJSYGCXMB-UHFFFAOYSA-N pyrazine thiophene Chemical compound S1C=CC=C1.N1=CC=NC=C1.S1C=CC=C1 UFBAKNJSYGCXMB-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 238000013300 spontaneous hypertensive rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229940127230 sympathomimetic drug Drugs 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- YJSKZIATOGOJEB-UHFFFAOYSA-N thieno[2,3-b]pyrazine Chemical compound C1=CN=C2SC=CC2=N1 YJSKZIATOGOJEB-UHFFFAOYSA-N 0.000 description 1
- RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical compound C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 description 1
- AWLILQARPMWUHA-UHFFFAOYSA-M thiopental sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC([S-])=NC1=O AWLILQARPMWUHA-UHFFFAOYSA-M 0.000 description 1
- 229960000340 thiopental sodium Drugs 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 201000002327 urinary tract obstruction Diseases 0.000 description 1
- 210000001177 vas deferen Anatomy 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Urology & Nephrology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37941495A | 1995-01-27 | 1995-01-27 | |
| US08/463,528 US5597823A (en) | 1995-01-27 | 1995-06-05 | Tricyclic substituted hexahydrobenz [e]isoindole alpha-1 adrenergic antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL116405A0 IL116405A0 (en) | 1996-03-31 |
| IL116405A true IL116405A (en) | 2001-09-13 |
Family
ID=27008615
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL11640595A IL116405A (en) | 1995-01-27 | 1995-12-15 | Hexahydrobenz [E] Transformed Tricyclic Isoindole, Alpha 1 - an antagonistic adrenergic composition containing it and its uses |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5597823A (fr) |
| EP (1) | EP0808318B1 (fr) |
| JP (1) | JP2001504797A (fr) |
| KR (1) | KR19980701700A (fr) |
| AT (1) | ATE194141T1 (fr) |
| AU (1) | AU705283B2 (fr) |
| CA (1) | CA2211212A1 (fr) |
| DE (1) | DE69609051T2 (fr) |
| DK (1) | DK0808318T3 (fr) |
| ES (1) | ES2149451T3 (fr) |
| GR (1) | GR3034485T3 (fr) |
| IL (1) | IL116405A (fr) |
| MX (1) | MX9705674A (fr) |
| PT (1) | PT808318E (fr) |
| WO (1) | WO1996022992A1 (fr) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL120302A0 (en) * | 1996-03-27 | 1997-06-10 | Pfizer | Use of alpha1-adrenoreceptor antagonists in the prevention and treatment of benign prostatic hyperplasia |
| US6177430B1 (en) | 1997-03-27 | 2001-01-23 | Pfizer Inc | Use of α1-adrenoreceptor antagonists in the prevention and treatment of benign prostatic hyperplasia |
| AR008395A1 (es) * | 1996-07-09 | 2000-01-19 | Astra Pharma Prod | Compuesto derivado de pirimidina, composicion farmaceutica que lo comprende, procedimiento para prepararlo, y compuesto intermediario util parallevar a cabo dicho procedimiento. |
| US5891882A (en) * | 1996-12-06 | 1999-04-06 | Abbott Laboratories | Benzopyranopyrrole and benzopyranopyridine α-1 adenergic compounds |
| EP1023068A4 (fr) * | 1997-06-18 | 2001-05-16 | Merck & Co Inc | ANTAGONISTES DES ADRENORECEPTEURS ALPHA 1a |
| SG72827A1 (en) * | 1997-06-23 | 2000-05-23 | Hoffmann La Roche | Phenyl-and aminophenyl-alkylsulfonamide and urea derivatives |
| US6410554B1 (en) | 1998-03-23 | 2002-06-25 | Merck & Co., Inc. | Combination therapy for the treatment of benign prostatic hyperplasia |
| WO1999048530A1 (fr) * | 1998-03-23 | 1999-09-30 | Merck & Co., Inc. | Therapie combinee pour le traitement de l'hyperplasie prostatique benigne |
| US6133275A (en) * | 1998-05-06 | 2000-10-17 | Abbott Laboratories | 3-phenylpyrrolidine alpha-1 adrenergic compounds |
| US6232320B1 (en) | 1998-06-04 | 2001-05-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| WO2000010983A1 (fr) * | 1998-08-20 | 2000-03-02 | Abbott Laboratories | Procede de preparation d'isomeres regiospecifiques de pyrazine substituee |
| KR100585240B1 (ko) * | 1998-08-20 | 2006-06-01 | 토야마 케미칼 컴퍼니 리미티드 | 질소함유 복소환 카르복사미드 유도체 또는 그 염 및 이를함유하는 항바이러스제 |
| CZ20012350A3 (cs) * | 1998-12-24 | 2001-09-12 | Aventis Pharmaceuticals Products Inc. | Substituované (aminoiminomethyl nebo aminomethyl) benzoheteroarylové sloučeniny |
| US6867203B2 (en) | 1998-12-29 | 2005-03-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory and immune-suppressive compounds |
| US10022078B2 (en) | 2004-07-13 | 2018-07-17 | Dexcom, Inc. | Analyte sensor |
| JP2005104838A (ja) | 2003-01-09 | 2005-04-21 | Tanabe Seiyaku Co Ltd | 縮合フラン化合物 |
| US7524853B2 (en) * | 2003-06-10 | 2009-04-28 | Solvay Pharmaceuticals B.V. | Compounds and their use in therapy |
| US7465739B2 (en) * | 2003-06-10 | 2008-12-16 | Solvay Pharmaceuticals B.V. | Compounds and their use in therapy |
| US7754709B2 (en) * | 2003-06-10 | 2010-07-13 | Solvay Pharmaceuticals Bv | Tetracyclic thiophenepyrimidinone compounds as inhibitors of 17β hydroxysteroid dehydrogenase compounds |
| US7920906B2 (en) | 2005-03-10 | 2011-04-05 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
| US9247900B2 (en) | 2004-07-13 | 2016-02-02 | Dexcom, Inc. | Analyte sensor |
| US9414777B2 (en) | 2004-07-13 | 2016-08-16 | Dexcom, Inc. | Transcutaneous analyte sensor |
| EP1828197B1 (fr) * | 2004-12-13 | 2009-05-13 | Solvay Pharmaceuticals GmbH | NOUVEAUX DÉRIVÉS SUBSTITUÉS DE THIOPHÈNEPYRIMIDINONE EN TANT QU'INHIBITEURS DE LA 17ß-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE |
| RU2409581C2 (ru) * | 2004-12-13 | 2011-01-20 | Зольвай Фармасьютиклз Гмбх | НОВЫЕ ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ ТИОФЕНПИРИМИДИНОНА В КАЧЕСТВЕ ИНГИБИТОРОВ 17β-ГИДРОКСИСТЕРОИД-ДЕГИДРОГЕНАЗЫ |
| PT1888548E (pt) | 2005-05-26 | 2012-10-30 | Neuron Systems Inc | Derivado de quinolina para o tratamento de doenças da retina |
| ES2567133T3 (es) | 2005-06-23 | 2016-04-20 | Array Biopharma, Inc. | Proceso para preparar compuestos de benzoimidazol |
| CA2627349A1 (fr) * | 2005-11-03 | 2007-05-18 | Ilypsa, Inc. | Composes d'azaindole et leur utilisation en tant qu'inhibiteurs de phospholipases a2 |
| JP5041403B2 (ja) * | 2007-02-02 | 2012-10-03 | 国立大学法人北海道大学 | カフェイン類縁体 |
| JP5885670B2 (ja) | 2009-12-11 | 2016-03-15 | アルデイラ セラピューティクス, インコーポレイテッド | 黄斑変性の処置のための組成物および方法 |
| CN105073714A (zh) | 2012-12-20 | 2015-11-18 | 奥尔德拉医疗公司 | 迫位原醇 |
| JP6514114B2 (ja) | 2013-01-23 | 2019-05-15 | アルデイラ セラピューティクス, インコーポレイテッド | 毒性アルデヒド関連疾患および処置 |
| KR20150120380A (ko) | 2013-01-25 | 2015-10-27 | 알데이라 테라퓨틱스, 아이엔씨. | 황반 변성의 치료에서 신규한 트랩 |
| WO2017035077A1 (fr) | 2015-08-21 | 2017-03-02 | Aldeyra Therapeutics, Inc. | Composés deutérés et leurs utilisations |
| EP3454858A4 (fr) | 2016-05-09 | 2020-01-15 | Aldeyra Therapeutics, Inc. | Polythérapie de troubles et de maladies inflammatoires oculaires |
| AU2018234919A1 (en) | 2017-03-16 | 2019-09-19 | Aldeyra Therapeutics, Inc. | Polymorphic compounds and uses thereof |
| EP3694500A4 (fr) | 2017-10-10 | 2021-06-30 | Aldeyra Therapeutics, Inc. | Traitement de troubles inflammatoires |
| US12006298B2 (en) | 2018-08-06 | 2024-06-11 | Aldeyra Therapeutics, Inc. | Polymorphic compounds and uses thereof |
| EP3962894A4 (fr) | 2019-05-02 | 2023-01-11 | Aldeyra Therapeutics, Inc. | Composés polymorphes et leurs utilisations |
| US12098132B2 (en) | 2019-05-02 | 2024-09-24 | Aldeyra Therapeutics, Inc. | Process for preparation of aldehyde scavenger and intermediates |
| EP4149470A4 (fr) | 2020-05-13 | 2024-04-24 | Aldeyra Therapeutics, Inc. | Formulations pharmaceutiques et leurs utilisations |
| CN112079832A (zh) * | 2020-10-30 | 2020-12-15 | 黑龙江中医药大学 | 一种治疗子宫肌瘤的药物及其制备方法 |
| CN114957090B (zh) * | 2021-12-31 | 2023-09-19 | 淮阴师范学院 | 稠合异吲哚衍生物的制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5049564A (en) * | 1989-11-17 | 1991-09-17 | Abbott Laboratories | 5-HT selective agents |
| GB9123857D0 (en) * | 1991-11-09 | 1992-01-02 | Smithkline Beecham Plc | Novel compounds |
-
1995
- 1995-06-05 US US08/463,528 patent/US5597823A/en not_active Expired - Fee Related
- 1995-12-15 IL IL11640595A patent/IL116405A/en not_active IP Right Cessation
-
1996
- 1996-01-11 MX MX9705674A patent/MX9705674A/es unknown
- 1996-01-11 ES ES96903340T patent/ES2149451T3/es not_active Expired - Lifetime
- 1996-01-11 DE DE69609051T patent/DE69609051T2/de not_active Expired - Fee Related
- 1996-01-11 WO PCT/US1996/000072 patent/WO1996022992A1/fr not_active Ceased
- 1996-01-11 DK DK96903340T patent/DK0808318T3/da active
- 1996-01-11 PT PT96903340T patent/PT808318E/pt unknown
- 1996-01-11 JP JP52286796A patent/JP2001504797A/ja active Pending
- 1996-01-11 AU AU47457/96A patent/AU705283B2/en not_active Ceased
- 1996-01-11 AT AT96903340T patent/ATE194141T1/de not_active IP Right Cessation
- 1996-01-11 CA CA002211212A patent/CA2211212A1/fr not_active Abandoned
- 1996-01-11 KR KR1019970705096A patent/KR19980701700A/ko not_active Ceased
- 1996-01-11 EP EP96903340A patent/EP0808318B1/fr not_active Expired - Lifetime
-
2000
- 2000-09-26 GR GR20000402174T patent/GR3034485T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| MX9705674A (es) | 1997-10-31 |
| PT808318E (pt) | 2000-12-29 |
| GR3034485T3 (en) | 2000-12-29 |
| DE69609051T2 (de) | 2001-03-22 |
| DE69609051D1 (de) | 2000-08-03 |
| JP2001504797A (ja) | 2001-04-10 |
| AU705283B2 (en) | 1999-05-20 |
| WO1996022992A1 (fr) | 1996-08-01 |
| DK0808318T3 (da) | 2000-10-16 |
| ATE194141T1 (de) | 2000-07-15 |
| CA2211212A1 (fr) | 1996-08-01 |
| EP0808318A1 (fr) | 1997-11-26 |
| AU4745796A (en) | 1996-08-14 |
| US5597823A (en) | 1997-01-28 |
| KR19980701700A (ko) | 1998-06-25 |
| ES2149451T3 (es) | 2000-11-01 |
| EP0808318B1 (fr) | 2000-06-28 |
| IL116405A0 (en) | 1996-03-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM9K | Patent not in force due to non-payment of renewal fees |