IE50572B1 - 3-hydroxymethyldibenzo(b,f)thiepins and dibenzo(b,f)thiepin-3-carboxaldehydes as prostaglandin antagonists,process for their preparation and pharmaceutical compositions - Google Patents
3-hydroxymethyldibenzo(b,f)thiepins and dibenzo(b,f)thiepin-3-carboxaldehydes as prostaglandin antagonists,process for their preparation and pharmaceutical compositionsInfo
- Publication number
- IE50572B1 IE50572B1 IE245580A IE245580A IE50572B1 IE 50572 B1 IE50572 B1 IE 50572B1 IE 245580 A IE245580 A IE 245580A IE 245580 A IE245580 A IE 245580A IE 50572 B1 IE50572 B1 IE 50572B1
- Authority
- IE
- Ireland
- Prior art keywords
- thiepin
- carboxaldehyde
- dioxide
- dibenzo
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 75
- 230000008569 process Effects 0.000 title claims description 42
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 title claims description 23
- 239000002089 prostaglandin antagonist Substances 0.000 title description 6
- 238000002360 preparation method Methods 0.000 title description 4
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 72
- -1 iodo, amino Chemical group 0.000 claims abstract description 27
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 5
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims abstract description 4
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims abstract description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 4
- 125000003396 thiol group Chemical class [H]S* 0.000 claims abstract 2
- 239000002253 acid Substances 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 238000006722 reduction reaction Methods 0.000 claims description 18
- 230000009467 reduction Effects 0.000 claims description 16
- 150000003180 prostaglandins Chemical class 0.000 claims description 11
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 10
- LKXZQGNECLTKHZ-UHFFFAOYSA-N benzo[b][1]benzothiepin-2-ylmethanol Chemical compound C1=CC2=CC=CC=C2SC2=CC(CO)=CC=C21 LKXZQGNECLTKHZ-UHFFFAOYSA-N 0.000 claims description 8
- 229940094443 oxytocics prostaglandins Drugs 0.000 claims description 8
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 claims description 8
- QYILYESZVGJJBO-UHFFFAOYSA-N (11-oxobenzo[b][1]benzothiepin-2-yl)methanol Chemical compound C1=CC2=CC=CC=C2S(=O)C2=CC(CO)=CC=C21 QYILYESZVGJJBO-UHFFFAOYSA-N 0.000 claims description 7
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical class [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 6
- 150000001299 aldehydes Chemical class 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 230000001603 reducing effect Effects 0.000 claims description 6
- 125000005907 alkyl ester group Chemical group 0.000 claims description 5
- 229910000085 borane Inorganic materials 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- KFNBVDGSQOKIEB-UHFFFAOYSA-N thiepine-3-carbaldehyde Chemical compound O=CC1=CSC=CC=C1 KFNBVDGSQOKIEB-UHFFFAOYSA-N 0.000 claims description 4
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 claims description 4
- NYFDVYBQHBRTNS-UHFFFAOYSA-N (11,11-dioxobenzo[b][1]benzothiepin-2-yl)methanol Chemical compound C1=CC2=CC=CC=C2S(=O)(=O)C2=CC(CO)=CC=C21 NYFDVYBQHBRTNS-UHFFFAOYSA-N 0.000 claims description 3
- CFHCNNSCZXMXGE-UHFFFAOYSA-N 3-fluorobenzo[b][1]benzothiepine-9-carbaldehyde Chemical compound C1=CC2=CC(F)=CC=C2SC2=CC(C=O)=CC=C21 CFHCNNSCZXMXGE-UHFFFAOYSA-N 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- KWSLGOVYXMQPPX-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenyl]-2h-tetrazole Chemical compound FC(F)(F)C1=CC=CC(C2=NNN=N2)=C1 KWSLGOVYXMQPPX-UHFFFAOYSA-N 0.000 claims description 3
- 239000007868 Raney catalyst Substances 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 230000037020 contractile activity Effects 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
- 229910001379 sodium hypophosphite Inorganic materials 0.000 claims description 3
- JENJNUZVWMQXIQ-UHFFFAOYSA-N (11-oxo-5,6-dihydrobenzo[b][1]benzothiepin-2-yl)methanol Chemical compound C1CC2=CC=CC=C2S(=O)C2=CC(CO)=CC=C21 JENJNUZVWMQXIQ-UHFFFAOYSA-N 0.000 claims description 2
- DPWASNSLYPQZBE-UHFFFAOYSA-N (3-fluoro-11,11-dioxobenzo[b][1]benzothiepin-9-yl)methanol Chemical compound C1=CC2=CC(F)=CC=C2S(=O)(=O)C2=CC(CO)=CC=C21 DPWASNSLYPQZBE-UHFFFAOYSA-N 0.000 claims description 2
- IXDAVLZXWOAACI-UHFFFAOYSA-N 11,11-dioxobenzo[b][1]benzothiepine-2-carbaldehyde Chemical compound C1=CC2=CC=CC=C2S(=O)(=O)C2=CC(C=O)=CC=C21 IXDAVLZXWOAACI-UHFFFAOYSA-N 0.000 claims description 2
- MCPZAVRDERXLIE-UHFFFAOYSA-N 3-chlorobenzo[b][1]benzothiepine-9-carbaldehyde Chemical compound C1=CC2=CC(Cl)=CC=C2SC2=CC(C=O)=CC=C21 MCPZAVRDERXLIE-UHFFFAOYSA-N 0.000 claims description 2
- BXTFBAPZEZQOQV-UHFFFAOYSA-N 3-hydroxy-11,11-dioxobenzo[b][1]benzothiepine-9-carbaldehyde Chemical compound C1=CC2=CC=C(C=O)C=C2S(=O)(=O)C2=CC=C(O)C=C21 BXTFBAPZEZQOQV-UHFFFAOYSA-N 0.000 claims description 2
- TZAMAJLMCUYUIH-UHFFFAOYSA-N 3-hydroxybenzo[b][1]benzothiepine-9-carbaldehyde Chemical compound C1=CC2=CC(O)=CC=C2SC2=CC(C=O)=CC=C21 TZAMAJLMCUYUIH-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052782 aluminium Inorganic materials 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 2
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 1
- KBGWBRSHMXTTHY-UHFFFAOYSA-N 11-oxo-5,6-dihydrobenzo[b][1]benzothiepine-2-carbaldehyde Chemical compound C1CC2=CC=CC=C2S(=O)C2=CC(C=O)=CC=C21 KBGWBRSHMXTTHY-UHFFFAOYSA-N 0.000 claims 1
- XDQQZRCGWCZTNH-UHFFFAOYSA-N 3-chloro-11,11-dioxobenzo[b][1]benzothiepine-9-carbaldehyde Chemical compound C1=CC2=CC=C(C=O)C=C2S(=O)(=O)C2=CC=C(Cl)C=C21 XDQQZRCGWCZTNH-UHFFFAOYSA-N 0.000 claims 1
- LJKLXIMSLKVVAP-UHFFFAOYSA-N 3-chloro-11-oxobenzo[b][1]benzothiepine-9-carbaldehyde Chemical compound C1=CC2=CC=C(C=O)C=C2S(=O)C2=CC=C(Cl)C=C21 LJKLXIMSLKVVAP-UHFFFAOYSA-N 0.000 claims 1
- JSMDNBKJVYHUPY-UHFFFAOYSA-N 3-methoxy-11,11-dioxobenzo[b][1]benzothiepine-9-carbaldehyde Chemical compound C1=CC2=CC=C(C=O)C=C2S(=O)(=O)C2=CC=C(OC)C=C21 JSMDNBKJVYHUPY-UHFFFAOYSA-N 0.000 claims 1
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims 1
- 239000004411 aluminium Substances 0.000 claims 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims 1
- 229910000091 aluminium hydride Inorganic materials 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 5
- 208000006673 asthma Diseases 0.000 abstract description 5
- 150000002148 esters Chemical class 0.000 abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 abstract description 4
- 125000001246 bromo group Chemical group Br* 0.000 abstract description 4
- 201000009961 allergic asthma Diseases 0.000 abstract description 3
- 206010027654 Allergic conditions Diseases 0.000 abstract description 2
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 abstract description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 abstract description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 2
- 125000001309 chloro group Chemical group Cl* 0.000 abstract description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 abstract 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical compound C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 abstract 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 abstract 1
- 125000004414 alkyl thio group Chemical group 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- 125000001589 carboacyl group Chemical group 0.000 abstract 1
- 125000004663 dialkyl amino group Chemical group 0.000 abstract 1
- 125000001153 fluoro group Chemical group F* 0.000 abstract 1
- 239000000047 product Substances 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 15
- 239000000543 intermediate Substances 0.000 description 14
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 229910052500 inorganic mineral Inorganic materials 0.000 description 13
- 239000011707 mineral Substances 0.000 description 13
- 235000010755 mineral Nutrition 0.000 description 13
- 239000002585 base Substances 0.000 description 11
- 230000003647 oxidation Effects 0.000 description 11
- 238000007254 oxidation reaction Methods 0.000 description 11
- ASJSKZXRWOAFGL-UHFFFAOYSA-N 11,11-dioxobenzo[b][1]benzothiepine-2-carboxylic acid Chemical compound C1=CC2=CC=CC=C2S(=O)(=O)C2=CC(C(=O)O)=CC=C21 ASJSKZXRWOAFGL-UHFFFAOYSA-N 0.000 description 10
- YOUSMYQBLMLPTA-UHFFFAOYSA-N 5,6-dihydrobenzo[b][1]benzothiepine-2-carboxylic acid Chemical compound C1CC2=CC=CC=C2SC2=CC(C(=O)O)=CC=C21 YOUSMYQBLMLPTA-UHFFFAOYSA-N 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
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- 150000007513 acids Chemical class 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
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- 150000003457 sulfones Chemical class 0.000 description 7
- 150000003462 sulfoxides Chemical class 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- UEFWAXXDZWNZOC-UHFFFAOYSA-N 5,6-dihydrobenzo[b][1]benzothiepine-2-carbaldehyde Chemical compound C1CC2=CC=CC=C2SC2=CC(C=O)=CC=C21 UEFWAXXDZWNZOC-UHFFFAOYSA-N 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 150000001451 organic peroxides Chemical class 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 5
- 150000003551 thiepines Chemical class 0.000 description 5
- MGKWHVFUUWIIJD-UHFFFAOYSA-N 11,11-dioxobenzo[b][1]benzothiepine-2-carbonitrile Chemical compound C1=CC2=CC=C(C#N)C=C2S(=O)(=O)C2=CC=CC=C21 MGKWHVFUUWIIJD-UHFFFAOYSA-N 0.000 description 4
- WTURFORPERPPRJ-UHFFFAOYSA-N 2-(3-bromophenyl)sulfanylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1SC1=CC=CC(Br)=C1 WTURFORPERPPRJ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
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- 230000009471 action Effects 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
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- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- BISQTCXKVNCDDA-UHFFFAOYSA-N thiepine Chemical compound S1C=CC=CC=C1 BISQTCXKVNCDDA-UHFFFAOYSA-N 0.000 description 4
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 3
- WCRVTUYFKZMSOA-UHFFFAOYSA-N 3-methylsulfanylbenzo[b][1]benzothiepine-9-carbaldehyde Chemical group C1=CC2=CC(SC)=CC=C2SC2=CC(C=O)=CC=C21 WCRVTUYFKZMSOA-UHFFFAOYSA-N 0.000 description 3
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- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- KMAWVRYYKYVCNR-UHFFFAOYSA-N benzo[b][1]benzothiepine Chemical compound C1=CC2=CC=CC=C2SC2=CC=CC=C21 KMAWVRYYKYVCNR-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
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- 238000005406 washing Methods 0.000 description 3
- WLZDRPBYKFIRCN-UHFFFAOYSA-N (3-fluoro-11-oxo-5,6-dihydrobenzo[b][1]benzothiepin-9-yl)methanol Chemical group C1CC2=CC(F)=CC=C2S(=O)C2=CC(CO)=CC=C21 WLZDRPBYKFIRCN-UHFFFAOYSA-N 0.000 description 2
- UHSCRCBZBMARHZ-UHFFFAOYSA-N (3-fluoro-11-oxobenzo[b][1]benzothiepin-9-yl)methanol Chemical group C1=CC2=CC(F)=CC=C2S(=O)C2=CC(CO)=CC=C21 UHSCRCBZBMARHZ-UHFFFAOYSA-N 0.000 description 2
- IQFRYJSSBWPKTR-UHFFFAOYSA-N (3-fluoro-5,6-dihydrobenzo[b][1]benzothiepin-9-yl)methanol Chemical group C1CC2=CC(F)=CC=C2SC2=CC(CO)=CC=C21 IQFRYJSSBWPKTR-UHFFFAOYSA-N 0.000 description 2
- MBRYCZRCIDHCGN-UHFFFAOYSA-N (3-fluorobenzo[b][1]benzothiepin-9-yl)methanol Chemical group C1=CC2=CC(F)=CC=C2SC2=CC(CO)=CC=C21 MBRYCZRCIDHCGN-UHFFFAOYSA-N 0.000 description 2
- OGTJSJQSHISWFE-UHFFFAOYSA-N (3-methoxybenzo[b][1]benzothiepin-9-yl)methanol Chemical compound C1=CC2=CC(OC)=CC=C2SC2=CC(CO)=CC=C21 OGTJSJQSHISWFE-UHFFFAOYSA-N 0.000 description 2
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- VXRXKWNHELOMAR-UHFFFAOYSA-N [9-(hydroxymethyl)-5,6-dihydrobenzo[b][1]benzothiepin-3-yl]methanol Chemical group C1CC2=CC(CO)=CC=C2SC2=CC(CO)=CC=C21 VXRXKWNHELOMAR-UHFFFAOYSA-N 0.000 description 1
- 206010000210 abortion Diseases 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940006138 antiglaucoma drug and miotics prostaglandin analogues Drugs 0.000 description 1
- 229940111131 antiinflammatory and antirheumatic product propionic acid derivative Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- VSYDFZCPPSQOFJ-UHFFFAOYSA-N benzo[b][1]benzothiepine 11,11-dioxide Chemical compound C1=CC2=CC=CC=C2S(=O)(=O)C2=CC=CC=C21 VSYDFZCPPSQOFJ-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229910001919 chlorite Inorganic materials 0.000 description 1
- 229910052619 chlorite group Inorganic materials 0.000 description 1
- QBWCMBCROVPCKQ-UHFFFAOYSA-N chlorous acid Chemical compound OCl=O QBWCMBCROVPCKQ-UHFFFAOYSA-N 0.000 description 1
- 230000002517 constrictor effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- JSYGRUBHOCKMGQ-UHFFFAOYSA-N dichloramine Chemical class ClNCl JSYGRUBHOCKMGQ-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- HTBVGZAVHBZXMS-UHFFFAOYSA-N lithium;tris[(2-methylpropan-2-yl)oxy]alumane Chemical compound [Li].[Al+3].CC(C)(C)[O-].CC(C)(C)[O-].CC(C)(C)[O-] HTBVGZAVHBZXMS-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical group O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 229940071182 stannate Drugs 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- NBOMNTLFRHMDEZ-UHFFFAOYSA-N thiosalicylic acid Chemical class OC(=O)C1=CC=CC=C1S NBOMNTLFRHMDEZ-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D337/00—Heterocyclic compounds containing rings of more than six members having one sulfur atom as the only ring hetero atom
- C07D337/02—Seven-membered rings
- C07D337/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D337/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D337/14—[b,f]-condensed
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9775979A | 1979-11-27 | 1979-11-27 | |
| US06/097,755 US4237160A (en) | 1979-11-27 | 1979-11-27 | 3-Hydroxymethyldibenzo[b,f]thiepins as prostaglandin antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE802455L IE802455L (en) | 1981-05-27 |
| IE50572B1 true IE50572B1 (en) | 1986-05-14 |
Family
ID=26793604
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE245580A IE50572B1 (en) | 1979-11-27 | 1980-11-26 | 3-hydroxymethyldibenzo(b,f)thiepins and dibenzo(b,f)thiepin-3-carboxaldehydes as prostaglandin antagonists,process for their preparation and pharmaceutical compositions |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0029587B1 (OSRAM) |
| DE (1) | DE3068250D1 (OSRAM) |
| DK (1) | DK502780A (OSRAM) |
| ES (1) | ES497132A0 (OSRAM) |
| GR (1) | GR71609B (OSRAM) |
| IE (1) | IE50572B1 (OSRAM) |
| PT (1) | PT72111B (OSRAM) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4535171A (en) * | 1982-11-18 | 1985-08-13 | Merck Frosst Canada, Inc. | Dibenzo[b,f]thiepin-3-carboxaldehydes as prostaglandin antagonists |
| US4622403A (en) * | 1983-10-11 | 1986-11-11 | Merck Frosst Canada, Inc. | 6-H dibenz[b,f]thiepin compounds |
| US4663307A (en) * | 1983-10-26 | 1987-05-05 | Merck Frosst Canada, Inc. | Anti-allergic and anti-thromboembolic 6H-dibenz-[b,e][1,4]-oxathiepin derivatives, compositions, and method of use therefor |
| US5334628A (en) * | 1984-06-09 | 1994-08-02 | Kaken Pharmaceutical Co., Ltd. | Amine derivatives, processes for preparing the same and fungicides containing the same |
| EP0805155B1 (en) * | 1994-09-28 | 2002-03-13 | Nippon Suisan Kaisha, Ltd. | Novel antioxidant tricyclic fused heterocyclic compound |
| WO2002056995A1 (en) * | 2001-01-18 | 2002-07-25 | Nicholas Jackson | Water filter |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4205170A (en) * | 1976-12-03 | 1980-05-27 | Nippon Chemiphar Company, Limited | Propionic acid derivatives |
| PT68303A (en) * | 1977-07-26 | 1978-08-01 | Merck & Co Inc | Process for the preparation of dibenzo/b,f/thiepin |
| IT7850376A0 (it) * | 1977-07-26 | 1978-07-19 | Merck & Co Inc | Composizioni di dibenzo(b.f)tiepina e procedimento per la loro preparazione |
-
1980
- 1980-11-20 DE DE8080107205T patent/DE3068250D1/de not_active Expired
- 1980-11-20 EP EP19800107205 patent/EP0029587B1/en not_active Expired
- 1980-11-25 ES ES497132A patent/ES497132A0/es active Granted
- 1980-11-26 PT PT7211180A patent/PT72111B/pt unknown
- 1980-11-26 IE IE245580A patent/IE50572B1/en unknown
- 1980-11-26 GR GR63467A patent/GR71609B/el unknown
- 1980-11-26 DK DK502780A patent/DK502780A/da not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| PT72111B (en) | 1982-06-25 |
| EP0029587A1 (en) | 1981-06-03 |
| PT72111A (en) | 1980-12-01 |
| DK502780A (da) | 1981-05-28 |
| ES8300742A1 (es) | 1982-11-16 |
| DE3068250D1 (en) | 1984-07-19 |
| IE802455L (en) | 1981-05-27 |
| ES497132A0 (es) | 1982-11-16 |
| EP0029587B1 (en) | 1984-06-13 |
| GR71609B (OSRAM) | 1983-06-17 |
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