FI57262C - Foerfarande foer framstaellning av nya terapeutiskt aktiva 3,4,5,6-tetrahydro-(1,3)tiazolo(4,3-a)isokinolinderivat - Google Patents
Foerfarande foer framstaellning av nya terapeutiskt aktiva 3,4,5,6-tetrahydro-(1,3)tiazolo(4,3-a)isokinolinderivat Download PDFInfo
- Publication number
- FI57262C FI57262C FI1644/74A FI164474A FI57262C FI 57262 C FI57262 C FI 57262C FI 1644/74 A FI1644/74 A FI 1644/74A FI 164474 A FI164474 A FI 164474A FI 57262 C FI57262 C FI 57262C
- Authority
- FI
- Finland
- Prior art keywords
- formula
- compound
- group
- tetrahydro
- cyano
- Prior art date
Links
- 230000001225 therapeutic effect Effects 0.000 title description 3
- 230000004913 activation Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 57
- 229910052799 carbon Inorganic materials 0.000 claims description 40
- -1 nitro, phenyl Chemical group 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 150000003839 salts Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 150000002367 halogens Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 8
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 4
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 238000006136 alcoholysis reaction Methods 0.000 claims description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
- 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 claims description 2
- 150000008065 acid anhydrides Chemical class 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 125000005277 alkyl imino group Chemical group 0.000 claims 1
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 claims 1
- 239000013522 chelant Substances 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 67
- 239000000243 solution Substances 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 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
- 239000000047 product Substances 0.000 description 20
- 238000009835 boiling Methods 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 13
- 238000001816 cooling Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000000155 melt Substances 0.000 description 7
- NSSYQQHRGFBARY-UHFFFAOYSA-N 3h-[1,3]thiazolo[4,3-a]isoquinoline Chemical compound C1=CC=C2C3=CSCN3C=CC2=C1 NSSYQQHRGFBARY-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 241000282472 Canis lupus familiaris Species 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000017531 blood circulation Effects 0.000 description 5
- 150000002537 isoquinolines Chemical class 0.000 description 5
- 230000002107 myocardial effect Effects 0.000 description 5
- 125000002560 nitrile group Chemical group 0.000 description 5
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 210000004351 coronary vessel Anatomy 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- JLTCWSBVQSZVLT-CDIPANDDSA-N (2s)-n-[(2s)-6-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxohexan-2-yl]-1-[(4r,7s,10s,13s,16s,19r)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-benzyl-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosan Chemical compound NCCCC[C@@H](C(=O)NCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](N)CSSC1.C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 JLTCWSBVQSZVLT-CDIPANDDSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
- 102000005320 Posterior Pituitary Hormones Human genes 0.000 description 3
- 108010070873 Posterior Pituitary Hormones Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- KLOIYEQEVSIOOO-UHFFFAOYSA-N carbocromen Chemical compound CC1=C(CCN(CC)CC)C(=O)OC2=CC(OCC(=O)OCC)=CC=C21 KLOIYEQEVSIOOO-UHFFFAOYSA-N 0.000 description 3
- 229960005003 carbocromen Drugs 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- IYRMNDOLPONSCJ-UHFFFAOYSA-N isoquinolin-2-ium;chloride Chemical compound Cl.C1=NC=CC2=CC=CC=C21 IYRMNDOLPONSCJ-UHFFFAOYSA-N 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 230000036284 oxygen consumption Effects 0.000 description 3
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 2
- 241000320529 Allobates femoralis Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 210000001198 duodenum Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- ISJBQSJDQZLCSF-UHFFFAOYSA-N (4-chlorophenyl)azanium;chloride Chemical compound [Cl-].[NH3+]C1=CC=C(Cl)C=C1 ISJBQSJDQZLCSF-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- MVJZWRRXDKDIIG-UHFFFAOYSA-N 1,1-dimethoxy-3,4-dihydro-2h-isoquinoline Chemical compound C1=CC=C2C(OC)(OC)NCCC2=C1 MVJZWRRXDKDIIG-UHFFFAOYSA-N 0.000 description 1
- NTASFODDPBHBAM-UHFFFAOYSA-N 1-hydroxyethylazanium;chloride Chemical compound [Cl-].CC([NH3+])O NTASFODDPBHBAM-UHFFFAOYSA-N 0.000 description 1
- IOYIDSMWPLNHRC-UHFFFAOYSA-N 2h-isoquinoline-1-thione Chemical class C1=CC=C2C(S)=NC=CC2=C1 IOYIDSMWPLNHRC-UHFFFAOYSA-N 0.000 description 1
- ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 description 1
- DTBDAFLSBDGPEA-UHFFFAOYSA-N 3-Methylquinoline Natural products C1=CC=CC2=CC(C)=CN=C21 DTBDAFLSBDGPEA-UHFFFAOYSA-N 0.000 description 1
- RBJOTRVJJWIIER-UHFFFAOYSA-N 3-phenylisoquinoline Chemical compound C1=CC=CC=C1C1=CC2=CC=CC=C2C=N1 RBJOTRVJJWIIER-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- QWYXMMWYYGXJDS-UHFFFAOYSA-N COC1=C(C=C2C(=C1)CCN3C2=C(SC3NC(=O)C4=CC=CC=C4)C#N)OC Chemical compound COC1=C(C=C2C(=C1)CCN3C2=C(SC3NC(=O)C4=CC=CC=C4)C#N)OC QWYXMMWYYGXJDS-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 235000014653 Carica parviflora Nutrition 0.000 description 1
- 241000243321 Cnidaria Species 0.000 description 1
- 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 1
- 241000699670 Mus sp. Species 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical group NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- TZEYHTCZIQZAPS-UHFFFAOYSA-N [1,3]thiazolo[4,5-h]isoquinoline Chemical class C1=CN=CC2=C(SC=N3)C3=CC=C21 TZEYHTCZIQZAPS-UHFFFAOYSA-N 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- XDLDASNSMGOEMX-UHFFFAOYSA-N benzene benzene Chemical compound C1=CC=CC=C1.C1=CC=CC=C1 XDLDASNSMGOEMX-UHFFFAOYSA-N 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 125000005998 bromoethyl group Chemical group 0.000 description 1
- LMSPNMQWIZCFIP-UHFFFAOYSA-N butan-1-ol;n,n-dimethylformamide Chemical compound CCCCO.CN(C)C=O LMSPNMQWIZCFIP-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000004112 carboxyamino group Chemical group [H]OC(=O)N([H])[*] 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000000911 decarboxylating effect Effects 0.000 description 1
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- UTKNBHYJLFLZRD-UHFFFAOYSA-N isoquinolin-2-ium;hydroxide Chemical compound [OH-].C1=[NH+]C=CC2=CC=CC=C21 UTKNBHYJLFLZRD-UHFFFAOYSA-N 0.000 description 1
- KFQTXYLBJPPYAI-UHFFFAOYSA-N isoquinoline dihydrate hydrochloride Chemical compound O.O.Cl.C1=NC=CC2=CC=CC=C12 KFQTXYLBJPPYAI-UHFFFAOYSA-N 0.000 description 1
- DZHTWJSZRWZPIH-UHFFFAOYSA-N isoquinoline;1,3-thiazole Chemical class C1=CSC=N1.C1=NC=CC2=CC=CC=C21 DZHTWJSZRWZPIH-UHFFFAOYSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 150000007519 polyprotic acids Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound 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
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- KIWUVOGUEXMXSV-UHFFFAOYSA-N rhodanine Chemical compound O=C1CSC(=S)N1 KIWUVOGUEXMXSV-UHFFFAOYSA-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
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- 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
- A61P11/16—Central respiratory analeptics
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI791377A FI60566C (fi) | 1973-05-30 | 1979-04-27 | Foerfarande foer framstaellning av 2h 4h-5,6-dihydro-1,2-tiazolo(3,2-a)isokinolinderivat med hjaertmuskelns kontraktilitet foerhoejande verkan |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HUCI001381 | 1973-05-30 | ||
| HUCI1381A HU170680B (forum.php) | 1973-05-30 | 1973-05-30 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI164474A7 FI164474A7 (forum.php) | 1974-12-01 |
| FI57262B FI57262B (fi) | 1980-03-31 |
| FI57262C true FI57262C (fi) | 1980-07-10 |
Family
ID=10994482
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI1644/74A FI57262C (fi) | 1973-05-30 | 1974-05-29 | Foerfarande foer framstaellning av nya terapeutiskt aktiva 3,4,5,6-tetrahydro-(1,3)tiazolo(4,3-a)isokinolinderivat |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US3979397A (forum.php) |
| JP (3) | JPS6014038B2 (forum.php) |
| AR (1) | AR213611A1 (forum.php) |
| AT (1) | AT349018B (forum.php) |
| BE (1) | BE815679A (forum.php) |
| BG (1) | BG22391A3 (forum.php) |
| CA (1) | CA1037042A (forum.php) |
| CH (2) | CH622807A5 (forum.php) |
| CS (2) | CS227001B2 (forum.php) |
| DD (1) | DD119595A5 (forum.php) |
| DE (1) | DE2426267C2 (forum.php) |
| DK (1) | DK151028C (forum.php) |
| EG (1) | EG11439A (forum.php) |
| ES (1) | ES426773A1 (forum.php) |
| FI (1) | FI57262C (forum.php) |
| FR (1) | FR2241309B1 (forum.php) |
| HU (1) | HU170680B (forum.php) |
| IL (1) | IL44895A (forum.php) |
| NL (1) | NL176944C (forum.php) |
| NO (1) | NO150281C (forum.php) |
| PL (1) | PL101194B1 (forum.php) |
| SE (1) | SE419647B (forum.php) |
| SU (1) | SU569291A3 (forum.php) |
| YU (1) | YU37172B (forum.php) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4163786A (en) * | 1973-05-30 | 1979-08-07 | Chinoin Pharmaceutical And Chemical Works Ltd. | Thiazoloisoquinolines with coronary and respiratory effects |
| US4062850A (en) * | 1973-05-30 | 1977-12-13 | Chinoin Pharmaceutical And Chemical Works Ltd. | Thiazoloisoquinolines with coronary and respiratory effects |
| NL169076C (nl) * | 1975-08-06 | 1982-06-01 | Rhone Poulenc Ind | Werkwijze voor het bereiden of vervaardigen van farmacologische preparaten met een analgetische en antipyretische werking, alsmede werkwijze voor het bereiden van geneeskrachtige verbindingen, welke geschikt zijn voor gebruik in dergelijke preparaten. |
| US4108999A (en) * | 1977-02-22 | 1978-08-22 | Rhone-Poulenc Industries | Thiazolo[3,4-b]isoquinoline derivatives, pharmaceutical compositions containing them and pharmaceutical methods using them |
| NL7908655A (nl) * | 1978-12-07 | 1980-06-10 | Rhone Poulenc Ind | Nieuwe thienopyridine-derivaten, de bereiding ervan, alsmede farmaceutische preparaten, die de nieuwe derivaten bevatten. |
| HU178454B (en) * | 1979-07-02 | 1982-05-28 | Chinoin Gyogyszer Es Vegyeszet | Process for preparing new isoquinoline derivatives containing sulphur |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3042671A (en) * | 1959-10-07 | 1962-07-03 | Pfizer & Co C | Benzopyridocolines |
| US3455933A (en) * | 1966-11-15 | 1969-07-15 | American Home Prod | Thiazolo and thiazino isoquinoline derivatives |
| US3665007A (en) * | 1970-05-04 | 1972-05-23 | Squibb & Sons Inc | Thiazolo (3,4-a) benzimidazoles and derivatives thereof |
-
1973
- 1973-05-30 HU HUCI1381A patent/HU170680B/hu unknown
-
1974
- 1974-05-24 IL IL44895A patent/IL44895A/xx unknown
- 1974-05-27 AT AT433674A patent/AT349018B/de not_active IP Right Cessation
- 1974-05-28 CS CS743796A patent/CS227001B2/cs unknown
- 1974-05-28 FR FR7418415A patent/FR2241309B1/fr not_active Expired
- 1974-05-28 SE SE7407049A patent/SE419647B/xx not_active IP Right Cessation
- 1974-05-28 US US05/473,918 patent/US3979397A/en not_active Expired - Lifetime
- 1974-05-28 CS CS746737A patent/CS226901B1/cs unknown
- 1974-05-29 DD DD178843A patent/DD119595A5/xx unknown
- 1974-05-29 CH CH733674A patent/CH622807A5/de not_active IP Right Cessation
- 1974-05-29 AR AR253962A patent/AR213611A1/es active
- 1974-05-29 FI FI1644/74A patent/FI57262C/fi active
- 1974-05-29 SU SU7402033764A patent/SU569291A3/ru active
- 1974-05-29 NO NO741939A patent/NO150281C/no unknown
- 1974-05-29 CA CA201,128A patent/CA1037042A/en not_active Expired
- 1974-05-29 YU YU1480/74A patent/YU37172B/xx unknown
- 1974-05-29 DE DE2426267A patent/DE2426267C2/de not_active Expired
- 1974-05-29 DK DK289774A patent/DK151028C/da not_active IP Right Cessation
- 1974-05-29 BE BE144870A patent/BE815679A/xx not_active IP Right Cessation
- 1974-05-30 ES ES426773A patent/ES426773A1/es not_active Expired
- 1974-05-30 BG BG026826A patent/BG22391A3/xx unknown
- 1974-05-30 JP JP49060321A patent/JPS6014038B2/ja not_active Expired
- 1974-05-30 NL NLAANVRAGE7407280,A patent/NL176944C/xx not_active IP Right Cessation
- 1974-05-30 PL PL1974171518A patent/PL101194B1/pl unknown
- 1974-06-29 EG EG74194A patent/EG11439A/xx active
-
1979
- 1979-02-12 CH CH135379A patent/CH620220A5/de not_active IP Right Cessation
-
1982
- 1982-01-04 JP JP57000010A patent/JPS591714B2/ja not_active Expired
- 1982-01-04 JP JP57000009A patent/JPS5842195B2/ja not_active Expired
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4690930A (en) | Pyrazolo[4,3-c]quinoline-3-one and imidazo[4,3-c]cinnolin-3-one derivatives and their use as psychotropic agents | |
| CA1216291A (en) | Imidazoquinoxaline compounds | |
| HU198030B (en) | Process for production of derivatives of benzotiasole and benzotiophen and medical preparatives containing these compounds as active substance | |
| FI60010B (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 4-(2-imidazolin-2-ylamino)-2,1,3-bensotiadiazoler | |
| NO145139B (no) | Analogifremgangsmaate til fremstilling av terapeutisk aktive heteroarylbenzoksepin-eddiksyrer og estere herav | |
| PT90744B (pt) | Processo para a preparacao de carboxamidas biciclicas, de composicoes farmaceuticas que as contem e de produtos intermediarios usados na sua preparacao | |
| FI57262C (fi) | Foerfarande foer framstaellning av nya terapeutiskt aktiva 3,4,5,6-tetrahydro-(1,3)tiazolo(4,3-a)isokinolinderivat | |
| JPH0471914B2 (forum.php) | ||
| DK149816B (da) | Analogifremgangsmaade til fremstilling af tetrahydrothieno(3,2-c)pyridinderivater | |
| US6800623B2 (en) | Method of treating schizophrenia | |
| IE61070B1 (en) | Antiarrhythmic agents | |
| US20100009974A1 (en) | Cycloalkylated benzothiadiazines, a process for their preparation and pharmaceutical compostions containing them | |
| US3468888A (en) | 2-substituted pyrimido(1,2-a) benzimidazoles | |
| WO1994017075A1 (en) | Diazepin derivatives and antiviral compositions | |
| US3842082A (en) | 4-piperazinyl-10h-thieno(3,2-c)(1)benzazepines | |
| US3546227A (en) | 2,3-dihydro-1h-benz(d,e)isoquinoline carboxamidines | |
| US3354164A (en) | S-triazolo-[3, 4-a] isoquinolines and process | |
| US4163786A (en) | Thiazoloisoquinolines with coronary and respiratory effects | |
| US4994448A (en) | Condensed quinolinium and isoquinolinium derivatives | |
| FI60566B (fi) | Foerfarande foer framstaellning av 2h,4h-5,6-dihydro-1,2-tiazolo/3,2-a/isokinolinderivat med hjaertmuskelns kontraktilitet foerhoejande verkan | |
| US3539576A (en) | 1,2,3,7,8,12b-hexahydrobenzo(1,2)cyclohepta(3,4,5 - d,e) isoquinolinomethyleneamidoximes and esters thereof | |
| NO813693L (no) | Fremgangsmaate til fremstilling av nye lactamforbindelser | |
| FI77863C (fi) | Foerfarande foer framstaellning av 2-(2-tienyl)-imidazo/4,5-b/pyridinderivat och farmaceutiskt laempliga syraadditionssalter daerav. | |
| US3423412A (en) | Benzopyrroloquinazolinones | |
| PT744399E (pt) | Conversao de 8-cloroquinolinas substituidas em 8-hidroxiquinolinas substituidas |