CA1119180A - Derivatives of trans-3-hydroxy-4-amino-chromans - Google Patents
Derivatives of trans-3-hydroxy-4-amino-chromansInfo
- Publication number
- CA1119180A CA1119180A CA000275337A CA275337A CA1119180A CA 1119180 A CA1119180 A CA 1119180A CA 000275337 A CA000275337 A CA 000275337A CA 275337 A CA275337 A CA 275337A CA 1119180 A CA1119180 A CA 1119180A
- Authority
- CA
- Canada
- Prior art keywords
- dimethyl
- trans
- group
- dihydro
- pyran
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 44
- 150000001875 compounds Chemical class 0.000 claims abstract description 36
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 239000000460 chlorine Substances 0.000 claims abstract description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 10
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 43
- 239000002904 solvent Substances 0.000 claims description 27
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 11
- -1 salt 1-[trans-2,2-dimethyl -3-hydroxy-4-piperidinochroman-6-yl] ethanone oxime methane sulfonate Chemical class 0.000 claims description 10
- 150000002430 hydrocarbons Chemical group 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
- NARWYSCMDPLCIQ-UHFFFAOYSA-N ethane;hydrochloride Chemical compound Cl.CC NARWYSCMDPLCIQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 239000012279 sodium borohydride Substances 0.000 claims description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
- GAPNGBASTKZZLM-KGLIPLIRSA-N [(3S,4R)-6-carbamoyl-2,2-dimethyl-4-(propan-2-ylamino)-3,4-dihydrochromen-3-yl] methanesulfonate Chemical compound CS(=O)(=O)O[C@H]1[C@@H](C2=C(OC1(C)C)C=CC(=C2)C(N)=O)NC(C)C GAPNGBASTKZZLM-KGLIPLIRSA-N 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims 5
- NMPPOXQBIFUGRB-SJORKVTESA-N 1-[(3s,4r)-3-hydroxy-2,2-dimethyl-4-piperidin-1-yl-3,4-dihydrochromen-6-yl]ethanone Chemical compound N1([C@H]2[C@H](O)C(C)(C)OC3=CC=C(C=C32)C(=O)C)CCCCC1 NMPPOXQBIFUGRB-SJORKVTESA-N 0.000 claims 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims 4
- CSTVRVLCNLYBKP-CABCVRRESA-N 1-[(3s,4r)-3-hydroxy-2,2-dimethyl-4-(propan-2-ylamino)-3,4-dihydrochromen-6-yl]ethanone Chemical compound C1=C(C(C)=O)C=C2[C@@H](NC(C)C)[C@H](O)C(C)(C)OC2=C1 CSTVRVLCNLYBKP-CABCVRRESA-N 0.000 claims 3
- 230000003301 hydrolyzing effect Effects 0.000 claims 3
- BRZLIINFOFCAEJ-CABCVRRESA-N (3s,4r)-3-hydroxy-2,2-dimethyl-4-piperidin-1-yl-3,4-dihydrochromene-6-carboxamide Chemical compound N1([C@@H]2C3=CC(=CC=C3OC([C@H]2O)(C)C)C(N)=O)CCCCC1 BRZLIINFOFCAEJ-CABCVRRESA-N 0.000 claims 2
- HHPHMEFAEUXBAX-UHFFFAOYSA-N 1-(2,2-dimethyl-1a,7b-dihydrooxireno[2,3-c]chromen-6-yl)ethanone Chemical compound O1C(C)(C)C2OC2C2=CC(C(=O)C)=CC=C21 HHPHMEFAEUXBAX-UHFFFAOYSA-N 0.000 claims 2
- UEPQIXMALSFCGA-KGLIPLIRSA-N (3s,4r)-3-hydroxy-2,2-dimethyl-4-(propan-2-ylamino)-3,4-dihydrochromene-6-carbonitrile Chemical compound C1=C(C#N)C=C2[C@@H](NC(C)C)[C@H](O)C(C)(C)OC2=C1 UEPQIXMALSFCGA-KGLIPLIRSA-N 0.000 claims 1
- LSPMNHVVDOUFHQ-RCPFAERMSA-N (3s,4r)-3-hydroxy-2,2-dimethyl-4-piperidin-1-yl-3,4-dihydrochromene-6-carbonitrile;hydrochloride Chemical compound Cl.N1([C@@H]2C3=CC(=CC=C3OC([C@H]2O)(C)C)C#N)CCCCC1 LSPMNHVVDOUFHQ-RCPFAERMSA-N 0.000 claims 1
- VVNNVZBVYJUECD-LIOBNPLQSA-N 1-[(3s,4r)-3-hydroxy-2,2-dimethyl-4-(propan-2-ylamino)-3,4-dihydrochromen-6-yl]ethanone;hydrochloride Chemical compound Cl.C1=C(C(C)=O)C=C2[C@@H](NC(C)C)[C@H](O)C(C)(C)OC2=C1 VVNNVZBVYJUECD-LIOBNPLQSA-N 0.000 claims 1
- XUOKKNSMURHWLM-PPPUBMIESA-N 1-[(3s,4r)-3-hydroxy-2,2-dimethyl-4-piperidin-1-yl-3,4-dihydrochromen-6-yl]ethanone;hydrochloride Chemical compound Cl.N1([C@H]2[C@H](O)C(C)(C)OC3=CC=C(C=C32)C(=O)C)CCCCC1 XUOKKNSMURHWLM-PPPUBMIESA-N 0.000 claims 1
- WXLPKTIAUMCNDX-UHFFFAOYSA-N 2h-pyran-3-ol Chemical compound OC1=CC=COC1 WXLPKTIAUMCNDX-UHFFFAOYSA-N 0.000 claims 1
- CNXYPUUAPXKSBM-UHFFFAOYSA-N 8ah-chromen-3-ol Chemical compound C1=CC=CC2=CC(O)=COC21 CNXYPUUAPXKSBM-UHFFFAOYSA-N 0.000 claims 1
- SLFLDOVYONEODM-CABCVRRESA-N C1=C(C(C)=NO)C=C2[C@@H](NC(C)C)[C@H](O)C(C)(C)OC2=C1 Chemical compound C1=C(C(C)=NO)C=C2[C@@H](NC(C)C)[C@H](O)C(C)(C)OC2=C1 SLFLDOVYONEODM-CABCVRRESA-N 0.000 claims 1
- HRWKICOYYKMFMK-CVEARBPZSA-N CS(=O)(=O)O[C@H]1[C@@H](C2=C(OC1(C)C)C=CC(=C2)C(N)=O)N2CCCCC2 Chemical compound CS(=O)(=O)O[C@H]1[C@@H](C2=C(OC1(C)C)C=CC(=C2)C(N)=O)N2CCCCC2 HRWKICOYYKMFMK-CVEARBPZSA-N 0.000 claims 1
- DCPURKLEEJEGDX-SJORKVTESA-N N1([C@H]2[C@H](O)C(C)(C)OC3=CC=C(C=C32)C(=NO)C)CCCCC1 Chemical compound N1([C@H]2[C@H](O)C(C)(C)OC3=CC=C(C=C32)C(=NO)C)CCCCC1 DCPURKLEEJEGDX-SJORKVTESA-N 0.000 claims 1
- 150000002118 epoxides Chemical class 0.000 claims 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims 1
- APMKKPHGMDRZAF-WDEREUQCSA-N methyl (1ar,7bs)-2,2-dimethyl-1a,7b-dihydrooxireno[2,3-c]chromene-6-carboxylate Chemical compound O1C(C)(C)[C@@H]2O[C@H]2C2=CC(C(=O)OC)=CC=C21 APMKKPHGMDRZAF-WDEREUQCSA-N 0.000 claims 1
- TVBZFAJRSSQJLS-CVEARBPZSA-N methyl (3S,4R)-2,2-dimethyl-3-methylsulfonyloxy-4-pyrrolidin-1-yl-3,4-dihydrochromene-6-carboxylate Chemical compound CS(=O)(=O)O[C@H]1[C@@H](C2=C(OC1(C)C)C=CC(=C2)C(=O)OC)N2CCCC2 TVBZFAJRSSQJLS-CVEARBPZSA-N 0.000 claims 1
- 125000004423 acyloxy group Chemical group 0.000 abstract description 4
- 230000003276 anti-hypertensive effect Effects 0.000 abstract description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 11
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000002924 oxiranes Chemical class 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000002274 desiccant Substances 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- 150000002923 oximes Chemical class 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QSILYWCNPOLKPN-UHFFFAOYSA-N 3-chloro-3-methylbut-1-yne Chemical compound CC(C)(Cl)C#C QSILYWCNPOLKPN-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000002220 antihypertensive agent Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
- YDEQIYMIVRCVAH-UHFFFAOYSA-N 2,2-dimethylchromene-6-carbonitrile Chemical compound C1=C(C#N)C=C2C=CC(C)(C)OC2=C1 YDEQIYMIVRCVAH-UHFFFAOYSA-N 0.000 description 2
- XPKQHJJKXONCHR-UHFFFAOYSA-N 2-amino-3,4-dihydrochromen-2-ol Chemical class C1=CC=C2OC(N)(O)CCC2=C1 XPKQHJJKXONCHR-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000008371 chromenes Chemical class 0.000 description 2
- ZAJTXVHECZCXLH-UHFFFAOYSA-N desmethoxyencecalin Natural products O1C(C)(C)C=CC2=CC(C(=O)C)=CC=C21 ZAJTXVHECZCXLH-UHFFFAOYSA-N 0.000 description 2
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- YDRQSXWFCMMQFF-PFEYMTCDSA-N (2r,4s)-3-hydroxy-2,3-dimethyl-4-(propan-2-ylamino)-2,4-dihydrochromene-6-carbonitrile;hydrochloride Chemical compound Cl.N#CC1=CC=C2O[C@H](C)C(O)(C)[C@@H](NC(C)C)C2=C1 YDRQSXWFCMMQFF-PFEYMTCDSA-N 0.000 description 1
- 125000004755 (C2-C7) acylamino group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- SAXKWTPDZMBKSQ-UHFFFAOYSA-N 2,2-dimethylchromene Chemical compound C1=CC=C2C=CC(C)(C)OC2=C1 SAXKWTPDZMBKSQ-UHFFFAOYSA-N 0.000 description 1
- HRDCVMSNCBAMAM-UHFFFAOYSA-N 3-prop-2-ynoxyprop-1-yne Chemical compound C#CCOCC#C HRDCVMSNCBAMAM-UHFFFAOYSA-N 0.000 description 1
- BJBUSSBIFHSXBR-UHFFFAOYSA-N 4-(2-methylbut-3-yn-2-yloxy)benzonitrile Chemical compound C#CC(C)(C)OC1=CC=C(C#N)C=C1 BJBUSSBIFHSXBR-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-UHFFFAOYSA-N 0.000 description 1
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 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
- ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- 229940124538 antidiuretic agent Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000005518 carboxamido group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- ACGDKVXYNVEAGU-UHFFFAOYSA-N guanethidine Chemical compound NC(N)=NCCN1CCCCCCC1 ACGDKVXYNVEAGU-UHFFFAOYSA-N 0.000 description 1
- 229960003602 guanethidine Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- MBRSMEJRVNZDLP-CABCVRRESA-N methyl (3s,4r)-3-hydroxy-2,2-dimethyl-4-pyrrolidin-1-yl-3,4-dihydrochromene-6-carboxylate Chemical compound N1([C@H]2[C@H](O)C(C)(C)OC3=CC=C(C=C32)C(=O)OC)CCCC1 MBRSMEJRVNZDLP-CABCVRRESA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- YOEWQQVKRJEPAE-UHFFFAOYSA-L succinylcholine chloride (anhydrous) Chemical compound [Cl-].[Cl-].C[N+](C)(C)CCOC(=O)CCC(=O)OCC[N+](C)(C)C YOEWQQVKRJEPAE-UHFFFAOYSA-L 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/68—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with nitrogen atoms directly attached in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrane Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000376467A CA1139765A (en) | 1976-04-02 | 1981-04-28 | Amino chromanols |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB13536/76A GB1511187A (en) | 1976-04-02 | 1976-04-02 | Chromans |
| GB13536/76 | 1976-04-02 | ||
| GB33178/76 | 1976-04-10 | ||
| GB3317876 | 1976-08-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1119180A true CA1119180A (en) | 1982-03-02 |
Family
ID=26249838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000275337A Expired CA1119180A (en) | 1976-04-02 | 1977-04-01 | Derivatives of trans-3-hydroxy-4-amino-chromans |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US4251537A (en, 2012) |
| JP (1) | JPS52122372A (en, 2012) |
| AU (1) | AU503934B2 (en, 2012) |
| CA (1) | CA1119180A (en, 2012) |
| CH (1) | CH632262A5 (en, 2012) |
| DE (2) | DE2713670A1 (en, 2012) |
| DK (1) | DK147777A (en, 2012) |
| ES (1) | ES457417A1 (en, 2012) |
| FR (1) | FR2346346A1 (en, 2012) |
| IE (1) | IE44977B1 (en, 2012) |
| IL (1) | IL51648A (en, 2012) |
| NL (2) | NL7703440A (en, 2012) |
| NZ (1) | NZ183551A (en, 2012) |
| SE (1) | SE7703715L (en, 2012) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0028064B1 (en) | 1979-09-28 | 1983-07-20 | Beecham Group Plc | Chromanol derivatives, a process for their preparation and a pharmaceutical composition comprising them |
| DE3064285D1 (en) | 1979-09-28 | 1983-08-25 | Beecham Group Plc | Chromanol derivatives, a process for their preparation and a pharmaceutical composition comprising them |
| EP0046652B1 (en) * | 1980-08-21 | 1985-05-22 | Beecham Group Plc | Chromanol derivatives, their production and pharmaceutical compositions containing them |
| US4447622A (en) * | 1981-09-22 | 1984-05-08 | Council Of Scientific And Industrial Research Rafi Marg | Preparation of l- and d-isomers of dl-3,4-trans-2,2-disubstituted-3,4-diarylchromans and derivatives thereof |
| DE3274350D1 (en) * | 1981-09-25 | 1987-01-08 | Beecham Group Plc | Pharmaceutically active benzopyran compounds |
| ZM7682A1 (en) * | 1981-09-25 | 1983-05-23 | Beecham Group Plc | Active compounds |
| US4404207A (en) * | 1981-11-06 | 1983-09-13 | Riker Laboratories, Inc. | Antimicrobial 8-substituted benzo [IJ]quinolizines |
| DE3364145D1 (de) * | 1982-04-08 | 1986-07-24 | Beecham Group Plc | Antihypertensive benzopyranols |
| DE3368057D1 (en) * | 1982-05-21 | 1987-01-15 | Beecham Group Plc | Pharmaceutically active aminobenzopyrans |
| GB8308063D0 (en) * | 1983-03-24 | 1983-05-05 | Beecham Group Plc | Active compounds |
| EP0139992B1 (en) * | 1983-09-01 | 1988-12-28 | Beecham Group Plc | Chromanol derivatives |
| PT84806B (pt) * | 1986-05-03 | 1989-12-29 | Beecham Group Plc | Processo para a preparacao de benzopiranos |
| DE3703227A1 (de) * | 1987-02-04 | 1988-08-18 | Hoechst Ag | Substituierte 3,4-dihydro-2h-benzopyrane, verfahren zu ihrer herstellung, ihre verwendung sowie pharmazeutische praeparate auf basis dieser verbindungen |
| IL88035A0 (en) * | 1987-10-27 | 1989-06-30 | American Home Prod | Benzopyran derivatives,their preparation and pharmaceutical compositions containing them |
| DE3823533A1 (de) * | 1988-07-12 | 1990-02-08 | Beiersdorf Ag | Substituierte 4-heterocyclyl-2h-benzo(b)pyrane, verfahren und 4-hydroxy-3-brom-, 3,4-oxiranyl-3,4-dehydro-2h-benzo(b)pyrane als zwischenprodukte zu ihrer herstellung, sowie sie enthaltende pharmazeutsche praeparate |
| DE3827532A1 (de) * | 1988-08-13 | 1990-03-01 | Hoechst Ag | 6-aroyl-substituierte 3,4-dihydro-2h-benzopyrane, verfahren zu ihrer herstellung, ihre verwendung sowie pharmazeutische praeparate auf basis dieser verbindungen |
| US4997846A (en) * | 1988-12-09 | 1991-03-05 | Researche Syntex France, S.A. | Novel benzopyranylpyrrolinone derivatives |
| US4908378A (en) * | 1989-04-12 | 1990-03-13 | American Home Products Corporation | Benzopyran derivatives and antihypertensive use thereof |
| DE3923839A1 (de) * | 1989-07-19 | 1991-01-31 | Beiersdorf Ag | Benzopyran-derivate, verfahren zu ihrer herstellung und ihre verwendung sowie die verbindungen enthaltende zubereitungen |
| US5837702A (en) * | 1993-10-07 | 1998-11-17 | Bristol-Myers Squibb Co. | 4-arylamino-benzopyran and related compounds |
| US5612323A (en) * | 1995-06-07 | 1997-03-18 | Bristol-Myers Squibb Company | Phosphinic ester substituted benzopyran derivatives |
| US5629429A (en) * | 1995-06-07 | 1997-05-13 | Bristol-Myers Squibb Company | Process for preparing 4-arylamino-benzopyran and related compounds |
| US5869478A (en) * | 1995-06-07 | 1999-02-09 | Bristol-Myers Squibb Company | Sulfonamido substituted benzopyran derivatives |
| US5612370A (en) * | 1995-06-07 | 1997-03-18 | Bristol-Myers Squibb Company | Phenylglycine and phenylalaninen amido benzopyran derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1495526A (en) * | 1974-05-31 | 1977-12-21 | Beecham Group Ltd | Chroman derivatives |
| DE3274350D1 (en) * | 1981-09-25 | 1987-01-08 | Beecham Group Plc | Pharmaceutically active benzopyran compounds |
-
1977
- 1977-03-09 NZ NZ183551A patent/NZ183551A/xx unknown
- 1977-03-11 IL IL51648A patent/IL51648A/xx unknown
- 1977-03-28 FR FR7709151A patent/FR2346346A1/fr active Granted
- 1977-03-28 DE DE19772713670 patent/DE2713670A1/de not_active Withdrawn
- 1977-03-28 DE DE2760316A patent/DE2760316C3/de not_active Expired - Lifetime
- 1977-03-29 CH CH394477A patent/CH632262A5/de not_active IP Right Cessation
- 1977-03-30 SE SE7703715A patent/SE7703715L/xx unknown
- 1977-03-30 JP JP3603477A patent/JPS52122372A/ja active Granted
- 1977-03-30 NL NL7703440A patent/NL7703440A/xx active Search and Examination
- 1977-03-31 ES ES457417A patent/ES457417A1/es not_active Expired
- 1977-04-01 IE IE694/77A patent/IE44977B1/en unknown
- 1977-04-01 CA CA000275337A patent/CA1119180A/en not_active Expired
- 1977-04-01 AU AU23875/77A patent/AU503934B2/en not_active Expired
- 1977-04-01 DK DK147777A patent/DK147777A/da not_active IP Right Cessation
-
1978
- 1978-12-18 US US05/970,199 patent/US4251537A/en not_active Expired - Lifetime
-
1984
- 1984-09-06 NL NL8402722A patent/NL8402722A/nl active Search and Examination
Also Published As
| Publication number | Publication date |
|---|---|
| DK147777A (da) | 1977-10-03 |
| IL51648A (en) | 1982-08-31 |
| FR2346346A1 (fr) | 1977-10-28 |
| AU503934B2 (en) | 1979-09-27 |
| SE7703715L (sv) | 1977-10-03 |
| JPS52122372A (en) | 1977-10-14 |
| NZ183551A (en) | 1978-09-20 |
| DE2713670A1 (de) | 1977-10-06 |
| US4251537A (en) | 1981-02-17 |
| DE2760316C2 (en, 2012) | 1993-12-23 |
| IE44977L (en) | 1977-10-02 |
| FR2346346B1 (en, 2012) | 1980-03-07 |
| DE2760316C3 (de) | 1993-12-23 |
| NL8402722A (nl) | 1984-12-03 |
| ES457417A1 (es) | 1978-07-16 |
| CH632262A5 (de) | 1982-09-30 |
| IE44977B1 (en) | 1982-06-02 |
| NL7703440A (nl) | 1977-10-04 |
| AU2387577A (en) | 1978-10-12 |
| IL51648A0 (en) | 1977-05-31 |
| JPS6112910B2 (en, 2012) | 1986-04-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1119180A (en) | Derivatives of trans-3-hydroxy-4-amino-chromans | |
| US4542149A (en) | 4-Amino-benzo[b]pyran-3-ol derivatives | |
| US4647670A (en) | Trans-3,4-dihydro-2,2-dimethyl-6-nitro-4-(2-oxo-pyrrolidinyl)2H-1-benzopyran-3-ol | |
| US4446113A (en) | Benzopyrans | |
| US4481214A (en) | 4-Acylaminobenzopyrans useful as anti-hypertensive agents | |
| EP0028064B1 (en) | Chromanol derivatives, a process for their preparation and a pharmaceutical composition comprising them | |
| US4610992A (en) | Trans-4-(2-thiaoxo-1-pyrrolidinyl or piperidinyl)-2H-benzo[b]pyran-3-ol derivatives useful in treating hypertension | |
| EP0028449B1 (en) | Chromanol derivatives, a process for their preparation and a pharmaceutical composition comprising them | |
| US6040308A (en) | Chroman derivatives | |
| AU626549B2 (en) | Chroman derivatives | |
| US5130322A (en) | Chroman derivatives | |
| US5112839A (en) | Chroman derivatives | |
| AU628395B2 (en) | Chroman derivatives | |
| US4327099A (en) | Pyrano derivatives, a process for their preparation and their use | |
| AU645373B2 (en) | Chroman derivatives | |
| US4629734A (en) | Benzopyrans | |
| US4677116A (en) | Antihypertensive chroman derivatives | |
| CA1139765A (en) | Amino chromanols | |
| US4353906A (en) | Chromanol derivatives and their use for treating hypertension | |
| WO1994014799A1 (en) | Benzopyran derivatives | |
| CA2022693A1 (en) | Chroman derivatives | |
| CA2027097A1 (en) | Chroman derivatives | |
| EP0264234A1 (en) | Novel benzofurans and a novel method of preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |