CA1329391C - Pyrrolidine derivatives - Google Patents
Pyrrolidine derivativesInfo
- Publication number
- CA1329391C CA1329391C CA000565552A CA565552A CA1329391C CA 1329391 C CA1329391 C CA 1329391C CA 000565552 A CA000565552 A CA 000565552A CA 565552 A CA565552 A CA 565552A CA 1329391 C CA1329391 C CA 1329391C
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- compound
- salt
- carboxy
- formula
- 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 - Fee Related
Links
- 150000003235 pyrrolidines Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 144
- 150000003839 salts Chemical class 0.000 claims abstract description 139
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 137
- 238000000034 method Methods 0.000 claims abstract description 68
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 66
- 125000005843 halogen group Chemical group 0.000 claims abstract description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
- 239000001257 hydrogen Substances 0.000 claims abstract description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 27
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims abstract description 23
- 125000000213 sulfino group Chemical group [H]OS(*)=O 0.000 claims abstract description 7
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 4
- 208000006673 asthma Diseases 0.000 claims abstract description 4
- 201000008383 nephritis Diseases 0.000 claims abstract description 4
- -1 phenylcarbamoyl Chemical group 0.000 claims description 149
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 37
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 24
- 125000006239 protecting group Chemical group 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 238000003379 elimination reaction Methods 0.000 claims description 14
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 7
- ANUJKHAASWWIFK-YLDLQSEOSA-N (z)-6-[(2s,4r)-1-(4-chlorophenyl)sulfonyl-4-[(4-chlorophenyl)sulfonylamino]pyrrolidin-2-yl]hex-5-enoic acid Chemical compound C([C@@H](C[C@H]1\C=C/CCCC(=O)O)NS(=O)(=O)C=2C=CC(Cl)=CC=2)N1S(=O)(=O)C1=CC=C(Cl)C=C1 ANUJKHAASWWIFK-YLDLQSEOSA-N 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 238000005886 esterification reaction Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 125000006833 (C1-C5) alkylene group Chemical group 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 67
- 238000002360 preparation method Methods 0.000 abstract description 24
- 125000002252 acyl group Chemical group 0.000 abstract description 12
- 125000005026 carboxyaryl group Chemical group 0.000 abstract description 12
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 140
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 110
- 101150041968 CDC13 gene Proteins 0.000 description 104
- 238000006243 chemical reaction Methods 0.000 description 85
- 239000000243 solution Substances 0.000 description 77
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- 239000002904 solvent Substances 0.000 description 70
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 238000005160 1H NMR spectroscopy Methods 0.000 description 61
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 52
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
- 239000012267 brine Substances 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 26
- 235000019341 magnesium sulphate Nutrition 0.000 description 26
- 239000003921 oil Substances 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 24
- 239000002253 acid Substances 0.000 description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 159000000000 sodium salts Chemical class 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 238000001816 cooling Methods 0.000 description 17
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 239000003480 eluent Substances 0.000 description 16
- 150000002148 esters Chemical class 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 230000002411 adverse Effects 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 13
- 229920002554 vinyl polymer Polymers 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 11
- 238000006722 reduction reaction Methods 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 10
- 235000011167 hydrochloric acid Nutrition 0.000 description 10
- 229960000443 hydrochloric acid Drugs 0.000 description 10
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- 229910052783 alkali metal Inorganic materials 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 125000005907 alkyl ester group Chemical group 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 238000010792 warming Methods 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- 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 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
- 150000004678 hydrides Chemical class 0.000 description 6
- 150000007529 inorganic bases Chemical class 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 150000007524 organic acids Chemical class 0.000 description 6
- 150000007530 organic bases Chemical class 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 6
- LQANGKSBLPMBTJ-BRSNVKEHSA-N (z)-7-[(1s,2s,3r,4r)-3-[(e,3s)-3-hydroxyoct-1-enyl]-5-oxabicyclo[2.2.1]heptan-2-yl]hept-5-enoic acid Chemical compound C1[C@@H]2CO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O LQANGKSBLPMBTJ-BRSNVKEHSA-N 0.000 description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 5
- 210000004623 platelet-rich plasma Anatomy 0.000 description 5
- OGKNVYAZTUGWMF-OLZOCXBDSA-N tert-butyl (2s,4r)-4-[(4-chlorophenyl)sulfonylamino]-2-formylpyrrolidine-1-carboxylate Chemical compound C1[C@@H](C=O)N(C(=O)OC(C)(C)C)C[C@@H]1NS(=O)(=O)C1=CC=C(Cl)C=C1 OGKNVYAZTUGWMF-OLZOCXBDSA-N 0.000 description 5
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 229910052802 copper Inorganic materials 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 239000012948 isocyanate Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 229910052697 platinum Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- IOLQYMRFIIVPMQ-YUMQZZPRSA-N 1-o-tert-butyl 2-o-methyl (2s,4s)-4-aminopyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1C[C@H](N)CN1C(=O)OC(C)(C)C IOLQYMRFIIVPMQ-YUMQZZPRSA-N 0.000 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 description 3
- DZLNVVXVGSXIRX-CABCVRRESA-N 4-chloro-n-[(3r,5s)-1-(4-chlorophenyl)sulfonyl-5-formylpyrrolidin-3-yl]benzenesulfonamide Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N[C@H]1CN(S(=O)(=O)C=2C=CC(Cl)=CC=2)[C@H](C=O)C1 DZLNVVXVGSXIRX-CABCVRRESA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 150000008065 acid anhydrides Chemical class 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 3
- 150000001540 azides Chemical class 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 125000001589 carboacyl group Chemical group 0.000 description 3
- 238000010531 catalytic reduction reaction Methods 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 229910017052 cobalt Inorganic materials 0.000 description 3
- 239000010941 cobalt Substances 0.000 description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- BYLPQKKONXCPRF-LSDHHAIUSA-N n-[(3s,5r)-1-(benzenesulfonyl)-5-formylpyrrolidin-3-yl]benzenesulfonamide Chemical compound C([C@H](C[C@@H]1C=O)NS(=O)(=O)C=2C=CC=CC=2)N1S(=O)(=O)C1=CC=CC=C1 BYLPQKKONXCPRF-LSDHHAIUSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- FNJAWEIVVBANHD-USOCOWCUSA-N (z)-6-[(2s,4r)-1-(4-chlorophenyl)sulfonyl-4-[(4-chlorophenyl)sulfonylamino]pyrrolidin-2-yl]-2-methylhex-5-enoic acid Chemical compound C([C@@H](C[C@H]1\C=C/CCC(C)C(O)=O)NS(=O)(=O)C=2C=CC(Cl)=CC=2)N1S(=O)(=O)C1=CC=C(Cl)C=C1 FNJAWEIVVBANHD-USOCOWCUSA-N 0.000 description 2
- NTVZEZVFIMLQMA-YLDLQSEOSA-N (z)-6-[(2s,4r)-1-(4-chlorophenyl)sulfonyl-4-[[4-(trifluoromethyl)phenyl]sulfonylamino]pyrrolidin-2-yl]hex-5-enoic acid Chemical compound C([C@@H](C[C@H]1\C=C/CCCC(=O)O)NS(=O)(=O)C=2C=CC(=CC=2)C(F)(F)F)N1S(=O)(=O)C1=CC=C(Cl)C=C1 NTVZEZVFIMLQMA-YLDLQSEOSA-N 0.000 description 2
- DAWCICVVYOVJNT-WCGUUESXSA-N (z)-6-[(2s,4r)-4-[(4-chlorophenyl)sulfonylamino]-1-thiophen-2-ylsulfonylpyrrolidin-2-yl]hex-5-enoic acid Chemical compound C([C@@H](C[C@H]1\C=C/CCCC(=O)O)NS(=O)(=O)C=2C=CC(Cl)=CC=2)N1S(=O)(=O)C1=CC=CS1 DAWCICVVYOVJNT-WCGUUESXSA-N 0.000 description 2
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- PUMIMBRIQBVRIW-HIPQDABWSA-N methyl 3-[(e)-2-[(2s,4r)-1-(4-chlorophenyl)sulfonyl-4-[(4-chlorophenyl)sulfonylamino]pyrrolidin-2-yl]ethenyl]benzoate Chemical compound COC(=O)C1=CC=CC(\C=C\[C@H]2N(C[C@@H](C2)NS(=O)(=O)C=2C=CC(Cl)=CC=2)S(=O)(=O)C=2C=CC(Cl)=CC=2)=C1 PUMIMBRIQBVRIW-HIPQDABWSA-N 0.000 description 1
- PUMIMBRIQBVRIW-XZENCKKOSA-N methyl 3-[(z)-2-[(2s,4r)-1-(4-chlorophenyl)sulfonyl-4-[(4-chlorophenyl)sulfonylamino]pyrrolidin-2-yl]ethenyl]benzoate Chemical compound COC(=O)C1=CC=CC(\C=C/[C@H]2N(C[C@@H](C2)NS(=O)(=O)C=2C=CC(Cl)=CC=2)S(=O)(=O)C=2C=CC(Cl)=CC=2)=C1 PUMIMBRIQBVRIW-XZENCKKOSA-N 0.000 description 1
- FCEGXKMFVDCTLP-QLIIXQJQSA-N methyl 4-[(e)-2-[(2s,4r)-4-[(4-chlorophenyl)sulfonylamino]pyrrolidin-2-yl]ethenyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1\C=C\[C@H]1NC[C@H](NS(=O)(=O)C=2C=CC(Cl)=CC=2)C1 FCEGXKMFVDCTLP-QLIIXQJQSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- BLWYXBNNBYXPPL-UHFFFAOYSA-N methyl pyrrolidine-2-carboxylate Chemical compound COC(=O)C1CCCN1 BLWYXBNNBYXPPL-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- BYLPQKKONXCPRF-HUUCEWRRSA-N n-[(3r,5r)-1-(benzenesulfonyl)-5-formylpyrrolidin-3-yl]benzenesulfonamide Chemical compound C([C@@H](C[C@@H]1C=O)NS(=O)(=O)C=2C=CC=CC=2)N1S(=O)(=O)C1=CC=CC=C1 BYLPQKKONXCPRF-HUUCEWRRSA-N 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910000480 nickel oxide Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- GNRSAWUEBMWBQH-UHFFFAOYSA-N oxonickel Chemical compound [Ni]=O GNRSAWUEBMWBQH-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 229910003445 palladium oxide Inorganic materials 0.000 description 1
- JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 229940074439 potassium sodium tartrate Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- FGVVTMRZYROCTH-UHFFFAOYSA-N pyridine-2-thiol N-oxide Chemical compound [O-][N+]1=CC=CC=C1S FGVVTMRZYROCTH-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 229940001607 sodium bisulfite Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LZWOXEHMQORMLQ-HIFRSBDPSA-N tert-butyl (2s,4r)-2-acetyl-4-[(4-chlorophenyl)sulfonylamino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)C)C[C@H]1NS(=O)(=O)C1=CC=C(Cl)C=C1 LZWOXEHMQORMLQ-HIFRSBDPSA-N 0.000 description 1
- PFAZIDHWRUSDLP-OLZOCXBDSA-N tert-butyl (2s,4r)-2-formyl-4-[(4-methoxyphenyl)sulfonylamino]pyrrolidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C=O)C1 PFAZIDHWRUSDLP-OLZOCXBDSA-N 0.000 description 1
- PJGRTZLAHQGBCA-KGLIPLIRSA-N tert-butyl (2s,4r)-2-formyl-4-[(4-methylphenyl)sulfonylamino]pyrrolidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C=O)C1 PJGRTZLAHQGBCA-KGLIPLIRSA-N 0.000 description 1
- HNAFWWZLROOWAD-OLZOCXBDSA-N tert-butyl (2s,4r)-4-(benzenesulfonamido)-2-formylpyrrolidine-1-carboxylate Chemical compound C1[C@@H](C=O)N(C(=O)OC(C)(C)C)C[C@@H]1NS(=O)(=O)C1=CC=CC=C1 HNAFWWZLROOWAD-OLZOCXBDSA-N 0.000 description 1
- WTVNNKQXHOBQML-WYIOMSSPSA-N tert-butyl (2s,4r)-4-[(4-chlorophenyl)sulfonylamino]-2-[(e)-2-(4-methoxycarbonylphenyl)ethenyl]pyrrolidine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1\C=C\[C@H]1N(C(=O)OC(C)(C)C)C[C@H](NS(=O)(=O)C=2C=CC(Cl)=CC=2)C1 WTVNNKQXHOBQML-WYIOMSSPSA-N 0.000 description 1
- WTVNNKQXHOBQML-WLEBJDBUSA-N tert-butyl (2s,4r)-4-[(4-chlorophenyl)sulfonylamino]-2-[(z)-2-(4-methoxycarbonylphenyl)ethenyl]pyrrolidine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1\C=C/[C@H]1N(C(=O)OC(C)(C)C)C[C@H](NS(=O)(=O)C=2C=CC(Cl)=CC=2)C1 WTVNNKQXHOBQML-WLEBJDBUSA-N 0.000 description 1
- YTMYKOCTVAVKGK-STQMWFEESA-N tert-butyl (2s,4s)-4-(benzenesulfonamido)-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound C1[C@@H](CO)N(C(=O)OC(C)(C)C)C[C@H]1NS(=O)(=O)C1=CC=CC=C1 YTMYKOCTVAVKGK-STQMWFEESA-N 0.000 description 1
- HNAFWWZLROOWAD-STQMWFEESA-N tert-butyl (2s,4s)-4-(benzenesulfonamido)-2-formylpyrrolidine-1-carboxylate Chemical compound C1[C@@H](C=O)N(C(=O)OC(C)(C)C)C[C@H]1NS(=O)(=O)C1=CC=CC=C1 HNAFWWZLROOWAD-STQMWFEESA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 229960004319 trichloroacetic acid Drugs 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8710352 | 1987-05-01 | ||
| GB878710352A GB8710352D0 (en) | 1987-05-01 | 1987-05-01 | Pyrrolidine derivatives |
| GB878716438A GB8716438D0 (en) | 1987-07-13 | 1987-07-13 | Pyrrolidine derivatives |
| GB8716438 | 1987-07-13 | ||
| GB878730027A GB8730027D0 (en) | 1987-12-23 | 1987-12-23 | Pyrrolidine derivatives |
| GB8730027 | 1987-12-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1329391C true CA1329391C (en) | 1994-05-10 |
Family
ID=27263412
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000565552A Expired - Fee Related CA1329391C (en) | 1987-05-01 | 1988-04-29 | Pyrrolidine derivatives |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4916152A (enExample) |
| EP (1) | EP0289911B1 (enExample) |
| JP (1) | JPS63295553A (enExample) |
| KR (1) | KR970005190B1 (enExample) |
| CN (1) | CN1020899C (enExample) |
| AR (1) | AR247879A1 (enExample) |
| AU (1) | AU613360B2 (enExample) |
| CA (1) | CA1329391C (enExample) |
| DE (1) | DE3881755T2 (enExample) |
| DK (1) | DK233888A (enExample) |
| ES (1) | ES2054729T3 (enExample) |
| FI (1) | FI88716C (enExample) |
| HU (1) | HU208671B (enExample) |
| IE (1) | IE62862B1 (enExample) |
| IL (1) | IL86173A (enExample) |
| NO (1) | NO173330C (enExample) |
| PH (1) | PH24950A (enExample) |
| PT (1) | PT87359B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5130323A (en) * | 1988-10-31 | 1992-07-14 | Fujisawa Pharmaceutical Co., Ltd. | Pyrrolidine derivatives |
| US5264453A (en) * | 1988-10-31 | 1993-11-23 | Fujisawa Pharmaceutical Co., Ltd. | Pyrrolidine derivatives |
| FR2685325B1 (fr) * | 1991-12-20 | 1994-02-04 | Adir Cie | Nouveaux derives de pyrrolidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| FR2687146B1 (fr) * | 1992-02-12 | 1994-04-01 | Adir Cie | Nouveaux derives de pyrrolidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| RU94046180A (ru) * | 1992-07-02 | 1996-10-27 | Фудзисава Фармасьютикал Ко. | Способ получения производного пирролидина и его соли, исходный продукт и способ его получения |
| KR100671658B1 (ko) | 2005-01-05 | 2007-01-19 | 삼성에스디아이 주식회사 | 마스크 프레임 및 이를 사용한 마스크 고정방법 |
| AU2008340355B2 (en) * | 2007-12-04 | 2015-01-22 | Tekmira Pharmaceuticals Corporation | Targeting lipids |
| CN109912487B (zh) * | 2019-03-25 | 2023-01-10 | 山东理工大学 | 一种合成1-对甲苯磺酰基-2-乙烯基-1氢-吡咯的方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3577440A (en) * | 1968-12-23 | 1971-05-04 | Robins Co Inc A H | 1-substituted-3-amido-pyrrolidines |
| US4282243A (en) * | 1972-04-03 | 1981-08-04 | A. H. Robins Company, Inc. | Optical isomers of 4-amino-N-(1-cyclohexyl-3-pyrrolidinyl)-N-methylbenzamide |
| US4210660A (en) * | 1978-12-20 | 1980-07-01 | Yamanouchi Pharmaceutical Co., Ltd. | Benzamide derivatives |
| DE3165669D1 (en) * | 1980-06-23 | 1984-09-27 | Squibb & Sons Inc | Azido, imido, amido and amino derivatives of mercaptoacyl prolines and pipecolic acids having hypotensive activity |
| GB8509703D0 (en) * | 1985-04-16 | 1985-05-22 | Fujisawa Pharmaceutical Co | Pyrrolidine derivatives |
| US4785119A (en) * | 1985-10-11 | 1988-11-15 | Tokyo Kasei Kogyo Co., Ltd. | 3-aminopyrrolidine compound and process for preparation thereof |
| JPH07108898B2 (ja) * | 1986-08-20 | 1995-11-22 | 大日本製薬株式会社 | ３−アミノピロリジン誘導体およびその塩の製造法 |
| US5130323A (en) * | 1988-10-31 | 1992-07-14 | Fujisawa Pharmaceutical Co., Ltd. | Pyrrolidine derivatives |
-
1988
- 1988-04-26 PH PH36844A patent/PH24950A/en unknown
- 1988-04-26 EP EP88106637A patent/EP0289911B1/en not_active Expired - Lifetime
- 1988-04-26 ES ES88106637T patent/ES2054729T3/es not_active Expired - Lifetime
- 1988-04-26 JP JP63107305A patent/JPS63295553A/ja active Granted
- 1988-04-26 DE DE88106637T patent/DE3881755T2/de not_active Expired - Fee Related
- 1988-04-26 IL IL86173A patent/IL86173A/xx not_active IP Right Cessation
- 1988-04-27 IE IE126088A patent/IE62862B1/en not_active IP Right Cessation
- 1988-04-28 US US07/187,240 patent/US4916152A/en not_active Expired - Fee Related
- 1988-04-28 DK DK233888A patent/DK233888A/da not_active Application Discontinuation
- 1988-04-29 CA CA000565552A patent/CA1329391C/en not_active Expired - Fee Related
- 1988-04-29 NO NO881884A patent/NO173330C/no unknown
- 1988-04-29 AU AU15348/88A patent/AU613360B2/en not_active Ceased
- 1988-04-29 PT PT87359A patent/PT87359B/pt not_active IP Right Cessation
- 1988-04-29 HU HU882232A patent/HU208671B/hu not_active IP Right Cessation
- 1988-04-29 AR AR88310720A patent/AR247879A1/es active
- 1988-04-29 FI FI882015A patent/FI88716C/fi not_active IP Right Cessation
- 1988-04-30 KR KR1019880005091A patent/KR970005190B1/ko not_active Expired - Fee Related
- 1988-04-30 CN CN88102511A patent/CN1020899C/zh not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE3881755T2 (de) | 1993-10-21 |
| FI88716B (fi) | 1993-03-15 |
| AU1534888A (en) | 1988-11-03 |
| CN88102511A (zh) | 1988-11-23 |
| IL86173A0 (en) | 1988-11-15 |
| HUT48579A (en) | 1989-06-28 |
| DK233888A (da) | 1988-11-02 |
| EP0289911B1 (en) | 1993-06-16 |
| EP0289911A3 (en) | 1989-08-16 |
| HU208671B (en) | 1993-12-28 |
| NO881884D0 (no) | 1988-04-29 |
| FI882015A0 (fi) | 1988-04-29 |
| PT87359B (pt) | 1992-08-31 |
| IL86173A (en) | 1992-02-16 |
| NO173330B (no) | 1993-08-23 |
| AU613360B2 (en) | 1991-08-01 |
| KR880013889A (ko) | 1988-12-22 |
| CN1020899C (zh) | 1993-05-26 |
| IE62862B1 (en) | 1995-03-08 |
| AR247879A1 (es) | 1995-04-28 |
| IE881260L (en) | 1988-11-01 |
| FI882015L (fi) | 1988-11-02 |
| NO173330C (no) | 1993-12-01 |
| KR970005190B1 (ko) | 1997-04-14 |
| DK233888D0 (da) | 1988-04-28 |
| FI88716C (fi) | 1993-06-28 |
| PH24950A (en) | 1990-12-26 |
| NO881884L (no) | 1988-11-02 |
| PT87359A (pt) | 1989-05-31 |
| US4916152A (en) | 1990-04-10 |
| JPS63295553A (ja) | 1988-12-01 |
| DE3881755D1 (de) | 1993-07-22 |
| ES2054729T3 (es) | 1994-08-16 |
| JPH0546335B2 (enExample) | 1993-07-13 |
| EP0289911A2 (en) | 1988-11-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed |