DD145749A5 - Verfahren zur herstellung von mercaptoacylderivaten von substituierten prolinen - Google Patents
Verfahren zur herstellung von mercaptoacylderivaten von substituierten prolinen Download PDFInfo
- Publication number
- DD145749A5 DD145749A5 DD79214896A DD21489679A DD145749A5 DD 145749 A5 DD145749 A5 DD 145749A5 DD 79214896 A DD79214896 A DD 79214896A DD 21489679 A DD21489679 A DD 21489679A DD 145749 A5 DD145749 A5 DD 145749A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- proline
- general formula
- methyl
- radical
- trans
- Prior art date
Links
- 150000003148 prolines Chemical class 0.000 title claims 2
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 183
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 49
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical class OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 23
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 18
- 229910052740 iodine Inorganic materials 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 229910052717 sulfur Chemical group 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 235000013930 proline Nutrition 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 153
- 229960002429 proline Drugs 0.000 description 127
- -1 alkyl radical Chemical class 0.000 description 124
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 104
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 101
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 98
- 239000000243 solution Substances 0.000 description 83
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 40
- 239000000203 mixture Substances 0.000 description 40
- 150000003254 radicals Chemical class 0.000 description 32
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 31
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 239000007787 solid Substances 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 23
- 235000011114 ammonium hydroxide Nutrition 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 23
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 22
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 21
- 239000010410 layer Substances 0.000 description 19
- 239000002253 acid Substances 0.000 description 18
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 18
- 229930182821 L-proline Natural products 0.000 description 17
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- 230000007062 hydrolysis Effects 0.000 description 15
- 238000006460 hydrolysis reaction Methods 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 14
- 229910000029 sodium carbonate Inorganic materials 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 230000008859 change Effects 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 229910052786 argon Inorganic materials 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 238000005245 sintering Methods 0.000 description 11
- 159000000000 sodium salts Chemical class 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 229910021529 ammonia Inorganic materials 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 8
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 8
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 8
- 125000001153 fluoro group Chemical group F* 0.000 description 8
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 230000001681 protective effect Effects 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 229910001923 silver oxide Inorganic materials 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 150000003946 cyclohexylamines Chemical class 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- RNXKXUOGQKYKTH-UHNVWZDZSA-N (2s,4r)-4-methoxypyrrolidine-2-carboxylic acid Chemical compound CO[C@H]1CN[C@H](C(O)=O)C1 RNXKXUOGQKYKTH-UHNVWZDZSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 4
- 102000005862 Angiotensin II Human genes 0.000 description 4
- 101800000733 Angiotensin-2 Proteins 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 229950006323 angiotensin ii Drugs 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 229940099112 cornstarch Drugs 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- PSPOEQSCJVBCDR-UHFFFAOYSA-N 3-oxobutanethioyl chloride Chemical compound CC(=O)CC(Cl)=S PSPOEQSCJVBCDR-UHFFFAOYSA-N 0.000 description 3
- UNUDUTMFKRKUIJ-UHFFFAOYSA-N 4-oxopentanethioyl chloride Chemical compound CC(=O)CCC(Cl)=S UNUDUTMFKRKUIJ-UHFFFAOYSA-N 0.000 description 3
- 101800000734 Angiotensin-1 Proteins 0.000 description 3
- 102400000344 Angiotensin-1 Human genes 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- YEESUBCSWGVPCE-UHFFFAOYSA-N azanylidyneoxidanium iron(2+) pentacyanide Chemical compound [Fe++].[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.N#[O+] YEESUBCSWGVPCE-UHFFFAOYSA-N 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 239000011261 inert gas Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 229960002460 nitroprusside Drugs 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 150000003147 proline derivatives Chemical class 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 125000001424 substituent group Chemical group 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
- 238000005406 washing Methods 0.000 description 3
- 239000008215 water for injection Substances 0.000 description 3
- WWVCWLBEARZMAH-QWRGUYRKSA-N (2s,4s)-4-hydroxy-1-phenylmethoxycarbonylpyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](O)C[C@@H](C(O)=O)N1C(=O)OCC1=CC=CC=C1 WWVCWLBEARZMAH-QWRGUYRKSA-N 0.000 description 2
- RNXKXUOGQKYKTH-WHFBIAKZSA-N (2s,4s)-4-methoxypyrrolidine-2-carboxylic acid Chemical compound CO[C@@H]1CN[C@H](C(O)=O)C1 RNXKXUOGQKYKTH-WHFBIAKZSA-N 0.000 description 2
- 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 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OWYXECDHFKMMRJ-UHFFFAOYSA-N CCC(Cl)=[S+]C(C)=O Chemical compound CCC(Cl)=[S+]C(C)=O OWYXECDHFKMMRJ-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
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- 159000000001 potassium salts Chemical class 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- GAPYKZAARZMMGP-UHFFFAOYSA-N pyridin-1-ium;acetate Chemical compound CC(O)=O.C1=CC=NC=C1 GAPYKZAARZMMGP-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical 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
- JREMHUJYFXNYSW-UHFFFAOYSA-N s-(2-carbonochloridoyl-3,3,3-trifluoropropyl) ethanethioate Chemical compound CC(=O)SCC(C(Cl)=O)C(F)(F)F JREMHUJYFXNYSW-UHFFFAOYSA-N 0.000 description 1
- MJZHAVYNYFDSMZ-UHFFFAOYSA-N s-(3-chloro-2-methyl-3-oxopropyl) benzenecarbothioate Chemical compound ClC(=O)C(C)CSC(=O)C1=CC=CC=C1 MJZHAVYNYFDSMZ-UHFFFAOYSA-N 0.000 description 1
- LUDPWTHDXSOXDX-UHFFFAOYSA-N s-(3-chloro-2-methyl-3-oxopropyl) ethanethioate Chemical compound ClC(=O)C(C)CSC(C)=O LUDPWTHDXSOXDX-UHFFFAOYSA-N 0.000 description 1
- IOLUCUQNAZTKMN-UHFFFAOYSA-N s-(3-chloropropyl) ethanethioate Chemical compound CC(=O)SCCCCl IOLUCUQNAZTKMN-UHFFFAOYSA-N 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- BQCADISMDOOEFD-NJFSPNSNSA-N silver-110 Chemical compound [110Ag] BQCADISMDOOEFD-NJFSPNSNSA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- XJJBXZIKXFOMLP-ZETCQYMHSA-N tert-butyl (2s)-pyrrolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCN1 XJJBXZIKXFOMLP-ZETCQYMHSA-N 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- PMMYEEVYMWASQN-IMJSIDKUSA-N trans-4-Hydroxy-L-proline Natural products O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 1
- PMMYEEVYMWASQN-IUYQGCFVSA-N trans-4-hydroxy-D-proline Chemical compound O[C@@H]1CN[C@@H](C(O)=O)C1 PMMYEEVYMWASQN-IUYQGCFVSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000003039 volatile agent 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
- C07D207/12—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
- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
-
- 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
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)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93288378A | 1978-08-11 | 1978-08-11 | |
| KR1019790002731A KR830002450B1 (ko) | 1978-08-11 | 1979-08-10 | 치환 프로린의 메르캅토아실 유도체의 제조방법 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD145749A5 true DD145749A5 (de) | 1981-01-07 |
Family
ID=26626596
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD79214896A DD145749A5 (de) | 1978-08-11 | 1979-08-09 | Verfahren zur herstellung von mercaptoacylderivaten von substituierten prolinen |
Country Status (30)
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4483861A (en) * | 1978-10-31 | 1984-11-20 | Santen Pharmaceutical Co., Ltd. | Antihypertensive sulfur-containing compounds |
| CA1132985A (en) * | 1978-12-22 | 1982-10-05 | John Krapcho | Ketal and thioketal derivatives of mercaptoacyl prolines |
| US4347371A (en) * | 1978-12-30 | 1982-08-31 | Santen Pharmaceutical Co., Ltd. | Disulfide compounds |
| US4234489A (en) * | 1979-06-25 | 1980-11-18 | E. R. Squibb & Sons, Inc. | Pyroglutamic acid derivatives and analogs |
| US4288368A (en) * | 1979-07-30 | 1981-09-08 | E. R. Squibb & Sons, Inc. | Dithioacylproline derivatives |
| US4291040A (en) * | 1979-10-22 | 1981-09-22 | E. R. Squibb & Sons, Inc. | Mercaptoacyl derivatives of 4-disubstituted prolines and 4-substituted dehydroprolines |
| US4692458A (en) * | 1980-03-05 | 1987-09-08 | University Of Miami | Anti-hypertensive agents |
| AU542211B2 (en) * | 1980-03-07 | 1985-02-14 | Gruppo Lepetit S.P.A. | Mercaptocycloalkyl carbonyl prolines |
| GB2070586A (en) * | 1980-03-21 | 1981-09-09 | Squibb & Sons Inc | Derivatives of Proline or Pipecolic Acid |
| US4284624A (en) | 1980-05-02 | 1981-08-18 | E. R. Squibb & Sons, Inc. | Mixed disulfides |
| US4390695A (en) * | 1980-06-23 | 1983-06-28 | E. R. Squibb & Sons, Inc. | Imido, amido and amino derivatives of mercaptoacyl prolines and pipecolic acids |
| US4578474A (en) * | 1980-06-23 | 1986-03-25 | E. R. Squibb & Sons, Inc. | Imido, amido and amino derivatives of mercaptoacyl prolines and pipecolic acids |
| US4316905A (en) * | 1980-07-01 | 1982-02-23 | E. R. Squibb & Sons, Inc. | Mercaptoacyl derivatives of various 4-substituted prolines |
| US4332726A (en) * | 1980-08-25 | 1982-06-01 | E. R. Squibb & Sons, Inc. | Purification of mercaptoacyl amino acids |
| US4307110A (en) * | 1980-09-12 | 1981-12-22 | E. R. Squibb & Sons, Inc. | Mercaptoacyl derivatives of 3-substituted proline derivatives |
| US4311705A (en) * | 1980-10-06 | 1982-01-19 | E. R. Squibb & Sons, Inc. | Carboxyalkanoyl and hydroxycarbamoylalkanoyl derivatives of substituted prolines |
| US4312809A (en) | 1980-10-31 | 1982-01-26 | E. R. Squibb & Sons, Inc. | Lactam derivatives of mercaptoacylamino acids |
| US4462943A (en) * | 1980-11-24 | 1984-07-31 | E. R. Squibb & Sons, Inc. | Carboxyalkyl amino acid derivatives of various substituted prolines |
| US4384123A (en) * | 1980-12-04 | 1983-05-17 | E. R. Squibb & Sons, Inc. | Phosphinylalkanoyl substituted prolines |
| US4337201A (en) * | 1980-12-04 | 1982-06-29 | E. R. Squibb & Sons, Inc. | Phosphinylalkanoyl substituted prolines |
| US4416831A (en) | 1981-04-27 | 1983-11-22 | E. R. Squibb & Sons, Inc. | Amino and substituted amino phosphinylalkanoyl compounds |
| US4374131A (en) | 1981-04-27 | 1983-02-15 | E. R. Squibb & Sons, Inc. | Amino and substituted amino phosphinyl-alkanoyl compounds |
| US4416833A (en) | 1981-05-04 | 1983-11-22 | E. R. Squibb & Sons, Inc. | Substituted carbonyl phosphinyl-alkanoyl compounds |
| US4381297A (en) | 1981-05-04 | 1983-04-26 | E. R. Squibb & Sons, Inc. | Substituted carbonyl phosphinyl-alkanoyl compounds |
| US4497953A (en) * | 1981-06-01 | 1985-02-05 | E. R. Squibb & Sons, Inc. | Imido, amido and amino derivatives of mercaptoacyl prolines and pipecolic acids |
| US4377701A (en) * | 1981-09-21 | 1983-03-22 | E. R. Squibb & Sons, Inc. | 4-Methylene-1-[[(alranoyl or arylcarbonyl)mercapto]acyl]proline and pipecolic acid |
| US4555506A (en) * | 1981-12-24 | 1985-11-26 | E. R. Squibb & Sons, Inc. | Phosphorus containing compounds and use as hypotensives |
| US4560680A (en) * | 1982-03-15 | 1985-12-24 | E. R. Squibb & Sons, Inc. | Aminoalkyl and related substituted phosphinic acid angiotensin converting enzyme inhibitors |
| US4452791A (en) * | 1982-03-15 | 1984-06-05 | E. R. Squibb & Sons, Inc. | Aminoalkyl and related substituted phosphinic acid angiotensin converting enzyme inhibitors |
| US4616005A (en) * | 1982-06-23 | 1986-10-07 | E. R. Squibb & Sons, Inc. | Phosphonyl hydroxyacyl amino acid derivatives as antihypertensives |
| US4703043A (en) * | 1982-06-23 | 1987-10-27 | E. R. Squibb & Sons, Inc. | Phosphonyl hydroxyacyl amino acid derivatives as antihypertensive |
| US4452790A (en) * | 1982-06-23 | 1984-06-05 | E. R. Squibb & Sons, Inc. | Phosphonyl hydroxyacyl amino acid derivatives as antihypertensives |
| US4567166A (en) * | 1982-07-14 | 1986-01-28 | E. R. Squibb & Sons, Inc. | Amino and substituted amino phosphinylalkanoyl compounds useful for treating hypertension |
| EP0187037A3 (en) * | 1984-12-21 | 1988-03-23 | Takeda Chemical Industries, Ltd. | Piperidine derivatives, their production and use |
| CA2021409A1 (en) * | 1989-08-21 | 1991-02-22 | Donald S. Karanewsky | Phosphonate substituted amino or imino acids useful as antihypertensives |
| JPH05344844A (ja) * | 1992-06-12 | 1993-12-27 | Suzumo Kiko Kk | 焼おむすびせんべいの製造方法 |
| EP0640594A1 (en) | 1993-08-23 | 1995-03-01 | Fujirebio Inc. | Hydantoin derivative as metalloprotease inhibitor |
| US5435286A (en) * | 1994-05-02 | 1995-07-25 | Cummins Engine Company, Inc. | Ball link assembly for vehicle engine drive trains |
| US7659305B2 (en) | 2002-10-31 | 2010-02-09 | Pfizer Inc. | Therapeutic proline derivatives |
| GB0225379D0 (en) * | 2002-10-31 | 2002-12-11 | Pfizer Ltd | Therapeutic proline derivatives |
| WO2006038119A1 (en) * | 2004-10-08 | 2006-04-13 | Warner-Lambert Company Llc | Stereoselective synthesis of n-protected alkoxy prolines |
| GB0715626D0 (en) * | 2007-08-10 | 2007-09-19 | Generics Uk Ltd | Crystalline form of zofenopril calcium |
| US8853421B2 (en) | 2008-02-27 | 2014-10-07 | Generics [Uk] Limited | Crystalline forms of zofenopril calcium |
| CN101981004B (zh) * | 2008-02-27 | 2014-09-17 | 基因里克斯(英国)有限公司 | 晶体形式 |
| SI23949A (sl) | 2011-12-19 | 2013-06-28 | Silverstone Pharma | Nove kristalne soli zofenoprila, postopek za njihovo dobivanje in njihova uporaba v terapiji |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2340092A2 (fr) * | 1976-02-09 | 1977-09-02 | Roussel Uclaf | Nouveaux derives de l'acide 3-quinoleine carboxylique, leur procede de preparation et leur application comme medicament |
| AU509899B2 (en) * | 1976-02-13 | 1980-05-29 | E.R. Squibb & Sons, Inc. | Proline derivatives and related compounds |
| US4116962A (en) * | 1976-12-03 | 1978-09-26 | E. R. Squibb & Sons, Inc. | Pyrrolidine and piperidine-2-carboxylic acid derivatives |
| US4113715A (en) * | 1977-01-17 | 1978-09-12 | E. R. Squibb & Sons, Inc. | Amino acid derivatives |
| US4108886A (en) * | 1977-03-11 | 1978-08-22 | E. R. Squibb & Sons, Inc. | Thiopropanoylamino acid derivatives |
| PH15381A (en) * | 1978-02-21 | 1982-12-17 | Squibb & Sons Inc | Halogen substituted mercaptoacylamino acids |
| US4154934A (en) * | 1978-08-11 | 1979-05-15 | E. R. Squibb & Sons, Inc. | Mercaptoacylamino derivatives of heterocyclic carboxylic acids |
-
1979
- 1979-07-16 CA CA000331877A patent/CA1144930A/en not_active Expired
- 1979-07-17 NZ NZ191036A patent/NZ191036A/en unknown
- 1979-07-18 ZA ZA00793633A patent/ZA793633B/xx unknown
- 1979-07-18 GR GR59635A patent/GR72420B/el unknown
- 1979-07-18 IN IN524/DEL/79A patent/IN152712B/en unknown
- 1979-07-24 AU AU49190/79A patent/AU530690B2/en not_active Expired
- 1979-07-30 FR FR7919590A patent/FR2435469A1/fr active Granted
- 1979-08-01 PH PH22842A patent/PH15030A/en unknown
- 1979-08-03 IT IT49954/79A patent/IT1117782B/it active Protection Beyond IP Right Term
- 1979-08-07 DE DE2932021A patent/DE2932021C2/de not_active Expired - Lifetime
- 1979-08-07 YU YU1923/79A patent/YU41876B/xx unknown
- 1979-08-08 AT AT0541679A patent/AT379589B/de not_active IP Right Cessation
- 1979-08-09 DD DD79214896A patent/DD145749A5/de not_active IP Right Cessation
- 1979-08-09 CS CS795462A patent/CS228118B2/cs unknown
- 1979-08-10 NL NL7906120A patent/NL193374C/nl active Protection Beyond IP Right Term
- 1979-08-10 FI FI792498A patent/FI69834C/fi not_active IP Right Cessation
- 1979-08-10 CH CH737579A patent/CH642064A5/de not_active IP Right Cessation
- 1979-08-10 SE SE7906722A patent/SE447477B/sv active Protection Beyond IP Right Term
- 1979-08-10 BE BE0/196688A patent/BE878191A/fr not_active IP Right Cessation
- 1979-08-10 KR KR1019790002731A patent/KR830002450B1/ko not_active Expired
- 1979-08-10 ES ES483311A patent/ES483311A1/es not_active Expired
- 1979-08-10 SU SU792800304A patent/SU1066460A3/ru active
- 1979-08-10 PT PT70049A patent/PT70049A/pt unknown
- 1979-08-10 RO RO98428A patent/RO78870B/ro unknown
- 1979-08-10 LU LU81593A patent/LU81593A1/xx active Protection Beyond IP Right Term
- 1979-08-10 GB GB7927867A patent/GB2028327B/en not_active Expired
- 1979-08-10 DK DK335879A patent/DK154553C/da not_active IP Right Cessation
- 1979-08-10 AR AR277678A patent/AR229081A1/es active
- 1979-08-10 JP JP10272279A patent/JPS5527199A/ja active Granted
- 1979-08-10 IE IE1544/79A patent/IE48802B1/en active Protection Beyond IP Right Term
-
1988
- 1988-12-21 JP JP63323204A patent/JPH01287069A/ja active Pending
-
1999
- 1999-06-04 LU LU90403C patent/LU90403I2/fr unknown
- 1999-08-04 NL NL990024C patent/NL990024I2/nl unknown
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