SE436648B - Analogiforfarande for framstellning av 5-(2-pyrroyl)-1,2-dihydro-3h-pyrrolo/1,2-a/pyrrol-1-karbonsyraderivat - Google Patents
Analogiforfarande for framstellning av 5-(2-pyrroyl)-1,2-dihydro-3h-pyrrolo/1,2-a/pyrrol-1-karbonsyraderivatInfo
- Publication number
- SE436648B SE436648B SE7803549A SE7803549A SE436648B SE 436648 B SE436648 B SE 436648B SE 7803549 A SE7803549 A SE 7803549A SE 7803549 A SE7803549 A SE 7803549A SE 436648 B SE436648 B SE 436648B
- Authority
- SE
- Sweden
- Prior art keywords
- formula
- methyl
- solution
- dihydro
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 27
- 238000002360 preparation method Methods 0.000 title claims description 8
- -1 2-PYRROYL Chemical class 0.000 title description 37
- 150000001875 compounds Chemical class 0.000 claims description 69
- 239000002253 acid Substances 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 33
- 231100000252 nontoxic Toxicity 0.000 claims description 22
- 230000003000 nontoxic effect Effects 0.000 claims description 22
- 150000002148 esters Chemical class 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 5
- 150000007513 acids Chemical class 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 150000001735 carboxylic acids Chemical group 0.000 claims 1
- 239000000243 solution Substances 0.000 description 67
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000000203 mixture Substances 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 238000010992 reflux Methods 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 239000002904 solvent Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 230000035935 pregnancy Effects 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- RNJOKCPFLQMDEC-UHFFFAOYSA-N 4(R),8-dimethyl-trans-2-nonenoyl-CoA Chemical compound COC(=O)CC(=O)CC(=O)OC RNJOKCPFLQMDEC-UHFFFAOYSA-N 0.000 description 7
- CWQMWCYKYMHGHX-UHFFFAOYSA-N 5-(1-methylpyrrole-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylic acid Chemical compound CN1C=CC=C1C(=O)C1=CC=C2N1CCC2C(O)=O CWQMWCYKYMHGHX-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000012384 transportation and delivery Methods 0.000 description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 6
- 210000003754 fetus Anatomy 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000000725 suspension Substances 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 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000012300 argon atmosphere Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 230000008602 contraction Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000001632 sodium acetate Substances 0.000 description 5
- 235000017281 sodium acetate Nutrition 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- NMPVEAUIHMEAQP-UHFFFAOYSA-N 2-Bromoacetaldehyde Chemical compound BrCC=O NMPVEAUIHMEAQP-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 125000005907 alkyl ester group Chemical group 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000006114 decarboxylation reaction Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 229960004592 isopropanol Drugs 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 230000036407 pain Effects 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 3
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 235000010210 aluminium Nutrition 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 229960001948 caffeine Drugs 0.000 description 3
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 3
- 229960001231 choline Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 230000027950 fever generation Effects 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 3
- 239000001095 magnesium carbonate Substances 0.000 description 3
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- ASPZPNMMJSPPJA-UHFFFAOYSA-N methyl 1-(2-hydroxyethyl)-2-(2-methoxy-2-oxoethyl)pyrrole-3-carboxylate Chemical compound COC(=O)CC1=C(C(=O)OC)C=CN1CCO ASPZPNMMJSPPJA-UHFFFAOYSA-N 0.000 description 3
- GNBBNKMUZPMMTA-UHFFFAOYSA-N n,n,1-trimethylpyrrole-2-carboxamide Chemical compound CN(C)C(=O)C1=CC=CN1C GNBBNKMUZPMMTA-UHFFFAOYSA-N 0.000 description 3
- VZRWJMZZHDOBIO-UHFFFAOYSA-N n,n-dimethyl-1h-pyrrole-2-carboxamide Chemical compound CN(C)C(=O)C1=CC=CN1 VZRWJMZZHDOBIO-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 238000000197 pyrolysis Methods 0.000 description 3
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical class OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- IIYSNNBEZBAQCQ-UHFFFAOYSA-N 1-butylpyrrole Chemical compound CCCCN1C=CC=C1 IIYSNNBEZBAQCQ-UHFFFAOYSA-N 0.000 description 2
- KDYMOUGNHJDZKT-UHFFFAOYSA-N 1-butylpyrrole-2-carboxylic acid Chemical compound CCCCN1C=CC=C1C(O)=O KDYMOUGNHJDZKT-UHFFFAOYSA-N 0.000 description 2
- MFGOZCIHXVFZBC-UHFFFAOYSA-N 1-propylpyrrole Chemical compound CCCN1C=CC=C1 MFGOZCIHXVFZBC-UHFFFAOYSA-N 0.000 description 2
- UZNOGUIVJCIQGE-UHFFFAOYSA-N 1-propylpyrrole-2-carboxylic acid Chemical compound CCCN1C=CC=C1C(O)=O UZNOGUIVJCIQGE-UHFFFAOYSA-N 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 2
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 2
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- 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 2
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical compound NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960004887 ferric hydroxide Drugs 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 239000011874 heated mixture Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- IEECXTSVVFWGSE-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Fe+3] IEECXTSVVFWGSE-UHFFFAOYSA-M 0.000 description 1
- 229910021506 iron(II) hydroxide Inorganic materials 0.000 description 1
- NCNCGGDMXMBVIA-UHFFFAOYSA-L iron(ii) hydroxide Chemical compound [OH-].[OH-].[Fe+2] NCNCGGDMXMBVIA-UHFFFAOYSA-L 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 150000002696 manganese Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- LZFIVDPHDIVOQF-UHFFFAOYSA-N methoxycarbonyl 2-(1H-pyrrol-2-yl)acetate Chemical compound C(=O)(OC)OC(CC=1NC=CC=1)=O LZFIVDPHDIVOQF-UHFFFAOYSA-N 0.000 description 1
- GMKSAIRBTVHGTF-UHFFFAOYSA-N methyl 1-(2-iodoethyl)-2-(2-methoxy-2-oxoethyl)-4-methylpyrrole-3-carboxylate Chemical compound COC(=O)CC1=C(C(=O)OC)C(C)=CN1CCI GMKSAIRBTVHGTF-UHFFFAOYSA-N 0.000 description 1
- DGIZMTRZVXQPGD-UHFFFAOYSA-N methyl 6-methyl-5-(1-methylpyrrole-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound COC(=O)C1CCN2C1=CC(C)=C2C(=O)C1=CC=CN1C DGIZMTRZVXQPGD-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 208000015994 miscarriage Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 210000002346 musculoskeletal system Anatomy 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 208000028173 post-traumatic stress disease Diseases 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
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- MOVMVQUDAAYLKA-UHFFFAOYSA-M potassium;5-(1-methylpyrrole-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound [K+].CN1C=CC=C1C(=O)C1=CC=C2N1CCC2C([O-])=O MOVMVQUDAAYLKA-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 208000026440 premature labor Diseases 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- QULKCUSWGSMLGU-UHFFFAOYSA-N propan-2-yl 5-(1-methylpyrrole-2-carbonyl)-2,3-dihydro-1H-pyrrolizine-1-carboxylate Chemical compound CC(C)OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CN1C QULKCUSWGSMLGU-UHFFFAOYSA-N 0.000 description 1
- JXEXPGZXUIDUHB-UHFFFAOYSA-N propan-2-yl 6-methyl-5-(1-methylpyrrole-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound CC(C)OC(=O)C1CCN2C1=CC(C)=C2C(=O)C1=CC=CN1C JXEXPGZXUIDUHB-UHFFFAOYSA-N 0.000 description 1
- 229940043274 prophylactic drug Drugs 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- FDDQRDMHICUGQC-UHFFFAOYSA-M pyrrole-1-carboxylate Chemical compound [O-]C(=O)N1C=CC=C1 FDDQRDMHICUGQC-UHFFFAOYSA-M 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 210000004357 third molar Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- OBROYCQXICMORW-UHFFFAOYSA-N tripropoxyalumane Chemical compound [Al+3].CCC[O-].CCC[O-].CCC[O-] OBROYCQXICMORW-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/34—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 two 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/783,090 US4097579A (en) | 1977-03-31 | 1977-03-31 | 5-(2-Pyrroyl)-1,2-dihydro-3H-pyrrolo 1,2-a!pyrrole-1-carboxylic acid derivatives and process for the production thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE7803549L SE7803549L (sv) | 1978-10-01 |
| SE436648B true SE436648B (sv) | 1985-01-14 |
Family
ID=25128138
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE7803549A SE436648B (sv) | 1977-03-31 | 1978-03-29 | Analogiforfarande for framstellning av 5-(2-pyrroyl)-1,2-dihydro-3h-pyrrolo/1,2-a/pyrrol-1-karbonsyraderivat |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US4097579A (de) |
| JP (1) | JPS53121792A (de) |
| AU (1) | AU518169B2 (de) |
| BE (1) | BE865247A (de) |
| CA (1) | CA1113938A (de) |
| DE (1) | DE2813373A1 (de) |
| ES (2) | ES468267A1 (de) |
| FR (1) | FR2385719A1 (de) |
| GB (1) | GB1581411A (de) |
| IE (1) | IE46506B1 (de) |
| IT (1) | IT1107833B (de) |
| NL (1) | NL7803378A (de) |
| NZ (1) | NZ186797A (de) |
| SE (1) | SE436648B (de) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4140698A (en) * | 1977-07-25 | 1979-02-20 | Syntex (Usa) Inc. | 1,2-Dihydro-3H-pyrrolo[1,2-a]pyrrole-1-nitriles |
| US4232038A (en) * | 1979-08-31 | 1980-11-04 | Syntex (U.S.A.) Inc. | 5-Alkylsulfinylbenzoyl- and 5-alkylsulfonylbenzoyl-1,2-dihydro-3H-pyrrolo[1,]pyrrole-1-carboxylic acids |
| US4344943A (en) * | 1980-06-09 | 1982-08-17 | Syntex (U.S.A.) Inc. | 6-Chloro- or 6-bromo-1,2-dihydro-3H-pyrrolo[1,2-a]-pyrrole-1-carboxylic acids and derivatives thereof |
| US4456759A (en) * | 1980-10-20 | 1984-06-26 | Syntex (U.S.A.) Inc. | 5-Benzoyl-7-halo-1,2-dihydro-3H-pyrrolo-[1,2-a]pyrrole-1,1-dicarboxylic acids and esters thereof |
| US4353829A (en) * | 1980-11-21 | 1982-10-12 | Syntex (U.S.A.) Inc. | Process for 5-aroylation of 1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic esters |
| US4434175A (en) | 1981-08-10 | 1984-02-28 | Merck & Co., Inc. | Nonsteroidal compounds as anti-inflammatory and analgesic agents |
| WO1983001382A1 (en) * | 1981-10-13 | 1983-04-28 | Mroszczak, Edward | Gastrointestinal sparing thioester pro-drugs |
| DE3368416D1 (en) * | 1982-02-25 | 1987-01-29 | Beecham Group Plc | Aroyl pyrrolizine compounds, process for their preparation and pharmaceutical compositions containing them |
| US4457941A (en) * | 1982-03-22 | 1984-07-03 | Syntex (U.S.A.) Inc. | Use of pyrrolo-pyrrole in treating microvascular diseases associated with diabetes |
| US4454151A (en) * | 1982-03-22 | 1984-06-12 | Syntex (U.S.A.) Inc. | Use of pyrrolo pyrroles in treatment of ophthalmic diseases |
| US4612325A (en) * | 1982-06-08 | 1986-09-16 | Syntex (U.S.A) Inc. | 5-Aroyl-6-alkylthio-1,2-dihydro-3H-pyrrolo(1,2-A)pyrrole-1-carboxylic acids and use thereof as analgesics and anti-inflammatories |
| US4511724A (en) * | 1982-06-10 | 1985-04-16 | Merck & Co., Inc. | 5-(Pyrrol-2-oyl)-1,2-dihydro-3H-pyrrolo [1,2-a]pyrrole derivatives as anti-inflammatory and analgesic agents |
| JPS5910589A (ja) * | 1982-06-10 | 1984-01-20 | メルク エンド カムパニー インコーポレーテツド | 抗炎症剤および鎮痛剤として新規な５−（ピロ−ル−２−オイル）−１，２−ジヒドロ−３Ｈ−ピロロ〔１，２−ａ〕ピロ−ル誘導体 |
| US4533671A (en) * | 1982-10-08 | 1985-08-06 | Merck & Co., Inc. | 5-(2,3-Dihydro-1H-pyrrolizin-5-oyl)-2-alkanoic or carboxylic acids and analogs as anti-inflammatory and analgesic agents |
| US4536512A (en) * | 1982-10-08 | 1985-08-20 | Merck & Co., Inc. | 5-(2,3-Dihydro-1H-pyrrolizin-5-oyl)-2,3-dihydro-1H-pyrrolizine-1-alkanoic or carboxylic acids and use thereof as anti-inflammatory and analgesic agents |
| EP0117675B1 (de) * | 1983-02-19 | 1986-07-23 | Beecham Group Plc | Benzofuran- und Benzothiophencarbonsäurederivate |
| US4622407A (en) * | 1984-04-26 | 1986-11-11 | Merck & Co., Inc. | Resolution of racemic derivatives of 5-(1-methyl-5-methylthiopyrrol-2-oyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-2-carboxylic acid and analogs |
| US4988822A (en) * | 1986-05-29 | 1991-01-29 | Syntex (U.S.A.) Inc. | Intermediates for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo(1,2-A)pyrrole-1,1-dicarboxylates |
| US4873340A (en) * | 1986-05-29 | 1989-10-10 | Syntex (U.S.A.) Inc. | Process for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo[1,2-A]pyrrole-1,1-dicarboxylates |
| US4874872A (en) * | 1987-01-14 | 1989-10-17 | Syntex (U.S.A.) Inc. | Process for preparing (+)-2,3-dihydro-1H-pyrrolo[1,2-A]pyrrole-1,7-dicarboxylates |
| HU198927B (en) * | 1987-01-14 | 1989-12-28 | Richter Gedeon Vegyeszet | Process for producing 1-/substituted aminomethyl/-octa-hydroindolo-(2,3-a)quinolizine derivatives, pharmaceutically applicable acid addition salts thereof, as well as pharmaceutical compositions comprising same |
| US4835288A (en) * | 1987-01-14 | 1989-05-30 | Syntex Inc. | Process for preparing (+)-2,3-dihydro-1H-pyrrolo[1,2-a]pyrrole-1,7-dicarboxylates |
| US4849526A (en) * | 1987-01-14 | 1989-07-18 | Syntex (U.S.A.) Inc. | Process for preparing (±)-2,3-dihydro-1H-pyrrolo[1,2-A]pyrrole-1,7-dicarboxylates |
| US4874871A (en) * | 1987-03-25 | 1989-10-17 | Syntex (U.S.A.) Inc. | Process for preparing (+)-2,3-Dihydro-1H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid and related compounds |
| US5110493A (en) * | 1987-09-11 | 1992-05-05 | Syntex (U.S.A.) Inc. | Ophthalmic NSAID formulations containing a quaternary ammonium preservative and a nonionic surfactant |
| US5414011A (en) * | 1987-09-11 | 1995-05-09 | Syntex (U.S.A.) Inc. | Preservative system for ophthalmic formulations |
| AU7255394A (en) * | 1993-07-08 | 1995-02-06 | Cygnus Therapeutic Systems | Monolithic matrix transdermal delivery system |
| US5621115A (en) * | 1996-02-21 | 1997-04-15 | Ohmeda Pharmaceutical Products Division Inc. | Methods for preparing 5-aroyl-1,2-dihydro-3H-pyrrolo-[1,2-A]pyrrole-1-carboxylic acids |
| US6191285B1 (en) | 1997-07-03 | 2001-02-20 | Abbott Laboratories | Process for the preparation of ketorolac tromethamine |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL293572A (de) * | 1962-06-07 | |||
| US3846447A (en) * | 1972-08-03 | 1974-11-05 | Mcneilab Inc | Preparation of 5-aroyl-pyrroles and intermediates therefor |
| JPS539789A (en) * | 1976-07-14 | 1978-01-28 | Syntex Inc | Production of 55*22floyl** * 55*22thenoyl** * 55*33 floyl** and 55*33thenoyl** 1*22dihydroo3hhpyroro * 1*22a*pyrolee11carboxylic acid derivative |
-
1977
- 1977-03-31 US US05/783,090 patent/US4097579A/en not_active Expired - Lifetime
-
1978
- 1978-03-23 BE BE186219A patent/BE865247A/xx not_active IP Right Cessation
- 1978-03-27 ES ES468267A patent/ES468267A1/es not_active Expired
- 1978-03-28 GB GB12084/78A patent/GB1581411A/en not_active Expired
- 1978-03-28 DE DE19782813373 patent/DE2813373A1/de active Granted
- 1978-03-29 NZ NZ186797A patent/NZ186797A/xx unknown
- 1978-03-29 CA CA299,870A patent/CA1113938A/en not_active Expired
- 1978-03-29 SE SE7803549A patent/SE436648B/sv not_active IP Right Cessation
- 1978-03-29 IE IE605/78A patent/IE46506B1/en unknown
- 1978-03-30 JP JP3616678A patent/JPS53121792A/ja active Granted
- 1978-03-30 AU AU34611/78A patent/AU518169B2/en not_active Expired
- 1978-03-30 NL NL7803378A patent/NL7803378A/xx not_active Application Discontinuation
- 1978-03-30 FR FR7809294A patent/FR2385719A1/fr active Granted
- 1978-03-30 IT IT67706/78A patent/IT1107833B/it active
-
1979
- 1979-01-02 ES ES476535A patent/ES476535A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| SE7803549L (sv) | 1978-10-01 |
| FR2385719B1 (de) | 1980-07-18 |
| IT7867706A0 (it) | 1978-03-30 |
| IE46506B1 (en) | 1983-06-29 |
| JPS53121792A (en) | 1978-10-24 |
| NZ186797A (en) | 1979-12-11 |
| CA1113938A (en) | 1981-12-08 |
| DE2813373A1 (de) | 1978-10-05 |
| FR2385719A1 (fr) | 1978-10-27 |
| ES468267A1 (es) | 1979-10-01 |
| IE780605L (en) | 1978-09-30 |
| AU518169B2 (en) | 1981-09-17 |
| ES476535A1 (es) | 1979-12-01 |
| IT1107833B (it) | 1985-12-02 |
| AU3461178A (en) | 1979-10-04 |
| US4097579A (en) | 1978-06-27 |
| JPS647997B2 (de) | 1989-02-10 |
| DE2813373C2 (de) | 1989-11-09 |
| GB1581411A (en) | 1980-12-10 |
| NL7803378A (nl) | 1978-10-03 |
| BE865247A (fr) | 1978-09-25 |
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