FI63407C - Foerfarande foer framstaellning av terapeutiskt anvaendbara 5-2-furoyl)- 5-(2-tenoyl)- 5-(3-furoyl)- och 5-(3-tenoyl)- 21,dihydro-3h-pyrrolo(1,2-a)pyrrol-1-karboxylsyraderivat - Google Patents
Foerfarande foer framstaellning av terapeutiskt anvaendbara 5-2-furoyl)- 5-(2-tenoyl)- 5-(3-furoyl)- och 5-(3-tenoyl)- 21,dihydro-3h-pyrrolo(1,2-a)pyrrol-1-karboxylsyraderivat Download PDFInfo
- Publication number
- FI63407C FI63407C FI772154A FI772154A FI63407C FI 63407 C FI63407 C FI 63407C FI 772154 A FI772154 A FI 772154A FI 772154 A FI772154 A FI 772154A FI 63407 C FI63407 C FI 63407C
- Authority
- FI
- Finland
- Prior art keywords
- pyrrolo
- pyrrole
- dihydro
- formula
- acid
- Prior art date
Links
- -1 3-FUROYL Chemical class 0.000 title claims description 82
- 230000001225 therapeutic effect Effects 0.000 title 2
- 150000001875 compounds Chemical class 0.000 claims description 74
- 239000002253 acid Substances 0.000 claims description 58
- 238000006243 chemical reaction Methods 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 33
- 238000002360 preparation method Methods 0.000 claims description 33
- 150000007513 acids Chemical class 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 231100000252 nontoxic Toxicity 0.000 claims description 9
- 230000003000 nontoxic effect Effects 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 239000011593 sulfur Chemical group 0.000 claims description 6
- 229910052717 sulfur Chemical group 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 3
- 150000001768 cations Chemical class 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 3
- WHUPVXKPBHOKTR-UHFFFAOYSA-N C1CN2C=CC=C2C1C(=O)C3=CSC=C3 Chemical compound C1CN2C=CC=C2C1C(=O)C3=CSC=C3 WHUPVXKPBHOKTR-UHFFFAOYSA-N 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- 239000000243 solution Substances 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 36
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- ISBAYGCFVXGYFW-UHFFFAOYSA-N 5-(thiophene-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylic acid Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CS1 ISBAYGCFVXGYFW-UHFFFAOYSA-N 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- FDDQRDMHICUGQC-UHFFFAOYSA-M pyrrole-1-carboxylate Chemical compound [O-]C(=O)N1C=CC=C1 FDDQRDMHICUGQC-UHFFFAOYSA-M 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 235000019439 ethyl acetate Nutrition 0.000 description 22
- FDDQRDMHICUGQC-UHFFFAOYSA-N pyrrole-1-carboxylic acid Chemical class OC(=O)N1C=CC=C1 FDDQRDMHICUGQC-UHFFFAOYSA-N 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 150000002148 esters Chemical class 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 14
- 238000010992 reflux Methods 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 229910052708 sodium Inorganic materials 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- 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 9
- 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 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 230000035935 pregnancy Effects 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical class CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 7
- 210000003754 fetus Anatomy 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 239000011591 potassium Substances 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- NMPVEAUIHMEAQP-UHFFFAOYSA-N 2-Bromoacetaldehyde Chemical compound BrCC=O NMPVEAUIHMEAQP-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000008602 contraction Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 210000002683 foot Anatomy 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- HZKXABCPABDVLS-UHFFFAOYSA-N propan-2-yl 2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OC(C)C)CCN21 HZKXABCPABDVLS-UHFFFAOYSA-N 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- VQFAIAKCILWQPZ-UHFFFAOYSA-N bromoacetone Chemical compound CC(=O)CBr VQFAIAKCILWQPZ-UHFFFAOYSA-N 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 4
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 238000000197 pyrolysis Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000001632 sodium acetate Substances 0.000 description 4
- 235000017281 sodium acetate Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-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
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical class OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 3
- ICPQARMBESXDTH-UHFFFAOYSA-N 3h-pyrrolizine-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CCN21 ICPQARMBESXDTH-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- 125000005907 alkyl ester group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 150000001805 chlorine compounds Chemical class 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
- 238000006114 decarboxylation reaction Methods 0.000 description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 159000000003 magnesium salts Chemical class 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- OKJLPZAJOCGBEJ-UHFFFAOYSA-N methyl 1-(2-hydroxyethyl)-2-(2-methoxy-2-oxoethyl)-4-methylpyrrole-3-carboxylate Chemical compound COC(=O)CC1=C(C(=O)OC)C(C)=CN1CCO OKJLPZAJOCGBEJ-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
- YLLVCPMOJDVCPF-UHFFFAOYSA-N methyl 1-(2-iodoethyl)-2-(2-methoxy-2-oxoethyl)pyrrole-3-carboxylate Chemical compound COC(=O)CC1=C(C(=O)OC)C=CN1CCI YLLVCPMOJDVCPF-UHFFFAOYSA-N 0.000 description 3
- JMOGNZPGTWZITL-UHFFFAOYSA-N methyl 2-(2-methoxy-2-oxoethyl)-1-(2-methylsulfonyloxyethyl)pyrrole-3-carboxylate Chemical compound COC(=O)CC1=C(C(=O)OC)C=CN1CCOS(C)(=O)=O JMOGNZPGTWZITL-UHFFFAOYSA-N 0.000 description 3
- GLKZDYDVSBCMAA-UHFFFAOYSA-N n,n-dimethylfuran-3-carboxamide Chemical compound CN(C)C(=O)C=1C=COC=1 GLKZDYDVSBCMAA-UHFFFAOYSA-N 0.000 description 3
- CDXVCHCOBYAVHR-UHFFFAOYSA-N n,n-dimethylthiophene-2-carboxamide Chemical compound CN(C)C(=O)C1=CC=CS1 CDXVCHCOBYAVHR-UHFFFAOYSA-N 0.000 description 3
- CMZHFIPCSRETSP-UHFFFAOYSA-N n,n-dimethylthiophene-3-carboxamide Chemical compound CN(C)C(=O)C=1C=CSC=1 CMZHFIPCSRETSP-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 208000000995 spontaneous abortion Diseases 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 229960000281 trometamol Drugs 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- YVNBPFCIKDDTSM-UHFFFAOYSA-N 2,3-dihydro-1h-pyrrolizine-1,7-dicarboxylic acid Chemical compound C1=CC(C(O)=O)=C2C(C(=O)O)CCN21 YVNBPFCIKDDTSM-UHFFFAOYSA-N 0.000 description 2
- NCQOINXMWJWQHV-UHFFFAOYSA-N 4-chloro-n,n-dimethylthiophene-2-carboxamide Chemical compound CN(C)C(=O)C1=CC(Cl)=CS1 NCQOINXMWJWQHV-UHFFFAOYSA-N 0.000 description 2
- LRSUMIDCSTUMHW-UHFFFAOYSA-N 4-chlorothiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC(Cl)=CS1 LRSUMIDCSTUMHW-UHFFFAOYSA-N 0.000 description 2
- MJZOIWGYLLMPGF-UHFFFAOYSA-N 5-(5-methylthiophene-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylic acid Chemical compound S1C(C)=CC=C1C(=O)C1=CC=C2N1CCC2C(O)=O MJZOIWGYLLMPGF-UHFFFAOYSA-N 0.000 description 2
- QXJGPMJZRCHZPM-UHFFFAOYSA-N 5-(thiophene-3-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylic acid Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C=1C=CSC=1 QXJGPMJZRCHZPM-UHFFFAOYSA-N 0.000 description 2
- 206010000234 Abortion spontaneous Diseases 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- 230000001754 anti-pyretic effect Effects 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000003637 basic solution Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000035606 childbirth Effects 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical compound NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 230000008774 maternal effect Effects 0.000 description 2
- RCYRFVQGTJTDQC-UHFFFAOYSA-N methyl 2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)CCN21 RCYRFVQGTJTDQC-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 208000015994 miscarriage Diseases 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000004118 muscle contraction Effects 0.000 description 2
- 210000000754 myometrium Anatomy 0.000 description 2
- CXBLJKFKCLWTJR-UHFFFAOYSA-N n,n-dimethylfuran-2-carboxamide Chemical compound CN(C)C(=O)C1=CC=CO1 CXBLJKFKCLWTJR-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000012074 organic phase Substances 0.000 description 2
- GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical compound O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 229960002895 phenylbutazone Drugs 0.000 description 2
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- YAFUOVLZFNFVPB-UHFFFAOYSA-N propan-2-yl 5-(thiophene-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound CC(C)OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CS1 YAFUOVLZFNFVPB-UHFFFAOYSA-N 0.000 description 2
- DFZGDMZKLKDUPD-UHFFFAOYSA-N propan-2-yl 5-(thiophene-3-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound CC(C)OC(=O)C1CCN2C1=CC=C2C(=O)C=1C=CSC=1 DFZGDMZKLKDUPD-UHFFFAOYSA-N 0.000 description 2
- ZWGGNSNXUKGCHT-UHFFFAOYSA-N propan-2-yl 6-methyl-2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound C1=C(C)C=C2C(C(=O)OC(C)C)CCN21 ZWGGNSNXUKGCHT-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000011833 salt mixture Substances 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- YTLYLLTVENPWFT-UPHRSURJSA-N (Z)-3-aminoacrylic acid Chemical compound N\C=C/C(O)=O YTLYLLTVENPWFT-UPHRSURJSA-N 0.000 description 1
- XHHPPESHFGNBLU-UHFFFAOYSA-N 1-(2-iodoethyl)pyrrole Chemical compound ICCN1C=CC=C1 XHHPPESHFGNBLU-UHFFFAOYSA-N 0.000 description 1
- NTQHXAYIETUMLC-UHFFFAOYSA-N 1-(thiophene-2-carbonyl)-2,3-dihydropyrrolizine-1-carboxylic acid Chemical compound C1(=CC=CS1)C(=O)C1(C=2N(CC1)C=CC=2)C(=O)O NTQHXAYIETUMLC-UHFFFAOYSA-N 0.000 description 1
- DMRXISNUOWIOKV-UHFFFAOYSA-N 1-bromobutan-2-ol Chemical compound CCC(O)CBr DMRXISNUOWIOKV-UHFFFAOYSA-N 0.000 description 1
- DDKNWTWTCVDWQK-UHFFFAOYSA-N 1-bromohexan-2-ol Chemical compound CCCCC(O)CBr DDKNWTWTCVDWQK-UHFFFAOYSA-N 0.000 description 1
- AMCWGHNIYLEOOO-UHFFFAOYSA-N 1-bromopentan-2-ol Chemical compound CCCC(O)CBr AMCWGHNIYLEOOO-UHFFFAOYSA-N 0.000 description 1
- CYXQJHOJIQTXLE-UHFFFAOYSA-N 2,3-dihydro-1h-pyrrolizine Chemical compound C1=CN2CCCC2=C1 CYXQJHOJIQTXLE-UHFFFAOYSA-N 0.000 description 1
- VDVJQFLGCFFFBP-UHFFFAOYSA-N 2,3-dihydropyrrole-1-carboxylic acid Chemical compound OC(=O)N1CCC=C1 VDVJQFLGCFFFBP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 1
- HGDYZULTRRRRFK-UHFFFAOYSA-N 2-bromo-2-chloroacetaldehyde Chemical compound ClC(Br)C=O HGDYZULTRRRRFK-UHFFFAOYSA-N 0.000 description 1
- QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 1
- GOIBVEITNMUDAL-UHFFFAOYSA-N 3-bromo-n,n-dimethylthiophene-2-carboxamide Chemical compound CN(C)C(=O)C=1SC=CC=1Br GOIBVEITNMUDAL-UHFFFAOYSA-N 0.000 description 1
- JCQNDRHCHGDWOM-UHFFFAOYSA-N 3-methylbutyl 5-(thiophene-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound CC(C)CCOC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CS1 JCQNDRHCHGDWOM-UHFFFAOYSA-N 0.000 description 1
- XNHOYPHTFOBZRQ-UHFFFAOYSA-N 4-bromo-n,n-dimethylfuran-2-carboxamide Chemical compound CN(C)C(=O)C1=CC(Br)=CO1 XNHOYPHTFOBZRQ-UHFFFAOYSA-N 0.000 description 1
- MFTKCVJAHGAWML-UHFFFAOYSA-N 4-chloro-n,n-dimethylfuran-2-carboxamide Chemical compound CN(C)C(=O)C1=CC(Cl)=CO1 MFTKCVJAHGAWML-UHFFFAOYSA-N 0.000 description 1
- JWQMRBBWZUKWFJ-UHFFFAOYSA-N 4-chlorothiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=CS1 JWQMRBBWZUKWFJ-UHFFFAOYSA-N 0.000 description 1
- VNOPZLYAKAXKDH-UHFFFAOYSA-N 5-(3-methylthiophene-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylic acid Chemical compound C1=CSC(C(=O)C=2N3CCC(C3=CC=2)C(O)=O)=C1C VNOPZLYAKAXKDH-UHFFFAOYSA-N 0.000 description 1
- DQFYKEZYJXMKMF-UHFFFAOYSA-N 5-(4-chlorothiophene-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylic acid Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC(Cl)=CS1 DQFYKEZYJXMKMF-UHFFFAOYSA-N 0.000 description 1
- WFNLUYMSCZSOCF-UHFFFAOYSA-N 5-(furan-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylic acid Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CO1 WFNLUYMSCZSOCF-UHFFFAOYSA-N 0.000 description 1
- HJGYPFYQWFQPBY-UHFFFAOYSA-N 5-(furan-3-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylic acid Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C=1C=COC=1 HJGYPFYQWFQPBY-UHFFFAOYSA-N 0.000 description 1
- YCJKKQRKIVZSLB-UHFFFAOYSA-N 5-bromo-n,n-dimethylfuran-2-carboxamide Chemical compound CN(C)C(=O)C1=CC=C(Br)O1 YCJKKQRKIVZSLB-UHFFFAOYSA-N 0.000 description 1
- MTJOLAGVIMFWPP-UHFFFAOYSA-N 5-bromo-n,n-dimethylthiophene-2-carboxamide Chemical compound CN(C)C(=O)C1=CC=C(Br)S1 MTJOLAGVIMFWPP-UHFFFAOYSA-N 0.000 description 1
- LMDCNPJBIXSFBE-UHFFFAOYSA-N 5-chloro-n,n-dimethylfuran-2-carboxamide Chemical compound CN(C)C(=O)C1=CC=C(Cl)O1 LMDCNPJBIXSFBE-UHFFFAOYSA-N 0.000 description 1
- CDISMUAEFLKTDV-UHFFFAOYSA-N 5-chloro-n,n-dimethylthiophene-2-carboxamide Chemical compound CN(C)C(=O)C1=CC=C(Cl)S1 CDISMUAEFLKTDV-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- WFBWJDVKCZZAPQ-UHFFFAOYSA-N 6-methyl-5-(thiophene-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylic acid Chemical compound CC=1C=C2C(C(O)=O)CCN2C=1C(=O)C1=CC=CS1 WFBWJDVKCZZAPQ-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- HMLZDEGMPMIKJG-UHFFFAOYSA-N C1(=CC=CS1)C(=O)C1=CC=C2N1CCC2C(=O)OCCCCCCCCCCCC Chemical compound C1(=CC=CS1)C(=O)C1=CC=C2N1CCC2C(=O)OCCCCCCCCCCCC HMLZDEGMPMIKJG-UHFFFAOYSA-N 0.000 description 1
- SMGFULOUGIVADP-UHFFFAOYSA-N CCC(CN1C2=CC=C1C(C1=CC=CS1)=O)C2=O Chemical compound CCC(CN1C2=CC=C1C(C1=CC=CS1)=O)C2=O SMGFULOUGIVADP-UHFFFAOYSA-N 0.000 description 1
- 101100421745 Caenorhabditis elegans sms-1 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- JJLJMEJHUUYSSY-UHFFFAOYSA-L Copper hydroxide Chemical compound [OH-].[OH-].[Cu+2] JJLJMEJHUUYSSY-UHFFFAOYSA-L 0.000 description 1
- 239000005750 Copper hydroxide Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699667 Mus spretus Species 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 208000005107 Premature Birth Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000036029 Uterine contractions during pregnancy Diseases 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 231100000460 acute oral toxicity Toxicity 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- TUBOMBAGCVMRNV-UHFFFAOYSA-L calcium;5-(thiophene-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound [Ca+2].[O-]C(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CS1.[O-]C(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CS1 TUBOMBAGCVMRNV-UHFFFAOYSA-L 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910001956 copper hydroxide Inorganic materials 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000000911 decarboxylating effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- DZIUBZBUCNXSDD-UHFFFAOYSA-N dimethyl 2,3-dihydro-1h-pyrrolizine-1,7-dicarboxylate Chemical compound C1=CC(C(=O)OC)=C2C(C(=O)OC)CCN21 DZIUBZBUCNXSDD-UHFFFAOYSA-N 0.000 description 1
- CEALXSHFPPCRNM-UHFFFAOYSA-L disodium;carboxylato carbonate Chemical class [Na+].[Na+].[O-]C(=O)OC([O-])=O CEALXSHFPPCRNM-UHFFFAOYSA-L 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960004887 ferric hydroxide Drugs 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- QNVRIHYSUZMSGM-UHFFFAOYSA-N hexan-2-ol Chemical compound CCCCC(C)O QNVRIHYSUZMSGM-UHFFFAOYSA-N 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
- 210000000548 hind-foot Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 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
- BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 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
- 229960003646 lysine Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate 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
- SVBNALVVXYMENY-UHFFFAOYSA-L magnesium;5-(thiophene-2-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound [Mg+2].[O-]C(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CS1.[O-]C(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CS1 SVBNALVVXYMENY-UHFFFAOYSA-L 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- OZXMKUVSMKQTLY-UHFFFAOYSA-N methyl 1-(2-hydroxyethyl)-2-methylpyrrole-3-carboxylate Chemical compound CC=1N(C=CC=1C(=O)OC)CCO OZXMKUVSMKQTLY-UHFFFAOYSA-N 0.000 description 1
- JIPKLZVKWCJYEX-UHFFFAOYSA-N methyl 2-(1h-pyrrol-2-yl)acetate Chemical compound COC(=O)CC1=CC=CN1 JIPKLZVKWCJYEX-UHFFFAOYSA-N 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- ALCVSGCMWIKVCT-UHFFFAOYSA-N n,n,3-trimethylfuran-2-carboxamide Chemical compound CN(C)C(=O)C=1OC=CC=1C ALCVSGCMWIKVCT-UHFFFAOYSA-N 0.000 description 1
- WMXONGPBIYYCSH-UHFFFAOYSA-N n,n,3-trimethylthiophene-2-carboxamide Chemical compound CN(C)C(=O)C=1SC=CC=1C WMXONGPBIYYCSH-UHFFFAOYSA-N 0.000 description 1
- SVGCDOPLALFUBU-UHFFFAOYSA-N n,n,4-trimethylfuran-2-carboxamide Chemical compound CN(C)C(=O)C1=CC(C)=CO1 SVGCDOPLALFUBU-UHFFFAOYSA-N 0.000 description 1
- ACLYTWUEWCFTCV-UHFFFAOYSA-N n,n,4-trimethylthiophene-2-carboxamide Chemical compound CN(C)C(=O)C1=CC(C)=CS1 ACLYTWUEWCFTCV-UHFFFAOYSA-N 0.000 description 1
- RBRPPMKUMKRPET-UHFFFAOYSA-N n,n,5-trimethylthiophene-2-carboxamide Chemical compound CN(C)C(=O)C1=CC=C(C)S1 RBRPPMKUMKRPET-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- OSFGNZOUZOPXBL-UHFFFAOYSA-N nitric acid;trihydrate Chemical compound O.O.O.O[N+]([O-])=O OSFGNZOUZOPXBL-UHFFFAOYSA-N 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
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002265 prevention Effects 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
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940043274 prophylactic drug Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000000050 smooth muscle relaxant Substances 0.000 description 1
- GSVXBWAZMYSUAR-UHFFFAOYSA-M sodium;5-(furan-3-carbonyl)-2,3-dihydro-1h-pyrrolizine-1-carboxylate Chemical compound [Na+].[O-]C(=O)C1CCN2C1=CC=C2C(=O)C=1C=COC=1 GSVXBWAZMYSUAR-UHFFFAOYSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- 125000001874 trioxidanyl group Chemical group [*]OOO[H] 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
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/38—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)
- Health & Medical Sciences (AREA)
- Organic Chemistry (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)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US70485776A | 1976-07-14 | 1976-07-14 | |
| US70485776 | 1976-07-14 | ||
| US05/771,283 US4087539A (en) | 1976-07-14 | 1977-02-23 | 5-(2-Furoyl)-, 5-(2-thenoyl)-, 5-(3-furoyl)- and 5-(3-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid derivatives and process for the production thereof |
| US77128377 | 1977-02-23 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI772154A7 FI772154A7 (enrdf_load_stackoverflow) | 1978-01-15 |
| FI63407B FI63407B (fi) | 1983-02-28 |
| FI63407C true FI63407C (fi) | 1983-06-10 |
Family
ID=27107392
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI772154A FI63407C (fi) | 1976-07-14 | 1977-07-11 | Foerfarande foer framstaellning av terapeutiskt anvaendbara 5-2-furoyl)- 5-(2-tenoyl)- 5-(3-furoyl)- och 5-(3-tenoyl)- 21,dihydro-3h-pyrrolo(1,2-a)pyrrol-1-karboxylsyraderivat |
Country Status (26)
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4097579A (en) * | 1977-03-31 | 1978-06-27 | Syntex (U.S.A.) Inc. | 5-(2-Pyrroyl)-1,2-dihydro-3H-pyrrolo 1,2-a!pyrrole-1-carboxylic acid derivatives and process for the production thereof |
| US4140698A (en) * | 1977-07-25 | 1979-02-20 | Syntex (Usa) Inc. | 1,2-Dihydro-3H-pyrrolo[1,2-a]pyrrole-1-nitriles |
| 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 |
| 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 |
| 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 |
| 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 |
-
1977
- 1977-05-17 JP JP5697877A patent/JPS539789A/ja active Granted
- 1977-07-07 GR GR53906A patent/GR61607B/el unknown
- 1977-07-07 AR AR268357A patent/AR218631A1/es active
- 1977-07-07 DK DK307677A patent/DK152652C/da not_active IP Right Cessation
- 1977-07-08 NL NL7707652A patent/NL7707652A/xx not_active Application Discontinuation
- 1977-07-08 PT PT66779A patent/PT66779B/pt unknown
- 1977-07-08 CH CH4005/84A patent/CH651045A5/de not_active IP Right Cessation
- 1977-07-08 IE IE1422/77A patent/IE45302B1/en unknown
- 1977-07-08 IL IL52492A patent/IL52492A/xx unknown
- 1977-07-08 CH CH848877A patent/CH644861A5/de not_active IP Right Cessation
- 1977-07-11 NZ NZ184611A patent/NZ184611A/xx unknown
- 1977-07-11 GB GB28923/77A patent/GB1554076A/en not_active Expired
- 1977-07-11 FI FI772154A patent/FI63407C/fi not_active IP Right Cessation
- 1977-07-12 CS CS774647A patent/CS208724B2/cs unknown
- 1977-07-12 CA CA282,600A patent/CA1100140A/en not_active Expired
- 1977-07-12 FR FR7721559A patent/FR2361396A1/fr active Granted
- 1977-07-13 SE SE7708142A patent/SE434644B/xx not_active IP Right Cessation
- 1977-07-13 ES ES460705A patent/ES460705A1/es not_active Expired
- 1977-07-13 IT IT68631/77A patent/IT1117314B/it active
- 1977-07-13 AU AU26976/77A patent/AU513385B2/en not_active Expired
- 1977-07-13 NO NO772493A patent/NO147563C/no unknown
- 1977-07-13 PL PL1977199602A patent/PL111408B1/pl unknown
- 1977-07-13 SU SU772504151A patent/SU664566A3/ru active
- 1977-07-13 DE DE19772731662 patent/DE2731662A1/de active Granted
- 1977-12-29 SU SU772558960A patent/SU793400A3/ru active
-
1978
- 1978-05-24 ES ES470213A patent/ES470213A1/es not_active Expired
-
1981
- 1981-04-30 HK HK175/81A patent/HK17581A/xx unknown
- 1981-12-30 MY MY371/81A patent/MY8100371A/xx unknown
-
1983
- 1983-02-28 YU YU475/83A patent/YU43156B/xx unknown
- 1983-02-28 YU YU476/83A patent/YU43157B/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4087539A (en) | 5-(2-Furoyl)-, 5-(2-thenoyl)-, 5-(3-furoyl)- and 5-(3-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid derivatives and process for the production thereof | |
| JPS6254792B2 (enrdf_load_stackoverflow) | ||
| NO874834L (no) | Fremgangsmaate for fremstilling av terapeutisk aktive tienopyridinoner. | |
| SU1217260A3 (ru) | Способ получени 6-хлор/или бром/-1,2-дигидро-3 @ -пирроло/1,2- @ / пиррол-1-карбоновых кислот или их фармацевтически приемлемых солей | |
| FI63406C (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara 5-entsoyl-1,2-dihydro-3h-pyrrolo(1,2-a)pyrrol-1-karboxylsyr adrivat | |
| FI63407C (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara 5-2-furoyl)- 5-(2-tenoyl)- 5-(3-furoyl)- och 5-(3-tenoyl)- 21,dihydro-3h-pyrrolo(1,2-a)pyrrol-1-karboxylsyraderivat | |
| PL145196B1 (en) | Method of obtaining novel 2-ketoindolo-1-carbonamides | |
| PL103100B1 (pl) | Sposob wytwarzania nowych acyloaminopochodnych piecioczlonowych zwiazkow heterocyklicznych | |
| AU619896B2 (en) | Novel substituted thienopyrans as antihypertensive agents | |
| EP0114632B1 (en) | 5-(4-vinyl- or 4-ethynylbenzoyl)-1,2-dihydro-3h-pyrrolo-(1,2-a)-pyrrole-1-carboxylic acids and derivatives thereof | |
| Chakrabarti et al. | 5-Acyl-3-substituted benzofuran-2 (3H)-ones as potential antiinflammatory agents | |
| AU2009251195A1 (en) | Production of chirally pure alpha-amino acids and n-sulfonyl alpha-amino acids | |
| L Khokra et al. | Rational Design and Synthesis of Biologically Active Disubstituted 2 (3H) Furanones and Pyrrolone Derivatives as Potent and Safer Non Steroidal Anti-inflammatory Agents | |
| JP3878128B2 (ja) | チエノピロリジノン | |
| EP0011282B1 (de) | Thienylbenzoesäurederivate, Verfahren zu ihrer Herstellung und pharmazeutische Präparate auf Basis dieser Verbindungen | |
| CS255887B2 (en) | Process for preparing derivatives of 5,6-dihydro-4h-cyclopent/b/-6-thiophene | |
| US5015656A (en) | Organic compounds and their use as pharmaceuticals | |
| IE60102B1 (en) | New derivatives of 1-styrenesulphonyl-2-oxo-5-hydroxy pyrrolidine, the process and the intermediates for their preparation, their application as medicaments and the compositions containing them | |
| DK152653B (da) | Analogifremgangsmaade til fremstilling af (dl)-eller (l)-5-(2-furoyl)-, 5-(2-thenoyl)-, 5-(3-furoyl)- eller 5-(3-thenoyl)-1,2-dihydro-3h-pyrrolooe1,2-aaapyrrol-1-carboxylsyreestere eller salte | |
| FR2488257A1 (fr) | Derives de benzazepine et leur utilisation en pharmacie | |
| GB2320715A (en) | Derivatives of Carboxyalkyl Azulenes and Azulene-1-Carboxylic Acid | |
| CH644862A5 (en) | 5-(2- and 3-furoyl)- and 5-(2- and 3-thenoyl)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and their salts and esters | |
| DK151336B (da) | Analogifremgangsmaade til fremstilling af en (dl)- eller (l)-5-benzoyl-1,2-dihydro-3h-pyrrol(1,2-a)pyrrol-1-carboxylsyre | |
| MXPA00009418A (en) | PYRROLO[1,2-a]PYRAZINE sPLA2 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: SYNTEX (U.S.A.) INC. |