FR2498183A1 - Nouveaux derives d'acides guanidinocyclohexanecarboxyliques, leur procede de preparation et leur application en therapeutique - Google Patents
Nouveaux derives d'acides guanidinocyclohexanecarboxyliques, leur procede de preparation et leur application en therapeutique Download PDFInfo
- Publication number
- FR2498183A1 FR2498183A1 FR8201032A FR8201032A FR2498183A1 FR 2498183 A1 FR2498183 A1 FR 2498183A1 FR 8201032 A FR8201032 A FR 8201032A FR 8201032 A FR8201032 A FR 8201032A FR 2498183 A1 FR2498183 A1 FR 2498183A1
- Authority
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- France
- Prior art keywords
- acid
- trans
- mixture
- derivative
- halogen atom
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- KGJCJJUTABSQOH-UHFFFAOYSA-N 1-(diaminomethylideneamino)cyclohexane-1-carboxylic acid Chemical class NC(=N)NC1(C(O)=O)CCCCC1 KGJCJJUTABSQOH-UHFFFAOYSA-N 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title claims description 10
- 230000001225 therapeutic effect Effects 0.000 title description 2
- -1 INDANYL Chemical class 0.000 claims abstract description 37
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical class F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims description 62
- 125000005843 halogen group Chemical group 0.000 claims description 13
- JBRMEFWJFBHUKG-UHFFFAOYSA-N 4-[(diaminomethylideneamino)methyl]cyclohexane-1-carboxylic acid Chemical compound NC(N)=NCC1CCC(C(O)=O)CC1 JBRMEFWJFBHUKG-UHFFFAOYSA-N 0.000 claims description 9
- QCVUPSYRZFNUBN-MEZFUOHNSA-N Cl.NC(=N)NC[C@H]1CC[C@H](C(O)=O)CC1 Chemical compound Cl.NC(=N)NC[C@H]1CC[C@H](C(O)=O)CC1 QCVUPSYRZFNUBN-MEZFUOHNSA-N 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 102000012479 Serine Proteases Human genes 0.000 claims description 6
- 108010022999 Serine Proteases Proteins 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 230000003266 anti-allergic effect Effects 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 208000006673 asthma Diseases 0.000 abstract description 6
- 229910052736 halogen Inorganic materials 0.000 abstract description 5
- 150000002367 halogens Chemical class 0.000 abstract description 5
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical class C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 abstract 1
- 230000007815 allergy Effects 0.000 abstract 1
- KHUXNRRPPZOJPT-UHFFFAOYSA-N phenoxy radical Chemical class O=C1C=C[CH]C=C1 KHUXNRRPPZOJPT-UHFFFAOYSA-N 0.000 abstract 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 79
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
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- 239000013078 crystal Substances 0.000 description 55
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000000706 filtrate Substances 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 238000002844 melting Methods 0.000 description 27
- 230000008018 melting Effects 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
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- 239000002904 solvent Substances 0.000 description 15
- 125000003118 aryl group Chemical group 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical group C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 12
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- 230000000694 effects Effects 0.000 description 8
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
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- 208000003455 anaphylaxis Diseases 0.000 description 6
- MNWFXJYAOYHMED-UHFFFAOYSA-N hexane carboxylic acid Natural products CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 229940125782 compound 2 Drugs 0.000 description 5
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 5
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 5
- 210000003630 histaminocyte Anatomy 0.000 description 5
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- 229940126062 Compound A Drugs 0.000 description 4
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 4
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- 108091007433 antigens Proteins 0.000 description 4
- 150000001718 carbodiimides Chemical class 0.000 description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
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- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 3
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- VSMDINRNYYEDRN-UHFFFAOYSA-N 4-iodophenol Chemical compound OC1=CC=C(I)C=C1 VSMDINRNYYEDRN-UHFFFAOYSA-N 0.000 description 1
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- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- QHPQWRBYOIRBIT-UHFFFAOYSA-N 4-tert-butylphenol Chemical compound CC(C)(C)C1=CC=C(O)C=C1 QHPQWRBYOIRBIT-UHFFFAOYSA-N 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 229930185605 Bisphenol Natural products 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
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- 241000700199 Cavia porcellus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
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- BNPRHGVDJVKUNM-GJTSMBTKSA-N Cl.C1C[C@@H](CNC(=N)N)CC[C@@H]1C(=O)OC1=CC=CC=C1 Chemical compound Cl.C1C[C@@H](CNC(=N)N)CC[C@@H]1C(=O)OC1=CC=CC=C1 BNPRHGVDJVKUNM-GJTSMBTKSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
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- 108060005987 Kallikrein Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
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- 239000002841 Lewis acid Substances 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
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- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101000605527 Rattus norvegicus Kallikrein-1 Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- 102000057032 Tissue Kallikreins Human genes 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 150000008366 benzophenones Chemical class 0.000 description 1
- QPYXDTXYDDXHQK-UHFFFAOYSA-N bis(2,4-dichlorophenyl) sulfite Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)OC1=CC=C(Cl)C=C1Cl QPYXDTXYDDXHQK-UHFFFAOYSA-N 0.000 description 1
- VMHTVCWRLHHZJO-UHFFFAOYSA-N bis(4-chlorophenyl) sulfite Chemical compound C1=CC(Cl)=CC=C1OS(=O)OC1=CC=C(Cl)C=C1 VMHTVCWRLHHZJO-UHFFFAOYSA-N 0.000 description 1
- UVTCDOMXZCRQQS-UHFFFAOYSA-N bis(4-methylphenyl) sulfite Chemical compound C1=CC(C)=CC=C1OS(=O)OC1=CC=C(C)C=C1 UVTCDOMXZCRQQS-UHFFFAOYSA-N 0.000 description 1
- ZNMROZJFHALUOA-UHFFFAOYSA-N bis(4-tert-butylphenyl) sulfite Chemical compound C1=CC(C(C)(C)C)=CC=C1OS(=O)OC1=CC=C(C(C)(C)C)C=C1 ZNMROZJFHALUOA-UHFFFAOYSA-N 0.000 description 1
- IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical compound C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- HLVXFWDLRHCZEI-UHFFFAOYSA-N chromotropic acid Chemical compound OS(=O)(=O)C1=CC(O)=C2C(O)=CC(S(O)(=O)=O)=CC2=C1 HLVXFWDLRHCZEI-UHFFFAOYSA-N 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004802 cyanophenyl group Chemical group 0.000 description 1
- JEVCWSUVFOYBFI-UHFFFAOYSA-N cyanyl Chemical compound N#[C] JEVCWSUVFOYBFI-UHFFFAOYSA-N 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical class OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- FPIQZBQZKBKLEI-UHFFFAOYSA-N ethyl 1-[[2-chloroethyl(nitroso)carbamoyl]amino]cyclohexane-1-carboxylate Chemical compound ClCCN(N=O)C(=O)NC1(C(=O)OCC)CCCCC1 FPIQZBQZKBKLEI-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000008384 ileus Diseases 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 231100000037 inhalation toxicity test Toxicity 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 125000006303 iodophenyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- JKRHDMPWBFBQDZ-UHFFFAOYSA-N n'-hexylmethanediimine Chemical compound CCCCCCN=C=N JKRHDMPWBFBQDZ-UHFFFAOYSA-N 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 229960003540 oxyquinoline Drugs 0.000 description 1
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940066827 pertussis vaccine Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 108700029318 rat female Proteins 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- CSABAZBYIWDIDE-UHFFFAOYSA-N sulfino hydrogen sulfite Chemical class OS(=O)OS(O)=O CSABAZBYIWDIDE-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen 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
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
- C07D215/32—Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP728481A JPS57122061A (en) | 1981-01-22 | 1981-01-22 | Novel cyclohexanecarboxylic acid derivative and its preparation |
| JP728681A JPS57122060A (en) | 1981-01-22 | 1981-01-22 | Carboxylic acid ester and its preparation |
| JP728381A JPS57122059A (en) | 1981-01-22 | 1981-01-22 | Novel cyclohexanecarboxylic acid derivative and its preparation |
| JP1083281A JPS57126463A (en) | 1981-01-29 | 1981-01-29 | Novel carboxylic ester and its preparation |
| JP1083181A JPS57126462A (en) | 1981-01-29 | 1981-01-29 | Novel carboxylic ester and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FR2498183A1 true FR2498183A1 (fr) | 1982-07-23 |
| FR2498183B1 FR2498183B1 (en, 2012) | 1985-05-10 |
Family
ID=27518804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FR8201032A Granted FR2498183A1 (fr) | 1981-01-22 | 1982-01-22 | Nouveaux derives d'acides guanidinocyclohexanecarboxyliques, leur procede de preparation et leur application en therapeutique |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4465851A (en, 2012) |
| KR (1) | KR880001104B1 (en, 2012) |
| BE (1) | BE891790A (en, 2012) |
| BR (1) | BR8200212A (en, 2012) |
| CA (1) | CA1180716A (en, 2012) |
| CH (1) | CH652119A5 (en, 2012) |
| DE (1) | DE3201817A1 (en, 2012) |
| FR (1) | FR2498183A1 (en, 2012) |
| IT (1) | IT1191163B (en, 2012) |
| NL (1) | NL8200110A (en, 2012) |
| SE (1) | SE455789B (en, 2012) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0585130A3 (en) * | 1992-08-27 | 1994-06-08 | Shiseido Co Ltd | External preparation for skin containing a depigmentation agent |
| EP0775692A4 (en) * | 1994-08-30 | 1997-12-17 | Teikoku Chem Ind Co Ltd | ESTER DERIVATIVE OF GUANIDINOMETHYLCYCLOHEXANECARBOXYLIC ACID |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPO227896A0 (en) * | 1996-09-13 | 1996-10-03 | Fujisawa Pharmaceutical Co., Ltd. | Novel compounds and their preparation |
| AP1224A (en) | 1998-03-19 | 2003-11-14 | Bristol Myers Squibb Co | Biphasic controlled release delivery system for high solubility pharmaceuticals and method. |
| GB9908410D0 (en) | 1999-04-13 | 1999-06-09 | Pfizer Ltd | Pyridines |
| KR101942590B1 (ko) | 2010-07-09 | 2019-01-25 | 비에이치브이 파르마, 인크. | 레모글리플로진을 포함하는 짧은 반감기 약제용의 즉시/지연 조합 방출 전달 시스템 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE885263A (fr) * | 1979-09-20 | 1981-01-16 | Nippon Chemiphar Co | Derives d'acides cyclohexane-carboxyliques |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA929942A (en) * | 1968-10-14 | 1973-07-10 | Okano Atsuji | Esters and their production |
| JPS5339419B2 (en, 2012) * | 1972-10-19 | 1978-10-21 | ||
| JPS5140075A (en, 2012) * | 1974-09-30 | 1976-04-03 | Tokyo Shibaura Electric Co | |
| SE460667B (sv) * | 1979-09-20 | 1989-11-06 | Nippon Chemiphar Co | Cyklohexankarboxylsyraderivat, foerfarande foer framstaellning daerav samt naemnda derivat foer terapeutisk anvaendning |
-
1982
- 1982-01-04 US US06/336,707 patent/US4465851A/en not_active Expired - Lifetime
- 1982-01-13 NL NL8200110A patent/NL8200110A/nl not_active Application Discontinuation
- 1982-01-13 BR BR8200212A patent/BR8200212A/pt unknown
- 1982-01-15 BE BE0/207062A patent/BE891790A/fr not_active IP Right Cessation
- 1982-01-20 CA CA000394507A patent/CA1180716A/en not_active Expired
- 1982-01-20 SE SE8200309A patent/SE455789B/sv not_active IP Right Cessation
- 1982-01-21 IT IT67060/82A patent/IT1191163B/it active
- 1982-01-21 CH CH380/82A patent/CH652119A5/fr not_active IP Right Cessation
- 1982-01-21 DE DE19823201817 patent/DE3201817A1/de active Granted
- 1982-01-22 KR KR8200269A patent/KR880001104B1/ko not_active Expired
- 1982-01-22 FR FR8201032A patent/FR2498183A1/fr active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE885263A (fr) * | 1979-09-20 | 1981-01-16 | Nippon Chemiphar Co | Derives d'acides cyclohexane-carboxyliques |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0585130A3 (en) * | 1992-08-27 | 1994-06-08 | Shiseido Co Ltd | External preparation for skin containing a depigmentation agent |
| US5690914A (en) * | 1992-08-27 | 1997-11-25 | Shiseido Co., Ltd | External preparation for skin |
| EP0775692A4 (en) * | 1994-08-30 | 1997-12-17 | Teikoku Chem Ind Co Ltd | ESTER DERIVATIVE OF GUANIDINOMETHYLCYCLOHEXANECARBOXYLIC ACID |
| US6284791B1 (en) | 1994-08-30 | 2001-09-04 | Teikoku Chemical Industries Co., Ltd. | Guanidinomethyl cyclohexane carboxylic acid ester derivatives |
| US6831190B1 (en) | 1994-08-30 | 2004-12-14 | Teikoku Chemical Industries Co., Ltd. | Guanidinomethyl cyclohexane carboxylic acid ester derivatives |
| EP1449828A3 (en) * | 1994-08-30 | 2004-12-22 | Nagase ChemteX Corporation | Guanidinomethyl cyclohexane carboxylic acid ester derivatives |
| US6960681B2 (en) | 1994-08-30 | 2005-11-01 | Nagase Chemtex Corporation | Guanidinomethyl cyclohexane carboxylic acid ester derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3201817A1 (de) | 1982-08-19 |
| KR880001104B1 (ko) | 1988-06-29 |
| IT8267060A0 (it) | 1982-01-21 |
| SE8200309L (sv) | 1982-07-23 |
| NL8200110A (nl) | 1982-08-16 |
| FR2498183B1 (en, 2012) | 1985-05-10 |
| KR830009011A (ko) | 1983-12-17 |
| BR8200212A (pt) | 1982-11-09 |
| BE891790A (fr) | 1982-04-30 |
| CH652119A5 (fr) | 1985-10-31 |
| IT1191163B (it) | 1988-02-24 |
| SE455789B (sv) | 1988-08-08 |
| DE3201817C2 (en, 2012) | 1991-03-07 |
| CA1180716A (en) | 1985-01-08 |
| US4465851A (en) | 1984-08-14 |
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| ST | Notification of lapse |