LU86259A1 - AROMATIC AMIDES, THEIR PREPARATION PROCESS AND THEIR USE IN HUMAN OR VETERINARY MEDICINE AND IN COSMETICS - Google Patents
AROMATIC AMIDES, THEIR PREPARATION PROCESS AND THEIR USE IN HUMAN OR VETERINARY MEDICINE AND IN COSMETICS Download PDFInfo
- Publication number
- LU86259A1 LU86259A1 LU86259A LU86259A LU86259A1 LU 86259 A1 LU86259 A1 LU 86259A1 LU 86259 A LU86259 A LU 86259A LU 86259 A LU86259 A LU 86259A LU 86259 A1 LU86259 A1 LU 86259A1
- Authority
- LU
- Luxembourg
- Prior art keywords
- formula
- radical
- acid
- compounds according
- methyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 10
- 239000002537 cosmetic Substances 0.000 title claims description 9
- 150000008430 aromatic amides Chemical class 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 36
- -1 Aromatic amide compounds Chemical class 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 19
- 150000003254 radicals Chemical class 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 7
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
- 239000005711 Benzoic acid Substances 0.000 claims description 6
- 229940095102 methyl benzoate Drugs 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 230000000699 topical effect Effects 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000000539 amino acid group Chemical group 0.000 claims description 4
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 150000002337 glycosamines Chemical class 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 230000000241 respiratory effect Effects 0.000 claims description 3
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 claims 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 claims description 2
- MSWZFWKMSRAUBD-CBPJZXOFSA-N 2-amino-2-deoxy-D-mannopyranose Chemical compound N[C@@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-CBPJZXOFSA-N 0.000 claims description 2
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical compound [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- 239000004472 Lysine Substances 0.000 claims description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 2
- 150000005840 aryl radicals Chemical class 0.000 claims description 2
- 230000037396 body weight Effects 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229960002442 glucosamine Drugs 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 1
- 208000025747 Rheumatic disease Diseases 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000000552 rheumatic effect Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 208000002874 Acne Vulgaris Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 206010000496 acne Diseases 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- CPWIUCQCJRWWTH-UHFFFAOYSA-N 5,5,8,8-tetramethyl-6,7-dihydronaphthalene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=C2C(C)(C)CCC(C)(C)C2=C1 CPWIUCQCJRWWTH-UHFFFAOYSA-N 0.000 description 2
- 206010003645 Atopy Diseases 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- OENHQHLEOONYIE-UKMVMLAPSA-N beta-Carotene Chemical compound CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000003659 hair regrowth Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000029443 keratinization disease Diseases 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- PNCWHIAZZSDHPU-UHFFFAOYSA-N 2-benzylsulfanylethanamine Chemical compound NCCSCC1=CC=CC=C1 PNCWHIAZZSDHPU-UHFFFAOYSA-N 0.000 description 1
- ZIMGGGWCDYVHOY-UHFFFAOYSA-N 3-hydroxy-2-imino-6-(1-piperidinyl)-4-pyrimidinamine Chemical compound N=C1N(O)C(N)=CC(N2CCCCC2)=N1 ZIMGGGWCDYVHOY-UHFFFAOYSA-N 0.000 description 1
- 208000020154 Acnes Diseases 0.000 description 1
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 208000002506 Darier Disease Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 239000004097 EU approved flavor enhancer Substances 0.000 description 1
- 206010021197 Ichthyoses Diseases 0.000 description 1
- 206010023369 Keratosis follicular Diseases 0.000 description 1
- 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 1
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000052812 Ornithine decarboxylases Human genes 0.000 description 1
- 108700005126 Ornithine decarboxylases Proteins 0.000 description 1
- 206010033554 Palmoplantar keratoderma Diseases 0.000 description 1
- GBFLZEXEOZUWRN-VKHMYHEASA-N S-carboxymethyl-L-cysteine Chemical compound OC(=O)[C@@H](N)CSCC(O)=O GBFLZEXEOZUWRN-VKHMYHEASA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- NUZWLKWWNNJHPT-UHFFFAOYSA-N anthralin Chemical compound C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O NUZWLKWWNNJHPT-UHFFFAOYSA-N 0.000 description 1
- 239000000058 anti acne agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003656 anti-hair-loss Effects 0.000 description 1
- 230000002682 anti-psoriatic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940124340 antiacne agent Drugs 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- GDLBFKVLRPITMI-UHFFFAOYSA-N diazoxide Chemical compound ClC1=CC=C2NC(C)=NS(=O)(=O)C2=C1 GDLBFKVLRPITMI-UHFFFAOYSA-N 0.000 description 1
- 229960004042 diazoxide Drugs 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229960002311 dithranol Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000037336 dry skin Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- WDCDAAMJNUHOIY-UHFFFAOYSA-N ethyl acetate;2-propan-2-yloxypropane Chemical compound CCOC(C)=O.CC(C)OC(C)C WDCDAAMJNUHOIY-UHFFFAOYSA-N 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 206010021198 ichthyosis Diseases 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000003780 keratinization Effects 0.000 description 1
- 201000004607 keratosis follicularis Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000002741 leukoplakia Diseases 0.000 description 1
- 201000011486 lichen planus Diseases 0.000 description 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- ZHIPSMIKSRYZFV-UHFFFAOYSA-N methyl 4-amino-3-methylbenzoate Chemical compound COC(=O)C1=CC=C(N)C(C)=C1 ZHIPSMIKSRYZFV-UHFFFAOYSA-N 0.000 description 1
- LZXXNPOYQCLXRS-UHFFFAOYSA-N methyl 4-aminobenzoate Chemical compound COC(=O)C1=CC=C(N)C=C1 LZXXNPOYQCLXRS-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229960003632 minoxidil Drugs 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N n-octadecyl alcohol Natural products CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 201000008743 palmoplantar keratosis Diseases 0.000 description 1
- 229940059574 pentaerithrityl Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000002294 steroidal antiinflammatory agent Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- SLYPOVJCSQHITR-UHFFFAOYSA-N tioxolone Chemical compound OC1=CC=C2SC(=O)OC2=C1 SLYPOVJCSQHITR-UHFFFAOYSA-N 0.000 description 1
- 229960003070 tioxolone Drugs 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
-
- 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
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
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Description
V * ‘ 1V * ‘1
La présente invention a pour objet de nouveaux composés amides aromatiques, leur procédé de préparation et leur utilisation en médecine humaine ou vétérinaire et en cosmétique.The present invention relates to new aromatic amide compounds, their preparation process and their use in human or veterinary medicine and in cosmetics.
Ces nouveaux composés amides aromatiques trouvent une application 5 dans le traitement topique et systémique des affections dermatologiques liées à un désordre de la kératinisation (différenciation-prolifération) et d'affections dermatologiques ou autres à composantes inflammatoires et/ou immunoallergiques et dans les maladies de dégénérescence du tissu conjonctif ainsi qu’une activité antitumorale. En outre ces composés peuvent être 10 utilisés dans le traitement de l'atopie qu’elle soit cutanée ou respiratoire et du psoriasis rhumatoïde.These new aromatic amide compounds find application in the topical and systemic treatment of dermatological conditions linked to a disorder of keratinization (differentiation-proliferation) and of dermatological or other affections with inflammatory and / or immunoallergic components and in degenerative diseases connective tissue as well as anti-tumor activity. In addition, these compounds can be used in the treatment of atopy, whether cutaneous or respiratory, and rheumatoid psoriasis.
Ils trouvent également une application dans le domaine ophtalmologique, notamment pour le traitement des cornéopathies.They also find an application in the ophthalmological field, in particular for the treatment of corneopathies.
Les amides aromatiques selon l'invention, du fait de leurs 15 propriétés biochimiques, appartiennent à la classe des "Différines" et peuvent être représentés par la formule générale suivante: CH, CH3 o 20 {I) 25 dans laquelle: R, représente -0R„ ou - N i 3 v, r» représentant un atome d'hydrogène, un radical alkyle inférieur, un radical mono ou polyhydroxyalkyle, r' et r" représentant un atome d'hydrogène, un radical alkyle inférieur, un radical mono ou polyhydroxyalkyle, un radical aryle ou benzyle éventuellement substitué(s), un reste d'aminoacide ou de sucre aminé ou pris ensemble forment un hétérocycle, R2 représente un atome d'hydrogène ou un radical alkyle inférieur, 35 \ /CH3 et X représente C , -0- ou -S-The aromatic amides according to the invention, because of their biochemical properties, belong to the class of "Differins" and can be represented by the following general formula: CH, CH3 or 20 (I) 25 in which: R, represents - 0R „or - N i 3 v, r” representing a hydrogen atom, a lower alkyl radical, a mono or polyhydroxyalkyl radical, r 'and r "representing a hydrogen atom, a lower alkyl radical, a mono radical or polyhydroxyalkyl, an optionally substituted aryl or benzyl radical, an amino acid residue or an amino sugar or taken together form a heterocycle, R2 represents a hydrogen atom or a lower alkyl radical, 35 \ / CH3 and X represents C , -0- or -S-
/ X/ X
et les sels desdits amides aromatiques de formule (I) lorsque R^ représente un atome d'hydrogène.and the salts of said aromatic amides of formula (I) when R ^ represents a hydrogen atom.
Lorsque les composés selon l'invention se présentent sous forme de \ ' λ 2 sels, il peut s’agir de sels d'un métal alcalin ou alcalino-terreux ou encore de zinc ou d'une amine organique.When the compounds according to the invention are in the form of \ 'λ 2 salts, it may be salts of an alkali or alkaline earth metal or alternatively of zinc or an organic amine.
Par radical alkyle inférieur, on doit entendre un radical ayant de 1 à 6 atomes de carbone notamment les radicaux méthyle, éthyle, isopropyle, 5 butyle et tertiobutyle.The term “lower alkyl radical” should be understood to mean a radical having from 1 to 6 carbon atoms, in particular the methyl, ethyl, isopropyl, butyl and tert-butyl radicals.
Par radical monohydroxyalkyle, on doit entendre un radical ayant 2 ou 3 atomes de carbone, notamment un radical 2-hydroxyéthyle, 2-hydroxypropyle ou 3-hydroxypropyle.The term “monohydroxyalkyl radical” should be understood to mean a radical having 2 or 3 carbon atoms, in particular a 2-hydroxyethyl, 2-hydroxypropyl or 3-hydroxypropyl radical.
Par radical polyhydroxyalkyle, on doit entendre un radical contenant 1Q de 3 à 6 atomes de carbone et de 2 à 5 groupes hydroxyles tels que les radicaux 2,3-dihydroxypropyle, 2,3,4-trihydroxybutyle, 2,3,4,5-tétrahydroxy-pentyle ou le reste du penta-érythritol.The term “polyhydroxyalkyl radical” should be understood to mean a radical containing 1Q of 3 to 6 carbon atoms and of 2 to 5 hydroxyl groups such as the 2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl, 2,3,4,5 radicals. -tetrahydroxy-pentyl or the rest of penta-erythritol.
Par radical aryle, on doit entendre un radical phényle éventuellement substitué par un atome d'halogène, un hydroxyle ou une fonction 15 nitro.By aryl radical is meant a phenyl radical optionally substituted by a halogen atom, a hydroxyl or a nitro function.
Par reste d'aminoacide, on doit entendre un reste dérivant par exemple de la lysine ou de la glycine.The term “amino acid residue” should be understood to mean a residue deriving for example from lysine or from glycine.
Par reste d'un sucre aminé, on doit entendre un reste dérivant de glucosamine, de galactosamine ou de mannosamine.The remainder of an amino sugar should be understood to mean a residue derived from glucosamine, galactosamine or mannosamine.
2Q Lorsque les radicaux r' et r" pris ensemble forment un hétérocycle, celui-ci est de préférence un radical pipéridino, pipérazino, morpholino, pyrrolidino ou (2-hydroxyéthyl)-4-pipérazino.When the radicals r 'and r "taken together form a heterocycle, the latter is preferably a piperidino, piperazino, morpholino, pyrrolidino or (2-hydroxyethyl) -4-piperazino radical.
Parmi les composés de formule (I) ci-dessus préférés, on peut notamment citer les suivants: 25 - l'acide 4-(5,6,7,8-tétrahydro-5,5,8,8-tétraméthyl-2 naphtamido)-benzoïque, le 4-(5,6,7,8-tétrahydro-5,5,8,8-tétraméthyl-2 naphtamido)-benzoate de méthyle, - l'acide 4-(5,6,7,8-tétrahydro-5,5,8,8-tétraméthyl-2 3Q naphtamido)-3-méthyl benzoïque, le 4-(5,6,7,8-tétrahydro-5,5,8,8-tétraméthyl-2 naphtamido)-3-méthyl benzoate de méthyle, - l'acide 4-(2,3-dihydro-4,4-diméthyl-6-benzothio-pyrannecarboxamido)-benzoïque, 35 - le 4-(2,3-dihydro-4,4-diméthyl-6-benzothio- pyrannecarboxamido)-benzoate de méthyle, - le 4-(2,3-dihydro-4,4-diméthyl-6-benzothio-pyrannecarboxamido)-benzoate de 2,3-dihydroxypropyle, - le 4-(2,3-dihydro-4,4-diméthyl-6-benzothio-40. pyrannecarboxamido)-benzoate de 2-hydroxyéthyle, et • 3 - le morpholide de l’acide 4-(2,3-dihydro-4,4-dimé-thyl-6-benzothiopyrannecarboxamido-benzoïque.Among the compounds of formula (I) above which are preferred, the following may be mentioned in particular: 25 - 4- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2 naphtamido acid) ) -benzoic acid, 4- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2 naphtamido) -methyl benzoate, - acid 4- (5,6,7,8 -tetrahydro-5,5,8,8-tetramethyl-2 3Q naphtamido) -3-methyl benzoic, 4- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2 naphtamido) -3-methyl methyl benzoate, - 4- (2,3-dihydro-4,4-dimethyl-6-benzothio-pyrannecarboxamido) -benzoic acid, 35 - 4- (2,3-dihydro-4, 4-dimethyl-6-benzothio-pyrannecarboxamido) -methyl benzoate, - 4- (2,3-dihydro-4,4-dimethyl-6-benzothio-pyrannecarboxamido)-2,3-dihydroxypropyl benzoate, - 4 - (2,3-dihydro-4,4-dimethyl-6-benzothio-40. Pyrannecarboxamido) -benzoate of 2-hydroxyethyl, and • 3 - the acid morpholide 4- (2,3-dihydro-4, 4-dimé-thyl-6-benzothiopyrannecarboxamido-benzoïque.
La présente invention a également pour objet le procédé de préparation des composés de formule I selon le schéma réactionnel suivant: c«3™3 9 0*3 CB3 · O 2 (i’ (2) ' ^VC028The present invention also relates to the process for the preparation of the compounds of formula I according to the following reaction scheme: c “3 ™ 3 9 0 * 3 CB3 · O 2 (i’ (2) '^ VC028
”CH3^/CH3 G I I”CH3 ^ / CH3 G I I
1 ) KOH ,CH,OH f (la) -^ l JL ü ' 2) H+ (Ib) R2 r* CON"'" ch3 ch3 O [ Π ^ db) —C,P:L> ΗΝ<Γ’ *2 X (ici » L’étape principale de cette préparation consiste à faire réagir en milieu anhydre, dans un solvant organique de préférence le tétrahydrofuranne et en présence d’une amine tertiaire, une forme activée d’un acide carboxylique, par exemple un chlorure d’acide de formule (JL)» sur un p-aminobenzoate d’alkyle éventuellement substitué en position 3 (2), la réaction étant conduite à température ambiante et sous agitation.1) KOH, CH, OH f (la) - ^ l JL ü '2) H + (Ib) R2 r * CON "'" ch3 ch3 O [Π ^ db) —C, P: L> ΗΝ <Γ '* 2 X (here »The main stage of this preparation consists in reacting in an anhydrous medium, in an organic solvent preferably tetrahydrofuran and in the presence of a tertiary amine, an activated form of a carboxylic acid, for example a chloride acid of formula (JL) "on an alkyl p-aminobenzoate optionally substituted in position 3 (2), the reaction being carried out at room temperature and with stirring.
A partir de l’ester (la) on accède par saponification à l’acide correspondant (Ib) qui peut ensuite être activé, par exemple à l’aide de Ν,Ν’-carbonyldiimidazole (CDI), et transformé en amide de formule (le) par r f action d’une amine de formule HN«·'^ (r’ et r” ayant les memesFrom the ester (la), the corresponding acid (Ib) is accessed by saponification which can then be activated, for example using Ν, Ν'-carbonyldiimidazole (CDI), and transformed into the amide of formula (le) by rf action of an amine of formula HN “· '^ (r' and r” having the same
\rH\ rH
significations que données ci-dessus).meanings given above).
. ’ i 4 «. ’I 4’
Lorsque R^ représente un radical monohydroxy ou polyhydroxyalkyle, il est préférable de préparer l'acide (Ib) à partir de l'ester méthylique (la) (R^-CHg) et ensuite d'estérifier l'acide ainsi obtenu en ester de l'alcool mono ou polyhydrique choisi selon les méthodes connues.When R ^ represents a monohydroxy or polyhydroxyalkyl radical, it is preferable to prepare the acid (Ib) from the methyl ester (la) (R ^ -CHg) and then to esterify the acid thus obtained as ester of mono or polyhydric alcohol chosen according to known methods.
5 La présente invention a également pour objet à titre de médicament les composés de formule (I) telle que définie ci-dessus.The present invention also relates, as medicament, to the compounds of formula (I) as defined above.
Ces composés présentent une excellente activité dans le test d'inhibition de l'ornithine décarboxylase après induction, par "tape stripping", chez le rat nu (M. Bouclier et al DERMATOLOGICA, 169 n°4 1984). Ce 1Q test est admis comme mesure de l'action inhibitrice de certains composés sur les phénomènes de prolifération cellulaire.These compounds exhibit excellent activity in the inhibition test of ornithine decarboxylase after induction, by "tape stripping", in the naked rat (M. Bouclier et al DERMATOLOGICA, 169 no. 4 1984). This 1Q test is accepted as a measure of the inhibitory action of certain compounds on the phenomena of cell proliferation.
Ces composés conviennent particulièrement bien pour traiter les affections dermatologiques liées à un désordre de la kératinisation (différenciation-prolifération) ainsi que les affections dermatologiques, ou 15 autres, à composante inflammatoire et/ou immunoallergique notamment: - les acnés vulgaires, comédoniennes ou polymorphes, les acnés séniles, solaires, et les acnés médicamenteuses ou professionnelles.These compounds are particularly suitable for treating dermatological affections linked to a disorder of keratinization (differentiation-proliferation) as well as dermatological affections, or others, with an inflammatory and / or immunoallergic component, in particular: - vulgar, comedonian or polymorphic acnes, senile, solar acne, and medical or professional acne.
- les formes étendues et/ou sévères de psoriasis, et les autres troubles de la kératinisation, et notamment les ichtyoses et états 2Q ichtyosiformes - la maladie de Darier, - les kératodermies palmo-plantaires, - les leucoplasies et états leucoplasiformes, le lichen plan - toutes proliférations dermatologiques bénignes ou malignes, 25 sévères ou étendues.- extensive and / or severe forms of psoriasis, and other keratinization disorders, and in particular ichthyoses and ichthyosiform states 2Q - Darier's disease, - palmoplantar keratoderma, - leukoplakias and leukoplasiform states, lichen planus - all benign or malignant dermatological proliferation, 25 severe or extensive.
Ils sont également actifs dans le traitement des tumeurs, du psoriasis rhumatoïde, des atopies cutanées ou respiratoires ainsi que dans le traitement de certains problèmes ophtalmologiques relatifs aux cornéopathies.They are also active in the treatment of tumors, rheumatoid psoriasis, cutaneous or respiratory atopy and in the treatment of certain ophthalmological problems relating to corneopathies.
La présente invention a donc également pour objet des compositions 3q médicamenteuses contenant au moins un composé de formule (I) tel que défini ci-dessus, ou un de ses sels.The present invention therefore also relates to medicinal compositions 3q containing at least one compound of formula (I) as defined above, or one of its salts.
La présente invention a donc aussi pour objet une nouvelle composition médicamenteuse, destinée notamment au traitement des affections susmentionnées, caractérisée par le fait qu'elle comporte, dans un support 35 pharmaceutique acceptable, au moins un composé de formule (I) et/ou un de ses sels.A subject of the present invention is therefore also a new medicinal composition, intended in particular for the treatment of the aforementioned conditions, characterized in that it comprises, in an acceptable pharmaceutical carrier, at least one compound of formula (I) and / or a of its salts.
Les composés selon l'invention présentent une bonne stabilité à la lumière et à l'oxygène.The compounds according to the invention exhibit good stability to light and to oxygen.
Les composés selon l'invention sont généralement administrés à une 4Q dose journalière d'environ 0,01mg/Kg à 2mg/Kg de poids corporel.The compounds according to the invention are generally administered at a daily dose of approximately 0.01 mg / kg to 2 mg / kg of body weight.
55
Connue support des compositions, on peut utiliser tout support conventionnel, le composé actif se trouvant soit à l'état dissous, soit à l'état dispersé dans le véhicule.Known support for the compositions, any conventional support can be used, the active compound being either in the dissolved state or in the dispersed state in the vehicle.
L'administration peut être effectuée par voie entérale, parentérale, 5 topique ou oculaire. Par voie entérale, les médicaments peuvent se présenter sous forme de comprimés, de gélules, de dragées, de sirops, de suspensions, de solutions, de poudres, de granulés, d'émulsions. Par voie parentérale, les compositions peuvent se présenter sous forme de solutions ou suspensions pour perfusion ou pour injection.Administration can be by enteral, parenteral, topical or ocular route. Enterally, the drugs can be in the form of tablets, capsules, dragees, syrups, suspensions, solutions, powders, granules, emulsions. Parenterally, the compositions may be in the form of solutions or suspensions for infusion or for injection.
10 Par voie topique, les compositions pharmaceutiques à base des composés selon l'invention se présentent sous forme d'onguents, de teintures, de crèmes, de pommades, de poudres, de timbres, de tampons imbibés, de solutions, de lotions, de gels, de sprays ou encore de suspensions.10 Topically, the pharmaceutical compositions based on the compounds according to the invention are in the form of ointments, tinctures, creams, ointments, powders, patches, soaked pads, solutions, lotions, gels, sprays or suspensions.
Ces compositions par voie topique peuvent se présenter soit sous 15 forme anhydre, soit sous forme aqueuse selon l'indication clinique.These topical compositions can be in either anhydrous or aqueous form depending on the clinical indication.
Par voie oculaire, ce sont principalement des collyres.By eye, these are mainly eye drops.
Ces compositions contiennent au moins un composé de formule (I) tel que défini ci-dessus ou un de ses sels, à une concentration de préférence comprise entre 0,0001 et 5% par rapport au poids total de la composition.These compositions contain at least one compound of formula (I) as defined above or one of its salts, at a concentration preferably of between 0.0001 and 5% relative to the total weight of the composition.
20 Les composés de formule (I), selon l'invention, trouvent également une application dans le domaine cosmétique, en particulier dans l'hygiène corporelle et capillaire et notamment pour le traitement des peaux à tendance acnéique, pour la repousse des cheveux, l'anti-chute, pour lutter contre l'aspect gras de la peau ou des cheveux, dans la protection contre les effets 25 néfastes du soleil ou dans le traitement des peaux physiologiquement sèches.The compounds of formula (I) according to the invention also find application in the cosmetic field, in particular in body and hair hygiene and in particular for the treatment of acne-prone skin, for hair regrowth, anti-hair loss, to combat the oily appearance of the skin or the hair, in protection against the harmful effects of the sun or in the treatment of physiologically dry skin.
La présente invention vise donc également une composition cosmétique contenant, dans un support cosmétiquement acceptable, au moins un composé de formule (I) ou un de ses sels, cette composition se présentant notamment sous forme de lotion, gel, savon ou shampooing.The present invention therefore also relates to a cosmetic composition containing, in a cosmetically acceptable carrier, at least one compound of formula (I) or one of its salts, this composition being in particular in the form of a lotion, gel, soap or shampoo.
30 La concentration en composé de formule (I), dans les compositions cosmétiques, est comprise entre 0,0001 et 0,1% en poids et de préférence entre 0,001 et 0,01% en poids.The concentration of compound of formula (I), in the cosmetic compositions, is between 0.0001 and 0.1% by weight and preferably between 0.001 and 0.01% by weight.
Les compositions médicamenteuses et cosmétiques selon l'invention peuvent contenir des additifs inertes ou même pharmacodynamiquement ou 35 cosmétiquement actifs et notamment: des agents hydratants comme la thiamorpholinone et ses dérivés ou l'urée; des agents antiséborrhéiques ou antiacnéiques, tels que la S-carboxyméthylcystéine, la S-benzyl-cystéamine, leurs sels et leurs dérivés, la tioxolone ou le peroxyde de benzoyle; des antibiotiques comme l'érythromycine et ses esters, la néomycine, les 40 tétracyclines ou les polyméthylène-4,5 isothiazolinones-3; des agents t 6 favorisant la repousse des cheveux, comme le "Minoxidil" (2,4-diamino-6-pipéridino-pyrimidine-3-oxyde) et ses dérivés, le Diazoxide (7-chloro 3-méthyl-l,2,4-benzothiadiazine 1,1-dioxyde) et le Phénytoïn (5,5-diphénylimidazolidine-2,4-dione); des agents anti-inflammatoires 5 stéroïdiens et non stéroïdiens; des caroténoïdes et, notamment le ß -carotène; des agents anti-psoriasiques tels que l'anthraline et ses dérivés et les acides eicosatétraynoïque-5,8,11,14 et triynoïque-5,8,11, leur esters et leurs amides.The medicinal and cosmetic compositions according to the invention may contain inert additives or even pharmacodynamically or cosmetically active and in particular: hydrating agents such as thiamorpholinone and its derivatives or urea; antiseborrhoeic or anti-acne agents, such as S-carboxymethylcysteine, S-benzyl-cysteamine, their salts and their derivatives, tioxolone or benzoyl peroxide; antibiotics such as erythromycin and its esters, neomycin, 40 tetracyclines or polymethylene-4,5 isothiazolinones-3; agents t 6 promoting hair regrowth, such as "Minoxidil" (2,4-diamino-6-piperidino-pyrimidine-3-oxide) and its derivatives, Diazoxide (7-chloro 3-methyl-1,2), 4-benzothiadiazine 1,1-dioxide) and Phenytoin (5,5-diphenylimidazolidine-2,4-dione); steroidal and nonsteroidal anti-inflammatory agents; carotenoids and, in particular, ß -carotene; anti-psoriatic agents such as anthralin and its derivatives and eicosatetraynoic-5,8,11,14 and triynoic-5,8,11 acids, their esters and their amides.
Les compositions selon l'invention peuvent également contenir des 10 agents d'amélioration de la saveur, des agents conservateurs, des agents stabilisants, des agents régulateurs d'humidité, des agents régulateurs de pH, des agents modificateurs de pression osmotique, des agents émulsionnants, des filtres UV-A et UV-B, des anti-oxydants tels que de 1' a -tocophérol, le butylhydroxy-anisole ou le butylhydroxy toluène.The compositions according to the invention can also contain flavor enhancers, preserving agents, stabilizing agents, humidity regulating agents, pH regulating agents, osmotic pressure modifying agents, emulsifying agents , UV-A and UV-B filters, antioxidants such as α-tocopherol, butylhydroxy-anisole or butylhydroxy toluene.
15 On va maintenant donner, à titre d'illustration et sans aucun caractère limitatif, plusieurs exemples de préparation des composés actifs de formule (I) selon l'invention ainsi que des exemples de compositions les contenant.We will now give, by way of illustration and without any limiting character, several examples of preparation of the active compounds of formula (I) according to the invention as well as examples of compositions containing them.
EXEMPLE 1 20 Préparation de l'ester methyligue de l'acide 4-(5,6,7,8-tétra- hydro-5,5,8,8-tétraméthyl-2-naphtamido)-3-méthyl benzoïque♦EXAMPLE 1 Preparation of the methyl ester of 4- (5,6,7,8-tetra-hydro-5,5,8,8-tetramethyl-2-naphtamido) -3-methyl benzoic acid ♦
Dans un ballon, on introduit 3,3g (0,02 mole) de 4-amino-3-méthyl-benzoate de méthyle, 50ml de tétrahydrofuranne et 3,1ml (0,022 mole) de triéthylamine. On ajoute goutte à goutte 5,5g (0,022 mole) du chlorure de 25 l'acide 5,6,7,8-tétrahydro-5,5,8,8-tétraméthyl-2-naphtoïque. On agite deux heures à température ambiante, jette dans l'eau, extrait au chlorure de méthylène, décante la phase organique, sèche sur sulfate de magnésium et évapore. On recueille un solide que l'on recristallise dans un mélange (80-20) éther isopropylique-acétate d'éthyle. On obtient ainsi 6,1g du produit attendu 30 (Rdt 80,5%) de point de fusion : 179-180°C.3.3 g (0.02 mole) of methyl 4-amino-3-methyl-benzoate, 50 ml of tetrahydrofuran and 3.1 ml (0.022 mole) of triethylamine are introduced into a flask. 5.5 g (0.022 mole) of the 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthoic acid chloride are added dropwise. The mixture is stirred for two hours at room temperature, thrown into water, extracted with methylene chloride, the organic phase is decanted, dried over magnesium sulfate and evaporated. A solid is collected which is recrystallized from a mixture (80-20) of isopropyl ether-ethyl acetate. 6.1 g of the expected product 30 are thus obtained (yield 80.5%) of melting point: 179-180 ° C.
Analyse élémentaire: C% H% N% 0%Elementary analysis: C% H% N% 0%
Calculé: 76.30 7.94 3.56 12.20Calculated: 76.30 7.94 3.56 12.20
Trouvé: 76.24 7.91 3.57 12.25 35 EXEMPLE 2Found: 76.24 7.91 3.57 12.25 35 EXAMPLE 2
Préparation de l'acide 4-(5,6,7,8-tétrahydro-5,5,8,8-tétraméthyl-2-naphtamido)-3-méthyl benzoïque.Preparation of 4- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtamido) -3-methyl benzoic acid.
Dans un ballon, on introduit 2g (0,005 mole) de l'ester obtenu à l'exemple 1 et 100ml de soude méthanolique IM. On chauffe à reflux deux 40. heures, évapore à sec, reprend par de l'eau, acidifie à pH 1 avec de l'acide ., * λ 7 chlorhydrique concentré et extrait à l'éther. Après décantation de la phase organique, on sèche sur sulfate de magnésium et évapore. On recueille un solide blanc que l'on recristallise dans l'acétate d'éthyle. On obtient ainsi 1,5g de l'acide attendu (Rdt 79%) de point de fusion : 229-230°C.2g (0.005 mole) of the ester obtained in Example 1 and 100ml of methanolic IM soda are introduced into a flask. The mixture is refluxed for two hours, evaporated to dryness, taken up in water, acidified to pH 1 with acid., * Λ 7 concentrated hydrochloric acid and extracted with ether. After decanting the organic phase, it is dried over magnesium sulfate and evaporated. A white solid is collected which is recrystallized from ethyl acetate. 1.5 g of the expected acid are thus obtained (yield 79%), melting point: 229-230 ° C.
5 Analyse élémentaire: C% H% N% 0%5 Elementary analysis: C% H% N% 0%
Calculé: 75.96 7.70 3.69 12.65Calculated: 75.96 7.70 3.69 12.65
Trouvé: 76.14 7.95 3.67 12.76 EXEMPLE 3 10 Préparation de l'ester méthylique de l'acide 4-(5,6,7,8-tétrahy- dro-5,5,8,8-tétraméthyl-2-naphtamido)-benzoïque.Found: 76.14 7.95 3.67 12.76 EXAMPLE 3 10 Preparation of 4- (5,6,7,8-tetrahy-dro-5,5,8,8-tetramethyl-2-naphthamido) acid methyl ester .
Dans un ballon, on introduit 15,1g (0,1 mole) de p-amino benzoate de méthyle, 70ml de tétrahydrofuranne et 15,4ml (0,11 mole) de triéthylamine. On ajoute goutte à goutte 27,6g (0,11 mole) de chlorure de l'acide 15 5,6,7,8-tétrahydro-5,5,8,8-tétraméthyl-2-naphtoïque dans 50ml de tétrahydrofuranne et agite à température ambiante deux heures. On jette dans l'eau, extrait au chlorure de méthylène, décante la phase organique, sèche sur sulfate de magnésium et évapore. Après recristallisation dans l’acétate d'éthyle, on obtient 32,5g de produit attendu (Rdt 89%) de point de fusion: 20 204-205°C.15.1 g (0.1 mole) of methyl p-amino benzoate, 70 ml of tetrahydrofuran and 15.4 ml (0.11 mole) of triethylamine are introduced into a flask. 27.6 g (0.11 mol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthoic acid chloride in 50 ml of tetrahydrofuran are added dropwise. at room temperature two hours. It is thrown into water, extracted with methylene chloride, the organic phase is decanted, dried over magnesium sulfate and evaporated. After recrystallization from ethyl acetate, 32.5 g of expected product are obtained (yield 89%), melting point: 20 204-205 ° C.
Analyse élémentaire: C% H% N% 0%Elementary analysis: C% H% N% 0%
Calculé : 75.59 7.45 3.83 13.13Calculated: 75.59 7.45 3.83 13.13
Trouvé: 75.39 7.20 3.96 13.10 25 EXEMPLE 4Found: 75.39 7.20 3.96 13.10 25 EXAMPLE 4
Préparation de l'acide 4-(5,6,7,8-tétrahydro-5,5,8,8-tétraméthyl-2-naphtamido benzoïque.Preparation of 4- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtamido benzoic acid.
Dans un ballon, on introduit 10g (0,0273 mole) de l'ester obtenu à l'exemple 3 et 200ml de soude méthanolique IM. On chauffe a reflux huit 30 heures, puis évapore à sec, reprend par de l'eau, acidifie avec de l'acide chlorhydrique à pH = 1 et extrait à l'éther. On décante la phase organique puis sèche sur sulfate de magnésium et évapore. On recristallise dans l'acétate d'éthyle et obtient 8,1g de produit attendu (Rdt 85%) de point de fusion: 260-26l°C.10 g (0.0273 mole) of the ester obtained in Example 3 and 200 ml of methanolic IM soda are introduced into a flask. The mixture is refluxed for eight 30 hours, then evaporated to dryness, taken up in water, acidified with hydrochloric acid to pH = 1 and extracted with ether. The organic phase is decanted and then dried over magnesium sulfate and evaporated. Recrystallized from ethyl acetate and 8.1g of expected product (yield 85%) melting point: 260-26l ° C.
35 Analyse élémentaire: C% H% N% 0%35 Elementary analysis: C% H% N% 0%
Calculé : 75.18 7.17 3.99 13.66Calculated: 75.18 7.17 3.99 13.66
Trouvé: 75.21 7.36 3.81 13.72 8Found: 75.21 7.36 3.81 13.72 8
EXEMPLES DE FORMULATIONFORMULATION EXAMPLES
A. VOIE ORALEA. ORAL ROUTE
5 (a) comprimé de 0,2g - Acide 4-(5,6,7,8-tétrahydro-5,5,8,8-tétra- méthyl-2-naphtamido) benzoïque............... 0,001g - Amidon....................................... 0,114g - Phosphate bicalcique......................... 0,020g 10 - Silice....................................... 0,020g - Lactose...................................... 0,030g - Talc........... 0,010g - Stéarate de magnésium........................ 0,005g (b) Suspension buvable en ampoules de 5ml 15 - Acide 4-(5,6,7,8-tétrahydro-5,5,8,8-tétraméthyl-2- naphtamido)-benzoïque........................ 0,001g - Glycérine.................................... 0,500g - Sorbitol à 70%............................... 0,500g - Saccharinate de sodium....................... 0,010g 20 - Parahydroxybenzoate de méthyle............... 0,040g - Arôme........................................ qs - Eau purifiée qsp............................. 5,00ml B. VOIE TOPIQUE 25 (c) Crème huile-dans-11eau anionique - Acide 4-(5,6,7,8-tétrahydro-5,5,8,8-tétraméthyl-2- naphtamido)-3-méthyl benzoïque............... 0,010g - Dodécylsulfate de sodium..................... 0,800g 30 - Glycérol..................................... 2,000g - Alcool stéarylique........................... 20,000g - Triglycérides d'acide caprique/caprylique vendu par la Société DYNAMIT NOBEL sous la dénomination de "Miglyol 812"................ 20,000g 35 - Conservateur qs - Eau déminéralisée............................ 100,000g ’ « 9 ’ (d) Onguent - Ester méthylique de l’acide 4-(5,6,7,8-tétrahydro- 5,5,8,8-tétraméthyl-2-naphtamido)-3-méthyl benzoïque.................................... 0,020g 5 - Myristate d'isopropyle....................... 81,700g - Huile de vaseline fluide..................... 9,100g - Silice ("Aérosil 200" de la Société DEGUSSA). 9,180g5 (a) 0.2g tablet - 4- (5,6,7,8-tetrahydro-5,5,8,8-tetra-methyl-2-naphtamido) benzoic acid ......... ...... 0.001g - Starch ....................................... 0.114 g - Dicalcium phosphate ......................... 0.020g 10 - Silica ................ ....................... 0.020g - Lactose ....................... ............... 0.030g - Talc ........... 0.010g - Magnesium stearate .............. .......... 0.005g (b) Oral suspension in 5ml ampoules 15 - Acid 4- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphtamido ) -benzoic ........................ 0.001g - Glycerin ................... ................. 0.500g - Sorbitol 70% .......................... ..... 0.500g - Sodium saccharinate ....................... 0.010g 20 - Methyl parahydroxybenzoate ......... ...... 0.040g - Aroma ........................................ qs - Purified water qs ............................. 5.00 ml B. TOPICAL ROUTE 25 (c) Oil-in-cream Anionic water - Acid 4- (5,6,7,8-tetrahydro-5,5,8,8-té tramethyl-2- naphtamido) -3-methyl benzoic ............... 0.010g - Sodium dodecyl sulfate .................. ... 0.800g 30 - Glycerol ..................................... 2,000g - Stearyl alcohol ........................... 20,000g - Triglycerides of capric / caprylic acid sold by the company DYNAMIT NOBEL under the name of "Miglyol 812 "................ 20,000g 35 - Preservative qs - Demineralized water ........................ .... 100,000g '' 9 '(d) Ointment - Methyl ester of 4- (5,6,7,8-tetrahydro- 5,5,8,8-tetramethyl-2-naphtamido) acid -3 -methyl benzoic .................................... 0.020g 5 - Isopropyl myristate ... .................... 81,700g - Fluid petroleum jelly oil ..................... 9,100g - Silica ("Aerosil 200" from the company DEGUSSA). 9.180g
Claims (18)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LU86259A LU86259A1 (en) | 1986-01-21 | 1986-01-21 | AROMATIC AMIDES, THEIR PREPARATION PROCESS AND THEIR USE IN HUMAN OR VETERINARY MEDICINE AND IN COSMETICS |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LU86259A LU86259A1 (en) | 1986-01-21 | 1986-01-21 | AROMATIC AMIDES, THEIR PREPARATION PROCESS AND THEIR USE IN HUMAN OR VETERINARY MEDICINE AND IN COSMETICS |
| LU86259 | 1986-01-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| LU86259A1 true LU86259A1 (en) | 1987-09-03 |
Family
ID=19730619
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LU86259A LU86259A1 (en) | 1986-01-21 | 1986-01-21 | AROMATIC AMIDES, THEIR PREPARATION PROCESS AND THEIR USE IN HUMAN OR VETERINARY MEDICINE AND IN COSMETICS |
Country Status (1)
| Country | Link |
|---|---|
| LU (1) | LU86259A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0350846A3 (en) * | 1988-07-14 | 1990-11-07 | F. Hoffmann-La Roche Ag | Condensed heterocyclic compounds and their use in therapy |
| EP0405028A1 (en) * | 1988-06-29 | 1991-01-02 | Allergan, Inc | Thiochroman esters of phenols and terephthalates having retinoid-like activity |
| WO1992017426A3 (en) * | 1991-03-26 | 1992-11-12 | Allergan Inc | 7-chromanyl esters of phenols and benzoic acids having retinoid-like activity |
-
1986
- 1986-01-21 LU LU86259A patent/LU86259A1/en unknown
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0405028A1 (en) * | 1988-06-29 | 1991-01-02 | Allergan, Inc | Thiochroman esters of phenols and terephthalates having retinoid-like activity |
| EP0350846A3 (en) * | 1988-07-14 | 1990-11-07 | F. Hoffmann-La Roche Ag | Condensed heterocyclic compounds and their use in therapy |
| US5300522A (en) * | 1988-07-14 | 1994-04-05 | Hoffmann-La Roche Inc. | Condensed heterocyclic compounds and pharmaceutical use thereof |
| WO1992017426A3 (en) * | 1991-03-26 | 1992-11-12 | Allergan Inc | 7-chromanyl esters of phenols and benzoic acids having retinoid-like activity |
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