N-ARYLPHENYLACETAMIDE DERIVATIVES AND MEDICINAL COMPOSITIONS CONTAINING THE SAME

• Main Authors: SHIMIZU, ISAO, KAWASHIMA, KATSUYOSHI, ADACHI, KEIJI, NIIDOME, KAZUMI, ISHII, DAISUKE, MORIE, TOSHIYA
• Format: Patent
• Language: English; French; German
• Published: 30.08.2006
• Edition: 7
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

N-Arylphenylacetamide derivatives (I) are new. N-Arylphenylacetamide derivatives of formula (I) and their salts, hydrates and solvates are new. [Image] R 1OAlk, OH, halo, NO 2, NH 2, NHAlk, N(Alk) 2, NHSO 2Alk or NHSO 2Ar; Alk : 1-6C alkyl; Ar : aryl; R 2H, COAlk, COAr, (CH 2) mNR 6R 7, (CH 2) mOH or (CH 2) qCOOH; m : 0-2; q : 1-4; R 6Alk 1, 2 or 3C hydroxyalkyl, 2 or 3C aminoalkyl, CHO, COAlk 1, 1-4C alkoxycarbonyl, COAr or COOAlk 1Ar; R 7H, Alk 1, 2 or 3C hydroxyalkyl or 2 or 3C aminoalkyl; R 3H, halo, Alk, 1-4C alkoxy, Ar or CHO; Alk 11-3C alkyl; R 46-10C alkyl, YR 8 or piperidin-1-yl, morpholin-4-yl or thiomorpholin-4-yl all optionally substituted by 1 or 2 Alk, Cyc, halo, CF 3, 1-4C alkoxycarbonyl, Ar, AlkAr, OAlk 1 or OH or by a spiro ring; Y : bond, 1-3C alkylene, 2 or 3C alkenylene, 2 or 3C alkynylene, CO(CH 2) p, 2 or 3C alkylenecarbonyl, O, O(CH 2) 2, O(CH 2) 3 or CONH(CH 2) p; p : 0-3; Cyc : 3-7C cycloalkyl; R 8Ar 1 (optionally substituted by 1-3 halo, Alk, Cyc, 2-6C alkenyl, 2-6C alkynyl, CF 3, trifluoroethyl, Ar, AlkAr, OAlk, OCF 3, OCyc, OAr, OAlk 1Ar, COOAlk, COCyc, CHO, NO 2, NH 2, N(Alk) 2, CN, OH, SAlk 1, 1-4C alkoxycarbonyl-1-3C alkyl, Alk 1COOH, 1-4C alkoxycarbonyl, COOAlk 1Ar, COOH or SO 2NH 2), 5-7C cycloalkenyl (optionally substituted by 1-4 Alk, Cyc, halo, CF 3, 1-4C alkoxycarbonyl, Ar, AlkAr, OAlk 1 or OH) or a group of formula (i); Ar 15 or 6 membered mono or polycyclic aryl optionally containing 1-3 N, O or S; R a-R dH, Alk, Cyc, halo, CF 3, 1-4C alkoxycarbonyl, Ar, AlkAr, OAlk 1 or OH; or R a+R bO or S; or R c+R dspiro ring; or R a+R b+R c6-15C polycyclic alkyl; n : 1-6; R 5H, halo, Alk, CF 3, OAlk 1, OCF 3, CN, NH 2, NO 2, OH, COOH, CH 2OCOAlk or Ar; or R 4+R 5fused tetralone or indole ring optionally monosubstituted by 1-8C alkyl, 1-8C alkenyl (sic), Alk 1Ar, Alk 1Cyc, SO 2Ar, 1-8C alkylidene (optionally substituted by Ar or Cyc) or 1-8C alkenylidene (sic); provided that when R 4para-YR 8 and Y = 1-3C alkylene or 2 or 3C alkenylene then R 8 is not pyrrolyl, pyrazolyl, imidazolyl, triazolyl or pyrimidyl optionally substituted by NH 2, Alk, Ar or SAlk 1. [Image] ACTIVITY : Analgesic; Antimanic; Antiallergic; Antiinflammatory; Antiarthritic; Antirheumatic; Uropathic; Cerebroprotective; Antiasthmatic; Dermatological; Ophthalmological; Antiulcer; Anorectic. In a phenyl-1,4-benzoquinone induced writhing test in ddY mice N-(3-cyclohexylphenyl)-4-hydroxy-3-methoxyphenylacetamide (Ia) had an ED 5 0 value of 0.014 mg/kg s.c. compared to 1.15 mg/kg s.c. for capsaicin. MECHANISM OF ACTION : Vanilloid-Antagonist.