New 4-(omega-arylalkyl)phenylalkanoic acid derivs. - used as LTB4 inhibitors for treating eczema, psoriasis, acne, arthritis, asthma, allergies or inflammatory bowel disease

摘要

Phenylalkanoic acids, their salts and/or derivs. of formula (I) are new. In (I), R1 is pyridyl, quinolyl, naphthyl or R6R7-phenyl; R6 and R7 are H, halo, Me, OH, trihalomethyl (esp. CF3), NO2, NH2 (opt. substd. by alkyl, esp. 1 or 2 Me), phenyl, tert. butyl, -NR9-COR5 or -NH-SO2R8; R8 is phenyl, Me or trihalomethyl (esp. CF3); R9 is H or Me; R2 is bond, CO, CH2, or CHOH; R3 is bond, CO, S, O, SO2, HOCO or CH2; R4 is bond, OCH2 or -CR10R11-; R10 and R11 are H and/or Me; R5 is H, alkyl, (esp. Me or Et), or alkali metal (esp. Na or K); m is 0-3; n is 4-7. (I) are derived from pentanoic, hexanoic, heptanoic or octanoic acids, or their Me or Et esters. (I) may be prepd. by reacting acid chloride of formula (1) R-(CH2)m-CoCl with aryl alkyl ester of formula (ii) where R13 is R3 other than CO or SO2; R15 is alkyl). Reaction is under usual conditions for Friedel-crafts acylation and the ester prods. can be hydrolysed conventionally. USE/ADVANTAGE - (I) are inhibitors of leucotriene-A4 hydrolysis so are useful for treatment of chronic inflammation esp. rheumatic diseases (esp. arthritis), psoriasis, eczema, acne and other skin conditions; intestinal inflammatory lesions; allergy and asthma. They are administered orally, rectally or parenterally, pref. in unit doses of 10-150 mg.