Patent IL-133290-A (IL)
Title: Compositions containing compounds having retinoid-like activity and reduced skin toxicity lacking teratogenic effects
IPC: A61K31/16
Filed: 1993-06-07
Abstract: A non-teratogenic pharmaceutical composition, administering to a female mammal, including a female human being, who is in a child bearing age or pregnant, for treating or preventing one or more of the diseases and conditions selected from the group consisting of dermatoses, malignant hyperproliferative diseases, atherosclerosis and restenosis resulting from neointimal hyperproliferation, non- malignant hyperproliferative diseases, autoimmune diseases, immunological disorders, chronic inflammatory diseases, diseases associated with lipid metabolism and transport such as dyslipidemias, dry eye syndrome, for promoting wound healing, and for reversing and preventing the effects of sun damage to skin, containing an effective dose of a compound of the formula 1440 כ" ג בסיון התשס" א - June 14, 2001 where the symbols are defined as follows: R1 is lower alkyl, Cl, Br, or I; R2 is H, lower alkyl, Cl, Br, or I; R3 is lower alkyl, Cl, Br, I, OR11, SR11, OCOR11, SCOR11, NH2, NHR11, N(R11)2, NHCOR12, or NR11-COR11; R5 and R6 independently are H, lower alkyl, Cl, Br, I, lower alkoxy or lower alkylthio of 1 to 6 carbons; or R5 and R6 may be absent; A is (CH2)n where n is 0-5, lower branched chain alkyl having 3 to 6 carbons, cycloalkyl having 3 double bonds, alkynyl having 2 to 6 carbons and 1 or 2 triple bonds; B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9R10- -CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13O, -COR7, CR7(OR12)2, or CR7OR13O, where R7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R8 is an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R8 is phenyl or lower alkylphenyl, R9 and R10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or phenyl or lower alkylphenyl, R11 is alkyl of 1 to 10 carbons, phenyl or lower alkylphenyl, R12 is lower alkyl, and R13 is divalent alkyl radical of 2-5 carbons; X1 is CR5 or N, and in case X1 is N it can be located in any unsubstituted position of the 6-membered aromatic ring; Y is phenyl, thienyl, furyl, pyrrolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, thiazolyl, imidazolyl and oxazolyl; Z is independently H, lower alkyl, lower alkoxy, lower alkylthio, lower alkenyl having one or more double bonds, lower alkenyloxy having one or more double bonds, or lower thioalkenyloxy having one or more double bonds, or Z represents - (CR14)4-, or Z represents - (CR14)=(CR14) -C(R14)2-, or Z represents (CR14)=)CR14) -X2-, or Z represents -C(R14)2- C(R14)2- X2-, or Z represents-C(R14)2- CR14=CR14-X2-, or Z represents -C(R14)2 -C(R14)2- C(R14)2- C(R14)2-, or Z represents -C(R14)2- -C(R14)2-C (R14)2-X2- where R14 independently is H, lower alkyl, lower alkoxy, lower alkylthio, Cl, Br, or l, X2 is O, S, or NR15 and R15 is H or lower alkyl; the dashed circle in the 5 membered ring of formula (ii) indicates the presence of two double bonds in the 5 membered ring, and X3 is O, S, NH or N-lower alkyl, and the X3 group can be located in any unsubstituted position of the 5-membered aromatic ring. 1441 כ" ג בסיון התשס" א - June 14, 2001