O- or S-substituted tetrahydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity

A compound of the formula:

• where R1 is independently H or alkyl of 1 to 6 carbons;
• X2 is S or O;
• Z is —CO—CR1═CR1—;
• R2 is hydrogen, lower alkyl of 1 to 6 carbons;
• R3 is hydrogen, lower alkyl of 1 to 6 carbons or F;
• m is an integer having the value of 0-3;
• o is an integer having the value of 0-4;
• Y is thienyl;
• A is (CH2)q where q is 0-5, lower branched chain alkyl having 3-6 carbons, cycloalkyl having 3-6 carbons, alkenyl having 2-6 carbons and 1 or 2 double bonds, alkynyl having 2-6 carbons and 1 or 2 triple bonds;
• B is COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9R10, —CH2OH, CH2 OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13o0, —COR7, CR7(OR12)2, CR7OR13O, or Si(C1-6alkyl)3, 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 (trimethylsilyl)alkyl where the alkyl group has 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 5-10 carbons, or phenyl or lower alkylphenyl, R11 is lower alkyl, phenyl or lower alkylphenyl, R12 is lower alkyl, and R13 is divalent alkyl radical of 2-5 carbons;
• R4 is hydrogen, alkyl of 1 to 10 carbons, CH2COOH or CH2CO2R8;
• R5 is hydrogen, alkyl of 1 to 10 carbons, 2-tetrahydropyranyl, CH2OCH3 or COR12.

A compound of the formula:

• wherein X1 is (C(R1)2)n where R1 is independently H or alkyl of 1 to 6 carbons, and n is an integer between 0 and 2;
• X2 is S or O;
• Z is —(CR1═CR1)n′—where n′is an integer having the value 1-2,
• —COO—,
• —OCO—;
• —CSO—;
• —OCS—;
• —CO—CR1═CR1—;
• R2 is hydrogen, lower alkyl of 1 to 6 carbons, F, Cl, Br, I, CF3, fluoro substituted alkyl of 1 to 6 carbons, OH, SH, alkoxy of 1 to 6 carbons, or alkylthio of 1 to 6 carbons;
• R3 is hydrogen, lower alkyl of 1 to 6 carbons or F;
• m is an integer having the value of 0-3;
• o is an integer having the value of 0-4;
• R4 is hydrogen, alkyl of 1 to 10 carbons, alkenyl of 2 to 10 carbons and having 1 to 3 double bonds, alkynyl having 2 to 10 carbons and 1 to 3 triple bonds, carbocyclic aryl selected from the group consisting of phenyl, C1-C10-alkylphenyl, naphthyl, C1-C10-alkylnaphthyl, phenyl-C1-C10alkyl, napthyl-C1-C10alkyl;
• CN, (CH2)pCO2H or (CH2)pCO2R8 where p is an integer between 0 to 10;
• R5 is hydrogen, alkyl of 1 to 10 carbons, fluoro-substituted alkyl of 1 to 10 carbons, alkenyl of 2 to 10 carbons and having 1 to 3 double bonds, alkynyl having 2 to 10 carbons and 1 to 3 triple bonds, carbocyclic aryl selected from the group consisting of phenyl, C1-C10-alkylphenyl, naphthyl, C1-C10-alkylnaphthyl, phenyl-C1-C10alkyl, napthyl-C1-C10alkyl;
• Si(C1-6alkyl)3, COR14, camphanoyl, or 2-tetrahydropyranyl;
• Y is selected from a group consisting of thienyl and furyl, said heteroaryl groups being optionally substituted with one or two R2 groups;
• A is (CH2)q where q is 0-5, lower branched chain alkyl having 3-6 carbons, cycloalkyl having 3-6 carbons, alkenyl having 2-6 carbons and 1 or 2 double bonds, alkynyl having 2-6 carbons and 1 or 2 triple bonds;
• B is COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9R10, —CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13O, —COR7, CR7(OR12)2, CR7OR13O, or Si(C1-6alkyl)3, 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 (trimethylsilyl)alkyl where the alkyl group has 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 5-10 carbons, or phenyl or lower alkylphenyl, R11 is lower alkyl, phenyl or lower alkylphenyl, R12 is lower alkyl, and R13 is divalent alkyl radical of 2-5 carbons, and
• R14 is hydrogen, alkyl of 1 to 10 carbons, alkenyl of 2 to 10 carbons and having 1 to 3 double bonds, alkynyl having 2 to 10 carbons and 1 to 3 triple bonds, carbocyclic aryl selected from the group consisting of phenyl, C1-C10-alkylphenyl, naphthyl, C1-C10-alkylnaphthyl, phenyl-C1-C10alkyl, napthyl-C1-C10alkyl.