| 主权项 |
1. A method for treating chemotherapy and/or radiation therapy side effects in a mammal undergoing chemotherapy and/or radiation therapy, the method comprising a step of administering to the mammal a therapeutically effective amount of at least one Retinoic Acid Receptor (RAR) antagonist or a RAR inverse agonist which binds to receptors of the RARα, RARβ and RARγ subtypes, wherein the RAR antagonist or RAR inverse agonist has the chemical structure according to Formula (I): or a pharmaceutically acceptable salt thereof; wherein X is S or O R2 independently are hydrogen, a 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 independently is hydrogen, lower alkyl of 1 to 6 carbons, or F; m is an integer having the value of 0-3; n is an integer having the value of 0-4; o is an integer having the value of 0-3; Z is —CONR1—, —CSNR1—, —NR1CO—, —NR1CS—, —C═C—, —C═C—, —N═N—, —N═CR1—, —CR1═N—, —COO—, —OCO—; —OSO—; —OCS—, or —(CR1═CR1)n′—, where n′ is an integer from 0 to 5; Y is a phenyl or naphthyl group, or a heteroaryl selected from a group consisting of pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, imidazolyl, and pyrrazolyl, the phenyl and heteroaryl groups being optionally substituted with one or two R2 groups, or when Z is —(CR1═CR1)n— and n′ is 3, 4, or 5, then Y represents a direct valence bond between said (CR2═CR2)n′ group and A; A is (CH2)q, where q is 0-5, a lower branched chain alkyl having 3 to 6 carbons, cycloalkyl having 3 to 6 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, or alkynyl having 2-6 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, CR7OR12O, or a tri-lower alkylsilyl; R7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons; R8 is an alkyl group of 1 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons, a cycloalkyl group of 3 to 10 carbons, phenyl or a lower alkylphenyl; R9 and R10 independently are hydrogen, an alkyl group of 1 to 10 carbons, a cycloalkyl group of 3 to 10 carbons, phenyl, or a lower alkylphenyl; R11 is a lower alkyl, phenyl, or lower alkylphenyl; R12 is a lower alkyl; R13 is a divalent alkyl radical of 2 to 5 carbons; R14 is (R15)r-phenyl, (R15)r-naphthyl, or (R15)r-heteroaryl, wherein the heteroaryl group has 1 to 3 heteroatoms selected from the group consisting of O, S and N, and r is an integer having the values of 0-5; and R15 is independently H, F, Cl, Br, I, NO2, N(R8)2, N(R8)COR8, NR8CON(R8)2, OH, OCOR8, ORB, CN, an alkyl group having 1 to 10 carbons, a fluoro substituted alkyl group having 1 to 10 carbons, an alkenyl group having 2 to 10 carbons and 1 to 3 double bonds, an alkynyl group having 2 to 10 carbons and 1 to 3 triple bonds, or a trialkylsilyl or trialkylsilyloxy group, where the alkyl groups independently have 1 to 6 carbons. |
