N-(PYRID-4-YL)AMIDES AND N-(PYRIMIDIN-4-YL)AMIDES AND THEIR PHARMACEUTICAL AND COSMETIC USE

摘要

N-(pyrid-4-yl)amides and N-(pyrimidin-4-yl)amides of formula (1) are described that are potent modulators (e.g., inhibitors) of an androgen receptor, and which are useful, for example, in the treatment of a dermatological disease or disorder; a disease or disorder of the sebaceous gland(s); acne; hyperseborrhoea; oily skin, seborrhoeic dermatitis; hyperpilosity or hirsutism; atopic dermatitis; or androgenic alopecia; especially acne. Also described, are compositions (e.g., pharmaceutical compositions, cosmetic compositions) comprising the compounds; methods of preparing the compositions; methods of modulating (e.g., inhibiting) and androgen receptors using the compounds and/or compositions; and medical and/or cosmetic use of the compounds and compositions.

主权项

1. A compound of formula (1), or a pharmaceutically acceptable salt, hydrate, or solvate thereof: wherein:
R1 is C1-6 alkyl, C3-7 cycloalkyl, C1-6 alkyloxy, —S(O)m—C1-6 alkyl, C1-6 fluoroalkyl, C1-6 fluoroalkyloxy, C1-6 alkyl-OH, —(CH2)i—C1-6 alkyloxy, —(CH2)i—O—C1-6 fluoroalkyl, CORa, CN, NO2, NR5R6, or a halogen atom;R2 is a hydrogen atom, C1-6 alkyl, C3-7 cycloalkyl, C1-6 alkyloxy, —S(O)n—C1-6 alkyl, C1-6 fluoroalkyl, C1-6 fluoroalkyloxy, C1-6 alkyl-OH, —(CH2)k—C1-6 alkyloxy, —(CH2)l—O—C1-6 fluoroalkyl, CORb, CN, NO2, NR5′R6′, OH, or a halogen atom;R3 and R4 are identical or different and are a hydrogen atom, C1-12 alkyl, C3-9 cycloalkyl, C1-6 fluoroalkyl, —C1-6 alkyl-OH, —(CH2)p—C1-6 alkyloxy, —(CH2)q—C3-9 cycloalkyl, —(CH2)r—C1-6 fluoroalkyl, —(CH2)s—O—C1-6 fluoroalkyl, phenyl, heteroaryl, heterocyclyl group, —(CH2)t-phenyl, or —(CH2)v-heteroaryl, wherein each phenyl and heteroaryl is optionally substituted with one to three identical or different Rc groups;and additionally, R3 and R4, together with the carbon atom carrying them, may form a C3-9 cycloalkyl group or a heterocyclyl group, such as tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydro-1-oxo-thiopyranyl, or tetrahydro-1,1-dioxo-thiopyranyl;Rc is C1-6 alkyl, C3-7 cycloalkyl, C1-6 alkyloxy, —S(O)u—C1-6 alkyl, C1-6 fluoroalkyl, C1-6 fluoroalkyloxy, C1-6alkyl-OH, CORd, CN, NO2, NR9R10, OH, or a halogen atom;Ra, Rb, and Rd are identical or different and are C1-6 alkyl, C1-6 alkyloxy, or NR7R8;R5, R5′, R6, R6′, R7, R8, R9 and R10 are identical or different and are a hydrogen atom, C1-6 alkyl, C3-7 cycloalkyl, or —(CH2)w—C3-7cycloalkyl;and additionally, R5 and R6, together with the nitrogen atom carrying them, may form a heterocyclyl group;and additionally, R5′ and R6′, together with the nitrogen atom carrying them, may form a heterocyclyl group;and additionally, R7 and R8, together with the nitrogen atom carrying them, may form a heterocyclyl group;and additionally, R9 and R10, together with the nitrogen atom carrying them, may form a heterocyclyl group;i, j, k, I, p, q, r, s, t, v, and w are different or identical and are 1, 2 or 3;m, n, and u are different or identical and are 0, 1 or 2; andX is CH or N.