Male contraceptive compositions and methods of use

A method of reducing or inhibiting spermatogenesis in a healthy fertile male subject, the method comprising administering an effective amount of a compound or a salt thereof that inhibits a bromodomain testis-specific protein (BRDT) to the male subject, wherein the compound is of Formula (I):

• wherein:
• X is N or CR5;
• R5 is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• RB is H, alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, haloalkyl, hydroxy, alkoxy, or —COO—R3, wherein alkyl is optionally substituted with halogen or —OH;
• ring A is phenyl or thienyl;
• each RA is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, amino, or —OH;
• or any two RA together with the atoms to which each is attached, can form a fused aryl or heteroaryl group;
• R is alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• each of which is optionally substituted with halogen, alkyl, amino, —OH, or aryl;
• R1 is —(CH2)n-L, in which n is 0-3 and L is H, —COO—R3, —CO—R3, —CO—N(R3R4), —S(O)2—R3, —S(O)2—N(R3R4), N(R3R4), N(R4)C(O)R3, aryl optionally substituted with alkyl, halogen, amino, or —OH, or heteroaryl optionally substituted with alkyl, halogen, amino, or —OH;
• R2 is H, D (deuterium), halogen, or alkyl optionally substituted with halogen, amino, or —OH;
• each R3 is independently selected from the group consisting of:
• (i) H, aryl, or heteroaryl;
• (ii) heterocycloalkyl;
• (iii) —C1-C8 alkyl, —C2-C8 alkenyl or —C2-C8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• —C3-C12 cycloalkyl, substituted —C3-C12 cycloalkyl, —C3-C12 cycloalkenyl, or substituted —C3-C12 cycloalkenyl, each of which may be optionally substituted with halogen, alkyl, amino, —OH, or heterocyclyl;
• (iv) N═CR4R6;
• each R4 is independently H, alkyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH)2, —SO2Na, or —OH;
• or R3 and R4 are taken together with the nitrogen atom to which they are attached to form a 4-10-membered ring;
• R6 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH)2, —SO2Na, or —OH;
• or R4 and R6 are taken together with the carbon atom to which they are attached to form a 4-10-membered ring;
• m is 0, 1, 2, or 3;
• wherein the compound contains a fluorine or chlorine atom.