| 主权项 |
1. A method of reducing or inhibiting spermatogenesis in a healthy fertile male subject in need thereof, the method comprising administering an amount of a compound represented by structural formula (I) sufficient to induce at least one of azoospermia, oligozoospermia, or asthenozoospermia:wherein
X is N or CR5; R5 is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted; RB is H, alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, haloalkyl, hydroxy, alkoxy, or —COO—R3, each of which is optionally substituted; ring A is aryl or heteroaryl; each RA is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted; 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; R1 is —(CH2)n-L, in which n is 0-3 and L is —COO—R3, —CO—R3, —CO—N(R3R4), —S(O)2—R3, —S(O)2—N(R3R4), N(R3R4), N(R4)C(O)R3, optionally substituted aryl, or optionally substituted heteroaryl; R2 is H, D, (deuterium), halogen, or optionally substituted alkyl; each R3 is independently selected from the group consisting of: (i) H, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; (ii) heterocycloalkyl or substituted 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; and (iv) NH2, N═CR4R6; each R4 is independently H, alkyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted; 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; 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;provided that
(a) if ring A is thienyl, X is N, R is phenyl or substituted phenyl, R2 is H, RB is methyl, and R1 is —(CH2)n-L, in which n is 1 and L is —CO—N(R3R4), then R3 and R4 are not taken together with nitrogen atom to which they are attached to form a morpholino ring; (b) if ring A is thienyl, X is N, R is substituted phenyl, R2 is H, RB is methyl, and R1 is —(CH2)n-L, in which n is 1 and L is —CO—N(R3R4), and one of R3 and R4 is H, then the other of R3 and R4 is not methyl, hydroxyethyl, alkoxy, phenyl, substituted phenyl, pyridyl or substituted pyridyl; and (c) if ring A is thienyl, X is N, R is substituted phenyl, R2 is H, RB is methyl, and R1 is —(CH2)n-L, in which n is 1 and L is —COO—R3 is not methyl or ethyl, or a pharmaceutically acceptable salt thereof,
thereby inducing a contraceptive effect in the healthy fertile male subject. |
