Male contraceptive compositions and methods of use
View Patent ↗The invention relates to compositions and methods for effecting male contraception.
1. 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 CR 5 ;
R 5 is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
R B is H, alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, haloalkyl, hydroxy, alkoxy, or —COO—R 3 , wherein alkyl is optionally substituted with halogen or —OH;
ring A is phenyl or thienyl;
each R A is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, amino, or —OH; or any two R A 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;
R 1 is —(CH 2 ) n -L, in which n is 0-3 and L is H, —COO—R 3 , —CO—R 3 , —CO—N(R 3 R 4 ), —S(O) 2 —R 3 , —S(O) 2 —N(R 3 R 4 ), N(R 3 R 4 ), N(R 4 )C(O)R 3 , aryl optionally substituted with alkyl, halogen, amino, or —OH, or heteroaryl optionally substituted with alkyl, halogen, amino, or —OH;
R 2 is H, D (deuterium), halogen, or alkyl optionally substituted with halogen, amino, or —OH;
each R 3 is independently selected from the group consisting of:
(i) H, aryl, or heteroaryl;
(ii) heterocycloalkyl;
(iii) —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl or —C 2 -C 8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, alkyl, amino, —OH, or heterocyclyl;
(iv) N═CR 4 R 6 ;
each R 4 is independently H, alkyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH;
or R 3 and R 4 are taken together with the nitrogen atom to which they are attached to form a 4-10-membered ring;
R 6 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH; or R 4 and R 6 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.
2. A method of reducing the rate of male fertility in a healthy fertile male subject, the method comprising administering an effective amount of a compound or a salt thereof that inhibits a BRDT to the male subject, wherein the compound is of Formula (I):
wherein:
X is N or CR 5 ;
R 5 is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
R B is H, alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, haloalkyl, hydroxy, alkoxy, or —COO—R 3 , wherein alkyl is optionally substituted with halogen or —OH;
ring A is phenyl or thienyl;
each R A is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, amino, or —OH; or any two R A 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;
R 1 is —(CH 2 ) n -L, in which n is 0-3 and L is H, —COO—R 3 , —CO—R 3 , —CO—N(R 3 R 4 ), —S(O) 2 —R 3 , —S(O) 2 —N(R 3 R 4 ), N(R 3 R 4 ), N(R 4 )C(O)R 3 , aryl optionally substituted with alkyl, halogen, amino, or —OH, or heteroaryl optionally substituted with alkyl, halogen, amino, or —OH;
R 2 is H, D (deuterium), halogen, or alkyl optionally substituted with halogen, amino, or —OH;
each R 3 is independently selected from the group consisting of:
(i) H, aryl, or heteroaryl;
(ii) heterocycloalkyl;
(iii) —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl or —C 2 -C 8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, alkyl, amino, —OH, or heterocyclyl;
(iv) N═CR 4 R 6 ;
each R 4 is independently H, alkyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH;
or R 3 and R 4 are taken together with the nitrogen atom to which they are attached to form a 4-10-membered ring;
R 6 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH; or R 4 and R 6 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.
3. The method of claim 1 , wherein the method comprises administering the compound or a salt thereof in an amount sufficient to reduce sperm number and/or reduce sperm motility.
4. The method of claim 1 , wherein the method comprises administering the compound or a salt thereof in an amount sufficient to induce azoospermia, oligozoospermia, and/or asthenozoospermia.
5. The method of claim 4 , wherein the method induces a contraceptive effect in the subject.
6. The method of claim 1 , wherein the compound or a salt thereof is administered to the subject orally, transdermally, or by injection.
7. The method of claim 6 , wherein the compound or a salt thereof is administered in the form of a tablet or capsule.
8. The method of claim 6 , wherein the compound or a salt thereof is administered by parenteral injection, intramuscular injection, intravenous injection, subcutaneous implantation, subcutaneous injection, or transdermal preparation.
9. The method of claim 1 , wherein the compound or a salt thereof is administered in combination with a pharmaceutically acceptable carrier, excipient, or diluent.
10. The method of claim 1 , wherein the compound is JQ1 or a compound of Formula II:
wherein
X is N or CR 5 ;
R 5 is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted;
R B is H, alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, haloalkyl, hydroxy, alkoxy, or —COO—R 3 , each of which wherein alkyl is optionally substituted with halogen or —OH;
each R A is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, amino, or —OH; or any two R A 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;
R′ 1 is H, —COO—R 3 , —CO—R 3 , optionally substituted aryl, or optionally substituted heteroaryl, each of which is optionally substituted with halogen, amino, or —OH;
each R 3 is independently selected from the group consisting of:
(i) H, aryl, substituted aryl, or heteroaryl, or substituted heteroaryl;
(ii) heterocycloalkyl or substituted heterocycloalkyl;
(iii) —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl or —C 2 -C 8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, alkyl, amino, —OH, or heterocyclyl;
m is 0, 1, 2, or 3, or salt thereof;
wherein the compound contains a fluorine or chlorine atom.
11. The method of claim 10 , wherein the subject is human.
12. The method of claim 2 , wherein the method comprises administering the compound or a salt thereof in an amount sufficient to reduce sperm number and/or reduce sperm motility.
13. The method of claim 2 , wherein the method comprises administering the compound or a salt thereof in an amount sufficient to induce azoospermia, oligozoospermia, and/or asthenozoospermia.
14. The method of claim 13 , wherein the method induces a contraceptive effect in the subject.
15. The method of claim 2 , wherein the compound or a salt thereof is administered to the subject orally, transdermally, or by injection.
16. The method of claim 15 , wherein the compound or a salt thereof is administered in the form of a tablet or capsule.
17. The method of claim 15 , wherein the compound or a salt thereof is administered by parenteral injection, intramuscular injection, intravenous injection, subcutaneous implantation, subcutaneous injection, or transdermal preparation.
18. The method of claim 2 , wherein the compound or a salt thereof is administered in combination with a pharmaceutically acceptable carrier, excipient, or diluent.
19. The method of claim 2 , wherein the compound is JQ1 or a compound of Formula (I):
wherein:
X is N or CR 5 ;
R 5 is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
R B is H, alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, haloalkyl, hydroxy, alkoxy, or —COO—R 3 , wherein alkyl is optionally substituted with halogen or —OH;
ring A is phenyl or thienyl;
each R A is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, amino, or —OH; or any two R A 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;
R 1 is —(CH 2 ) n -L, in which n is 0-3 and L is H, —COO—R 3 , —CO—R 3 , —CO—N(R 3 R 4 ), —S(O) 2 —R 3 , —S(O) 2 —N(R 3 R 4 ), N(R 3 R 4 ), N(R 4 )C(O)R 3 , aryl optionally substituted with alkyl, halogen, amino, or —OH, or heteroaryl optionally substituted with alkyl, halogen, amino, or —OH;
R 2 is H, D (deuterium), halogen, or alkyl optionally substituted with halogen, amino, or —OH;
each R 3 is independently selected from the group consisting of:
(i) H, aryl, or heteroaryl;
(ii) heterocycloalkyl;
(iii) —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl or —C 2 -C 8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, alkyl, amino, —OH, or heterocyclyl;
(iv) N═CR 4 R 6 ;
each R 4 is independently H, alkyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH;
or R 3 and R 4 are taken together with the nitrogen atom to which they are attached to form a 4-10-membered ring;
R 6 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH; or R 4 and R 6 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;
or a salt thereof;
wherein the compound contains a fluorine or chlorine atom.
20. The method of claim 2 , wherein the subject is human.
21. The method of claim 1 , wherein the compound is JQ1 or a compound of Formula III:
wherein
X is N or CR 5 ;
R 5 is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
R B is H, alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, haloalkyl, hydroxy, alkoxy, or —COO—R 3 , wherein alkyl is optionally substituted with halogen or —OH;
ring A is phenyl or thienyl;
each R A is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, amino, or —OH; or any two R A 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;
each R 3 is independently selected from the group consisting of:
(i) H, aryl, or heteroaryl;
(ii) heterocycloalkyl;
(iii) —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl or —C 2 -C 8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, alkyl, amino, —OH, or heterocyclyl; and
(iv) NH 2 , N═CR 4 R 6 ;
each R 4 is independently H, alkyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH;
or R 3 and R 4 are taken together with the nitrogen atom to which they are attached to form a 4-10-membered ring;
R 6 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH; or R 4 and R 6 are taken together with the carbon atom to which they are attached to form a 4-10-membered ring; and
m is 0, 1, 2, or 3;
wherein the compound contains a fluorine or chlorine atom.
22. The method of claim 1 , wherein the compound is JQ1 or a compound of Formula IV:
wherein
X is N or CR 5 ;
R 5 is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
R B is H, alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, haloalkyl, hydroxy, alkoxy, or —COO—R 3 , wherein alkyl is optionally substituted with halogen or —OH;
ring A is phenyl or thienyl;
each R A is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, amino, or —OH; or any two R A together with the atoms to which each is attached, can form a fused aryl or heteroaryl group;
R 1 is —(CH 2 ) n -L, in which n is 0-3 and L is H, —COO—R 3 , —CO—R 3 , —CO—N(R 3 R 4 ), —S(O) 2 —R 3 , —S(O) 2 —N(R 3 R 4 ), N(R 3 R 4 ), N(R 4 )C(O)R 3 , aryl optionally substituted with alkyl, halogen, amino, or —OH, or heteroaryl optionally substituted with alkyl, halogen, amino, or —OH;
R 2 is H, D (deuterium), halogen, or alkyl optionally substituted with halogen, amino, or —OH;
each R 3 is independently selected from the group consisting of:
(i) H, aryl, or heteroaryl;
(ii) heterocycloalkyl;
(iii) —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl or —C 2 -C 8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, alkyl, amino, —OH, or heterocyclyl; and
(iv) N═CR 4 R 6 ;
each R 4 is independently H, alkyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH;
or R 3 and R 4 are taken together with the nitrogen atom to which they are attached to form a 4-10-membered ring;
R 6 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH; or R 4 and R 6 are taken together with the carbon atom to which they are attached to form a 4-10-membered ring; and
m is 0, 1, 2, or 3;
wherein the compound contains a fluorine or chlorine atom.
23. The method of claim 1 , wherein the compound is JQ1 or a compound of Formulae V-XXII:
wherein:
R is H, aryl, substituted aryl, heteroaryl, heteroaryl, heterocycloalkyl, —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl, —C 2 -C 8 alkynyl, —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, alkyl, amino, —OH, or aryl;
R′ is H, aryl, substituted aryl, heteroaryl, heteroaryl, heterocycloalkyl, —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl, —C 2 -C 8 alkynyl, —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, amino, or —OH; and
X is a substituent of an aryl group;
wherein the compound contains a fluorine or chlorine atom.
24. The method of claim 2 , wherein the compound is JQ1 or a compound of Formula III:
wherein
X is N or CR 5 ;
R 5 is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
R B is H, alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, haloalkyl, hydroxy, alkoxy, or —COO—R 3 , wherein alkyl is optionally substituted with halogen or —OH;
ring A is phenyl or thienyl;
each R A is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, amino, or —OH; or any two R A 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;
each R 3 is independently selected from the group consisting of:
(i) H, aryl, or heteroaryl;
(ii) heterocycloalkyl;
(iii) —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl or —C 2 -C 8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, alkyl, amino, —OH, or heterocyclyl; and
(iv) NH 2 , N═CR 4 R 6 ;
each R 4 is independently H, alkyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH;
or R 3 and R 4 are taken together with the nitrogen atom to which they are attached to form a 4-10-membered ring;
R 6 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH; or R 4 and R 6 are taken together with the carbon atom to which they are attached to form a 4-10-membered ring; and
m is 0, 1, 2, or 3;
wherein the compound contains a fluorine or chlorine atom.
25. The method of claim 2 , wherein the compound is JQ1 or a compound of Formula IV:
wherein
X is N or CR 5 ;
R 5 is H, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
R B is H, alkyl, hydroxylalkyl, aminoalkyl, alkoxyalkyl, haloalkyl, hydroxy, alkoxy, or —COO—R 3 , wherein alkyl is optionally substituted with halogen or —OH;
ring A is phenyl or thienyl;
each R A is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, amino, or —OH; or any two R A together with the atoms to which each is attached, can form a fused aryl or heteroaryl group;
R 1 is —(CH 2 ) n -L, in which n is 0-3 and L is H, —COO—R 3 , —CO—R 3 , —CO—N(R 3 R 4 ), —S(O) 2 —R 3 , —S(O) 2 —N(R 3 R 4 ), N(R 3 R 4 ), N(R 4 )C(O)R 3 , aryl optionally substituted with alkyl, halogen, amino, or —OH, or heteroaryl optionally substituted with alkyl, halogen, amino, or —OH;
R 2 is H, D (deuterium), halogen, or alkyl optionally substituted with halogen, amino, or —OH;
each R 3 is independently selected from the group consisting of:
(i) H, aryl, or heteroaryl;
(ii) heterocycloalkyl;
(iii) —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl or —C 2 -C 8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, alkyl, amino, —OH, or heterocyclyl; and
(iv) N═CR 4 R 6 ;
each R 4 is independently H, alkyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH;
or R 3 and R 4 are taken together with the nitrogen atom to which they are attached to form a 4-10-membered ring;
R 6 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with halogen, alkyl, amino, —B(OH) 2 , —SO 2 Na, or —OH; or R 4 and R 6 are taken together with the carbon atom to which they are attached to form a 4-10-membered ring; and
m is 0, 1, 2, or 3;
wherein the compound contains a fluorine or chlorine atom.
26. The method of claim 2 , wherein the compound is JQ1 or a compound of Formulae V-XXII:
wherein:
R is H, aryl, substituted aryl, heteroaryl, heteroaryl, heterocycloalkyl, —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl, —C 2 -C 8 alkynyl, —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, alkyl, amino, —OH, or aryl;
R′ is H, aryl, substituted aryl, heteroaryl, heteroaryl, heterocycloalkyl, —C 1 -C 8 alkyl, —C 2 -C 8 alkenyl, —C 2 -C 8 alkynyl, —C 3 -C 12 cycloalkyl, substituted —C 3 -C 12 cycloalkyl, —C 3 -C 12 cycloalkenyl, or substituted —C 3 -C 12 cycloalkenyl, each of which may be optionally substituted with halogen, amino, or —OH; and
X is a substituent of an aryl group;
Y is C; and n is 1 in Formula (V);
wherein the compound contains a fluorine or chlorine atom.