Heterocyclic compounds
A compound of the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a pharmaceutically acceptable salt thereof has a superior inhibitory activity on cancer cell proliferation.
1 . A compound represented by the following formula (I):
wherein
Q is a hydrogen atom or is represented by any of the following formulas (II-1) to (II-8):
R 1 is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkylalkyl, or —(CO)—R 1a ;
R 1a is optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, or optionally substituted heteroaryl;
R 1b is a hydrogen atom, or 1 to 3 same or different alkyls;
Q 1a is a single bond, optionally substituted alkylene;
Q 1b is a hydrogen atom, hydroxy, halogen, cyano, -Q 1c , —COQ 1c , —CONQ 1c Q 1d , CONQ 1c -OQ 1d , —NQ 1c Q 1d , or —OQ 1c ;
Q 1c is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl;
Q 1d is a hydrogen atom or optionally substituted alkyl;
Q 2a is optionally substituted cycloalkylene;
Q 2b and Q 2c are the same or different and each is a hydrogen atom or optionally substituted alkyl;
U is —CO— or —CH 2 —;
R 2 is a hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or —X—N(R 2a )(R 2b );
X is an alkylene group;
R 2a and R 2b are the same or different and each is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, or optionally substituted cycloalkylalkyl;
V is an optionally substituted aryl ring, an optionally substituted heteroaryl ring, an optionally substituted partially saturated heteroaryl ring, or an optionally substituted heterocycloalkyl ring;
R 3 is a hydrogen atom, hydroxy, halogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, —C≡C—R 3a or —COOR 3b ;
R 3a is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl,
R 3b is a hydrogen atom or optionally substituted alkyl,
is represented by any of the following formulas (III-1) to (III-4):
R 4 is a hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocycloalkylalkyl, and
Ar 2 is an optionally substituted aryl ring or an optionally substituted heteroaryl ring; and
R 5 is a hydrogen atom, or optionally substituted alkyl; and
R 6 and R 7 are the same or different and each is a hydrogen atom or halogen,
or a pharmaceutically acceptable salt thereof.
2 . The compound according to claim 1 , wherein the compound is represented by the following formula (I-a):
wherein
R 1 is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkylalkyl, or —(CO)—R 1a ;
R 1a is optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, or optionally substituted heteroaryl;
is represented by any of the following formulas (II-1-a) to (II-6-a):
R 1b is a hydrogen atom, or 1 to 3 same or different alkyls;
R 2 is a hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or —X—N(R 2a )(R 2b );
X is an alkylene group;
R 2a and R 2b are the same or different and each is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, or optionally substituted cycloalkylalkyl;
Ar 1 is an optionally substituted aryl ring or an optionally substituted heteroaryl ring;
R 3 is a hydrogen atom, hydroxy, halogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, —C≡C—R 3a or —COOR 3b ;
R 3a is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl,
R 3b is a hydrogen atom or optionally substituted alkyl,
is represented by any of the following formulas (III-1) to (III-3):
R 4 is a hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocycloalkylalkyl, and
Ar 2 is an optionally substituted aryl ring or an optionally substituted heteroaryl ring; and
R 5 is a hydrogen atom, or optionally substituted alkyl,
or a pharmaceutically acceptable salt thereof.
3 . The compound according to claim 1 , wherein the compound is represented by the following formula (IV):
wherein each symbol is as defined in claim 1 ,
or a pharmaceutically acceptable salt thereof.
4 . The compound according to claim 1 , wherein the compound is represented by the following formula (IV-a):
wherein each symbol is as defined in claim 2 ,
or a pharmaceutically acceptable salt thereof.
5 . The compound according to claim 1 , wherein
Q is represented by any of the following formulas (VI-1) to (VI-3):
wherein each symbol is as defined in claim 1 ,
or a pharmaceutically acceptable salt thereof.
6 . The compound according to claim 1 , wherein
Q is represented by the following formulas (II-7):
and
Q 1a is an alkylene and Q 1b is —CONH-Q 1c , -Q 1d , —CO-Q 1a , —N(Q 1c )-Q 1d , wherein Q 1c is a hydrogen atom or an alkyl and Q 1d is a hydrogen atom or heterocycloalkyl optionally substituted by alkyl,
or a pharmaceutically acceptable salt thereof.
7 . The compound according to claim 2 , wherein
is represented by any of the following formulas (VI-1-a) to (VI-3-a):
or a pharmaceutically acceptable salt thereof.
8 . The compound according to claim 2 , wherein Ar 1 is an optionally substituted pyridine ring, an optionally substituted thiazole ring, an optionally substituted benzothiazole ring, or an optionally substituted quinoxaline ring, or a pharmaceutically acceptable salt thereof.
9 . The compound according to claim 8 , wherein
is represented by the following formula (VII-1-a), (VII-2-a), or (VII-3-a):
or a pharmaceutically acceptable salt thereof.
10 . The compound according to claim 1 , wherein
R 1 is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or —(CO)—R 1a ;
R 1a is optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, or optionally substituted heteroaryl;
R 1b is a hydrogen atom;
R 2 is optionally substituted alkyl, or optionally substituted arylalkyl;
R 3a is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl,
R 4 is optionally substituted alkyl,
Ar 2 is an optionally substituted aryl ring, and
R 5 is a hydrogen atom,
or a pharmaceutically acceptable salt thereof.
11 . The compound according to claim 1 , wherein
is represented by the following formula (V):
and
R 4 ′ is optionally substituted alkyl or optionally substituted cycloalkyl, or a pharmaceutically acceptable salt thereof.
12 . The compound according to claim 11 , wherein
R 4 ′ is an alkyl group,
or a pharmaceutically acceptable salt thereof.
13 . The compound according to claim 11 , wherein R 4 ′ is an isobutyl group, or a pharmaceutically acceptable salt thereof.
14 . The compound according to claim 1 , wherein R 2 is alkyl optionally substituted by alkylthio or alkylsulfonyl, or arylalkyl, or a pharmaceutically acceptable salt thereof.
15 . The compound according to claim 14 , wherein R 2 is isobutyl, neopentyl, sec-butyl, or benzyl, or a pharmaceutically acceptable salt thereof.
16 . The compound according to claim 1 , wherein R 1 is alkyl or alkyl substituted by 1 or 2 hydroxys, or a pharmaceutically acceptable salt thereof.
17 . The compound according to claim 1 , wherein R 3 is a hydrogen atom, hydroxy, or —C≡C—R 3a ; and R 3a is alkyl substituted by hydroxy, or a pharmaceutically acceptable salt thereof.
18 . A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier or diluent.