Nitrogen-containing aromatic derivatives
A compound represented by the general formula: wherein X 1 represents a nitrogen atom or a group represented by the formula —CR 10 ═; X 2 represents a nitrogen atom or a group represented by the formula —CR 11 ═; Y represents an oxygen atom or the like; R 1 represents a C 1-6 alkoxy group, an optionally substituted C 6-10 aryloxy group, a group represented by the formula —NR 12a R 12b or the like; R 2 represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, or the like; R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 10 and R 11 each independently represent a hydrogen atom, a halogen atom, an optionally substituted C 1-6 alkyl group, or the like; R 9 represents a group represented by the formula —NR 16a R 16b or the like; and R 12a , R 12b , R 16a and R 16b each independently represent a hydrogen atom, an optionally substituted C 1-6 alkyl group, or the like, a salt thereof, or a hydrate of the foregoing.
1. A compound represented by the general formula:
or a salt or hydrate thereof, wherein:
X 1 represents a group represented by the formula —CR 10 ═;
X 2 represents a group represented by the formula —CR 11 ═;
Y represents an oxygen atom, a sulfur atom, a sulfinyl group, a sulfonyl group, or a group represented by the formula —NR Y — (wherein R Y represents a hydrogen atom or a C 1-6 alkyl group);
R 1 represents an optionally substituted C 1-6 alkoxy group, an optionally substituted C 6-10 aryloxy group, a group represented by the formula —NR 12a R 12b , a group represented by formula (VIII):
(wherein Y A1 and Y A2 each independently represents a group represented by the formula -A 10 -A 11 -A 12 (wherein A 10 represents a single bond or an optionally substituted C1-6 alkylene; A 11 represents a single bond, an oxygen atom, a carbonyl group or a sulfonyl group; and A 12 represents a hydrogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a 5- to 10-membered heteroaryl group, a group represented by the formula —NR A10 R A11 , a group represented by the formula —OR A12 (wherein R A10 , R A11 and R A12 each independently represents a hydrogen atom, a C1-6 alkyl group or C 3-8 cycloalkyl group) or a group represented by the formula:
(wherein e represents 1 or 2; Z represents an oxygen atom, a group represented by the formula —CR X7 R X8 — or a group represented by the formula —NR X9 —; R X7 , R X8 and R X9 each independently represents a hydrogen atom, a hydroxyl group or a C 1-6 alkyl group)); and Y A3 represents a hydrogen atom or an optionally substituted C 1-6 alkyl group) or a group represented by the formula:
(wherein T1 represents an optionally substituted 5- to 10-membered aromatic heterocycle which may have X in the ring or an optionally substituted 3- to 10-membered heterocycle which may have X in the ring);
R 2 , R 3 , R 4 , R 5 , R 6 and R 8 each represents a hydrogen atom;
R 7 represents a halogen atom, a cyano group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, a group represented by the formula —CO—R 13 , a group represented by the formula —NR 14 —CO—R 13 , a group represented by the formula —SO 2 —R 15 , a group represented by the formula —NR 14 —SO 2 —R 15 , or a group represented by the formula —NR 16a R 16b ;
R 10 and R 11 each independently represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, a group represented by the formula —CO—R 13 , a group represented by the formula —NR 14 —CO—R 13 , a group represented by the formula —SO 2 —R 15 , a group represented by the formula —NR 14 —SO 2 —R 15 , or a group represented by the formula —NR 16a R 16b ;
R 9 represents a group represented by the formula —NR 16a R 16b ;
R 12a and R 12b each independently represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 3-6 alkenyl group, an optionally substituted C 3-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted 3- to 10-membered heterocyclic group, or an optionally substituted C 1-6 alkoxy group;
R 13 represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered heterocyclic group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 6-10 aryloxy group, a group represented by the formula —NR 12a R 12b , or a group represented by the formula:
(wherein T2 represents an optionally substituted 5- to 10-membered aromatic heterocycle or an optionally substituted 3- to 10-membered heterocycle);
R 14 represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, or a group represented by the formula —CO—R 13 ;
R 15 represents an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, or an optionally substituted 3- to 10-membered heterocyclic group;
R 16a and R 16b each independently represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 3-6 alkenyl group, an optionally substituted C 3-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 6-10 aryl group or an optionally substituted C 1-6 alkoxy group; and
X represents an oxygen atom, a sulfur atom, a carbonyl group, a sulfonyl group, a group represented by the formula —CR X1 R X2 —, or a group represented by the formula —NR X3 — (wherein R X1 , R X2 and R X3 each independently represents a hydrogen atom or a group represented by the formula -A 1 -A 2 -A 3 (wherein A 1 and A 2 each independently represents a single bond, an optionally substituted C 1-6 alkylene group or a carbonyl group; and A 3 represents a hydrogen atom, a C 3-8 cycloalkyl group, a group represented by the formula —NR A1 R A2 , or the formula —OR A3 (wherein, R A1 , R A2 and R A3 each independently represents a hydrogen atom or a C 1-6 alkyl group), or an optionally substituted group represented by the formula:
(wherein a represents 1 or 2))).
2. A compound represented by the general formula:
or a salt or hydrate thereof, wherein:
X 1 represents a group represented by the formula —CR 10 ═;
X 2 represents a group represented by the formula —CR 11 ═;
Y represents an oxygen atom, a sulfur atom, a sulfinyl group, a sulfonyl group, or a group represented by the formula —NR Y — (wherein R Y represents a hydrogen atom or a C 1-6 alkyl group);
R 1 represents an optionally substituted C 1-6 alkoxy group, an optionally substituted C 6-10 aryloxy group, a group represented by the formula —NR 12a R 12b , a group represented by formula (VIII):
(wherein Y A1 and Y A2 each independently represents a group represented by the formula -A 10 -A 11 -A 12 (wherein A 10 represents a single bond or an optionally substituted C1-6 alkylene; A 11 represents a single bond, an oxygen atom, a carbonyl group or a sulfonyl group; and A 12 represents a hydrogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a 5- to 10-membered heteroaryl group, a group represented by the formula —NR A10 R A11 , a group represented by the formula —OR A12 (wherein R A10 , R A11 and R A12 each independently represents a hydrogen atom, a C1-6 alkyl group or C 3-8 cycloalkyl group) or a group represented by the formula:
(wherein e represents 1 or 2; Z represents an oxygen atom, a group represented by the formula —CR X7 R X8 — or a group represented by the formula —NR X9 —; R X7 , R X8 and R X9 each independently represents a hydrogen atom, a hydroxyl group or a C 1-6 alkyl group)); and Y A3 represents a hydrogen atom or an optionally substituted C 1-6 alkyl group) or a group represented by the formula:
(wherein T1 represents an optionally substituted 5- to 10-membered aromatic heterocycle which may have X in the ring or an optionally substituted 3- to 10-membered heterocycle which may have X in the ring);
R 2 , R 3 , R 4 , R 5 , R 6 and R 8 each represents a hydrogen atom;
R 7 represents a halogen atom, a cyano group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, a group represented by the formula —CO—R 13 , a group represented by the formula —NR 14 —CO—R 13 , a group represented by the formula —SO 2 —R 15 , a group represented by the formula —NR 14 —SO 2 —R 15 , or a group represented by the formula —NR 16a R 16b ;
R 10 and R 11 each independently represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, a group represented by the formula —CO—R 13 , a group represented by the formula —NR 14 —CO—R 13 , a group represented by the formula —SO 2 —R 15 , a group represented by the formula —NR 14 —SO 2 —R 15 , or a group represented by the formula —NR 16a R 16b ;
R 9 represents a group represented by the formula —NR 16a R 16b ;
R 12a and R 12b each independently represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 3-6 alkenyl group, an optionally substituted C 3-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted 3- to 10-membered heterocyclic group, or an optionally substituted C 1-6 alkoxy group;
R 13 represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered heterocyclic group, an optionally substituted C 1-6 alkoxy group, an optionally substituted C 6-10 aryloxy group, a group represented by the formula —NR 12a R 12b , or a group represented by the formula:
(wherein T2 represents an optionally substituted 5- to 10-membered aromatic heterocycle or an optionally substituted 3- to 10-membered heterocycle);
R 14 represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, or a group represented by the formula —CO—R 13 ;
R 15 represents an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, or an optionally substituted 3- to 10-membered heterocyclic group;
R 16a and R 16b each independently represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 3-6 alkenyl group, an optionally substituted C 3-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 6-10 aryl group or an optionally substituted C 1-6 alkoxy group; and
X represents an oxygen atom, a sulfur atom, a carbonyl group, a sulfonyl group, a group represented by the formula —CR X1 R X2 —, or a group represented by the formula —NR X3 — (wherein R X1 , R X2 and R X3 each independently represents a hydrogen atom or a group represented by the formula -A 1 -A 2 -A 3 (wherein A 1 and A 2 each independently represents a single bond, an optionally substituted C 1-6 alkylene group or a carbonyl group; and A 3 represents a hydrogen atom, a C 3-8 cycloalkyl group, a group represented by the formula —NR A1 R A2 , or the formula —OR A3 (wherein, R A1 , R A2 and R A3 each independently represents a hydrogen atom or a C 1-6 alkyl group), or an optionally substituted group represented by the formula:
(wherein a represents 1 or 2))).
3. A compound according to claim 1 or 2 , wherein Y represents an oxygen atom, a group represented by the formula —NH—, or a group represented by the formula —N(CH 3 )—.
4. A compound according to claim 1 or 2 , wherein Y represents an oxygen atom.
5. A compound according to claim 1 or 2 , wherein both X 1 and X 2 represent —CH═.
6. A compound according to claim 1 or 2 , wherein R 7 represents a halogen atom or an optionally substituted C 1-6 alkyl group.
7. A compound according to claim 1 or 2 , wherein R 9 represents a group represented by the formula —NHR 17 , wherein R 17 represents an optionally substituted C 1-6 alkyl group, a C 3-6 alkynyl group, a C 3-8 cycloalkyl group or an optionally substituted C 6-10 aryl group.
8. A compound according to claim 1 or 2 , wherein R 9 represents a group represented by the formula —NR 18a R 18b , wherein R 18a and R 18b each independently represents a C 1-6 alkyl group.
9. A compound according to claim 1 or 2 , wherein R 9 represents a group represented by the formula —NHR 19 , wherein R 19 represents a C 1-6 alkyl group, a C 3-6 alkynyl group, a C 3-8 cycloalkyl group or a C 6-10 aryl group.
10. A compound according to claim 1 or 2 , wherein R 9 represents a group represented by the formula —NHR 20 , wherein R 20 represents a methyl group, an ethyl group or a cyclopropyl group.
11. A compound according to claim 1 or 2 , wherein R 9 represents a group represented by the formula —NH(CH 3 ).
12. A compound according to claim 1 or 2 , wherein R 1 represents a further optionally substituted group represented by formula (III′):
(wherein b 2 represents 0, 1 or 2; and X represents an oxygen atom, a sulfur atom, a carbonyl group, a sulfonyl group, a group represented by the formula —CR X1 R X2 —, or a group represented by the formula —NR X3 — (wherein R X1 , R X2 and R X3 each independently represents a hydrogen atom or a group represented by the formula -A 1 -A 2 -A 3 (wherein A 1 and A 2 each independently represents a single bond, an optionally substituted C 1-6 alkylene group or a carbonyl group; and A 3 represents a hydrogen atom, a C 3-8 cycloalkyl group, a group represented by the formula —NR A1 R A2 , or the formula —OR A3 (wherein, R A1 , R A2 and R A3 each independently represents a hydrogen atom or a C 1-6 alkyl group), or an optionally substituted group represented by the formula:
(wherein a represents 1 or 2))).
13. A compound according to claim 1 or 2 , wherein R 1 represents a group represented by formula (IV):
(wherein X represents an oxygen atom, a sulfur atom, a carbonyl group, a sulfonyl group, a group represented by the formula —CR X1 R X2 —, or a group represented by the formula —NR X3 — (wherein R X1 , R X2 and R X3 each independently represents a hydrogen atom or a group represented by the formula -A 1 -A 2 -A 3 (wherein A 1 and A 2 each independently represents a single bond, an optionally substituted C 1-6 alkylene group or a carbonyl group; and A 3 represents a hydrogen atom, a C 3-8 cycloalkyl group, a group represented by the formula —NR A1 R A2 , or the formula —OR A3 (wherein, R A1 , R A2 and R A3 each independently represents a hydrogen atom or a C 1-6 alkyl group), or an optionally substituted group represented by the formula:
(wherein a represents 1 or 2))).
14. A compound according to claim 13 , wherein X in formula (IV) represents an oxygen atom.
15. A compound according to claim 13 , wherein X in formula (IV) represents a group represented by formula (V):
(wherein R X4 represents a hydrogen atom or a group represented by the formula -A 4 -A 5 -A 6 (wherein A 4 and A 5 each independently represents a single bond, an optionally substituted C 1-6 alkylene or a carbonyl group; and A 6 represents a hydrogen atom, a C 3-8 cycloalkyl group or a group represented by the formula —NR A4 R A5 or the formula —OR A6 (wherein R A4 , R A5 and R A6 each independently represents a hydrogen atom or a C 1-6 alkyl group))).
16. A compound according to claim 13 , wherein X in formula (IV) represents a group represented by formula (VI):
(wherein R X5 and R X6 each independently represents a hydrogen atom or a group represented by the formula -A 7 -A 8 -A 9 (wherein A 7 and A 8 each independently represents a single bond, an optionally substituted C 1-6 alkylene group or a carbonyl group; and A 9 represents a hydrogen atom, a C 3-8 cycloalkyl group, a group represented by the formula —NR A7 R A8 , or the formula —OR A9 (wherein R A7 , R A8 , and R A9 each independently represents a hydrogen atom or a C 1-6 alkyl group), or a group represented by the formula:
(wherein c 1 represents 0, 1 or 2))).
17. A compound according to claim 16 , wherein one of R X5 and R X6 in the formula (VI) represents a hydroxyl group and the other represents a hydrogen atom or a C 1-6 alkyl group.
18. A compound according to claim 16 , wherein one of R X5 or R X6 in the formula (VI) represents a hydrogen atom and the other represents a group represented by the formula:
(wherein c 2 represents 1 or 2).
19. A compound according to claim 1 or 2 wherein R 1 represents a group represented by formula (VII):
(wherein R X51 and R X61 each independently represents a hydrogen atom or a group represented by the formula -A 71 -A 81 -A 91 (wherein A 71 and A 81 each independently represents a single bond, an optionally substituted C 1-6 alkylene group or a carbonyl group; and A 91 represents a hydrogen atom, a C 3-8 cycloalkyl group, a group represented by the formula —NR A71 R A81 , or the formula —OR A91 (wherein R A71 , R A81 , and R A91 each independently represents a hydrogen atom or a C 1-6 alkyl group), or a group represented by the formula:
(wherein c 11 represents 0, 1 or 2))).
20. A compound according to claim 1 or 2 , wherein R 1 represents a group represented by formula (VIII):
(wherein Y A1 and Y A2 each independently represents a group represented by the formula -A 10 -A 11 -A 12 (wherein A 10 represents a single bond or an optionally substituted C 1-6 alkylene group; A 11 represents a single bond, an oxygen atom, a carbonyl group, or a sulfonyl group; and A 12 represents a hydrogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a 5- to 10-membered heteroaryl group, a group represented by the formula —NR A10 R A11 , or the formula —OR A12 (wherein, R A10 , R A11 , and R A12 each independently represents a hydrogen atom, a C 1-6 alkyl group or a C 3-8 cycloalkyl group), or a group represented by the formula:
(wherein e represents 1 or 2; and Z represents an oxygen atom or a group represented by the formula —CR X7 R X8 — or the formula —NR X9 — (wherein R X7 , R X8 and R X9 each independently represents a hydrogen atom, a hydroxyl group or a C 1-6 alkyl group))); and Y A3 represents a hydrogen atom or an optionally substituted C 1-6 alkyl group).
21. A compound according to claim 20 , wherein one of Y A1 and Y A2 in the formula (VIII) represents a hydrogen atom and the other represents a group represented by the formula —(CH 2 ) 2 -A 13 -A 14 (wherein A 13 represents a single bond, a carbonyl group or a sulfonyl group; and A 14 represents a C 1-6 alkyl group, a group represented by the formula —NR A13 R A14 (wherein R A13 and R A14 each independently represents a hydrogen atom, a C 1-6 alkyl group or a C 3-8 cycloalkyl group), or a group represented by the formula:
(wherein e represents 1 or 2; and Z represents an oxygen atom or a group represented by the formula —CR X7 R X8 — or the formula —NR X9 — (wherein R X7 , R X8 and R X9 each independently represents a hydrogen atom, a hydroxyl group or a C 1-6 alkyl group))); and Y A3 in formula (VIII) represents a hydrogen atom.
22. A compound according to claim 1 or 2 , wherein R 1 represents a group selected from:
(wherein, each of the foregoing members being optionally substituted with a group selected from Substituent Group Alpha, wherein Substituent Group Alpha is a group consisting of a halogen atom, a hydroxyl group, a thiol group, a nitro group, a cyano group, a carboxyl group, an amino group, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, and a group selected from:
(wherein R N1 and R N2 each independently represents a hydrogen atom or a C 1-6 alkyl group)).
23. A compound according to claim 1 or 2 , wherein R 1 represents a group selected from:
24. A compound according to claim 1 or 2 , wherein R 1 represents a group selected from:
25. A compound according to claim 1 or 2 , wherein R 1 represents a group selected from:
26. A compound according to claim 1 , wherein the compound is selected from the group consisting of
(102) N1-methyl-3-chloro-5-(2-(((3-(diethylamino)propyl)amino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide;
(103) N1-methyl-3-chloro-5-(2-((4-(pyrrolidin-1-yl)piperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide;
(104) N1-methyl-3-chloro-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide;
(105) N1-methyl-3-chloro-5-(2-(((3-(4-hydroxypiperidino)propyl)amino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide;
(106) N1-methyl-3-chloro-5-(2-((4-(2-hydroxyethyl)piperazin-1-yl)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide;
(107) N4-(4-(3-chloro-1-(methylamino)carbonyl-1H-5-indolyl)oxy-2-pyridyl)-4-morpholinecarboxamide;
(108) N1-methyl-3-chloro-5-(2-((4-(ethylpiperazin-1-yl)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide;
(109) N1-ethyl-3-chloro-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide;
(110) N1-ethyl-3-chloro-5-(2-(((3-(4-hydroxypiperidino)propyl)amino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide;
(111) N1-ethyl-3-chloro-5-(2-(((3-(diethylamino)propyl)amino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide;
(112) N1,3-dimethyl-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide;
(113) N1,3-dimethyl-5-(2-((4-(pyrrolidin-1-yl)piperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide;
(114) N1-cylopropyl-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-3-methyl-1H-1-indolecarboxamide; and
(115) N1-cylopropyl-5-(2-((4-(2-hydroxyethyl)piperazin-1-yl)carbonyl)amino-4-pyridyl)oxy-3-methyl-1H-1-indolecarboxamide.
27. A compound according to claim 1 , wherein the compound is (25) N1-methyl-3-chloro-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide.