Fused heterotricyclic compounds, process for preparing the compounds and drugs containing the same
The present invention provides a novel compound having an excellent corticotrophin-releasing-factor receptor antagonistic activity. That is, it provides a compound represented by the following formula, a pharmacologically acceptable salt thereof or hydrates thereof. Wherein A, B and D are the same as or different from each other and each represents a group represented by the formula —(CR 1 R 2 ) m — (wherein R 1 and R 2 are the same as or different from each other and each represents a C 1-6 alkyl group etc.), —NR 3 — (wherein R 3 represetns hydrogen etc.) etc.; E and G are the same as or different from each other and each represents a group represented by the formula —(CR 6 R 7 ) p — (wherein R 6 and R 7 are the same as or different from each other and each represents hydrogen etc.; and p represents an integer of 0, 1 or 2); J represents a carbon atom or nitrogen atom, each substituted with C 1-6 alkyl group optionally substituted with a halogen atom, etc.; K and L are the same as or different from each other and each represents carbon atom or nitrogen atom; M means hydrogen, a halogen atom, an optionally substituted C 1-6 alkyl group etc.; and the partial structure means a single or double bond.
1. A compound represented by the formula:
wherein
R 2 is
a hydrogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 1-6 alkoxy group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy C 1-6 alkyl group, a C 3-8 cycloalkyl C 1-6 alkyl group or a C 1-6 alkyl-aryl group
R 3 is
(i) a hydrogen atom;
(ii) formula —COR 4 (wherein R 4 represents a C 1-6 alkyl group, an optionally substituted aryl C 1-4 alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl C 1-4 alkyl group or an optionally substituted heteroaryl group);
(iii) —S(O) n R 5 (wherein R 5 represents a C 1-6 alkyl group, an optionally substituted aryl C 1-4 alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl C 1-4 alkyl group or an optionally substituted heteroaryl group; and n is an integer of 0, 1 or 2);
(iv) a C 1-10 alkyl group optionally substituted with any of one or more groups defined in the following A group;
(v) a C 2-10 alkenyl group optionally substituted with any of one or more groups defined in the following A group;
(vi) a C 2-10 alkynyl group optionally substituted with any of one or more groups defined in the following A group;
(vii) an optionally substituted aryl group; or
(viii) a C 3-8 cycloalkyl group optionally fused with optionally substituted benzene ring and optionally substituted with a C 1-4 alkyl group);
the partial structure represents a single or double bond, and
the A group defined above is selected from at least one of the group consisting of:
(1) halogen atom,
(2) hydroxy group,
(3) nitro group,
(4) cyano group,
(5) carboxy group,
(6) a C 1-6 alkyloxycarbonyl group, and
(7) a group represented by the formula —S(O) r R 15 (wherein r is an integer of 0, 1 or 2; and R 15 represents:
(i) hydrogen atom;
(ii) a C 1-6 alkyl group;
(iii) a group represented by the formula —NR 16 R 17 (wherein R 16 and R 17 are the same as or different from each other and each represents hydrogen atom, a C 1-6 alkyl group optionally substituted with an optionally substituted aryl group, a C 1-4 alkylacyl group, an optionally substituted aryl C 1-4 alkyl group, an optionally substituted heteroaryl C 1-4 alkyl group, an optionally substituted aryl group or an optionally substituted heteroaryl group);
(iv) an optionally substituted aryl C 1-4 alkyl group;
(v) an optionally substituted aryl group;
(vi) an optionally substituted heteroaryl C 1-4 alkyl group; or
(vii) an optionally substituted heteroaryl group);
M′ represents a hydrogen atom, a halogen atom or a C 1-6 alkyl group;
R 7 ′ represents a hydrogen atom or a C 1-6 alkyl group; and
W′ represents a phenyl group, pyridyl group, thienyl group, or furyl group, each being optionally substituted; and
a pharmacologically acceptable salt thereof or hydrates thereof.
2. The compound as claimed in claim 1 , a pharmacologically acceptable salt thereof or hydrates thereof, wherein at least one selected from R 2 and R 3 are the same as or different from each other and each represents hydrogen atom, a C 1-6 alkyl group, a C 2-6 alkynyl group, a C 1-6 alkoxy C 1-6 alkyl group or a C 1-6 alkyl-aryl group.
3. A medicament which comprises the compound as claimed in claim 1 , a pharmacologically acceptable salt thereof or hydrates thereof, and a pharmacologically acceptable carrier.
4. A method for treating a disease to which at least one of CRF and CRF receptor relate, by administering a pharmaceutically effective dose of the compound as claimed in claim 1 , a pharmacologically acceptable salt thereof or hydrates thereof to a patient.
5. A method for treating a disease against which CRF receptor antagonism is efficacious, by administering a pharmaceutically effective dose of the compound as claimed in claim 1 , a pharmacologically acceptable salt thereof or hydrates thereof to a patient.