Fused ring compound having urea structure
The present invention relates to a novel fused ring compound having urea structure that exhibits excellent NAMPT activating effect, and a method using the same for treating/preventing metabolic disorder, cardiovascular and kidney disease, mitochondrial disease, neurodegenerative disease, ocular disease, and muscle wasting disorder. The present invention provides a compound represented by following formula (I) or a pharmacologically acceptable salt: wherein A, B, R 1 , R 2 and R 3 represent the same meanings as in the claims.
1. A compound of formula (I), or a pharmaceutically acceptable salt thereof:
wherein:
R 1 is a hydrogen atom or a halogen atom;
R 2 is a hydrogen atom; a phenyl group or a heteroaryl group optionally substituted with one or more Y; or a C 1 -C 6 alkyl group optionally substituted with a C 3 -C 6 cycloalkyl group;
R 3 is a hydrogen atom; a cyano group; a phenyl group or a heteroaryl group each optionally substituted with one or more Y; a C 1 -C 4 alkylcarbonyl group or a C 1 -C 4 alkyl group, each optionally substituted with one or more Z; or —C(═O)—Z;
each Y is independently selected from a C 1 -C 4 alkyl group, a C 1 -C 4 alkoxy group, a phenyl group, a C 1 -C 3 alkylsulfonyl group, a C 1 -C 3 haloalkyl group, a halogen atom, and a C 1 -C 3 alkyl group or a C 1 -C 3 alkoxy group substituted with a C 1 -C 3 alkoxy group;
each Z is independently selected from a C 1 -C 3 alkoxy group, a dioxanyl group, an 8-oxa-3-azabicyclo [3.2.1] octyl group, a C 1 -C 4 alkoxycarbonyl group, and an amino group or a C 3 -C 6 cycloalkylamino group each optionally substituted with one or more W; and
each W is independently selected from a phenyl group, a heteroaryl group, a C 1 -C 3 alkyl group, a C 1 -C 3 alkyl group substituted with phenyl, and a C 1 -C 3 alkyl group substituted with a heteroaryl group.
2. The compound of claim 1 , wherein A is
3. The compound of claim 1 , wherein A is
4. The compound of claim 1 , wherein A is
5. The compound of claim 1 , wherein B is
6. The compound of claim 1 , wherein ring B is
R 3 is a hydrogen atom; a cyano group; a C 1 -C 4 alkyl group;
a phenyl group or a heteroaryl group each optionally substituted with one or more Y; an ethylcarbonyl group or a methyl group each optionally substituted with one or more Z; or —C(═O)—Z; wherein each Y is independently selected from a C 1 -C 3 alkyl group, a C 1 -C 3 alkoxy group, a phenyl group, a halogen atom, a C 1 -C 3 alkylsulfonyl group, a C 1 -C 3 haloalkyl group, and a C 1 -C 3 alkyl group or a C 1 -C 3 alkoxy group each substituted with a C 1 -C 3 alkoxy group; wherein each Z is independently selected from a C 1 -C 2 alkoxy group, a dioxanyl group, an 8-oxa-3-azabicyclo [3.2.1] octyl group, and an amino group or a C 3 -C 6 cycloalkylamino group each optionally substituted with one or more W; and wherein each W is independently selected from a phenyl group, a heteroaryl group, a C 1 -C 3 alkyl group, a C 1 -C 3 alkyl group substituted with phenyl, and a C 1 -C 3 alkyl group substituted with a heteroaryl group.
7. The compound of claim 1 , wherein ring B is
R 3 is a hydrogen atom, a cyano group, a N-methylpyrazolyl group, a phenyl group, a methyl group, a 2-methoxyethyl group, a dioxanylmethyl group, or —C(═O)—Z; wherein Z is selected from an 8-oxa-3-azabicyclo [3.2.1] octyl group and an amino group optionally substituted with one or more W; and wherein each W is independently selected from a C 1 -C 3 alkyl group, a methylphenyl group, and a C 1 -C 3 alkyl group substituted with a heteroaryl group.
8. The compound of claim 1 , wherein R 1 is a hydrogen atom or a fluorine atom.
9. The compound of claim 1 , wherein R 2 is a hydrogen atom; a phenyl group, a pyrazolyl group, a pyridinyl group, or a pyrrole group each optionally substituted with one Y; or a C 1 -C 3 alkyl group optionally substituted with a C 3 -C 6 cycloalkyl group; wherein Y is selected from a phenyl group, a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 3 haloalkyl group, a C 1 -C 3 alkylsulfonyl group, a C 1 -C 3 alkoxy group, and a C 1 -C 3 alkyl group or a C 1 -C 3 alkoxy group substituted with a C 1 -C 3 alkoxy group.
10. The compound of claim 1 , wherein R 2 is a hydrogen atom; a phenyl group, a pyrazolyl group, or a pyridinyl group each optionally substituted with one Y; or a C 1 -C 3 alkyl group; wherein Y is selected from a C 1 -C 4 alkyl group, a methanesulfonyl group, an ethanesulfonyl group, a methoxy group, an ethoxy group, a 2-methoxyethoxy group, a phenyl group, a trifluoromethyl group, a difluoromethyl group, a 2-methoxyethyl group, and a chlorine atom.
11. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.
15. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition is formulated for oral administration, intravenous injection, subcutaneous injection, inhalation, nasal administration, dermal administration, or ophthalmic administration.
16. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition is in a tablet, or a capsule.
17. A method of treating a disease or condition mediated by nicotinamide phosphoribosyltransferase (NAMPT) activity in a mammal comprising administering a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to the mammal.
18. The method of claim 17 , wherein the disease or condition is a metabolic disorder, a cardiovascular disease, a kidney disease, a mitochondrial disease, a neurodegenerative disease, an ocular disease, or a muscle wasting disorder.
19. The method of claim 17 , wherein the mammal is a human.