Fused ring compound having urea structure

Patent metadata

Field	Value
Publication number	US-12263159-B2
Application number	US-202418420446-A
Country	US
Kind code	B2
Filing date	Jan 23, 2024
Priority date	Jul 5, 2018
Publication date	Apr 1, 2025
Grant date	Apr 1, 2025

Abstract

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, R1, R2 and R3 represent the same meanings as in the claims.

First claim

The invention claimed is:

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 th

Assignees

• Sanford Burnham Prebys Medical Discovery Inst

Inventors

• Nakamura Tsuyoshi
• Akiu Mayuko
• Tsuji Takashi
• Tanaka Jun
• Terayama Koji
• Yokoyama Mika
• Pinkerton Anthony B
• Sessions Edward Hampton

Classifications

• C07D498/08

  Bridged systems · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title

• C07D413/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title