Triazolones, tetrazolones, and imidazolones, or their salts, and pharmaceutical compositions comprising the same
AssigneeYuhan Corporation
InventorsHee Jae Tak, Eun Kyung Kim, Hyok Jun Cho, Cheol Hee Lim
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Abstract
The present technology provides triazolones, tetrazolones, and imidazolones, or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and uses thereof. The triazolones, tetrazolones, and imidazolones or their pharmaceutically acceptable salts exhibit inhibitory activity on VAP-1 and therefore can be usefully applied, e.g., for the treatment and prophylaxis of nonalcoholic hepatosteatosis (NASH).
Claims27
A compound of Formula 1:
- or a pharmaceutically acceptable salt thereof;
- wherein
- (i) X is N, and Y is N or CR2′;
- or
- (ii) X is CR3, and Y is N or CR2;
- R1 is hydrogen or fluoro;
- R2 is hydrogen, C1-3 alkyl, halogen, phenyl, or benzyl;
- R2′ is C1-3 alkyl, halogen, phenyl, or benzyl;
- R3 is hydrogen, C1-3 alkyl, or phenyl;
- n is 0 or 1;
- A is a C6-C10 aryl group or a 5- to 10-membered heteroaryl group, wherein said heteroaryl group has 1 to 5 heteroatom ring members independently selected from O, N, and S;
- and wherein said aryl group or said heteroaryl group is optionally substituted with one or two substituents independently selected from the group consisting of C1-3 alkyl, halogen, and —R;
- and
- R is a substituted or unsubstituted cyclic ring, optionally containing 1 to 5 heteroatom ring members independently selected from O, N, and S, and the cyclic ring is aromatic or non-aromatic.
A compound or a pharmaceutically acceptable salt thereof wherein the compound is:
A method of preparing a compound of Formula 1a:
- or a pharmaceutically acceptable salt thereof, wherein:
- (i) X is N, and Y is N or CR2′;
- or
- (ii) X is CR3, and Y is N or CR2;
- R1 is hydrogen or fluoro;
- R2 is hydrogen, C1-3 alkyl, halogen, phenyl, or benzyl;
- R2′ is C1-3 alkyl, halogen, phenyl, or benzyl;
- R3 is hydrogen, C1-3 alkyl, or phenyl;
- n is 0 or 1;
- A′ is a C6-C10 aryl group or a 5- to 10-membered heteroaryl group, wherein said heteroaryl group has 1 to 5 heteroatom ring members independently selected from O, N, and S;
- and
- R′ is selected from the group consisting of C1-3 alkyl, halogen, and —R;
- R is a substituted or unsubstituted cyclic ring, optionally containing 1 to 5 heteroatom ring members independently selected from O, N, and S, and the cyclic ring is aromatic or non-aromatic;
- the method comprising:
- (a) reacting a compound of Formula 2:
- wherein PG is an amine protecting group;
- with a compound of Formula 3:
- Z—R′ (Formula 3)
- wherein Z is —B(OH)2, B(C1-3alkoxy)2, or
- to obtain a compound of Formula 1aa:
- and
- (b) removing PG from the compound of Formula 1aa under reaction conditions to obtain the compound of Formula 1a or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.