Bicyclic pyridine derivative
The present disclosure provides bicyclic pyridine derivatives. A compound represented by formula I: or a pharmaceutically acceptable salt thereof, wherein X is a oxygen atom, sulfur atom, NR, or CR′R″, n is 0 or 1, R 1 , R 2a , R 2b , R 2c , R 2d , R, R′ and R″ are each independently a hydrogen atom, a halogen atom, optionally substituted C 1-6 alkyl, or an optionally substituted C 6-10 aryl, or two of R 2a , R 2b , R 2c , R 2d , R, R′, and R″, together with a carbon atom or a nitrogen atom to which they are attached, form a 3- to 6-membered saturated carbocyclic ring or saturated heterocyclic ring, and R 3a , R 3b , R 3c and R 5a and R 5b , are as defined in the description.
1 . A compound represented by formula I
or a pharmaceutically acceptable salt thereof,
wherein
X is an oxygen atom or a sulfur atom,
n is 0,
R 1 is a hydrogen atom, optionally substituted C 1-6 alkyl, or optionally substituted C 3-6 alkenyl,
R 2a and R 2b are each independently a hydrogen atom, a halogen atom, optionally substituted C 1-6 alkyl, or optionally substituted C 6 -10 aryl, or R 2a and R 2b , together with a carbon atom to which they are attached, form a 3- to 6-membered saturated carbocyclic ring,
R 3a , R 3b , and R 3c are each independently a hydrogen atom, optionally substituted C 1-6 alkyl, a halogen atom, —OR 4 , or optionally substituted C 6-10 aryl,
R 4 is optionally substituted C 1-6 alkyl or optionally substituted 3- to 6-membered saturated carbocyclic ring, and
R 5a and R 5b are each independently a hydrogen atom or optionally substituted C 1-6 alkyl, or R 5a and R 5b , together with a carbon atom to which they are attached, form a 3- to 6-membered saturated carbocyclic ring,
wherein,
the optionally substituted C 1-6 alkyl and optionally substituted C 3-6 alkenyl are optionally substituted with a halogen atom, hydroxy, or C 1-6 alkoxy, and
the optionally substituted C 6-10 aryl and optionally substituted 3- to 6-membered saturated carbocyclic ring are optionally substituted with a halogen atom, hydroxy, C 1-6 alkyl, or C 1-6 alkoxy,
provided that the following (1) to (19) are is excluded:
(1) a compound wherein n is 0, X is an oxygen atom, and R 2a and R 2b are hydrogen atoms.
2 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , represented by the following formula:
3 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , wherein R 1 is a hydrogen atom, or C 1-6 alkyl optionally substituted with a halogen atom.
4 . The compound or the pharmaceutically acceptable salt thereof of claim 3 , wherein R 1 is methyl.
5 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , wherein R 2a and R 2b are each independently a hydrogen atom, optionally substituted C 1-6 alkyl, or R 2a and R 2b , together with a carbon atom to which they are attached, form a 3- to 6-membered saturated carbocyclic ring.
6 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , wherein R 2a is a hydrogen atom, and R 2b is optionally substituted C 1-6 alkyl.
7 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , wherein R 3a , R 3b , and R 3c are each independently a hydrogen atom, optionally substituted C 1-6 alkyl, or a halogen atom.
8 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , wherein R 3a , R 3b , and R 3c are each a hydrogen atom.
9 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , wherein at least one of R 3a , R 3b , and R 3c is optionally substituted C 1-6 alkyl or a halogen atom.
10 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , wherein R 5a and R 5b are each a hydrogen atom.
11 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , wherein X is an oxygen atom.
12 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , wherein
R 1 is C 1-6 alkyl optionally substituted with a halogen atom, and
at least one of R 3a , R 3b , and R 3c is optionally substituted C 1-6 alkyl or a halogen atom.
13 . The compound or the pharmaceutically acceptable salt thereof of claim 12 , wherein
R 1 is methyl, and
at least one of R 3a , R 3b , and R 3c is methyl, a fluorine atom, or a chlorine atom.
14 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , wherein
X is an oxygen atom,
R 1 is C 1-6 alkyl optionally substituted with a halogen atom,
R 2a is a hydrogen atom, and R 2b is optionally substituted C 1-6 alkyl,
at least one of R 3a , R 3b , and R 3c is optionally substituted C 1-6 alkyl or a halogen atom, and
R 5a and R 5b are each a hydrogen atom.
15 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , selected from the following group of compounds:
1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine;
1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine;
N-methyl-1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine;
1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-methylmethanamine;
1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-(2H3)methylmethanamine;
rel-1-[(3'S)-5′-methyl-3′H-spiro[cyclopropane-1,2′-furo[3,2-b]pyridin]-3′-yl]methanamine;
rel-1-[(3'S)-5′-fluoro-3′H-spiro[cyclopropane-1,2′-furo[3,2-b]pyridin]-3′-yl]methanamine;
rel-1-[(3S)-2,2,5-trimethyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine;
rel-1-[(3'S)-3′H-spiro[cyclopropane-1,2′-furo[3,2-b]pyridin]-3′-yl]methanamine; and
rac-1-(5-fluoro-2,2-dimethyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl) methanamine.
16 . The compound or the pharmaceutically acceptable salt thereof of claim 1 , wherein R 5a and R 5b are each independently a hydrogen atom or optionally substituted C 1-6 alkyl.