US 12,275,730 B2
Azabenzimidazole compounds and pharmaceutical
Koya Oikawa, Muko (JP); Sho Hirai, Kyoto (JP); Kazuhiko Wakita, Muko (JP); and Akiko Fujibayashi, Muko (JP)
Assigned to NIPPON SHINYAKU CO., LTD., Kyoto (JP)
Appl. No. 17/053,380
Filed by NIPPON SHINYAKU CO., LTD., Kyoto (JP)
PCT Filed May 7, 2019, PCT No. PCT/JP2019/018201
§ 371(c)(1), (2) Date Nov. 6, 2020,
PCT Pub. No. WO2019/216294, PCT Pub. Date Nov. 14, 2019.
Claims priority of application No. 2018-089867 (JP), filed on May 8, 2018.
Prior Publication US 2021/0371412 A1, Dec. 2, 2021
Int. Cl. C07D 471/04 (2006.01); A61P 13/10 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 13/10 (2018.01); C07D 519/00 (2013.01)] 22 Claims
 
1. An azabenzimidazole compound of the formula [1]:

OG Complex Work Unit Chemistry
wherein:
R1 is a hydrogen atom or alkyl, or two R1 are taken together with adjacent carbon atom to form a 3- to 7-membered cycloalkyl or an oxygen-containing non-aromatic heterocycle;
R2 is a hydrogen atom, alkyl, cycloalkyl, alkyl substituted with cycloalkyl, or alkoxyalkyl;
R3 is a hydrogen atom, alkyl, or alkoxyalkyl;
R4 is pyridyl optionally substituted with one or two groups selected from the group consisting of alkyl, trihaloalkyl, alkoxy, cyano and cycloalkyl, or phenyl optionally substituted with 1 to 3 groups selected from the group consisting of trihaloalkyl, halogen, alkoxy and cycloalkyl;
A is a group of the formula A-1, A-2, A-3, A-4, or A-5:

OG Complex Work Unit Chemistry
wherein the bond on the left side of each group is attached to the 2-position of the azabenzimidazole in the formula [1], and the bond on the right side is attached to W in the formula [1], and R″ is a group selected from a hydrogen atom, halogen, alkyl, alkoxy or nitro;
W is a bond, or a group of the formula W-1, W-2, or W-3:

OG Complex Work Unit Chemistry
wherein R21 is a hydrogen atom or alkyl;
B is a group of the formula B-1, B-2, B-3, or B-4:

OG Complex Work Unit Chemistry
wherein
the bond on the left side of each group is attached to W in the formula [1],
the bond on the right side is attached to Y in the formula [1],
U1 is a nitrogen atom or CR41, and U2 is a nitrogen atom or CR42, and R41 and R42 are independently a hydrogen atom, alkyl, halogen or a hydroxyl group, m and n are independently 1, 2 or 3, and R31 and R32 are independently a hydrogen atom, alkyl, halogen or alkoxyalkyl, or R31 and R32 are taken together with adjacent carbon atoms to form an alkylene bridge, provided that R31 and R32 substitute at any substitutable position other than U1 and U2;
Y is a hydrogen atom, or a group of any one of the formula Y-1 to Y-4 and Y-11 to Y-16:

OG Complex Work Unit Chemistry
wherein
R51 is alkyl; p is 1, 2, or 3; q is 0, 1, or 2; r is 1, 2, or 3; T is O, S, SO2, or NR61 wherein
R61 is a hydrogen atom or alkyl; s is 0, 1, 2, or 3; and t is 0 or 1,
with the proviso that
(a) when W is a bond,
if B is B-1 or B-2 and U2 is a nitrogen atom, then Y is Y-1, Y-2, Y-3, or Y-4,
if B is B-1 or B-2 and U2 is CR42 wherein R42 is as defined above, then U1 is a nitrogen atom and Y is Y-11, Y-12, Y-13, Y-14, Y-15, or Y-16, and
if B is B-3 or B-4, then Y is a hydrogen atom;
(b) when W is W-1,
if B is B-1, U1 is a nitrogen atom, and U2 is a nitrogen atom, then Y is Y-1, Y-2, Y-3, or Y-4, and
if B is B-1, U1 is a nitrogen atom, and U2 is CR42 wherein R42 is as defined above, then Y is Y-11, Y-12, Y-13, Y-14, Y-15, or Y-16;
(c) when W is W-2,
if B is B-1 or B-2, U1 is a nitrogen atom, and U2 is a nitrogen atom, then Y is Y-1, Y-2, Y-3, or Y-4,
if B is B-1 or B-2, U1 is a nitrogen atom, and U2 is CR42 wherein R42 is as defined above, then Y is Y-11, Y-12, Y-13, Y-14, Y-15, or Y-16, and
if B is B-3 or B-4, then Y is a hydrogen atom; and
(d) when W is W-3,
if B is B-1, U1 is CR41 wherein R41 is as defined above, and U2 is a nitrogen atom, then Y is Y-1, Y-2, Y-3, or Y-4,
or a pharmaceutically acceptable salt thereof, or a solvate thereof.