US 12,440,481 B2
Esters and carbamates as modulators of sodium channels
Stephen Andrew Thomson, Del Mar, CA (US); Nadia Ahmad, Didcot (GB); Corey Anderson, Brighton, MA (US); Vijayalaksmi Arumugam, San Marcos, CA (US); Iuliana Luci Asgian, San Diego, CA (US); Joanne Louise Camp, Didcot (GB); Lev Tyler Dewey Fanning, San Marcos, CA (US); Sara Sabina Hadida Ruah, La Jolia, CA (US); Dennis Hurley, San Marcos, CA (US); Yvonne Schmidt, San Diego, CA (US); David Shaw, Oxford (GB); Urvi Patel, San Diego, CA (US); and Lidio Marx Carvalho Meireles, San Marcos, CA (US)
Assigned to VERTEX PHARMACEUTICALS INCORPORATED, Boston, MA (US)
Appl. No. 17/421,945
Filed by VERTEX PHARMACEUTICALS INCORPORATED, Boston, MA (US)
PCT Filed Jan. 9, 2020, PCT No. PCT/US2020/012905
§ 371(c)(1), (2) Date Jul. 9, 2021,
PCT Pub. No. WO2020/146612, PCT Pub. Date Jul. 16, 2020.
Claims priority of provisional application 62/790,886, filed on Jan. 10, 2019.
Prior Publication US 2022/0110923 A1, Apr. 14, 2022
Int. Cl. A61K 31/44 (2006.01); A61K 31/192 (2006.01); C07C 65/24 (2006.01); C07D 213/79 (2006.01)
CPC A61K 31/44 (2013.01) [A61K 31/192 (2013.01); C07C 65/24 (2013.01); C07D 213/79 (2013.01); C07B 2200/05 (2013.01)] 23 Claims
 
1. A compound of formula (I), (II), or (III)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
Q is C(O)ORo or NRnC(O)ORo;
Rn is H or C1-C6 alkyl;
each Ro is independently C1-C6 alkyl;
R1a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
R3a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy or C(O)ORo;
R4a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or —W—Rw;
R1b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
R3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
R4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
R2c is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
R3c is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
R4c is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
R5 is H, halo, OH, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or —W—(CH2)n—Rw;
R6 is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or —W—(CH2)n—Rw;
R7 is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or —W—(CH2)n—Rw;
R9 is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
R10 is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
R11 is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
R12 is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
R13 is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
each W is independently O or a single bond;
each Rw is independently 3-6 membered cycloalkyl, phenyl, or 5-6 membered heteroaryl, wherein said 3-6 membered cycloalkyl, phenyl, or 5-6 membered heteroaryl may be unsubstituted or may be substituted with 1-3 substituents selected from a group consisting of halo, C1-C6 alkyl, and C1-C6 haloalkyl; and
n is 0 or 1;
wherein the compound of formula (I), (II), or (III) is not methyl 5-(2-(2,4-dimethoxyphenoxy)-5-(trifluoromethyl)benzamido)picolinate or methyl 5-(4,5-dichloro-2-(4-fluoro-2-methoxyphenoxy)benzamido)picolinate.