US 11,834,441 B2
Substituted tetrahydrofurans as modulators of sodium channels
Steven John Durrant, Headington (GB); Nadia Ahmad, Berkshire (GB); Elizabeth Mary Beck, Abingdon (GB); Lidio Marx Carvalho Meireles, San Marcos, CA (US); Ewa Iwona Chudyk, Wantage (GB); Gorka Etxebarria Jardi, Badalona (ES); Bhairavi Galan, Abingdon (GB); Sara S. Hadida Ruah, La Jolla, CA (US); Dennis James Hurley, San Marcos, CA (US); Ronald Marcellus Knegtel, Abingdon (GB); Timothy Donald Neubert, San Diego, CA (US); Joanne Louise Pinder, Didcot (GB); Joseph Pontillo, San Diego, CA (US); Robert Pullin, Oxford (GB); Yvonne Schmidt, San Diego, CA (US); David Matthew Shaw, Oxford (GB); Sarah Skerratt, Cambridge (GB); Dean Stamos, Carlsbad, CA (US); Stephen Andrew Thomson, Durham, NC (US); Anisa Nizarali Virani, Thatcham (GB); and Christopher Wray, Berkshire (GB)
Assigned to VERTEX PHARMACEUTICALS INCORPORATED, Boston, MA (US)
Filed by Vertex Pharmaceuticals Incorporated, Boston, MA (US)
Filed on Dec. 4, 2020, as Appl. No. 17/112,156.
Claims priority of provisional application 62/944,869, filed on Dec. 6, 2019.
Prior Publication US 2021/0198241 A1, Jul. 1, 2021
Int. Cl. C07D 405/12 (2006.01); C07D 307/24 (2006.01); C07D 405/14 (2006.01)
CPC C07D 405/12 (2013.01) [C07D 307/24 (2013.01); C07D 405/14 (2013.01); C07B 2200/13 (2013.01)] 62 Claims
 
1. A compound of formula (I)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
X2a is N, N+—O−, or C—R2a;
X4a is N or N+—O−;
X5a is N, N+—O−, or C—R5a;
X6a is N, N+—O−, or C—R6a;
each R is independently H or C1-C6 alkyl;
R2a, R4a, R5a, and R6a are each independently H, halo, C1-C6 alkyl, or C1-C6 haloalkyl;
R4b1 and R4b2 are each independently H, C1-C6 alkyl, C3-C6 cycloalkyl, or C1-C6 haloalkyl;
R5b1 and R5b2 are each independently H, C1-C6 alkyl, C3-C6 cycloalkyl, or C1-C6 haloalkyl;
X3c is N or C—R3c;
X4c is N or C—R4c;
X5c is N or C—R5c;
X6c is N or C—R6c;
R2c is H, OH, halo, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or -L1-L2-(C3-C6 cycloalkyl), wherein said cycloalkyl of R2c is optionally substituted with 1-2 halo;
L1 is a bond or O;
L2 is a bond or C1-C6 alkylene;
R3c is H, halo, C1-C6 alkyl, or C1-C6 haloalkyl;
R4c is H, halo, C1-C6 alkyl, or C1-C6 haloalkyl;
R5c is H, halo, C1-C6 alkyl, or C1-C6 haloalkyl; and
R6c is H, halo, C1-C6 alkyl, or C1-C6 haloalkyl;
provided that no more than two of X2a, X4a, X5a, and X6a are N or N+—O−; and
provided that no more than one of X3c, X4c, X5c, and X6c are N.