US 11,701,370 B2
Phosphonium ion channel blockers and methods for use
Bridget McCarthy Cole, Quincy, MA (US); and James Lamond Ellis, Somerville, MA (US)
Assigned to Nocion Therapeutics, Inc., Waltham, MA (US)
Filed by Nocion Therapeutics, Inc., Waltham, MA (US)
Filed on Nov. 5, 2020, as Appl. No. 17/90,160.
Claims priority of provisional application 62/931,407, filed on Nov. 6, 2019.
Prior Publication US 2021/0128589 A1, May 6, 2021
Int. Cl. A61K 31/66 (2006.01); A61K 45/06 (2006.01); C07F 9/54 (2006.01); C07F 9/6568 (2006.01)
CPC A61K 31/66 (2013.01) [A61K 45/06 (2013.01); C07F 9/54 (2013.01); C07F 9/5442 (2013.01); C07F 9/65688 (2013.01)] 19 Claims
 
1. A compound represented by Formula (I)

OG Complex Work Unit Chemistry
wherein
Y− is a pharmaceutically acceptable anion;
RA and RB are each independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, ORI, NRJRK, NRLC(O)RM, CN, S(O)RN, S(O)2RN, SO2RQRP, SO2NRQRR, SO3RS, C(O)RU, and C(O)NRVRW;
RC is selected from H, D, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, ORI, NRJRK, NRLC(O)RM, CN, S(O)RN, S(O)2RN, SO2RORP, SO2NRQRR, SO3RS, CO2RT, C(O)RU, and C(O)NRVRW;
each of RI, RJ, RK, RL, RM, RN, RO, RP, RQ, RR, RS, RT, RU, RV, and RW is independently selected from H, D, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl;
X1 is selected from —CRXRY—, —NRZC(O)—, —NRZC(O)CRXRY, —OC(O)—, —SC(O)—, —C(O)NR1A—, —C(O)O—, —C(O)—, —(O)CS—, —NR1AS(O), —S(O)NR1A—, —NR1AC(O)NR1A—, —S(O)— and —S(O)2—;
each of RX, RY, RZ, and R1A is independently selected from H, D, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; or RX, RY, RZ, or R1A together with RD or RE and the atoms to which they are attached form an optionally substituted cycloalkyl or an optionally substituted heterocyclic ring;
each of RD and RE is independently selected from H, D, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, and substituted or unsubstituted cycloalkyl; or RD and RE together with the carbon to which they are attached form a substituted or unsubstituted C3-C6 cycloalkyl, or a substituted or unsubstituted 5- to 10-membered heterocyclic;
RH is selected from H, D, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl; substituted or unsubstituted heterocyclyl, substituted or unsubstituted—C6-C10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, substituted or unsubstituted —CH2-C6-C10 aryl and substituted or unsubstituted —CH2-5- to 10-membered heteroaryl;
RF and RG together with the P+ to which they are attached form an optionally substituted 5- to 10-membered heterocyclic ring having zero, one, or more heteroatoms in addition to the P+.