Claims for Patent: 11,618,748

Summary for Patent: 11,618,748

Title:	Dual mechanism inhibitors for the treatment of disease
Abstract:	Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved.
Inventor(s):	Mitchell A. deLong, Jill Marie Sturdivant, Susan M. Royalty
Assignee:	Alcon Inc
Application Number:	US17/243,272
Patent Claims:	1. A method of reducing intraocular pressure, comprising administration of a composition comprising a Rho kinase inhibitor and a pharmaceutically acceptable carrier to a subject in need thereof, wherein the administration is daily administration, weekly administration, or monthly administration, wherein the Rho kinase inhibitor is: or a pharmaceutically acceptable salt thereof, wherein R1, R2, and R3 are independently hydrogen, C1-C4 alkyl, aryl, C1-C4 alkyl aryl, C1-C4 alkyl heteroaryl, C1-C4 alkyl heterocyclyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 carbonyl, C1-C4 carbonylamino, C1-C4 alkoxy, C1-C4 sulfonyl, C1-C4 sulfonylamino, C1-C4 thioalkyl, C1-C4 carboxyl, or form a ring with each other or with A; A is C1-C4 alkyl, C1-C4 alkyl aryl, C1-C4 alkyl heteroaryl, or forms a ring structure with R1, R2 or R3; B is hydrogen, an aryl group, a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, C1-C22 alkyl, C1-C22 alkyl aryl, C1-C22 alkyl heteroaryl, C2-C22 alkenyl, C2-C22 alkynyl, C1-C22 carbonyl, C1-C22 carbonylamino, C1-C22 alkoxy, C1-C22 sulfonyl, C1-C22 sulfonylamino, C1-C22 thioalkyl, or C1-C22 carboxyl; X1, X2, and X3 are, independently, hydrogen, hydroxyl, halogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, amino, aminocarbonyl, nitro, cyano, C1-C4 carbonyl, C1-C4 carbonylamino, C1-C4 alkoxy, C1-C4 sulfonyl, C1-C4 sulfonylamino, C1-C4 thioalkyl, or C1-C4 carboxyl; the double circle indicates an aromatic or heteroaromatic ring; and each Z is independently a bond, C1-C4 alkyl, heteroalkyl, or an O atom. 2. The method of claim 1, wherein the administration is ocular administration. 3. The method of claim 1, wherein the amount of the compound administered is about 0.001 to about 100 mg/kg subject body weight. 4. The method of claim 1, wherein the administration is once daily, twice per day, or 4 times per day. 5. The method of claim 2, wherein the administration is once daily, twice per day, or 4 times per day. 6. The method of claim 3, wherein the administration is once daily, twice per day, or 4 times per day. 7. The method of claim 1, wherein the administration is once weekly or twice weekly. 8. The method of claim 2, wherein the administration is once weekly or twice weekly. 9. The method of claim 3, wherein the administration is once weekly or twice weekly. 10. The method of claim 1, wherein the administration is once a month. 11. The method of claim 2, wherein the administration is once a month. 12. The method of claim 3, wherein the administration is once a month. 13. A method of treating glaucoma or ocular hypertension, comprising administration of a composition comprising a Rho kinase inhibitor and a pharmaceutically acceptable carrier to a subject in need thereof, wherein the administration is daily administration, weekly administration, or monthly administration, wherein the Rho kinase inhibitor is: or a pharmaceutically acceptable salt thereof. 14. The method of claim 13, wherein the administration is ocular administration. 15. The method of claim 13, wherein the amount of the compound administered is about 0.001 to about 100 mg/kg subject body weight. 16. The method of claim 13, wherein the administration is once daily, twice per day, or 4 times per day. 17. The method of claim 14, wherein the administration is once daily, twice per day, or 4 times per day. 18. The method of claim 15, wherein the administration is once daily, twice per day, or 4 times per day. 19. The method of claim 13, wherein the administration is once weekly or twice weekly. 20. The method of claim 14, wherein the administration is once weekly or twice weekly. 21. The method of claim 15, wherein the administration is once weekly or twice weekly. 22. The method of claim 13, wherein the administration is once a month. 23. The method of claim 14, wherein the administration is once a month. 24. The method of claim 15, wherein the administration is once a month.