Claims for Patent: 9,956,192

Summary for Patent: 9,956,192

Title:	Selective histone deactylase 6 inhibitors
Abstract:	Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula (I). Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed. ##STR00001##
Inventor(s):	Sotomayor; Eduardo M. (Tampa, FL), Bergman; Joel (Chicago, IL), Kozikowski; Alan (Chicago, IL), Woan; Karrune Veeraprasert (Gainesville, FL), Villagra; Alejandro V. (Tampa, FL)
Assignee:	H. Lee Moffitt Cancer Center and Research Institute, Inc. (Tampa, FL) Board of Trustees of The University of Illinois (Urbana, IL)
Application Number:	15/231,187
Patent Claims:	1. A method of treating melanoma in a subject, comprising: administering to the subject a therapeutically effective amount of a compound having Formula I: ##STR00034## wherein A is C.sub.1-C.sub.8 alkyl, phenyl, pyridyl, oxazolidyl, or pyrimidyl optionally substituted with one or more groups chosen from C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.4 alkoxy, or halo; and R.sup.1 and R.sup.2 are, independently, hydrogen, or are C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.3 alkylaryl, or C.sub.1-C.sub.3 alkylheteroaryl optionally substituted with acetyl, C.sub.1-C.sub.5 alkyl, --NR.sup.6R.sup.7, C.sub.1-C.sub.4 alkoxy, carbonyl, halo, or hydroxy; or R.sup.1 and R.sup.2 are joined such that together they form an alkylene bridge comprising 2 atoms so that a 5-membered ring is formed with the --NC(O)N-- moiety, in which case A is as defined above or hydrogen, and which 5-membered ring is optionally substituted with R.sup.1', R.sup.2', R.sup.1'', and R.sup.2'', which are independently, hydrogen, or are C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.3 alkylaryl, or C.sub.1-C.sub.3 alkylheteroaryl, any of which is optionally substituted with amino, C.sub.1-C.sub.4 alkoxy, halo, or hydroxy; or R.sup.1' and R.sup.1'' together or R.sup.2'' and R.sup.2' together form a carbonyl (i.e., .dbd.O); or R.sup.1' and R.sup.2' are null and R.sup.1'' and R.sup.2'' together form a fused phenyl group; and R.sup.6 and R.sup.7 are independently H, C.sub.1-C.sub.4 alkyl, or are joined such that together they form an alkylene bridge comprising 4 or 5 atoms so that a 5 or 6-membered ring is formed with the nitrogen; or a pharmaceutically acceptable salt or hydrate thereof. 2. The method of claim 1, wherein R.sup.1 and R.sup.2 are both hydrogen. 3. The method of claim 1, wherein A is phenyl. 4. The method of claim 1, wherein A is phenyl substituted with one or more C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.4 alkoxyl, or halo. 5. The method of claim 1, wherein A is ortho-methoxyl substituted phenyl. 6. The method of claim 1, wherein A is pyridyl or pyridyl substituted with C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.4 alkoxyl, or halo. 7. The method of claim 1, wherein A is n-propyl, i-propyl, n-butyl, t-butyl, s-butyl, i-butyl, n-pentyl, i-pentyl, or s-pentyl group. 8. The method of claim 1, wherein R.sup.1 is hydrogen or C.sub.1-C.sub.8 alkyl is optionally substituted with C.sub.1-C.sub.3 alkyl, --NR.sup.6R.sup.7, C.sub.1-C.sub.4 alkoxy, carbonyl, or hydroxy. 9. The method of claim 1, wherein R.sup.1 is C.sub.1-C.sub.8 alkyl. 10. The method of claim 1, wherein R.sup.1 is C.sub.1-C.sub.8 alkyl optionally substituted with acetyl, NH.sub.2, N(C.sub.1-C.sub.4 alkyl).sub.2, C.sub.1-C.sub.4 alkoxy, carbonyl, halo, or hydroxy. 11. The method of claim 1, wherein R.sup.1 is hydrogen. 12. The method of claim 1, wherein R.sup.2 is hydrogen or C.sub.1-C.sub.8 alkyl optionally substituted with C.sub.1-C.sub.5 alkyl, --NR.sup.6R.sup.7, C.sub.1-C.sub.4 alkoxy, carbonyl, or hydroxy. 13. The method of claim 1, wherein R.sup.2 is C.sub.1-C.sub.5 alkyl, or C.sub.1-C.sub.5 alkyl substituted with a methoxy, --NR.sup.6R.sup.7, carbonyl, or hydroxy. 14. The method of claim 1, wherein R.sup.2 is C.sub.1-C.sub.3 alkylheteroaryl. 15. The method of claim 1, wherein R.sup.2 is C.sub.1-C.sub.3 alkyl substituted with a phenyl, hydroxy substituted phenyl, methoxy substituted phenyl, halo substituted phenyl, or amino substituted phenyl. 16. The method of claim 1, wherein the compound has Formula I-A: ##STR00035## wherein each W is CH or any one or two W is N and the others are CH; and R.sup.5 is hydrogen, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.4 alkoxy, or halo, or a pharmaceutically acceptable salt or hydrate thereof. 17. The method of claim 1, wherein the compound has Formula I-B: ##STR00036## wherein each W is CH or any one or two W is N and the others are CH; and R.sup.5 is C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.4 alkoxy, or halo, or a pharmaceutically acceptable salt or hydrate thereof. 18. The method of claim 1, wherein the compound has Formula I-C: ##STR00037## wherein A is C.sub.1-C.sub.8 alkyl, phenyl, pyridyl, oxazolidyl, or pyrimidyl optionally substituted with one or more groups chosen from C.sub.1-C.sub.5 alkyl, C.sub.1-C.sub.4 alkoxy, or halo; and R.sup.1', R.sup.2', and R.sup.2'', are independently, hydrogen, or are C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.3 alkylaryl, or C.sub.1-C.sub.3 alkylheteroaryl, any of which is optionally substituted with amino, C.sub.1-C.sub.4 alkoxy, halo, or hydroxy; or R.sup.1' and R.sup.1'' together or R.sup.2'' and R.sup.2' together form a carbonyl; or R.sup.1' and R.sup.2' are null and R.sup.1'' and R.sup.2'' together form a fused phenyl group, or a pharmaceutically acceptable salt or hydrate thereof. 19. The method of claim 18, wherein R.sup.1' and R.sup.1'' or R.sup.2' and R.sup.2'' are both methyl. 20. The method of claim 18, wherein R.sup.1' is hydrogen and R.sup.1'' is methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, benzyl, methylphenol, methylphenylmethoxy, or methylphenylamino or R.sup.2' is hydrogen and R.sup.2'' is methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, benzyl, methylphenol, methylphenylmethoxy, or methylphenylamino. 21. The method of claim 1, wherein R.sup.1' and R.sup.1'' or R.sup.2' and R.sup.2'' form a carboxyl group. 22. The method of claim 1, wherein the compound is chosen from: ##STR00038## ##STR00039## ##STR00040## ##STR00041## ##STR00042## 23. The method of claim 1, wherein the compound is Tubstatin A. 24. The method of claim 1, wherein the compound is administered with one or more of ipilimumab, revlimid, velcade, vemurafenib, ST-3-06, ST-2-92, Tubstatin A, Tubacin. 25. The method of claim 1, wherein the inhibitor is combined with a STAT3 inhibitor.

Details for Patent 9,956,192

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bristol-myers Squibb Company	YERVOY	ipilimumab	Injection	125377	03/25/2011		2032-03-07