Claims for Patent: 8,193,182

Summary for Patent: 8,193,182

Title:	Substituted isoquinolin-1(2H)-ones, and methods of use thereof
Abstract:	Chemical entities of Formula I: ##STR00001## that modulate PI3 kinase activity, pharmaceutical compositions containing the chemical entities, and methods of using these chemical entities for treating diseases and conditions associated with P13 kinase activity are described herein.
Inventor(s):	Ren; Pingda (San Diego, CA), Liu; Yi (San Diego, CA), Wilson; Troy Edward (San Marino, CA), Li; Liansheng (San Diego, CA), Chan; Katrina (San Diego, CA), Rommel; Christian (La Jolla, CA)
Assignee:	Intellikine, Inc. (La Jolla, CA)
Application Number:	12/503,776
Patent Claims:	1. A compound of Formula I-1: ##STR00666## or its pharmaceutically acceptable salt thereof, wherein B is a moiety of Formula II: ##STR00667## wherein W.sub.c is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl, and q is an integer of 0, 1, 2, 3, or 4; X is a bond or --(CH(R.sup.9)).sub.z--, and z is an integer of 1; Y is --N(R.sup.9)--; W.sub.d is: ##STR00668## R.sup.1 is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, amido, alkoxycarbonyl, sulfonamido, halo, cyano, or nitro; R.sup.2 is alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, heteroarylalkyl, alkoxy, amino, halo, cyano, hydroxy or nitro; R.sup.3 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, alkoxy, amido, amino, alkoxycarbonyl sulfonamido, halo, cyano, hydroxy or nitro; and each instance of R.sup.9 is independently hydrogen, alkyl, or heterocycloalkyl. 2. The compound of claim 1, wherein B is a moiety of Formula II: ##STR00669## wherein W.sub.c is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; q is an integer of 0 or 1; R.sup.1 is hydrogen, alkyl, or halo; R.sup.2 is alkyl or halo; and R.sup.3 is hydrogen, alkyl, or halo. 3. The compound of claim 1 wherein X is --(CH(R.sup.9)).sub.z--, and Y is --NH--. 4. The compound of claim 1 wherein R.sup.3 is --H, --CH.sub.3, --CH.sub.2CH.sub.3, --CF.sub.3, --Cl or --F. 5. The compound of claim 2 wherein X is --(CH(R.sup.9)).sub.z--, wherein R.sup.9 is methyl and z=1; and W.sub.d is ##STR00670## 6. The compound of claim 1 wherein the compound is predominately in an (S)-stereochemical configuration. 7. The compound of claim 1 wherein the compound has a structure of Formula V-A2: ##STR00671## 8. The compound of claim 2 wherein R.sup.3 is methyl or chloro. 9. The compound of claim 7 wherein B is a moiety of Formula II: ##STR00672## wherein W.sub.c is aryl or cycloalkyl. 10. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 11. The pharmaceutical composition of claim 10 wherein B is a moiety of Formula II: ##STR00673## wherein W.sub.c is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; q is an integer of 0 or 1; R.sup.1 is hydrogen, alkyl, or halo; R.sup.2 is alkyl or halo; and R.sup.3 is hydrogen, alkyl, or halo. 12. The pharmaceutical composition of claim 10 wherein X is --(CH(R.sup.9)).sub.z--, wherein R.sup.9 is methyl and z=1; and W.sub.d is ##STR00674## 13. A compound selected from: ##STR00675## ##STR00676## ##STR00677## ##STR00678## ##STR00679## ##STR00680## ##STR00681## ##STR00682## ##STR00683## ##STR00684## ##STR00685## 14. The compound of claim 13, wherein the compound is selected from: ##STR00686## ##STR00687## ##STR00688## ##STR00689## 15. The compound of claim 13, wherein the compound is selected from: ##STR00690## ##STR00691## 16. The compound of claim 13, wherein the compound is the S-enantiomer having an enantiomeric purity selected from greater than about 55%, greater than about 80%, greater than about 90%, and greater than about 95%. 17. The compound of claim 15, wherein the compound is the S-enantiomer having an enantiomeric purity selected from greater than about 55%, greater than about 80%, greater than about 90%, and greater than about 95%. 18. The compound of claim 17, wherein the compound is selected from: ##STR00692## ##STR00693## 19. The compound of claim 18, wherein the compound is ##STR00694## 20. The compound of claim 18, wherein the compound is ##STR00695## 21. The compound of claim 18, wherein the compound is ##STR00696## 22. A compound having the following structure: ##STR00697## or a pharmaceutically acceptable salt thereof. 23. A compound having the following structure: ##STR00698## or a pharmaceutically acceptable salt thereof. 24. A compound having the following structure: ##STR00699## or a pharmaceutically acceptable salt thereof. 25. The pharmaceutical composition of claim 10, comprising a plurality of pharmaceutically acceptable excipients. 26. A pharmaceutical composition comprising a compound of claim 14 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 27. A pharmaceutical composition comprising a compound of claim 15 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 28. A pharmaceutical composition comprising a compound of claim 18 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 29. The pharmaceutical composition of claim 28 further comprising a plurality of pharmaceutically acceptable excipients. 30. A pharmaceutical composition comprising a compound of claim 22, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 31. A pharmaceutical composition comprising a compound of claim 23, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 32. A pharmaceutical composition comprising a compound of claim 24, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 33. The pharmaceutical composition of any one of claim 30, 31, or 32, further comprising a plurality of pharmaceutically acceptable excipients. 34. The compound of claim 7, wherein R.sup.3 is methyl or chloro. 35. The compound of claim 34, wherein R.sup.9 is methyl or ethyl. 36. The compound of claim 35, wherein B is substituted or unsubstituted phenyl. 37. The compound of claim 35, wherein B is substituted or unsubstituted cycloalkyl. 38. The compound of claim 36, wherein B is phenyl that is unsubstituted or substituted with fluoro. 39. The compound of claim 38, wherein B is phenyl that is substituted with one fluoro in the ortho or meta position of the phenyl ring.