|Title:||Inhibitors of human phosphatidylinositol 3-kinase delta|
|Abstract:||Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K.delta.) activity, and methods of treating diseases, such as disorders of immunity and inflammation, in which PI3K.delta. plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3K.delta., while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3K.delta. activity, including compounds that selectively inhibit PI3K.delta. activity. Methods of using PI3K.delta. inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3K.delta. inhibitory compounds to inhibit PI3K.delta.-mediated processes in vitro and in vivo.|
|Inventor(s):||Sadhu; Chanchal (Bothell, WA), Dick; Ken (Bothell, WA), Treiberg; Jennifer (Bothell, WA), Sowell; C. Gregory (Mukilteo, WA), Kesicki; Edward A. (Bothell, WA), Oliver; Amy (Bothell, WA)|
|Assignee:||ICOS Corporation (Indianapolis, IN)|
|Filing Date:||Oct 07, 2009|
|Claims:||1. A compound of formula IV ##STR00093## wherein Y is null; R.sup.10 is selected from the group consisting of H, halo, OH, OCH.sub.3, CH.sub.3, and CF.sub.3; R.sup.11 is selected from the group consisting of H, OCH.sub.3, and halo; R.sup.12 is selected from the group consisting of phenyl, halophenyl, and alkylphenyl; R.sup.d, independently, is selected from the group consisting of NH.sub.2, NH(C.sub.1-3alkyl), N(C.sub.1-3alkyl).sub.2, and C.sub.1-3alkyl; and q is 1 or 2; or a pharmaceutically acceptable salt thereof; provided that: (a) at least one of R.sup.10 and R.sup.11 is different from 6-halo or 6,7-dimethoxy groups; and (b) R.sup.12 is different from 4-chlorophenyl. |
2. The compound of claim 1, wherein R.sup.12 is alkylphenyl, or a pharmaceutically acceptable salt thereof.
3. The compound of claim 2, wherein R.sup.10 is CH.sub.3 and R.sup.11 is H, or a pharmaceutically acceptable salt thereof.
4. The compound of claim 3, wherein R.sup.d is NH.sub.2, or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1, wherein the compound is 2-(6-aminopurin-9-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one, or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient.
7. A pharmaceutical composition comprising an effective amount of a compound of 2-(6-aminopurin-9-ylmethyl)-5-methyl-3-o-tolyl-3H-quinazolin-4-one or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient.
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