Icos Corporation

Gilead Calistoga LLC

Kamal Deep Puri

Kerry W Fowler

Edward A Kesicki

Jennifer Anne Treiberg

Amy Oliver

Fuqiang Ruan

Danwen Huang

Hua Chee Ooi

Jerry B Evarts

Brian Lannutti

Neill A Giese

Amy R Oliver

Compounds that inhibit PI3K&#x3b4; activity, including compounds that selectively inhibit PI3K&#x3b4; activity, are disclosed. Methods of preparing such compounds are also disclosed, including the preparation and use of the compound tert-butyl (S)-(1-(5-fluoro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)propyl)carbamate of formula (110) as a precursor to synthesize an exemplary compound disclosed in this application, (S)-2-(1-((9H-purin-6-yl)amino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K&#x3b4;) activity, and methods of treating diseases, such as disorders of immunity and inflammation in which PI3K&#x3b4; plays a role in leukocyte function, using the compounds also are disclosed. 

Tert-butyl (s)-(1-(5-fluoro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)propyl)carbamate precursor of a quinazolinone inhibitor of human phosphatidylinositol 3-kinase delta and a process for preparing thereof

Compounds that inhibit PI3K&#x3b4; activity, including compounds that selectively inhibit PI3K&#x3b4; activity, are disclosed. Methods of preparing such compounds are also disclosed, including the use of (S)-2-(1-aminopropyl)-5-fluoro-3-phenylquinazolin-4(3H)-one as a precursor to synthesize an exemplary compound disclosed in this application, (S)-2-(1-((9H-purin-6-yl)amino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K&#x3b4;) activity, and methods of treating diseases, such as disorders of immunity and inflammation in which PI3K&#x3b4; plays a role in leukocyte function, using the compounds also are disclosed.

(S)-2-(1-aminopropyl)-5-fluoro-3-phenylquinazolin-4(3H)-one precursor of a quinazolinone as inhibitor of human phosphatidylinositol 3-kinase delta

Compounds that inhibit PI3K&#x3b4; activity, including compounds that selectively inhibit PI3K&#x3b4; activity, are disclosed. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K&#x3b4;) activity, and methods of treating diseases, such as disorders of immunity and inflammation in which PI3K&#x3b4; plays a role in leukocyte function, using the compounds also are disclosed. An exemplary compound disclosed in this application is shown below: 

5-fluoro-3-phenyl-2-[1-(9h-purin-6-ylamino)propyl]-3h-quinazolin-4-one as an inhibitor of human phosphatidylinositol 3-kinase delta

Compounds that inhibit PI3K&#x3b4; activity, including compounds that selectively inhibit PI3K&#x3b4; activity, are disclosed. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K&#x3b4;) activity, and methods of treating diseases, such as disorders of immunity and inflammation in which PI3K&#x3b4; plays a role in leukocyte function, using the compounds also are disclosed. Exemplary compounds disclosed in this application are shown below: 

5-fluoro-3-phenyl-2-[1-(9H-purin-6-ylamino)propyl]-3H-quinazolin-4-one and 6-fluoro-3-phenyl-2-[1-(9H-purin-6-ylamino)ethyl]-3H-quinazolin-4-one as inhibitors of human phosphatidylinositol 3-kinase delta

5-fluoro-3-phenyl-2[1-(9H-purin-6-ylamino)propyl]-3H-quinazolin-4-one and 6-fluoro-3-phenyl-2-[1-(9H-purin-6-ylamino)ethyl]-3H-quinazolin-4-one as inhibitors of human phosphatidylinositol 3-kinase delta

Compounds that inhibit PI3K&#x3b4; activity, including compounds that selectively inhibit PI3K&#x3b4; activity, are disclosed. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K&#x3b4;) activity, and methods of treating diseases, such as disorders of immunity and inflammation in which PI3K&#x3b4; plays a role in leukocyte function, using the compounds also are disclosed. An exemplary compound disclosed in this application is shown below. 

6-fluoro-3-phenyl-2-[1-(9H-purin-6-ylamino)-ethyl]-3H-quinazolin-4-one as an inhibitor of human phosphatidylinositol 3-kinase delta

The invention provides a class of substituted quinazolinone compounds and methods of treating diseases mediated by PI3K&#x3b4; activity. The disclosed compounds are useful in treating diseases such as bone-resorption disorders; and cancer, especially hematopoietic cancers, lymphomas, multiple myelomas and leukemia. The compounds are also useful in disrupting or inhibiting cellular processes such as leukocyte function or accumulation, neutrophils function, lymphocyte proliferation, and endogenous immune responses.

Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta

Compounds that inhibit PI3K&#x3b4; activity, including compounds that selectively inhibit PI3K&#x3b4; activity, are disclosed. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform PI3K&#x3b4; activity, and methods of treating diseases, such as disorders of immunity and inflammation in which PI3K&#x3b4; plays a role in leukocyte function, using the compounds also are disclosed. An exemplary compound disclosed in this application is shown below. 

6-fluoro-3-phenyl-2-[1-(9H-purin-6-ylamino)ethyl]-3H-quinazolin-4-one as an inhibitor of human phosphatidylinositol 3-kinase delta

Compounds that inhibit P13K&#x3b4; activity, including compounds that selectively inhibit P13K&#x3b4; activity, are disclosed. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (P13K&#x3b4;) activity, and methods of treating diseases, such as disorders of immunity and inflammation in which P13K&#x3b4; plays a role in leukocyte function, using the compounds also are disclosed.

The invention provides methods that relate to a novel therapeutic strategy for the treatment of hematological malignancies and inflammatory diseases. In particular, the method comprises administration of a compound of formula I, 

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Lynnwood, WA, United States of America

Kamal Deep Puri