Icos Corporation

Eli Lilly and Company

Myriad Genetics, Inc.

Deltagen Research Labs, LLC

Danwen Huang

Kerry W Fowler

Edward A Kesicki

Jennifer Anne Treiberg

Amy Oliver

Fuqiang Ruan

Hua Chee Ooi

Kamal Deep Puri

Joshua O Odingo

Cynthia Darshini Jesudason

Jaimie Karyn Rueter

Thomas Little

Qin Jiang

Pavel E Zhichkin

Marcin Stasiak

Graham Beaton

Wilna J Moree

Russell Dahl

Maher Qabar

David L McElligott

Jessymol Mathew

Erik Christenson

Phyllis S Goldman

David John Fairfax

Gary G Deng

Helge A Reisch

Anthony J Demaggio

Ren Hua Song

Lisa H Bourdon

Jaimie E Bertino

Dan Herendeen

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

The invention provides certain azetidinyloxyphenylpyrrolidine compounds, particularly compounds of formula I, and pharmaceutical compositions thereof. The invention further provides methods of using a compound of formula I to treat overactive bladder. 

Azetidinyloxyphenylpyrrolidine compounds

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

The invention provides certain azetidinyloxyphenylpyrrolidine compounds, particularly compounds of formula I wherein R is hydrogen or methyl, and pharmaceutical compositions thereof. The invention further provides methods of using a compound of formula I to treat overactive bladder. 

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.

Reverse-turn mimetics and methods relating to the same having the following structure are disclosed: including pharmaceutically acceptable salts and stereoisomers thereof, wherein R, R, Rand Rare as defined herein. Such compounds have utility over a wide range of applications, including use as diagnostic and therapeutic agents. In particular, compounds of this invention, and pharmaceutical compositions containing such compounds, are neurokinin (tachykinin) antagonists. Libraries containing the reverse-turn mimetics of this invention are also disclosed.

Reverse-turn mimetics and compositions and methods relating thereto

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Bellevue, WA, United States of America

Danwen Huang