Icos Corporation

Bellerophon Bcm LLC

Other

Genesis Molecular Technologies, Inc.

Fred Hutchinson Cancer Center

Ikaria Inc.

3+2 Pharma, LLC

Fuqiang Ruan

Edward A Kesicki

Kerry W Fowler

Jennifer Anne Treiberg

Amy Oliver

Danwen Huang

Hua Chee Ooi

Kamal Deep Puri

Thomas L Deckwerth

Martin D Meglasson

Edward A Wintner

Amy R Oliver

Provided are compounds of formula (I): or a cosmeceutically acceptable or pharmaceutically acceptable salts thereof. Additionally provided are pharmaceutical and/or cosmeceutical compositions and formulations comprising the compounds and/or the cosmeceutically acceptable or pharmaceutically acceptable salts thereof, therapeutic and/or cosmetic methods using same for modulating (e.g., inhibiting) CREB binding protein (CBP)/β-catenin mediated signaling in treating skin related diseases, conditions or disorders (e.g., dermatitis, psoriasis, scarring, alopecia, etc.) mediated by aberrant CBP/β-catenin signaling, and cosmetic methods for treating skin conditions (e.g., aging, etc.) mediated by aberrant CBP/β-catenin signaling.

Substituted imidazo[l,2-a]pyrazines and pyrazino[l,2-a] pyrimidines as topical agents for dermatological applications

Provided are compounds of formula (Ia), (Ib) and (IIa), and pharmaceutically acceptable salts thereof. Additionally provided are compositions and pharmaceutical compositions comprising the compounds, therapeutic methods using same for modulating (e.g., inhibiting) CREB binding protein (CBP)/&#x3b2;-catenin mediated signaling in treating a condition, disease or disorder (e.g., fibrosis, cancer, neurological conditions, metabolic disorders (e.g., diabetes, etc.), and skin conditions (dermatitis, psoriasis, scarring, alopecia, etc.) mediated by aberrant CBP/&#x3b2;-catenin signaling, and cosmetic methods for treating skin conditions (e.g., aging, etc.). Additionally, provided are methods for enhancing vaccine efficacy using the compounds and compositions. Further provided are methods for efficiently synthesizing a clinical grade drug, comprising use, in a penultimate, or last reaction step under GMP conditions, of an intermediate 2-propynyl-compound to form a clinical grade isoxazole derivative (e.g., via 3+2 cycloaddition).

CBP/catenin signaling pathway inhibitors and uses thereof

Provided are compounds of formula (I): or cosmeceutically acceptable or pharmaceutically acceptable salts thereof. Additionally provided are cosmeceutical and/or pharmaceutical compositions comprising the compounds of formula (I), or the cosmeceutically acceptable or pharmaceutically acceptable salts thereof. Also provided are therapeutic and/or cosmetic methods using the cosmeceutical and/or pharmaceutical compositions comprising the compounds of formula (I), or the cosmeceutically acceptable or pharmaceutically acceptable salts thereof, for modulating cyclic adenosine monophosphate response element binding (CREB)-binding protein (CBP)/&#x3b2;-catenin mediated signaling in treating skin related diseases, conditions, or disorders mediated by aberrant CBP/&#x3b2;-catenin signaling and cosmetic methods for treating skin conditions mediated by aberrant CBP/&#x3b2;-catenin signaling.

Substituted imidazo[1,2-a]pyrazines and pyrazino[1,2-a]pyrimidines as topical agents for dermatological applications

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

In recognition of the unmet need to develop novel therapeutic agents, the present invention discloses a novel class of heterocycles as dual inhibitors of BRD4 and class I PI3Ks. The compounds claimed herein could be used alone or in combination therapies for the effective treatment of a wide range of age-related diseases, including cancer. The present invention also provides methods for preparing compounds of the invention thereto.

Heterocyclic compounds and uses 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

The present application discloses a novel class of heterocycles as class I PI3Ks inhibitors. The compounds claimed herein could be used alone or in combination therapies for the treatment of a wide range of disorders such as autoimmune, inflammatory and allergic diseases, asthma, COPD, parasitic infections, diabetes, and cancer.

Heterocyclic compounds as inhibitors of class I PI3KS

Described are bifunctional NOTA-based derivatives capable of conjugating with alginate and with metal ions, as well as NOTA-alginate conjugates which can be labeled with stable or radioactive metal ions. Also described are conjugation methods of the bifunctional NOTA-based linker with alginate, and methods of using radiometal-labeled NOTA-alginate conjugates or other radio-labeled alginate conjugates as imaging reagents.

Labeled alginate conjugates for molecular imaging applications

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

Compositions and methods of treating or preventing disease or injury to a human patient or biological material undergoing ischemic or hypoxic conditions.

Growing community of inventors

Bellevue, WA, United States of America

Fuqiang Ruan