Described herein are compounds and pharmaceutical compositions containing such compounds which inhibit transglutaminase 2 (TG2). Also described herein are methods for using such TG2 inhibitors, alone or in combination with other compounds, for treating diseases or conditions that would benefit from TG2 inhibition.

Provided herein are methods, kits, and pharmaceutical compositions that include a PI3 kinase inhibitor for treating cancers or hematologic disorders.

Provided herein are methods, kits, and pharmaceutical compositions that include a PI3 kinase inhibitor for treating cancers or hematologic disorders.

A compound of formula (I)

##STR00001##

or a pharmaceutically acceptable salt and tautomers thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, in the treatment of diseases and conditions in which modulation of STING (Stimulator of Interferon Genes) is beneficial, for example inflammation, allergic and autoimmune diseases, infectious diseases, cancer, pre-cancerous syndromes and as vaccine adjuvants

HIV replication inhibitors of formula

##STR00001##

N-oxides, pharmaceutically acceptable addition salts, quaternary amines or stereoisomeric forms thereof, wherein -a.sup.1=a.sup.2-a.sup.3=a.sup.4- is —CH═CH—CH═CH—, —N═CH—CH═CH—, —N═CH—N═CH—, —N═CH—CH═N—, —N═N—CH═CH—; -b.sup.1=b.sup.2-b.sup.3=b.sup.4- is —CH═CH—CH═CH—, —N═CH—CH═CH—, —N═CH—N═CH—, —N═CH—CH═N—, —N═N—CH═CH—; n and m is 0, 1, 2, 3 and in certain cases also 4; R.sup.1 is hydrogen; aryl; formyl; C.sub.1-6alkylcarbonyl; optionally substituted C.sub.1-6alkyl; C.sub.1-6alkyloxycarbonyl; R.sup.2 is OH; halo; optionally substituted C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6alkynyl; substituted carbonyl; carboxyl; CN; nitro; amino; substituted amino; polyhalomethyl; polyhalomethylthio; —S(═O).sub.pR.sup.6; C(═NH)R.sup.6; R.sup.2a is CN; amino; substituted amino; optionally substituted C.sub.1-6alkyl; halo; optionally substituted C.sub.1-6alkyloxy; substituted carbonyl; —CH═N—NH—C(═O)—R.sup.16; optionally substituted C.sub.1-6alkyloxyC.sub.1-6alkyl; substituted C.sub.2-6alkenyl or C.sub.2-6alkynyl; —C(═N—O—R.sup.8)—C.sub.1-4alkyl; R.sup.7 or X—R.sup.7; R.sup.3 is CN; amino; C.sub.1-6alkyl; halo; optionally substituted C.sub.1-6alkyloxy; substituted carbonyl; —CH═N—NH—C(═O)—R.sup.16; substituted C.sub.1-6alkyl; optionally substituted C.sub.1-6alkyloxyC.sub.1-6alkyl; substituted C.sub.2-6alkenyl or C.sub.2-6alkynyl; —C(═N—O—R.sup.8)—C.sub.1-4alkyl; R.sup.7; —X—R.sup.7; R.sup.4 is halo; OH; optionally substituted C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6alkynyl; C.sub.3-7cycloalkyl; C.sub.1-6alkyloxy; CN; nitro; polyhaloC.sub.1-6alkyl; polyhaloC.sub.1-6alkyloxy; substituted carbonyl; formyl; amino; mono- or di(C.sub.1-4alkyl)amino or R.sup.7; -A-B— is —CR.sup.5═N—, —N═N—, —CH.sub.2—CH.sub.2—, —CS—NH—, —CO—NH—, —CH═CH—;
pharmaceutical compositions comprising these; methods for the preparation of these compounds and compositions; the use of these compounds for the prevention or the treatment of HIV infection.

One aspect of the invention provides polymer conjugated MetAP2 inhibitors. While not being bound by any particular theory, it is believed that coupling the MetAP2 inhibitory core via the linkers described herein provides compounds with superior efficacy to the parent small molecules and superior pharmacokinetic profiles. In one aspect of the invention, the polymer conjugated MetAP2 inhibitors are useful in methods of treating disease, comprising administering to a subject in need thereof a therapeutically effective amount of a polymer conjugated MetAP2 inhibitor.

One aspect of the invention provides polymer conjugated MetAP2 inhibitors. While not being bound by any particular theory, it is believed that coupling the MetAP2 inhibitory core via the linkers described herein provides compounds with superior efficacy to the parent small molecules and superior pharmacokinetic profiles. In one aspect of the invention, the polymer conjugated MetAP2 inhibitors are useful in methods of treating disease, comprising administering to a subject in need thereof a therapeutically effective amount of a polymer conjugated MetAP2 inhibitor.

Polymorphs of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one, compositions thereof, methods for their preparation, and methods for their use are disclosed. Solvent forms of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one, compositions thereof, methods for their preparation, and methods for their use are also disclosed.

Polymorphs of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one, compositions thereof, methods for their preparation, and methods for their use are disclosed. Solvent forms of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one, compositions thereof, methods for their preparation, and methods for their use are also disclosed.

Certain embodiments are directed to non-hydrolysable ATP analogs and adenosine receptor antagonists that inhibit migration and growth of cancer cells.