Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

An RNA methyltransferase inhibitor comprising sulfonamide-based compounds and/or pyrazoline-based compounds is provided

The present invention describes the use of a 5HT3-antagonist, in combination with a 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine, to reduce adverse effects and to facilitate the neuroprotective treatment of a patient suffering from a synucleinopathic disorder to enable a therapeutically effective 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine daily dose without the dose-limiting adverse effects caused by pramipexole when administered alone.

The present invention describes the use of a 5HT3-antagonist, in combination with a 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine, to reduce adverse effects and to facilitate the neuroprotective treatment of a patient suffering from a synucleinopathic disorder to enable a therapeutically effective 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine daily dose without the dose-limiting adverse effects caused by pramipexole when administered alone.

The present invention describes the use of a 5HT3-antagonist, in combination with a 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine, to reduce adverse effects and to facilitate the neuroprotective treatment of a patient suffering from a synucleinopathic disorder to enable a therapeutically effective 6-propylamino-4,5,6,7-tetrahydro-1,3-benzothiazole-2-amine daily dose without the dose-limiting adverse effects caused by pramipexole when administered alone.

The present disclosure relates to methods of inhibiting replication of a respiratory virus, and methods of treating or preventing a respiratory virus infection in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a N-glycosylation pathway inhibitor.

A compound of formula (I) ##STR00001##
wherein X is 0, C=0 or S; Y is N or CH; R.sub.2 and R.sub.4 are each independently H, —(CH.sub.2).sub.pCOOH, —(CH.sub.2).sub.pCON(R.sup.5).sub.2 or —(CH.sub.2).sub.pCOOC.sub.1-6alkyl; or R.sub.2 and R.sub.4 together form a 6-membered phenyl ring fused to the five membered ring; each R.sub.1 is independently selected from H, halo (e.g. fluoro or chloro), C.sub.6-10aryl, C.sub.7-12arylalkyl, C.sub.2-12 alkenyl; OC.sub.1-12 alkyl, OC.sub.2-12 alkenyl or a C.sub.1-12 alkyl group; each R.sup.5 is H or C.sub.1-6 alkyl; each p is 0 to 3; n is 1 to 4; or a salt, ester, solvate, N-oxide, or prodrug thereof, e.g. a salt thereof.

A compound of formula (I) ##STR00001##
wherein X is 0, C=0 or S; Y is N or CH; R.sub.2 and R.sub.4 are each independently H, —(CH.sub.2).sub.pCOOH, —(CH.sub.2).sub.pCON(R.sup.5).sub.2 or —(CH.sub.2).sub.pCOOC.sub.1-6alkyl; or R.sub.2 and R.sub.4 together form a 6-membered phenyl ring fused to the five membered ring; each R.sub.1 is independently selected from H, halo (e.g. fluoro or chloro), C.sub.6-10aryl, C.sub.7-12arylalkyl, C.sub.2-12 alkenyl; OC.sub.1-12 alkyl, OC.sub.2-12 alkenyl or a C.sub.1-12 alkyl group; each R.sup.5 is H or C.sub.1-6 alkyl; each p is 0 to 3; n is 1 to 4; or a salt, ester, solvate, N-oxide, or prodrug thereof, e.g. a salt thereof.

Methods of expanding tumor infiltrating lymphocytes (TILs) using a potassium channel agonist, such as a K.sub.Ca3.1 (IK channel) agonist, and uses of such expanded TILs in the treatment of diseases such as cancer are disclosed herein.