This invention relates to macrocyclic deaza-purinones derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.

This invention relates to macrocyclic deaza-purinones derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.

The present invention relates to a novel compound that has antiviral activity, in particular, inhibitory activity against the integrase of the human immunodeficiency virus (HIV).

The subject of this invention is a novel annelated 9-hydroxy-1,8-dioxo-1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrazine-7-carboxamide of general formula 1 or 2, or any stereoisomer, any pharmaceutically acceptable salt, any solvate, or any crystalline or polycrystalline form thereof

##STR00001## wherein ring A.sup.1 is an optionally methyl-substituted 5-7 membered saturated heterocycle or heterobicycle; ring A.sup.2 is a 5-6 membered optionally methyl-substituted saturated or partially saturated monocyclic heterocycle; ring A.sup.3 is a 5-6 membered monocyclic saturated cycloalkane or tetrahydro-2H-pyran; R is a 5-7 membered optionally substituted with one, two, or three optionally identical substituents monocyclic or bicyclic heterocyclic radical comprising 1-4 heteroatoms selected from the series O, S, and N except (2S,5R,13aS)-8-hydroxy-7,9-dioxo-N-{[3-(trifluoromethyl)-pyridin-2-yl]methyl}-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopurido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide (formula A4) and (1R,4S,12aR)-N-[(3,5-difluoropyridin-2-yl)methyl]-7-hydroxy-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide (formula A5).

The present invention relates to compounds of formula (I), wherein R.sup.1 to R.sup.3 and n are as described herein, and their pharmaceutically acceptable salt thereof, and compositions including the compounds and methods of using the compounds.

##STR00001##

The present invention relates to compounds of formula (I), wherein R.sup.1 to R.sup.3 and n are as described herein, and their pharmaceutically acceptable salt thereof, and compositions including the compounds and methods of using the compounds.

##STR00001##

Novel rapamycin analogs and uses thereof are disclosed herein. The rapamycin analogs of the present disclosure show increased mTORC1 specificity and lowered mTORC2 specificity relative to rapamycin.

Novel rapamycin analogs and uses thereof are disclosed herein. The rapamycin analogs of the present disclosure show increased mTORC1 specificity and lowered mTORC2 specificity relative to rapamycin.

A process for preparing a sodium (2R,5S,13aR)-7,9-dioxo-10-((2,4,6-trifluorobenzyl) carbamoyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido [1′,2′:4,5] pyrazino[2,1-b][1,3]oxazepin-8-olate of Formula 1 and its polymorphic form thereof.

##STR00001##

A process for preparing a sodium (2R,5S,13aR)-7,9-dioxo-10-((2,4,6-trifluorobenzyl) carbamoyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido [1′,2′:4,5] pyrazino[2,1-b][1,3]oxazepin-8-olate of Formula 1 and its polymorphic form thereof.

##STR00001##

A process for preparing a sodium (2R,5S,13aR)-7,9-dioxo-10-((2,4,6-trifluorobenzyl) carbamoyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido [1′,2′:4,5] pyrazino[2,1-b][1,3]oxazepin-8-olate of Formula 1 and its polymorphic form thereof.

##STR00001##