gsk1265744 and dolutegravir

gsk1265744 has been researched along with dolutegravir* in 1 studies

Other Studies

1 other study(ies) available for gsk1265744 and dolutegravir

Article	Year
Carbamoyl pyridone HIV-1 integrase inhibitors 3. A diastereomeric approach to chiral nonracemic tricyclic ring systems and the discovery of dolutegravir (S/GSK1349572) and (S/GSK1265744). Journal of medicinal chemistry, 2013, Jul-25, Volume: 56, Issue:14 We report herein the discovery of the human immunodeficiency virus type-1 (HIV-1) integrase inhibitors dolutegravir (S/GSK1349572) (3) and S/GSK1265744 (4). These drugs stem from a series of carbamoyl pyridone analogues designed using a two-metal chelation model of the integrase catalytic active site. Structure-activity studies evolved a tricyclic series of carbamoyl pyridines that demonstrated properties indicative of once-daily dosing and superior potency against resistant viral strains. An inherent hemiaminal ring fusion stereocenter within the tricyclic carbamoyl pyridone scaffold led to a critical substrate controlled diastereoselective synthetic strategy whereby chiral information from small readily available amino alcohols was employed to control relative and absolute stereochemistry of the final drug candidates. Modest to extremely high levels of stereochemical control were observed depending on ring size and position of the stereocenter. This approach resulted in the discovery of 3 and 4, which are currently in clinical development. Topics: Animals; Dogs; HeLa Cells; Heterocyclic Compounds, 3-Ring; HIV Integrase Inhibitors; Humans; Macaca fascicularis; Male; Oxazines; Piperazines; Pyridones; Rats; Rats, Sprague-Dawley; Stereoisomerism; Structure-Activity Relationship	2013

Article

Year

Carbamoyl pyridone HIV-1 integrase inhibitors 3. A diastereomeric approach to chiral nonracemic tricyclic ring systems and the discovery of dolutegravir (S/GSK1349572) and (S/GSK1265744).

Journal of medicinal chemistry, 2013, Jul-25, Volume: 56, Issue:14

We report herein the discovery of the human immunodeficiency virus type-1 (HIV-1) integrase inhibitors dolutegravir (S/GSK1349572) (3) and S/GSK1265744 (4). These drugs stem from a series of carbamoyl pyridone analogues designed using a two-metal chelation model of the integrase catalytic active site. Structure-activity studies evolved a tricyclic series of carbamoyl pyridines that demonstrated properties indicative of once-daily dosing and superior potency against resistant viral strains. An inherent hemiaminal ring fusion stereocenter within the tricyclic carbamoyl pyridone scaffold led to a critical substrate controlled diastereoselective synthetic strategy whereby chiral information from small readily available amino alcohols was employed to control relative and absolute stereochemistry of the final drug candidates. Modest to extremely high levels of stereochemical control were observed depending on ring size and position of the stereocenter. This approach resulted in the discovery of 3 and 4, which are currently in clinical development.

Topics: Animals; Dogs; HeLa Cells; Heterocyclic Compounds, 3-Ring; HIV Integrase Inhibitors; Humans; Macaca fascicularis; Male; Oxazines; Piperazines; Pyridones; Rats; Rats, Sprague-Dawley; Stereoisomerism; Structure-Activity Relationship

2013