The Experts below are selected from a list of 1554 Experts worldwide ranked by ideXlab platform
Masahiro Fuji - One of the best experts on this subject based on the ideXlab platform.
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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, 2013Co-Authors: Brian A Johns, Takashi Kawasuji, Teruhiko Taishi, David Temelkoff, Hiroshi Yoshida, Akiyama Toshiyuki, Yoshiyuki Taoda, Hitoshi Murai, Ryuichi Kiyama, Masahiro FujiAbstract: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.
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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, 2013Co-Authors: Brian A Johns, Takashi Kawasuji, Teruhiko Taishi, David Temelkoff, Hiroshi Yoshida, Yoshiyuki Taoda, Hitoshi Murai, Ryuichi Kiyama, Toshiyuki Akiyama, Masahiro FujiAbstract: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 a...
Brian A Johns - One of the best experts on this subject based on the ideXlab platform.
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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, 2013Co-Authors: Brian A Johns, Takashi Kawasuji, Teruhiko Taishi, David Temelkoff, Hiroshi Yoshida, Akiyama Toshiyuki, Yoshiyuki Taoda, Hitoshi Murai, Ryuichi Kiyama, Masahiro FujiAbstract: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.
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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, 2013Co-Authors: Brian A Johns, Takashi Kawasuji, Teruhiko Taishi, David Temelkoff, Hiroshi Yoshida, Yoshiyuki Taoda, Hitoshi Murai, Ryuichi Kiyama, Toshiyuki Akiyama, Masahiro FujiAbstract: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 a...
Takashi Kawasuji - One of the best experts on this subject based on the ideXlab platform.
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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, 2013Co-Authors: Brian A Johns, Takashi Kawasuji, Teruhiko Taishi, David Temelkoff, Hiroshi Yoshida, Akiyama Toshiyuki, Yoshiyuki Taoda, Hitoshi Murai, Ryuichi Kiyama, Masahiro FujiAbstract: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.
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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, 2013Co-Authors: Brian A Johns, Takashi Kawasuji, Teruhiko Taishi, David Temelkoff, Hiroshi Yoshida, Yoshiyuki Taoda, Hitoshi Murai, Ryuichi Kiyama, Toshiyuki Akiyama, Masahiro FujiAbstract: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 a...
Teruhiko Taishi - One of the best experts on this subject based on the ideXlab platform.
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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, 2013Co-Authors: Brian A Johns, Takashi Kawasuji, Teruhiko Taishi, David Temelkoff, Hiroshi Yoshida, Akiyama Toshiyuki, Yoshiyuki Taoda, Hitoshi Murai, Ryuichi Kiyama, Masahiro FujiAbstract: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.
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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, 2013Co-Authors: Brian A Johns, Takashi Kawasuji, Teruhiko Taishi, David Temelkoff, Hiroshi Yoshida, Yoshiyuki Taoda, Hitoshi Murai, Ryuichi Kiyama, Toshiyuki Akiyama, Masahiro FujiAbstract: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 a...
David Temelkoff - One of the best experts on this subject based on the ideXlab platform.
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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, 2013Co-Authors: Brian A Johns, Takashi Kawasuji, Teruhiko Taishi, David Temelkoff, Hiroshi Yoshida, Akiyama Toshiyuki, Yoshiyuki Taoda, Hitoshi Murai, Ryuichi Kiyama, Masahiro FujiAbstract: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.
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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, 2013Co-Authors: Brian A Johns, Takashi Kawasuji, Teruhiko Taishi, David Temelkoff, Hiroshi Yoshida, Yoshiyuki Taoda, Hitoshi Murai, Ryuichi Kiyama, Toshiyuki Akiyama, Masahiro FujiAbstract: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 a...
