865300-86-3

Upstream product

• 1080623-42-2 ethyl 2-amino-2-(1-(3-chloro-4-fluorobenzyl)-2-oxo-3-(phenylsulfinyl)piperidin-4-yl)acetate 
• 1549803-42-0 C₁₆H₁₈ClFN₂O₃ 
• 4755-77-5 Ethyl oxalyl chloride 
• 675-20-7 piperidin-2-one 
• 192702-01-5 3-chloro-4-fluorobenzyl bromide 
• 865300-49-8 1-(3-chloro-4-fluorobenzyl)piperidin-2-one 
• 1080623-41-1 1-(3-chloro-4-fluorobenzyl)-3-(phenylsulfinyl)piperidin-2-one 
• 1080623-43-3 amino-[1-(3-chloro-4-fluorobenzyl)-2-oxopiperidin-(4Z)-ylidene]acetic acid ethyl ester 
• 865300-50-1 ethyl 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate 

Downstream Products

• 1080623-44-4 methanesulfonic acid (R)-4-{[6-(3-chloro-4-fluorobenzyl)-3-methanesulfonyloxy-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carbonyl]-methyl-amino}-2,2-dimethyl-3-(tetrahydropyran-2-yloxy)-butyl ester 
• 1080623-40-0 methanesulfonic acid (R)-4-{[6-(3-chloro-4-fluorobenzyl)-3,4-bis(methanesulfonyloxy)-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carbonyl]-methyl-amino}-2,2-dimethyl-3-(tetrahydropyran-2-yloxy)-butyl ester 
• 1019339-38-8 (4R)-11-(3-chloro-4-fluorobenzyl)-9-methoxy-2,5,5-trimethyl-4-((tetrahydro-2H-pyran-2-yl)oxy)-3,4,5,6,12,13-hexahydro-2H-[1,4]diazocino[2,1-a][2,6]naphthyridine-1,8,10(11H)-trione 
• 865300-81-8 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylic acid 

Relevant academic research and scientific papers

Asymmetric Synthesis of a Potent HIV-1 Integrase Inhibitor

The development of a practical asymmetric total synthesis of the potent HIV-1 integrase inhibitor 5 is described. Key transformations include construction of the naphthridine core in a highly efficient manner followed by cyclization of the 8-membered ring. Control of the atropisomers of intermediates and final compound 5 is also described.

Discovery of 2-Pyridinone Aminals: A Prodrug Strategy to Advance a Second Generation of HIV-1 Integrase Strand Transfer Inhibitors

The search for new molecular constructs that resemble the critical two-metal binding pharmacophore required for HIV integrase strand transfer inhibition represents a vibrant area of research within drug discovery. Here we present the discovery of a new class of HIV integrase strand transfer inhibitors based on the 2-pyridinone core of MK-0536. These efforts led to the identification of two lead compounds with excellent antiviral activity and preclinical pharmacokinetic profiles to support a once-daily human dose prediction. Dose escalating PK studies in dog revealed significant issues with limited oral absorption and required an innovative prodrug strategy to enhance the high-dose plasma exposures of the parent molecules.

SUBSTITUTED NAPHTHYRIDINEDIONE DERIVATIVES AS HIV INTEGRASE INHIBITORS

The present invention relates to Substituted Naphthyridinedione Derivatives and pharmaceutically acceptable salts thereof. The present invention also relates to compositions comprising at least one Substituted Naphthyridinedione Derivative, and methods of using the Substituted Naphthyridinedione Derivatives for treating or preventing HIV infection in a subject.

Crystalline forms of an HIV integrase inhibitor

Crystalline forms of a hexahydro-diazocinonaphthyridine trione compound are disclosed. The compound and its crystalline forms thereof are HIV integrase inhibitors useful for the prophylaxis or treatment of HIV infection or for the prophylaxis, treatment or delay in the onset or progression of AIDS.

HIV INTEGRASE INHIBITORS

Hydroxy (tetra- or hexa-)hydronaphthyridine dione compounds of Formula (I) are inhibitors of HIV integrase and inhibitors of HIV replication wherein X1, X2, R4 and R5 are defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.