1053733-51-9

Basic information

• Product Name: (3aS,4R,8R,8aS)-5,7-Bis-(3-acetyl-benzyl)-2,2-dimethyl-4,8-bis-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-hexahydro-1,3-dioxa-5,7-diaza-azulen-6-one
• CAS NO: 1053733-51-9
• Molecular Weight: 772.941
• Mol File: 1053733-51-9.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: (3aS,4R,8R,8aS)-5,7-Bis-(3-acetyl-benzyl)-2,2-dimethyl-4,8-bis-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-hexahydro-1,3-dioxa-5,7-diaza-azulen-6-one(CAS DataBase Reference)
• NIST Chemistry Reference: (3aS,4R,8R,8aS)-5,7-Bis-(3-acetyl-benzyl)-2,2-dimethyl-4,8-bis-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-hexahydro-1,3-dioxa-5,7-diaza-azulen-6-one(1053733-51-9)
• EPA Substance Registry System: (3aS,4R,8R,8aS)-5,7-Bis-(3-acetyl-benzyl)-2,2-dimethyl-4,8-bis-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-hexahydro-1,3-dioxa-5,7-diaza-azulen-6-one(1053733-51-9)

Safety Data

• Hazardous Substances Data: 1053733-51-9(Hazardous Substances Data)

Upstream product

• 1053247-90-7 C₂₇H₃₄N₈O₄ 
• 1053742-77-0 (S)-1-{(4S,5S)-5-[(S)-1-Hydroxy-2-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethyl]-2,2-dimethyl-[1,3]dioxolan-4-yl}-2-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethanol 
• 1053719-61-1 (R)-1-{(4S,5S)-5-[(R)-1-Amino-2-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethyl]-2,2-dimethyl-[1,3]dioxolan-4-yl}-2-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethylamine 
• 188947-78-6 1-(6-bromo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)ethan-1-one 
• 105655-01-4 6-bromo-3, 4-dihydro-2H-benzo[β][1, 4]oxazine 
• 188947-79-7 6-bromo-4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine 
• 107986-49-2 N-(5-bromo-2-hydroxyphenyl)acetamide 
• 40925-68-6 2-amino-4-bromo-phenol 
• 36749-01-6 2-acetamido-4-bromophenyl acetate 
• 7693-52-9 4-bromo-2-nitrophenol 
• 106-41-2 4-bromo-phenol 
• 75-16-1 methylmagnesium bromide 

Relevant articles and documents

Improved P1/P1' substituents for cyclic urea based HIV-1 protease inhibitors: Synthesis, structure-activity relationship, and X-ray crystal structure analysis

We present several novel P1/P1' substituents that can replace the characteristic benzyl P1/P1' moiety of the cyclic urea based HIV protease inhibitor series. These substituents typically provide 5-10-fold improvements in binding affinity compared to the unsubstituted benzyl analogs. The best substituent was the 3,4-(ethylenedioxy)benzyl group. Proper balancing of the molecule's lipophilicity facilitated the transfer of this improved binding affinity into a superior cellular antiviral activity profile. Several analogs were evaluated further for protein binding and resistance liabilities. Compound 18 (IC90 = 8.7 nM) was chosen for oral bioavailability studies based on its log P and solubility profile. A 10 mg/kg dose in dogs provided modest bioavailability with C(max) = 0.22 μg/mL. X-ray crystallographic analysis of two analogs revealed several interesting features responsible for the 3,4-(ethylenedioxy)benzyl-substituted analog's potency: (1) Comparing the two complexes revealed two distinct binding modes for each P1/P1' substituent; (2) The ethylenedioxy moieties are within 3.6 A? of Pro 81 providing additional van der Waals contacts missing from the parent structure; (3) The enzyme's Arg 8 side chain moves away from the P1 substituent to accommodate the increased steric volume while maintaining a favorable hydrogen bond distance between the para oxygen substituent and the guanidine NH.