169601-99-4

Upstream product

• 119-61-9 benzophenone 
• 105-45-3 acetoacetic acid methyl ester 
• 35468-80-5 Methyl-5-hydroxy-3-oxo-5,5-diphenylpentanoat 

Downstream Products

• 169601-71-2 3-bromo-5,6-dihydro-4-hydroxy-6,6-diphenyl-2H-pyran-2-one 
• 1449584-20-6 2-(4-chlorophenyl)-3-methyl-7,7-diphenyl-7,8-dihydropyrano[4,3-b]pyran-5(2H)-one 
• 1449584-21-7 methyl 4-(3-methyl-5-oxo-7,7-diphenyl-2,5,7,8-tetrahydropyrano[4,3-b]pyran-2-yl)benzoate 
• 1449584-18-2 3-methyl-2-(4-nitrophenyl)-7,7-diphenyl-7,8-dihydropyrano[4,3-b]pyran-5(2H)-one 
• 1449584-19-3 2-(4-methoxyphenyl)-3-methyl-7,7-diphenyl-7,8-dihydropyrano[4,3-b]pyran-5(2H)-one 

Relevant academic research and scientific papers

Structure-based optimization of hydroxylactam as potent, cell-active inhibitors of lactate dehydrogenase

Structure-based design was utilized to optimize 6,6-diaryl substituted dihydropyrone and hydroxylactam to obtain inhibitors of lactate dehydrogenase (LDH) with low nanomolar biochemical and single-digit micromolar cellular potencies. Surprisingly the replacement of a phenyl with a pyridyl moiety in the chemical structure revealed a new binding mode for the inhibitors with subtle conformational change of the LDHA active site. This led to the identification of a potent, cell-active hydroxylactam inhibitor exhibiting an in vivo pharmacokinetic profile suitable for mouse tumor xenograft study.

Annulation of 2H-pyran onto 1-Oxa- or 1-azacyclohexane-2,4-diones and their analogues via sequential condensation with -substituted enals and 6π-electrocyclization

2H-Pyrans are constructed on a 1-oxa- or 1-azacyclohexane-2,4-dione core via Knoevenagel condensation with enals followed by 6π.electrocyclization, which are readily catalyzed with ethylenediammonium diacetate. This formal [3 + 3] strategy constitutes CO

4-hydroxy-5,6-dihydropyrones. 2. Potent non-peptide inhibitors of HIV protease

The 4-hydroxy-5,6-dihydropyrone template was utilized as a flexible scaffolding from which to build potent active site inhibitors of HIV protease. Dihydropyrone 1c (5,6-dihydro-4-hydroxy-6-phenyl-3-[(2- phenylethyl)thio]-2H-pyran-2-one) was modeled in the active site of HIV protease utilizing a similar binding mode found for the previously reported 4-hydroxybenzopyran-2-ones. Our model led us to pursue the synthesis of 6,6- disubstituted dihydropyrones with the aim of filling S1 and S2 and thereby increasing the potency of the parent dihydropyrone 1c which did not fill S2. Toward this end we attached various hydrophobic and hydrophilic side chains at the 6-position of the dihydropyrone to mimic the natural and unnatural amino acids known to be effective substrates at P2 and P2'. Parent dihydropyrone 1c (IC50 = 2100 nM) was elaborated into compounds with greater than a 100-fold increase in potency [18c, IC50 = 5 nM, 5-(3,6- dihydro-4-hydroxy-6-oxo-2-phenyl-5-[2-phenylethyl)thio]-2H-pyran-2- yl)pentanoic acid and 12c, IC50 = 51 nM, 5,6-dihydro-4-hydroxy-6-phenyl-6- (2-phenylethyl)-3-[(2-phenyl-ethyl)thio]-2H-pyran-2-one]. Optimization of the 3-position fragment to fill S1' and S2' afforded potent HIV protease inhibitor 49 [IC50 = 10 nM, 3-[(2-tert-butyl-5-methylphenyl)sulfanyl]-5,6- dihydro-4-hydroxy-6-phenyl-6-(2-phenylethyl)-2H-pyran-2-one]. The resulting low molecular weight compounds (475) have one or no chiral centers and are readily synthesized.