169802-93-1

Upstream product

• 151-50-8 potassium cyanide 
• 98-86-2 acetophenone 
• 120-57-0 piperonal 
• 20102-12-9 2-hydroxy-2-phenylpropionitrile 
• 109-77-3 malononitrile 
• 644-34-8 3,4-methylenedioxychalcone 
• 644-34-8 (E)-3-(benzo[d][1,3]dioxol-5-yl)-1-phenylprop-2-en-1-one 

Downstream Products

• 169802-94-2 2-benzo[1,3]dioxol-5-yl-4-oxo-4-phenyl-butyric acid methyl ester 
• 7512-78-9 2(5H)-furanone, 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-phenyl-4-(phenylmethyl)- 

Relevant academic research and scientific papers

Cyano-borrowing reaction: Nickel-catalyzed direct conversion of cyanohydrins and aldehydes/ketones to β-cyano ketone

A direct nickel-catalyzed, high atom- and step-economical reaction of cyanohydrins with aldehydes or ketones via an unprecedented "cyano-borrowing reaction" has been developed. Cleavage of the C-CN bond of cyanohydrins followed by aldol condensation and conjugate addition of cyanide to α,β-unsaturated ketones proceeded to deliver a range of racemic β-cyano ketones with good to high yields. The practical procedure with the use of a commercial and less-toxic CN source bodes well for wide application of this protocol.

Cyanation of α,β-unsaturated enones by malononitrile in open air under metal-catalyst-free conditions

Cyanation of α,β-unsaturated enones by employing malononitrile as the organic cyanation source has been disclosed, which proceeds efficiently at room temperature in open air under metal-catalyst-free conditions. The Royal Society of Chemistry 2012.

Structure-activity relationships in a series of orally active γ- hydroxy butenolide endothelin antagonists

The design of potent and selective non-peptide antagonists of endothelin-1 (ET-1) and its related isopeptides are important tools defining the role of ET in human diseases. In this report we will describe the detailed structure-activity relationship (SAR) studies that led to the discovery of a potent series of butenolide ET(A) selective antagonists. Starting from a micromolar screening hit, PD012527, use of Topliss decision tree analysis led to the discovery of the nanomolar ET(A) selective antagonist PD155080. Further structural modifications around the butenolide ring led directly to the subnanomolar ET(A) selective antagonist PD156707, IC50's = 0.3 (ET(A)) and 780 nM (ET(B)). This series of compounds exhibited functional activity exemplified by PD156707. This derivative inhibited the ET(A) receptor mediated release of arachidonic acid from rabbit renal artery vascular smooth muscle cells with an IC50 = 1.1 nM and also inhibited the ET-1 induced contraction of rabbit femoral artery rings (ET(A) mediated) with a pA2 = 7.6. PD156707 also displayed in vivo functional activity inhibiting the hemodynamic responses due to exogenous administration of ET-1 in rats in a dose dependent fashion. Evidence for the pH dependence of the open and closed tautomerization forms of PD156707 was demonstrated by an NMR study. X- ray crystallographic analysis of the closed butenolide form of PD156707 shows the benzylic group located on the same side of the butenolide ring as the γ- hydroxyl and the remaining two phenyl groups on the butenolide ring essentially orthogonal to the butenolide ring. Pharmacokinetic parameters for PD156707 in dogs are also presented.