131401-46-2

Upstream product

• 39027-95-7 9H-carbazole-9-carbaldehyde 
• 7396-44-3 benzyl diethylphosphonoacetate 
• 1068-55-9 isopropylmagnesium chloride 
• 100-39-0 benzyl bromide 
• 78-84-2 isobutyraldehyde 
• 5437-45-6 Benzyl bromoacetate 
• 1775-44-6 (2E)-4-methylpent-2-enoic acid 
• 100-51-6 benzyl alcohol 
• 77509-00-3 phenylmethyl 4-methylpentanoate 
• 646-07-1 4-Methylpentanoic acid 

Downstream Products

• 131401-50-8 Benzyl 2-Hydroxyimino-4-methylpentanoate 
• 211308-49-5 benzyl (2S,3R)-2,3-dihydroxy-4-methylpentanoate 
• 330944-30-4 benzyl 4-methyl-3-pentenoate 
• 428512-42-9 benzyl (4R,5S)-5-isopropyl-1,3,2-dioxathiolane-4-carboxylate 2,2-dioxide 
• 211308-50-8 (2S,3R)-2,3-Bis-(tert-butyl-dimethyl-silanyloxy)-4-methyl-pentanoic acid benzyl ester 
• 330944-31-5 (4-methyl)-3-pentenyl (S)-2-[(1,1-dimethylethyl)diphenylsilyl]oxypropanoate 
• 330944-29-1 (1S)-1-[(4-methyl)pent-3-enyloxycarbonyl]ethyl 3-oxocyclohex-1-enecarboxylate 

Relevant academic research and scientific papers

COVALENT RAS INHIBITORS AND USES THEREOF

The disclosure features compounds, or pharmaceutically acceptable salts thereof, alone and in combination with other therapeutic agents, pharmaceutical compositions, and protein conjugates thereof, capable of modulating biological processes including Ras, and their uses in the treatment of cancers.

RAS INHIBITORS

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Stereoseleetive synthesis of polysubstituted alkenes through a phosphine-mediated three-component system of aldehydes, α-halo carbonyl compounds, and terminal alkenes

A study was conducted to demonstrate stereoselective synthesis of polysubstituted alkenes through a phosphine-mediated three-component system of aldehydes, α-halo carbonyl compounds, and terminal alkenes. Triphenylphosphine, α-halo carbonyl compounds, and methyl acrylate were added to a solution of aldehyde in chloroform or 1-propanol under nitrogen at room temperature. The resulting mixture was stirred at the specified temperature until transformation was completely observed by thin layer chromatography (TLC) analysis. The mixture was cooled to room temperature and purified by column chromatography on silica gel, eluting with petroleum ether/ethyl acetate. The study demonstrated that the first one-pot and three-component reaction of aldehydes, α-haloacetates, and terminal alkenes was developed in the presence of phenylphosphine to produce a wide range of trisubstituted alkenes with significant stereoselectivity.

Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: Discovery of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl- benzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the treatment of hypercholesterolemia

In light of accumulating evidence that aggressive LDL-lowering therapy may offer increased protection against coronary heart disease, we undertook the design and synthesis of a novel series of HMG-CoA reductase inhibitors based upon a substituted pyrazole template. Optimizing this series using both structure-based design and molecular property considerations afforded a class of highly efficacious and hepatoselective inhibitors resulting in the identification of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzyl- carbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the treatment of hypercholesterolemia.

Novel pyrazole-based HMG CoA reductase inhibitors

Novel compounds and pharmaceutical compositions useful as hypocholesterolemic and hypolipidemic agents are described. More specifically, potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (“HMG CoA reductase”) are described. Methods of using such compounds and compositions to treat subjects, including humans, suffering from hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, Alzheimer's Disease, benign prostatic hypertrophy (BPH), diabetes and osteoporosis are also described.

A simple one-pot organometallic formylation/trapping sequence using N-formylcarbazole

Treatment of a range of sp3-, sp2- and sp-nucleophiles with N-formyl carbazole leads to the formation of the metastable anionic carbazole carbinols. In the presence of a second nucleophilic reagent such as phosphonoacetate or an organolithium, these collapse on warming to the aldehyde which is trapped in situ to afford the α,β-unsaturated esters or secondary carbinols respectively.

Synthesis of the antibiotically active part of agrocin 84

Phosphitylation of bis-O-silylated threo-2,3-dihydroxy-4- methylpentanamide and condensation of the resulting N-acylphosphorodiamidite with 2'-O-acetyl-3'-deoxyarabinoadenosine led, after oxidation and deprotection, to the isolation of the title compound.