160007-27-2

Upstream product

• 1205-62-5 4-nitrobenzylphosphonic acid 
• 2609-49-6 diethyl p-nitrobenzylphosphonate 
• 100-11-8 1-bromomethyl-4-nitro-benzene 

Downstream Products

• 331948-63-1 N,N-dimethyl-P-(4-nitrobenzyl)phosphonamidic chloride 
• 162210-26-6 2-(4-nitrobenzyl)-1,3,2-dioxaphosphorinan-2-oxide 
• 3900-19-4 (4-nitro-benzyl)-phosphonic acid dibutyl ester 
• 132573-81-0 C₁₃H₂₂N₃O₂PS 
• 132573-77-4 N,N-dimethyl-P-(4-nitrobenzyl)phosphonamidithionic chloride 
• 162210-29-9 2-(4-nitrobenzyl)-1,3,2-dioxaphosphepan-2-oxide 
• 162210-34-6 2-(4-aminobenzyl)-1,3,2-dioxaphosphepan-2-oxide 

Relevant academic research and scientific papers

Designing anti-inflammatory drugs from parasitic worms: A synthetic small molecule analogue of the acanthocheilonema viteae product ES-62 prevents development of collagen-induced arthritis

In spite of increasing evidence that parasitic worms may protect humans from developing allergic and autoimmune diseases and the continuing identification of defined helminth-derived immunomodulatory molecules, to date no new anti-inflammatory drugs have been developed from these organisms. We have approached this matter in a novel manner by synthesizing a library of drug-like small molecules based upon phosphorylcholine, the active moiety of the anti-inflammatory Acanthocheilonema viteae product, ES-62, which as an immunogenic protein is unsuitable for use as a drug. Following preliminary in vitro screening for inhibitory effects on relevant macrophage cytokine responses, a sulfone-containing phosphorylcholine analogue (11a) was selected for testing in an in vivo model of inflammation, collagen-induced arthritis (CIA). Testing revealed that 11a was as effective as ES-62 in protecting DBA/1 mice from developing CIA and mirrored its mechanism of action in downregulating the TLR/IL-1R transducer, MyD88. 11a is thus a novel prototype for anti-inflammatory drug development.

AMINO PYRIMIDINE ANTICANCER COMPOUNDS

Compounds of Formula (1), as shown below and defined herein: and pharmaceutically acceptable salts, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancers mediated at least in part by FAK.

Orally active CCR5 antagonists as anti-HIV-1 agents 2: Synthesis and biological activities of anilide derivatives containing a pyridine N-oxide moiety

In order to develop orally active CCR5 antagonists, we investigated 1-benzoxepine derivatives containing new polar substituents, such as phosphonate, phosphine oxide or pyridine N-oxide moieties, as replacements for the previoiusly reported quaternary ammonium moiety. Among these compounds, the 2-(α-hydroxybenzyl)pyridine N-oxide 5e exhibited moderate CCR5 antagonistic activity and had an acceptable pharmacokinetic profile in rats. Subsequent chemical modification was performed and compound (S)-5f possessing the (S)-configuration hydroxy group was found to be more active than the (R)-isomer. Replacement of the 1-benzoxepine ring with a 4-methylphenyl group by a 1-benzazepine ring with a 4-[2-(butoxy)ethoxy]phenyl group enhanced the activity in the binding assay. In addition, introduction of a 3-trifluoromethyl group on the phenyl group of the anilide moiety led to greatly increased activity in the HIV-1 envelope-mediated membrane fusion assay. In particular, compound (S)-5s showed the most potent CCR5 antagonistic activity (IC 50=7.2 nM) and inhibitory effect (IC50=5.4 nM) in the fusion assay, together with good pharmacokinetic properties in rats.

Synthesis of novel 2-benzothiopyran and 3-benzothiepin derivatives and their stimulatory effect on bone formation

In a search for therapeutic agents for the treatment of osteoporosis and bone fracture, we found that 2-benzothiopyran-1-carboxamide derivatives 1, derived from ipriflavone as a lead compound, increase cellular alkaline phosphatase activity in cultures of rat bone marrow stromal cells. Further modification of 1 has led to the discovery of more potent 3-benzothiepin-2- carboxamide derivatives 2. Of these, 3-benzothiepin derivatives bearing a 4- (dialkoxyphosphorylmethyl)phenyl group on the 2-carboxamide moiety such as 2h and 2q exhibited significant improvement of activity compared to ipriflavone. Asymmetric synthesis of 2h and 2q revealed that the (-)-isomers possessed activities superior to those of the (+)-isomers. Further evaluation of these compounds using the mouse osteoblastic cell line MC3T3-E1 revealed that (-)- 2q enhanced the effect of bone morphogenetic protein. In addition, application of a sustained-release agent containing 2q increased the area of newly formed bone in a rat skull defect model. Based on these findings, (-)- 2q was selected for further investigation as a new drug stimulating bone formation. Synthesis and structure-activity relationships for this novel series of 2-benzothiopyran and 3-benzothiepin derivatives are detailed.

Nucleophilic Substitution in Benzylic Thiophosphinyl and Thiophosphonyl Chlorides: the Contribution of Elimination-Addition Pathways with Methylenethiooxophosphorane (Thiophosphene) Intermediates

For the reactions of ArCH2P(S)(Ph)Cl and ArCH2P(S)(NMe2)Cl with Et2NH, changing ArCH2 from benzyl to 4-nitrobenzyl increases the rates of substitution by factors of 80 and >103, respectively, and reduces markedly the ability to discriminate bet