88529-68-4

Upstream product

• 37622-90-5 4-ethoxycarbonylpyrazole 
• 595-91-5 triphenylacetic acid 
• 76-83-5 trityl chloride 
• 178619-89-1 5-amino-6,7-dichloro-2,3-dimethoxy-quinoxaline 

Downstream Products

• 1027618-57-0 1-trityl-4-ethoxymethylpyrazole 
• 1027618-54-7 trityl-4-methoxymethylpyrazole 
• 163009-37-8 diphenylmethyl 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-(trityloxyimino)acetamido]-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate 
• 163008-91-1 4-benzoylthiomethyl-1-(trityl)pyrazole 
• 88529-69-5 4-hydroxymethyl-1-(triphenylmethyl)-pyrazole 

Relevant academic research and scientific papers

Electrochemical Decarboxylative N-Alkylation of Heterocycles

An operationally simple method to employ nonactivated carboxylic acids as alkylating agents in the N-alkylation of heterocycles is reported through an electrochemically driven anodic decarboxylative process. A wide substrate scope across a range of heterocycles is demonstrated along with a series of applications that significantly reduce the step count required to access such medicinally relevant structures.

Property Focused Structure-Based Optimization of Small Molecule Inhibitors of the Protein-Protein Interaction between Menin and Mixed Lineage Leukemia (MLL)

Development of potent small molecule inhibitors of protein-protein interactions with optimized druglike properties represents a challenging task in lead optimization process. Here, we report synthesis and structure-based optimization of new thienopyrimidine class of compounds, which block the protein-protein interaction between menin and MLL fusion proteins that plays an important role in acute leukemias with MLL translocations. We performed simultaneous optimization of both activity and druglike properties through systematic exploration of substituents introduced to the indole ring of lead compound 1 (MI-136) to identify compounds suitable for in vivo studies in mice. This work resulted in the identification of compound 27 (MI-538), which showed significantly increased activity, selectivity, polarity, and pharmacokinetic profile over 1 and demonstrated a pronounced effect in a mouse model of MLL leukemia. This study, which reports detailed structure-activity and structure-property relationships for the menin-MLL inhibitors, demonstrates challenges in optimizing inhibitors of protein-protein interactions for potential therapeutic applications.

Re(I) and 99mTc(I) tricarbonyl complexes with ether-containing pyrazolyl-based chelators: Chemistry, biodistribution and metabolism We dedicate this paper to Professor Maria José Calhorda on the occasion of her 65th birthday.

Tris(pyrazolyl)methane chelators, L1-L3, containing one or two ether groups at different positions of the azole rings, were synthesized and fully characterized. These chelators enabled the synthesis of fac-[ 99mTc(CO)3{HC[4-(ROCH2)pz]3}] + (R = Me (Tc1), Et (Tc2)) and fac-[99mTc(CO) 3{HC[3,5-(EtOCH2)2pz]3}] + (Tc3) which were identified by HPLC in comparison with the rhenium counterparts. The evaluation of Tc1-Tc3 in CD-1 mice has shown that the number and/or nature of the ether groups greatly influence the biodistribution profile, pharmacokinetics and metabolic stability of these complexes. Tc1 and Tc2, bearing a unique ether substituent at the 4-position of the pyrazolyl ring, undergo metabolic transformation in vivo while Tc3 is not metabolized. The metabolization of Tc1 and Tc2 enhanced their rate of excretion but, most probably, also justify their negligible heart uptake in contrast with the high heart uptake of congener non-metabolizable complexes (99mTc-DMEOP and 99mTc-TMEOP), which have recently emerged as potential myocardial imaging agents. The attempts made to identify the metabolites of Tc1 and Tc2 have shown that the metabolization of these compounds must involve the ether functions with probable formation of carboxylic acid derivatives. A comparative study with the congener fac-[99mTc(CO)3{[4-(MeOCH 2)pz](CH2)2NH(CH2) 2NH2}]+ (Tc6) led us to confirm the formation of such type of metabolites. In fact, Tc6 is also metabolized in mice with formation of fac-[99mTc(CO)3{[4-(HOCH2)pz] (CH2)2NH(CH2)2NH2}] + (Tc7) and fac-[99mTc(CO)3{[4-(HOOC)pz] (CH2)2NH(CH2)2NH2}] + (Tc8), which were chemically identified by HPLC in comparison with the Re congeners (Re7 and Re8).

TRICARBONYL COMPLEXES WITH TRIDENTATE CHELATORS FOR MYOCARDIUM IMAGING

Chelators of the formulae (I), (II) and (III) and tricarbonyl complexes of radioisotopes of Tc and Re bound to them, for use in myocardial imaging.

Quinoxaline derivatives useful in therapy

Compounds of formula (I), wherein A represents N or CH; R1 and R2 independently represent C1-4 alkyl, halo or CF3 ; R3 represents C1-4 alkyl (optionally substituted), C3-7 cycloa

Cephalosporin derivatives

Novel cephalosporin derivatives and physiologically acceptable salts thereof which are useful as antibacterial agents against gram-negative and gram-positive bacteria, and a process for preparing these compounds are disclosed.