134557-76-9

Upstream product

• 102089-75-8 (-)-(1R)-1-[(1',1'-dimethylethoxycarbonyl)amino]-2-(methylsulfonyl)oxy-1-phenylethane 
• 110143-62-9 (S)-(+)-<2-<(methylsulfonyl)oxy>-1-phenylethyl>carbamic acid 1,1-dimethylethyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 126610-77-3 (R)-tert-butyl N-<1-phenyl-2-<(p-toluenesulfonyl)oxy>ethyl>carbamate 
• 67341-01-9 (R)-N-(tert-butoxycarbonyl)phenylglycinol 
• 56613-80-0 D-2-phenylglycinol 

Downstream Products

• 1172596-82-5 tert-butyl (R)-2-isothiocyanato-1-phenylethylcarbamate 
• 1580490-42-1 C₁₉H₁₉N₃S 
• 1580490-75-0 (R)-4-phenylimidazolidine-2-thione 
• 155273-91-9 (R)-(-)-N-<2,6-bis(1-methylethyl)phenyl>-N'-<2-<(butoxycarbonyl)amino>-2-phenylethyl>urea 

Relevant academic research and scientific papers

Identification of Clinical Candidate M2698, a Dual p70S6K and Akt Inhibitor, for Treatment of PAM Pathway-Altered Cancers

Herein, we report the discovery of a novel class of quinazoline carboxamides as dual p70S6k/Akt inhibitors for the treatment of tumors driven by alterations to the PI3K/Akt/mTOR (PAM) pathway. Through the screening of in-house proprietary kinase library, 4-benzylamino-quinazoline-8-carboxylic acid amide 1 stood out, with sub-micromolar p70S6k biochemical activity, as the starting point for a structurally enabled p70S6K/Akt dual inhibitor program that led to the discovery of M2698, a dual p70S6k/Akt inhibitor. M2698 is kinase selective, possesses favorable physical, chemical, and DMPK profiles, is orally available and well tolerated, and displayed tumor control in multiple in vivo studies of PAM pathway-driven tumors.

SUBSTITUTED DIHYDROPYRAZOLO PYRAZINE CARBOXAMIDE DERIVATIVES

The invention relates to substituted dihydropyrazolo pyrazine carboxamide derivatives and to processes for their preparation, and also to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular cardiovascular disorders, preferably thrombotic or thromboembolic disorders, and diabetes, and also urogenital and ophthalmic disorders.

Discovery and Optimization of Phosphopantetheine Adenylyltransferase Inhibitors with Gram-Negative Antibacterial Activity

In the preceding manuscript [Moreau et al. 2018, 10.1021/acs.jmedchem.7b01691] we described a successful fragment-based lead discovery (FBLD) strategy for discovery of bacterial phosphopantetheine adenylyltransferase inhibitors (PPAT, CoaD). Following several rounds of optimization two promising lead compounds were identified: triazolopyrimidinone 3 and 4-azabenzimidazole 4. Here we disclose our efforts to further optimize these two leads for on-target potency and Gram-negative cellular activity. Enabled by a robust X-ray crystallography system, our structure-based inhibitor design approach delivered compounds with biochemical potencies 4-5 orders of magnitude greater than their respective fragment starting points. Additional optimization was guided by observations on bacterial permeability and physicochemical properties, which ultimately led to the identification of PPAT inhibitors with cellular activity against wild-type E. coli.

Late-Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO2

A robust, click-chemistry-inspired procedure for radiolabeling of cyclic ureas was developed. This protocol, suitable for all carbon isotopes (11C, 13C, 14C), is based on the direct functionalization of carbon dioxide: the universal building block for carbon radiolabeling. The strategy is operationally simple and reproducible in different radiochemistry centers, exhibits remarkably wide substrate scope with short reaction times, and demonstrates superior reactivity as compared to previously reported systems. With this procedure, a variety of pharmaceuticals and an unprotected peptide were labeled with high radiochemical efficiency.

Bifunctional iminophosphorane organocatalysts for enantioselective synthesis: Application to the ketimine nitro-Mannich reaction

The design, synthesis, and development of a new class of modular, strongly basic, and tunable bifunctional Bronsted base/H-bond-donor organocatalysts are reported. These catalysts incorporate a triaryliminophosphorane as the Bronsted basic moiety and are readily synthesized via a last step Staudinger reaction of a chiral organoazide and a triarylphosphine. Their application to the first general enantioselective organocatalytic nitro-Mannich reaction of nitromethane to unactivated ketone-derived imines allows the enantioselective construction of β-nitroamines possessing a fully substituted carbon atom. The reaction is amenable to multigram scale-up, and the products are useful for the synthesis of enantiopure 1,2-diamine and α-amino acid derivatives.

Synthesis, SAR and evaluation of [1,4′]-bipiperidinyl-4-yl-imidazolidin-2-one derivatives as novel CCR5 antagonists

Elaboration of our previously disclosed spiropiperidine template led to the development of a series of novel CCR5 antagonists. Results of SAR exploration and preliminary lead characterization are described.

Synthesis of new pyrrolidine derivatives as inhibitors of α-mannosidase and of the growth of human glioblastoma cells

New 2-benzylamino-3,4-dihydroxypyrrolidines bearing aromatic and aliphatic amido side chains have been prepared. The influence of the amido substituents on the inhibitory activity of these diamines toward 24 commercially available glycosidases was determi

Functionalized pyrrolidines inhibit α-mannosidase activity and growth of human glioblastoma and melanoma cells

New substituted pyrrolidine-3,4-diol derivatives were prepared from D-(-)- and L-(+)-phenyl glycinol. The influence of the configuration and the substitution of the lateral side chain of these derivatives on the inhibition of 25 commercial glycosidases we

Structure-activity relationships of 1,3,5-triazine-2,4,6-triones as human gonadotropin-releasing hormone receptor antagonists

SAR studies of 1,3,5-triazine-2,4,6-triones as human gonadotropin-releasing hormone receptor antagonists resulted in potent compounds. The best compound from the series had a binding affinity of 2 nM.

Synthesis and receptor binding affinity of cholecystokinin receptor ligands: 2- and 1-indolyl derivatives of PD134308

The synthesis of two 'dipeptoids' structurally related to the CCK-B antagonist CI-988 (PD134308) is described. The 2- and 1-indolyl derivatives 4a,b were prepared in order to define the role of the tryptophan moiety in this series of 'dipeptoids'. They we