136159-62-1

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 6436-90-4 ethyl 2-(benzylamino)acetate 
• 100-52-7 benzaldehyde 
• 100-39-0 benzyl bromide 
• 84024-60-2 trans-3-phenylaziridine-2-carboxylic acid ethyl ester 
• 100-46-9 benzylamine 
• 42116-44-9 N-tert-butoxycarbonylbenzylamine 
• 105-36-2 ethyl bromoacetate 

Downstream Products

• 76315-01-0 N-benzyl-N-(tert-butoxycarbonyl)glycine 
• 753501-10-9 benzyl-(2-oxo-2-piperidin-1-yl-ethyl)-carbamic acid tert-butyl ester 
• 102179-28-2 N-Pyrrolidinocarbonylmethyl-benzylamin 
• 100875-44-3 1-(N-benzyl-glycyl)-piperidine 
• 121496-39-7 N-(tert-butoxycarbonyl)-N-benzylethanolamine 
• 6436-90-4 ethyl 2-(benzylamino)acetate 
• 136159-63-2 N-(t-butyloxycarbonyl)-N-benzylaminoacetaldehyde 

Relevant academic research and scientific papers

Design, Synthesis, and Pharmacokinetic Evaluation of Phosphate and Amino Acid Ester Prodrugs for Improving the Oral Bioavailability of the HIV-1 Protease Inhibitor Atazanavir

Phosphate and amino acid prodrugs of the HIV-1 protease inhibitor (PI) atazanavir (1) were prepared and evaluated to address solubility and absorption limitations. While the phosphate prodrug failed to release 1 in rats, the introduction of a methylene spacer facilitated prodrug activation, but parent exposure was lower than that following direct administration of 1. Val amino acid and Val-Val dipeptides imparted low plasma exposure of the parent, although the exposure of the prodrugs was high, reflecting good absorption. Screening of additional amino acids resulted in the identification of an l-Phe ester that offered an improved exposure of 1 and reduced levels of the circulating prodrug. Further molecular editing focusing on the linker design culminated in the discovery of the self-immolative l-Phe-Sar dipeptide derivative 74 that gave four-fold improved AUC and eight-fold higher Ctrough values of 1 compared with oral administration of the drug itself, demonstrating a successful prodrug approach to the oral delivery of 1.

Substrate-Controlled Diastereoselectivity Reversal in NHC-Catalyzed Cross-Benzoin Reactions Using N-Boc-N-Bn-Protected α-Amino Aldehydes

The effectiveness of utilizing N-Bn-N-Boc-α-amino aldehydes in cross-benzoin reactions with heteroaromatic aldehydes is demonstrated. The reaction is both chemoselective and syn-selective, making it complementary to the anti-selective cross-benzoin reaction of NHBoc-α-amino aldehydes. Good diastereoselectivity is obtained for a variety of amino aldehydes, including nonhindered ones. A Felkin-Anh model can be used to rationalize the observed diastereoselectivity.

The discovery of new human coagulation factor XIa (FXIa) inhibitors by synthesis, biological evaluation, and structure-based modeling

Factor XIa (FXIa) is an enzyme that is activated during the earliest stage of initiation of the intrinsic pathway of the blood coagulation mechanism. In this study, we attempted to discover a new FXIa inhibitor based on structure-based molecular modeling. We found that compound 16 exhibits satisfactory predicted properties while maintaining important binding interactions with FX1a.

β-Amino esters from the reductive ring opening of aziridine-2-carboxylates

A general study is undertaken to examine the scope of the reductive ring opening of aziridine-2-carboxylates with samarium diiodide. The competition between C-C and C-N bond cleavage is examined as a function of the nature of the N-substituent of the aziridine, the nature of the substituent in the 3-position of the aziridine, and whether the substituent in the 3-position is in a cis or trans relationship with the carboxylate in the 2-position. The desired C-N bond cleavage leads to β-amino esters that are the predominant products for most aziridines with an N-activating group. However, C-C cleavage products are observed with an aryl group in the 3-position; this can be particularly pronounced with cis-aziridines where a nearly equal mixture of the two is observed. Exclusive formation of the C-N cleavage product is observed for all aziridines with the strongly N-activating p-toluene sulfonate group. Similarly high selectivity is observed for the 2-trimethylsilylethyl sulfonate group (SES), which is easier to remove. The utility of these methods is illustrated in the synthesis of protected forms of (R)-β3-DOPA and l-DOPA from the same aziridine, the former by SmI2-mediated reductive opening at C-2 and the latter by palladium-mediated reductive opening at C-3.

Base-promoted c→n acyl rearrangement: An unconventional approach to α-amino acid derivatives

We have discovered that N-alkyl aminomalonates undergo a fast and selective intramolecular C→N acyl rearrangement reaction in the presence of a strong base, leading to N-protected glycinates in excellent yield. Moreover, the fact that the reaction proceeds through a nucleophilic enolate intermediate has been used for implementing a tandem rearrangement/alkylation sequence that has been applied to the preparation of synthetically relevant nonproteinogenic tertiary and quaternary N-alkyl α-amino acids in a very simple and reliable way.

Weinreb amide based synthetic equivalents for convenient access to 4-aryl-1,2,3,4-tetrahydroisoquinolines

New synthetic equivalents, N-methoxy-N-methyl-N′-phenylsulfonyl glycinamide and N-methoxy-N-methyl-N′-benzyl-N′-tert-butyloxy carbonyl glycinamide based on WA functionality were developed for the convenient synthesis of 4-aryl-1,2,3,4-tetrahydroisoquinoline framework. Two simple reactions, N-benzylation and addition of arylmagnesium halide on the WA functionality of the former afforded the key intermediate for convenient synthesis of N-phenylsulfonyl protected 4-aryl-1,2,3,4-tetrahydroisoquinoline, through reduction and acid promoted cyclization. With the latter, the addition of arylmagnesium halide on the WA functionality followed by the same protocol afforded the direct synthesis of 4-aryl-1,2,3,4-tetrahydroisoquinolines in good yields. The acid promoted cyclization step enabled concomitant removal of N-Boc protection.

Fluoro-olefins as peptidomimetic inhibitors of dipeptidyl peptidases

The feasibility of the fluoro-olefin function as a peptidomimetic group in inhibitors for dipeptidyl peptidase IV and II (DPP IV and DPP II) is investigated by evaluation of N-substituted Gly-Ψ[CF=C]pyrrolidines, Gly-Ψ[CF=C]piperidines, and Gly-Ψ[CF=C](2-cyano)pyrrolidines. Of this later class, the (Z)- and (E)-fluoro-olefin analogues were prepared and chemical stability in comparison with the parent amide was checked. Most of these compounds exhibited a strong binding preference toward DPP II with IC 50 values in the low micromolar range, while only low DPP IV inhibitory potential is seen.

ANAPLASTIC LYMPHOMA KINASE MODULATORS AND METHODS OF USE

The present invention comprises compounds and pharmaceutical compositions comprising the compounds that are inhibitors of ALK. The invention also comprises methods of using the compounds and compositions to treat diseases mediated by ALK, including diseases such as cancer, immunological disorders, cardiovascular diseases, and other degenerative disorders.

Novel acyclic ligands. 3. The syntheses of some amino amides derived from amino acids

The syntheses of variously protected amino amides derived from the reaction of oxalic esters with ethylenediamine and with the amino acids glycine, L-valine, and L-lysine are described in this paper. The products are potential contrast agents in magnetic resonance imaging (MRI).

BRADYKININ ANTAGONIST PEPTIDES INCORPORATING N-SUBSTITUTED GLYCINES

The present invention provides bradykinin type peptides containing N-substituted glycines, particularly bradykinin antagonist peptides useful for the treatment of conditions mediated by bradykinin including pain and inflammation.