33952-53-3

Upstream product

• 4530-20-5 BOC-glycine 
• 108-91-8 cyclohexylamine 
• 537710-06-8 N-Boc-glycine propargyl ester 
• 18185-77-8 tert-butyloxycarbonylglycine imidazolide 
• 83316-95-4 2-oxo-2-phenylethyl 2-(tert-butoxycarbonylamino)acetate 

Downstream Products

• 1181814-55-0 2-amino-N-(2-(cyclohexylamino)-2-oxoethyl)nicotinamide 
• 1181814-57-2 2-[(2-aminophenyl)formamido]-N-cyclohexylacetamide 
• 99976-73-5 1-cyclohexylpiperazin-2-one 
• 16817-90-6 2-amino-N-cyclohexylacetamide 

Relevant academic research and scientific papers

Glycinamide hydrochloride as a transient directing group: Synthesis of 2-benzylbenzaldehydes by C(sp3)?H arylation

Glycinamide hydrochloride as an inexpensive and commercially available transient directing group for the C(sp3)?H arylation of 2-methylbenzaldehydes is described. A series of practical 2-benzylbenzaldehydes bearing various functional groups are efficiently synthesized in satisfactory yield by this strategy. This method can also be extended to gram scale.

Identification of a new series of benzothiazinone derivatives with excellent antitubercular activity and improved pharmacokinetic profiles

Nitrobenzothiazinone (BTZ) is a promising scaffold with potent activity against M. tuberculosis by inhibiting decaprenylphosphoryl-beta-d-ribose 2′-oxidase (DprE1). But unfavorable durability poses a challenge to further development of this class of agents. Herein, a series of BTZs bearing a variety of different substituents at the C-2 position were designed and synthesized. Compounds were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Ra and were profiled for metabolic stability, plasma protein-binding capacity and pharmacokinetics in vivo. In general, these new BTZs containing N-piperazine, N-piperidine or N-piperidone moiety have excellent antitubercular activity and low cytotoxicity. Several of the compounds showed improved microsomal stability and lower plasma protein-binding, opening a new direction for further lead optimization. And we obtained compound 3o, which maintained good anti-tuberculosis activity (MIC = 8 nM) and presented better in vitro ADME/T and in vivo pharmacokinetic profiles than reported BTZ compound PBTZ169, which may serve as a candidate for the treatment of tuberculosis.

Palladium-Catalyzed β-C?H Arylation of Ketones Using Amino Amide as a Transient Directing Group: Applications to Synthesis of Phenanthridinone Alkaloids

The direct arylation of aromatic and aliphatic ketones was carried out via palladium-catalyzed inert C?H bond functionalization with 2-amino-N-isopropyl-acetamide as a new catalytic transient directing group. The reaction showed excellent functional group compatibility and site selectivity. We demonstrated that α-amino amide forming N,N-bidentate coordination with Pd catalyst is more favorable for the β-arylation of ketones than α-amino acid forming N,O-bidentate coordination with Pd catalyst under relatively mild conditions. This elegant approach provides straightforward access to important structural motifs in organic and medicinal chemistry and is demonstrated here in the efficient synthesis of phenanthridinone alkaloids. (Figure presented.).

Structure-Activity Relationship Studies of Pyrimido[5,4-b]indoles as Selective Toll-Like Receptor 4 Ligands

Previous high throughput screening studies led to the discovery of two novel, nonlipid-like chemotypes as Toll-like receptor 4 (TLR4) agonists. One of these chemotypes, the pyrimido[5,4-b]indoles, was explored for structure-activity relationship trends relative to production of TLR4 dependent cytokines/chemokines, resulting in a semioptimized lead (compound 1) that provided a starting point for further optimization studies. In this report, compounds belonging to three areas of structural modification were evaluated for biological activity using murine and human TLR4 reporter cells, primary murine bone marrow derived dendritic cells, and human peripheral blood mononuclear cells. The compounds bearing certain aryl groups at the C8 position, such as phenyl (36) and β-naphthyl (39), had potencies significantly greater than compound 1. Compound 36 displayed human TLR4 agonist activity at submicromolar concentrations. The computational analysis suggests that the improved potency of these C8-aryl derivatives may be the result of additional binding interactions at the interface of the TLR4/myeloid differentiation protein-2 (MD-2) complex.

Propargyl-Assisted Selective Amidation Applied in C-terminal Glycine Peptide Conjugation

Alkyl esters, such as propargyl esters, typically lack the electron-withdrawing inductive effects needed to participate in nucleophilic acyl substitution reactions. Herein, we report an unusual observation in which glycine propargyl ester derivatives displayed selective, base-independent reactivity towards linear alkylamines under mild, metal-free conditions. Through global reaction route mapping (GRRM) modeling calculations, it is predicted that these observations may be governed by factors related to hydrogen-bonding and intermolecular interactions, rather than electron-withdrawing inductive effects. Based on this concept of propargyl-assisted selective amidation, a direct application was made to develop a novel site-specific C-terminal glycine peptide bioconjugation technique as a proof-of-concept, which relies upon the selective reactivity of glycine propargyl esters over that of aspartate and glutamate side-chain-linked propargyl esters.

In silico and pharmacological screenings identify novel serine racemase inhibitors

d-Serine is a coagonist of the N-methyl-d-aspartate (NMDA)-type glutamate receptor and its biosynthesis is catalyzed by serine racemase (SR). The overactivation of the NMDA receptor has been implicated in the development of neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors of SR have potential against these pathological states. Here, we have developed novel inhibitors of SR by in silico screening and in vitro enzyme assay. The newly developed inhibitors have lower IC50 value comparing with that of malonate, one of the standard SR inhibitor. The structural features of novel inhibitors suggest the importance of central amide structure having a phenoxy substituent in their structure for the SR inhibitory activity. The present findings suggest the importance and rational development of new drugs for diseases of NMDAR overactivation.

ALPHA-AMINO-N-SUBSTITUTED AMIDES, PHARMACEUTICAL COMPOSITION CONTAINING THEM AND USES THEREOF

The present invention relates to filed of pharmaceutical chemistry. Disclosed are a series of α-amino-N-substituted amide compounds having a structure of the following formula, the pharmaceutically acceptable salts thereof, and the pharmaceutical composit

Divergent modes of enzyme inhibition in a homologous structure-activity series

A docking screen identified reversible, noncovalent inhibitors (e.g., 1) of the parasite cysteine protease cruzain. Chemical optimization of 1 led to a series of oxadiazoles possessing interpretable SAR and potencies as much as 500-fold greater than 1. De

Preparation of polymer-bound pyrazolone active esters for combinatorial chemistry

The preparation of solid-phase active esters from a new pyrazolone linker resin is described. N-Acylation using this resin provides various amide products with a high conversion rate and good purity under mild conditions. The polymer-bound pyrazolone linkers are stable in the reaction conditions and are resistant to hydrolysis. Moreover, this resin can also be reused repeatedly without a loss of reactivity.

PHENACYL ESTERS OF AMINO ACIDS AND PEPTIDES

The behavior of phenacyl esters under the conditions of peptide synthesis was investigated.The cleavage of phenacyl esters in reaction with primary amines, as a result of which the carboxyl group is liberated, was discovered.In the presence of lower alcohols the phenacyl esters can undergo transesterification.The phenacyl group is removed by treatment with zinc dust in mixtures of acetic acid with dimethylformamide or trifluoroethanol.