141406-83-9

Upstream product

• 117836-15-4 (S)-2-Benzyloxycarbonylamino-5-ethoxycarbonyloxy-5-oxo-pentanoic acid methyl ester 
• 112127-59-0 (S)-2-Benzyloxycarbonylamino-5-isobutoxycarbonyloxy-5-oxo-pentanoic acid methyl ester 
• 5672-83-3 Z-L-GluOMe 
• 13907-82-9 N²-benzyloxycarbonyl-L-glutamine methyl ester 
• 2650-64-8 Cbz-L-Gln 
• 23632-67-9 (S)-3-[3-(benzyloxycarbonyl)-5-oxooxazolidin-4-yl]propanoic acid 
• 75857-94-2 (5S)-N-(benzyloxycarbonyl)-5-methoxycarbonyl-2-pyrrolidinone 

Downstream Products

• 174361-33-2 (S)-2-Benzyloxycarbonylamino-5-(toluene-4-sulfonyloxy)-pentanoic acid methyl ester 
• 167170-11-8 N-(benzyloxycarbonyl)-5-bromonorvaline methyl ester 
• 1417900-08-3 (3S)-3-[(benzyloxycarbonyl)amino]-1-amino-piperidin-2-one 
• 1417900-09-4 (3S)-3-[(benzyloxycarbonyl)amino]-1-(methylamino)piperidin-2-one 
• 1417900-16-3 (3S)-1-{[3-(benzyloxycarbonyl)amino]-2-oxopiperidin-1-yl}urea 
• 1417900-17-4 (3S)-1-{[3-(benzyloxycarbonyl)amino]-2-oxopiperidin-1-yl}-1-methylurea 
• 1417900-18-5 (3S)-N-{[3-(benzyloxycarbonyl)amino]-2-oxopiperidin-1-yl}-N-methylcyanamide 
• 1030029-45-8 (S )-2-(((benzyloxy)carbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)pentanoic acid 
• 1030029-68-5 (S)-methyl 5-tert-butyldimethylsilyloxy-2-(benzyloxycarbonyl)aminopentanoate 
• 1159502-66-5 (S)-2-benzyloxycarbonylamino-5-(diethoxy-phosphoryl)-pentanoic acid methyl ester 
• 1159502-67-6 (S)-2-benzyloxycarbonylamino-5-(diethoxy-phosphoryl)-pentanoic acid 
• 18928-00-2 N,N’-{[(2S,5S)-3,6-dioxopiperazine-2,5-diyl]bis(propane-3,1-diyl)}bis(N-hydroxyacetamide) 

Relevant academic research and scientific papers

Synthesis of New Cyclomarin Derivatives and Their Biological Evaluation towards Mycobacterium Tuberculosis and Plasmodium Falciparum

Cyclomarins are highly potent antimycobacterial and antiplasmodial cyclopeptides isolated from a marine bacterium (Streptomyces sp.). Previous studies have identified the target proteins and elucidated a novel mode of action, however there are currently only a few studies examining the structure–activity relationship (SAR) for both pathogens. Herein, we report the synthesis and biological evaluation of 17 novel desoxycyclomarin-inspired analogues. Optimization via side chain modifications of the non-canonical amino acids led to potent lead structures for each pathogen.

MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS

Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

4-((R)-2-{[6-((S)-3-Methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}-3-phosphonopropionyl)piperazine-1-carboxylic Acid Butyl Ester (ACT-246475) and Its Prodrug (ACT-281959), a Novel P2Y12 Receptor Antagonist with a Wider Therapeutic Window in the Rat Than Clopidogrel

Recent post hoc analyses of several clinical trials with P2Y12 antagonists showed the need for new molecules being fully efficacious as antiplatelet agents and having a reduced propensity to cause major bleeding. We have previously reported the discovery of the 2-phenylpyrimidine-4-carboxamide analogs as P2Y12 antagonists with nanomolar potency in the disease-relevant platelet aggregation assay in human plasma. Herein we present the optimization steps that led to the discovery of clinical candidate ACT-246475 (30d). The key step was the replacement of the carboxylic acid functionality by a phosphonic acid group which delivered the most potent molecules of the program. In addition, low in vivo clearance in rat and dog was achieved for the first time. Since the bioavailability of 30d was low in rat and dog, we developed the bis((isopropoxycarbonyl)oxy)methyl ester prodrug (ACT-281959, 45). Compound 30d showed efficacy in the rat ferric chloride thrombosis model when administered intravenously as parent or orally as its prodrug 45. Moreover, 30d displays a wider therapeutic window as compared to clopidogrel in the rat surgical blood loss model.

Diastereoselective synthesis of cyclic β2,3-amino acids utilizing 4-substituted-1,3-oxazinan-6-ones

The 4-substituted-1,3-oxazinan-6-one scaffold is a versatile synthon enabling access to a diverse array of β-amino acid derivatives. In this study, the synthetic utility of the 1,3-oxazinan-6-one is expanded to include the diastereoselective synthesis of

An access to aza-Freidinger lactams and E-locked analogs

Freidinger lactams, possessing a peptide bond configuration locked to Z, are important key elements of conformationally restricted peptidomimetics. In the present work, the CαHi+1 unit has been replaced by N, leading to novel aza-Fre

BROAD SPECTRUM ANTIBIOTIC ARYLOMYCIN ANALOGS

Arylomycin analogs are provided, wherein the analogs can have broad spectrum bioactivity. Resistance to the antibiotic bioactivity of natural product arylomycin in a range of pathogenic bacterial species has been found to depend upon single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases), wherein the presence of a proline residue confers arylomycin resistance. Arylomycin analogs are provided herein that can overcome that resistance and provide for a broader spectrum of antibiotic bioactivity than can natural product arylomycins such as arylomycin A2. Methods for determining if a bacterial strain is susceptible to narrow spectrum arylomycin antibiotics, or if a broad spectum analog is required for treatment, is provided. Pharmaceutical compositions and methods of treatment of bacterial infections, and methods of synthesis of arylomycin analogs, are provided.

SUBSTITUTED 2-PHENYL-PYRIDINE DERIVATIVES

The present invention relates to compounds of formula I wherein R1, R2, R4, R5, Ra, Rb, n, W and Z are as defined in the application, their preparation and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.

PHOSPHONIC ACID DERIVATES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS

The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).

SUBSTITUTED 2-PHENYL-PYRIDINE DERIVATIVES

The present invention relates to compounds of formula (I) wherein R1, R2, R4, R5, Ra, Rb, n, W and Z are as defined in the application, their preparation and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.

Synthesis of (S)-2-amino-8-oxodecanoic acid (Aoda) and apicidin A

The synthesis of (S)-2-amino-8-oxodecanoic acid, a constituent of the cyclic tetrapeptides, the apicidins, was accomplished under photolytic conditions in the presence of tri-n-butyltin hydride using glutamic acid. This enabled a total synthesis of apicidin A to be completed.