15399-11-8

Upstream product

• 67-56-1 methanol 
• 1492-24-6 L-2-aminobutyric acid 
• 75266-40-9 N-benzyloxycarbonyl-L-α-vinylglycine methyl ester 
• 186581-53-3 diazomethane 
• 407578-43-2 (3S,6S)-3-isopropyl-6-ethylpiperazine-2,5-dione 
• 56762-93-7 methyl (S)-2-(benzyloxycarbonylamino)-4-methylmercaptobutanoate 
• 2491-18-1 (S)-methyl 2-amino-4-(methylthio)butanoate hydrochloride 
• 7324-11-0 (S)-2-amino-butanamide 
• 34306-42-8 Boc-Abu 
• 75266-39-6 methyl (S)-2-<<(benzyloxy)carbonyl>amino>-4-(methylsulfinyl)butanoate 

Downstream Products

• 5959-29-5 S-(+)-2-amino-n-butyric acid hydrochloride 
• 53726-14-0 (S)-2-amino-butanamide hydrochloride 
• 7324-11-0 (S)-2-amino-butanamide 
• 164453-64-9 (3S,6S)-3,6-diethylpiperazine-2,5-dione 
• 7652-88-2 α-Z-N^ε-BOC-L-Lysyl>-L-α-amino-buttersaeure-methylester 

Relevant academic research and scientific papers

Continuous-flow protocol for the synthesis of enantiomerically pure intermediates of anti epilepsy and anti tuberculosis active pharmaceutical ingredients

Continuous-flow production of chiral intermediates plays an important role in the development of building blocks for Active Pharmaceutical Ingredients (APIs), being α-amino acids and their derivatives widely applied as building blocks. In this work we developed two different strategies for the synthesis of intermediates used on the synthesis of levetiracetam/brivaracetam and ethambutol. The results obtained show that methionine methyl ester can be continuously converted to the desired ethambutol intermediate by RANEY Nickel dessulfurization/reduction strategy whereas levetiracetam/brivaracetam intermediates could be synthesized by both RANEY Nickel (without H2) and Pd/C-H2 approach or by photochemical desulfurization.

Cyclic dipeptides. A stereocontrolled synthesis of (2S,3R,6R)- and (2R,3R,6R)-6-tert-butoxycarbonylamino-3-methoxycarbonyl-2-methyl-5-oxo perhydro-1,4-thiazepine

A stereoselective synthesis of the title compounds, starting from commercially available amino acids, is described. The absolute stereochemistry of 3a and 3b has been deduced on the basis of 1H NMR and chemical degradation studies. The formation of only these two isomers has been rationalized in terms of molecular mechanics calculations.

Markedly Different Acyl Papain Structures Deacylate at Similar Rates: Resonance Raman Spectroscopic and Kinetic Evidence

Resonance Raman (RR) spectroscopy has been used to determine the structure of the acyl group in a series of dithioacyl papains in which the side chain of the substrates P1 amino acid residue has been extended from 2 (CH3CH2-) to 3 (CH3CH2CH2-), and to 4 (CH3CH2CH2CH2-) carbon atoms in a linear chain. A conformational analysis was carried out on the corresponding ethyl ester model compounds, N-(methyloxycarbonyl)-L-phenylalanyl-L-ethylglycine, N-(methyloxycarbonyl)-L-phenylalanyl-L-norvaline, and N-(methyloxycarbonyl)-L-phenylalanyl-L-norleucine ethyl dithio esters, based on the RR spectra and known conformational states of glycine and alanine-based dithio esters. Comparison of the RR spectra of the model compounds with those of the corresponding N-(methyloxycarbonyl)-L-phenylalanyl-L-ethylglycine, -L-norvaline, and -L-norleucine dithioacyl papains shows that the acyl fragments adopt an A-like structure in the active site. An A-like structure is characterized by a large (near ±160°) nitrogen to thiol sulfur torsional angle about the NHCHR'-CS single bond. This conformation is in marked contrast to that found for N-acylglycine dithioacyl papains which have a small (near ±15°) NHCH2-CS(thiol) torsional angle in the P1 residue giving rise to the so-called B conformer. Thus we have evidence that the two classes of substrate give rise to two substantially different acyl group structures in the active site. However, for the ethylglycine, norvaline, and norleucine dithioacyl papains the deacylation rate constants (kcat's) are only ca. 3 times greater than kcat for the most reactive W-acylglycine substrate. Thus deacylation can occur from both A- and B-type dithioacyl papains with only a small kinetic penalty for the latter. The existence of an A-type conformer in the active site and the need to maintain binding in the oxyanion hole raise the possibility that the acyl group is binding backwards, i.e. in the S1' and S2' binding sites.

Preparation and biological evaluation of soluble tetrapeptide epoxyketone proteasome inhibitors

A series of novel tetrapeptidyl epoxyketone inhibitors of 20S proteasome was designed and synthesized. To fully understand the SAR, various groups at R1, R2, R3, R4 and R5 positions, including aromatic and aliphatic substituents were designed, synthesized and biologically assayed. Based on the enzymatic results, seven compounds were selected to evaluate their cellular activities and soluble compound 36 showed strong potency against human multiple myeloma (MM) cell lines. Microsomal stability results indicated that compound 36 was more stable in mice, rat and human microsomes than marketed carfilzomib. The in vivo activities of this compound were evaluated with the xenograft mice models of MM cell lines ARH77 and RPMI-8226 with luciferase expression and the T/C value of the two models were 49.5% and 37.6%, respectively. To evaluate the potential cardiovascular toxicity, inhibition of hERG ion channel in HEK293 cells by compound 36 and carfilzomib was carried out. The results indicated that 36 had no binding affinity for the hERG ion channel while carfilzomib could bind it with IC50 of 92.1 μM.

Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors

The simultaneous inhibition of polo-like kinase 1 (PLK1) and BRD4 bromodomain by a single molecule could lead to the development of an effective therapeutic strategy for a variety of diseases in which PLK1 and BRD4 are implicated. Compound 23 has been found to be a potent dual kinase-bromodomain inhibitor (BRD4-BD1 IC50 = 28 nM, PLK1 IC50 = 40 nM). Compound 6 was found to be the most selective PLK1 inhibitor over BRD4 in our series (BRD4-BD1 IC50 = 2579 nM, PLK1 IC50 = 9.9 nM). Molecular docking studies with 23 and BRD4-BD1/PLK1 as well as with 6 corroborate the biochemical assay results.

BET (bromodomain and extraterminal domain)/HDAC (histone deacetylase) double-target inhibitor, and preparation method and application thereof

The invention discloses a BET (bromodomain and extraterminal domain)/HDAC (histone deacetylase) double-target inhibitor, and a preparation method and application thereof. The structure of the double-target inhibitor is as shown in the specification, wherein n=2-6. Compared with the prior art, the double-target inhibitor has the advantage that pharmacophore of a BET inhibitor BI-2536 and pharmacophore of an HDAC inhibitor are spliced by a Linker to obtain a novel BET/HDAC inhibitor with BET/HDAC double-target inhibition effect. The preparation method is simple, mild in condition and easy to implement.

DIHYDROPTERIDINONE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF

Dihydroperidinone derivatives, preparation process and pharmaceutical use thereof are disclosed. Specially, new dihydroperidinone derivatives represented by general formula (I), wherein each substituent of the general formula (I) is defined as in the description, their preparation process, pharmaceutical compositions comprising said derivatives and their use as therapeutical agents, especially as Plk kinase inhibitors are disclosed.

DIHYDROPTERIDINONE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF

Dihydroperidinone derivatives, preparation process and pharmaceutical use thereof are disclosed. Specially, new dihydroperidinone derivatives represented by general formula (I), wherein each substituent of the general formula (I) is defined as in the description, their preparation process, pharmaceutical compositions comprising said derivatives and their use as therapeutical agents, especially as Plk kinase inhibitors are disclosed.

QUINAZOLINEDIONE CHYMASE INHIBITORS

Disclosed are small molecule inhibitors which are useful in treating various diseases and conditions involving Chymase.

PROCESSES FOR THE PREPARATION OF LEVETIRACETAM, ITS INTERMEDIATE AND THE USE OF LEVETIRACETAM IN PHARMACEUTICAL COMPOSITIONS

The invention relates to processes for the preparation of (S)-2-aminobutanamide of Formula I, and to the use of the compound of Formula I as intermediate for the preparation of levetiracetam of Formula (II).The invention also relates to a process for the preparation of levetiracetam and pharmaceutical compositions that include the levetiracetam.