721927-59-9

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 1334286-16-6 (R)-((2-azido-3-methoxypropoxy)methyl)benzene 
• 79069-15-1 N-(tert-butyloxycarbonyl)-O-benzyl-L-serinol 
• 95715-85-8 2-(tert-butoxycarbonylamino)-3-hydroxypropionic acid methyl ester 
• 95715-86-9 (S)-2,2-dimethyl-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester 4-methyl ester 
• 862372-14-3 methyl (R)-2-(tert-butoxycarbonylamino)-3-methoxypropanoate 
• 183793-48-8 ((S)-2-Benzyloxy-1-methoxymethyl-ethyl)-carbamic acid tert-butyl ester 
• 3262-72-4 (S)-N-(tert-butoxycarbonyl)serine 
• 51293-47-1 N-tert-butoxycarbonyl-(S)-O-methyl-serin 
• 543-27-1 isobutyl chloroformate 
• 856417-65-7 2-((tert-butoxycarbonyl)amino)-3-methoxypropanoic acid 
• 134167-07-0 (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-methoxypropanoate 
• 2766-43-0 N-tert-butyloxycarbonyl-L-serine methyl ester 
• 1332856-11-7 C₁₆H₂₅NO₄ 

Relevant academic research and scientific papers

ERK INHIBITOR AND USE THEREOF

Disclosed are a compound (as shown in formula I) as an extracellular signal-regulated kinase (ERK) inhibitor, a pharmaceutical composition thereof, a preparation method therefor, and use thereof in treating ERK-mediated diseases. Said compound plays a role by regulating a plurality of processes such as cell proliferation, apoptosis, migration and angiogenesis.

Biosurfactants from Marine Cyanobacteria Collected in Sabah, Malaysia

Chemical investigation of the organic extract from Moorea bouillonii, collected in Sabah, Malaysia, led to the isolation of three new chlorinated fatty acid amides, columbamides F (1), G (2), and H (3). The planar structures of 1-3 were established by a combination of mass spectrometric and NMR spectroscopic analyses. The absolute configuration of 1 was determined by Marfey's analysis of its hydrolysate and chiral-phase HPLC analysis after conversion and esterification with Ohrui's acid, (1S,2S)-2-(anthracene-2,3-dicarboximido)cyclohexanecarboxylic acid. Compound 1 showed biosurfactant activity by an oil displacement assay. Related known fatty acid amides columbamide D and serinolamide C exhibited biosurfactant activity with critical micelle concentrations of about 0.34 and 0.78 mM, respectively.

Discovery of a Potent and Selective Oral Inhibitor of ERK1/2 (AZD0364) That Is Efficacious in Both Monotherapy and Combination Therapy in Models of Nonsmall Cell Lung Cancer (NSCLC)

The RAS/MAPK pathway is a major driver of oncogenesis and is dysregulated in approximately 30% of human cancers, primarily by mutations in the BRAF or RAS genes. The extracellular-signal-regulated kinases (ERK1 and ERK2) serve as central nodes within this pathway. The feasibility of targeting the RAS/MAPK pathway has been demonstrated by the clinical responses observed through the use of BRAF and MEK inhibitors in BRAF V600E/K metastatic melanoma; however, resistance frequently develops. Importantly, ERK1/2 inhibition may have clinical utility in overcoming acquired resistance to RAF and MEK inhibitors, where RAS/MAPK pathway reactivation has occurred, such as relapsed BRAF V600E/K melanoma. We describe our structure-based design approach leading to the discovery of AZD0364, a potent and selective inhibitor of ERK1 and ERK2. AZD0364 exhibits high cellular potency (IC50 = 6 nM) as well as excellent physicochemical and absorption, distribution, metabolism, and excretion (ADME) properties and has demonstrated encouraging antitumor activity in preclinical models.

Dihydroimidazopyrazinone compound, composition containing compound, and application of compound or composition

The invention provides a dihydroimidazopyrazinone compound, a composition containing the compound, and an application of the compound or the composition. The dihydroimidazopyrazinone compound is a compound represented by formula (I), or a tautomer, a stereoisomer, a prodrug, a crystal form, a pharmaceutically acceptable salt, a hydrate or a solvent compound thereof. The compound and the composition thereof can be used for treating RAS/RAF/MEK/ERK kinase-regulated proliferative diseases, and have excellent pharmacokinetic properties.

DIHYDROIMIDAZOPYRAZINONE DERIVATIVES USEFUL IN THE TREATMENT OF CANCER

The present disclosure concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1, R2 and R3 have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer.

SUBSTITUTED 3,4-DIHYDROPYRROLO[1,2-A]PYRAZIN-1 (2H)-ONE DERIVATIVES AS KINASE INHIBITORS

Compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1, R2, R3, R4, R5 and R6 have any of the meanings defined hereinbefore in the description, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer are disclosed.

Combining Mass Spectrometric Metabolic Profiling with Genomic Analysis: A Powerful Approach for Discovering Natural Products from Cyanobacteria

An innovative approach was developed for the discovery of new natural products by combining mass spectrometric metabolic profiling with genomic analysis and resulted in the discovery of the columbamides, a new class of di- and trichlorinated acyl amides with cannabinomimetic activity. Three species of cultured marine cyanobacteria, Moorea producens 3L, Moorea producens JHB, and Moorea bouillonii PNG, were subjected to genome sequencing and analysis for their recognizable biosynthetic pathways, and this information was then compared with their respective metabolomes as detected by MS profiling. By genome analysis, a presumed regulatory domain was identified upstream of several previously described biosynthetic gene clusters in two of these cyanobacteria, M. producens 3L and M. producens JHB. A similar regulatory domain was identified in the M. bouillonii PNG genome, and a corresponding downstream biosynthetic gene cluster was located and carefully analyzed. Subsequently, MS-based molecular networking identified a series of candidate products, and these were isolated and their structures rigorously established. On the basis of their distinctive acyl amide structure, the most prevalent metabolite was evaluated for cannabinomimetic properties and found to be moderate affinity ligands for CB1. (Chemical Equation Presented)

Docking model of the nicotinic acetylcholine receptor and nitromethylene neonicotinoid derivatives with a longer chiral substituent and their biological activities

In the present study, nitromethylene neonicotinoid derivatives possessing substituents that contain a sulfur atom, oxygen atom or aromatic ring at position 5 on the imidazolidine ring were synthesized to evaluate their affinity for the nicotinic acetylcholine receptor (nAChR) and their insecticidal activity against adult female houseflies. Comparing the receptor affinity of the alkylated derivative with the receptor affinity of compounds possessing either ether or thioether groups revealed that conversion of the carbon atom to a sulfur atom did not influence the receptor affinity, whereas conversion to an oxygen atom was disadvantageous for the receptor affinity. The receptor affinity of compounds possessing a benzyl or phenyl group was lower than that of the unsubstituted compound. Analysis of the three-dimensional quantitative structure-activity relationship using comparative molecular field analysis demonstrated that steric hindrance of the receptor should exist around the C3 of an n-butyl group attached at position 5 on the imidazolidine ring. A docking study of the nAChR-ligand model suggested that the ligand-binding region expands as the length of the substituent increases by brushing against the amino acids that form the binding region. The insecticidal activity of the compounds was positively correlated with the receptor affinity by considering log P and the number of heteroatoms, including sulfur and oxygen atoms, in the substituents, suggesting that the insecticidal activity is influenced by the receptor affinity, hydrophobicity, and metabolic stability of the compounds.

Chiral pool approach for the synthesis of functionalized amino acids: Synthesis of antiepileptic drug (R)-lacosamide

An efficient total synthesis of (R)-lacosamide 1 has been achieved from N-Boc-N,O-isopropylidene-l-serinol 2 which could easily be obtained from natural l-serine. Our synthesis of 1 starting from 2 using chiral pool strategy resulted in 54% overall yield.

PROCESS FOR THE SYNTHESIS OF ANTIEPILEPTIC DRUG LACOSAMIDE

The present invention relates to the improved and efficient process for the synthesis of antiepileptic drug Lacosamide in high enantiopurity (>98% ee) and better yield. More particularly, the present invention relates to improved and efficient, cost effective process for synthesis of desired (R) isomer of Lacosamide starting from commercially available (S)-benzyl glycidyl ether.