81196-09-0

Usage

Chemical Properties

White crystalline powder

InChI:InChI=1/C13H17NO4/c1-13(2,3)18-12(17)10(11(15)16)8-4-6-9(14)7-5-8/h4-7,10H,14H2,1-3H3,(H,15,16)

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 1197-55-3 4-aminophenylacetic acid 
• 897648-31-6 ethyl 2-(4-((tert-butoxycarbonyl)amino)phenyl)acetate 
• 58632-95-4 2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile 

Downstream Products

• 172607-50-0 (4-{[5-({2-[(4-Methoxy-benzyl)-pyridin-2-yl-amino]-ethyl}-methyl-amino)-pentylcarbamoyl]-methyl}-phenyl)-carbamic acid tert-butyl ester 
• 208185-23-3 {4-[(1-Benzyl-piperidin-4-ylcarbamoyl)-methyl]-phenyl}-carbamic acid tert-butyl ester 
• 223546-50-7 9-fluorenylmethyl-N-Boc-4-aminophenylacetate 
• 583868-50-2 N-[4-(aminomethyl)benzyl]-8-(1-{4-[(4-aminophenyl)acetyl]amino}butanoyl)-4-piperidinyl-2-(1-naphthylmethyl)-1,3-dioxo-2,3,5,8-tetrahydo-1H-[1,2,4]triazolo [1,2-a]pyridazine-5-carboxamide 
• 748148-97-2 (4-{[6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-methyl}-phenyl)-carbamic acid tert-butyl ester 
• 748148-88-1 (4-{[6-amino-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-methyl}-phenyl)-carbamic acid tert-butyl ester 
• 1000934-11-1 C₁₇H₂₅N₃O₃ 
• 882873-15-6 tert-butyl N-{4-[2-(dimethylamino)-2-oxoethyl]phenyl}carbamate 
• 1190069-99-8 tert-butyl 4-[2-({4-[(difluoromethyl)thio]phenyl}amino)-2-oxoethyl]phenylcarbamate 
• 878011-50-8 1-(2-(4-aminophenylacetyl)-hexahydropyrrolo[3,4-c]pyrrol-5-(1H)-yl)-3-methylbutan-1-one 
• 1266336-30-4 tert-butyl (4-(2-(cyclopropylamino)-2-oxoethyl)phenyl)-carbamate 

Relevant academic research and scientific papers

Synthesis and antitumour evaluation of indole-2-carboxamides against paediatric brain cancer cells

Paediatric glioblastomas are rapidly growing, devastating brain neoplasms with an invasive phenotype. Radiotherapy and chemotherapy, which are the current therapeutic adjuvant to surgical resection, are still associated with various toxicity profiles and only marginally improve the course of the disease and life expectancy. A considerable body of evidence supports the antitumour and apoptotic effects of certain cannabinoids, such as WIN55,212-2, against a wide spectrum of cancer cells, including gliomas. In fact, we previously highlighted the potent cytotoxic activity of the cannabinoid ligand 5 against glioblastoma KNS42 cells. Taken together, in this study, we designed, synthesised, and evaluated several indoles and indole bioisosteres for their antitumour activities. Compounds 8a, 8c, 8f, 12c, and 24d demonstrated significant inhibitory activities against the viability (IC50 = 2.34-9.06 μM) and proliferation (IC50 = 2.88-9.85 μM) of paediatric glioblastoma KNS42 cells. All five compounds further retained their antitumour activities against two atypical teratoid/rhabdoid tumour (AT/RT) cell lines. When tested against a medulloblastoma DAOY cell line, only 8c, 8f, 12c, and 24d maintained their viability inhibitory activities. The viability assay against non-neoplastic human fibroblast HFF1 cells suggested that compounds 8a, 8c, 8f, and 12c act selectively towards the panel of paediatric brain tumour cells. In contrast, compound 24d and WIN55,212-2 were highly toxic toward HFF1 cells. Due to their structural resemblance to known cannabimimetics, the most potent compounds were tested in cannabinoid 1 and 2 receptor (CB1R and CB2R) functional assays. Compounds 8a, 8c, and 12c failed to activate or antagonise both CB1R and CB2R, whereas compounds 8f and 24d antagonised CB1R and CB2R, respectively. We also performed a transcriptional analysis on KNS42 cells treated with our prototype compound 8a and highlighted a set of seven genes that were significantly downregulated. The expression levels of these genes were previously shown to be positively correlated with tumour growth and progression, indicating their implication in the antitumour activity of 8a. Overall, the drug-like and selective antitumour profiles of indole-2-carboxamides 8a, 8c, 8f, and 12c substantiate the versatility of the indole scaffold in cancer drug discovery. This journal is

Identification and Profiling of a Novel Diazaspiro[3.4]octane Chemical Series Active against Multiple Stages of the Human Malaria Parasite Plasmodium falciparum and Optimization Efforts

A novel diazaspiro[3.4]octane series was identified from a Plasmodium falciparum whole-cell high-throughput screening campaign. Hits displayed activity against multiple stages of the parasite lifecycle, which together with a novel sp3-rich scaffold provided an attractive starting point for a hit-to-lead medicinal chemistry optimization and biological profiling program. Structure-activity-relationship studies led to the identification of compounds that showed low nanomolar asexual blood-stage activity (50 nM) together with strong gametocyte sterilizing properties that translated to transmission-blocking activity in the standard membrane feeding assay. Mechanistic studies through resistance selection with one of the analogues followed by whole-genome sequencing implicated the P. falciparum cyclic amine resistance locus in the mode of resistance.

1H-pyrrole[2,3-b]pyridine derivative as well as synthesis method and application thereof

The invention relates to the technical field of organic synthesis, in particular to a 1H-pyrrole[2,3-b]pyridine derivative as well as a synthesis method and application thereof. The synthesis method comprises the following steps: with p-aminophenylacetic

Hypoxia-Activated Prodrugs of PERK Inhibitors

Tumour hypoxia plays an important role in tumour progression and resistance to therapy. Under hypoxia unfolded proteins accumulate in the endoplasmic reticulum (ER) and this stress is relieved through the protein kinase R-like ER kinase (PERK) signalling

Design and synthesis of (aza)indolyl maleimide-based covalent inhibitors of glycogen synthase kinase 3β

As an important kinase in multiple signal transduction pathways, GSK-3β has been an attractive target for chemical probe discovery and drug development. Compared to numerous reversible inhibitors that have been developed, covalent inhibitors of GSK-3β are

Pharmacomodulation of the antimalarial plasmodione: Synthesis of biaryl-and N-arylalkylamine analogues, antimalarial activities and physicochemical properties

With the aim of increasing the structural diversity on the early antimalarial drug plasmodione, an efficient and versatile procedure to prepare a series of biaryl- and N-arylalkylamines as plasmodione analogues is described. Using the naturally occurring and commercially available menadione as starting material, a 2-step sequence using a Kochi-Anderson reaction and subsequent Pd-catalyzed Suzuki-Miyaura coupling was developed to prepare three representative biphenyl derivatives in good yields for antimalarial evaluation. In addition, synthetic methodologies to afford 3-benzylmenadione derivatives bearing a terminal -N(Me)2 or -N(Et)2 in different positions (ortho, meta and para) on the aryl ring of the benzylic chain of plasmodione were investigated through reductive amination was used as the optimal route to prepare these protonable N-arylalkylamine privileged scaffolds. The antimalarial activities were evaluated and discussed in light of their physicochemical properties. Among the newly synthesized compounds, the para-position of the substituent remains the most favourable position on the benzyl chain and the carbamate -NHBoc was found active both in vitro (42 nM versus 29 nM for plasmodione) and in vivo in Plasmodium berghei-infected mice. The measured acido-basic features of these new molecules support the cytosol-food vacuole shuttling properties of non-protonable plasmodione derivatives essential for redox-cycling. These findings may be useful in antimalarial drug optimization.

METHODS AND COMPOSITIONS INVOLVING RAD51 INHIBITORS

The present invention concerns methods and compositions involving inhibitors and of RAD51, a protein involved in homologous recombination. In some embodiments, there are methods for sensitizing cells to the effects of DNA damaging agents, which can have p

An optimized RAD51 inhibitor that disrupts homologous recombination without requiring michael acceptor reactivity

Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is

INHIBITORS OF P38 MAP KINASE

Compounds of formula (I) are p38 MAP kinase inhibitors useful for the treatment of autoimmune and inflammatory diseases: wherein: G is -N= or -CH=; D is an optionally substituted divalent mono- or bi-cyclic aryl or heteroaryl radical having 5 - 13 ring members; R6 is hydrogen or optionally substituted CrC3 alkyl; P represents hydrogen and U represents a radical of formula (IA); or U represents hydrogen and P represents a radical of formula (IA); wherein A represents an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members; z is O or 1; -X1-L1-Y- is a linker radical or bond; R1 is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular esterase enzymes to a carboxylic acid group; and R2 and R3 are as defined in the claims.

2-ARYLCARBOXAMIDE-NITROGENEOUS HETEROCYCLE COMPOUND

A compound represented bv the formula [I]: [wherein R1 and R2 are the same or different and each represents C1-6 alkyl, C3-8 cycloalkyl, et al; R3a, R3b, and R4 are the same or different and each represents hydrogen, C1-6 alkyl, et al; X represents -N-, -CH-, et al; Y1 represents a single bond, C1-3 alkylene, et al; Y2 represents C1-4 alkylene, oxy(C1-4 alkylene), et al; Ar1 represents a monocyclic aromatic carbocyclic group, monocyclic aromatic heterocyclic group, et al; and Ar2 represents a 5- or 6-membered aromatic carbocyclic group, aromatic heterocyclic group, et al]. This compound functions as a melanin-concentrating hormone receptor antagonist and is useful as, e.g., a therapeutic agent for obesity, et al.