17872-55-8

Usage

InChI:InChI=1/C6H12O4/c1-6(3-7,4-8)5(9)10-2/h7-8H,3-4H2,1-2H3

Upstream product

• 186581-53-3 diazomethane 
• 4767-03-7 2,2-bis(hydroxymethyl)propionic acid 
• 50-00-0 formaldehyd 
• 13169-01-2 1-methoxypropyne 
• 67-56-1 methanol 
• 18107-18-1 diazomethyl-trimethyl-silane 

Downstream Products

• 4767-03-7 2,2-bis(hydroxymethyl)propionic acid 
• 27315-40-8 2-Chloro-5-methyl-2-oxo-2λ⁵-[1,3,2]dioxaphosphinane-5-carboxylic acid methyl ester 
• 27315-41-9 2-Hydroxy-5-methyl-2-oxo-2λ⁵-[1,3,2]dioxaphosphinane-5-carboxylic acid methyl ester 
• 27247-48-9 2-(4-Bromo-phenylamino)-5-methyl-2-oxo-2λ⁵-[1,3,2]dioxaphosphinane-5-carboxylic acid methyl ester 
• 27247-47-8 5-Methyl-2-oxo-2-phenylamino-2λ⁵-[1,3,2]dioxaphosphinane-5-carboxylic acid methyl ester 
• 27247-45-6 2-Cyclohexylamino-5-methyl-2-oxo-2λ⁵-[1,3,2]dioxaphosphinane-5-carboxylic acid methyl ester 
• 27247-49-0 2-(4-Methoxy-phenylamino)-5-methyl-2-oxo-2λ⁵-[1,3,2]dioxaphosphinane-5-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Self-interrupted synthesis of sterically hindered aliphatic polyamide dendrimers

2,2-Bis(azidomethyl)propionic acid was prepared in four steps and 85% yield from the commercially available 2,2-bis(hydroxymethyl) propionic acid and used as the starting building block for the divergent, convergent, and double-stage convergent-divergent iterative methods for the synthesis of dendrimers and dendrons containing ethylenediamine (EDA), piperazine (PPZ), and methyl 2,2- bis(aminomethyl)propionate (COOMe) cores. These cores have the same multiplicity but different conformations. A diversity of synthetic methods were used for the synthesis of dendrimers and dendrons. Regardless of the method used, a self-interruption of the synthesis was observed at generation 4 for the dendrimer with an EDA core and at generation 5 for the one with a PPZ core, whereas for the COOMe core, self-interruption was observed at generation 6 dendron, which is equivalent to generation 5 dendrimer. Molecular modeling and molecular-dynamics simulations demonstrated that the observed self-interruption is determined by the backfolding of the azide groups at the periphery of the dendrimer. The latter conformation inhibits completely the heterogeneous hydrogenation of the azide groups catalyzed by 10% Pd/carbon as well as homogeneous hydrogenation by the Staudinger method. These self-terminated polyamide dendrimers are enzymatically and hydrolytically stable and also exhibit antimicrobial activity. Thus, these nanoscale constructs open avenues for biomedical applications.

Synthesis and spectral characteristics of 2,2-bis(hydroxymethyl)propionic acid derivatives as model compounds for the estimation of properties of modified hyperbranched polyesters polyols

New amino and carboxy derivatives of methyl 2,2-bis(hydroxymethyl)propionate have been synthesized as models of terminal fragments of hyperbranched polyester polyamines and polyesters polycarboxylic acids, and their spectral characteristics have been stud

Norbornadienes: Robust and Scalable Building Blocks for Cascade "click" Coupling of High Molecular Weight Polymers

Herein, we report the development of a scalable and synthetically robust building block based on norbornadiene (NBD) that can be broadly incorporated into a variety of macromolecular architectures using traditional living polymerization techniques. By tak

Studies toward novel peptidomimetic inhibitors of thioredoxin-thioredoxin reductase system

Thioredoxins (Trx) are ubiquitous multifunctional low-molecular weight proteins that together with thioredoxin reductases (TrxR) participate in the maintenance of protein thiol homeostasis in NADPH-dependent reactions. An increasing number of data reveal that the Trx-TrxR system is an attractive target for anticancer therapies. In this work, we have elaborated a new and simple synthetic approach employing Ugi reaction to synthesize several new inhibitors of this system. The influence of various electrophilic fragments of this new class of compounds on the inhibition of the Trx-TrxR system was evaluated. As a result, a new compound 19a (SK053), which inhibits the activity of the Trx-TrxR system and exhibits antitumor activity, was obtained. Biologic analyses revealed that 19a inhibits induction of NF-κB and AP-1 and decreases H2O2 scavenging capacity in tumor cells. Altogether, we show that 19a is a novel potential antitumor peptidomimetic inhibitor that can be used as a starting compound for further optimization.

Identification of 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1, 1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea hydrochloride (CEP-32496), a highly potent and orally efficacious inhibitor of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF) V600E

The Ras/RAF/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway plays a central role in the regulation of cell growth, differentiation, and survival. Expression of mutant BRAFV600E results in constitutive activation of the MAPK pathway, which can lead to uncontrolled cellular growth. Herein, we describe an SAR optimization campaign around a series of quinazoline derived BRAFV600E inhibitors. In particular, the bioisosteric replacement of a metabolically sensitive tert-butyl group with fluorinated alkyl moieties is described. This effort led directly to the identification of a clinical candidate, compound 40 (CEP-32496). Compound 40 exhibits high potency against several BRAFV600E-dependent cell lines and selective cytotoxicity for tumor cell lines expressing mutant BRAFV600E versus those containing wild-type BRAF. Compound 40 also exhibits an excellent PK profile across multiple preclinical species. In addition, significant oral efficacy was observed in a 14-day BRAFV600E-dependent human Colo-205 tumor xenograft mouse model, upon dosing at 30 and 100 mg/kg BID.

PYRAZOLE-ISOQUINOLINE UREA DERIVATIVES AS P38 KINASE INHIBITORS

The present invention provides kinase inhibitors of Formula (I) wherein R1, R2, and X are as described herein, or a pharmaceutically acceptable salt thereof.

KINASE INHIBITORS

The present invention provides kinase inhibitors of Formula (I). Wherein R1, R2, X and Z are as described herein, or a pharmaceutically acceptable salt thereof.

An algorithm-directed two-component library synthesized via solid-phase methodology yielding potent and orally bioavailable p38 MAP kinase inhibitors

Previously we reported the identification of RPR200765A, a potent orally bioavailable pyridine - imidazole inhibitor of p38 mitogen-activated protein (MAP) kinase which suppressed paw swelling and joint pathology in streptococcal cell wall-induced arthrit