223128-33-4

Usage

Uses

Used as a primary and secondary intermediate for pharmaceutical.

InChI:InChI=1/C11H13ClO2/c1-8(2)9-3-5-10(6-4-9)14-7-11(12)13/h3-6,8H,7H2,1-2H3

Upstream product

• 79-37-8 oxalyl dichloride 
• 1643-16-9 2-(4-isopropylphenoxy)acetic acid 
• 90719-32-7 (S)-4-Benzyl-2-oxazolidinone 
• 99-89-8 4-Isopropylphenol 
• 1401223-60-6 tert-butyl 2-(4-isopropylphenoxy)acetate 
• 184878-97-5 methyl (4-(1-methylethyl)phenoxy)acetate 

Downstream Products

• 1246091-45-1 O,O-dimethyl-1-(4-isopropylphenoxyacetoxy)ethylphosphonate 
• 1246091-36-0 O,O-dimethyl-1-(4-isopropylphenoxyacetoxy)-1-(2-chlorophenyl)methylphosphonate 
• 1401223-27-5 N-isopropyl-2-(4-isopropylphenoxy)-N-((3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)methyl)acetamide 

Relevant academic research and scientific papers

Staphylococcus aureus rnpa inhibitors: Computational-guided design, synthesis and initial biological evaluation

Antibiotic resistance is spreading worldwide and it has become one of the most important issues in modern medicine. In this context, the bacterial RNA degradation and processing machinery are essential processes for bacterial viability that may be exploited for antimicrobial therapy. In Staphylococcus aureus, RnpA has been hypothesized to be one of the main players in these mech-anisms. S. aureus RnpA is able to modulate mRNA degradation and complex with a ribozyme (rnpB), facilitating ptRNA maturation. Corresponding small molecule screening campaigns have recently identified a few classes of RnpA inhibitors, and their structure activity relationship (SAR) has only been partially explored. Accordingly, in the present work, using computational modeling of S. aureus RnpA we identified putative crucial interactions of known RnpA inhibitors, and we used this information to design, synthesize, and biologically assess new potential RnpA inhibitors. The present results may be beneficial for the overall knowledge about RnpA inhibitors belonging to both RNPA2000-like thiosemicarbazides and JC-like piperidine carboxamides molecular classes. We evaluated the importance of the different key moieties, such as the dichlorophenyl and the piperidine of JC2, and the semithiocarbazide, the furan, and the i-propylphenyl ring of RNPA2000. Our efforts could provide a foundation for further computational-guided investigations.

Discovery and development of a novel class of phenoxyacetyl amides as highly potent TRPM8 agonists for use as cooling agents

The paper presents the activity trends for a novel series of phenoxyacetyl amides as human TRPM8 receptor agonists. This series encompasses in vitro activity values ranging from the micromolar to the picomolar levels. Sensory evaluation of these molecules highlights their relevance as cooling agents for oral applications. The positive outcome of the complete evaluation of N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide resulted in its approval for Generally Recognized As Safe (GRAS) status by the Flavor & Extract Manufacturer Association (FEMA) as FEMA 4809.

Design, synthesis and structure-activity relationship studies of novel phenoxyacetamide-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes

The free fatty acid receptor 1 (FFA1) has attracted extensive attention as a novel antidiabetic target in the last decade. Several FFA1 agonists reported in the literature have been suffered from relatively high molecular weight and lipophilicity. We have previously reported the FFA1 agonist 1. Based on the common amide structural characteristic of SAR1 and NIH screened compound, we here describe the continued structure-activity exploration to decrease the molecular weight and lipophilicity of the compound 1 series by converting various amide linkers. All of these efforts lead to the discovery of the preferable lead compound 18, a compound with considerable agonistic activity, high LE and LLE values, lower lipophilicity than previously reported agonists, and appreciable efficacy on glucose tolerance in both normal and type 2 diabetic mice.

Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors

Screening of the 50 000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50 = 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 = 27 nM). Detailed SAR studies indicate that the amide moiety and the two phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl in the para position (not ortho or meta) of the A-ring and a m-pyridyl group as B-ring, significantly improve activity. Compound 11ad (IC50 = 0.37 μM) is more potent than 1 (IC50 = 3.5 μM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further preclinical investigation of this class as noncovalent proteasome inhibitors.

PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS

Focused library synthesis and medicinal chemistry on an oxadiazole- isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring?s para-position and meta-pyridyl group at the B- ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer)

COMPOUND LIBRARIES

The present invention relates to compounds capable of binding to the active site of protein kinase enzymes. The invention further relates to libraries of compounds and a family of libraries of compounds for use in screening programmes against protein kinases as well as the individual compounds for use in hit to lead and lead optimisation projects, and similar stages in the drug discovery process. The invention also provides methods for making compounds and libraries.

Amidocarboxylic acid derivatives

Amidocarboxylic acid derivatives of the formula: wherein R1 represents a hydrogen atom, etc.; R2 represents an alkylene group; R3 represents a hydrogen atom, etc.; R4 represents a hydrogen atom, etc.; X represents a substituted or unsubstituted aryl group, etc.,; Y represents an oxygen atom, etc.; Z represents an alkylene group, etc.; and W represents an alkyl group, etc.; and pharmacologically acceptable salts thereof and pharmacologically acceptable esters thereof are useful as the active ingredient of pharmaceutical compositions. They may be used to treat specified diseases, including diabetes mellitus, hyperlipemia, arteriosclerosis, hypertension, etc.

Preparation of C8-amine and acetylamine adducts of 2′-deoxyguanosine suitably protected for DNA synthesis

(Equation presented) C8-Amine and acetylamine adducts of 2′-deoxyguanosine were synthesized. Our approach provides solutions for the coupling of aromatic amines to a protected 8-bromo-2′-deoxyguanosine derivative, for the selective acetylation of the coup