34036-16-3

Usage

Uses

Used in Pharmaceutical Industry:
5-METHYL-3-OXO-HEXANOIC ACID ETHYL ESTER is used as a synthetic intermediate for the preparation of (dichloropyridinyl)(isopropyldimethypyrazolopyridinylmethyl)cyanoguanidine analogs. These analogs act as S1PR2 antagonists, which are important in the development of drugs targeting various diseases, including autoimmune disorders and cancer.

InChI:InChI=1/C9H16O3/c1-4-12-9(11)6-8(10)5-7(2)3/h7H,4-6H2,1-3H3

Upstream product

• 108-10-1 4-methyl-2-pentanone 
• 105-58-8 Diethyl carbonate 
• 141-97-9 ethyl acetoacetate 
• 108-12-3 isopentanoyl chloride 
• 141-78-6 ethyl acetate 
• 625-28-5 Isovaleronitrile 
• 105-36-2 ethyl bromoacetate 
• 133827-52-8 ethyl 3-methyl-5-oxo-2,5-dihydroisoxazole-4-carboxylate sodium salt 
• 75-30-9 2-iodo-propane 
• 1723-25-7 ethyl 2,3-dioxobutyrate 
• 590-86-3 isovaleraldehyde 
• 2033-24-1 cycl-isopropylidene malonate 
• 64-17-5 ethanol 
• 146380-12-3 5-(1-hydroxy-3-methylbutylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 

Downstream Products

• 1879-00-1 2,6-dimethyl-7-octene-4-one 
• 41747-23-3 2-[1-(4-Chloro-cyclohex-3-enyl)-ethyl]-5-methyl-3-oxo-hexanoic acid ethyl ester 
• 50627-09-3 4-methyl-2-oxo-pentanal oxime 
• 120467-66-5 1,1-bis(p-chlorophenyl)-2-ethoxycarbonyl-5-methylhexan-3-one 
• 64123-72-4 5-isopropyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one 
• 147314-98-5 benzoic acid 1-(ethoxycarbonyl)-4-methyl-2-oxopentyl ester 
• 412320-87-7 Menthandion-(3,5) 
• 871838-05-0 6'-(3-benzyloxy-propyl)-6,2'-diisobutyl[2,3']bipyridinyl-5-carboxylic acid ethyl ester 
• 871838-06-1 6''-(3-benzyloxy-propyl)-6,2',2''-triisobutyl-[2,3';6',3'']terpyridine-5-carboxylic acid ethyl ester 
• 871838-04-9 6-(3-benzyloxy-propyl)-2-isobutyl-nicotinic acid ethyl ester 
• 137860-49-2 4'-(5-Hydroxy-3-isobutyl-1-methyl-1H-pyrazol-4-ylmethyl)-biphenyl-2-carbonitrile 
• 137860-50-5 4'-[5-Hydroxy-3-isobutyl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-4-ylmethyl]-biphenyl-2-carbonitrile 
• 137860-51-6 [4-(2'-Cyano-biphenyl-4-ylmethyl)-5-isobutyl-2-methyl-2H-pyrazol-3-yloxy]-acetic acid ethyl ester 
• 137860-53-8 4'-[5-(2-Hydroxy-ethoxy)-3-isobutyl-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-4-ylmethyl]-biphenyl-2-carbonitrile 

Relevant academic research and scientific papers

Design, synthesis and evaluation of pyrazole derivatives as non-nucleoside hepatitis B virus inhibitors

In continuation of our efforts toward the discovery of potent non-nucleoside hepatitis B virus (HBV) inhibitors with novel structures, we have employed bioisosterism and hybrid pharmacophore-based strategy to explore the chemically diverse space of bioactive compounds. In this article, the original thiazole platform was replaced with pyrazole scaffold to yield the optimal pharmacophore moieties in order to generate novel non-nucleoside HBV inhibitors with desirable potency. Some of the new compounds were able to inhibit HBV activity in the low micromolar range. In particular, compound 6a3 displayed the most potent activity against the secretion of HBsAg and HBeAg with IC50of 24.33?μM and 2.22?μM, respectively. The preliminary structure-activity relationship (SAR) of this new series of compounds was investigated, which may help designing more potent molecules.

Synthetic Scope of Br?nsted Acid-Catalyzed Reactions of Carbonyl Compounds and Ethyl Diazoacetate

The comprehensive study of the reactions of carbonyl compounds and ethyl diazoacetate in the presence of a Br?nsted acid catalyst is described. In result, a broad range of 3-oxo-esters were synthesized from a variety of ketones and aliphatic aldehydes by 1,2-aryl/alkyl/hydride shift. Aryl-methyl ketones produced only aryl-migrated products, whereas other ketones yielded a mixture of products. For diaryl ketones, the identity of two inseparable migrated products was confirmed by two-dimensional NMR spectroscopy.

Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones

Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.

Design, diversity-oriented synthesis and biological evaluation of novel heterocycle derivatives as non-nucleoside HBV capsid protein inhibitors

The capsid assembly is a significant phase for the hepatitis B virus (HBV) lifespan and is an essential target for anti-HBV drug discovery and development. Herein, we used scaffold hopping, bioisosterism, and pharmacophore hybrid-based strategies to design and synthesize six series of various heterocycle derivatives (pyrazole, thiazole, pyrazine, pyrimidine, and pyridine) and screened for in vitro anti-HBV non-nucleoside activity. Drug candidate NZ-4 and AT-130 were used as lead compounds. Several compounds exhibited prominent anti-HBV activity compared to lead compound NZ-4 and positive drug Lamivudine, especially compound II-8b, showed the most prominent anti-HBV DNA replication activity (IC50 = 2.2 ± 1.1 μM). Also compounds IV-8e and VII-5b showed the best in vitro anti-HBsAg secretion (IC50 = 3.8 ± 0.7 μM, CC50 > 100 μM) and anti-HBeAg secretion (IC50 = 9.7 ± 2.8 μM, CC50 > 100 μM) respectively. Besides, II-8b can interact HBV capsid protein with good affinity constants (KD = 60.0 μM), which is equivalent to lead compound NZ-4 ((KD = 50.6 μM). The preliminary structure-activity relationships (SARs) of the newly synthesized compounds were summarized, which may help researchers to discover more potent anti-HBV agents.

Five Roads That Converge at the Cyclic Peroxy-Criegee Intermediates: BF3-Catalyzed Synthesis of β-Hydroperoxy-β-peroxylactones

We have discovered synthetic access to β-hydroperoxy-β-peroxylactones via BF3-catalyzed cyclizations of a variety of acyclic precursors, β-ketoesters and their silyl enol ethers, alkyl enol ethers, enol acetates, and cyclic acetals, with H2O2. Strikingly, independent of the choice of starting material, these reactions converge at the same β-hydroperoxy-β-peroxylactone products, i.e., the peroxy analogues of the previously elusive cyclic Criegee intermediate of the Baeyer-Villiger reaction. Computed thermodynamic parameters for the formation of the β-hydroperoxy-β-peroxylactones from silyl enol ethers, enol acetates, and cyclic acetals confirm that the β-peroxylactones indeed correspond to a deep energy minimum that connects a variety of the interconverting oxygen-rich species at this combined potential energy surface. The target β-hydroperoxy-β-peroxylactones were synthesized from β-ketoesters, and their silyl enol ethers, alkyl enol ethers, enol acetates, and cyclic acetals were obtained in 30-96% yields. These reactions proceed under mild conditions and open synthetic access to a broad selection of β-hydroperoxy-β-peroxylactones that are formed selectively even in those cases when alternative oxidation pathways can be expected. These β-peroxylactones are stable and can be useful for further synthetic transformations.

GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES

Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula II.

GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES

Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (I), as follows: wherein R1, R2, R4, W, X, Y, and G, are defined herein.

GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES

Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (III); wherein R1c, R2C, R4C, Wc, Yc, Zc and Gc, are defined herein.

Total synthesis and biological evaluation of the antibiotic lysocin E and its enantiomeric, epimeric, and N-demethylated analogues

Lysocin E, a macrocyclic peptide, exhibits potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) through a novel mechanism. The first total synthesis of lysocin E was achieved by applying a full solidphase strategy. The developed approach also provides rapid access to the enantiomeric, epimeric, and N-demethylated analogues of lysocin E. Significantly, the antibacterial activity of the unnatural enantiomer was comparable to that of the natural isomer, suggesting the absence of chiral recognition in its mode of action.

Evaluation of several routes to advanced pregabalin intermediates: Synthesis and enantioselective enzymatic reduction using ene-reductases

This publication describes the evaluation of four synthetic routes to the advanced pregabalin (Lyrica) intermediate 7. Asymmetric reduction of (E)-7 with an ene-reductase (OPR1 from Lycopersicon esculentum) gave a saturated cyanoester intermediate 5 with the desired S stereocenter in ≥99% ee. OPR1 also catalyzed the reduction of (Z)-7 to (S)-5, but with lower conversion and selectivity.