18997-19-8

Usage

Uses

Used in Pharmaceutical Synthesis:
Chloromethyl pivalate is used as a reagent for the synthesis of pivaloyloxy methyl ester of ofloxacin, which serves as a prodrug. This application takes advantage of its reactivity with sodium salts and its ability to form esters, enhancing the drug's bioavailability and effectiveness.
Additionally, Chloromethyl pivalate is used as a reagent during the synthesis of an isoindoline-annulated, tricyclic sultam library. This process involves microwave-assisted, continuous-flow organic synthesis, highlighting the compound's utility in modern, efficient drug development techniques.
Used in the Production of Sulbactam Pivoxil:
Chloromethyl pivalate reacts with the sodium salt of sulbactam to yield sulbactam pivoxil, a semi-synthetic beta-lactamase inhibitor. This reaction showcases the compound's role in the development of antibiotics, contributing to the fight against bacterial resistance.

InChI:InChI=1/C6H11ClO2/c1-6(2,3)5(8)9-4-7/h4H2,1-3H3

Upstream product

• 598-98-1 Methyl pivalate 
• 49715-04-0 chlorosulfuric acid chloromethyl ester 
• 75-98-9 Trimethylacetic acid 
• 74-97-5 chlorobromomethane 
• 1184-88-9 sodium pivalate 
• 19455-23-3 potassium pivalate 
• 50-00-0 formaldehyd 
• 3282-30-2 pivaloyl chloride 

Downstream Products

• 25031-08-7 6-aminopenicillanic acid pivaloyloxymethyl ester 
• 25031-07-6 (pivaloyloxy)methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 
• 54149-01-8 (pivaloyloxy)methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 
• 35409-23-5 (6R)-3-acetoxymethyl-7t-((R)-2-azido-2-phenyl-acetylamino)-5ξ,8-dioxo-(6rH)-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 2,2-dimethyl-propionyloxymethyl ester 
• 59367-64-5 6β-((R)-2-formylamino-2-phenyl-acetylamino)-penicillanic acid 2,2-dimethyl-propionyloxymethyl ester 
• 63491-70-3 (6R)-7t-((R)-2-tert-butoxycarbonylamino-2-phenyl-acetylamino)-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-5ξ,8-dioxo-(6rH)-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 2,2-dimethyl-propionyloxymethyl ester 
• 73403-42-6 (6R)-3-acetoxymethyl-7t-(2-nitro-phenylsulfanylamino)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 2,2-dimethyl-propionyloxymethyl ester 
• 91418-01-8 1-(2,2-Dimethyl-propionyloxymethyl)-1-(4-hydroxy-4,4-diphenyl-but-2-ynyl)-pyrrolidinium; chloride 
• 66898-66-6 2-<<3-(trifluormetil)fenil>amino>benzoato de pivaloiloximetilo 
• 83475-16-5 1-(2,2-dimethyl-1-oxopropoxy)methyl L-N-(phenylmethoxycarbonyl) tyrosinate 
• 66898-65-5 2-<(2,3-dimetilfenil)amino>benzoato de pivaloiloximetilo 
• 79751-22-7 2-(Benzylidenamino)-2-(pivaloyloxymethyl)propansaeure-methylester-N-oxid 
• 87589-21-7 4-(tert-Butoxycarbonylamino-methyl)-cyclohexanecarboxylic acid 2,2-dimethyl-propionyloxymethyl ester 
• 69388-79-0 (pivaloyloxy)methyl 6,6-dihydropenicillanate S,S-dioxide 

Relevant academic research and scientific papers

Novel multifunctional acyloxyalkyl ester prodrugs of 5-aminolevulinic acid display improved anticancer activity independent and dependent on photoactivation

Multifunctional acyloxyalkyl ester prodrugs of 5-aminolevulinic acid in cancer cell lines inhibited the proteasome and induced apoptosis and heme synthesis. The most potent prodrug was butyryloxymethyl 5-amino-4-oxopentanoate (1a). The metabolically released formaldehyde from the prodrugs was the dominant factor affecting cell viability by a ROS-dependent mechanism and was responsible for rapid phosphorylation of H2AX, suppression of the cell survival protein c-myc, and transient elevation in the expression of p21. 1a, which differs from 2a by releasing butyric instead of pivalic acid, was a more potent inducer of heme and acetylated H4 expression and induced apoptosis through activation of caspase 9. 1a and 1b specifically increased the level of the photosensitizer protoporphyrin 9, leading to enhancement of cell death by photodynamic therapy (PDT). The advantage of these multifunctional prodrugs over 5-ALA is their greater potency in the non-PDT mechanism of cancer cell killing and their ability to also augment PDT.

Effects of vehicles and prodrug properties and their interactions on the delivery of 6-mercaptopurine through skin: Bisacyloxymethyl-6-mercaptopurine prodrugs

A series of S6,9-bisacyloxymethyl-6-mercaptopurine (6,9-bis-6-MP) prodrug derivatives was synthesized and characterized. The solubilities of the derivatives in solvents (vehicles), which exhibited a wide range of polarities from water to oleic acid, were measured. The abilities of the prodrugs to deliver 6-mercaptopurine (6-MP) from the vehicles have also been determined, and experimental fluxes and permeability coefficients (K(p)) have been calculated for a large number of prodrug:vehicle combinations. Generally the best prodrugs of the series in terms of delivering 6-MP, regardless of the vehicle, were the first two members -the bisacetyl- and the bispropionyloxymethyl-6-mercaptopurine prodrugs. This result has been attributed mainly to the increased water solubility of these two prodrugs compared with that of 6-MP and the other prodrugs, since all of the prodrugs are much more lipid soluble than 6-MP. For three vehicles -isopropyl myristate, propylene glycol, and water- there was a good correlation between log experimental K(p) for the delivery of 6-MP by the prodrugs from those vehicles and the theoretical solubility parameters of the prodrugs. The stabilities of the bisacetyl-(2), bispropionyl-(3), and bisbutyryloxymethyl-6-mercaptopurine (4) derivatives were determined in buffer and in buffer containing enzymes leached from the dermis. Prodrug 2 was more stable than 3 or 4 in the buffer containing the enzymes, while 4 was more stable than 2 or 3 in the plain buffer.

Atmospheric oxidation mechanism of methyl pivalate, (CH3)3CC(O)OCH3

Smog chamber/FTIR techniques were used to study the Cl atom and OH radical initiated oxidation of methyl pivalate, (CH3)3CC(O)OCH3, in the presence of NOx in 700 torr of N2/O2 diluent at 296 K. The Cl atom initiated oxidation of methyl pivalate in the presence of 15-600 torr of O2 and 10-30 mtorr of NOx in 700 torr total pressure of N2 diluent at 296 K yielded HCHO, CO, acetone, CO2 and CH3OC(O)O2NO2. OH radical initiated oxidation of methyl pivalate in air produced acetone in a 51% yield. Flash photolysis-resonance fluorescence techniques were used to measure the rate constant for the reaction of OH radicals with methyl pivalate at 250-370 K. The rate constant showed a weak temperature dependence, increasing at both low and high temperature from a minimum value of about 1.2 × 10-12 cc/molecule-sec near room temperature. The data obtained were used to formulate a detailed mechanism describing the atmospheric oxidation of methyl pivalate. This mechanism gave predictions of the effects of methyl pivalate on O3 formation and other measures of reactivity that were in good agreement with results of environmental chamber experiments. It should be used in future airshed models to predict the effects of methyl pivalate emissions on air quality.

Substituted pyrazole compound, preparation method, pharmaceutical composition and applications thereof

The invention discloses a substituted pyrazole compound represented by a formula I, and a preparation method, a pharmaceutical composition and applications thereof, wherein the compound has characteristics of good stability, excellent solubility, low cytotoxicity and remarkable neuroprotective effect, can effectively prevent and treat nerve cell injury, and is an ideal medicinal compound for preventing or treating cerebral stroke, cerebral embolism, cerebral stroke sequelae, cerebral stroke dyskinesia, mitochondrial encephalomyopathy and amyotrophic lateral sclerosis of spinal cord.

RODENTICIDAL NORBORMIDE ANALOGUES

The present invention relates to norbormide analogues having rodenticidal activity; rodenticidal compositions comprising the analogues; uses of the analogues as rodenticides; uses of the analogues in the manufacture of rodenticidal compositions; and methods for controlling rodents using the compositions.

Design and synthesis of prodrugs of the rat selective toxicant norbormide

Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2- pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. However, one major drawback of NRB as a viable rodenticide relates to an evolutionary aversion developed by the rat leading to sub-lethal dosing due to either its unpleasant 'taste' or rapid onset of effects. A series of NRB prodrugs were prepared in an effort to 'mask' this acute response. Their synthesis and biological evaluation (in vitro vasoconstrictory activity, in vitro hydrolytic and enzymatic stability and lethality/palatability in vivo) is described. Compound 19 displayed the most promising profile with respect to a delay in the onset of symptoms and was subsequently demonstrated to be significantly more palatable to rats.

PRODRUGS OF FUSED HETEROCYCLIC INHIBITORS OF D-AMINO ACID OXIDASE

The invention relates to prodrugs of fused heterocyclic inhibitors of D-amino oxidase (DAAO) and methods of treating diseases and conditions, wherein modulation of D-amino acid oxidase activity, D-serine levels, D-serine oxidative products and NMDA receptor activity in the nervous system of a mammalian subject is effective.

Design, synthesis, and cholesterol-lowering efficacy for prodrugs of berberrubine

In order to enhance oral bioavailability of berberine (BBR) for its cholesterol-lowering efficacy in vivo, a series of ester or ether prodrugs of berberrubine (M1), which is an active metabolite of BBR after first-pass metabolism, were designed, semi-synthesized, and evaluated. Among these M1 prodrugs, compound 5g possessing palmitate at the 9-position showed a moderate Log P value and esterase hydrolysis rate for releasing M1 in blood. Its cholesterol-lowering efficacy in vivo was evaluated in hyperlipidemic SD rats. Compound 5g (100 mg/kg/d) reduced blood CHO and LDL-c by 35.8% and 45.5%, respectively, similar to that by BBR. It also exhibited a good safety in rats with no side-effect on liver and kidney function. Therefore, the design of M1 prodrug appears to be an effective strategy to improve pharmacokinetic feature of BBR for its lipid-lowering efficacy in vivo.

Prodrugs of protein tyrosine kinase inhibitors

Novel compounds and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as oncologic and immunologic disorders.

Bioreversible quaternary N-acyloxymethyl derivatives of the tertiary amines bupivacaine and lidocaine - Synthesis, aqueous solubility and stability in buffer, human plasma and simulated intestinal fluid

Design of water-soluble prodrugs may constitute a means to improve the oral bioavailability of drugs suffering from dissolution rate-limited absorption. The model drug bupivacaine containing a tertiary amine function has been converted into bioreversible quaternary N-acyloxymethyl derivatives. The pH-independent solubility of the N-butanoyloxymethyl derivate exceeded 1000 mg ml-1 corresponding approximately to a 10,000-fold increase in water solubility compared to that of bupivacaine base. The kinetics of hydrolysis of the prodrugs was studied in the pH range 0.1-9.8 (37°C). Decomposition was found to follow first-order kinetics and U-shaped pH-rate profiles were constructed. The observed differences between the hydrolytic lability of the derivatives might most likely be ascribed to steric effects. In most cases, the prodrugs were quantitatively converted into bupivacaine. However, for the hydrolysis of the N-butanoyloxymethyl derivative at neutral to slightly alkaline pH parallel formation of bupivacaine (～80%) and an unknown compound X (～20%) was observed. LC-MS analysis of the latter compound suggests that an aromatic imide structure has been formed from an intramolecular acyl transfer reaction involving a nucleophilic attack of the amide nitrogen atom on the ester carbonyl carbon atom. Whereas the derivatives were poor substrates for plasma enzymes; they were hydrolyzed rapidly to parent bupivacaine in the presence of pancreatic enzymes (simulated intestinal fluid) at 37°C. The data indicate that such prodrugs possess sufficient stability in the acidic environment of the stomach to reach the small intestine in intact form where they can be cleaved efficiently by action of pancreatic enzymes prior to drug absorption. Thus, the N-acyloxymethyl approach might be of potential utility to enhance oral bioavailability of tertiary amines exhibiting pKa values below approximately 6 and intrinsic solubilities in the low μM range.