6092-54-2Relevant academic research and scientific papers
Photo-on-Demand Synthesis of Chloroformates with a Chloroform Solution Containing an Alcohol and Its One-Pot Conversion to Carbonates and Carbamates
Liang, Fengying,Suzuki, Yuto,Tsuda, Akihiko,Yanai, Masaki
supporting information, (2020/04/21)
Chloroformates are key reagents for synthesizing carbonates and carbamates. The present study reports a novel photo-on-demand in situ synthesis of chloroformates with a CHCl3 solution containing a primary alkyl alcohol. It further allowed the one-pot synthesis of carbonates and carbamates through subsequent addition of alcohols or amines, respectively.
Anti-HIV-Active Nucleoside Triphosphate Prodrugs
Jia, Xiao,Schols, Dominique,Meier, Chris
, p. 6003 - 6027 (2020/07/10)
We disclose a study on nucleoside triphosphate (NTP) analogues in which the γ-phosphate is covalently modified by two different biodegradable masking units and d4T as nucleoside analogue that enable the delivery of d4TTP with high selectivity in phosphate buffer (pH 7.3) and by enzyme-triggered reactions in human CD4+ T-lymphocyte CEM cell extracts. This allows the bypass of all steps normally needed in the intracellular phosphorylation. These TriPPPro-nucleotides comprising an acyloxybenzyl (AB; ester) or an alkoxycarbonyloxybenzyl (ACB; carbonate) in combination with an ACB moiety are described as NTP delivery systems. The introduction of these two different groups led to the selective formation of γ-(ACB)-d4TTPs by chemical hydrolysis and in particular by cell extract enzymes. γ-(AB)-d4TTPs are faster cleaved than γ-(ACB)-d4TTPs. In antiviral assays, the compounds are highly active against HIV-1 and HIV-2 in wild-type CEM/O cells and more importantly in thymidine kinase-deficient CD4+ T-cells (CEM/TK-).
Neuraminic acid inhibitor prodrug composition and use thereof
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Paragraph 0109; 0112-0114, (2016/10/20)
Provided are a compound as represented by formula Ia, or pharmaceutically acceptable salt, solvate, polymorph, enantiomer or racemic mixture thereof. As a neuraminidase inhibitor prodrug, the compound can improve the half-life in vivo of the neuraminidase inhibitor. Also provided are a preparation method of the compound, pharmaceutical composition containing the compound, and uses of the compound and the pharmaceutical composition in the preparation of neuraminidase inhibitor drugs for treating related diseases.
In vitro radical scavenging and cytotoxic activities of novel hybrid selenocarbamates
Romano, Beatriz,Plano, Daniel,Encío, Ignacio,Palop, Juan Antonio,Sanmartín, Carmen
, p. 1716 - 1727 (2015/03/30)
Novel selenocyanate and diselenide derivatives containing a carbamate moiety were synthesised and evaluated in vitro to determine their cytotoxic and radical scavenging properties. Cytotoxic activity was tested against a panel of human cell lines including CCRF-CEM (lymphoblastic leukaemia), HT-29 (colon carcinoma), HTB-54 (lung carcinoma), PC-3 (prostate carcinoma), MCF-7 (breast adenocarcinoma), 184B5 (non-malignant, mammary gland derived) and BEAS-2B (non-malignant, derived from bronchial epithelium). Most of the compounds displayed high antiproliferative activity with GI50 values below 10 μM in MCF-7, CCRF-CEM and PC-3 cells. Radical scavenging properties of the new selenocompounds were confirmed testing their ability to scavenge DPPH and ABTS radicals. Based on the activity of selenium-based glutathione peroxidases (GPxs), compounds 1a, 2e and 2h were further screened for their capacity to reduce hydrogen peroxide under thiol presence. Results suggest that compound 1a mimics GPxs activity. Cytotoxic parameters, radical scavenging activity and ADME profile point to 1a as promising drug candidate.
Practical synthesis of N-alkyl-N-alkyloxycarbonylaminomethyl prodrug derivatives of acetaminophen, theophylline, and 6-mercaptopurine
Majumdar, Susruta,Sloan, Kenneth B.
, p. 3537 - 3548 (2007/10/03)
We report a novel synthesis of N-alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of acetaminophen, theophylline, and 6-mercaptopurine by alkylation of the corresponding drug molecule with N-alkyl-N- alkyloxycarbonylaminomethyl chlorides in good yield. Most of the alkylating agents were efficiently synthesized by chloromethylation of N-alkyl carbamic acid alkyl esters, which in turn were made from alkyl amines and alkyl chloroformates. In cases where the alkyl chloroformates were not available, synthesis of N-alkyl carbamic acid alkyl esters was accomplished by converting an alcohol to a chloroformate or to an activated acylating agent such as acyl imidazoles or p-nitrophenylcarbonate esters, followed by their reaction with alkyl amines. Copyright Taylor & Francis Group, LLC.
Method for the preparation of aliphatic chloroformates
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Page/Page column 7-8, (2008/06/13)
A method for preparing an aliphatic chloroformate comprising, introducing a mixture of at least one aliphatic hydroxyl compound, phosgene, at least one solvent, and optionally at least one organic base into a flow reactor to obtain a unidirectional flowing reaction mixture. The at least one aliphatic hydroxyl compound comprises at least one aliphatic hydroxyl group. The unidirectional flowing reaction mixture is maintained at a temperature between about 0° C. and about 60° C. to produce a single product stream comprising an aliphatic chloroformate.
Topical delivery of a model phenolic drug: Alkyloxycarbonyl prodrugs of acetaminophen
Wasdo, Scott C.,Sloan, Kenneth B.
, p. 940 - 946 (2007/10/03)
Purpose. To determine whether the delivery of a phenolic parent drug by its alkyloxycarbonyl (AOC) prodrugs through hairless mouse skin would show similar dependencies on water and lipid solubilities that similar prodrugs of more polar heterocyclic amide and imide parent drugs have shown. Methods. Flux through hairless mouse skin from suspensions in isopropyl myristate (JMIPM), solubilities in IPM (SIPM) and water (SAQ), and partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K IPM:4.0) were measured for two series of AOC derivatives of acetaminophen (APAP); their solubilities in pH 4.0 buffer (S4.0) were estimated from SIPM/KIPM: 4.0. Log JMIPM values were calculated from the n = 43 coefficients for the parameters in the transformed Potts-Guy (Roberts-Sloan) equation, and the average error of prediction (Δ log J′IPM) was calculated. The J MIPM, SIPM, S4.0, and molecular weight (MW) data for this series and two other series were combined with the n = 43 database to give a n = 61 database, and new best fit coefficients were determined for the Roberts-Sloan equation: log JMIPM = x + y log SIPM (1 - y) log S4.0 - z MW. Results. All of the 4-AOC-APAP derivatives underperformed based on their predicted log JMIPM (Δ log J′MIPM = 0.275 ± 0.147 log units) and, although the two more water soluble members of this more lipid soluble series were more effective than APAP, they were only marginally so: 2 = -0.322, 0.530, 0.00337 and 0.92, respectively. Conclusions. The topical delivery of a model phenolic drug by its AOC prodrugs through hairless mouse skin from IPM shows the same dependence on SIPM, S 4.0, and MW as the delivery of polar heterocycles by their similar prodrugs.
AMINOBENZOPHENONES AS INHIBITORS OF IL-1-BETA AND TNF-ALPHA
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Page 13-14; 15-16, (2010/02/08)
The present invention relates to compounds of formula (I) wherein R1, R2 and R3 independently represent one or more, same or different substituents selected from the group consisting of hydrogen, halogen, hydroxy, mercapto, trifluoromethyl, amino, (C1-C3)alkyl, (C2-C3)olefinic group, (C1-C3)alkoxy, (C1-C3)alkylthio, (C1-C6)alkylamino, (C1-C3)alkoxycarbonyl, cyano, carbamoyl, or phenyl; R1 and R2 further represented by nitro and R3 by carboxy; R4 represents hydrogen, (C1-C3)alkyl, or allyl; Q represents a bond, or -C(R6)(R7)(-O-C=O)-, in which formula R6 and R7 independently represent hydrogen, trifluoromethyl, or (C1-C4)alkyl; Y represents either (C5-C15)alkyl, (C2-C15)olefinic group, (C3-C10)monocyclic hydrocarbon, or phenyl, any of which may be optionally substituted with one or more, same or different substituents represented by the formula R5; or (C1-C4)alkyl substituted with at least one or more substituents with the formula R5; or Y represents a group of formula -CH2-(Z-O)n-Z where Z is a (C1-C3)alkyl, where n is a integer > 1 and no continuous linear sequence of atoms in the group Y > 15; R5 represents halogen, hydroxy, mercapto, trifluoromethyl, amino, (C1-C3)alkoxy, (C1-C3)alkylthio, (C1-C6)alkylamino, (C1-C3)alkoxycarbonyl, cyano, azido, nitro, -COOH, -CONH2, -CONHR', or -COONR'R' wherein R' stands for (C1-C3)alkyl; X represents oxygen or sulphur, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof. The compounds are valuable in the human and veterinary therapy.
Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for caspases and other enzymes and the use thereof
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, (2008/06/13)
The present invention relates to novel fluorescent dyes, novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of caspases and other enzymes involved in apoptosis in whole cells, cell lines and tissue samples derived from any living organism or organ. The reporter molecules and assay processes can be used in drug screening procedures to identify compounds which act as inhibitors or inducers of the caspase cascade in whole cells or tissues. The reagents and assays described herein are also useful for determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs. The present invention also relates to novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of type 2 methionine aminopeptidase, dipeptidyl peptidase IV, calpain, aminopeptidase, HIV protease, adenovirus protease, HSV-1 protease, HCMV protease and HCV protease.
Tricyclic triazolobenzazepine derivatives, process for producing the same, and antiallergic
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, (2008/06/13)
Tricyclic triazolobenzazepine derivatives in the form or a prodrug are provided. The compounds according to the present invention are those represented by formula (I) and pharmacologically acceptable salts and solvates thereof. The compounds are useful as antiallergic agents and exhibit excellent bioavailability. wherein R1 represents hydrogen, OH, alkyl or phenyl alkyl,R2, R3, R4, and R5 represent hydrogen, halogen, optionally protected hydroxyl, formyl, optionally substituted alkyl, alkenyl, alkoxy or the like, andQ represents a group selected from the following groups (i) to (iv), halogen, or alkoxy:
