39096-01-0Relevant articles and documents
ADENOSINE RECEPTOR BINDING COMPOUNDS
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Paragraph 00248, (2020/02/06)
The present invention relates to pharmaceutical compounds and compositions of Formula (I) and methods of treatment using the compounds and compositions, especially for the treatment and/or prevention of a proliferation disorder, such as cancer. Compounds of Formula (I) as further described herein are shown modulators of the adenosine A2A receptor and exhibit antiproliferative activity. Accordingly, these compounds are useful to treat proliferative disorders such as cancer, and other adenosine receptor-related conditions including an inflammatory disease, renal disease, diabetes, vascular disease, lung disease, or an autoimmune disease.
Gamma radiolysis of hydrophilic diglycolamide ligands in concentrated aqueous nitrate solution
Horne, Gregory P.,Wilden, Andreas,Mezyk, Stephen P.,Twight, Liam,Hupert, Michelle,St?rk, Andrea,Verboom, Willem,Mincher, Bruce J.,Modolo, Giuseppe
supporting information, p. 17005 - 17013 (2019/11/26)
The radiation chemistry of a series of hydrophilic diglycolamides (DGAs: TEDGA, Me-TEDGA, Me2-TEDGA, and TPDGA) has been investigated under neutral pH, concentrated aqueous nitrate solution conditions. A combination of steady-state gamma and time-resolved pulsed electron irradiation experiments, supported by advanced analytical techniques and multi-scale modeling calculations, have demonstrated that: (i) the investigated hydrophilic DGAs undergo first-order decay with an average dose constant of (-3.18 ± 0.23) × 10-6 Gy-1; (ii) their degradation product distributions are similar to those under pure water conditions, except for the appearance of NOx adducts; and (iii) radiolysis is driven by hydroxyl and nitrate radical oxidation chemistry moderated by secondary degradation product scavenging reactions. Overall, the radiolysis of hydrophilic DGAs in concentrated, aqueous nitrate solutions is significantly slower and less structurally sensitive than under pure water conditions, similar to their lipophilic analogs. Acid hydrolysis, not radiolysis, is expected to limit their useful lifetime. These findings are promising for the deployment of hydrophilic DGAs as actinide aqueous phase stripping and hold-back agents, due to the presence of high concentrations of nitrate in envisioned large-scale process conditions.
METHOD FOR PRODUCING MONOMETHYL FUMARATE COMPOUNDS
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Page/Page column 36, (2017/07/14)
The present invention relates to a novel method for preparing monomethyl fumarate, which can preferably be used in the treatment and/or prevention of systemic diseases, autoimmune diseases, inflammatory diseases such as multiple sclerosis and psoriasis. Further, the present invention relates to the use of specific compounds as intermediates in the process for preparing a monomethyl fumarate prodrug.
3-Aminocarbonyl-substituted benzoylcyclohexanediones and their use as herbicides
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Page/Page column 9, (2011/09/16)
What is described are 3-aminocarbonyl-substituted benzoylcyclohexanediones of the formula (I) as herbicides. In this formula (I), R1 to R5 are radicals such as hydrogen, organic radicals such as alkyl, and other radicals such as halo
Development of 3-methoxy-4-benzyloxybenzyl alcohol (MBBA) resin as polymer-supported synthesis support: Preparation and benzyl ether cleavage by DDQ oxidation
Huang, Qiang,Zheng, Bao-Zhong,Long, Quan
experimental part, p. 203 - 207 (2010/11/04)
3-Methoxy-4-benzyloxybenzyl alcohol (MBBA) resin was synthesized by a two-step sequence under microwave irradiation involving the reaction of commercially available Merrifield resin with vanillin, followed by reduction with sodium borohydride. MBBA resin was treated with bromides in the presence of sodium hydride to afford the corresponding resin-bound benzyl ethers. Cleavage of the resin-bound benzyl ethers from the MBBA resin was carried out using 2,3-dichloro-5,6-dicyanobenzoqunone (DDQ) to give the corresponding alcohols in good yields. Moreover, the recovery, regeneration, and reuse of this polymer support could be achieved easily. MBBA resin can be developed as a kind of solid-phase synthesis bead of alcohols. Indian Academy of Sciences.
A novel method for the synthesis of 2,2-dimethyl-1,3-dioxolan-4-one, and its reactions with secondary amines
Boyko, Vyacheslav I.,Rodik, Roman V.,Severenchuk, Inna N.,Voitenko, Zoya V.,Kalchenko, Vitaly I.
, p. 2095 - 2096 (2008/02/12)
A novel method for the synthesis of 2,2-dimethyl-1,3-dioxolan-4-one, as well as the syntheses of amides of glycolic acid via its reaction with secondary amines, is described. Georg Thieme Verlag Stuttgart.
Stability studies of some glycolamide ester prodrugs of niflumic acid in aqueous buffers and human plasma by HPLC with UV detection
Talath, Sirajunisa,Shirote, Pramod J.,Lough, W. John,Gadad, Andanappa K.
, p. 631 - 639 (2008/02/12)
Glycolamide esters (compounds 1-17) of 2-(3-trifluoromethyl-phenylamino) nicotinic acid (niflumic acid, CAS 4394-00-7) have been synthesized and evaluated as possible prodrugs. In-vitro hydrolysis studies were conducted at selected pH values (1.2, 3.5, 4.8, 7.4 and 7.8) and in human plasma at 37 ± 0.5 °C using HPLC with UV detection. The aqueous (pH 7.4 and 7.8) and enzymatic rates of hydrolysis were substantially affected by the nature of promoieties in this series. The compounds showed good chemical stability in the buffers of low pH values (1.2, 3.5 and 4.8) and appreciable hydrolysis under alkaline conditions and in human plasma. They exhibited long hydrolytic half-lives of 7-46 h in aqueous buffer solutions (pH 7.4 and 7.8) and 14-21 min in human plasma, respectively. It was observed that N,N-disubstituted and cyclic glycolamide derivatives showed 2 fold more hydrolysis in the alkaline pH than monosubstituted derivatives, whereas the piperidino and thiomorpholino derivatives did not undergo chemical hydrolysis. The compounds contain two possible sites for hydrolysis with an increased hydrolytic susceptibility at the terminal aliphatic carbonyl site in aqueous buffers and human plasma solutions. They were found to be cleaved at two hydrolytic carbonyls, namely the nicotinyl (2-5% in enzymatic hydrolysis) and the aliphatic site (7-55% and 70-85% in buffer and plasma hydrolysis, respectively) as revealed by HPLC analysis. The glycolamide ester prodrugs of niflumic acid underwent chemical and enzymatic hydrolysis to release mainly the metabolite 2- (3-trifluoromethyl-phenylamino) nicotinic acid carboxymethyl ester (III) and not the parent drug 2-(3-trifluoromethyl-phenylamino) nicotinic acid. The structure of the metabolite was confirmed by liquid chromatography-mass spectroscopy (LCMS). ECV · Editio Cantor Verlag.
Prodrugs of phosphonates
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, (2008/06/13)
There are disclosed novel oral prodrugs of phosphonate nucleotide analogs which are hydrolyzable under physiological conditions to yield compounds which are useful as antiviral agents, especially as agents effective against RNA and DNA viruses. They may also find use as antitumor agents.
Cyclic imidate salts in acyclic stereochemistry: Diastereoselective syn-epoxidation of 2-alkyl-4-enamides to epoxyamides
Maligres,Weissman,Upadhyay,Cianciosi,Reamer,Purick,Sager,Rossen,Eng,Askin,Volante,Reider
, p. 3327 - 3338 (2007/10/03)
Reaction of 2-alkyl-4-enamides with I+ and aqueous sodium bicarbonate results in the diastereoselective formation of the corresponding iodohydrins with essentially no iodolactone by-product. The reaction appears to proceed through a cyclic imidate type intermediate. This methodology has been successfully employed for the synthesis of the epoxide intermediate of the orally active HIV-1 protease inhibitor MK-639 (indinavir sulfate).
Synthesis, Oral Bioavailability Determination, and in Vitro Evaluation of Prodrugs of the Antiviral Agent 9-adenine (PMEA)
Starrett, John E.,Tortolani, David R.,Russell, John,Hitchcock, Michael J. M.,Whiterock, Valerie,et al.
, p. 1857 - 1864 (2007/10/02)
A series of phosphonate prodrugs were evaluated in an attempt to increase the oral bioavailability of the anti-HIV agent 9-adenine (PMEA; 1).The majority of the bis(alkyl ester) and bis(alkyl amide) prodrugs were prepared by alcohol or amine displacement of dichlorophosphonate 2.Basic hydrolysis of the bis(esters) or bis(amides) provides the corresponding monoesters or momoamides.Synthesis of bis phosphonates 10a-c was accomplished by alkylation of PMEA with the appropriate chloromethyl ether in the presence of N,N'-dicyclohexylmorpholinecarboxamidine.The systemic levels of PMEA following oral administration of a PMEA prodrug to rats were determined by measuring the concentration of PMEA in the urine for 48 h after administration of the prodrug.The oral bioavailability of PMEA employing this method was determined to be 7.8percent.Oral dosing with bis(alkyl) phosphonates 3a,b resulted in apparent absorption of the prodrugs (equal or >40percent), although neither of the esters were completely cleaved to liberate the parent phosphonate PMEA.The mono(alkyl esters) 7a-e and 8a,b exhibited poor oral bioavailability (equal or phosphonates 10a-c demonstrated significantly improved oral bioavailabilities of 17.6percent, 14.6percent, and 15.4percent, respectively.When evaluated in vitro against HSV-2, (acyloxy)alkyl phosphonates 10a-c were greater than 200-fold more active than PMEA.
