- Microwave-assisted synthesis and biological evaluation of novel uracil derivatives inhibiting human thymidine phosphorylase
-
New 5-chloro-6-substituted-uracil derivatives have been prepared by microwave assisted-synthesis and tested in vitro as thymidine phosphorylase inhibitors. One of these compounds showed potent inhibitory activity, with an IC50 value in the subm
- Corelli, Federico,Botta, Maurizio,Lossani, Andrea,Pasquini, Serena,Spadari, Silvio,Focher, Federico
-
-
Read Online
- Preparation method of (2-methylamine-ethyl)-tert-butyl carbamate
-
The invention discloses a preparation method of (2-methylamine-ethyl)-tert-butyl carbamate, and belongs to the technical field of organic chemical synthesis. The preparation method comprises followingsteps: 1, imidazole is dissolved in dichloromethane, and di-tert-butyl dicarbonate ester is added at room temperature, reaction is carried out for 2 to 3h at room temperature, and water washing drying are carried out so as to obtain an intermediate; and 2, the intermediate is dissolved in toluene, N-methylethylenediamine is added, an obtained mixture is heated to 60 to 70 DEG C, reaction is carried out for 2 to 4h, reduced pressure distillation is carried out to remove toluene, and purification is carried out so as to obtain (2-methylamine-ethyl)-tert-butyl carbamate. The operation steps arefew; by-product content is reduced with ensured (2-methylamine-ethyl)-tert-butyl carbamate synthesis yield; cost is relatively low; and batch production requirements are satisfied.
- -
-
Paragraph 0024-0029
(2019/07/01)
-
- Design and synthesis of novel PRMT1 inhibitors and investigation of their binding preferences using molecular modelling
-
Protein arginine methyltransferase 1 (PRMT1) catalyses the methylation of substrate arginine by transferring the methyl group from SAM (S-adenosyl-L-methionine), which leads to the formation of S-adenosyl homocysteine (SAH) and methylated arginine. We have shown previously that the Asp84 on PRMT1 could be a potential inhibitor binding site. In the current study, 28 compounds were designed and synthesized that were predicted to bind the Asp84 and substrate arginine sites together. Among them, 6 compounds were identified as potential PRMT1 inhibitors, and showed strong inhibitory effects on cancer cell lines, especially HepG2. The most potent PRMT1 inhibitor, compound 13d, was selected for molecular dynamic simulations to investigate binding poses. Based on the free energy calculations and structural analysis, we predicted that the ethylenediamine group would tightly bind to Asp84, and the trifluoromethyl group should occupy part of substrate arginine binding site, which is consistent with our original goal. Our results show for the first time that PRMT1 inhibitors can target the Asp84 binding site, which will be helpful for future drug discovery studies.
- Yang, Hao,Ouyang, Yifan,Ma, Hao,Cong, Hui,Zhuang, Chunlin,Lok, Wun-Taai,Wang, Zhe,Zhu, Xuanli,Sun, Yutong,Hong, Wei,Wang, Hao
-
p. 4635 - 4642
(2017/09/29)
-
- MACROCYCLIC ACTIVIN-LIKE RECEPTOR KINASE INHIBITORS
-
The present invention relates to macrocyclic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of Activin-like receptor kinases, more in particular ALK1 and/or ALK2 and/or mutants thereof, for use in the diagnosis, prevention and/or treatment of ALK1-kinase and/or ALK2-kinase associated diseases. Moreover, the present invention provides methods of using said compounds, for instance as a medicine or diagnostic agent.
- -
-
Page/Page column 101
(2016/10/04)
-
- An enzyme and its optional [...] modified ketone and inhibitor composition comprising (by machine translation)
-
PROBLEM TO BE SOLVED: ketone-containing acrylic misuse, abuse or overload is prevented for a new takable amt. provitamin drag pain. SOLUTION: a compound represented by the following formula is represented, in which the drag oxystyrene provitamin hydrocodone ketone-containing acrylic. Pre-selected drug profile is modified and the ketone and schisandrin [...] holding hung contg. compsn. method for administration to a patient. Selected drawing: no (by machine translation)
- -
-
-
- COMPOUNDS AND METHODS
-
Disclosed are compounds having formula I, wherein X1, X2, X3, R1, R2, R3, R4, R5, Y, A, Z, L, m and n are as defined herein, and methods of making and using the same.
- -
-
Page/Page column 40; 43
(2013/03/26)
-
- IMMUNOMODULATORY CONJUGATES
-
The present invention provides an immunomodulatory compound comprising a carbohydrate polymer comprising mannose, wherein the carbohydrate polymer is conjugated to at least one immune modulator. The present invention also provides for the use of this compound in immunomodulatory compositions for vaccination and gene therapy methods, together with processes for its preparation.
- -
-
Page/Page column 100
(2013/05/23)
-
- COMPOSITIONS COMPRISING ENZYME-CLEAVABLE OPIOID PRODRUGS AND INHIBITORS THEREOF
-
Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise an opioid prodrug that provides enzymatically-controlled release of an opioid, and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the opioid from the opioid prodrug so as to attenuate enzymatic cleavage of the opioid prodrug.
- -
-
-
- COMPOSITIONS COMPRISING ENZYME-CLEAVABLE OPIOID PRODRUGS AND INHIBITORS THEREOF
-
The present disclosure provides pharmaceutical compositions, and their methods of use, where the pharmaceutical compositions comprise a prodrug that provides enzymatically-controlled release of a drug and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the drug from the prodrug so as to attenuate enzymatic cleavage of the prodrug. The disclosure provides pharmaceutical compositions which comprise an enzyme inhibitor and a prodrug that contains an enzyme-cleavable moiety that, when cleaved, facilitates release of the drug.
- -
-
-
- COMPOSITIONS COMPRISING ENZYME-CLEAVABLE PRODRUGS OF ACTIVE AGENTS AND INHIBITORS THEREOF
-
The present disclosure provides pharmaceutical compositions, and their methods of use, where the pharmaceutical compositions comprise a prodrug that provides enzymatically-controlled release of a drug and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the drug from the prodrug so as to attenuate enzymatic cleavage of the prodrug. The disclosure provides pharmaceutical compositions which comprise an enzyme inhibitor and a prodrug that contains an enzyme-cleavable moiety that, when cleaved, facilitates release of the drug.
- -
-
-
- COMPOSITIONS COMPRISING ENZYME-CLEAVABLE PRODRUGS OF ACTIVE AGENTS AND INHIBITORS THEREOF
-
The present disclosure provides pharmaceutical compositions, and their methods of use, where the pharmaceutical compositions comprise a prodrug that provides enzymatically-controlled release of a drug and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the drug from the prodrug so as to attenuate enzymatic cleavage of the prodrug. The disclosure provides pharmaceutical compositions which comprise an enzyme inhibitor and a prodrug that contains an enzyme-cleavable moiety that, when cleaved, facilitates release of the drug.
- -
-
-
- FATTY ACID ACETYLATED SALICYLATES AND THEIR USES
-
The invention relates to Fatty Acid Acetylated Salicylate Derivatives; compositions comprising an effective amount of a Fatty Acid Acetylated Salicylate Derivative; and methods for treating or preventing an inflammatory disorder comprising the administration of an effective amount of a Fatty Acid Acetylated Salicylate Derivative.
- -
-
Page/Page column 120
(2010/03/04)
-
- COMPLEX COMPOUND AND MRI PROBE MADE OF SAME
-
Novel gadolinium complex compounds responsive to ions and compounds other than zinc ion, as well as MRI probes made of the compounds are disclosed. Since the gadolinium complex compounds of the present invention such as that represented by the following structural formula exhibit responsiveness to potassium ion, calcium ion, glucose or the like, by using the gadolinium complex compounds of the present invention as a MRI probe, the ion or compound in a living body can be detected and concentration distribution thereof may be determined.
- -
-
Page/Page column 18-19
(2008/06/13)
-
- Substituted piperidine compounds useful as modulators of chemokine receptor activity
-
The invention provides compounds of formula (I) wherein R1, R2, R3, R6, Z, Q, m, n, X1, X2, X3, X4 and T are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them, and their use in therapy, especially for the treatment of chemokine receptor related diseases and conditions
- -
-
Page/Page column 77
(2008/06/13)
-
- THIAZOLIDINE DERIVATIVES
-
An object of the present invention is to provide novel thiazolidine derivatives which are useful as drugs. The thiazolidine derivatives according to the present invention are compounds represented by the following general formula [I] and salts thereof, wherein R 1is alkyl, hydroxy, alkoxy, alkoxyalkyl, phenyl, phenylalkyl, phenylalkoxy, phenoxy, phenoxyalkyl, amino, alkylamino or a nonaromatic heterocycle; R 2is H or alkyl; R 3is H, alkyl or phenyl; R 4is H or alkyl; R 5is alkyl, halogenoalkyl, hydroxy, alkoxy, phenyl, phenylalkoxy, phenoxy, carboxyl, alkoxycarbonyl, phenylalkoxycarbonyl or an aromatic heterocycle; A 1is alkylene; and A 2is alkylene.
- -
-
-
- ORALLY ACTIVE RENIN INHIBITORS
-
This invention relates to compounds of the formula STR1 wherein Q, Z, D, E, R 3, R 4, R 5 and R 6 are defined as below, and the pharmaceutically acceptable salts thereof are disclosed. The compounds are useful as antihypertensive agents.
- -
-
-
- Orally active renin inhibitors
-
This invention relates to compounds of the formula wherein Q, Z, D, E, R3, R?, R? and R? are defined as below, and the pharmaceutically acceptable salts thereof are disclosed. The compounds are useful as antihypertensive agents.
- -
-
-
- Cyclization-Activated Prodrugs. Basic Carbamates of 4-Hydroxyanisole
-
A series of basic carbamates of 4-hydroxyanisole was prepared and evaluated as progenitors of this melanocytotoxic phenol.All of the carbamates were relatively stable at low pH but released 4-hydroxyanisole cleanly at pH 7.4 at rates that were structure dependent.A detailed study of the N-methyl-N-carbamate showed that generation of the parent phenol followed first-order kinetics with t1/2 = 36.3 min at pH 7.4, 37 deg C, and was accompanied by formation of N,N'-dimethylimidazolidinone.These basic carbamates are examples of cyclization-activated prodrugs in which generation of the active drug is not linked to enzymatic cleavage but rather depends solely upon a predictable, intramolecular cyclization-elimination reaction.
- Saari, Walfred S.,Schwering, John E.,Lyle, Paulette A.,Smith, Steven J.,Engelhardt, Edward L.
-
-