2-Desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) is a more water-soluble analogue of the quinazoline-based thymidylate synthase (TS) inhibitor, N10-propargyl-5,8-dideazafolic acid (CB3717). A 3-fold loss in TS inhibitory activity (murine and human TS, Ki = 10 nM) was accompan...

The in vitro metabolism of a variety of 5,8-dideazafolate and 5,8-dideazaisofolate analogues by pig liver folylpolyglutamate synthetase and the specificity of the enzyme for some polyglutamate derivatives of these analogues have been investigated. All 4-oxo-quinazoline analogues were metabolized...

Six new analogues of 5,8-dideazaisofolic acid and 5,8-dideazaisoaminopterin were synthesized in an effort to obtain enhanced antitumor activity. The modifications included the replacement of the 2-amino group by hydrogen or methyl as well as the inclusion of a methyl substituent at position 9. B...

The new folate analogue, 2-desamino-2-methyl-5,8-dideazaisofolic acid, 2c, was synthesized and evaluated using a variety of biochemical and antitumor assays. For purposes of comparison, its 2-desamino, 2b, and 2-amino, 2a, counterparts, as well as N10-propargyl-5,8-dideazafolic acid, 1a, and the...

N-[5-[N-(2-Amino-5-chloro-3,4-dihydro-4-oxoquinazolin-6-yl)methylamino]-2-thenoyl]-l-glutamic acid (Figure 1, Scheme 2) and N-[5-[N-(5-chloro-3,4-dihydro-2-methyl-4-oxoquinazolin-6-yl)methylamino]-2-thenoyl]-l-glutamic acid (Figure 1, Scheme 3), the first reported thiophene analogues of 5-chloro...

A series of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety were designed and synthesized and their cytotoxic activities against five cancer cell lines (NCI-H226, SK-N-SH, HT29, MKN45, and MDA-MB-231) were screened in vitro. Most of them showed moderate to e...

We demonstrated a copper(I)-catalyzed coupling reaction of aryl boronic acids with N,O-acetals and N,N-aminals leading to the synthesis of α-aryl glycines and diarylmethylamines. Under an ambient atmosphere, this catalytic system could be applied to the activation of a C(sp3)-O bond of N,O-acet...

.Polyethylene glycol electrolyte lavage solution (PEG-ELS) is widely used for colon cleansing prior to colonoscopy and colonic surgery. It has recently been shown that coadministration of PEG-ELS and mosapride citrate hydrate (mosapride), a selective 5-HT4–receptor agonist, is clinically useful...

A simple method for determination of mosapride citrate and its metabolite, des-p-fluorobenzyl mosapride (M-1), in equine muscle, liver, kidney, adipose tissue and intestine by liquid chromatography–tandem mass spectrometry has been developed. (±)-4-Amino-5-chloro-2-ethoxy-N-[[4-(2-chlorobenzyl...

.Mosapride citrate (mosapride), a prokinetic agent with 5-HT4–receptor agonistic activity, is known to enhance gastric emptying and alleviate symptoms in patients with functional dyspepsia (FD). As hyperalgesia and delayed gastric emptying play an important role in the pathogenesis of FD, we us...

.Mosapride citrate hydrate (mosapride) has been known to act as a 5-HT4 agonist and to enhance gastric emptying. However, its mode of action, such as time course and dosage effect, on gastric emptying has not been clarified. This study aimed to clarify these points by the breath test using [1-13...

To develop a novel combination tablet which contained 100 mg trimebutine maleate and 5 mg mosapride citrate (TMCT) for the treatment of functional dyspepsia, the wet granulation method was used to prepare TMCTs with various amounts of diluents and stabilizers. The levels of impurities, the stabi...

Simple, rapid and sensitive spectrophotometric methods were developed for the determination of carbamazepine and mosapride citrate drugs in pure and pharmaceutical dosage forms. These methods are based on ion pair and charge transfer complexation reactions. The first method is based on the react...

Prokinetic drugs are used for the management of gastrointestinal motility disorders in horses; however, little is known about their efficacy in donkeys. Therefore, the aim of the present study was to evaluate the effect of different doses of mosapride citrate on duodenal and cecal motility in no...

ObjectiveConstipation is one of the most common gastrointestinal complications suspected to degrade the quality of life in diabetic patients. Mosapride citrate is a novel selective 5-HT4 receptor agonist, which enhances gastric emptying and motility in the upper gastrointestinal tract facilitati...

ObjectivesVocal process granulomas have a high tendency for persistence despite many treatment alternatives. Anti-reflux medications or botulinum toxin A injections are the main current therapies. There are no studies that compare the effects on vocal process granuloma of proton pump inhibitors ...

Computational modeling was applied to study the intermolecular interactions in the pre-polymerization mixture and find a suitable functional monomer to use in the design of a new molecularly imprinted polymer (MIP) for mosapride citrate which is considerably a large molecule (as the citrate ion ...

Histone deacetylases (HDACs) are attractive therapeutic targets for the treatment of cancer and other diseases. It has four classes (I-IV), among them especially class I isozyme are involved in promoting tumor cells proliferation, angiogenesis, differentiation, invasion and metastasis and also v...

A series of novel quinazoline derivatives bearing various C-6 benzamide substituents were synthesized and evaluated as EGFR inhibitors, and most showed significant inhibitory potency against EGFR kinase. In particular, compound 6g possessed potent inhibitory activity against EGFR wild-type (IC50...

Dimethyl and morpholinyl carbamoyl imines of trifluoropyruvate 1a,b were synthesized and studied in cyclocondensation and cycloaddition reactions. Cyclocondensation of carbamoyl imines 1a,b with benzyl urea, benzamidine, 3-aminocrotonitryl, 6-aminouracil, and acetylacetone led to 5-membered trif...