A scaleable synthetic route is described to obtain 2-(4-acetylpiperadin-1-yl)-6-[3,5-bis(trifluoromethyl)phenylmethyl]-4-(2-methylphenyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one (1, KRP-103) as a neurokinin (NK)(1) antagonist. The key step in the synthesis is the intramolecular cyclization of N-[3,5-bis(trifluoromethyl)phenylmethyl]-N-(3-hydroxypropyl)-4-chloro-6-(2-methylpheny...

BACKGROUND Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catabolizes 5-fluorouracil (5-FU), which is widely used for chemotherapy in patients with advanced colorectal cancer (CRC). However, the clinical importance of tumor dihydropyrimidine dehydrogenase (DPD) expression in patients with CRC treated with 5-FU remains unclear. MATERIALS AND METHODS We investigated DPD activities in n...

Four series of N-Mannich bases of 3,4-dihydropyrimidine-2(1H)-thiones 7a-g, 8a-g, 9a-g and 10a-g (DHPMs) have been prepared by Mannich reaction with seven different heterocyclic secondary amino compounds 6a-g and formaldehyde 5. In this reaction, four different derivatives of 3,4-dihydropyrimidine-2(1H)-thiones 4a-d have been used as hydrogen active compound. These precursors have been derived ...

Dihydropyrimidine scaffold has a wide range of potential pharmacological activities such as antiviral, antitubercular, antimalarial, anti-inflammatory, and anticancer properties. 5-Lipoxygenase enzyme is an enzyme responsible for the metabolism of arachidonic acid to leukotrienes. The elevated levels of this enzyme and its metabolites in cancer cells have a direct relation on the development of...

PURPOSE Complete or partial loss of dihydropyrimidine dehydrogenase (DPD) function has been described in cancer patients with intolerance to fluoropyrimidine drugs like 5-fluorouracil (5-FU) or Xeloda. The intention of this population study is to assess and to evaluate gene variations in the entire coding region of the dihydropyrimidine dehydrogenase gene (DPYD), which could be implicated in DP...

Azospirillum brasilense glutamate synthase (GltS) is the prototype of bacterial NADPH-dependent enzymes, a class of complex iron-sulfur flavoproteins essential in ammonia assimilation processes. The catalytically active GltS alpha beta holoenzyme and its isolated alpha and beta subunits (162 and 52 kDa, respectively) were analyzed using synchrotron radiation x-ray solution scattering. The GltS ...

The curtius rearrangement of Ethyl 1 (2 – azido – 2 oxoethyl) – 6 – methyl – 2 – oxo – 4 – (3 – substituted) 1, 2, 3, 4 – tetrahydropyrimidine -5 – carboxylate prepared from the readily accessible 4 (1 – substituted) – 5 ethoxy carbonyl – 6 methyl] 3, 4 – dihydropyrimidine – 2 (1H) – one was investigated in presence of ethanol, substituted phenols and substituted amines. The resulting carbamate...

The cellular and clinical pharmacology of fluoropyrimidines is characterized by marked interpatient variability in tumor response and patient tolerance. Understanding the metabolic pathways followed by 5-fluorouracil (5-FU) has led to new strategies to optimize therapy with these important agents. The "fluoropyrimidine phenotype" of tumor cells can be used to determine whether therapy with thes...