100599-91-5Relevant articles and documents
Arylbiamidines: Synthesis and structural studies en route to anticancer applications
Grytsai, Oleksandr,Gon?alves, Leticia Christina Pires,Bardovskyi, Rostyslav,Hamouda-Tekaya, Nedra,Rocchi, Stéphane,Ronco, Cyril,Benhida, Rachid
, p. 11893 - 11897 (2021)
Biamidines are a unique and poorly studied class of nitrogenous compounds prone to tautomerization and H-bonding. Four series of heteroaryl diarylbiamidines were synthesized and the antimelanoma activity and physicochemical properties of the resulting 37 new compounds were evaluated. The dimethylthiazolyl 3-bromophenyl biamidine derivative B6 inhibits the growth of six different melanoma cell lines, having higher activity than the positive control drug, the B-RAF inhibitor PLX4032. This study introduces diarylbiamidines as promising frameworks for drug discovery.
Pyrimidine derivatives and processes for the preparation thereof
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Page column 19, (2008/06/13)
The present invention relates to novel pyrimidine derivatives of formula (I) or pharmaceutically acceptable salts thereof which possess an excellent anti-secretory activity, pharmaceutical compositions containing the same as an active ingredient, their novel intermediates, and processes for the preparation thereof wherein: when A is piperidin-1-yl or —NH—B, wherein B is C3-C4alkyl, C3-C4alkenyl, C3-C7cycloalkyl, C1-C3alkoxyethyl, phenylethl which may be substituted or unsubstituted, 3-trifluoromethylphenylmethyl, 1-naphthylmethyl, 4-methylthiazol-2-yl or 4-phenylthiazol-2-yl, R1is hydrogen or methyl; and R2, R3, R4and R5are hydrogen; or when A is a group of formula (II); when R1is hydroxymethyl or C1-C3alkoxymethyl, R2, R3, R4, R5and R6are hydrogen; and R7is hydrogen or halogen; or when R1is hydrogen or methyl, R7is hydrogen or halogen; and one or two of R2, R3, R4, R5and R6is hydroxy, methoxy, or a group of formula (III) wherein Z is C1-C4alkyl, substituted or unsubstituted C1-C4alkenyl, cyloalkyl, benzyloxyalkyl, alkoxycarbonylalkyl, morpholinomethyl, piperidinomethyl, 4-substituted-piperazinomethyl, substituted or unsubstituted phenyl, naphthyl, substituted or unsubstituted benzyl, thiophen-2-yl-methyl, 1-substituted-pyrrolidin-2-yl or —CHR8NHR9, wherein R8is hydrogen, methyl, isopropyl, benzyl, benzyloxymethyl, methylthioethyl, benzyloxycarbonylmethyl, carbamolymethyl, carbamoylethyl, or 1-benzylimidazol-4-ylmethyl and R9is hydrogen or t-butoxycarbonyl; and the others are hydrogen or methyl.
Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor histamine antagonists
Young,Mitchell,Brown,Ganellin,Griffiths,Jones,Rana,Saunders,Smith,Sore,Wilks
, p. 656 - 671 (2007/10/02)
A rational approach to the design of centrally acting agents is presented, based initially upon a comparison of the physicochemical properties of three typical histamine H2 receptor antagonists which do not readily cross the blood-brain barrier with those of the three brain-penetrating drugs clonidine (6), mepyramine (7), and imipramine (8). A good correlation was found between the logarithms of the equilibrium brain/blood concentration ratios in the rat and the partition parameter, Δ log P, defined as log P (1-octanol/water) - log P (cyclohexane/water), which suggests that brain penetration might be improved by reducing overall hydrogen-bonding ability. This model has been employed as a guide in the design of novel brain-penetrating H2 antagonists by the systematic structural modification of representatives of different structural types of H2 antagonists. Although marked increases in brain penetration amongst congeners of cimetidine (1), ranitidine (9), and tiotidine (10) were achieved, no compound was found with an acceptable combination of H2 antagonist activity (-log K(B) in the guinea pig atrium > 7.0) and brain penetration (steady-state brain/blood concentration ratio > 1.0). Conversely, structural modification of N-[[(piperidinylmethyl)phenoxy]propyl]acetamide (30) led to several potent, novel compounds which readily cross the blood-brain barrier. One of these, zolantidine (SK&F 95282, 41), whose -log K(B) is 7.46 and steady-state brain/blood ratio is 1.4, has been identified for use in studying histaminergic H2 receptor mechanisms in brain. Comparison of Δ log P values with the logarithms of the brain/blood ratios for 20 structurally diverse compounds for which data became available confirms a highly significant correlation and supports the general validity of this model.
