123367-26-0Relevant articles and documents
Phenylamino-pyrimidine (PAP) - Derivatives: A new class of potent and highly selective PDGF-Receptor autophosphorylation inhibitors
Zimmermann, Juerg,Buchdunger, Elisabeth,Mett, Helmut,Meyer, Thomas,Lydon, Nicholas B.,Traxler, Peter
, p. 1221 - 1226 (1996)
Phenylamino-pyrimidines represent a novel class of inhibitors of the PDGF-receptor autophosphorylation with a high degree of selectivity versus other tyrosine and serine/threonine kinases. Optimum activity of ca 10 nM (IC50) was observed when the phenylamino-group which is attached to the pyrimidine carries a benzamide-moiety with a lipophilic substituent in 4-position. Copyright
Imatinib intermediate as a two in one dual channel sensor for the recognition of Cu2+ and I- ions in aqueous media and its practical applications
Patil, Samadhan R.,Nandre, Jitendra P.,Jadhav, Devising,Bothra, Shilpa,Sahoo,Devi, Manisha,Pradeep, Chullikkattil P.,Mahulikar, Pramod P.,Patil, Umesh D.
, p. 13299 - 13306 (2014)
An imatinib intermediate, 6-methyl-N-[4-(pyridin-3-yl)pyrimidin-2-yl] benzene-1,3-diaminepyridopyrimidotoluidine (PPT-1), was developed for the colorimetric sensing of Cu2+ ions in aqueous solution. With Cu 2+, the receptor PPT-1 showed a highly selective naked-eye detectable color change from colorless to red over the seventy other tested cations. The colorimetric sensing ability of PPT-1 was successfully utilized in the preparation of test strips and supported silica for the real samples analysis to detect Cu2+ ions from 100% aqueous environment. Moreover, the iodide-sensing ability of receptor PPT-1 was explored among the ten examined anions.
New bis-, tris- and tetrakis(pyrazolyl)borate ligands with 3-pyridyl and 4-pyridyl substituents: Synthesis and coordination chemistryt
Adams, Harry,Batten, Stuart R.,Davies, Graham M.,Duriska, Martin B.,Jeffery, John C.,Jensen, Paul,Lu, Jinzhen,Motson, Graham R.,Coles, Simon J.,Hursthouse, Michael B.,Ward, Michael D.
, p. 1910 - 1923 (2005)
The new ligands dihydrobis[3-(4-pyridyl)pyrazol-1-yl]borate [Bp 4ph]-, hydrotris[3-(4-pyridyl)pyrazol-1-yl]borate [Tp 4py]-, tetrakis[3-(4-pyridyl)pyrazol-l-yl]borate [Tkp 4py]-, dihydrobis[3-(3-pyridyl)pyrazol-l-yl]borate [Bp 3py]-, hydrotris[3-(3-pyridyl)pyrazol-1-yl]borate [Tp 3py]- and tetrakis[3-(3-pyridyl)pyrazol-l-yl]borate [Tkp 48]- are derivatives of the well known bis-, tris- and tetrakis-(pyrazolyl)borate cores, bearing 4-pyridyl or 3-pyridyl substituents attached to the pyrazolyl C3 positions. These pyridyl groups cannot chelate to the metal ions in the poly(pyrazolyl) cavity but are externally directed. Structural studies on a range of metal complexes show how, in many cases, coordination of these pendant pyridyl groups to the M(pyrazolyl) n core of an adjacent metal complex fragment results in formation of coordination oligomers or polymeric networks. [Tl(Bp3py)], [Tl(Bp4ph)] and [Tl(Tp4py] form one-dimensional polymeric chains via coordination of one of their pendant pyridyl units to the Tl(I) centre of an adjacent complex fragment; in contrast, in [Tl(Tp3py)] coordination of all three pendant pyridyl units to separate Tl(I) neighbours results in formation of a two-dimensional polymeric sheet. In [Tl(Tkp 3py)] and [Tl(Tkp4py)] the Tl(I) is coordinated by two or three of the four pyrazolyl arms, respectively; bridging interactions of pendant 4-pyridyl groups with adjacent Tl(I) centres result in a two-dimensional sheet forming in each case. In Ag(Tkp4py) each Ag(I) ion is coordinated by two pyrazolyl rings, and two bridging pyridyl ligands from other complex units, resulting in a one-dimensional chain consisting of pairs of cross-linked zigzag chains. In contrast to these polymeric coordination networks, the structures of [Cu(Tp4py)] and [(Tp3py)Cd(CH3CO2)] are dimers, with a pendant pyridyl residue from the first metal centre attaching to a vacant coordination site on the second, and vice versa; these dimers are stabilised by π-stacking interactions between sections of the two ligands. [Ni(Tp3py)2] is monomeric, with an octahedral coordination geometry arising from two tris(pyrazolyl)borate chelates; the array of pendant 3-pyridyl groups is involved only in intramolecular hydrogen-bonding. [(Tp 4py)Re(CO)3] is also monomeric, with & facial arrangement of three pyrazolyl ligands and three carbonyls, with the pendant 4-pyridyl groups not further coordinated. [(Tp3py)Re(CO) 3], based on the related ligand hydrotris[3-(2-pyridyl)pyrazol-1-yl] borate, has a similar fac-(CO)3(pyrazolyl)3 coordination geometry. The Royal Society of Chemistry 2005.
Acid-base profiling of imatinib (Gleevec) and its fragments
Szakács, Zoltán,Béni, Szabolcs,Varga, Zoltán,?rfi, László,Kéri, Gy?rgy,Noszál, Béla
, p. 249 - 255 (2005)
The site-specific basicities of imatinib (Gleevec, a new signal transduction inhibitor drug of chronic myeloid leukemia) and two of its fragment compounds were quantitated in terms of protonation macroconstants, microconstants, and group constants by NMR-pH and pH-potentiometric titrations. Sequential protonation of imatinib follows the N34, N11, N31, N13 order, in which N11 and N31 show commensurable basicity, but negligible intramolecular interaction. Fragment compounds include two "halves" of imatinib, and their moiety-specific basicities confirm the NMR-based protonation sequence of the parent compound. NMR-pH profiles, macro- and/or microscopic protonation schemes, and species-specific distribution diagrams are presented. On the basis of these data, imatinib is shown to be predominantly neutral, monocationic, and tricationic at intestinal, blood, and gastric pH, respectively. The molecular hypotheses on imatinib binding to the Bcr-Abl oncogene fusion protein are interpreted at the site-specific level in view of the moiety basicities of imatinib.
Discovery of highly potent tubulin polymerization inhibitors: Design, synthesis, and structure-activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines
Huo, Xian-Sen,Jian, Xie-Er,Ou-Yang, Jie,Chen, Lin,Yang, Fang,Lv, Dong-Xin,You, Wen-Wei,Rao, Jin-Jun,Zhao, Pei-Liang
, (2021/05/10)
By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells). In addition, 5e dose-dependently arrested HeLa in G2/M phase through the alterations of the expression levels of p-cdc2 and cyclin B1, and caused HeLa cells apoptosis by regulation of expressions of cleaved PARP. Further evidence demonstrated that 5e effectively inhibited tubulin polymerization and was 3-fold more powerful than positive control CA-4. Moreover, molecular docking analysis indicated that 5e overlapped well with CA-4 in the colchicine-binding site. These studies demonstrated that 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine skeleton might be used as the leading unit to develop novel tubulin polymerization inhibitors as potential anticancer agents.
Structure-Based Discovery of Pyrimidine Aminobenzene Derivatives as Potent Oral Reversal Agents against P-gp- And BCRP-Mediated Multidrug Resistance
Qiu, Qianqian,Zou, Feng,Li, Huilan,Shi, Wei,Zhou, Daoguang,Zhang, Ping,Li, Teng,Yin, Ziyu,Cai, Zilong,Jiang, Yuxuan,Huang, Wenlong,Qian, Hai
, p. 6179 - 6197 (2021/06/01)
Overexpression of ATP binding cassette (ABC) transporters, including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), is an important factor leading to multidrug resistance (MDR) in cancer treatments. Three subclasses of dual inhibitors of P-gp and BCRP were designed based on the active moieties of BCRP inhibitors, tyrosine kinase inhibitors, and P-gp inhibitors, of which compound 21 possessed low cytotoxicity, high reversal potency, and good lipid distribution coefficient. 21 also increased the accumulation of Adriamycin (ADM) and Mitoxantrone (MX), blocked Rh123 efflux, and made no change in the protein expression of P-gp and BCRP. Importantly, coadministration of 21 can significantly improve the oral bioavailability of paclitaxel (PTX). It was also demonstrated that 21 significantly inhibited the growth of K562/A02 xenograft tumors by increasing the sensitivity of ADM in vivo. In summary, 21 has the potential to overcome MDR caused by P-gp and BCRP and to improve the oral bioavailability of PTX.
