125055-50-7Relevant articles and documents
Synthesis and inverse virtual screening of new bi-cyclic structures towards cancer-relevant cellular targets
Bhogal, Amrit,Biancalani, Claudio,Cesari, Nicoletta,Cilibrizzi, Agostino,Crocetti, Letizia,Floresta, Giuseppe,Giovannoni, Maria Paola,Nazir, Shabnam,Vergelli, Claudia
, (2022/02/21)
We report here synthetic approaches to access new classes of small molecules based on three heterocyclic scaffolds, i.e. 3,7-dihydropyrimido[4,5-d]pyridazine-4,8-dione, 1,8-naphthyridin-4(1H)-one and 4H-pyrido[1,2-a]pyrimidin-4-one. The bi-cyclic structure 3,7-dihydropyrimido[4,5-d]pyridazine-4,8-dione is a new heterocycle, described here for the first time. In silico methodologies of inverse virtual screening have been used to preliminary analyse the molecules, in order to explore their potential as hits for chemical biology investigations. Our computational study has been conducted with 43 synthetically accessible small molecules towards 31 cellular proteins involved in cancer pathogenesis. Binding energies were quantified using molecular docking calculations, allowing to define the relative affinities of the ligands for the cellular targets. Through this methodology, 16 proteins displayed effective interactions with distinct small molecules within the matrix. In addition, 23 ligands have demonstrated high affinity for at least one cellular protein, using as reference the co-crystallised ligand in the X-ray structure. The evaluation of ADME and drug score for selected hits also highlights that these new molecular series can serve as sources of lead candidates for further structure optimisation and biological studies.
Nitrogen bridgehead compounds. Part 92.* Synthesis of 4-oxo-4H-pyrido[1,2-a]pyriniidine-3-carboxamides, -3-acetamides and their tetrahydro derivatives
Hermecz, Istvan,Vasvari-Debreczy, Lelle,Horvath, Agnes,Sipos, Judit,Balogh, Maria,Podanyi, Benjamin,Kovacs, Katalin
, p. 515 - 528 (2007/10/03)
N-Substituted 4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides (6-45), -3-acetamides (59-61) and 1,6-dimethyl-4-oxo-1,6,7,8-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carhoxamides (63-73) were synthesized in the reaction of amines and mixed anhydrides, prepared from 4-oxo-4H-pyrido[1,2-a]-pyrimidine-3-carboxylic acids (4), -3-acetic acids (58) and 1,6-dimethyl-4-oxo-1,6,7,8-tetrahydropyrido-[1,2-a]pyrimidine-3-carhoxylic acid (62) with methyl or ethyl chloroformate in the presence of triethylamine. Whereas the reaction of 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-acetic acid (53) with 2-phenylethylamines in boilings xylene gave the appropriate N-substituted 3-acetamides (54) and (55), reaction of 6-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-acetic acid (56) with 2-phenylethylamine afforded a pyrrolidin-5-one derivative (57). 3-Acetic hydrazides (47, 48) and (50) were prepared from ethyl 4-oxo-4H-pyrido[1,2-a]pyrimidine-3-acetates (46) and the 6,7,8,9-tetrahydro derivative (49) with hydrazine hydrate. Both 4-oxo-4H-pyrido[1,2-a]pyrimidine-3-acetic hydrazide (47) and 6,7,8,9-tetrahydro-3-acetic hydrazide (50) were converted to 6,7,8,9-tetrahydro-3-acetamides (51, 52) by refluxing them in ethanol over Raney Ni.
Pyridopyrimidine derivatives useful in treatment of ulcers
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, (2008/06/13)
The present invention relates to novel 4-oxo-4H-pyrido[1,2-a]pyrimidine -3-carbonamide derivatives of the general formula (I) and the acid addition salts thereof, pharmaceutical compositions containing them and a process for their preparation. In the gene
