ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Pyridazine derivatives R 0500 Pyridazine Derivatives. Part 40. Reactivity of 5-Alkynylpyridazin-3... more Pyridazine derivatives R 0500 Pyridazine Derivatives. Part 40. Reactivity of 5-Alkynylpyridazin-3(2H)-ones Toward Hydrochloric Acid. -A mild and efficient cleavage of the Mom group in pyridazinones (I) bearing acid-sensitive alkynyl substituents with aluminium chloride or boron tribromide is reported. Treatment of (I) with hydrochloric acid affords 5-alkynylpyridazinones (II) or 5-(2-chloroalkenyl)pyridazinones (III) depending on the nature of the alkynyl group at position 5. -(COELHO, A.; NOVOA, H.; PEETERS, O. M.; BLATON, N.; ALVARADO, M.; SOTELO*, E.; Tetrahedron 61 (2005) 20, 4785-4791; Dep. Quim. Org., Fac. Farm.
Four new diaza analogues (14, 15, 23, and 24) of the conformationally constrained aminobutyrophen... more Four new diaza analogues (14, 15, 23, and 24) of the conformationally constrained aminobutyrophenone derivatives QF0104B (5) and QF0108B (6) were synthesized (Schemes 2 and 3), and evaluated for their binding affinities (Table) towards the serotonin 5-HT2A and 5-HT2C, and the dopamine D2 receptors. Among the new compounds, the quinazoline derivative 15 (=7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydroquinazolin-5-one) exhibited the highest affinities towards the serotonin 5-HT2A and dopamine D2 receptors, and it is in the borderline of potential atypical antipsychotics. The cinnoline derivative 23 (=7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydro-3-methylcinnolin-5-one) displayed high selectivity in its binding profile towards the 5-HT2C compared to both the 5-HT2A and D2 receptors.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
This paper describes the synthesis of a new series of 7-amino-5-aryl-6-cyano-5,8-dihydropyrido-[2... more This paper describes the synthesis of a new series of 7-amino-5-aryl-6-cyano-5,8-dihydropyrido-[2,3-d]pyrimidin-4(3H)-ones 3 from the reaction of 6-amino-4-pyrimidinones 1 with arylidene derivatives of malonodinitrile 2. The structure of the final compounds was determined on the basis of nmr measurements, especially by 1H, 1H-, 1H, 13C COSY, DEPT, HMBC and HMQC experiments.
... Acknowledgements. This work was supported by the Xunta de Galicia (Spain) under grant PGIDT01... more ... Acknowledgements. This work was supported by the Xunta de Galicia (Spain) under grant PGIDT01PXI20309PR. M. Alvarado (on leave from Universidad de Nariño, Colombia) is grateful to the Agencia Española de Cooperación Internacional (AECI) for a predoctoral fellowship. ...
This paper describes the synthesis of a new series of 6-amino-4-aryl-5-cyanopyrazolo[3,4-b]pyridi... more This paper describes the synthesis of a new series of 6-amino-4-aryl-5-cyanopyrazolo[3,4-b]pyridines 4 and 4-aryl-5-cyano-6H-pyrazolo[3,4-b]pyridin-6-ones 5 from the reaction of 5-amino-3-methyl-1-phenylpyrazole 1 with arylidene derivatives of malonodinitrile 2 and ethyl cyanoacetate 3. The structure of the final compounds was determined on the basis of nmr measurements, especially by 1H, 1H-, 1H, 13C-COSY, DEPT and X-ray diffraction.
The present study is part of a long-term research project aiming to gain insight into the mechani... more The present study is part of a long-term research project aiming to gain insight into the mechanism of action of atypical antipsychotics. Here we describe a 3D-QSAR study carried out on a series of butyrophenones with affinity for the serotonin-2A receptor, aligned by docking into the binding site of a receptor model. The series studied has two peculiarities: (i) all the compounds have a chiral center and can be represented by two enantiomeric structures, and (ii) many of the structures can bind the receptor in two alternative orientations, posing the problem of how to select a single representative structure for every compound. We have used an original solution consisting of the simultaneous use of multiple structures, representing different configurations, binding conformations, and positions. The final model showed good statistical quality (n = 426, r2 = 0.84, q2LOO = 0.81) and its interpretation provided useful information, not obtainable from the simple inspection of the ligand-receptor complexes.
The title compounds 4 and 5 have been prepared in one-step reaction from 6-amino-4-pyrimidinones ... more The title compounds 4 and 5 have been prepared in one-step reaction from 6-amino-4-pyrimidinones 1, the corresponding 4-substituted benzaldehyde 2 and ethyl cyanoacetate 3 in very good yields. The structure of the final compounds was determined on the basis of nmr measurements, especially by 1H, 1H-, 1H,13C COSY, and DEPT.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Compound (VII) shows the highest antipsychotic activity off all tested compounds. -(ALVARADO, M.;... more Compound (VII) shows the highest antipsychotic activity off all tested compounds. -(ALVARADO, M.; COELHO, A.; MASAGUER, C. F.; RAVINA*, E.; BREA, J.; PADIN, J. F.; LOZA, M. I.; Bioorg. Med. Chem. Lett. 15 (2005) 12, 3063-3066; Dep. Quim. Org., Fac. Farm.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Pyridazine derivatives R 0500 Pyridazine Derivatives. Part 40. Reactivity of 5-Alkynylpyridazin-3... more Pyridazine derivatives R 0500 Pyridazine Derivatives. Part 40. Reactivity of 5-Alkynylpyridazin-3(2H)-ones Toward Hydrochloric Acid. -A mild and efficient cleavage of the Mom group in pyridazinones (I) bearing acid-sensitive alkynyl substituents with aluminium chloride or boron tribromide is reported. Treatment of (I) with hydrochloric acid affords 5-alkynylpyridazinones (II) or 5-(2-chloroalkenyl)pyridazinones (III) depending on the nature of the alkynyl group at position 5. -(COELHO, A.; NOVOA, H.; PEETERS, O. M.; BLATON, N.; ALVARADO, M.; SOTELO*, E.; Tetrahedron 61 (2005) 20, 4785-4791; Dep. Quim. Org., Fac. Farm.
Four new diaza analogues (14, 15, 23, and 24) of the conformationally constrained aminobutyrophen... more Four new diaza analogues (14, 15, 23, and 24) of the conformationally constrained aminobutyrophenone derivatives QF0104B (5) and QF0108B (6) were synthesized (Schemes 2 and 3), and evaluated for their binding affinities (Table) towards the serotonin 5-HT2A and 5-HT2C, and the dopamine D2 receptors. Among the new compounds, the quinazoline derivative 15 (=7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydroquinazolin-5-one) exhibited the highest affinities towards the serotonin 5-HT2A and dopamine D2 receptors, and it is in the borderline of potential atypical antipsychotics. The cinnoline derivative 23 (=7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydro-3-methylcinnolin-5-one) displayed high selectivity in its binding profile towards the 5-HT2C compared to both the 5-HT2A and D2 receptors.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
This paper describes the synthesis of a new series of 7-amino-5-aryl-6-cyano-5,8-dihydropyrido-[2... more This paper describes the synthesis of a new series of 7-amino-5-aryl-6-cyano-5,8-dihydropyrido-[2,3-d]pyrimidin-4(3H)-ones 3 from the reaction of 6-amino-4-pyrimidinones 1 with arylidene derivatives of malonodinitrile 2. The structure of the final compounds was determined on the basis of nmr measurements, especially by 1H, 1H-, 1H, 13C COSY, DEPT, HMBC and HMQC experiments.
... Acknowledgements. This work was supported by the Xunta de Galicia (Spain) under grant PGIDT01... more ... Acknowledgements. This work was supported by the Xunta de Galicia (Spain) under grant PGIDT01PXI20309PR. M. Alvarado (on leave from Universidad de Nariño, Colombia) is grateful to the Agencia Española de Cooperación Internacional (AECI) for a predoctoral fellowship. ...
This paper describes the synthesis of a new series of 6-amino-4-aryl-5-cyanopyrazolo[3,4-b]pyridi... more This paper describes the synthesis of a new series of 6-amino-4-aryl-5-cyanopyrazolo[3,4-b]pyridines 4 and 4-aryl-5-cyano-6H-pyrazolo[3,4-b]pyridin-6-ones 5 from the reaction of 5-amino-3-methyl-1-phenylpyrazole 1 with arylidene derivatives of malonodinitrile 2 and ethyl cyanoacetate 3. The structure of the final compounds was determined on the basis of nmr measurements, especially by 1H, 1H-, 1H, 13C-COSY, DEPT and X-ray diffraction.
The present study is part of a long-term research project aiming to gain insight into the mechani... more The present study is part of a long-term research project aiming to gain insight into the mechanism of action of atypical antipsychotics. Here we describe a 3D-QSAR study carried out on a series of butyrophenones with affinity for the serotonin-2A receptor, aligned by docking into the binding site of a receptor model. The series studied has two peculiarities: (i) all the compounds have a chiral center and can be represented by two enantiomeric structures, and (ii) many of the structures can bind the receptor in two alternative orientations, posing the problem of how to select a single representative structure for every compound. We have used an original solution consisting of the simultaneous use of multiple structures, representing different configurations, binding conformations, and positions. The final model showed good statistical quality (n = 426, r2 = 0.84, q2LOO = 0.81) and its interpretation provided useful information, not obtainable from the simple inspection of the ligand-receptor complexes.
The title compounds 4 and 5 have been prepared in one-step reaction from 6-amino-4-pyrimidinones ... more The title compounds 4 and 5 have been prepared in one-step reaction from 6-amino-4-pyrimidinones 1, the corresponding 4-substituted benzaldehyde 2 and ethyl cyanoacetate 3 in very good yields. The structure of the final compounds was determined on the basis of nmr measurements, especially by 1H, 1H-, 1H,13C COSY, and DEPT.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Compound (VII) shows the highest antipsychotic activity off all tested compounds. -(ALVARADO, M.;... more Compound (VII) shows the highest antipsychotic activity off all tested compounds. -(ALVARADO, M.; COELHO, A.; MASAGUER, C. F.; RAVINA*, E.; BREA, J.; PADIN, J. F.; LOZA, M. I.; Bioorg. Med. Chem. Lett. 15 (2005) 12, 3063-3066; Dep. Quim. Org., Fac. Farm.
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Papers by Mario Alvarado