Efficient Synthesis of Chiral Isoquinoline and Pyrido[1,2-b]-isoquinoline Derivatives via Intramolecular Heck Reactions

Sánchez-Sancho, Francisco; Mann, Enrique; Herradón, Bernardo

doi:10.1002/1615-4169(20010430)343:4<360::aid-adsc360>3.0.co;2-2

Cited by 27 publications

(2 citation statements)

References 9 publications

(12 reference statements)

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“…27 Tyrosinol 22 has been described to proceed by LiBH 4 reduction of the methyl ester in quantitative yield. 28 However, in our hands, this procedure afforded a mixture of products from which the expected compound 22 was isolated in low yield. Therefore, a similar protocol as above was followed.…”

Section: Resultsmentioning

confidence: 79%

Synthesis and Biological Activity of New Potential Agonists for the Human Adenosine A_2A Receptor

Bosch

Campos²,

Niubo³

et al. 2004

J. Med. Chem.

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New adenosine derivatives have been synthesized and tested as putative agonists of adenosine receptors. Compounds 2-6 derive from the introduction of several types of substituents (electron donating, electron withdrawing, and halogens) in the para-position of the phenyl ring of the parent compound 1, and compound 7 lacks the hydroxyl group of amino alcohol 1. In radioligand binding assays using recombinant human A(1), A(2A), A(2B), and A(3) receptors, all compounds showed very low or negligible affinity for A(1) and A(2B) receptors but compounds 3, 5, and 7 displayed a remarkably potent affinity for the A(2A) receptor with K(i) values of 1-5 nM. Bromo derivative 3 displayed a selectivity A(1)/A(2A) = 62 and A(3)/A(2A) = 16 whereas the presence of a hydroxyl group (compound 5) improved the selectivity of A(1)/A(2A) and A(3)/A(2A) to 120- and 28-fold, respectively. When the methoxy derivative 4 lacks the hydroxyl group on the side chain (compound 7), the binding affinity for A(2A) is increased to 1 nM, improving selectivity ratios to 356- and 100-fold against A(1) and A(3), respectively. In Chinese hamster ovary cells transfected with human A(2A) and A(2B) receptors, most compounds showed a remarkable activity for the A(2A) receptor, except chloro derivative 2, with EC(50) values ranging from 1.4 to 8.8 nM. The compounds behaved as good A(2A) agonists, and all were more selective than 5'-(N-ethylcarboxamino)adenosine (NECA), with A(2B)/A(2A) ratios of cAMP accumulation ranging from 48 for compound 2 to 666 for compound 7 while the corresponding A(2B)/A(2A) ratio for NECA was only 9. Compounds 1, 3, 5, and 7 also displayed higher selectivities than NECA up to 100-fold in isolated aortas of rat and guinea pig. In guinea pig tracheal rings precontracted by carbachol, compounds 2 and 4 were more potent than adenosine (100-fold) and NECA (10-fold), whereas compounds 1 and 7 displayed similar effects to NECA. Pretreatment of the tracheal rings with A(2), A(2A), and A(2B) receptor antagonists 3,7-dimethyl-l-propargylxanthine, 8-(3-chlorostyryl)caffeine, and alloxazine produced a marked inhibition of the tracheal relaxations induced by compounds 1, 2, and 4, but none of the compounds showed selectivity toward any of the adenosine receptors.

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Section: Resultsmentioning

confidence: 79%

Synthesis and Biological Activity of New Potential Agonists for the Human Adenosine A_2A Receptor

Bosch

Campos²,

Niubo³

et al. 2004

J. Med. Chem.

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“…In connection with our long-standing interest on the structure ( − ) and reactivity ( − ) of aromatic compounds, we have undertaken a thorough computational study on chlorinated biphenyls. Comprehensive research on the bioactivity of chlorinated biphenyls requires a complete set of physicochemical properties.…”

Section: Introductionmentioning

confidence: 99%

Computational Studies on Biphenyl Derivatives. Analysis of the Conformational Mobility, Molecular Electrostatic Potential, and Dipole Moment of Chlorinated Biphenyl: Searching for the Rationalization of the Selective Toxicity of Polychlorinated Biphenyls (PCBs)

Chana

Concejero

Frutos

et al. 2002

Chem. Res. Toxicol.

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With the objective to understand how the pattern and degree of chlorination influence on the properties of the title molecules, a computational study on biphenyl and all the chlorinated biphenyls (from 1 to 10 chlorine atoms, 209 congeners) has been undertaken. The study includes conformational searches (and further refinement by molecular dynamics simulations) and the ab initio calculation of the molecular electrostatic potential (MEP) and the dipole moments for all the congeners. The most significant property is the MEP, finding a good correlation between the MEPs and the substitution pattern on chlorinated biphenyls. The most toxic congeners possess highly positive values of electrostatic potential on the aromatic rings and highly negative values of electrostatic potential on the chlorine atoms. Additionally, we have found that the toxic congeners possess conformations with low dipole moments, a fact that may be linked to the ready accumulation on the adipose tissue. The results on the geometry and electrostatic properties of chlorinated biphenyls can be useful to rationalize their selective toxicities.

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Rearrangements in Carbohydrate Templates to the Way to Peptide‐Scaffold Hybrids and Functionalized Heterocycles

Herradón

Miguel

Mann

2016

Domino and Intramolecular Rearrangement Reactions as Advanced Synthetic Methods in Glycoscience

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Efficient Synthesis of Chiral Isoquinoline and Pyrido[1,2-b]-isoquinoline Derivatives via Intramolecular Heck Reactions

Cited by 27 publications

References 9 publications

Synthesis and Biological Activity of New Potential Agonists for the Human Adenosine A_2A Receptor

Synthesis and Biological Activity of New Potential Agonists for the Human Adenosine A_2A Receptor

Computational Studies on Biphenyl Derivatives. Analysis of the Conformational Mobility, Molecular Electrostatic Potential, and Dipole Moment of Chlorinated Biphenyl: Searching for the Rationalization of the Selective Toxicity of Polychlorinated Biphenyls (PCBs)

Rearrangements in Carbohydrate Templates to the Way to Peptide‐Scaffold Hybrids and Functionalized Heterocycles

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Efficient Synthesis of Chiral Isoquinoline and Pyrido[1,2-b]-isoquinoline Derivatives via Intramolecular Heck Reactions

Cited by 27 publications

References 9 publications

Synthesis and Biological Activity of New Potential Agonists for the Human Adenosine A2A Receptor

Synthesis and Biological Activity of New Potential Agonists for the Human Adenosine A2A Receptor

Computational Studies on Biphenyl Derivatives. Analysis of the Conformational Mobility, Molecular Electrostatic Potential, and Dipole Moment of Chlorinated Biphenyl: Searching for the Rationalization of the Selective Toxicity of Polychlorinated Biphenyls (PCBs)

Rearrangements in Carbohydrate Templates to the Way to Peptide‐Scaffold Hybrids and Functionalized Heterocycles

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Product

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Synthesis and Biological Activity of New Potential Agonists for the Human Adenosine A_2A Receptor

Synthesis and Biological Activity of New Potential Agonists for the Human Adenosine A_2A Receptor