Discovery of Functionally Selective 7,8,9,10-Tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazines as GABAA Receptor Agonists at the α3 Subunit was written by Russell, Michael G. N.;Carling, Robert W.;Atack, John R.;Bromidge, Frances A.;Cook, Susan M.;Hunt, Peter;Isted, Catherine;Lucas, Matt;McKernan, Ruth M.;Mitchinson, Andrew;Moore, Kevin W.;Narquizian, Robert;Macaulay, Alison J.;Thomas, David;Thompson, Sally-Anne;Wafford, Keith A.;Castro, Jose L.. And the article was included in Journal of Medicinal Chemistry in 2005.Safety of 6-Methyl-2-pyridinemethanol This article mentions the following:
7,8,9,10-Tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazine I (R1 = Ph; R2 = 2-pyridylmethyl) was previously identified as a potent partial agonist for the α3 receptor subtype with 5-fold selectivity in binding affinity over α1. This paper describes a detailed investigation of the substituents on this core structure at both the 3- and 6-positions. Despite evaluating a wide range of groups, the maximum selectivity that could be achieved in terms of affinity for the α3 subtype over the α1 subtype was 12-fold (for I [R1 = Ph; R2 = 4-(HOCH2)C6H4CH2]). Although most analogs showed no selectivity in terms of efficacy, some of them, e.g. I (R1 = Ph; R2 = 3,5-dimethyl-2-pyridylmethyl, pyrazol-1-ylmethyl), did show partial agonism at α1 and antagonism at α3. However, two analogs I (R1 = Ph; R2 = 1-methyl-1,2,4-triazol-3-ylmethyl, 2-propyl-1,2,4-triazol-3-ylmethyl), containing triazole substituents in the 6-position, showed significantly higher efficacy for the α3 subtype over the α1 subtype. This was the first indication that selectivity in efficacy in the required direction could be achieved in this series. In the experiment, the researchers used many compounds, for example, 6-Methyl-2-pyridinemethanol (cas: 1122-71-0Safety of 6-Methyl-2-pyridinemethanol).
6-Methyl-2-pyridinemethanol (cas: 1122-71-0) belongs to alcohols. Similar to water, an alcohol can be pictured as having an sp3 hybridized tetrahedral oxygen atom with nonbonding pairs of electrons occupying two of the four sp3 hybrid orbitals. A multistep synthesis may use Grignard-like reactions to form an alcohol with the desired carbon structure, followed by reactions to convert the hydroxyl group of the alcohol to the desired functionality.Safety of 6-Methyl-2-pyridinemethanol
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts