59-98-3Relevant articles and documents
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Ohashi et al.
, p. 703,705 (1968)
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Kubiczek,Neugebauer
, p. 815,818 (1949)
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Semi-empirical computation on mechanism of imidazolines and benzimidazoles synthesis and their QSAR studies
Hazarika, Swapnali,Konwar, Dilip,Bora, Manas Jyoti
, p. 5073 - 5078 (2015/01/09)
A green, mild and anaerobic synthesis of imidazolines and benzimidazoles from aldehydes and diamines using I2/KI/K2CO3/H2O system has been investigated by semi-empirical methods. The observed efficient direction of the above synthesis has been modeled from a comparison of the energies of four possible transition states arising from mono and di additions of iodines in the configured molecules. In the reaction I1 B is the most favorable transition state [TS] which is shown to be 20 Kcal/mol by PM3 analyses. The resulting trends of relative transition states energies are in excellent agreement with the experimental observations. Also, the bond order, bond length, heat of formation is in good agreement to the formation of product B. In order to establish the suitable mechanism of the reaction a quantitative structure activity relationship analysis has been made using hydrophobicity as the molecular descriptor. In this analysis the values of refractivity, polarizability, hydration energy, electron affinity, ionization potential and dipole moment of the compounds have been correlated with their hydrophobicity which has been taken as the molecular property.
Optimisation of imidazole compounds as selective TAAR1 agonists: Discovery of RO5073012
Galley, Guido,Stalder, Henri,Goergler, Annick,Hoener, Marius C.,Norcross, Roger D.
supporting information; experimental part, p. 5244 - 5248 (2012/09/07)
A series of imidazole compounds has been identified which affords potent and selective partial and full agonists of the TAAR1 receptor. Starting from 2-benzyl-imidazoline screening hits, a series of structurally related 2-benzyl- and 4-benzyl-imidazoles was investigated first, but it proved highly challenging to obtain compounds having sufficient selectivity against the adrenergic alpha 2 receptor. This issue could be successfully addressed by modification of the linker region and SAR exploration led to the discovery of highly selective isopropyl-substituted 4-aminomethyl-imidazole compounds. The work culminated in the identification of the selective TAAR1 partial agonist RO5073012 (4-chlorophenyl)-(1H-imidazol-4-ylmethyl)-isopropyl-amine, 24), which has a good pharmacokinetic profile after oral administration in rodents. RO5073012 has been found to be active in a behavioural rat model which is considered indicative for schizophrenia.
