Reference of 17680-55-6, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.17680-55-6, Name is 7-Bromo-1,2,3,4-tetrahydroisoquinoline, molecular formula is C9H10BrN. In a article£¬once mentioned of 17680-55-6
Application of the goldilocks effect to the design of potent and selective inhibitors of phenylethanolamine N-methyltransferase: Balancing pKa and steric effects in the optimization of 3-methyl-1,2,3,4- tetrahydroisoquinoline inhibitors by beta-fluorination
3-Methyl-1,2,3,4-tetrahydroisoquinolines (3-methyl-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT), but are not selective due to significant affinity for the alpha2-adrenoceptor. Fluorination of the methyl group lowers the pKa of the THIQ amine from 9.53 (CH3) to 7.88 (CH2F), 6.42 (CHF2), and 4.88 (CF3). This decrease in pKa results in a reduction in affinity for the alpha2-adrenoceptor. However, increased fluorination also results in a reduction in PNMT inhibitory potency, apparently due to steric and electrostatic factors. Biochemical evaluation of a series of 3-fluoromethyl-THIQs and 3-trifluoromethyl-THIQs showed that the former were highly potent inhibitors of PNMT, but were often nonselective due to significant affinity for the alpha2-adrenoceptor, while the latter were devoid of alpha2-adrenoceptor affinity, but also lost potency at PNMT. 3-Difluoromethyl-7-substituted-THIQs have the proper balance of both steric and pKa properties and thus have enhanced selectivity versus the corresponding 3-fluoromethyl-7-substituted-THIQs and enhanced PNMT inhibitory potency versus the corresponding 3-trifluoromethyl-7-substituted- THIQs. Using the “Goldilocks Effect” analogy, the 3-fluoromethyl-THIQs are too potent (too hot) at the alpha2-adrenoceptor and the 3-trifluoromethyl-THIQs are not potent enough (too cold) at PNMT, but the 3-difluoromethyl-THIQs are just right. They are both potent inhibitors of PNMT and highly selective due to low affinity for the alpha2- adrenoceptor. This seems to be the first successful use of the beta-fluorination of aliphatic amines to impart selectivity to a pharmacological agent while maintaining potency at the site of interest.
A reaction mechanism is the microscopic path by which reactants are transformed into products. Each step is an elementary reaction. In my other articles, you can also check out more blogs about 17680-55-6
Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem