107186-82-3Relevant academic research and scientific papers
Some Benzyl-Substituted Imidazoles, Triazoles, Tetrazoles, Pyridinethiones, and Structural Relatives as Multisubstrate Inhibitors of Dopamine β-Hydroxylase. 4. Structure-Activity Relationships at the Copper Binding Site
Kruse, Lawrence I.,Kaiser, Carl,DeWolf, Walter E.,Finkelstein, Joseph A.,Frazee, James S.,et al.
, p. 781 - 789 (2007/10/02)
Structure-activity relationships (SAR) were determined for novel multisubstrate inhibitors of dopamine β-hydroxylase (DBH; EC 1.14.17.1) by examining the effects upon in vitro inhibitory potencies resulting from structural changes at the copper-binding region of inhibitor.Attempts were made to determine replacement groups for the thione sulfur atom of the prototypical inhibitor 1-(4-hydroxybenzyl)imidazole-2-thione described previously.The synthesis and evaluation of oxygen and nitrogen analogues of the soft thione group demonstrated the sulfur atom to be necessary for optimal activity.An additional series of imidazole-2-thione relatives was prepared in an effort to probe the relationship between the pKa of the ligand group and inhibitor potency.In vitro inhibitory potency was shown not to correlate with ligand pKa over a range of approximately 10 pKa units, and a rationale for this is advanced.Additional ligand modifications were prepared in order to explore bulk tolerance at the enzyme oxygen binding site and to determine the effects of substituting a six-membered ligand group for the five-membered imidazole-2-thione ligand.
4-Aralkyl-5-substituted-1,2,4-triazole-5-thiols
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, (2008/06/13)
Compounds of formula (I) and pharmaceutically acceptable salts thereof are described in which, n is 0 to 5; X1 to X5 are any accessible combination of hydrogen, halogen, C1 6alkyl, C1 6alkoxy, cyano, nitro, SONH2, SO2NH2, SO2CH3, SO2CH2F, SO2CHF2, SO2CF3, CF3, CHO, OH, CH2OH, CO2H, or CO2CpH2p+1wherein p is 1 to 4; R1 is phenyl substituted by X1 to X5, C1 4alkyl, C3 6cycloalkyl, or an arylC1 4alkyl group substituted by X1 to X5; R2 is hydrogen, C1 4alkyl or (CH2)m-CO2R3; m is 0 to 5; and R3 is H or C1 4alkyl. These compounds are dopamine-β-hydroxylase inhibitors. Pharmaceutical compositions are described as are methods of use. Processes for the preparation of these compounds are described.
Dopamine-β-hydroxylase inhibitors
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, (2008/06/13)
Potent dopamine-β-hydroxylase inhibitors having the Formula STR1 that are useful to inhibit dopamine-β-hydroxylase activity, pharmaceutical compositions including these inhibitors, and methods of using these inhibitors to inhibit dopamine-β-hydroxylase activity in mammals. Also disclosed are novel intermediates useful in preparing the presently invented inhibitors.
