QSAR with electrotopological state atom index: Antiadrenergic activity of <i style="mso-bidi-font-style:normal"><span style="font-size:12.0pt; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language:AR-SA" lang="EN-IN">N,N</span></i><span style="font-size:12.0pt;font-family:"Times New Roman";mso-fareast-font-family: "Times New Roman";mso-ansi-language:EN-IN;mso-fareast-language:EN-IN; mso-bidi-language:AR-SA" lang="EN-IN">-dimethyl-2-bromo-2-phenylethylamines</span>

Abstract

The electrotopological state atom index developed by Hall and Kier is a structural descriptor encoding both electronic feature and topological environment of each skeletal atom of a molecule. It has two basic components: (1) intrinsic electrotopological state of an atom; (2) perturbation factor (effect of environment).

<span style="font-size:12.0pt;font-family:" times="" new="" roman";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-in;mso-fareast-language:="" en-in;mso-bidi-language:ar-sa"="" lang="EN-IN">The index has been projected to have potential to determine pharmacophore moieties of biologically active congeneric compounds. Antiadrenergic activity of a series of twenty two substituted <i>N, </i><i style="mso-bidi-font-style:normal">N</i>-dimethyl-2-bromo-2-phenylethylamines are subjected to quantitative structure activity <span style="font-size:12.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" hiddenhorzocr;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" ar-sa"="" lang="EN-IN">relationship <span style="font-size:12.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-in;mso-fareast-language:en-in;mso-bidi-language:ar-sa"="" lang="EN-IN">studies with electrotopological state atom index and the bromine atom is predicted to be the most important for the mediation of <span style="font-size: 12.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:hiddenhorzocr;="" mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:ar-sa"="" lang="EN-IN">the <span style="font-size:12.0pt;font-family:" times="" new="" roman";="" mso-fareast-font-family:"times="" roman";mso-ansi-language:en-in;mso-fareast-language:="" en-in;mso-bidi-language:ar-sa"="" lang="EN-IN">activity. This is corroborated by a previous report that the compounds act with the receptor site through formation of an ethyleneiminium ion for which abstraction of bromine atom from the molecules is a pre- requisite. The study reveals the power of the index in identifying atoms and fragments which are important for biological activity and also supports the presumption that this atom level descriptor of molecular structure will have significant contribution in future drug design studies.</span></span></span></span></span>