A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model

<table class="table-group" id="tab4"><tr><td><table class="table"><tr><td class="thead-hr" colspan="5"><hr/></td></tr><tr class="thead"><td align="left">Compound</td><td align="center"><i>α</i>1</td><td align="center"><i>α</i>2</td><td align="center"><i>α</i>3</td><td align="center"><i>α</i>5</td></tr><tr><td class="thead-hr" colspan="5"><hr/></td></tr><tr><td align="left">SH-053-2′F-R-CH<sub>3</sub> (<b>2</b>)</td><td align="center">111/154</td><td align="center">124/185</td><td align="center">125/220</td><td align="center">183/387</td></tr><tr><td align="left">SH-053-2′F-S-CH<sub>3</sub> (<b>17</b>)</td><td align="center">116/164</td><td align="center">170/348</td><td align="center">138/301</td><td align="center">218/389</td></tr><tr class="table-tr"><td colspan="5"><hr class="tbody-hr"/></td></tr></table></td></tr><tr class="table-fn"><td><svg height="9.90116pt" id="M202" style="vertical-align:-0.04981041pt" version="1.1" viewbox="-0.0498162 -9.85135 4.60763 9.90116" width="4.60763pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z" id="g190-98"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="439" vert-adv-y="439"></glyph.data></g></svg>Efficacy at <i>α</i><svg height="6.1673pt" id="M203" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -5.96091 7.39387 6.1673" width="7.39387pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M536 404C536 423 520 448 491 448C445 448 398 404 308 283L286 338C255 416 242 448 217 448C182 448 138 402 92 341L111 321C149 368 169 378 178 378C188 378 198 363 214 320L254 212C185 117 138 65 107 65C98 65 85 69 82 75C79 82 73 86 65 86C44 86 23 60 23 39C23 7 44 -12 71 -12C119 -12 168 33 265 177L306 61C321 17 347 -12 373 -12C413 -12 465 33 507 96L491 119C459 84 432 60 413 60C395 60 378 92 358 148L321 250C341 279 369 310 389 332C417 363 439 382 456 382C466 382 475 376 481 368C486 361 492 358 496 358C513 358 536 381 536 404Z" id="g113-121"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="559" vert-adv-y="559"></glyph.data></g></svg><i>β</i>3<i>γ</i>2 <svg height="11.9479pt" id="M204" style="vertical-align:-3.181499pt" version="1.1" viewbox="-0.0498162 -8.7664 41.6322 11.9479" width="41.6322pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M692 302H438V274C537 267 543 260 543 188V103C543 61 531 48 511 37C489 26 458 20 424 20C231 20 146 188 146 333C146 517 258 630 411 630C507 630 582 597 606 474L634 480C627 546 622 601 619 636C586 643 510 665 426 665C230 665 44 552 44 321C44 122 191 -15 411 -15C491 -15 573 7 635 21C629 49 628 81 628 116V202C628 261 632 266 692 274V302Z" id="g121-69"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="715" vert-adv-y="715"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,9.295,0)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z" id="g121-63"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="691" vert-adv-y="691"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,18.278,0)"><path d="M372 352C427 368 507 407 507 502C507 548 486 592 451 616C420 638 376 650 301 650H44V622C124 616 128 610 128 527V123C128 40 122 34 36 28V0H257C336 0 402 12 453 40C512 72 548 124 548 191C548 291 471 335 372 350V352ZM213 362V558C213 591 216 602 226 608C235 614 258 618 282 618C377 618 415 558 415 490C415 406 369 362 260 362H213ZM213 328H258C380 328 450 283 450 181C450 76 377 35 296 34C231 34 213 53 213 125V328Z" id="g121-64"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="588" vert-adv-y="588"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,25.609,0)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z" id="g121-63"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="691" vert-adv-y="691"></glyph.data></g><g transform="matrix(.0091,0,0,-0.0091,34.723,3.132)"><path d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z" id="g190-66"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="691" vert-adv-y="691"></glyph.data></g></svg> receptor subtypes as % of control current at 100 nM and 1 <i>μ</i>M concentrations. Data presented as percent over baseline (100) at concentrations of 100 nM/1 <i>μ</i>M.<br/></td></tr></table>

Oocyte electrophysiological data of benzodiazepines<svg height="9.90116pt" id="M201" style="vertical-align:-0.04981041pt" version="1.1" viewbox="-0.0498162 -9.85135 4.60763 9.90116" width="4.60763pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z" id="g190-98"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="439" vert-adv-y="439"></glyph.data></g></svg> [<a href="/journals/ijmc/2015/430248/#B15">87</a>].

International Journal of Medicinal Chemistry

tab4

Table 4

Table 4: A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model 