2′-Acetoxycocaine: Difference between revisions

| verifiedrevid = 460432750

| ImageFile = 2'-Acetoxycocaine.svg

| ImageSize = 200px

| ImageAlt =

| IUPACName = Methyl 4β-<nowiki/>{[2-(acetyloxy)benzoyl]oxy}tropane-2β-carboxylate

| SystematicName = Methyl (1''R'',2''R'',3''S'',5''S'')-3-{[2-(acetyloxy)benzoyl]oxy}-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate

|Section1={{Chembox Identifiers

| CASNo = 192648-66-1

| CASNo_Ref = {{cascite|correct|??}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = R3WS363295

| PubChem = 10713606

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 8888946

| SMILES = CN1C2C[C@H](OC(C3=C(OC(C)=O)C=CC=C3)=O)[C@H](C(OC)=O)C1CC2

| InChI = 1/C19H23NO6/c1-11(21)25-15-7-5-4-6-13(15)18(22)26-16-10-12-8-9-14(20(12)2)17(16)19(23)24-3/h4-7,12,14,16-17H,8-10H2,1-3H3/t12-,14+,16-,17+/m0/s1

| InChIKey = BGTCUQCBSAMJBH-JSQNDZKTBL

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C19H23NO6/c1-11(21)25-15-7-5-4-6-13(15)18(22)26-16-10-12-8-9-14(20(12)2)17(16)19(23)24-3/h4-7,12,14,16-17H,8-10H2,1-3H3/t12-,14+,16-,17+/m0/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = BGTCUQCBSAMJBH-JSQNDZKTSA-N

|Section2={{Chembox Properties

| C=19 | H=23 | N=1 | O=6

| Appearance =

| Density =

| MeltingPt =

| BoilingPt =

| Solubility = }}

|Section3={{Chembox Hazards

| MainHazards =

| FlashPt =

| AutoignitionPt = }}

'''2′-Acetoxycocaine''' ('''''ortho''-acetoxy-cocaine''') is a [[List of cocaine analogues|cocaine analog]], with a quicker effect onset than cocaine. The acetoxy branch renders the molecule a [[Quantitative structure–activity relationship|QSAR]] of a 4-fold increase over [[cocaine]] in its binding potency for the dopamine transporter & a 35-fold enhanced affinity for the norepinephrine transporter. It also has a reduced selectivity for the serotonin transporter (though only due to its greater increase at NET & DAT binding being of such an order of magnitude more by comparison). In overall binding affinity (not uptake inhibition) it displaces ligands better across the board than cocaine in all monoamine categories. [[Salicylmethylecgonine]] would be an intermediate metabolite ''[[in vivo]]'' in humans (therefore affecting the overall effect profile of the administered 2′-acetoxy analog via its metabolic route; giving it nearly three times the affinity for DAT, after onset, and greaten the affinity that is would have for NET by a halve more than on upon initial exposure, after rapid [[acetylation|deacetylation]].) 2′-Acetoxycocaine has a closer to optimum LogP (a square value of 2) for [[blood–brain barrier]] penetration (cocaine being higher and logarithmically four times the optimal [[lipophilicity]] allowing too much of the compound to be dumped out directly into fatty tissue instead of reaching its target site) this would make it a [[prodrug]] to salicylmethylecgonine due to the latter having a less (and the ''ortho''-acetoxy analog having a more) efficacious LogP than its cocaine parent.

{| class="wikitable sortable"

|+Binding comparison between cocaine and [[List of cocaine analogues|semi-synthetic derivative]] ''o''-acetoxy-cocaine<ref>{{cite journal | last1 = Singh | first1 = Satendra | display-authors = etal | year = 2000 | title = Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists | url=https://www.erowid.org/archive/rhodium/pdf/cocaineanalogs.pdf#49 | journal = Chem. Rev. | volume = 100 | issue = 3 | pages = 925–1024 | doi=10.1021/cr9700538 | pmid = 11749256}}</ref>

! Compound

! DAT

[³H]WIN 35428

! 5-HTT

[³H]Paroxetine

! NET

[³H]Nisoxetine

! Selectivity

5-HTT/DAT

! Selectivity

NET/DAT

! [[Partition coefficient|LogP]]^'''ɑ'''

|-

| Cocaine ||249 ± 37||615 ± 120||2500 ± 70||2.5||10.0||2.62

|-

| 2′(''ortho'')-Acetoxycocaine ||70 ± 1||219 ± 20||72 ± 9||3.1||1.0||2.45

|-

| [[Salicylmethylecgonine|2′(''ortho'')-Hydroxycocaine]]<br><small>''(human metabolite of 2′(''ortho'')-acetoxycocaine)''</small> ||25 ± 4||143 ± 21||48 ± 2||5.7||1.9||2.89

|}

*^'''ɑ'''<small>Predictive algorithm used is dynamic and subject to change as database expands, should be taken as suggestive values, and only putative/uncertain as exact quantitative value is concerned.</small><ref>{{Cite web |url=http://www.molinspiration.com/cgi-bin/properties |title=Molinspiration Cheminformatics: Calculation of Molecular Properties and Bioactivity Score |access-date=2016-02-09 |archive-date=2020-12-18 |archive-url=https://web.archive.org/web/20201218050318/http://www.molinspiration.com/cgi-bin/properties |url-status=dead }}</ref>