:UR-144

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid =

| IUPAC_name = (1-pentylindol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone

| tradename = different brandnames, typical example: "TMCP-018", "KM-X1", "UR-144", "MN-001", "YX-17"

| image = UR-144.svg

| width =

| pregnancy_category =

| legal_AU =

| legal_BR = F2

| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-07-24 |title=RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |url-status=live |archive-url=https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |archive-date=2023-08-27 |access-date=2023-08-27 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-07-25}}

| legal_CA = Schedule II

| legal_DE = Anlage II

| legal_US = Schedule I

| legal_UK = Class B

| legal_NZ = Temporary Class

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 1199943-44-6

| ATC_prefix =

| ATC_suffix =

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 571773

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C21H29NO/c1-6-7-10-13-22-14-16(15-11-8-9-12-17(15)22)18(23)19-20(2,3)21(19,4)5/h8-9,11-12,14,19H,6-7,10,13H2,1-5H3

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = NBMMIBNZVQFQEO-UHFFFAOYSA-N

| PubChem = 44626619

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = 1TYA7HVP1B

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 24634882

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = C22781

| C=21 | H=29 | N=1 | O=1

| smiles = CCCCCN1C=C(C2=CC=CC=C21)C(=O)C3C(C3(C)C)(C)C

}}

UR-144 (TMCP-018, KM-X1, MN-001, YX-17) is a drug invented by Abbott Laboratories,{{cite patent |country= WO |number= 2006069196 |status= application |title= 3-Cycloalkylcarbonyl indoles as cannabinoid receptor ligands |pubdate= 2006-06-29 |inventor= Pace JM, Tietje K, Dart MJ, Meyer MD |assign1= Abbott Laboratories }} that acts as a selective full agonist of the peripheral cannabinoid receptor CB₂, but with much lower affinity for the psychoactive CB₁ receptor.

Pharmacology

UR-144 has high affinity for the CB₂ receptor with a K_i of 1.8 nM but 83x lower affinity for the CB₁ receptor with a K_i of 150 nM.{{cite journal | vauthors = Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, El-Kouhen OF, Yao BB, Hsieh GC, Pai M, Zhu CZ, Chandran P, Meyer MD | display-authors = 6 | title = Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity | journal = Journal of Medicinal Chemistry | volume = 53 | issue = 1 | pages = 295–315 | date = January 2010 | pmid = 19921781 | doi = 10.1021/jm901214q }}

UR-144 was found to possess an EC₅₀ of 421 nM for human CB₁ receptors, and 72 nM for human CB₂ receptors.{{cite journal | vauthors = Banister SD, Stuart J, Kevin RC, Edington A, Longworth M, Wilkinson SM, Beinat C, Buchanan AS, Hibbs DE, Glass M, Connor M, McGregor IS, Kassiou M | display-authors = 6 | title = Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135 | journal = ACS Chemical Neuroscience | volume = 6 | issue = 8 | pages = 1445–1458 | date = August 2015 | pmid = 25921407 | doi = 10.1021/acschemneuro.5b00107 | url = https://zenodo.org/record/47750 }} UR-144 produces bradycardia and hypothermia in rats at a dose of 10 mg/kg, suggesting weak cannabinoid-like activity.

Chemically it is closely related to other 2,2,3,3-tetramethylcyclopropyl synthetic cannabinoids like A-796,260 and A-834,735 but with a different substitution on the 1-position of the indole core, in these compounds its 1-pentyl group is replaced with alkylheterocycles like 1-(2-morpholinoethyl) and 1-(tetrahydropyran-4-ylmethyl).

Legality

The UK ACMD recommended that generic prohibition legislation be extended to include UR-144 in October 2012.{{cite web | url=https://www.gov.uk/government/publications/acmd-further-consideration-of-the-synthetic-cannabinoids | title=Further consideration of the synthetic cannabinoids | publisher=UK Advisory Council on the Misuse of Drugs | date=18 October 2012 | access-date=13 December 2014 | pages=14}} The UK Home Office accepted the recommendation and enacted legislation to ban UR-144 as a class B drug along with a number of other drugs on February 26, 2013 as a part of [http://www.legislation.gov.uk/uksi/2013/239/made The Misuse of Drugs Act 1971 (Amendment) Order 2013].

UR-144 was detected in Korea, 2012. This molecule is very close to KM-X1, MN-001, YX-17 and Kr-11.{{cite journal | vauthors = Almada M, Alves P, Fonseca BM, Carvalho F, Queirós CR, Gaspar H, Amaral C, Teixeira NA, Correia-da-Silva G | display-authors = 6 | title = Synthetic cannabinoids JWH-018, JWH-122, UR-144 and the phytocannabinoid THC activate apoptosis in placental cells | journal = Toxicology Letters | volume = 319 | pages = 129–137 | date = February 2020 | pmid = 31730886 | doi = 10.1016/j.toxlet.2019.11.004 | s2cid = 208061836 | doi-access = free }}

UR-144 (Abbott patent) has been detected as an ingredient of synthetic cannabis smoking blends in New Zealand, and subsequently banned from sale as a temporary class drug on 6 April 2012.[http://www.health.govt.nz/our-work/mental-health-and-addictions/drug-policy/temporary-class-drug-notices Temporary Class Drug Notices. New Zealand Ministry of Health] It has also been encountered in smoking blends and subsequently banned in Russia.{{cite journal | vauthors = Sobolevsky T, Prasolov I, Rodchenkov G | title = Detection of urinary metabolites of AM-2201 and UR-144, two novel synthetic cannabinoids | journal = Drug Testing and Analysis | volume = 4 | issue = 10 | pages = 745–753 | date = October 2012 | pmid = 23042760 | doi = 10.1002/dta.1418 }}

As of October 2015 UR-144 is a controlled substance in China.{{cite web | url=http://www.sfda.gov.cn/WS01/CL0056/130753.html | title=关于印发《非药用类麻醉药品和精神药品列管办法》的通知 | publisher=China Food and Drug Administration | date=27 September 2015 | language=Chinese | access-date=1 October 2015}}

UR-144 is banned in the Czech Republic.{{cite web | url=http://www.mzcr.cz/Admin/_upload/files/3/Nov%C3%A9%20PL.pdf | title=Látky, o které byl doplněn seznam č. 4 psychotropních látek (příloha č. 4 k nařízení vlády č. 463/2013 Sb.) | publisher=Ministerstvo zdravotnictví | language=Czech}}

Detection

A forensic standard of UR-144 is available, and the compound has been posted on the Forendex website of potential drugs of abuse.Southern Association of Forensic Scientists http://forendex.southernforensic.org/index.php/detail/index/1218 An ELISA immunoassay technique for detecting UR-144 in urine as part of general drug screens has been developed by Tulip Biolabs, Inc. An Homogeneous Immunoassay that runs on most Clinical Chemistry Analyzers and detects several UR and XLR synthetic cannabinoids has been developed and introduced by Immunalysis Inc. Pomona USA.

:UR-144

Pharmacology

Legality

Detection

See also

References

Further reading