MN-25

{{Short description|Chemical compound}}

{{Drugbox

| verifiedrevid = 459128585

| IUPAC_name = 7-methoxy-1-(2-morpholin-4-ylethyl)-N-[(1R,3S,4S)-2,2,4-trimethyl-3-bicyclo[2.2.1]heptanyl]indole-3-carboxamide

| image = MN-25 structure.svg

| image_class = skin-invert-image

| width =

| pregnancy_category =

| legal_CA = Schedule II

| legal_DE = NpSG

| legal_UK = Class B

| legal_status =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 501926-82-5

| CAS_number2 = 501927-29-3

| index_label =

| index2_label = 2-methyl derivative

| ATC_prefix =

| ATC_suffix =

| UNII = 8WXU5YRE25

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

| PubChem = 71308243

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

| DrugBank =

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

| ChemSpiderID = 26286811

| ChEMBL = 3234671

| synonyms = N-[(S)-Fenchyl]-1-[2-(morpholin-4-yl)ethyl]-7-methoxyindole-3-carboxamide

| C=26|H=37|N=3|O=3

| smiles = COC1=C(N(CCN2CCOCC2)C=C3C(N[C@H]4[C@@]5(C)CC[C@H](C5)C4(C)C)=O)C3=CC=C1

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

| StdInChI = 1S/C26H37N3O3/c1-25(2)18-8-9-26(3,16-18)24(25)27-23(30)20-17-29(11-10-28-12-14-32-15-13-28)22-19(20)6-5-7-21(22)31-4/h5-7,17-18,24H,8-16H2,1-4H3,(H,27,30)/t18-,24-,26+/m1/s1

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

| StdInChIKey = VQGDMQICNRCQEH-UFKXBGGNSA-N

}}

MN-25 (UR-12) is a drug invented by Bristol-Myers Squibb,{{cite patent | country = WO | number = 0158869 | status = application | title = Cannabinoid Receptor Modulators, Their Processes of Preparation, and use of Cannabinoid Receptor Modulators for Treating Respiratory and Non-Respiratory Diseases | pubdate = 16 August 2001 | fdate= 8 February 2001 |pridate= 11 February 2000 | inventor = Leftheris K, Zhao R, Chen BC, Kiener P, Wu H, Pandit CR, Wrobleski S, Chen P, Hynes J, Longphre M, Norris DJ, Spergel S, Tokarski J |assign1= Bristol-Myers Squibb }} that acts as a reasonably selective agonist of peripheral cannabinoid receptors.{{cite journal | vauthors = Zhao R, Wang B, Wu H, Hynes J, Leftheris K, Balasubramanian B, Barrish JC, Chen BC | title = Improved procedure for the preparation of 7-methoxy-2-methyl-1-(2-morpholinoethyl)-1H-indole-3-carboxylic acid, key intermediate in the synthesis of novel 3-amidoindole and indolopyridone cannabinoid ligands | journal = Arkivoc | date = 20 December 2009 | volume = 2010 | issue = 6 | pages = 89–95 | doi = 10.3998/ark.5550190.0011.610 | doi-access = free | hdl = 2027/spo.5550190.0011.610 | hdl-access = free }} It has moderate affinity for CB₂ receptors with a K_i of 11 nM, but 22x lower affinity for the psychoactive CB₁ receptors with a K_i of 245 nM. The indole 2-methyl derivative has the ratio of affinities reversed however, with a K_i of 8 nM at CB₁ and 29 nM at CB₂,{{cite journal | vauthors = Hynes J, Leftheris K, Wu H, Pandit C, Chen P, Norris DJ, Chen BC, Zhao R, Kiener PA, Chen X, Turk LA, Patil-Koota V, Gillooly KM, Shuster DJ, McIntyre KW | display-authors = 6 | title = C-3 Amido-indole cannabinoid receptor modulators | journal = Bioorganic & Medicinal Chemistry Letters | volume = 12 | issue = 17 | pages = 2399–402 | date = September 2002 | pmid = 12161142 | doi = 10.1016/S0960-894X(02)00466-3 }}{{cite journal | vauthors = Wrobleski ST, Chen P, Hynes J, Lin S, Norris DJ, Pandit CR, Spergel S, Wu H, Tokarski JS, Chen X, Gillooly KM, Kiener PA, McIntyre KW, Patil-Koota V, Shuster DJ, Turk LA, Yang G, Leftheris K | title = Rational design and synthesis of an orally active indolopyridone as a novel conformationally constrained cannabinoid ligand possessing antiinflammatory properties | journal = Journal of Medicinal Chemistry | volume = 46 | issue = 11 | pages = 2110–6 | date = May 2003 | pmid = 12747783 | doi = 10.1021/jm020329q }} which contrasts with the usual trend of 2-methyl derivatives having increased selectivity for CB₂ (cf. JWH-018 vs JWH-007, JWH-081 vs JWH-098).{{cite journal | vauthors = Huffman JW, Padgett LW | title = Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes | journal = Current Medicinal Chemistry | volume = 12 | issue = 12 | pages = 1395–411 | year = 2005 | pmid = 15974991 | doi = 10.2174/0929867054020864 }}{{cite journal | vauthors = Manera C, Tuccinardi T, Martinelli A | title = Indoles and related compounds as cannabinoid ligands | journal = Mini Reviews in Medicinal Chemistry | volume = 8 | issue = 4 | pages = 370–87 | date = April 2008 | pmid = 18473928 | doi = 10.2174/138955708783955935 }}

Chemically, it is closely related to another indole-3-carboxamide synthetic cannabinoid, Org 28611, but with a different cycloalkyl substitution on the carboxamide, and the cyclohexylmethyl group replaced by morpholinylethyl, as in JWH-200 or A-796,260. Early compounds such as these have subsequently led to the development of many related indole-3-carboxamide cannabinoid ligands.{{cite journal | vauthors = Adam JM, Cairns J, Caulfield W, Cowley P, Cumming I, Easson M, etal |title= Design, synthesis, and structure–activity relationships of indole-3-carboxamides as novel water soluble cannabinoid CB1 receptor agonists |doi= 10.1039/c0md00022a |journal= MedChemComm|publisher= Royal Society of Chemistry|volume= 1 |pages= 54–60 |year= 2010 }}{{cite journal | vauthors = Kiyoi T, York M, Francis S, Edwards D, Walker G, Houghton AK, Cottney JE, Baker J, Adam JM | title = Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists | journal = Bioorganic & Medicinal Chemistry Letters | volume = 20 | issue = 16 | pages = 4918–21 | date = August 2010 | pmid = 20634067 | doi = 10.1016/j.bmcl.2010.06.067 }}{{cite journal | vauthors = Moir EM, Yoshiizumi K, Cairns J, Cowley P, Ferguson M, Jeremiah F, Kiyoi T, Morphy R, Tierney J, Wishart G, York M, Baker J, Cottney JE, Houghton AK, McPhail P, Osprey A, Walker G, Adam JM | title = Design, synthesis, and structure-activity relationship study of bicyclic piperazine analogs of indole-3-carboxamides as novel cannabinoid CB1 receptor agonists | journal = Bioorganic & Medicinal Chemistry Letters | volume = 20 | issue = 24 | pages = 7327–30 | date = December 2010 | pmid = 21074434 | doi = 10.1016/j.bmcl.2010.10.061 }}{{cite journal | vauthors = Blaazer AR, Lange JH, van der Neut MA, Mulder A, den Boon FS, Werkman TR, Kruse CG, Wadman WJ | title = Novel indole and azaindole (pyrrolopyridine) cannabinoid (CB) receptor agonists: design, synthesis, structure-activity relationships, physicochemical properties and biological activity | journal = European Journal of Medicinal Chemistry | volume = 46 | issue = 10 | pages = 5086–98 | date = October 2011 | pmid = 21885167 | doi = 10.1016/j.ejmech.2011.08.021 }}