Chemistry:MN-25

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Short description: Chemical compound
MN-25
MN-25 structure.svg
Clinical data
Other namesN-[(S)-Fenchyl]-1-[2-(morpholin-4-yl)ethyl]-7-methoxyindole-3-carboxamide
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC26H37N3O3
Molar mass439.600 g·mol−1
3D model (JSmol)
  (verify)

MN-25 (UR-12) is a drug invented by Bristol-Myers Squibb,[1] that acts as a reasonably selective agonist of peripheral cannabinoid receptors.[2] It has moderate affinity for CB2 receptors with a Ki of 11 nM, but 22x lower affinity for the psychoactive CB1 receptors with a Ki of 245 nM. The indole 2-methyl derivative has the ratio of affinities reversed however, with a Ki of 8 nM at CB1 and 29 nM at CB2,[3][4] 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).[5][6]

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.[7][8][9][10]

See also

References

  1. ↑ 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, "Cannabinoid Receptor Modulators, Their Processes of Preparation, and use of Cannabinoid Receptor Modulators for Treating Respiratory and Non-Respiratory Diseases", WO patent application 0158869, published 16 August 2001, assigned to Bristol-Myers Squibb
  2. ↑ "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". Arkivoc 2010 (6): 89–95. 20 December 2009. doi:10.3998/ark.5550190.0011.610. 
  3. ↑ "C-3 Amido-indole cannabinoid receptor modulators". Bioorganic & Medicinal Chemistry Letters 12 (17): 2399–402. September 2002. doi:10.1016/S0960-894X(02)00466-3. PMID 12161142. 
  4. ↑ "Rational design and synthesis of an orally active indolopyridone as a novel conformationally constrained cannabinoid ligand possessing antiinflammatory properties". Journal of Medicinal Chemistry 46 (11): 2110–6. May 2003. doi:10.1021/jm020329q. PMID 12747783. 
  5. ↑ "Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes". Current Medicinal Chemistry 12 (12): 1395–411. 2005. doi:10.2174/0929867054020864. PMID 15974991. 
  6. ↑ "Indoles and related compounds as cannabinoid ligands". Mini Reviews in Medicinal Chemistry 8 (4): 370–87. April 2008. doi:10.2174/138955708783955935. PMID 18473928. 
  7. ↑ "Design, synthesis, and structure–activity relationships of indole-3-carboxamides as novel water soluble cannabinoid CB1 receptor agonists". MedChemComm (Royal Society of Chemistry) 1: 54–60. 2010. doi:10.1039/c0md00022a. 
  8. ↑ "Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists". Bioorganic & Medicinal Chemistry Letters 20 (16): 4918–21. August 2010. doi:10.1016/j.bmcl.2010.06.067. PMID 20634067. 
  9. ↑ "Design, synthesis, and structure-activity relationship study of bicyclic piperazine analogs of indole-3-carboxamides as novel cannabinoid CB1 receptor agonists". Bioorganic & Medicinal Chemistry Letters 20 (24): 7327–30. December 2010. doi:10.1016/j.bmcl.2010.10.061. PMID 21074434. 
  10. ↑ "Novel indole and azaindole (pyrrolopyridine) cannabinoid (CB) receptor agonists: design, synthesis, structure-activity relationships, physicochemical properties and biological activity". European Journal of Medicinal Chemistry 46 (10): 5086–98. October 2011. doi:10.1016/j.ejmech.2011.08.021. PMID 21885167. 

Further reading

  1. "C-3 Amido-indole cannabinoid receptor modulators". Bioorganic & Medicinal Chemistry Letters 12 (17): 2399–402. September 2002. doi:10.1016/s0960-894x(02)00466-3. PMID 12161142. 
  2. "Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity". Journal of Medicinal Chemistry 53 (1): 295–315. January 2010. doi:10.1021/jm901214q. PMID 19921781. 
  3. "Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI". British Journal of Pharmacology 153 (2): 367–79. January 2008. doi:10.1038/sj.bjp.0707506. PMID 17965748. 



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