N-(S)-Fenchyl-1-(2-morpholinoethyl)-7-methoxyindole-3-carboxamide

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N-(S)-Fenchyl-1-(2-morpholinoethyl)-7-methoxyindole-3-carboxamide
UR-12 structure.png
Systematic (IUPAC) name
7-methoxy-1-(2-morpholinoethyl)-N-((1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl)-1H-indole-3-carboxamide
Clinical data
Legal status
  • uncontrolled
Identifiers
CAS number 501926-82-5 YesY
501927-29-3 (2-methyl derivative)
ATC code ?
PubChem CID 44307202
ChemSpider 26286811 YesY
Chemical data
Formula C26H37N3O3 
Mol. mass 439.59 g/mol
 YesY (what is this?)  (verify)

7-methoxy-1-(2-morpholinoethyl)-N-((1S,4R)-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl)-1H-indole-3-carboxamide (N-[(S)-fenchyl]-1-[2-(morpholin-4-yl)ethyl]-7-methoxyindole-3-carboxamide, UR-12, MN-25) 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 11nM, but 22x lower affinity for the psychoactive CB1 receptors with a Ki of 245nM. The indole 2-methyl derivative has the ratio of affinities reversed however, with a Ki of 8nM at CB1 and 29nM 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]

2-methyl derivative

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 a large number of related indole-3-carboxamide cannabinoid ligands.[7][8][9][10]

See also[edit]

References[edit]

  1. ^ CANNABINOID RECEPTOR MODULATORS, THEIR PROCESSES OF PREPARATION, AND USE OF CANNABINOID RECEPTOR MODULATORS IN TREATING RESPIRATORY AND NON-RESPIRATORY DISEASES. WO 2001/58869
  2. ^ Rulin Zhao, et al. 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 (vi):89-95.
  3. ^ Hynes, J., et al. (2002). "C-3 Amido-Indole cannabinoid receptor modulators". Bioorganic & Medicinal Chemistry Letters 12 (17): 2399–402. doi:10.1016/S0960-894X(02)00466-3. PMID 12161142.  edit
  4. ^ Wrobleski, Stephen T., et al. (2003). "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. doi:10.1021/jm020329q. PMID 12747783. 
  5. ^ Huffman, J. W.; Padgett, L. W. (2005). "Recent Developments in the Medicinal Chemistry of Cannabimimetic Indoles, Pyrroles and Indenes". Current Medicinal Chemistry 12 (12): 1395–1411. doi:10.2174/0929867054020864. PMID 15974991.  edit
  6. ^ Manera, C.; Tuccinardi, T.; Martinelli, A. (2008). "Indoles and Related Compounds as Cannabinoid Ligands". Mini Reviews in Medicinal Chemistry 8 (4): 370–387. doi:10.2174/138955708783955935. PMID 18473928.  edit
  7. ^ Adam, J. M., et al. (2010). "Design, synthesis, and structure–activity relationships of indole-3-carboxamides as novel water soluble cannabinoid CB1 receptor agonists". MedChemComm 1: 54. doi:10.1039/c0md00022a.  edit
  8. ^ Kiyoi T, et al. (August 2010). "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. doi:10.1016/j.bmcl.2010.06.067. PMID 20634067. 
  9. ^ Moir EM, et al. (December 2010). "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. doi:10.1016/j.bmcl.2010.10.061. PMID 21074434. 
  10. ^ Blaazer, A. R. et al. (2011). "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): 5086–5098. doi:10.1016/j.ejmech.2011.08.021. PMID 21885167.  edit

Further reading[edit]

1. John Hynes., et al. C3 AMIDO-INDOLE CANNABINOID RECEPTOR MODULATORS. Bioorganic and Medical Chemistry Letters. Volume 12 issue 17, 2 September 2002 pages 2399-2402

2. Frost, J. M., et al. (2010). "Indol -3-ylcycloalkyl Ketones: Effects of N1 Substituted Indole Side Chain Variations on CB2 Cannabinoid Receptor Activity". Journal of Medicinal Chemistry 53 (1): 295. doi :10.1021/ jm901214q. PMID 19921781

3. Chin CL, et al. (January 2008). "Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI". British Journal of Pharmacology 153 (2): 367–79. doi :10.1038/ sj.bjp .0707506. PMC 2219521. PMID 17965748