DAA-1106

Last updated

DAA-1106
DAA-1106 structure.png
Identifiers
  • N-(2-Phenoxy-5-fluorophenyl)-N-(2,5-dimethoxybenzyl)acetamide
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C23H22FNO4
Molar mass 395.430 g·mol−1
3D model (JSmol)
  • COC1=CC(CN(C(C)=O)C2=CC(F)=CC=C2OC3=CC=CC=C3)=C(O[11CH3])C=C1
  • InChI=1S/C23H22FNO4/c1-16(26)25(15-17-13-20(27-2)10-12-22(17)28-3)21-14-18(24)9-11-23(21)29-19-7-5-4-6-8-19/h4-14H,15H2,1-3H3https://drugs.ncats.io/drug/696AIN172A#
  • Key:DCRZYADKQRHHSF-UHFFFAOYSA-N
   (verify)

DAA-1106 is a drug which acts as a potent and selective agonist at the peripheral benzodiazepine receptor, also known as the mitochondrial 18 kDa translocator protein or TSPO, but with no affinity at the GABAA receptor. It has anxiolytic effects in animal studies. [1] [2] [3] DAA-1106 has a sub-nanomolar binding affinity (Ki) of 0.28 nM, and has been used extensively in its 3H or 11C radiolabelled form to map TSPO in the body and brain, which has proved especially helpful in monitoring the progress of neurodegenerative diseases such as Alzheimer's disease. [4] [5] [6] [7] [8] [9]

DAA-1106 is used in combination with positron emission tomography (PET) scanning to examine neuroinflammation in vivo . [10]

References

  1. ↑ Okuyama S, Chaki S, Yoshikawa R, Ogawa S, Suzuki Y, Okubo T, Nakazato A, Nagamine M, Tomisawa K (1999). "Neuropharmacological profile of peripheral benzodiazepine receptor agonists, DAA1097 and DAA1106". Life Sciences. 64 (16): 1455–64. doi:10.1016/S0024-3205(99)00079-X. PMID   10321725.
  2. ↑ Okubo T, Yoshikawa R, Chaki S, Okuyama S, Nakazato A (January 2004). "Design, synthesis and structure-affinity relationships of aryloxyanilide derivatives as novel peripheral benzodiazepine receptor ligands". Bioorganic & Medicinal Chemistry. 12 (2): 423–38. doi:10.1016/j.bmc.2003.10.050. PMID   14723961.
  3. ↑ James ML, Selleri S, Kassiou M (2006). "Development of ligands for the peripheral benzodiazepine receptor" (PDF). Current Medicinal Chemistry. 13 (17): 1991–2001. doi:10.2174/092986706777584979. hdl: 2158/222808 . PMID   16842193.
  4. ↑ Venneti S, Lopresti BJ, Wang G, Slagel SL, Mason NS, Mathis CA, Fischer ML, Larsen NJ, Mortimer AD, Hastings TG, Smith AD, Zigmond MJ, Suhara T, Higuchi M, Wiley CA (September 2007). "A comparison of the high-affinity peripheral benzodiazepine receptor ligands DAA1106 and (R)-PK11195 in rat models of neuroinflammation: implications for PET imaging of microglial activation". Journal of Neurochemistry. 102 (6): 2118–31. doi:10.1111/j.1471-4159.2007.04690.x. PMID   17555551. S2CID   3788208.
  5. ↑ Venneti S, Wang G, Nguyen J, Wiley CA (October 2008). "The positron emission tomography ligand DAA1106 binds with high affinity to activated microglia in human neurological disorders". Journal of Neuropathology and Experimental Neurology. 67 (10): 1001–10. doi:10.1097/NEN.0b013e318188b204. PMC   2669281 . PMID   18800007.
  6. ↑ Ji B, Maeda J, Sawada M, Ono M, Okauchi T, Inaji M, Zhang MR, Suzuki K, Ando K, Staufenbiel M, Trojanowski JQ, Lee VM, Higuchi M, Suhara T (November 2008). "Imaging of peripheral benzodiazepine receptor expression as biomarkers of detrimental versus beneficial glial responses in mouse models of Alzheimer's and other CNS pathologies". Journal of Neuroscience. 28 (47): 12255–67. doi:10.1523/JNEUROSCI.2312-08.2008. PMC   2755188 . PMID   19020019.
  7. ↑ Doorduin J, de Vries EF, Dierckx RA, Klein HC (2008). "PET imaging of the peripheral benzodiazepine receptor: monitoring disease progression and therapy response in neurodegenerative disorders". Current Pharmaceutical Design. 14 (31): 3297–315. doi:10.2174/138161208786549443. PMID   19075709.
  8. ↑ Gulyás B, Makkai B, Kása P, Gulya K, Bakota L, Várszegi S, Beliczai Z, Andersson J, Csiba L, Thiele A, Dyrks T, Suhara T, Suzuki K, Higuchi M, Halldin C (January 2009). "A comparative autoradiography study in post mortem whole hemisphere human brain slices taken from Alzheimer patients and age-matched controls using two radiolabelled DAA1106 analogues with high affinity to the peripheral benzodiazepine receptor (PBR) system". Neurochemistry International. 54 (1): 28–36. doi:10.1016/j.neuint.2008.10.001. PMID   18984021. S2CID   21033494.
  9. ↑ Wang M, Gao M, Hutchins GD, Zheng QH (June 2009). "Synthesis of [11C]FEDAA1106 as a new PET imaging probe of peripheral benzodiazepine receptor expression". European Journal of Medicinal Chemistry. 44 (6): 2748–53. doi:10.1016/j.ejmech.2008.08.001. PMID   18790550.
  10. ↑ "NCATS Inxight: Drugs — DAA-1106 C-11". drugs.ncats.io. Retrieved 2020-11-17.


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