DAA-1106

DAA-1106
Identifiers
	IUPAC name N-(2-Phenoxy-5-fluorophenyl)-N-(2,5-dimethoxybenzyl)acetamide;
CAS Number	220551-92-8;
PubChem CID	10430788;
ChemSpider	8606215;
UNII	3A8IVT5Q3P;
CompTox Dashboard (EPA)	DTXSID30439829 ;
Chemical and physical data
Formula	C23H22FNO4
Molar mass	395.430 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COC1=CC(CN(C(C)=O)C2=CC(F)=CC=C2OC3=CC=CC=C3)=C(O[11CH3])C=C1;
	InChI 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 (K_i) 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

^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ "NCATS Inxight: Drugs — DAA-1106 C-11". drugs.ncats.io. Retrieved 2020-11-17.

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[pmid10321725-1] 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.

[pmid14723961-2] 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.

[pmid16842193-3] 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.

[pmid17555551-4] 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.

[pmid18800007-5] 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.

[pmid19020019-6] 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.

[pmid19075709-7] 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.

[pmid18984021-8] 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.

[pmid18790550-9] 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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v t e Anxiolytics (N05B)
5-HT_1ARTooltip 5-HT1A receptor agonists	Buspirone Gepirone Tandospirone
GABA_ARTooltip GABAA receptor PAMsTooltip positive allosteric modulators	Benzodiazepines: Adinazolam Alprazolam Bromazepam Camazepam Chlordiazepoxide Clobazam Clonazepam Clorazepate Clotiazepam Cloxazolam Diazepam^# Ethyl loflazepate Etizolam Fludiazepam Halazepam Ketazolam Lorazepam^# Medazepam Nordazepam Oxazepam Pinazepam Prazepam; Others: Alpidem^‡ Barbiturates (e.g., phenobarbital) Carbamates (e.g., meprobamate) Carisoprodol Chlormezanone^‡ Ethanol (alcohol) Etifoxine
Hypnotics	Zopiclone
Gabapentinoids (α₂δ VDCC blockers)	Gabapentin Gabapentin enacarbil Phenibut Pregabalin
Antidepressants	SSRIsTooltip Selective serotonin reuptake inhibitors (e.g., escitalopram) SNRIsTooltip Serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine) SARIsTooltip Serotonin antagonist and reuptake inhibitors (e.g., trazodone) TCAsTooltip Tricyclic antidepressants (e.g., clomipramine^#) TeCAsTooltip Tetracyclic antidepressants (e.g., mirtazapine) MAOIsTooltip Monoamine oxidase inhibitors (e.g., phenelzine); Others: Agomelatine Bupropion Tianeptine Vilazodone Vortioxetine
Antipsychotics	Quetiapine Flupentixol
Sympatholytics (Antiadrenergics)	Alpha-1 blockers (e.g., prazosin) Alpha-2 agonists (e.g., clonidine, dexmedetomidine, guanfacine) Beta blockers (e.g., propranolol)
Others	Benzoctamine Cycloserine Fabomotizole Hydroxyzine Lorpiprazole Mebicar Mepiprazole Nicotine Opipramol Oxaflozane^‡ Phenaglycodol Phenibut Picamilon Selank Tiagabine Tofisopam Validolum
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III

v t e Translocator protein modulators
Agonists	Alpidem DAA-1097 DAA-1106 DBI 17-50 fragment Deuterated etifoxine Dithranol (anthralin) Diazepam Diazepam binding inhibitor (DBI) DPA-713 DPA-714 Emapunil Etifoxine FGIN-1-27 FGIN-1-43 GML-1 Olesoxime Ro5-4864 SSR-180,575 W-18 YL-IPA08
Antagonists	PK-11195