DDD-016

DDD-016
Identifiers
	IUPAC name 5-methyl-13-thia-1,5-diazapentacyclo[10.8.1.02,7.08,21.015,20]henicosa-2(7),8(21),9,11,15,17,19-heptaene;
CAS Number	1260506-25-9;
PubChem CID	49839235;
Chemical and physical data
Formula	C19H18N2S
Molar mass	306.43 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1CCC2=C(C1)C3=C4N2C5=CC=CC=C5CSC4=CC=C3;
	InChI InChI=1S/C19H18N2S/c1-20-10-9-17-15(11-20)14-6-4-8-18-19(14)21(17)16-7-3-2-5-13(16)12-22-18/h2-8H,9-12H2,1H3; Key:VBNQJCKPRLQJSO-UHFFFAOYSA-N;

DDD-016 is a novel pentacyclic compound initially designed and synthesized as a potential atypical antipsychotic, with its receptor binding affinities screened across a broad panel of over 80 central nervous system and other receptors.^[1] As part of a series of investigational compounds—which also includes DDD-024, DDD-025, and DDD-029^[2] stands out for its proposed anti-psychotic activity, believed to be mediated through dual serotonin 5-HT_2A and dopamine D2 receptor antagonism.^[3]

Synthesis

A Goldberg reaction between 2-aminothiophenol [137-07-5] (1) and 2-bromobenzyl bromide [3433-80-5] (2) gives 5,11-Dihydrodibenzo[b,e][1,4]thiazepine, [3048-78-0] (3). Nitrosylation with nitrous acid gives (4). This is then reduced to the amino group. Condensation with 1-methyl-4-piperidone [1445-73-4] gives (5). Fischer indole synthesis completes the synthesis.

{Note that the Goldberg reaction is being replaced by the Hartwig amination.}

References

^ Bandyopadhyaya A, Rajagopalan DR, Rath NP, Herrold A, Rajagopalan R, Napier TC, et al. (2012). "The synthesis and receptor binding affinities of DDD-016, a novel, potential, atypical antipsychotic". MedChemComm. 3 (5): 580. doi:10.1039/c2md00311b.
^ Rajagopalan R, Bandyopadhyaya A, Rajagopalan DR, Rajagopalan P (January 2014). "The synthesis and comparative receptor binding affinities of novel, isomeric pyridoindolobenzazepine scaffolds". Bioorganic & Medicinal Chemistry Letters. 24 (2): 576–579. doi:10.1016/j.bmcl.2013.12.024. PMID 24365159.
^ Rajagopalan P, Tracey H, Chen Z, Bandyopadhyaya A, Veeraraghavan S, Rajagopalan DR, et al. (July 2014). "DDD-028: a potent potential non-opioid, non-cannabinoid analgesic for neuropathic and inflammatory pain". Bioorganic & Medicinal Chemistry Letters. 24 (14): 3088–3091. doi:10.1016/j.bmcl.2014.05.016. PMID 24863744.
^ Rajagopalan P (August 1984). "Synthetic CNS agents. 1. (+/-)-1,2,3,4,4a,5,10,10a-Octahydro-5,10[1',2'] -benzenobenz[g]isoquinoline hydrochloride. A new, highly potent, potential antidepressant". Journal of Medicinal Chemistry. 27 (8): 946–947. doi:10.1021/jm00374a002. PMID 6747994.

[1] Bandyopadhyaya A, Rajagopalan DR, Rath NP, Herrold A, Rajagopalan R, Napier TC, et al. (2012). "The synthesis and receptor binding affinities of DDD-016, a novel, potential, atypical antipsychotic". MedChemComm. 3 (5): 580. doi:10.1039/c2md00311b.

[Rajagopalan_2014-2] Rajagopalan R, Bandyopadhyaya A, Rajagopalan DR, Rajagopalan P (January 2014). "The synthesis and comparative receptor binding affinities of novel, isomeric pyridoindolobenzazepine scaffolds". Bioorganic & Medicinal Chemistry Letters. 24 (2): 576–579. doi:10.1016/j.bmcl.2013.12.024. PMID 24365159.

[3] Rajagopalan P, Tracey H, Chen Z, Bandyopadhyaya A, Veeraraghavan S, Rajagopalan DR, et al. (July 2014). "DDD-028: a potent potential non-opioid, non-cannabinoid analgesic for neuropathic and inflammatory pain". Bioorganic & Medicinal Chemistry Letters. 24 (14): 3088–3091. doi:10.1016/j.bmcl.2014.05.016. PMID 24863744.

[4] Rajagopalan P (August 1984). "Synthetic CNS agents. 1. (+/-)-1,2,3,4,4a,5,10,10a-Octahydro-5,10[1',2'] -benzenobenz[g]isoquinoline hydrochloride. A new, highly potent, potential antidepressant". Journal of Medicinal Chemistry. 27 (8): 946–947. doi:10.1021/jm00374a002. PMID 6747994.

[1]

[2]

[3]

[4]

Synthesis

See also

References