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NE-100
Identifiers
	IUPAC name 4-Methoxy-3-(2-phenylethoxy)-N,N-dipropylbenzeneethanamine;
CAS Number	149860-29-7 ;
PubChem CID	9841596;
IUPHAR/BPS	6679;
ChemSpider	8017311;
UNII	RN9I7K5RVN;
CompTox Dashboard (EPA)	DTXSID701030382 ;
Chemical and physical data
Formula	C23H33NO2
Molar mass	355.522 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCCN(CCC)CCC1=CC(=C(C=C1)OC)OCCC2=CC=CC=C2;
	InChI InChI=1S/C23H33NO2/c1-4-15-24(16-5-2)17-13-21-11-12-22(25-3)23(19-21)26-18-14-20-9-7-6-8-10-20/h6-12,19H,4-5,13-18H2,1-3H3; Key:YBLIQJGXRLZBCZ-UHFFFAOYSA-N;

NE-100 or 4-methoxy-3-(2-phenylethoxy)-N,N-dipropylbenzeneethanamine is a selective sigma-1 receptor antagonist, with a reported binding affinity of K_i = 1.03 ± 0.01 nM, and more than 205 times selectivity over the sigma-2 receptor.^[1]^[2]

NE-100 was one of the earliest selective sigma-1 receptor ligands reported and has been widely used as a pharmacological tool. The original, eight step synthesis of NE-100 was reported by Atsuro Nakazato and colleagues of Taisho Pharmaceutical Company in 1999.^[3] More recently, Michael Kassiou and co-workers have reported a more expedient synthesis of NE-100 that proceeds in 56% unoptimized yield over 4 steps.^[4]

References

^ Okuyama S, Nakazato A (1999). "NE-100: A novel sigma receptor antagonist". CNS Drug Rev. 2 (2): 226–237. doi:10.1111/j.1527-3458.1996.tb00299.x.
^ Berardi F, Ferorelli S, Colabufo NA, Leopoldo M, Perrone R, Tortorella V (2001). "A multireceptorial binding reinvestigation on an extended class of sigma ligands: N-[omega-(indan-1-yl and tetralin-1-yl)alkyl] derivatives of 3,3-dimethylpiperidine reveal high affinities towards sigma1 and EBP sites". Bioorg. Med. Chem. 9 (5): 1325–35. doi:10.1016/s0968-0896(01)00011-6. PMID 11377189.
^ Nakazato A, Ohta K, Sekiguchi Y, Okuyama S, Chaki S, Kawashima Y, Hatayama K (1999). "Design, Synthesis, Structure-Activity Relationships, and Biological Characterization of Novel Arylalkoxyphenylalkylamine s Ligands as Potential Antipsychotic Drugs". Journal of Medicinal Chemistry. 42 (6): 1076–1087. doi:10.1021/jm980212v. PMID 10090790.
^ Banister SD, Moussa IA, Jorgensen WT, Chua SW, Kassiou M (2011). "Molecular hybridization of 4-azahexacyclo[5.4.1.0^2,6.0^3,10.0^5,9.0^8,11]dodecane-3-ol with sigma (s) receptor ligands modulates off-target activity and subtype selectivity". Bioorg. Med. Chem. Lett. 21 (12): 3622–3626. doi:10.1016/j.bmcl.2011.04.098. PMID 21555222.

[Okuyama_1999-1] Okuyama S, Nakazato A (1999). "NE-100: A novel sigma receptor antagonist". CNS Drug Rev. 2 (2): 226–237. doi:10.1111/j.1527-3458.1996.tb00299.x.

[Berardi_2001-2] Berardi F, Ferorelli S, Colabufo NA, Leopoldo M, Perrone R, Tortorella V (2001). "A multireceptorial binding reinvestigation on an extended class of sigma ligands: N-[omega-(indan-1-yl and tetralin-1-yl)alkyl] derivatives of 3,3-dimethylpiperidine reveal high affinities towards sigma1 and EBP sites". Bioorg. Med. Chem. 9 (5): 1325–35. doi:10.1016/s0968-0896(01)00011-6. PMID 11377189.

[Nakazato_1999-3] Nakazato A, Ohta K, Sekiguchi Y, Okuyama S, Chaki S, Kawashima Y, Hatayama K (1999). "Design, Synthesis, Structure-Activity Relationships, and Biological Characterization of Novel Arylalkoxyphenylalkylamine s Ligands as Potential Antipsychotic Drugs". Journal of Medicinal Chemistry. 42 (6): 1076–1087. doi:10.1021/jm980212v. PMID 10090790.

[Banister_2011-4] Banister SD, Moussa IA, Jorgensen WT, Chua SW, Kassiou M (2011). "Molecular hybridization of 4-azahexacyclo[5.4.1.0^2,6.0^3,10.0^5,9.0^8,11]dodecane-3-ol with sigma (s) receptor ligands modulates off-target activity and subtype selectivity". Bioorg. Med. Chem. Lett. 21 (12): 3622–3626. doi:10.1016/j.bmcl.2011.04.098. PMID 21555222.

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