HP-505

HP-505
Identifiers
	IUPAC name 3-phenyl-3H-spiro[isobenzofuran-1,4'-piperidine];
CAS Number	59142-94-8;
PubChem CID	191510;
ChemSpider	166303;
ChEMBL	ChEMBL436281;
CompTox Dashboard (EPA)	DTXSID20974577 ;
Chemical and physical data
Formula	C18H19NO
Molar mass	265.356 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1(C2OC3(CCNCC3)C4=C2C=CC=C4)=CC=CC=C1;
	InChI InChI=1S/C18H19NO/c1-2-6-14(7-3-1)17-15-8-4-5-9-16(15)18(20-17)10-12-19-13-11-18/h1-9,17,19H,10-13H2; Key:ZFJQWOMHWFYLPD-UHFFFAOYSA-N;

HP-505 is a triple reuptake inhibitor that was investigated by Hoechst-Roussel Pharmaceuticals.[1] In mice, HP-505 was a potent inhibitor of tetrabenazine-induced ptosis which may indicate antidepressant activity.[2]

Pharmacology

HP-505 IC₅₀ (µM)[1]
5-HT	NE	DA	NE:5-HT	DA:5-HT
0.19 ± 0.04	0.34 ± 0.1	0.66 ± 0.15	1.8	3.5

The inhibitory effect of HP-505 on serotonin reuptake is approximately 1.8 and 3.5 times stronger than on norepinephrine and dopamine, respectively.[1] Subsequent investigations have found that HP-505 acts on presynaptic dopamine transporters and is devoid of anticholinergic effects.[3]

Synthesis

The N-methylated analog is called HP-365 [59142-29-9].

An older synthesis is available, although more modern methods exist now:[4]

HP-365 patent:[5]

References

Meyerson LR, Ong HH, Martin LL, Ellis DB (June 1980). "Effect of antidepressant agents on beta-adrenergic receptor and neurotransmitter regulatory systems". Pharmacology, Biochemistry, and Behavior. 12 (6): 943–948. doi:10.1016/0091-3057(80)90457-8. PMID 6105676. S2CID 45400599.
Klioze SS, Bauer VJ, Geyer HM (April 1977). "Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 2. Compounds containing a heteroatom attached to nitrogen". Journal of Medicinal Chemistry. 20 (4): 610–612. doi:10.1021/jm00214a039. PMID 850252.
Puri SK, Mantione CR, Petko W, Ellis DB (1979). "Spiroisobenzofuran Piperidine Derivatives. Interaction with Pre- and Post-Synaptic Dopaminergic Sites". In Usdin E, Kopin IJ, Barchas J (eds.). Catecholamines: Basic and Clinical Frontiers. Pergamon. pp. 514–516. doi:10.1016/B978-1-4832-8363-0.50158-0. ISBN 978-1-4832-8363-0.
Maier, C. A., Wünsch, B. (1 January 2002). "Novel Spiropiperidines as Highly Potent and Subtype Selective σ-Receptor Ligands. Part 1". Journal of Medicinal Chemistry. 45 (2): 438–448. doi:10.1021/jm010992z. ISSN 1520-4804 0022-2623, 1520-4804. {{cite journal}}: Check |issn= value (help)
Victor J. Bauer & Raymond W. Kosley, Jr., U.S. Patent 3,959,475 (1976 to CNA Holdings LLC).

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[BETA-1] Meyerson LR, Ong HH, Martin LL, Ellis DB (June 1980). "Effect of antidepressant agents on beta-adrenergic receptor and neurotransmitter regulatory systems". Pharmacology, Biochemistry, and Behavior. 12 (6): 943–948. doi:10.1016/0091-3057(80)90457-8. PMID 6105676. S2CID 45400599.

[2] Klioze SS, Bauer VJ, Geyer HM (April 1977). "Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 2. Compounds containing a heteroatom attached to nitrogen". Journal of Medicinal Chemistry. 20 (4): 610–612. doi:10.1021/jm00214a039. PMID 850252.

[3] Puri SK, Mantione CR, Petko W, Ellis DB (1979). "Spiroisobenzofuran Piperidine Derivatives. Interaction with Pre- and Post-Synaptic Dopaminergic Sites". In Usdin E, Kopin IJ, Barchas J (eds.). Catecholamines: Basic and Clinical Frontiers. Pergamon. pp. 514–516. doi:10.1016/B978-1-4832-8363-0.50158-0. ISBN 978-1-4832-8363-0.

[4] Maier, C. A., Wünsch, B. (1 January 2002). "Novel Spiropiperidines as Highly Potent and Subtype Selective σ-Receptor Ligands. Part 1". Journal of Medicinal Chemistry. 45 (2): 438–448. doi:10.1021/jm010992z. ISSN 1520-4804 0022-2623, 1520-4804. {{cite journal}}: Check |issn= value (help)

[5] Victor J. Bauer & Raymond W. Kosley, Jr., U.S. Patent 3,959,475 (1976 to CNA Holdings LLC).