3-PPP

3-PPP (N-n-propyl-3-(3-hydroxyphenyl)piperidine) is a mixed sigma σ₁ and σ₂ receptor agonist (with similar affinity for both subtypes, though slightly higher affinity for the latter)^[1] and D₂ receptor partial agonist which is used in scientific research.^[2][3] It shows stereoselectivity in its pharmacodynamics.^[2] (+)-3-PPP is the enantiomer that acts as an agonist of the sigma receptors;^[3] it is also an agonist of both D₂ presynaptic and postsynaptic receptors.^[2] Conversely, (−)-3-PPP, also known as preclamol (INNTooltip International Nonproprietary Name), acts as an agonist of presynaptic D₂ receptors but as an antagonist of postsynaptic D₂ receptors, and has antipsychotic effects.^[2][4] 3-PPP has also been reported to be a monoamine reuptake inhibitor and possibly to act at adrenergic receptors or some other non-sigma receptor.^[5]

3-PPP

Clinical data
Other names	Preclamol
Identifiers
IUPAC name (±)-3-(1-Propylpiperidin-3-yl)phenol
CAS Number	75240-91-4 Y 85966-89-8 ((+)-isomer)
PubChem CID	55445
ChemSpider	50067
UNII	ND3NDM2EHM
ChEBI	CHEBI:125440
ChEMBL	ChEMBL276500
CompTox Dashboard (EPA)	DTXSID7048453
Chemical and physical data
Formula	C14H21NO
Molar mass	219.328 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCCN1CCCC(C1)C2=CC(=CC=C2)O
InChI InChI=1S/C14H21NO/c1-2-8-15-9-4-6-13(11-15)12-5-3-7-14(16)10-12/h3,5,7,10,13,16H,2,4,6,8-9,11H2,1H3 Key:HTSNFXAICLXZMA-UHFFFAOYSA-N

Synthesis

ChemDrug Synthesis:^[6][7][8] Patent:^[9] Short & Efficient:^[10] Sino:^[11]

The Grignard reagent was prepared for 3-Bromoanisole [2398-37-0] (1) and this was reacted with 3-Bromopyridine [626-55-1] (2) to give 3-(3-methoxyphenyl)pyridine [4373-67-5] (3). Reaction with 1-bromopropane [106-94-5] occurred to give the quaternary salt PC13695099 (4a). {Alternatively catalytic hydrogenation of 3 could be attempted directly to give 3-(3-methoxyphenyl)piperidine [79601-21-1] (4b). A second reductive amination with propionic acid was then performed.} Catalytic hydrogenation of the quat cation gave 3-(3-methoxyphenyl)-1-propylpiperidine [86562-23-4] (5). Demethylation with hydrogen bromide then completed the synthesis of preclamol (6).

See also

• 3-Phenylpiperidine
• 4-PPBP
• Alazocine
• OSU-6162
• PF-219,061