JZ-IV-10

JZ-IV-10

Systematic (IUPAC) name
(+)-2-([(3R,4S)-1-methyl-4-(4-chlorophenyl)piperidin-3-yl]methylthio)-N-isopropylacetamide
Clinical data
Pregnancy cat.	?
Legal status	?
Identifiers
ATC code	?
PubChem	CID 11291199
Chemical data
Formula	C18H27ClN2OS
Mol. mass	354.937 g/mol
SMILES	eMolecules & PubChem
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JZ-IV-10 is a piperidine derivative related to nocaine which is a highly potent triple reuptake inhibitor (SNDRI). The eugeroic modafinil, was used as a lead to fuel these compounds' discovery (J. Zhou, et al. 2004). Although it turns out that the QSAR of the pharmacophoric elements do not appear to be strongly similar. The other isomers were also prepared, although they are weaker than the R,S probes invented in the current study (R. He, et al. 2005).

JZ #	R	X	Y	[3H]NE	[3H]DA	[3H]5HT
III-82 → ?	Me	-CO2H	70.2 → ?	121.2 → ?	269.9 → ?
III-48 → III-59	Ester	OMe	25 → 53	80 → 231	208 → 809
IV-22 → ?	H	10 → 31.1	114 → 107.8	170 → 774.9
IV-25 → IV-37	Me	Amide	NH2	39 → 178	159 → 209	557 → 5790
	H	10 → 31.1	114 → 107.8	170 → 774.9
III-62 → III-85	Me	HNOH	15 → 12	85 → 55	227 → 1795
IV-5 → IV-14	HNMe	25 → 86	13 → 164	110 → 2033
IV-23 → IV-27	-NMe2	27 → 1249	116 → 2884	88 → 924
IV-10 → IV-15	NHPri	0.8 → 20	1.0 → 248	1.1 → 473
IV-7 → IV-16	-N(CH2)5	0.68 → 460	83 → 379	4.5 → 825
III-84 → IV-34	H2	OH	0.94 → 42	16 → 12	158 → 2183
IV-35 → IV-36	OMe	6 → 25	50 → 15	191 → 469
III-86 → III-91	OAc	3.6 → 29	35 → 9	57 → 87
III-87 → III-90	OBz	4.5 → 18	68 → 32	6.7 → 199
IV-17 → IV-21	Het	31.5 → 217.6	125.7 → 1,653	220.9 → 1,079

Upon "treatment" of the ligands with (H₂O₂ + AcOH) the sulfur atom is oxidized. The resultant molecules then lose most of their potency. This is not a major concern though (c.f. cimetidine, ranitidine). Little has been reported about the SAR of modafinil itself, and it is interesting to consider how these new findings could be applied retrospectively. The NRI selective molecules were employed as brain imaging agents to unravel details about the NE transporter. NRIs are important probes, but they do not function as robust reinforcers.