JZ-IV-10
Encyclopedia
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).
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.
Piperidine
Piperidine is an organic compound with the molecular formula 5NH. This heterocyclic amine consists of a six-membered ring containing five methylene units and one nitrogen atom...
derivative related to nocaine
Nocaine
-CPCA is a stimulant drug similar in structure to RTI-31, but lacking the two-carbon bridge of the tropane skeleton This compound was first developed as a substitute agent for cocaine.Since this time a large number of substituted phenylpiperidine derivatives have been discovered, hybridizing the...
which is a highly potent triple reuptake inhibitor (SNDRI). The eugeroic modafinil
Modafinil
Modafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
, was used as a lead to fuel these compounds' discovery (J. Zhou, et al. 2004). Although it turns out that the QSAR
Quantitative structure-activity relationship
Quantitative structure–activity relationship or QSPR is the process by which chemical structure is quantitatively correlated with a well defined process, such as biological activity or chemical reactivity.For example, biological activity can be expressed quantitatively as the concentration of a...
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 | ||||||
| 27 → 1249 | 116 → 2884 | 88 → 924 | ||||
| IV-10 → IV-15 | NHPri | 0.8 → 20 | 1.0 → 248 | 1.1 → 473 | ||
| IV-7 → IV-16 | ||||||
| 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
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
+ 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
Cimetidine
Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
, ranitidine
Ranitidine
Ranitidine is a histamine H2-receptor antagonist that inhibits stomach acid production. It is commonly used in treatment of peptic ulcer disease and gastroesophageal reflux disease . Ranitidine is also used alongside fexofenadine and other antihistamines for the treatment of skin conditions...
). 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.