Identifiers
(1R,2S,3S,5S)-3-(4-chlorophenyl)-8-methyl-2-(3-phenyl-1,2-oxazol-5-yl)-8-azabicyclo[3.2.1]octane
PubChem CID
Chemical and physical data
C23H23ClN2O
378.90 g·mol−1
3D model (JSmol)
CN1[C@H]2CC[C@@H]1[C@H]([C@H](C2)C3=CC=C(C=C3)Cl)C4=CC(=NO4)C5=CC=CC=C5
InChI=1S/C23H23ClN2O/c1-26-18-11-12-21(26)23(19(13-18)15-7-9-17(24)10-8-15)22-14-20(25-27-22)16-5-3-2-4-6-16/h2-10,14,18-19,21,23H,11-13H2,1H3/t18-,19+,21+,23-/m0/s1
Key:ZGCYMNJHHKQEGA-KPYOPSEVSA-N
RTI(-4229)-177 (2β-(3-phenylisoxazol-5-yl)-3β-(4-chlorophenyl)tropane, β-CPPIT) is a synthetic stimulant drug from the phenyltropane family, which acts as a DRI with micromolar affinity for the SERT.[1] RTI-177 has an unusually long duration of action of 20 hours or more, substantially longer than the related compound RTI-336 from which it differs in molecular structure only by the absence of a p-methyl group.[2]
"the nonselective monoamine transporter inhibitor RTI-126 and the DAT-selective inhibitors RTI-150 and RTI-336 both had a faster rate of onset (30 min) and a short duration of action (4h). In contrast, the nonselective monoamine transporter inhibitor RTI-112 had a slower rate of onset (30–60 min) and a longer duration of action (10h). The DAT-selective inhibitors RTI-171 and RTI-177 also had slower rates of onset (30–120 min), but RTI-171 had a short duration of action (2.5 h) while RTI-177 had a very long duration of action (20 h)."[3]
RTI
X
R
[3H]CFT
[3H]Nisoxetine
[3H]Paroxetine
—
—
89.1
3298 (1986)
1045 (45)
177
1.28
504 (304)
2420 (220)
1.58
398 (239)
5110 (465)
1.62
299 (180)
6400 (582)
p-cresyl
4.09
1714 (1033)
5741 (522)
p-anisoyl
3.93
756 (450)
4027 (380)
In the Lindsey paper, RTI-177 was wrongly considered to be a dual inhibitor of the NET, although this was later found out to be incorrect.[citation needed]
"In acute toxicity studies in male rats, 3β-(4-chlorophenyl)-2β-[3-(4’-methylphenyl)isoxazol-5-yl]tropane (RTI-336) possessed an LD50 of 180 mg/kg after oral administration, compared with 49 mg/kg for RTI-177 (unpublished results, Howell 2005; Table 9). These results suggested that RTI-336 was a better candidate than RTI-177 for further preclinical development."[2]
Also the potency of the heterocyclic compounds is not as great as would be predicted based on in vitro test results.
Others
VMATsTooltip Vesicular monoamine transporters
Others
2-Carboxymethyl Esters
(3,4-Disubstituted Phenyl)-tropanes
Arylcarboxy
Carboxyalkyl
Acyl
β,α Stereochemistry
α,β Stereochemistry
Heterocycles: 3-Substituted-isoxazol-5-yl
Heterocycles: 3-Substituted-1,2,4-oxadiazole
N-alkyl
N-replaced (S,O,C)
Irreversible
Nortropanes (N-demethylated)