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RTI-51

From Wikipedia, the free encyclopedia
Chemical compound
Pharmaceutical compound
RTI-51
Identifiers
  • methyl (1R,2S,3S,5S)-3-(4-bromophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
CAS Number
PubChemCID
UNII
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC16H20BrNO2
Molar mass338.245 g·mol−1
3D model (JSmol)
  • Brc1ccc(cc1)[C@H]2C[C@@H]3N(C)[C@H]([C@H]2C(=O)OC)CC3
  • InChI=1S/C16H20BrNO2/c1-18-12-7-8-14(18)15(16(19)20-2)13(9-12)10-3-5-11(17)6-4-10/h3-6,12-15H,7-9H2,1-2H3/t12-,13-,14+,15+/m1/s1 ☒N
  • Key:HNVGNUVAMRLMSG-KBXIAJHMSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

(–)-2β-Carbomethoxy-3β-(4-bromophenyl)tropane (RTI-4229-51,bromopane) is a semi-synthetic alkaloid in thephenyltropane group of psychostimulant compounds. First publicized in the 1990s, it has not been used enough to have gained a fully established profile. RTI-51 can be expected to have properties lying somewhere in betweenRTI-31 andRTI-55. It has a ratio of monoamine reuptake inhibition of dopamine > serotonin > norepinephrine (1.8:10.6:37.4 nM respectively) which is an unusual balance of effects not produced by other commonly used compounds (althoughRTI-121 is similar, but moreDAT selective).[1] It has been used in its76Brradiolabelled form to map the distribution of dopamine transporters in the brain.[2]

Modern research seems to confirm the above hypothesis.[3] However, earlier work produced more scattered results.[4] Based upon what is obvious from the table, RTI-31, RTI-51, and RTI-55 are all similarly potent TRIs.[5][6]

MATIC50 (andKi) for simplephenyltropanes with 1R,2S,3Sstereochemistry.[7]
Compound[3H]CFT[3H]DA[3H]Nisoxetine[3H]NE[3H]Paroxetine[3H]5-HT
Cocaine[8]89.1275cf. 2413300 (1990)119cf. 1611050 (45)177cf. 112
WIN 35,065-22349.8920 (550)37.21960 (178)173
WIN 35,42813.923.0835 (503)38.6692 (63)101
RTI-311.13.6837 (22)5.8644.5 (4.0)5.00
RTI-113[9]1.985.252,9262422,340391
RTI-511.7?37.4 (23)?10.6 (0.96)?
RTI-551.31.9636 (22)7.514.21 (0.38)1.74
RTI-321.77.0260 (36)8.42240 (23)19.4

Data in above table is from rats brains (1995). More recent work has advocated using cloned human transporters.

See also

[edit]

References

[edit]
  1. ^Singh S (March 2000). "Chemistry, design, and structure-activity relationship of cocaine antagonists".Chemical Reviews.100 (3):925–1024.doi:10.1021/cr9700538.PMID 11749256.
  2. ^Loch C, Müller L, Ottaviani M, Halldin C, Farde L, Maziere B. Synthesis of 2β-carbomethoxy-3β-(4-[76Br]bromophenyl)tropane ([76Br]β-CBT), a PET tracer for in vivo imaging of the dopamine uptake sites.Journal of labelled compounds & radiopharmaceuticals. 1995; 36(4):385-392.
  3. ^Wee S, Carroll FI, Woolverton WL (February 2006)."A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants".Neuropsychopharmacology.31 (2):351–62.doi:10.1038/sj.npp.1300795.PMID 15957006.S2CID 7224342.
  4. ^Stathis M, Scheffel U, Lever SZ, Boja JW, Carroll FI, Kuhar MJ (June 1995)."Rate of binding of various inhibitors at the dopamine transporter in vivo".Psychopharmacology.119 (4):376–84.doi:10.1007/BF02245852.PMID 7480516.S2CID 20022021.
  5. ^Kimmel HL, Carroll FI, Kuhar MJ (December 2001). "Locomotor stimulant effects of novel phenyltropanes in the mouse".Drug and Alcohol Dependence.65 (1):25–36.doi:10.1016/S0376-8716(01)00144-2.PMID 11714587.
  6. ^Kuhar MJ, Carroll FI, Bharat N, Landry DW (August 2001). "Anticocaine catalytic antibodies have no affinity for RTI compounds: implications for treatment".Synapse.41 (2):176–8.doi:10.1002/syn.1072.PMID 11400184.S2CID 11862673.
  7. ^Carroll FI, Kotian P, Dehghani A, Gray JL, Kuzemko MA, Parham KA, et al. (January 1995). "Cocaine and 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid ester and amide analogues. New high-affinity and selective compounds for the dopamine transporter".Journal of Medicinal Chemistry.38 (2):379–88.doi:10.1021/jm00002a020.PMID 7830281.
  8. ^Kozikowski AP, Johnson KM, Deschaux O, Bandyopadhyay BC, Araldi GL, Carmona G, et al. (April 2003). "Mixed cocaine agonist/antagonist properties of (+)-methyl 4beta-(4-chlorophenyl)-1-methylpiperidine-3alpha-carboxylate, a piperidine-based analog of cocaine".The Journal of Pharmacology and Experimental Therapeutics.305 (1):143–50.doi:10.1124/jpet.102.046318.PMID 12649362.S2CID 29377097.
  9. ^Damaj MI, Slemmer JE, Carroll FI, Martin BR (June 1999). "Pharmacological characterization of nicotine's interaction with cocaine and cocaine analogs".The Journal of Pharmacology and Experimental Therapeutics.289 (3):1229–36.PMID 10336510.
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(3,4-Disubstituted Phenyl)-tropanes
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