RTI-51
Chemical compound
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Formula | C 16 H 20 Br N O 2 |
Molar mass | 338.245 g·mol −1 |
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(–)-2β-Carbomethoxy-3β-(4-bromophenyl)tropane ( RTI- 4229 -51 , bromopane ) is a semi-synthetic alkaloid in the phenyltropane 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 between RTI-31 and RTI-55 . Importantly it has a ratio of monoamine reuptake inhibition of D > S > N (1.8:10.6:37.4nM respectively) which is an unusual balance of effects not produced by other commonly used compounds (although RTI-121 is similar, but more DAT selective). [1] It has been used in its 76 Br radiolabelled form to map the distribution of dopamine transporters in the brain. [2]
Halogen | Atomic № | Atomic Weight | EN | Bond Length |
Fluorine | 9 | 19.0 | 4.0 | |
Chlorine | 17 | 35.5 | 3.2 | |
Bromine | 35 | 79.9 | 3.0 | |
Iodine | 53 | 127 | 2.7 | |
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]
MAT IC 50 (and K i ) for simple phenyltropanes with 1R,2S,3S stereochemistry . [7] | ||||||
Compound | [ 3 H] CFT | [ 3 H] DA | [ 3 H] Nisoxetine | [ 3 H] NE | [ 3 H] Paroxetine | [ 3 H] 5-HT |
Cocaine [8] | 89.1 | 275 cf. 241 | 3300 (1990) | 119 cf. 161 | 1050 (45) | 177 cf. 112 |
WIN 35,065-2 | 23 | 49.8 | 920 (550) | 37.2 | 1960 (178) | 173 |
WIN 35,428 | 13.9 | 23.0 | 835 (503) | 38.6 | 692 (63) | 101 |
RTI-31 | 1.1 | 3.68 | 37 (22) | 5.86 | 44.5 (4.0) | 5.00 |
RTI-113 [9] | 1.98 | 5.25 | 2,926 | 242 | 2,340 | 391 |
RTI-51 | 1.7 | ? | 37.4 (23) | ? | 10.6 (0.96) | ? |
RTI-55 | 1.3 | 1.96 | 36 (22) | 7.51 | 4.21 (0.38) | 1.74 |
RTI-32 | 1.7 | 7.02 | 60 (36) | 8.42 | 240 (23) | 19.4 |
Data in Above table from rats brains (1995). More recent work has advocated using cloned human transporter/s.
See also
References
- ↑ 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 .
- ↑ 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.
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .
2-Carboxymethyl Esters | |
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(3,4-Disubstituted Phenyl)-tropanes | |
Arylcarboxy | |
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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) |