RTI-51

(–)-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 ⁷⁶Br radiolabelled form to map the distribution of dopamine transporters in the brain.[2]

Comparison of halogens

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

RTI-51

Identifiers
IUPAC name methyl (1R,2S,3S,5S)-3-(4-bromophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
CAS Number	135367-08-7^Y
PubChem CID	22595194
CompTox Dashboard (EPA)	DTXSID40720932
Chemical and physical data
Formula	C16H20BrNO2
Molar mass	338.245 g·mol^−1
3D model (JSmol)	Interactive image
SMILES Brc1ccc(cc1)[C@H]2C[C@@H]3N(C)[C@H]([C@H]2C(=O)OC)CC3
InChI 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
^NY (what is this?)  (verify)

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 IC50 (and Ki) for simple phenyltropanes with 1R,2S,3S stereochemistry.[7]
Compound	[^3H]CFT	[^3H]DA	[^3H]Nisoxetine	[^3H]NE	[^3H]Paroxetine	[^3H]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

• List of cocaine analogues

References

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.
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.
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.
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.
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.