List of phenyltropanes

Lua error in package.lua at line 80: module 'strict' not found.

Phenyltropanes are a family of chemical compounds originally derived from structural modification of cocaine. These compounds present many different avenues of research into therapeutic applications, particularly in addiction treatment. Uses vary depending on their construction and structure-activity relationship ranging from the treating of cocaine dependency to understanding the dopamine reward system in the human brain to treating Alzheimer's & Parkinson's diseases. (Since 2008 there have been continual additions to the list and enumerations of the plethora of types of chemicals that fall into the category of this substance profile.) Many of the compounds were first elucidated in published material by the Research Triangle Institute and are thus named with "RTI" serial-numbers. Similarly, a number of others are named for Sterling-Winthrop pharmaceuticals ("WIN" serial-numbers) and Wake Forest University ("WF" serial-numbers).

3D rendering of troparil; which comprises a privileged scaffold of among the phenyltropane class of compounds.

File:Troparil structure.png

Troparil structure: c.f. U.S. Patent 5,496,953

1 2-Carboxymethyl esters
- 1.1 (3,4-Disubstituted phenyl)-tropanes
2 Carboxyaryl
3 Carboxyalkyl
4 Amides
5 Acyl
6 Ester reduction
7 β,α Stereochemistry
8 α,β Stereochemistry
9 Aryl-Tropenes
10 Heterocycles
- 10.1 3-Substituted-isoxazol-5-yl
- 10.2 3-Substituted-1,2,4-oxadiazole
11 η⁶-3β-(transition metal complexed phenyl)tropanes
12 2-Alkane/Alkene
13 N-alkyl
14 Tricyclic/N-constrained (inclu. N-bridged/fused/tethered)
15 3-(2-thiophene) and 3-(2-furan)
16 N-replaced (S,O,C)
17 Diaryl
18 Radiolabeled
- 18.1 Transition metal complexes
19 Irreversible
20 Nortropanes (N-demethylated)
21 Thiophenyltropanes
22 Select annotations of above
23 Sister substances
24 Cycloalkane-ring alterations of the tropane ring system
- 24.1 Azanonane
- 24.2 Azabornane
- 24.3 Piperidine analogues
25 Misc.
26 Phenyltropane based Benztropines
27 F&B series (Biotin side-chains etc.)
28 See also
29 References
30 External links

2-Carboxymethyl esters

File:Epibati-tropane.svg

Epibati-tropane: U.S. Patent 6,479,509 containing a nitrogen heteroatom in the benzene ring formation.

200px

File:Tamagnan.png

Tamagnan:^[1] pM activity for SERT

File:RTI-298.svg

RTI-298

(4′-)para-cis-propenyl-phenyl-methylecgonine. A rare SDRI compound with negligible NET affinity (>28,000 displacement value for NET ligand) that retains significant DAT & SERT affinity.

Like cocaine, phenyltropanes are considered a 'typical' or 'classical' (i.e. "cocaine-like") DAT re-uptake pump ligands in that they stabilize an "open-to-out" conformation on the dopamine transporter; despite the extreme similarity to phenyltropanes, benztropine and others are in suchwise not considered "cocaine-like" and are instead considered atypical inhibitors insofar as they stabilize what is considered a more inward-facing (closed-to-out) conformational state.^[2]

Considering the differences between PTs and cocaine: the difference in the length of the benzoyloxy and the phenyl linkage contrasted between cocaine and phenyltropanes makes for a shorter distance between the centroid of the aromatic benzene and the bridge nitrogen of the tropane in the latter PTs. This distance being on a scale of 5.6 Å for phenyltropanes and 7.7 Å for cocaine or analogs with the benzoyloxy intact.^{[lower-alpha 1]} The manner in which this sets phenyltropanes into the binding pocket at MAT is postulated as one possible explanation to account for PTs increased behavioral stimulation profile over cocaine.^{[lower-alpha 2]}

Certain phenyltropanes can be used as a smoking cessation aid. Blank spacings within tables for omitted data use "no data", "?", "-" or "—" interchangeably.

2β-carbmethoxy-3β-(4′-substituted phenyl)tropanes
Short Name (Singh's #)	X (para-substitution)	DA [³H]WIN 35428	5HT [³H]paroxetine	NE [³H]nisoxetine	selectivity 5-HTT/DAT	selectivity NET/DAT
cocaine	H	102 ± 12 241 ± 18^ɑ	1045 ± 89 112 ± 2^b	3298 ± 293 160 ± 15^c	10.2 0.5^d	32.3 0.7^e
WIN 35,065-2 (CPT) 11a	H	23 ± 5.0 49.8 ± 2.2^ɑ	1962 ± 61 173 ± 13^b	920 ± 73 37.2 ± 5.2^c	85.3 3.5^d	40.0 0.7^e
WIN 35,428 (CFT) 11b	F	14 (15.7 ± 1.4) 22.9 ± 0.4^ɑ	156 (810 ± 59) 100 ± 13^b	85 (835 ± 45) 38.6 ± 9.9^c	51.6 4.4^d	53.2 1.7^e
11k	NO₂	10.1 ± 0.10	?	?	?	?
RTI-29^[4]	NH₂	9.8	5110	151	—	—
RTI-31 11c	Cl	1.12 ± 0.06 3.68 ± 0.09^ɑ	44.5 ± 1.3 5.00 ± 0.05^b	37 ± 2.1 5.86 ± 0.67^c	39.7 1.3^d	33.0 1.7^e
RTI-32 11f	Me	1.71 ± 0.30 7.02 ± 0.30^ɑ	240 ± 27 19.38 ± 0.65^b	60 ± 0.53^e 8.42 ± 1.53^c	140 2.8^d	35.1 1.2^e
RTI-51	Br	1.69	10.6	37.4	—	—
Iometopane (RTI-55) 11e	I	1.26 ± 0.04 1.96 ± 0.09^ɑ	4.21 ± 0.3 1.74 ± 0.23^b	36 ± 2.7 7.51 ± 0.82^c	3.3 0.9^d	28.6 3.8^e
RTI-83 11g	Et	55 ± 2.1	28.4 ± 3.8	4030 ± 381	0.5	73.3
RTI-11w 11w	cis-propenyl	15 ± 1.2	7.1 ± 0.71	28,000 ± 300	0.5	1867
RTI-298^[5]	–≡–Ph	3.7	46.8	347	—	—
RTI-436	–CH=CHPh	3.09	335 (31)	1960 (1181)	—	—
RTI-430	–C≡C(CH₂)₂Ph	6.28	2128 (198)	1470 (886)	—	—
Tamagnan^[1]	p-thiophene	12	0.017	189	—	—
11d	Br	1.81 ± 0.30	10.6 ± 0.24	37.4 ± 5.2	5.8	20.7
11h	OH	12.1 ± 0.86	—	—	—	—
11i	OCH₃	8.14 ± 1.3	—	—	—	—
11j	NH₂	24.8 ± 1.3	—	—	—	—
11l	N₃	2.12 ± 0.13	—	—	—	—
11m	CF₃	13.1 ± 2.2	—	—	—	—
11n	NHCOCH₃	64.2 ± 2.6	—	—	—	—
11o	NHCOC₂H₅	121 ± 2.7	—	—	—	—
11p	NHCO₂C₃H₅	316 ± 48	—	—	—	—
11q	Sn(CH₃)₃	144 ± 37	—	—	—	—
11r	n-C₃H₇	68.5 ± 7.1	70.4 ± 4.1	3920 ± 130	1.0	57.2
11s	CH(CH₃)₂	597 ± 52	191 ± 9.5	75000 ± 5820	0.3	126
11t	CH-CH₂	1.24 ± 0.2	9.5 ± 0.8	78 ± 4.1	7.7	62.9
11u	C(=CH₂)CH₃	14.4 ± 0.3	3.13 ± 0.16	1330 ± 333	0.2	92.4
11v	trans-CH=CHCH₃	5.29 ± 0.53	11.4 ± 0.28	1590 ± 93	2.1	300
11x	CH₂CH=CH₂	32.8 ± 3.1	28.4 ± 2.4	2480 ± 229	0.9	75.6
11y	C≡CH	1.2 ± 0.1	4.4 ± 0.4	83.2 ± 2.8	3.7	69.3
11z	C≡CCH₃	2.37 ± 0.2	15.7 ± 1.5	820 ± 46	6.6	346
11aa	Ph	10.3 ± 2.6^f 29.4 ± 3.8^ɑ	—	—	—	—
11bb	3β-2-naphthyl	3.32 ± 0.08^f 3.53 ± 0.09^ɑ	—	—	—	—

^ɑK_i value for displacement of [³H]DA uptake.
^bK_i value for displacement of [³H]5-HT uptake.
^cK_i value for displacement of [³H]NE uptake.
^d[³H]5-HT uptake to [³H]DA uptake ratio.
^e[³H]NE uptake to [³H]DA uptake ratio.
^fIC₅₀ for displacement of [³H]cocaine.

*Para*-*meta*-substituted 2β-carbomethoxy-3α-(4′-substituted phenyl)tropanes^[3]
Compound	Short Name (S. Singh)	Y	X	DA	5HT	NE	Selectivity 5-HTT/DAT	Selectivity NET/DAT
250px
	16a	F	H	23 ± 7.8	-	-	-	-
	16b	Cl	H	10.6 ± 1.8	-	-	-	-
	16c	Br	H	7.93 ± 0.08^ɑ	-	-	-	-
	16d	I	H	26.1 ± 1.7	-	-	-	-
	16e	SnBu₃	H	1100 ± 170	-	-	-	-
	17a	CH₃	F	2.95 ± 0.58	-	-	-	-
	17b	CH₃	Cl	0.81 ± 0.05	10.5 ± 0.05	36.2 ± 1.0	13.0	44.7
	17c^[6] (Dichloropane) (RTI-111)	Cl	Cl	0.79 ± 0.08	3.13 ± 0.36	18.0 ± 0.8	4.0	22.8
	17d (RTI-97)	Br	NH₂	3.91 ± 0.59	181	282	-	-
	17e (RTI-88)	I	NH₂	1.35 ± 0.11	120 ± 4	1329 ± 124	88.9	984
	17f	I	N₃	4.93 ± 0.32	-	-	-	-

^ɑIC₅₀ determined in Cynomolgous monkey caudate-putamen

*Para*-*meta*(3′)-*meta*(5′)-(di-meta)-substituted 2β-carbomethoxy-(3′,4′,5′-substituted phenyl)tropanes^[7]
Short Name (All compounds tested as HCl salts)	X 3′-(meta)	Y 5′-(di-meta)	OR 4′-(para)	DAT IC₅₀ [³H](compound #)12	5-HTT K_i [³H]Paroxetine	NET K_i [³H]Nisoxetine	Selectivity NET/DAT Ratio K_i/IC₅₀	Selectivity NET/5-HTT Ratio K_i/K_i
Cocaine	-	-	-	89.1	95	1990	22	21
6	-	-	-	0.82 ± 0.05	0.95 ± 0.04	21.8 ± 0.6	27	23
7a	H	H	CH₃	6.5 ± 1.3	4.3 ± 0.5	1110 ± 64	171	258
7b	H	H	C₂H₅	92 ± 8	1.7 ± 0.4	1690 ± 50	18	994
7c	F	H	CH₃	16 ± 1	4.8 ± 0.5	270 ± 50	17	56
7d	Br	H	CH₃	47 ± 15	3.1 ± 0.1	160 ± 20	3	52
7f	Br	Br	CH₃	92 ± 22	2.9 ± 0.1	4100 ± 400^ɑ	45	1413
7e	I	H	CH₃	170 ± 60	3.5 ± 0.4	180 ± 20	1	51
7g	I	I	CH₃	1300 ± 200	7.5 ± 0.8	180 ± 20	4	667

^ɑN=2

*Para*-OCH₃-(3β-(4-Methoxyphenyl)tropane-2β-carboxylic acid ester analogues^[8]
Short Name (All compounds tested as HCl salts)	CO₂R (2β-substituted) (compound 9 is 2β=R)	DAT IC₅₀ [³H](compound #)12	5-HTT K_i [³H]Paroxetine	NET K_i [³H]Nisoxetine	Selectivity NET/DAT Ratio K_i/IC₅₀	Selectivity NET/5-HTT Ratio K_i/K_i
7a	CH₃	6.5 ± 1.3	4.3 ± 0.5	1110 ± 64	171	258
8a	(CH₃)₂CH	14 ± 3	135 ± 35	2010 ± 200	144	15
8b	cyclopropane	6.0 ± 2	29 ± 3	1230 ± 140	205	42
8c	cyclobutane	13 ± 3	100 ± 8	>3000	231	30
8d	O₂N…1,4-xylene…(CH₂)₂	42 ± 8	2.9 ± 0.2	330 ± 20	8	114
8e	H₂N…1,4-xylene…(CH₂)₂	7.0 ± 2	8.3 ± 0.4	2200 ± 300^ɑ	314	265
8f	CH₃CONH…1,4-xylene…(CH₂)₂	6.0 ± 1	5.5 ± 0.5	1460 ± 30	243	265
8g	H₂N…2-bromo-1,4-dimethylbenzene…(CH₂)₂	3.3 ± 1.4	4.1 ± 0.6	1850 ± 90	561	451
8h	H₂N…1,3-dibromo-2,5-dimethylbenzene…(CH₂)₂	15 ± 6	2.0 ± 0.4	2710 ± 250^ɑ	181	1360
8i	H₂N…2-iodo-1,4-dimethylbenzene…(CH₂)₂	2.5 ± 0.7	3.5 ± 1	2040 ± 300^ɑ	816	583
8j	H₂N…1,3-diiodo-2,5-dimethylbenzene…(CH₂)₂	102 ± 15	1.0 ± 0.1	2600 ± 200^ɑ	25	2600
9	3-(4-methylphenyl)-1,2-oxazole	18 ± 6	860 ± 170	>3000	167	3

^ɑN=2

(3,4-Disubstituted phenyl)-tropanes

200px

250px

Compound (+ S. Singh's name)	X	Y	2 Position	config	8	DA	5-HT	NE
RTI-318	β-naphthyl		CO₂Me	β,β	NMe	0.5	0.81	20
Dichloropane (RTI-111)^[6] 17c	Cl	Cl	CO₂Me	β,β	NMe	0.79	3.13	18.0
RTI-88 [recheck] 17e	NH₂	I	CO₂Me	β,β	NMe	1.35	1329	320
RTI-97 17d	NH₂	Br	CO₂Me	β,β	NMe	3.91	181	282
RTI-112	Cl	Me	CO₂Me	β,β	NMe	0.82	10.5	36.2
RTI-96	F	Me	CO₂Me	β,β	NMe	2.95	76	520
RTI-295	Et	I	CO₂Me	β,β	NMe	21.3	2.96	1349
RTI-353 (EINT)	Et	I	CO₂Me	β,β	NH	331	0.69	148
RTI-279	Me	I	CO₂Me	β,β	NH	5.98	1.06	74.3
RTI-280	Me	I	CO₂Me	β,β	NMe	3.12	6.81	484
Meltzer^[9]	catechol		CO₂Me	β,β	NMe	>100	?	?
Meltzer^[9]	OAc	OAc	CO₂Me	β,β	NMe	?	?	?

Multi-substituted structures of 2β-ester-3β-phenyltropanes^[3]
Compound	Short Name (S. Singh)	R	X	IC₅₀ (nM) DAT [³H]WIN 35428	IC₅₀ (nM) 5-HTT [³H]paroxetine	IC₅₀ (nM) NET [³H]nisoxetine	Selectivity 5-HTT/DAT	Selectivity NET/DAT
280px
	23a	CH(CH₃)₂	H	85.1 ± 2.5	23121 ± 3976	32047 ± 1491	272	376
	23b	C₆H₅	H	76.7 ± 3.6	106149 ± 7256	19262 ± 593	1384	251
	24a	CH(CH₃)₂	Cl	1.4 ± 0.13 6.04 ± 0.31^ɑ	1400 ± 7 128 ± 15^b	778 ± 21 250 ± 0.9^c	1000 21.2^d	556 41.4^e
	24b	cyclopropyl	Cl	0.96 ± 0.10	168 ± 1.8	235 ± 8.39	175	245
	24c	C₆H₅	Cl	1.99 ± 0.05 5.25 ± 0.76^ɑ	2340 ± 27 390 ± 34^b	2960 ± 220 242 ± 30^c	1176 74.3^d	1.3 41.6^e
	24d	C₆H₄-4-I	Cl	32.6 ± 3.9	1227 ± 176	967.6 ± 26.3	37.6	29.7
	24e	C₆H₄-3-CH₃	Cl	9.37 ± 0.52	2153 ± 143	2744 ± 140	230	293
	24f	C₆H₄-4-CH₃	Cl	27.4 ± 1.5	1203 ± 42	1277 ± 118	43.9	46.6
	24g	C₆H₄-2-CH₃	Cl	3.91 ± 0.23	3772 ± 384	4783 ± 387	965	1223
	24h	C₆H₄-4-Cl	Cl	55 ± 2.3	16914 ± 1056	4883 ± 288	307	88.8
	24i	C₆H₄-4-OCH₃	Cl	71 ± 5.6	19689 ± 1843	1522 ± 94	277	21.4
	24j	(CH₂)₂C₆H₄-4-NO₂	Cl	2.71 ± 0.13	-	-	-	-
	24k	(CH)₂C₆H₄-4-NH₂	Cl	2.16 ± 0.25	-	-	-	-
	24l	(CH₂)₂C₆H₃-3-I-4-NH₂	Cl	2.51 ± 0.25	-	-	-	-
	24m	(CH₂)₂C₆H₃-3-I-4-N₃	Cl	14.5 ± 0.94	-	-	-	-
	24n	(CH₂)₂C₆H₄-4-N₃	Cl	6.17 ± 0.57	-	-	-	-
	24o	(CH₂)₂C₆H₄-4-NCS	Cl	5.3 ± 0.6	-	-	-	-
	24p	(CH₂)₂C₆H₄-4-NHCOCH₂Br	Cl	1.73 ± 0.06	-	-	-	-
	25a	CH(CH₃)₂	I	0.43 ± 0.05 2.79 ± 0.13^ɑ	66.8 ± 6.53 12.5 ± 1.0^b	285 ± 7.6 41.2 ± 3.0^c	155 4.5^d	663 14.8^e
	25b	cyclopropyl	I	0.61 ± 0.08	15.5 ± 0.72	102 ± 11	25.4	167
	25c	C₆H₅	I	1.51 ± 0.34 6.85 ± 0.93^ɑ	184 ± 22 51.6 ± 6.2^b	3791 ± 149 32.7 ± 4.4^c	122 7.5^d	2510 4.8^e
	26a	CH(CH₃)₂	CH₃	6.45 ± 0.85 15.3 ± 2.08^ɑ	6090 ± 488 917 ± 54^b	1926 ± 38 73.4 ± 11.6^c	944 59.9^d	299 4.8^e
	26b	CH(C₂H₅)₂	CH₃	19.1 ± 1	4499 ± 557	3444 ± 44	235	180
	26c	cyclopropyl	CH₃	17.8 ± 0.76	485 ± 21	2628 ± 252	27.2	148
	26d	cyclobutyl	CH₃	3.74 ± 0.52	2019 ± 133	4738 ± 322	540	1267
	26e	cyclopentyl	CH₃	1.68 ± 0.14	1066 ± 109	644 ± 28	634	383
	26f	C₆H₅	CH₃	3.27 ± 0.06 9.13 ± 0.79^ɑ	24500 ± 1526 1537 ± 101^b	5830 ± 370 277 ± 23^c	7492 168^d	1783 30.3^e
	26g	C₆H₄-3-CH₃	CH₃	8.19 ± 0.90	5237 ± 453	2136 ± 208	639	261
	26h	C₆H₄-4-CH₃	CH₃	81.2 ± 16	15954 ± 614	4096 ± 121	196	50.4
	26i	C₆H₄-2-CH₃	CH₃	23.2 ± 0.97	11040 ± 504	25695 ± 1394	476	1107
	26j	C₆H₄-4-Cl	CH₃	117 ± 7.9	42761 ± 2399	9519 ± 864	365	81.3
	26k	C₆H₄-4-OCH₃	CH₃	95.6 ± 8.8	82316 ± 7852	3151 ± 282	861	33.0

^ɑKi value for displacement of [³H]DA uptake.
^bKi value for displacement of [³H]5-HT uptake.
^cKi value for displacement of [³H]NE uptake.
^d[³H]5-HT uptake to [³H]DA uptake ratio.
^e[³H]NE uptake to [³H]DA uptake ratio.

File:Exo-2-Phenyl-7-azabicyclo(2.2.1)heptane-1-carboxylic Acid.jpg

exo-2-phenyl-7-azabicyclo(2.2.1)heptane-1-carboxylic acid

With the carboxy ester function removed the resultant derived compound acts as a DAT substrate drug, thus an amphetaminergic releaser of MAT & VMAT, yet similar to phenyltropanes (that usually are only re-uptake ligands)^[10] cf. EXP-561 & BTQ.

2β-Carboxamide-3β-Phenyltropanes^[3]
Short Name (S. Singh)	R	X	IC₅₀ (nM) DAT [³H]WIN 35428	IC₅₀ (nM) 5-HTT [³H]Paroxetine	IC₅₀ (nM) NET [³H]Nisoxetine	Selectivity 5-HTT/DAT	Selectivity NET/DAT

29a	NH₂	CH₃	41.8 ± 2.45	6371 ± 374	4398 ± 271	152	105
29b	N(CH₂CH₃)₂	CH₃	24.7 ± 1.93	33928 ± 2192	6222 ± 729	1374	252
29c	N(OCH₃)CH₃	CH₃	2.55 ± 0.43	3402 ± 353	422 ± 26	1334	165
29d	4-morpholine	CH₃	11.7 ± 0.87	>100000	23601 ± 1156	>8547	2017

Carboxyaryl

200px

Compound	X	2 Position	config	8	DA	5-HT	NE
RTI-122	I	-CO₂Ph	β,β	NMe	1.50	184	3,791
RTI-113	Cl	-CO₂Ph	β,β	NMe	1.98	2,336	2,955
RTI-277	NO₂	-CO₂Ph	β,β	NMe	5.94	2,910	5,695
RTI-120 [recheck]	Me	-CO₂Ph	β,β	NMe	3.26	24,471	5,833
RTI-116	Cl	-CO₂(p-C₆H₄I)	β,β	NMe	33	1,227	968
RTI-203	Cl	CO₂(m-C₆H₄Me)	β,β	NMe	9.37	2153	2744
RTI-204	Cl	-CO₂(o-C₆H₄Me)	β,β	NMe	3.91	3,772	4,783
RTI-205	Me	-CO₂(m-C₆H₄Me)	β,β	NMe	8.19	5,237	2,137
RTI-206	Cl	-CO₂(p-C₆H₄Me)	β,β	NMe	27.4	1,203	1,278

Carboxyalkyl

300px

Code	X	2 Position	config	8	DA	5-HT	NE
RTI-77	Cl	CH₂C₂(3-iodo-p-anilino)	β,β	NMe	2.51	—	2247
RTI-121	I	-CO₂Prⁱ	β,β	NMe	0.43	66.8	285
RTI-153	I	-CO₂Prⁱ	β,β	NH	1.06	3.59	132
RTI-191	I	-CO₂Pr^cyc	β,β	NMe	0.61	15.5	102
RTI-114	Cl	-CO₂Prⁱ	β,β	NMe	1.40	1,404	778
RTI-278	NO₂	-CO₂Prⁱ	β,β	NMe	8.14	2,147	4,095
RTI-190	Cl	-CO₂Pr^cyc	β,β	NMe	0.96	168	235
RTI-193	Me	-CO₂Pr^cyc	β,β	NMe	1.68	1,066	644
RTI-117	Me	-CO₂Prⁱ	β,β	NMe	6.45	6,090	1,926
RTI-150	Me	-CO₂Bu^cyc	β,β	NMe	3.74	2,020	4,738
RTI-127	Me	-CO₂C(H)Et₂	β,β	NMe	19	4500	3444
RTI-338	ethyl	-CO₂C₂Ph	β,β	NMe	1104	7.41	3366

Use of a cyclopropyl ester appears to enable better MAT retention than does the choice of isopropyl ester.

Use of a ^cycBu resulted in greater DAT selectivity than did the ^cycPr homologue.

Amides

U.S. Patent 5,736,123

200px

200px

Code	X	2 Position	config	8	DA	NE	5-HT
RTI-106	Cl	CON(H)Me	β,β	NMe	12.4	1511	1312
RTI-118	Cl	CONH₂	β,β	NMe	11.5	4267	1621
RTI-222	Me	morpholinyl	β,β	NMe	11.7	—	>100K
RTI-129	Cl	CONMe₂	β,β	NMe	1.38	942	1079
RTI-146	Cl	CONHCH₂OH	β,β	NMe	2.05	144	98
RTI-147	Cl	CON(CH₂)₄	β,β	NMe	1.38	3,949	12,394
RTI-156	Cl	CON(CH₂)₅	β,β	NMe	6.61	5832	3468
RTI-170	Cl	CON(H)CH₂C≡CH	β,β	NMe	16.5	1839	4827
RTI-172	Cl	CON(H)NH₂	β,β	NMe	44.1	3914	3815
RTI-174	Cl	CONHCOMe	β,β	NMe	158	>43K	>125K
RTI-182	Cl	CONHCH₂COPh	β,β	NMe	7.79	1722	827
RTI-183✲	Cl	CON(OMe)Me	β,β	NMe	0.85	549	724
RTI-186	Me	CON(OMe)Me	β,β	NMe	2.55	442 (266)	3400 (309)
RTI-198	Cl	CON(CH₂)₃	β,β	NMe	6.57	990	813
RTI-196	Cl	CONHOMe	β,β	NMe	10.7	9907	>43K
RTI-201	Cl	CONHNHCOPh	β,β	NMe	91.8	>20K	>48K
RTI-208	Cl	CONO(CH₂)₃	β,β	NMe	1.47	998	2470
RTI-214	Cl	CON(-CH₂CH₂-)₂O	β,β	NMe	2.90	8545	>88K
RTI-215	Cl	CONEt₂	β,β	NMe	5.48	?	9432
RTI-217	Cl	CONH(m-C₆H₄OH)	β,β	NMe	4.78	>30K	>16K
RTI-218✲	Cl	CON(Me)OMe	β,β	NMe	1.19	520	1911
RTI-226	Cl	CONMePh	β,β	NMe	45.0	?	24K
RTI-227	I	CONO(CH₂)₃	β,β	NMe	0.75	446	230
RTI-229^[11]	I	CON(CH₂)₄	β,β	NMe	0.37	991	1,728

✲RTI-183 and RTI-218 suggest possible copy-error, seeing as "CON(OMe)Me" & "CON(Me)OMe" difference between methyl & methoxy render as the same.

Acyl

# (#)	X	Y	2 Position	config	8	DA	5-HT	NE
WF-23 (39n)	β-naphthyl		C(O)Et	β,β	NMe	0.115	0.394	No data
WF-31	-Prⁱ	H	C.O.Et	β,β	NMe	615	54.5	No data
WF-11 (39e)	Me	H	-C.O.Et	β,β	NMe	8.2	131	No data
WF-25 (39a)	H	H	-C.O.Et	β,β	NMe	48.3	1005	No data
WF-33	6-MeoBN		C(O)Et	α,β	NMe	0.13	2.24	No data

2β-acyl-3β-phenyltropane structures^{[lower-alpha 3]}
S. Singh's alphanumeric assignation (name)	R₁	R₂	DAT [¹²⁵I]RTI-55 IC₅₀ (nM)	5-HTT [³H]Paroxetine K_i (nM)	Selectivity 5-HTT/DAT
cocaine			173 ± 19	—	—
Troparil 11a (WIN 35065-2)			98.8 ± 12.2	—	—
WF-25 39a	C₂H₅	C₆H₅	48.3 ± 2.8	1005 ± 112	20.8
39b	CH₃	C₆H₅	114 ± 22	1364 ± 616	12.0
39c	C₂H₅	C₆H₄-4-F	15.3 ± 2.8	630 ± 67	41.2
39d	CH₃	C₆H₄-4-F	70.8 ± 13	857 ± 187	12.1
WF-11 39e	C₂H₅	C₆H₄-4-CH₃	8.2 ± 1.6	131 ± 1	16.0
(+)-39e	C₂H₅	C₆H₄-4-CH₃	4.21 ± 0.05	74 ± 12	17.6
(-)-39e	C₂H₅	C₆H₄-4-CH₃	1337 ± 122	>10000	—
39f	CH₃	C₆H₄-4-CH₃	9.8 ± 0.5	122 ± 22	12.4
39g	CH₃	C₆H₄-4-C₂H₅	152 ± 24	78.2 ± 22	0.5
39h	C₂H₅	C₆H₄-4-CH(CH₃)₂	436 ± 41	35.8 ± 4.4	0.08
39i	C₂H₅	C₆H₄-4-C(CH₃)₃	2120 ± 630	1771 ± 474	0.8
39j	C₂H₅	C₆H₄-4-C₆H₅	2.29 ± 1.08	4.31 ± 0.01	1.9
39k	C₂H₅	C₆H₄-2-CH₃	1287 ± 322	710000	>7.8
39l	C₂H₅	1-naphthyl	5.43 ± 1.27	20.9 ± 2.9	3.8
39m	CH₃	1-naphthyl	10.1 ± 2.2	25.6 ± 5.1	2.5
WF-23 39n	C₂H₅	2-naphthyl	0.115 ± 0.021	0.394 ± 0.074	3.5
39o	CH₃	2-naphthyl	0.28 ± 0.11	1.06 ± 0.36	3.8
39p	C₂H₅	C₆H₄-4-CH(C₂H₅)₂	270 ± 38	540 ± 51	2.0
39q	C₂H₅	C₆H₄-4-C₆H₁₁	320 ± 55	97 ± 12	0.30
39r	C₂H₅	C₆H₄-4-CH=CH₂	0.90 ± 0.34	3.2 ± 1.3	3.5
39s	C₂H₅	C₆H₄-4-C(=CH₂)CH₃	7.2 ± 2.1	0.82 ± 0.38	0.1

Ester reduction

Note: p-fluorophenyl is weaker than the others. RTI-145 is not peroxy, it is a methyl carbonate.

200px

Code	X	2 Position	config	8	DA	5-HT	NE
RTI-100	F	-CH₂OH	β,β	NMe	47	4741	no data
RTI-101	I	-CH₂OH	β,β	NMe	2.2	26	no data
RTI-99	Br	-CH₂OH	β,β	NMe	1.49	51	no data
RTI-93	Cl	-CH₂OH	β,β	NMe	1.53	204	43.8
RTI-105	Cl	-CH₂OAc	β,β	NMe	1.60	143	127
RTI-123	Cl	-CH₂OBz	β,β	NMe	1.78	3.53	393
RTI-145	Cl	-CH₂OCO₂Me	β,β	NMe	9.60	2.93	1.48

β,α Stereochemistry

300px

Compound (RTI #) (S. Singh's #)	X	2 Group	config	8	DA IC₅₀ (nM) [³H]WIN 35428	5-HT IC₅₀ (nM) [³H]paroxetine	NE IC₅₀ (nM) [³H]nisoxetine	selectivity 5-HTT/DAT	selectivity NET/DAT
RTI-140 20a	H	CO₂Me	β,α	NMe	101 ± 16	5,701 ± 721	2,076 ± 285	56.4	20.6
RTI-352 U.S. Patent 6,358,492 20d	I	CO₂Me	β,α	NMe	2.86 ± 0.16	64.9 ± 1.97	52.4 ± 4.9	22.8	18.4
RTI-549	Br	CO₂Me	β,α	NMe	—	—	—	—	—
RTI-319 U.S. Patent 7,011,813	BN	CO₂Me	β,α	NMe	1.1	11.4	70.2	—	—
RTI-286 U.S. Patent 7,011,813 20b	F	CO₂Me	β,α	NMe	21 ± 0.57	5062 ± 485	1231 ± 91	241	58.6
RTI-274 U.S. Patent 7,291,737	F	CH₂O(3′,4′-MD-phenyl)	β,α	NH	3.96	5.62	14.4	—	—
RTI-287	Et	CO₂Me	β,α	NMe	327	1687	17,819	—	—
20c					2.4 ± 0.2	998 ± 120	60.1 ± 2.4	416	25.0
20e					10.2 ± 0.08	4250 ± 422	275 ± 24	417	27.0

800px

α,β Stereochemistry

CA 2112084

Compound	DA (μM)	M.E.D. (mg/kg)	Dose (mg/kg)	Activity	Activity
(2R,3S)-2-(4-chlorophenoxymethyl)-8-methyl-3-(3-chlorophenyl)-8-azabicyclo[3.2.1]octane	0.39	<1	50	0	0
(2R,3S)-2-(carboxymethyl)-8-methyl-3-(2-naphthyl)-8-azabicyclo[3.2.1]octane	0.1	1	25	0	0
(2R,3S)-2-(carboxymethyl)-8-methyl-3-(3,4-dichlorophenyl)-8-azabicyclo[3.2.1]octane	0.016	0.25	50	+	+++

U.S. Patent 2,001,047,028

Compound	X	2 Group	config	8	DA	5-HT	NE
Brasofensine	Cl₂	methyl aldoxime	α,β	NMe	—	—	—
Tesofensine	Cl₂	ethoxymethyl	α,β	NMe	65	11	1.7
NS-2359 (GSK-372,475)	Cl₂	Methoxymethyl	α,β	NH	—	—	—

A1 WO 2004072075 A1

Test Compound	DA uptake IC₅₀(μM)	NE uptake IC₅₀(μM)	5-HT uptake IC₅₀(μM)
(2R,3S)-2-(2,3-dichlorophenoxymethyl)-8-methyl-3-(3-chlorophenyl)-8-azabicyclo[3.2.1]octane fumaric acid salt	0.062	0.035	0.00072
(2R,3S)-2-(Naphthaleneoxymethane)-8-methyl-3-(3-chlorophenyl)-8-azabicyclo[3.2.1]octane fumaric acid salt	0.062	0.15	0.0063
(2R,3S)-2-(2,3-dichlorophenoxymethyl)-8-H-3-(3-chlorophenyl)-8-azabicyclo[3.2.1]octane fumaric acid salt	0.10	0.048	0.0062
(2R,3S)-2-(Naphthlyloxymethane)-8-H-3-(3-chlorophenyl)-8-azabicyclo[3.2.1]octane fumaric acid salt	0.088	0.051	0.013

Aryl-Tropenes

WO2004113297

Test compound	DA-uptake IC₅₀(μM)	NA-uptake IC₅₀(μM)	5-HT-uptake IC₅₀(μM)
(+)-3-(4-Chlorophenyl)-8-H-aza-bicyclo[3.2.1]oct-2-ene	0.26	0.028	0.010
(+)-3-Napthalen-2-yl-8-azabicyclo[3.2.1]oct-2-ene	0.058	0.013	0.00034
(–)-8-Methyl-3-(naphthalen-2-yl)-8-azabicylo[3.2.1]oct-2-ene	0.034	0.018	0.00023

WO 9713770

8-AZABICYCLO[3.2.1]OCT-2-ENE DERIVATIVES
Test Compound	DA uptake IC₅₀(μM)	NE uptake IC₅₀(μM)	5-HT uptake IC₅₀(μM)
(±)-3-(3,4-Dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene	0.079	0.026	0.0047

U.S. Patent 2,001,047,028

Test Compound	DA uptake IC₅₀(μM)	NE uptake IC₅₀(μM)	5-HT uptake IC₅₀(μM)
(±)-3-(4-cyanophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene	18	4.9	0.047
(±)-3-(4-nitrophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene	1.5	0.5	0.016
(±)-3-(4-trifluoromethoxyphenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene	22.00	8.00	0.0036

File:LBT-999.svg

LBT-999, a radio-ligand.

Heterocycles

These heterocycles are sometimes referred to as the "bioisosteric equivalent" of the simpler esters from which they are derived. A potential disadvantage of leaving the ββ-ester unreacted is that in addition to being hydrolyzable, it can also epimerize^[12] to the energetically more favorable trans configuration. This can happen to cocaine also.

3-Substituted-isoxazol-5-yl

File:3-R-isoxazol-5-yl.svg

N-methylphenyltropanes with 1R β,β stereochemistry.
Code	X	R	DA	NE	5HT
RTI-165	Cl	3-methylisoxazol-5-yl	0.59	181	572
RTI-171	Me	3-methylisoxazol-5-yl	0.93	254	3818
RTI-180	I	3-methylisoxazol-5-yl	0.73	67.9	36.4
RTI-177	Cl	3-phenylisoxazol-5-yl	1.28	504	2418
RTI-176	Me	3-phenylisoxazol-5-yl	1.58	398	5110
RTI-181	I	3-phenylisoxazol-5-yl	2.57	868	100
RTI-184	H	methyl	43.3	—	6208
RTI-185	H	Ph	285	—	>12K
RTI-334	Cl	3-ethylisoxazol-5-yl	0.50	120	3086
RTI-335	Cl	isopropyl	1.19	954	2318
RTI-336	Cl	3-(4-methylphenyl)isoxazol-5-yl	4.09	1714	5741
RTI-337	Cl	3-t-butyl-isoxazol-5-yl	7.31	6321	37K
RTI-345	Cl	p-chlorophenyl	6.42	5290	>76K
RTI-346	Cl	p-anisyl	1.57	762	5880
RTI-347	Cl	p-fluorophenyl	1.86	918	7257
RTI-354	Me	3-ethylisoxazol-5-yl	1.62	299	6400
RTI-366	Me	R = isopropyl	4.5	2523 (1550)	42,900 (3900)
RTI-371	Me	p-chlorophenyl	8.74	>100K (60,200)	>100K (9090)
RTI-386	Me	p-anisyl	3.93	756 (450)	4027 (380)
RTI-387	Me	p-fluorophenyl	6.45	917 (546)	>100K (9400)

3-Substituted-1,2,4-oxadiazole

File:RTI-155.jpg

RTI-155

200px

Heterocyclic (N-methyl)phenyltropanes with 1R stereochemistry.
Code (Singh's #)	X	R	DA	NE	5HT	Selectivity 5-HTT/DAT	Selectivity NET/DAT
ααRTI-87	H	3-methyl-1,2,4-oxadiazole	204	36K	30K
βαRTI-119	H	3-methyl-1,2,4-oxadiazole	167	7K	41K
αβRTI-124	H	3-methyl-1,2,4-oxadiazole	1028	71K	33K
RTI-125 (32a)	Cl	3-methyl-1,2,4-oxadiazole	4.05 ± 0.57	363 ± 36	2584 ± 800	637	89.6
ββRTI-126^[13] (31)	H	3-methyl-1,2,4-oxadiazole	100 ± 6	7876 ± 551	3824 ± 420	38.3	788
RTI-130 (32c)	Cl	3-phenyl-1,2,4-oxadiazole	1.62 ± 0.02	245 ± 13	195 ± 5	120	151
RTI-141 (32d)	Cl	3-(p-anisyl)-1,2,4-oxadiazole	1.81 ± 0.19	835 ± 8	337 ± 40	186	461
RTI-143	Cl	3-(p-chlorophenyl)-1,2,4-oxadiazole	4.1	4069	404
RTI-144 (32f)	Cl	3-(p-bromophenyl)-1,2,4-oxadiazole	3.44 ± 0.36	1825 ± 170	106 ± 10	30.8	532
βRTI-151 (33)	Me	3-phenyl-1,2,4-oxadiazole	2.33 ± 0.26	60 ± 2	1074 ± 130	459	25.7
αRTI-152	Me	3-phenyl-1,2,4-oxadiazole	494	—	1995
RTI-154 (32b)	Cl	3-isopropyl-1,2,4-oxadiazole	6.00 ± 0.55	135 ± 13	3460 ± 250	577	22.5
RTI-155	Cl	3-cyclopropyl-1,2,4-oxadiazole	3.41	177	4362

File:RTI-470 structure.png

RTI-470 structure:^[14]

220px

N-methylphenyltropanes with 1R β,β stereochemistry.
Code	X	2 Group	DA	NE	5HT
RTI-157	Me	tetrazole	1557	>37K	>43K
RTI-163	Cl	tetrazole	911	—	5456
RTI-178	Me	5-phenyl-oxazol-2-yl	35.4	677	1699
RTI-188	Cl	5-phenyl-1,3,4-oxadiazol-2-yl	12.6	930	3304
RTI-189	Cl	5-phenyl-oxazol-2-yl	19.7	496	1116
RTI-194	Me	5-methyl-1,3,4-oxadiazol-2-yl	4.45	253	4885
RTI-195	Me	5-phenyl-1,3,4-oxadiazol-2-yl	47.5	1310	>22,000
RTI-199	Me	5-phenyl-1,3,4-thiadiazol-2-yl	35.9	>24,000	>51,000
RTI-200	Cl	5-phenyl-1,3,4-thiadiazol-2-yl	15.3	4142	>18,000
RTI-202	Cl	benzothiazol-2-yl	1.37	403	1119
RTI-219	Cl	5-phenylthiazol-2-yl	5.71	8516	10,342
RTI-262	Cl
RTI-370	Me	3-(p-cresyl)isoxazol-5-yl	8.74	6980	>100K
RTI-371	Cl	3-(p-chlorophenyl)isoxazol-5-yl	13	>100K	>100K
RTI-436	Me	-CH=CHPh^[15]	3.09	1960 (1181)	335 (31)
RTI-470	Cl	o-Cl-benzothiazol-2-yl	0.094	1590 (994)	1080 (98)
RTI-451	Me	benzothiazol-2-yl	1.53	476 (287)	7120 (647)

File:Heterocyclic phenyltropane syntheses p2.png

Above is taken from: RTI, Kuhar, et al. U.S. Patent 5,935,953 (1999).

N.B There are some alternative ways of making the tetrazole ring though. C.f. the sartan drugs synthesis schemes. Bu₃SnN₃ is a milder choice of reagent than hydrogen azide (c.f. Irbesartan).

η⁶-3β-(transition metal complexed phenyl)tropanes

Unlike metal complexed PTs created with the intention of making useful radioligands, 21a & 21b were produced seeing as their η⁶-coordinated moiety dramatically altered the electronic character and reactivity of the benzene ring, as well as such a change adding asymmetrical molecular volume to the otherwise planar arene ring unit of the molecule.^[3]

21a was twice as potent as both cocaine and troparil in displacement of β-CFT, as well as displaying high & low affinity K_i values in the same manner as those two compounds. Whereas its inhibition of DA uptake showed it as comparably equipotent to cocaine & troparil. 21b by contrast had a one hundred fold decrease in high-affinity site binding compared to cocaine and a potency 10× less for inhibiting DA uptake.

The discrepancy in binding for the two benzene metal chelates is assumed to be due to electrostatic differences rather than their respective size difference. The solid cone angles, measured by the steric parameter (i.e. θ) is θ=131° for Cr(CO)₃ whereas Cp*Ru was θ=187° or only 30% larger. The tricarbonyl moiety being considered equivalent cyclopenta dienyl (Cp) ligand.^[3]

Displacement of Receptor-Bound [³H]WIN 35428 and Inhibition of [³H]DA Uptake by Transition Metal Complexes of 3β-Phenyltropanes^[3]
Structure	Compound # (S. Singh) Systematic name	K_i (nM)^ɑ	IC₅₀ (nM)	selectivity binding/uptake
	Cocaine	32 ± 5 388 ±221	405	12.6
	11a	33 ± 17 314 ± 222	373	11.3
150px	21a [η⁶-(2β-carbomethoxy-3β-phenyl)tropane]tricarbonylchromium	17 ± 15^b 224 ± 83	418	24.6
210px	21b [η⁵-(pentamethylcyclopentadienyl)]-[η⁶-(2β-carbomethoxy-3β-phenyl)tropane]ruthenium-(II) triflate	2280 ± 183	3890	1.7

^ɑThe binding data fit a two-site model better than a one-site model
^bThe K_i value for the one-site model was 124 ± 10 nM

2-Alkane/Alkene

2-Alkane/Alkene-3-Phenyltropanes
Structure	Singh's #	R	X	DAT mazindol displacement	DA uptake	5-HT Uptake	Selectivity DA uptake/DAT binding
	11a WIN 35062-2			89.4	53.7	186	0.6
	11c			0.83 ± 00.7	28.5 ± 0.9		34.3
	11f			5.76	6.92	23.2	1.2
160px	41a	(CH₂)₂CH₃	H	12.2	6.89	86.8	0.6
190px	41b	(CH₂)₃C₆H₅	H	16 ± 2^a	43 ± 13^b		2.7
160px	42	(CH₂)₂CH₃	F	5.28	1.99	21.7	0.4
160px	43a	CH=CH₂	Cl	0.59 ± 0.15	2.47 ± 0.5		4.2
160px	43b	E-CH=CHCl	Cl	0.42 ± 0.04	1.13 ± 0.27		2.7
160px	43c	Z-CH=CHCl	Cl	0.22 ± 0.02	0.88 ± 0.05		4.0
160px	43d	E-CH=CHC₆H₅	Cl	0.31 ± 0.04	0.66 ± 0.01		2.1
160px	43e	Z-CH=CHC₆H₅	Cl	0.14 ± 0.07	0.31 ± 0.09		2.2
160px	43f	CH₂CH₃	Cl	2.17 ± 0.20	2.35 ± 0.52		1.1
160px	43g	(CH₂)₂CH₃	Cl	0.94 ± 0.08	1.08 ± 0.05		1.1
160px	43h	(CH₂)₃CH₃	Cl	1.21 ± 0.18	0.84 ± 0.05		0.7
160px	43i	(CH₂)₅CH₃	Cl	156 ± 15	271 ± 3		1.7
160px	43j	(CH₂)₂C₆H₅	Cl	1.43 ± 0.03	1.54 ± 0.08		1.0
160px	44a	(CH₂)₂CH₃	CH₃	1.57	1.10	10.3	0.7
160px	44b	(CH₂)₃CH₃	CH₃	1.82	1.31	15.1	0.7
110px	45	(CH₂)₂CH₃	H	74.9	30.2	389	0.4
110px	46	(CH₂)₂CH₃	F	21.1	12.1	99.6	0.6
110px	47a	(CH₂)₂CH₃	CH₃	8.91	11.8	50.1	1.3
120px	47b	(CH₂)₃CH₃	CH₃	11.4	10.1	51.0	0.9

^aK_i value for displacement of WIN 35428.
^bIC₅₀ value.

N-alkyl

200px

Compound	X	2 Group	config	8	DAT	SERT	NET
FP-β-CPPIT	Cl	3′-phenylisoxazol-5′-yl	β,β	NCH₂CH₂CH₂F	-	-	-
FE-β-CPPIT	Cl	(3′-phenylisoxazol-5′-yl)	β,β	NCH₂CH₂F	-	-	-
Altropane	F	CO₂Me	β,β	NCH₂CH=CHF	-	-	-
RTI-310 U.S. Patent 5,736,123	I	CO₂Me	β,β	N-Prⁿ	1.17	-	-
RTI-311	I	CO₂Me	β,β	NCH₂CH=CH₂	1.79	-	-
RTI-312 U.S. Patent 5,736,123	I	CO₂Me	β,β	NBuⁿ	0.76	-	-
RTI-313 U.S. Patent 5,736,123	I	CO₂Me	β,β	NCH₂CH₂CH₂F	1.67	-	-
Ioflupane	¹²³I	CO₂Me	β,β	NCH₂CH₂CH₂F	-	-	-
RTI-251	Cl	CO₂Me	β,β	NCH₂CO₂Et	1.93	10.1	114
RTI-252	Cl	CO₂Me	β,β	NCH₂CH₂CO₂Et	2.56	35.2	125
RTI-242	Cl	β,β (bridged) -C(O)CH(CO₂Me)CH₂N			7.67	227	510

Bi- and tri-cyclic aza compounds and their uses U.S. Patent 6,150,376 WO 0007994

Tricyclic/N-constrained (inclu. N-bridged/fused/tethered)

Constrained tropane:^[16]^[17]

Tricyclic tropanes^[18]

Compound	X	Y	R	SERT K_i (nM)	DAT K_i (nM)	NET K_i (nM)
1	Cl	Cl	CH₂OCOMe	1.6	1870	638
2	Br	Cl	CO₂Me	2.3	5420	459
3	I	Cl	CH₂OCOPh	0.06	>10K	>10K

U.S. Patent 6,150,376

File:Koz US6150376.png

Structures mentioned in US6150376 table of K_i data.

File:Alt2D-bridged-phenyltropane-no42a.jpg

Alternate 2D rendering of compound "42a" (from among the above 'bridged' phenyltropanes) to elucidate the potential overlaying structure of the place inhabited by the contrained nitrogen. Compare JNJ-7925476, tametraline and similar compounds.

Activity at monoamine transporters: Binding Affinities & MAT Inhibition of Bridged Phenyltropanes *K_i* (nM)
Compound # (S. Singh's #)	2β=R	[³H]Mazindol binding	[³H]DA uptake	[³H]5-HT uptake	[³H]NE uptake	selectivity [³H]5-HT/[³H]DA
cocaine	CO₂CH₃	375 ± 68	423 ± 147	155 ± 40	83.3 ± 1.5	0.4
(–)-40 (–)-128		54.3 ± 10.2	60.3 ± 0.4	1.76 ± 0.23	5.24 ± 0.07	0.03
(+)-40 (+)-128		79 ± 19	114 ± 28	1.48 ± 0.07	4.62 ± 0.31	0.01
(±)-40 (±)-128		61.7 ± 8.5	60.3 ± 0.4	2.32 ± 0.23	2.69 ± 0.12	0.04
29β		620	1420	8030	—	—
30β		186	492	97.7	—	—
31β		47.0	211	28.5	—	—
29α		4140	20100	3920	—	—
30α		3960	8850	696	1150	—
45 129		6.86 ± 0.43	24.0 ± 1.3	1.77 ± 0.04	1.06 ± 0.03	0.07
42a 131a	n-Bu	4.00 ± 0.07	2.23 ± 0.12	14.0 ± 0.6	2.99 ± 0.17	6.3
41a 130a	n-Bu	17.2 ± 1.13	10.2 ± 1.4	78.9 ± 0.9	15.0 ± 0.4	7.8
42b 131b	Et	3.61 ± 0.43	11.3 ± 1.1	25.7 ± 4.3	4.43 ± 0.01	2.3
50a 133a	n-Bu	149 ± 6	149 ± 2	810 ± 80	51.7 ± 12	5.4
49a 132a	n-Bu	13.7 ± 0.8	14.2 ± 0.1	618 ± 87	3.84 ± 0.35	43.5
(–)-4		10500	16500	1890	70900	—
(+)-4		18500	27600	4630	38300	—
(–)-5		9740	9050	11900	4650	—
(+)-5		6770	10500	25100	4530	—

Fused tropane-derivatives as neurotransmitter reuptake inhibitors. Singh notes that all bridged derivatives tested displayed 2.5—104 fold higher DAT affinity than cocaine. The ones 2.8—190 fold more potent at DAT also had increased potency at the other two MAT sites (NET & SERT); NET having 1.6—78× increased activity. (+)-128 additionally exhibited 100× greater potency @ SERT, whereas 132a & 133a had 4—5.2× weaker 5-HTT (i.e. SERT) activity. Front-bridged (e.g. 128 & 129) had a better 5-HT/DA reuptake ratio in favor of SERT, while the back-bridged (e.g. 130—133) preferred placement with DAT interaction.^[3] U.S. Patent 5,998,405

File:Fused Tropane.png

Fused Tropane: NeuroSearch A/S, Scheel-Krüger et al. U.S. Patent 5,998,405

Code	Compound	DA (μM)	NE (μM)	5-HT (μM)
1	(1 S,2S,4S,7R)-2-(3,4-Dichloro- phenyl)-8-azatricyclo[5.4.0.0^4,8]- undecan-11 -one O-methyl-oxime	0.012	0.0020	0.0033
2	(1 S,2S,4S,7R)-2-(3,4-Dichloro- phenyl)-8-azatricyclo[5.4.0.0^4,8]- undecan-11-one	0.18	0.035	0.0075
3	(1 S,3S,4S,8R)-3-(3,4-Dichloro-phenyl)-7-azatricyclo[5.3.0.04,8]- decan-5-one O-methyl-oxime	0.0160	0.0009	0.0032
4	(1 S,2S,4S,7R)-2-(3,4-Dichloro-phenyl)-8-azatricyclo[5.4.0.04,8]- undecan-11-ol	0.0750	0.0041	0.0028
5	(1 S,3S,4S,8R)-3-(3,4-Dichloro-phenyl)-7-azatricyclo[5.3.0.04,8]- decan-5-one	0.12	0.0052	0.0026
6	(1 S,3S,4S,8R)-3-(3,4-Dichloro- phenyl)-7-azatricyclo[5.3.0.04,8]-decan-5-ol	0.25	0.0074	0.0018
7	(1S,3S,4S,8R)-3- (3,4-Dichloro- phenyl)-7-azatricyclo[5.3.0.04,8]dec- 5-yl acetate	0.21	0.0061	0.0075
8	(1S,3S,4S,8R)-3-(3,4-Dichlorophenyl)-5-methoxy-7- azatricyclo[5.3.0.04,8]decane	0.022	0.0014	0.0001

1-Chloroethyl chloroformate is used to remove N-methyl of trans-aryltropanes.
2° amine is reacted with Br(CH₂)nCO₂Et.
Base used to abstract proton α- to CO₂Et group and complete the tricyclic ring closure step (Dieckmann cyclization).

To make a different type of analog (see Kozikowski patent above)

Remove N-Me
Add ɣ-bromo-chloropropane
Allow for cyclization with K₂CO₃ base and KI cat.

3-(2-thiophene) and 3-(2-furan)

File:Cocaine analogs - thiophenes and furans.svg

U.S. Patent 7,247,643

Code	Compound	DA (μM)	NE (μM)	5-HT (μM)
1	(2R,3S)-2-(2,3-Dichlorophenoxymethyl)-8-methyl-3-(2-thienyl)-8-aza-bicyclo[3.2.1]octanefumaric acid salt	0.30	0.0019	0.00052
2	(2R,3S)-2-(1-Naphthyloxymethyl)-8-methyl-3-(2-thienyl)-8-aza-bicyclo-[3.2.1]octane fumaric acid salt	0.36	0.0036	0.00042
3	(2R,3S)-2-(2,3-Dichlorophenoxymethyl)-8-methyl-3-(2-furanyl)-8-aza-bicyclo-[3.2.1]octane fumaric acid salt	0.31	0.00090	0.00036
4	(2R,3S)-2-(1-Naphthyloxymethyl)-8-methyl-3-(2-furanyl)-8-aza-bicyclo-[3.2.1]octane fumaric acid salt	0.92	0.0030	0.00053
5	(2R,3S)-2-(2,3-Dichlorophenoxymethyl)-8-H-3-(2-thienyl)-8-aza-bicyclo[3.2.1]octane fumaric acid salt	0.074	0.0018	0.00074
6	(2R,3S)-2-(1-Naphthyloxymethyl)-8-H-3-(2-thienyl)-8-aza-bicyclo[3.2.1]octane fumaric acid salt	0.19	0.0016	0.00054

N-replaced (S,O,C)

Compound	X	2 Group	config	8	DA	5-HT	NE
Tropoxane	Cl,Cl	CO₂Me	(racemic) β,β	O	3.3	6.5	No data

Diaryl

File:Hanna et al.png Hanna et al. (2007)^[19]	File:ZIENT.png ZIENT:^[20]

Radiolabeled

File:Radiolabel Tropane.png

Radiolabel Tropane:^[21] Page 64. G.A. Whitlock et al. Table 1 Potential SRI PET and SPECT ligands.

Code	SERT K_i (nM)	NET K_i (nM)	DAT K_i (nM)	Radiolabel	In vivo study	Refs.
1	0.2	102.2	29.9	¹¹C	Non-human primate	^[22]
2	0.2	31.7	32.6	¹¹C	Non-human primate	^[23]
3	0.05	24	3.47	¹²³I	Rat	^[24]
4	0.08	28	13	¹⁸F	Non-human primate	^[25]
5	0.11	450	22	¹¹C	Rat, monkey	^[26]

File:N-3-iodoprop-(2E)-ene-2β-carbomethoxy-3β-(4′-chlorophenyl)tropane.png

IPT (N-3-iodoprop-(2E)-ene-2β-carbomethoxy-3β-(4′-chlorophenyl)tropane), can be radiolabeled with ¹²³I or ¹²⁵I and used as a ligand to map several MATs

Transition metal complexes

"Transition metal" N-chelated phenyltropanes^[3]
Structure	Compound # (S. Singh)	X = para- / 4′- Substitution	Configuration	DAT (IC₅₀ nM) displacement of [H³]WIN 35428	5-HTT (IC₅₀ nM) [H³]Citalopram	Selectivity 5-HTT/DAT
	WIN 35428	F	-	11.0 ± 1.0	160 ± 20	14.5
	73 TRODAT-1^d	Cl	-	R=13.9, S=8.42^b	-	-
	74 TROTEC-1	F	-	high affinity site = 0.15 ± 0.04^c low affinity site = 20.3 ± 16.1^c	-	-
200px	89a	F	2β	5.99 ± 0.81	124 ± 17	20.7
200px	89b	F	2α	2960 ± 157	5020 ± 1880	1.7
200px	89c	3,4-Cl₂	2β	37.2 ± 3.4	264 ± 16	7.1
200px	89d	Cl	-	0.31 ± 0.03^ɑ	-	-

^ɑK_i value for displacement of [¹²⁵I]IPT radioligand.
^bR- & S- isomer values are K_i (nM) for displacement of [¹²⁵I]IPT with technetium-99m replaced by rhenium
^cIC₅₀ (nM) values for displacement of [³H]WIN 35428 with ligand tricarbonyltechnetium replaced with rhenium. (IC₅₀ for WIN 35428 were 2.62 ± 1.06 @ high affinity binding & 139 ± 72 @ low affinity binding sites)
^d[2-[[2-[[[3-(4-chlorophenyl)-7-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl]-(2-mercaptoethyl)amino]ethyl]amino]ethanethiolato-(3—)-N2, N2′, S2, S2′]oxo-[1R-(exo, exo)]-[99mTc]technetium

Irreversible

300px
Irreversible (phenylisothiocyanate) binding ligand (Lua error in package.lua at line 80: module 'strict' not found.)^[27] RTI-76:^[28] 4′-isothiocyanatophenyl (1R,2S,3S,5S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate. Also known as: 3β-(p-chlorophenyl)tropan-2β-carboxylic acid p-isothiocyanatophenylmethyl ester.

Note the contrast to the phenylisothiocyanate covalent binding site location as compared to the one on p-Isococ, a non-phenyltropane cocaine analogue.

Nortropanes (N-demethylated)

NS2359 (GSK-372,475)

It is well established that electrostatic potential around the para position tends to improve MAT binding. This is believed to also be the case for the meta position, although it is less studied. N-demethylation dramatically potentiates NET and SERT affinity, but the effects of this on DAT binding are insignificant.^[29] Of course, this is not always the case. For an interesting exception to this trend, see the Taxil document. There is ample evidence suggesting that N-demethylation of alkaloids occurs naturally in vivo via a biological enzyme. The fact that hydrolysis of the ester leads to inactive metabolites means that this is still the main mode of deactivation for analogues that have an easily metabolised 2-ester substituent. The attached table provides good illustration of the effect of this chemical transformation on MAT binding affinities. N.B. In the case of both nocaine and pethidine, N-demethyl compounds are more toxic and have a decreased seizure threshold.^[30]

Selected ββ Nortropanes
Code	X	DA	5HT	NE
RTI-142	F	4.39	68.6	18.8
RTI-98	I	0.69	0.36	11.0
RTI-110	Cl	0.62	4.13	5.45
RTI-173	Et	49.9	8.13	122

N-demethylating various β,β p-HC-phenyltropanes
X	[³H]Paroxetine	[³H]WIN 35,428	[³H]Nisoxetine
Ethyl	28.4 → 8.13	55 → 49.9	4,029 → 122
vinyl	9.5 → 2.25	1.24 → 1.73	78 → 14.9
Ethynyl	4.4 → 1.59	1.2 → 1.24	83.2 → 21.8
1-Propyl	70.4 → 26	68.5 → 212	3,920 → 532
trans-propenyl	11.4 → 1.3	5.29 → 28.6	1,590 → 54
cis-propenyl	7.09 → 1.15	15 → 31.6	2,800 → 147
Allyl	28.4 → 6.2	32.8 → 56.5	2,480 → 89.7
1-Propynyl	15.7 → 3.16	2.37 → 6.11	820 → 116
i-Propyl	191 → 15.1	597 → 310	75,000 → ?
2-Propenyl	3.13 → 0.6	14.4 → 23	1,330? → 144

N-Demethylating phenyltropanes to find a NRI
Isomer	4′	3′	NE	DA	5HT
β,β	Me	H	60 → 7.2	1.7 → 0.84	240 → 135
β,β	F	H	835 → 18.8	15.7 → 4.4	760 → 68.6
β,β	Cl	H	37 → 5.45	1.12 → 0.62	45 → 4.13
β,α	Me	H	270 → 9	10.2 → 33.6	4250 → 500
β,α	F	H	1200 → 9.8	21 → 32.6	5060 → 92.4
β,α	Cl	H	60 → 5.41	2.4 → 3.1	998 → 53.3
β,α	F	Me	148 → 4.23	13.7 → 9.38	1161 → 69.8
β,α	Me	F	44.7 → 0.86	7.38 → 9	1150 → 97.4

"Interest in NET selective drugs continues as evidenced by the development of atomoxetine, manifaxine, and reboxetine as new NET selective compounds for treating ADHD and other CNS disorders such as depression" (FIC, et al. 2005).^[31]

Thiophenyltropanes

800px

Select annotations of above

Phenyltropanes can be grouped by "N substitution" "Stereochemistry" "2-substitution" & by the nature of the 3-phenyl group substituent X.
Often this has dramatic effects on selectivity, potency, and duration, also toxicity, since phenyltropanes are highly versatile. For more examples of interesting phenyltropanes, see some of the more recent patents, e.g. U.S. Patent 6,329,520, U.S. Patent 7,011,813, U.S. Patent 6,531,483, and U.S. Patent 7,291,737.

Potency in vitro should not be confused with the actual dosage, as pharmacokinetic factors can have a dramatic influence on what proportion of an administered dose actually gets to the target binding sites in the brain, and so a drug that is very potent at binding to the target may nevertheless have only moderate potency in vivo. For example, RTI-336 requires a higher dosage than cocaine. Accordingly, the active dosage of RTI-386 is exceedingly poor despite the relatively high ex vivo DAT binding affinity.

Sister substances

Many molecular drug structures have exceedingly similar pharmarcology to phenyltropanes, yet by certain technicalities do not fit the phenyltropane moniker. These are namely classes of dopaminergic cocaine analogues that are in the piperidine class (a category that includes methylphenidate) or benztropine class (such as Difluoropine: which is extremely close to fitting the criteria of being a phenyltropane.) Whereas other potent DRIs are far removed from being in the phenyltropane structural family, such as Benocyclidine or Vanoxerine.

Cycloalkane-ring alterations of the tropane ring system

Azanonane

3-Phenyl-9-azabicyclo[3.3.1]nonane derivatives

[3.3.1]azanonane analogues displacement of bound [³H]WIN 35428^[3]
Structure	Compound # (S. Singh)	K_i (nM)
	Cocaine	32 ± 5 390 ± 220
	WIN 35065-2	33 ± 17 310 ± 220
150px	146a	4600 ± 510
175px	146b	5730 ± 570
150px	146c	3450 ± 310
150px	146d	3470 ± 350
100px	147	13900 ± 2010

Azabornane

3-Phenyl-7-azabicyclo[2.2.1]heptane derivatives

[2.2.1]azabornane analogues displacement of bound [³H]WIN 35428^[3]
Structure	Compound # (S. Singh)	K_i (nM)
	Cocaine	32 ± 5 390 ± 220
	WIN 3506-2	33 ± 17 310 ± 220
150px	155a	60,400 ± 4,800
150px 150px	155b	96,500 ± 42
150px	155c	5,620 ± 390
150px	155d	18,900 ± 1,700

Piperidine analogues

Phenyltropane piperidine analogues^[3]
Structure	Compound # (S. Singh)	X = para- / 4′- Substitution	R = 2-tropane position	DAT (IC₅₀ nM) [H³]WIN 35428 binding displacement	DA (IC₅₀ nM) [H³]DA uptake	Selectivity Uptake/Binding

	Cocaine	H	CO₂Me	102 ± 9	239 ± 1	2.3
150px
	(±)-166a	Cl	β-CO₂CH₃	53.7 ± 1.9	37.8 ± 7.9	0.7
	(-)-166a	Cl	β-CO₂CH₃	24.8 ± 1.6	85.2 ± 2.6	3.4
	(+)-166a	Cl	β-CO₂CH₃	1360 ± 125	5090 ± 172	3.7
150px
	(-)-167a	Cl	β-CO₂OH	75.3 ± 6.2	49.0 ± 3.0	0.6
	(+)-167a	Cl	β-CO₂OH	442 ± 32	—	—
150px
	(-)-168a	Cl	β-CO₂OAc	44.7 ± 10.5	62.9 ± 2.7	1.4
	(+)-168a	Cl	β-CO₂OAc	928 ± 43	2023 ± 82	2.2
150px
150px	(-)-169a	Cl	β-n-Pr	3.0 ± 0.5	8.3 ± 0.6	2.8
150px
150px	(-)-170a	H	β-CO₂CH₃	769 ± 19	—	—
150px
	(±)-166b	Cl	α-CO₂CH₃	197 ± 8	—	—
	(+)-166b	Cl	α-CO₂CH₃	57.3 ± 8.1	34.6 ± 3.2	0.6
	(-)-166b	Cl	α-CO₂CH₃	653 ± 38	195 ± 8	0.3
150px
150px	(+)-167b	Cl	α-CO₂OH	240 ± 18	683 ± 47	2.8
150px
150px	(+)-168b	Cl	α-CO₂OAc	461 ± 11	—	—
150px
150px	(+)-169b	Cl	α-n-Pr	17.2 ± 0.5	23.2 ± 2.2	1.3

Misc.

200px

Code	X	2 Position	config	8	DA	5-HT	NE
RTI-102	I	CO₂H	β,β	NMe	474	1928	43,400
RTI-103	Br	CO₂H	β,β	NMe	278	3070	17,400
RTI-104	F	CO₂H	β,β	NMe	2744	>100K	>100K
RTI-108	Cl	-CH₂Cl	β,β	NMe	2.64	98	129.8
RTI-241	Me	-CH₂CO₂Me	β,β	NMe	1.02	619	124
RTI-139	Cl	-CH₃	β,β	NMe	1.67	85	57
RTI-161	Cl	-C≡N	β,β	NMe	13.1	1887	2516
RTI-230	Cl	H₃C–C=CH₂	β,β	NMe	1.28	57	141
RTI-240	Cl	-CHMe₂	β,β	NMe	1.38	38.4	84.5
RTI-145	Cl	-CH₂OCO₂Me	β,β	NMe	9.60	2,932	1,478
RTI-158	Me	-C≡N	β,β	NMe	57	5095	1624
RTI-131	Me	-CH₂NH₂	β,β	NMe	10.5	855	120
RTI-164	Me	-CH₂NHMe	β,β	NMe	13.6	2246	280
RTI-132	Me	-CH₂NMe₂	β,β	NMe	3.48	206	137
RTI-239	Me	-CHMe₂	β,β	NMe	0.61	114	35.6
RTI-338	Et	-CO₂CH₂Ph	β,β	NMe	1104	7.41	3366
RTI-348	H	-Ph	β,β	NMe	28.2	>34,000	2670

Phenyltropane based Benztropines

Benztropine phenyltropane:^[32]

F&B series (Biotin side-chains etc.)

One patent claims a series of compounds with biotin-related sidechains are pesticides.^[13]

Code	X^{[clarification needed]}	2 Position^{[clarification needed]}	config	DA	NE	5-HT
RTI-224	Me	F1^c	β,β	4.49	—	155.6
RTI-233	Me	F2	β,β	4.38	516	73.6
RTI-235	Me	F3 d	β,β	1.75	402	72.4
RTI-236	Me	B1 d	β,β	1.63	86.8	138
RTI-237	Me	B2 d	β,β	7.27	258	363
RTI-244	Me	B3 d	β,β	15.6	1809	33.7
RTI-245	Cl	F4 c	β,β	77.3	—	—
RTI-246	Me	F4 c	β,β	50.3	3000	—
RTI-248	Cl	F6 c	β,β	9.73	4674	6.96
RTI-249	Cl	F1 c	β,β	8.32	5023	81.6
RTI-266	Me	F2	β,β	4.80	836	842
RTI-267	Me	F7 wrong	β,β	2.52	324	455
RTI-268	Me	F7 right	β,β	3.89	1014	382
RTI-269	Me	F8	β,β	5.55	788	986

800px 800px

References

Cite error: Invalid <references> tag; parameter "group" is allowed only.

Use <references />, or <references group="..." />

Cite error: Invalid <references> tag; parameter "group" is allowed only.

Use <references />, or <references group="..." />

External links

↑ ^1.0 ^1.1 Lua error in package.lua at line 80: module 'strict' not found.
↑ J Pharmacol Exp Ther. 2013 Jul; 346(1): 2–10. Fig. 1. Published online 2013 Jul. doi: 10.1124/jpet.111.191056
↑ ^3.00 ^3.01 ^3.02 ^3.03 ^3.04 ^3.05 ^3.06 ^3.07 ^3.08 ^3.09 ^3.10 ^3.11 ^3.12 ^3.13 Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists. Satendra Singh et al. Chem. Rev. 2000, 100. 925-1024. PubMed; Chemical Reviews (Impact Factor: 45.66). 04/2000; 100(3):925-1024 American Chemical Society; 2000, ISSN 0009-2665 ChemInform; May, 16th 2000, Volume 31, Issue 20, doi:10.1002/chin.200020238. Mirror hotlink.
↑ U.S. Patent 6,479,509 Method of promoting smoking cessation.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ ^6.0 ^6.1 Lua error in package.lua at line 80: module 'strict' not found.
↑ Monoamine Transporter Binding Properties of 3β-(Substituted phenyl)tropane-2β-carboxylic Acid Methyl Esters
↑ 3β-(4-Methoxyphenyl)tropane-2β-carboxylic Acid Ester Analogs
↑ ^9.0 ^9.1 Lua error in package.lua at line 80: module 'strict' not found.
↑ exo-2-Phenyl-7-azabicyclo[2.2.1]heptane-1-carboxylic Acid: A New Constrained Proline Analogue. Source: Tetrahedron Letters, Volume 36, Number 39, 25 September 1995, pp. 7123-7126(4)
↑ http://www3.interscience.wiley.com/journal/55001898/abstract
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ ^13.0 ^13.1 Methods for controlling invertebrate pests using cocaine receptor binding ligands. U.S. Patent 5,935,953
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ PMC 2671940
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.
↑ Lua error in package.lua at line 80: module 'strict' not found.

Cite error: <ref> tags exist for a group named "lower-alpha", but no corresponding <references group="lower-alpha"/> tag was found, or a closing </ref> is missing

[Tamagnan-1] 1.0 ^1.1 Lua error in package.lua at line 80: module 'strict' not found.

[2] J Pharmacol Exp Ther. 2013 Jul; 346(1): 2–10. Fig. 1. Published online 2013 Jul. doi: 10.1124/jpet.111.191056

[Singh2-3] 3.00 ^3.01 ^3.02 ^3.03 ^3.04 ^3.05 ^3.06 ^3.07 ^3.08 ^3.09 ^3.10 ^3.11 ^3.12 ^3.13 Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists. Satendra Singh et al. Chem. Rev. 2000, 100. 925-1024. PubMed; Chemical Reviews (Impact Factor: 45.66). 04/2000; 100(3):925-1024 American Chemical Society; 2000, ISSN 0009-2665 ChemInform; May, 16th 2000, Volume 31, Issue 20, doi:10.1002/chin.200020238. Mirror hotlink.

[6] U.S. Patent 6,479,509 Method of promoting smoking cessation.

[7] Lua error in package.lua at line 80: module 'strict' not found.

[RTI-111-8] 6.0 ^6.1 Lua error in package.lua at line 80: module 'strict' not found.

[9] Monoamine Transporter Binding Properties of 3β-(Substituted phenyl)tropane-2β-carboxylic Acid Methyl Esters

[10] 3β-(4-Methoxyphenyl)tropane-2β-carboxylic Acid Ester Analogs

[Meltzer-11] 9.0 ^9.1 Lua error in package.lua at line 80: module 'strict' not found.

[12] xo-2-Phenyl-7-azabicyclo[2.2.1]heptane-1-carboxylic Acid: A New Constrained Proline Analogue. Source: Tetrahedron Letters, Volume 36, Number 39, 25 September 1995, pp. 7123-7126(4)

[13] ttp://www3.interscience.wiley.com/journal/55001898/abstract

[15] Lua error in package.lua at line 80: module 'strict' not found.

[Nicholas-16] 13.0 ^13.1 Methods for controlling invertebrate pests using cocaine receptor binding ligands. U.S. Patent 5,935,953

[17] Lua error in package.lua at line 80: module 'strict' not found.

[18] Lua error in package.lua at line 80: module 'strict' not found.

[19] Lua error in package.lua at line 80: module 'strict' not found.

[20] Lua error in package.lua at line 80: module 'strict' not found.

[21] Lua error in package.lua at line 80: module 'strict' not found.

[22] Lua error in package.lua at line 80: module 'strict' not found.

[23] Lua error in package.lua at line 80: module 'strict' not found.

[24] Lua error in package.lua at line 80: module 'strict' not found.

[25] Lua error in package.lua at line 80: module 'strict' not found.

[26] Lua error in package.lua at line 80: module 'strict' not found.

[27] Lua error in package.lua at line 80: module 'strict' not found.

[28] Lua error in package.lua at line 80: module 'strict' not found.

[29] PMC 2671940

[30] Lua error in package.lua at line 80: module 'strict' not found.

[31] Lua error in package.lua at line 80: module 'strict' not found.

[32] Lua error in package.lua at line 80: module 'strict' not found.

[Spealman-33] Lua error in package.lua at line 80: module 'strict' not found.

[34] Lua error in package.lua at line 80: module 'strict' not found.

[35] Lua error in package.lua at line 80: module 'strict' not found.

[1]

[2]

[lower-alpha 1]

[lower-alpha 2]

[4]

[5]

[3]

[6]

[7]

[8]

[9]

[10]

[11]

[lower-alpha 3]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

v t e Phenyltropanes (classifications)
2-Carboxymethyl Esters	Troparil WIN 35428 RTI-31 RTI-32 RTI-51 RTI-55 RTI-83
(3,4-Disubstituted Phenyl)-tropanes	Dichloropane RTI-112 RTI-353
Arylcarboxy	RTI-113 RTI-120
Carboxyalkyl	RTI-121 RTI-150
Acyl	PTT/WF-11 WF-23 PIT/WF-21 WF-33
β,α Stereochemistry	RTI-352 RTI-274
α,β Stereochemistry	Brasofensine Tesofensine NS2359
Heterocycles: 3-Substituted-isoxazol-5-yl	RTI-177 RTI-336 RTI-371
Heterocycles: 3-Substituted-1,2,4-oxadiazole	RTI-126 RTI-371
N-alkyl	FP-β-CPPIT FE-β-CPPIT Altropane Ioflupane (¹²³I)
N-replaced (S,O,C)	Tropoxane
Irreversible	RTI-76
Nortropanes (N-demethylated)	NS2359 (GSK-372,475)

List of phenyltropanes

Contents

2-Carboxymethyl esters

(3,4-Disubstituted phenyl)-tropanes

Carboxyaryl

Carboxyalkyl

Amides

Acyl

Ester reduction

β,α Stereochemistry

α,β Stereochemistry

Aryl-Tropenes

Heterocycles

3-Substituted-isoxazol-5-yl

3-Substituted-1,2,4-oxadiazole

η6-3β-(transition metal complexed phenyl)tropanes

2-Alkane/Alkene

N-alkyl

Tricyclic/N-constrained (inclu. N-bridged/fused/tethered)

3-(2-thiophene) and 3-(2-furan)

N-replaced (S,O,C)

Diaryl

Radiolabeled

Transition metal complexes

Irreversible

Nortropanes (N-demethylated)

Thiophenyltropanes

Select annotations of above

Sister substances

Cycloalkane-ring alterations of the tropane ring system

Azanonane

Azabornane

Piperidine analogues

Misc.

Phenyltropane based Benztropines

F&B series (Biotin side-chains etc.)

See also

References

External links

Navigation menu

Search

η⁶-3β-(transition metal complexed phenyl)tropanes