List of Phenyltropanes - AbsoluteAstronomy.com

Such list of phenyltropane
Phenyltropane
Phenyltropanes were originally developed to reduce cocaine addiction and dependency. In general these compounds act as inhibitors of the plasmalemmal monoamine reuptake transporters. Although RTI holds a strong position in this field, they are not the only researchers that have prepared these...

s present many different avenues of research into therapeutic and addiction control depending on their construction and structure-activity relationship

Structure-activity relationship

The structure–activity relationship is the relationship between the chemical or 3D structure of a molecule and its biological activity. The analysis of SAR enables the determination of the chemical groups responsible for evoking a target biological effect in the organism...

ranging from the treating of cocaine dependency to understanding the dopamine reward system in the human brain to treating Alzheimer's

Alzheimer's disease

Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

& Parkinson's

Parkinson's disease

Parkinson's disease is a degenerative disorder of the central nervous system...

diseases. More recently there have been continual additions to the list and enumerations of the plethora of types of chemicals that fall into the category of being among one kind that would make it among others of this substance profile.

2-Carboxymethyl esters

Certain phenyltropanes can be used as a smoking cessation aid.

Selected Phenyltropanes
Short Name	X	DA	5HT	NE
WIN 35,065-2 (CPT)	H	23	1962	920
WIN 35,428 (CFT)	F	14	156	85
RTI-29	NH₂	9.8	5110	151
RTI-31 RTI-31 -2β-Carbomethoxy-3β-tropane is a synthetic analog of cocaine that acts as a stimulant. Semi-synthesis of this compound is dependent upon the availability of cocaine starting material. According to the article, RTI-31 is 64 x the strength of cocaine in terms of its potency to elicit...	Cl	1.12	44.5	37
RTI-32 RTI-32 -2β-Carbomethoxy-3β-tropane is a phenyltropane-based cocaine analog that is important in the field of medicinal chemistry for performing SAR.It has similar properties in vitro to related drugs such as RTI-31....	Me	1.71	240	60
RTI-51 RTI-51 -2β-Carbomethoxy-3β-tropane 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...	Br	1.69	10.6	37.4
Iometopane (RTI-55)	I	1.26	4.21	36
RTI-83 RTI-83 -2β-Carbomethoxy-3β-tropane is a phenyltropane derivative which represents a rare example of an SDRI or serotonin-dopamine reuptake inhibitor, a drug which inhibits the reuptake of the neurotransmitters serotonin and dopamine, while having little or no effect on the reuptake of the related...	Et	55	28	4030
RTI-298	–≡–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)

(3,4-Disubstituted phenyl)-tropanes

Compound	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)	Cl	Cl	CO₂Me	β,β	NMe	0.79	3.13	18.0
RTI-88 [recheck]	NH₂	I	CO₂Me	β,β	NMe	1.35	1329	320
RTI-97	NH₂	Br	CO₂Me	β,β	NMe	3.91	181	282
RTI-112 RTI-112 RTI-112 is a synthetic stimulant drug from the phenyltropane family. In contrast to RTI-113 which is DAT selective, RTI-112 is a nonselective triple reuptake inhibitor....	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 RTI-353 RTI-353 is a phenyltropane derived drug which acts as an SSRI.... (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

Arylcarboxy

2Ph> 2Ph > 2Ph > 2Ph > 2(p-C₆H₄I)> 2(o-C₆H₄Me)> 2(m-C₆H₄Me)> 2(p-C₆H₄Me)>

Compound	X	2 Position	config	8	DA	5-HT	NE
RTI-122	I
β,β	NMe	1.50	184	3,791
RTI-113 RTI-113 RTI-113 is a stimulant drug which acts as a potent and fully selective dopamine reuptake inhibitor . It has been suggested as a possible substitute drug for the treatment of cocaine addiction...	Cl
β,β	NMe	1.98	2,336	2,955
RTI-277	NO₂
β,β	NMe	5.94	2,910	5,695
RTI-120 RTI-120 -2β-Carbophenoxy-3β-tropane is a phenyltropane derivative which acts as a reasonably selective dopamine reuptake inhibitor, along with weaker inhibition of noradrenaline and serotonin reuptake. It has a reasonably fast rate of occupancy of dopamine transporters in the brain, though slower than... [recheck]	Me
β,β	NMe	3.26	24,471	5,833
RTI-116	Cl
β,β	NMe	33	1,227	968
RTI-203	Cl	CO₂(m-C₆H₄Me)	β,β	NMe	9.37	2153	2744
RTI-204	Cl
β,β	NMe	3.91	3,772	4,783
RTI-205	Me
β,β	NMe	8.19	5,237	2,137
RTI-206	Cl
β,β	NMe	27.4	1,203	1,278

Carboxyalkyl

2Prⁱ> 2Prⁱ> 2Pr^cyc> 2Prⁱ> 2Prⁱ > 2Pr^cyc> 2Pr^cyc> 2Prⁱ> 2Bu^cyc> 2C(H)Et₂> 2CH2Ph>

Code	X	2 Position	config	8	DA	5-HT	NE
RTI-77	Cl	CH2CH2(3-iodo-p-anilino)	β,β	NMe	2.51	—	2247
RTI-121 RTI-121 -2β-Carboisopropoxy-3β-tropane is a stimulant drug used in scientific research, which was developed in the early 1990s. RTI-121 is a phenyltropane based, highly selective dopamine reuptake inhibitor and is derived from methylecgonidine...	I
β,β	NMe	0.43	66.8	285
RTI-153	I
β,β	NH	1.06	3.59	132
RTI-191	I
β,β	NMe	0.61	15.5	102
RTI-114	Cl
β,β	NMe	1.40	1,404	778
RTI-278	NO₂
β,β	NMe	8.14	2,147	4,095
RTI-190	Cl
β,β	NMe	0.96	168	235
RTI-193	Me
β,β	NMe	1.68	1,066	644
RTI-117	Me
β,β	NMe	6.45	6,090	1,926
RTI-150	Me
β,β	NMe	3.74	2,020	4,738
RTI-127	Me
β,β	NMe	19	4500	3444
RTI-338	ethyl
β,β	NMe	1104	7.41	3366

Use of a cyclopropyl ester appears to enable better MAT

Monoamine transporter

Monoamine transporters are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters...

retention than does the choice of isopropyl

Isopropyl

In organic chemistry, isopropyl is a propyl with a group attached to the secondary carbon. If viewed as a functional group an isopropyl is an organic compound with a propyl group attached at its secondary carbon.The bond is therefore on the middle carbon....

ester.

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

Amides

RTI-183 and RTI-218 have the same structure??

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 RTI-229 -3β-tropane-2β-pyrrolidine carboxamide is a potent and long-lasting stimulant drug which was developed in the 1990s as part of a large group of related analogues from the phenyltropane family...	I	CON(CH₂)₄	β,β	NMe	0.37	991	1,728

Acyl

i >

Code	X	Y	2 Position	config	8	DA	5-HT	NE
WF-23	β-naphthyl		C(O)Et	β,β	NMe	0.115	0.394	No data
WF-31 2-Propanoyl-3-(4-isopropylphenyl)-tropane 2-Propanoyl-3--tropane is a cocaine analogue. Research shows WF-31 to be approximately ten times more potent than cocaine at binding to serotonin and at inhibiting serotonin uptake.- References :...
H	C.O.Et	β,β	NMe	615	54.5	No data
WF-11	Me	H
β,β	NMe	8.2	131	No data
WF-25	H	H
β,β	NMe	48.3	1005	No data
WF-33	6-MeoBN		C(O)Et	α,β	NMe	0.13	2.24	No data

Ester reduction

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

Carbonate

In chemistry, a carbonate is a salt of carbonic acid, characterized by the presence of the carbonate ion, . The name may also mean an ester of carbonic acid, an organic compound containing the carbonate group C2....

.

2OH > 2OH > 2OH > 2OH > 2OAc > 2OBz > 2OCO₂Me>

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

Misc.

2Cl > 2CO₂Me> 3> 2> 2OCO₂Me> 2NH₂> 2NHMe> 2NMe₂> 2> 2CH₂Ph>

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
β,β	NMe	2.64	98	129.8
RTI-241	Me
β,β	NMe	1.02	619	124
RTI-139	Cl
β,β	NMe	1.67	85	57
RTI-161	Cl
β,β	NMe	13.1	1887	2516
RTI-230	Cl	H₃C–Ç=CH₂	β,β	NMe	1.28	57	141
RTI-240	Cl
β,β	NMe	1.38	38.4	84.5
RTI-145	Cl
β,β	NMe	9.60	2,932	1,478
RTI-158	Me
β,β	NMe	57	5095	1624
RTI-131	Me
β,β	NMe	10.5	855	120
RTI-164	Me
β,β	NMe	13.6	2246	280
RTI-132	Me
β,β	NMe	3.48	206	137
RTI-239	Me
β,β	NMe	0.61	114	35.6
RTI-338	Et
β,β	NMe	1104	7.41	3366
RTI-348	H
β,β	NMe	28.2	>34,000	2670

F&B series

The compound of the present invention are useful pesticide

Pesticide

Pesticides are substances or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.A pesticide may be a chemical unicycle, biological agent , antimicrobial, disinfectant or device used against any pest...

Code	X	2 Position	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

Biotin

Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...

β,α Stereochemistry

Compound	X	2 Group	config	8	DA	5-HT	NE
RTI-140	H	CO₂Me	β,α	NMe	101	5,701	2,076
RTI-352 RTI-352 RTI-352 is a phenyltropane that is used as a radiolabeling ligand for the DAT. RTI-352 has been configured to have 1R,2S,3R stereochemistry and is therefore a geometric isomer of β-CIT....	I	CO₂Me	β,α	NMe	2.86	64.9	52.4
RTI-549	Br	CO₂Me	β,α	NMe
RTI-319	BN	CO₂Me	β,α	NMe	1.1	11.4	70.2
RTI-286	F	CO₂Me	β,α	NMe	21	5062	1231
RTI-274 RTI-274 RTI-274, or 2β--3α-nortropane is a phenyltropane homologue of paroxetine developed by the group led by F Ivy Carroll in the 1990s.-Introduction:...	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

α,β Stereochemistry

{| class="wikitable"
| Compound || X || 2 Group || config || 8 || DA||5-HT||NE
|-
| Brasofensine

Brasofensine

Brasofensine is a phenyltropane that had been under development for the treatment of Parkinson's and Alzheimer's disease...

|| Cl2 || methyl aldoxime || α,β || NMe || ||||
|-
| Tesofensine

Tesofensine

Tesofensine is a serotonin–noradrenaline–dopamine reuptake inhibitor from the phenyltropane family of drugs, which is being developed for the treatment of obesity...

|| Cl2 || ethoxymethyl || α,β || NMe ||65||11||1.7
|-
|NS-2359 (GSK-372,475)|| Cl2 || Methoxymethyl || α,β || NH || || ||
|}

Heterocycles

These heterocycles are sometimes referred to as the "bioisosteric

Bioisostere

In medicinal chemistry, bioisosteres are substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to a chemical compound. In drug design, the purpose of exchanging one bioisostere for another is to enhance the desired biological or...

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 to the energetically more favorable trans configuration. This can also happen to cocaine also.

3-Substituted-isoxazol-5-yl

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 RTI-171 -2β--3β-tropane is a phenyltropane derivative which acts as a selective dopamine reuptake inhibitor, with a relatively slow onset of action and short duration of effects found in animal studies....	Me	3-methylisoxazol-5-yl	0.93	254	3818
RTI-180	I	3-methylisoxazol-5-yl	0.73	67.9	36.4
RTI-177 RTI-177 RTI-177 is a synthetic stimulant drug from the phenyltropane family, which acts as a DRI with micromolar affinity for the SERT...	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-anisoyl	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 RTI-371 3β--2β-[3-isoxazol-5-yl]tropane is a phenyltropane derived drug which acts as a potent and selective dopamine reuptake inhibitor in vitro, yet unusually for this class of compound, both RTI-371 and the closely related compound RTI-370 failed to produce locomotor stimulation in mice...	Me	p-chlorophenyl	8.74	>100K (60,200)	>100K (9090)
RTI-386	Me	p-anisoyl	3.93	756 (450)	4027 (380)
RTI-387	Me	p-fluorophenyl	6.45	917 (546)	>100K (9400)

3-Substituted-1,2,4-oxadiazole

Heterocyclic (N-methyl)phenyltropanes with 1R stereochemistry.
Code	X	R	DA	NE	5HT
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	Cl	3-methyl-1,2,4-oxadiazole	4.05	363	2584
ββRTI-126	H	3-methyl-1,2,4-oxadiazole	100	7876	3824
RTI-130	Cl	3-phenyl-1,2,4-oxadiazole	1.62	245	195
RTI-141	Cl	3-(p-anisoyl)-1,2,4-oxadiazole	1.81	835	357
RTI-143	Cl	3-(p-chlorophenyl)-1,2,4-oxadiazole	4.1	4069	404
RTI-144	Cl	3-(p-bromophenyl)-1,2,4-oxadiazole	3.44	1825	106
βRTI-151	Me	3-phenyl-1,2,4-oxadiazole	2.33	60	1074
αRTI-152	Me	3-phenyl-1,2,4-oxadiazole	494	—	1995
RTI-154	Cl	3-isopropyl-1,2,4-oxadiazole	6	135	3460
RTI-155	Cl	3-cyclopropyl-1,2,4-oxadiazole	3.41	177	4362

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 RTI-371 3β--2β-[3-isoxazol-5-yl]tropane is a phenyltropane derived drug which acts as a potent and selective dopamine reuptake inhibitor in vitro, yet unusually for this class of compound, both RTI-371 and the closely related compound RTI-370 failed to produce locomotor stimulation in mice...	Cl	3-(p-chlorophenyl)isoxazol-5-yl	13	>100K	>100K
RTI-436	Me
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)

N-alkyl

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 Altropane Altropane, is a phenyltropane derivative which acts as a potent dopamine reuptake inhibitor and long-acting stimulant drug...	F	CO₂Me	β,β	NCH₂CH=CHF
RTI-310	I	CO₂Me	β,β	N-Prⁿ	1.17
RTI-311	I	CO₂Me	β,β	NCH₂CH=CH₂	1.79
RTI-312	I	CO₂Me	β,β	NBuⁿ	0.76
RTI-313	I	CO₂Me	β,β	NCH₂CH₂CH₂F	1.67
Ioflupane Ioflupane Ioflupane is the International Nonproprietary Name of a phenyltropane compound which is a neuro-imaging radiopharmaceutical drug, used by nuclear medicine physicians for the diagnosis of Parkinson's disease and the differential diagnosis of Parkinson's disease over other disorders presenting...	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

N-replaced (S,O,C)

{| class="wikitable"
| Compound || X || 2 Group || config || 8 || DA||5-HT||NE
|-
| Tropoxane

Tropoxane

Tropoxane is an aryloxytropane derivative drug developed by Organix Inc, which acts as a stimulant and potent dopamine and serotonin reuptake inhibitor. It is an analogue of dichloropane where the amine nitrogen has been replaced by an oxygen ether link , demonstrating that the amine nitrogen is...

|| Cl,Cl|| CO2Me ||(racemic) β,β || O ||3.3||6.5||No data
|}

Irreversible

Covalent bond

A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....

(phenylisothiocyanate) binding ligand
RTI-76: 4-isothiocyanatophenyl (1R,2S,3S,5S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate

Nortropanes (N-demethylated)

NS2359

NS-2359 is a serotonin-norepinephrine-dopamine reuptake inhibitor. It was under development by GlaxoSmithKline as an antidepressant, but was discontinued in 2009 when phase II clinical trials turned up disappointing results and did not support further effort by the company...

(GSK-372,475)

It is well established that electrostatic potential around the para position tends to improve MAT

Monoamine transporter

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. Of course, this is not always the case. For an interesting exception to this trend, see the Taxil

RTI-274

RTI-274, or 2β--3α-nortropane is a phenyltropane homologue of paroxetine developed by the group led by F Ivy Carroll in the 1990s.-Introduction:...

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 which 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.

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 archetypal '4HC-Tropanes.
X	[³H]Paroxetine	[³H]WIN 35,428	[³H]Nisoxetine
Ethyl Ethyl Ethyl may refer to:* Ethyl group, a functional group in organic chemistry* Ethyl Corporation, a fuel additive company* Ethanol, also known as ethyl alcohol* Cold Ethyl, a rock band founded by Nicke Andersson...	28.4 → 8.13	55 → 49.9	4,029 → 122
vinyl Vinyl A vinyl compound is any organic compound that contains a vinyl group ,which are derivatives of ethene, CH2=CH2, with one hydrogen atom replaced with some other group...	9.5 → 2.25	1.24 → 1.73	78 → 14.9
Ethynyl Ethynyl In organic chemistry, the term ethynyl designatesAn ethynyl group .The ethynyl radical ....	4.4 → 1.59	1.2 → 1.24	83.2 → 21.8
1-Propyl	70.4 → 26	68.5 → 212	3,920 → 532
t-propenyl Propenyl Propenyl is a chemical radical of propene .Propenyl groups bind water molecules inside rocks. The amount of water trapped in a rock varies by composition.-References:http://www.biology-online.org/dictionary/Propenyl...	11.4 → 1.3	5.29 → 28.6	1,590 → 54
c-propenyl	7.09 → 1.15	15 → 31.6	2,800 → 147
Allyl Allyl An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl...	28.4 → 6.2	32.8 → 56.5	2,480 → 89.7
1-Propynyl Propynyl In chemistry, propynyl is an propyl functional group bearing a triple bond. 2-Propynyl is known as propargyl group with the structure of HC≡C−CH2 and 1-propynyl group has the structure of CH3-C≡C-....	15.7 → 3.16	2.37 → 6.11	820 → 116
i-Propyl	191 → 15.1	597 → 310	75,000 → ?
2-Propenyl Propenyl Propenyl is a chemical radical of propene .Propenyl groups bind water molecules inside rocks. The amount of water trapped in a rock varies by composition.-References:http://www.biology-online.org/dictionary/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

Manifaxine

Manifaxine is a drug developed by GlaxoSmithKline through structural modification of radafaxine, the active metabolite of bupropion. It acts as a norepinephrine-dopamine reuptake inhibitor...

, and reboxetine

Reboxetine

Reboxetine is a drug marketed as an antidepressant for use in the treatment of clinical depression, panic disorder and ADD/ADHD, developed by Pharmacia . Its mesylate salt is sold under tradenames including Edronax, Norebox, Prolift, Solvex, Davedax or Vestra...

as new NET selective compounds for treating ADHD and other CNS disorders such as depression" (FIC, et al. 2005).

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. , , , and .

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 which 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

Dopamine transporter

The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...

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

Piperidine

Piperidine is an organic compound with the molecular formula 5NH. This heterocyclic amine consists of a six-membered ring containing five methylene units and one nitrogen atom...

class (a category that includes methylphenidate

Methylphenidate

Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...

) or benztropine

Benztropine

Benzatropine , also known as benztropine , is an anticholinergic marketed under the trade name Cogentin which is used in the treatment of Parkinson's disease, parkinsonism, akathisia, and dystonia.- Indications :...

class (such as Difluoropine

Difluoropine

--2β-Carbomethoxy-3α-tropane is a stimulant drug synthesised from tropinone, which acts as a potent and selective dopamine reuptake inhibitor...

: which is extremely close to fitting the criteria of being a phenyltropane.) Whereas other potent DRI

Dopamine reuptake inhibitor

A dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter...

s are far removed from being in the phenyltropane structural family, such as Benocyclidine

Benocyclidine

Benocyclidine , or benzothiophenylcyclohexylpiperidine , is a psychoactive drug and research chemical of the arylcyclohexylamine and piperidine chemical classes. It acts a potent and selective dopamine reuptake inhibitor and a stimulant...

or Vanoxerine

Vanoxerine

Vanoxerine is a piperazine derivative which is a potent and selective DRI. GBR-12909 binds to the target site on the DAT ~ 500 times more strongly than cocaine, but simultaneously inhibits the release of dopamine...

External links

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