Tropoxane (O-1072) is an aryloxytropane derivative drug developed by

Organix Inc Organix Inc is a US fine chemicals company specialising in chemical synthesis of analytical standards and custom synthesis of finished compounds and intermediates.{{Citation needed, date=February 2020 Chemistry Organix carries out research and de ...

., which acts as a

stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

and potent

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

and

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

reuptake inhibitor Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transmit ...

. It is an analogue of

dichloropane Dichloropane ((−)-2β-Carbomethoxy-3β-(3,4-dichlorophenyl)tropane, RTI-111, O-401) is a stimulant of the phenyltropane class that acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) with IC50 values of 3.13, 0.79 and ...

where the

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

nitrogen has been replaced by an oxygen

ether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be c ...

link (at the

bridgehead In military strategy, a bridgehead (or bridge-head) is the strategically important area of ground around the end of a bridge or other place of possible crossing over a body of water which at time of conflict is sought to be defended or taken over ...

position), demonstrating that the amine nitrogen is not required for DAT binding and reuptake inhibition.

Thia analog

The 8-thiabicyclo(3.2.1)octanes analogs such as

O-4210 O-4210 is a drug developed by Organix Inc which acts as a selective dopamine reuptake inhibitor, with good selectivity over the serotonin transporter but its activity at the noradrenaline transporter is not known. It is a thiatropane derivative, ...

have been prepared. A representative set of analogs is listed below. Thia

It had been hypothesized that transporter binding of the tropanes might include

ionic bonding Ionic bonding is a type of chemical bonding that involves the electrostatic attraction between oppositely charged ions, or between two atoms with sharply different electronegativities, and is the primary interaction occurring in ionic compounds. ...

of the central tropane nitrogen. But it turned out that at this site neither ionic nor

hydrogen bonding In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a l ...

is a prerequisite for potent monoamine reuptake inhibition. Oxa- and thia-analogs of RTI-111 are potent inhibitors, and even an ''N''-replacement by methylene holds the potency within the same magnitude. However, ''N''-quaternisation (''N''-dimethyl) considerably reduces DAT affinity. In this SAR, the focus is on seeing the effect of changing 8-NMe to S, O, or CH2. Both enantiomers, as well as the racemates are presented in several cases for comparison. Meltzer

References

{{Phenyltropanes Dopamine reuptake inhibitors Chloroarenes Methyl esters Oxygen heterocycles Heterocyclic compounds with 2 rings

Thia analog

See also

References