Pirandamine (AY-23,713) is a tricyclic

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. F ...

which acts as a selective serotonin reuptake inhibitor (SSRI). It was investigated in the 1970s as a potential

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

but clinical development was not commenced and it was never marketed. Pirandamine is

structurally A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

related to

tandamine Tandamine is a selective norepinephrine reuptake inhibitor with a tricyclic structure. It was developed in the 1970s as an antidepressant but was never commercialized. Tandamine is analogous to pirandamine, which, instead, acts as a selective s ...

, which, in contrast, is a selective

norepinephrine reuptake inhibitor A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epineph ...

Synthesis

Condensation of

1-indanone 1-Indanone is the organic compound with the formula C6H4(CH2)2CO. It is one of two isomeric benzocyclopentanones, the other being 2-indanone. It is a colorless solid. 1-Indanone is a substrate for the enzyme indanol dehydrogenase. Preparation ...

(1) with

ethyl bromoacetate Ethyl bromoacetate is the chemical compound with the formula CH2BrCO2C2H5. It is the ethyl ester of bromoacetic acid and is prepared in two steps from acetic acid. It is a lachrymator and has a fruity, pungent odor. It is also a highly toxic alky ...

and zinc affords Reformatsky reaction product 2; then reduction with LiAlH₄ gives diol 3. Dehydration with H₂SO₄ gives the indene ethanol 4. Acid catalyzed condensation of 4 with ethyl acetoacetate then gives the fused tetrahydropyran derivative 5 (no doubt by a scheme quite analogous to prodolic acid). The ester is then saponified to the corresponding acid, which is then converted to the dimethylamide (6). Reduction with LiAlH₄ completes the synthesis of the antidepressant agent pirandamine (7).

References

{{Tricyclics Dihydropyrans

Synthesis

See also

References