Pirandamine Explained

Pirandamine (AY-23,713) is a tricyclic derivative which acts as a selective serotonin reuptake inhibitor (SSRI).[1] [2] [3] It was investigated in the 1970s as a potential antidepressant but clinical development was not commenced and it was never marketed. Pirandamine is structurally related to tandamine, which, in contrast, is a selective norepinephrine reuptake inhibitor.

Synthesis

The Reformatsky reaction between 1-indanone [83-33-0] (1) and ethyl bromoacetate [105-36-2] in the presence of zinc gives ethyl 2-(1-hydroxy-2,3-dihydroinden-1-yl)acetate [1620-02-6] (2). The reduction of the ester with ester with LiAlH4 gives 1-(2-hydroxyethyl)-2,3-dihydroinden-1-ol, CID:130147665 (3). Acid catalyzed dehydration then leads to indene-3-ethanol [57931-97-2] (4'). Acid catalyzed condensation with ethyl acetoacetate [141-97-9] then gives CID:53692067 (5) The saponification of the ester to the corresponding acid [52001-26-0]. The reaction of this with ethyl chloroformate would give a mixed anhydride, and further reaction of this with dimethylamine then led to the amide [52001-28-2] (6). Reduction with lithium aluminium hydride completes the synthesis of pirandamine (7).

See also

Notes and References

  1. Pugsley T, Lippmann W . Effects of tandamine and pirandamine, new potential antidepressants, on the brain uptake of norepinephrine and 5-hydroxytryptamine and related activities . Psychopharmacology . 47 . 1 . 33–41 . May 1976 . 1085452 . 10.1007/BF00428698. 8354739 .
  2. Lippmann W, Pugsley TA . Pirandamine, a relatively selective 5-hydroxytryptamine uptake inhibitor . Pharmacological Research Communications . 8 . 4 . 387–405 . August 1976 . 1088377 . 10.1016/0031-6989(76)90039-4.
  3. Lippmann W, Seethaler K . Effects of tandamine and pirandamine, selective blockers of biogenic amine uptake mechanisms, on gastric acid secretion and ulcer formation in the rat . Life Sciences . 20 . 8 . 1393–400 . April 1977 . 853871 . 10.1016/0024-3205(77)90367-8.
  4. Web site: Prindamine CAS#: 21489-22-5.