# Mioflazine

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**Mioflazine** (R 51469) is a [compound](/source/Chemical_compound) that has garnered attention due to its potential protective effects against [myocardial ischemia](/source/Myocardial_ischemia). Primarily acting as a [nucleoside transport inhibitor](/source/Nucleoside_transporter),[1] mioflazine has been shown in preclinical studies to improve cardiac survival during ischemic episodes, modulate the dynamics of [nucleoside](/source/Nucleoside) accumulation during reperfusion, and exhibit unique pharmacological properties without significant [inotropic](/source/Inotrope) effects.[2]

Mioflazine is a member of [diphenylbutylpiperazine](/source/Diphenylbutylpiperazine) class. Other members of this class include [lidoflazine](/source/Lidoflazine), [draflazine](/source/Draflazine), and [soluflazine](/source/Soluflazine). R57974[3] has the same structure as mioflazine but is based on a 5,5-bis(4-fluorophenyl)pentyl] pendant sidechain.[4]

## Synthesis

A patented procedure for mioflazine was released,[5] and described in a book:[6]

(Ex XXV inter. 83; Ex XXXI inter. 115; Ex XXXIII inter. 125; Ex XXXV cmp. 27).

The first step involves reacting Piperazine-2-carboxamide [84501-64-4] (**1**) with [acetone](/source/Acetone) to form a cyclic aminal protecting group thus forming hexahydro-3,3-dimethylimidazo(1,5-a)pyrazin-1(5H)-one [83898-63-9] (**2**). The vacant piperazine secondary nitrogen is reacted with 2-Chloro-N-(2,6-dichlorophenyl)acetamide [3644-56-2] (**3**) giving N-(2,6-dichlorophenyl)hexahydro-3,3-dimethyl-1-oxoimidazo[1,5-a]pyrazine-7(1H)-acetamide [83898-62-8] (**4**). Acid hydrolysis removal of the cyclic aminal protecting group gives 3-Carbamoyl-N-(2,6-dichlorophenyl)piperazine-1-acetamide [83863-78-9] (**5**). The unmasked remaining piperazine secondary nitrogen is alkylated with 1,1'-(4-Iodobutylidene)bis(4-fluorobenzene) [51787-79-2] (**6**), completing the synthesis of mioflazine (**7**).

## References

1. Baer HP, Haq A, el-Soofi A, Serignese V, Paterson AR (May 1990). "Potencies of mioflazine and its derivatives as inhibitors of adenosine transport in isolated erythrocytes from different species". *The Journal of Pharmacy and Pharmacology*. **42** (5): 367–369. [doi:10.1111/j.2042-7158.1990.tb05432.x](https://doi.org/10.1111/j.2042-7158.1990.tb05432.x). [PMID 1976791](https://pubmed.ncbi.nlm.nih.gov/1976791)

1. Morton IK, Hall JM (1999). ["M"](http://link.springer.com/10.1007/978-94-011-4439-1_12). *Concise Dictionary of Pharmacological Agents*. Springer Netherlands. pp. 171–188. [doi:10.1007/978-94-011-4439-1_12](https://doi.org/10.1007/978-94-011-4439-1_12). ISBN 978-94-010-5907-7.

1. ["4-\[5,5-Bis(4-fluorophenyl)pentyl\]-1-\[2-(2,6-dichloroanilino)-2-oxoethyl\]piperazine-2-carboxamide"](https://pubchem.ncbi.nlm.nih.gov/compound/10031309). *PubChem*. U.S. National Library of Medicine.

1. Baer HP, Serignese V, Moorji A, Van Belle H (April 1991). "In vivo effectiveness of several nucleoside transport inhibitors in mice and hamsters". *Naunyn-Schmiedeberg's Archives of Pharmacology*. **343** (4): 365–369. [doi:10.1007/BF00179040](https://doi.org/10.1007/BF00179040). [PMID 1852220](https://pubmed.ncbi.nlm.nih.gov/1852220)

1. EP0068544 idem Georges Van Daele, US4766125 (1983 to Janssen Pharmaceutica NV).

1. The organic chemistry of drug synthesis, volume 4, Dan Lednicer & Lester Mitscher with Gunda Georg, Page 119.

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