Enecadin

Last updated

Enecadin
Enecadin.svg
Clinical data
Other namesNS-7
Identifiers
  • 4-(4-Fluorophenyl)-2-methyl-6-(5-piperidin-1-ylpentoxy)pyrimidine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C21H28FN3O
Molar mass 357.473 g·mol−1
3D model (JSmol)
  • CC1=NC(=CC(=N1)OCCCCCN2CCCCC2)C3=CC=C(C=C3)F
  • InChI=1S/C21H28FN3O/c1-17-23-20(18-8-10-19(22)11-9-18)16-21(24-17)26-15-7-3-6-14-25-12-4-2-5-13-25/h8-11,16H,2-7,12-15H2,1H3
  • Key:SZSHJTJCJOWMHM-UHFFFAOYSA-N

Enecadin (NS-7) was an investigational new drug developed as a neuroprotectant for use following cerebral infarction (stroke). It was originally discovered by Nippon Shinyaku and later out-licensed to Schering in 1999. [1]

Contents

Enecadin exerts its neuroprotective effects by blocking voltage-gated sodium and calcium channels, which play key roles in excitotoxicity during ischemic injury. By limiting pathological ion influx, the compound was shown to preserve neuronal integrity in experimental models of stroke, spinal cord injury, and retinal ischemia. [2] [3] [4]

The drug advanced to Phase II clinical trials for acute ischemic stroke, but development was discontinued after the trial was terminated. [5]

Synthesis

Patent: [6]

Enecadin synthesis.svg

A Claisen-Schmidt reaction between p-fluoroacetophenone [403-42-9] (1) and diethyl carbonate [105-58-8] (2) gives ethyl 3-(4-fluorophenyl)-3-oxopropanoate [1999-00-4] (3). Treatment with acetamidine hydrochloride [124-42-5] (4) leads to the formation of 4-(4-fluorophenyl)-6-hydroxy-2-methylpyrimidine [178430-09-6] (5). Halogenation with phosphoryl chloride led to 4-chloro-6-(4-fluorophenyl)-2-methylpyrimidine [178430-13-2] (6). Williamson ether synthesis with 5-piperidino-1-pentanol [2937-83-9] (7) completed the synthesis of Enecadin (8).

See also

References

  1. ↑ Small DL (April 2000). "NS-7 (Nippon Shinyaku)". IDrugs: The Investigational Drugs Journal. 3 (4): 460–465. PMID   16100702.
  2. ↑ Anger T, Madge DJ, Mulla M, Riddall D (1 January 2001). "Medicinal Chemistry of Neuronal Voltage-Gated Sodium Channel Blockers". Journal of Medicinal Chemistry. 44 (2): 115–137. doi:10.1021/jm000155h. PMID   11170622.
  3. ↑ Shimidzu T, Itoh Y, Tatsumi S, Hayashi S, Ukai Y, Yoshikuni Y, et al. (May 1997). "Blockade of voltage-sensitive sodium channels by NS-7, a novel neuroprotective compound, in the rat brain". Naunyn-schmiedeberg's Archives of Pharmacology. 355 (5): 601–608. doi:10.1007/pl00004990. PMID   9151299.
  4. ↑ Katsumata T, Muramatsu H, Nakamura H, Nishiyama Y, Aoki Y, Katayama Y (April 2003). "Neuroprotective effect of NS-7, a novel Na+ and Ca2+ channel blocker, in a focal ischemic model in the rat". Brain Research. 969 (1–2): 168–174. doi:10.1016/s0006-8993(03)02296-0. PMID   12676377.
  5. ↑ Clinical trial number NCT00331721 for "Tolerability of Enecadin (INN) in Acute Ischemic Stroke Trial - TEST" at ClinicalTrials.gov
  6. ↑ WO 1996007641,Chokai S, Ukai Y, Aoki T, Ideguchi K,"Heterocyclic derivative and medicine",published 1996-03-14, assigned to Nippon Shinyaku Co., Ltd.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.