M550 - Synthesis of 1,2,5,7-dithiadiazonan-6-ylidenecyanamide. A New Potential Cysteamine Derivate Radioprotector Compound

Molbank 2007, M550

http://www.mdpi.org/molbank/

Synthesis of 1,2,5,7-dithiadiazonan-6-ylidenecyanamide. A New Potential Cysteamine Derivate Radioprotector Compound

Enrique Angeles ^1,*, Italo Menconi ¹, Alberto Ramírez ¹, Ana María Velázquez ¹, Brígida Camacho ¹, Gerardo Ordónez ¹, Ignacio Martínez ¹, Sandra Díaz-Barriga ¹, Rafael López-Castañares ²

1 Laboratorio de Química Medicinal, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, México

2 Facultad de Química de la UAEM, Universidad Autónoma del Estado de México.

* Author to whom correspondence should be addressed. E-mail: [email protected]

Received: 19 January 2007 / Accepted: 24 February 2007 / Published: 30 May 2007

Keywords: Cysteamine, radioprotector, nine member ring.

Introduction

Radioprotectors have been described as a chemical compounds that protect certain normal tissues as opposed to tumors. [1] and have shown promise for protecting mammals against otherwise lethal effects of ionizing radiation; they are particular interest since they lack nitrogen, wich typically is present in antiradiation agents[2]. The action mechanism of radioprotectors is postulated that they act through their aminothiol derivative wich is libereted in vivo [3,4]. There has been reported in literature the synthesis of many radioprotector that interact with proteins [5] and also enhance its radiorpotective effect [6-8].Furthermore, the nucleophilic thiol grups present in radioprotectors, could also trap xenobiotic electrophilic intermediates originating from alkylating agents by formation of cavalent bonds.On the other hand some ciclic cysteamine radiportector realted compounds have been (I-IV) (Fig. 1).

1,2,5,7-dithiadiazonan-6-ylidenecyanamide (3) was prepared from dithiomethylcyanourea (1) and cistamine (2) in methanol as solvent . A solution of methanol (50 mL) and sodium hydroxyde was prepared and 1 (g, mmol) in methanol (mL) was added and heated at 40 °C for 15 minutes, after that a solution of 2 (g, mmol) in methanol was added . When the addition was completed, the reaction mixture was stirred at reflux for 24 hrs. The solvent was eliminated using rotavapor and reaction mixture was poured into water and extracted with ehtyl acetate. The product was crystallized after eliminated solvent and recrystallized from ethanol as white powder (85% yield).

Melting point: 152-154 ^oC (ethanol, uncorrected).

IR (cm^-1; KBr Disk) 3452 (N-H), 2220 (CN), 1609 (C=C).

¹H-NMR (300 MHz; CDCl₃; Me₄Si, δ_H): 9.50 (2H, s, NH), 3.76 (4H, m, N-CH₂-), 3.52 (4H, m, -S-CH₂-).

¹³C-NMR (75 MHz; CDCl₃; δ_C):177.9 (C=N), 117.6 (CN), 47.42(-N-CH₂-), 31.21 (-S-CH₂-).

MS m/z (rel %): 202(1.0 %), 172 (100%)

Elemental Analysis: Calculated for C₆H₁₀N₄S₂ (202): C 35.62 %, H 4.98 %, N 27.70 %, S 31.77 % ; found : C 35.70 %, H 5.01 %, N 27.56 %, S 31.91 %.

Acknowledgements

The authors wish to acknowledge to PAPIIT/UNAM Proyect No IN213606 and ALPHARMA SA de CV, by partially support this work. We would like to thank C.Barajas F.Sotres and D.Jiménez for their skillful technical assistance and DGSCA-UNAM for their support. As a part of Proyect Cátedra Química Medicinal of FESC-UNAM.

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