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Published on:June 2016
RGUHS Journal of Pharmaceutical Sciences, 2016; 6(2):26-31
Research Article | doi:10.5530/rjps.2016.2.2

Synthesis and Biological Activity of Xanthene Derivatives as Antiasthamatic Agents

Authors and affiliation (s):

Manish Sudesh Bhatia, Vikram Shivaji Waghmare, Prafulla Balkrishna Choudhari, Santosh Sahedeo Kumbhar*

Department of Pharmaceutical Chemistry, Drug Design and Development Group, Bharati Vidyapeeth College of Pharmacy, Near Chitranagari, Kolhapur-416013, Maharashtra, INDIA.


Plan: To develop some 1,3-dimethyl-7-[2-(piperazin-1-yl)acetyl]-2,3,6,7-tetrahydro-1H-purine-2,6-dione derivatives for their antiasthamatic activity. Objective: Xanthene derivatives are known for their vasodilatory activity. Development of Phosphodiesterase 3 inhibitors is current area of interest for development of anti-asthmatic agents. Many compounds containing xanthene nucleus are also found to possess a number of pharmacological activities. Thus a new series of 1,3-dimethyl-7-(2-(piperazin-1-yl)acetyl)-2,3,6,7-tetrahydro-1H-purine-2,6-dione has been synthesized, characterized and screened for the vasodilator activity. Methodology: In our present study the intermediate 27-(chloroacetyl)-1,3- dimethyl-3,7-dihydro-1H-purine-2,6-dione [A] was prepared via reaction of theophylline and chloroacetyl chloride. This compound was treated with Piperazine in presence of methanol followed by hydrazine hydrate to yield the key intermediate 1,3-dimethyl-7-(2-(piperazin-1-yl)acetyl)-2,3,6,7-tetrahydro-1H-purine-2,6-dione (B). This compound was treated with various substituted aromatic amines to get the title compounds [1-12]. The title compounds were characterized by MP, TLC, IR, UV, and NMR & Mass spectrum. The compounds were screened for pulmonary vasodilator activity. Outcome: All compounds showed significant activity compared to standard Cilostazol. 7-(2-{4-[1-(3,4-di-chlorophenyl) ethyl]piperazin-1-yl}acetyl)-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione (8) was most active derivative from the series. 7-(2-{4-[(2,4-di-nitrophenyl)methyl]piperazin-1-yl}acetyl)-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione (6) and 7-(2-{4-[1-(4-hydroxyphenyl)ethyl]piperazin-1-yl}acetyl)-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione (4) showed moderate to mild activity. Conclusion: Activity of the derivatives with di-chloro substitution indicated that the compounds with electron withdrawing groups are showing significant activity than other compounds which indicated mechanistic details of all the compounds in near future would lead to potent anti-asthmatic compounds.

Key words: Xanthene, Phosphodiesterase, Bioactivity, Smooth muscle relaxants.


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