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Synthesis of N-[3′-(acetylthio)alkanoyl] and N-[3′-mercaptoalkanoyl]-4-α(s)-(phenylmethyl) pyroglutamic acids and prolines as potent ACE inhibitors

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Abstract

Angiotensin converting enzyme (ACE) inhibitors have emerged as a revolution in antihypertensive therapy. Introduction of captopril, the first rationally designed ACE inhibitor, has encouraged researchers all over the world to design and synthesize target molecules controlling hypertension based on these lines. It has been observed that replacing proline part of captopril with 4-substituted prolines or 5-oxo-prolines led to significant enhancement in ACE inhibitory activity, and this observation prompted us to design and synthesize N-acyl 4-substituted pyroglutamates and prolinates with the objective of developing therapeutically better ACE inhibitors. Herein we describe an easy approach for N-acylation of 4-α(S)-(phenylmethyl) pyroglutamates with the aim of synthesizing N-[3′-(acetylthio)alkanoyl] and N-[3′-mercaptoalkanoyl]-4-α-(s)-(phenylmethyl) pyroglutamic acids and prolines as ACE inhibitors.

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Acknowledgements

The corresponding author is thankful to the Central Drug Research Institute, Lucknow, India, for providing infrastructural facilities to carry out above work and to SAIF, CDRI, Lucknow for providing analytical data.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Engineering and Technology, M. J. P. Rohilkhand University, Bareilly, UP, India

    Sharad Kumar Panday

  2. Pharmacology Division, Central Drug Research Institute, Lucknow, UP, India

    Madhu Dikshit

  3. Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, UP, India

    Dinesh Kumar Dikshit

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  1. Sharad Kumar Panday
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  2. Madhu Dikshit
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  3. Dinesh Kumar Dikshit
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Correspondence to Sharad Kumar Panday.

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Panday, S.K., Dikshit, M. & Dikshit, D.K. Synthesis of N-[3′-(acetylthio)alkanoyl] and N-[3′-mercaptoalkanoyl]-4-α(s)-(phenylmethyl) pyroglutamic acids and prolines as potent ACE inhibitors. Med Chem Res 18, 566–578 (2009). https://doi.org/10.1007/s00044-008-9150-z

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