Novel silaproline (Sip)-incorporated close structural mimics of potent antidepressant peptide drug rapastinel (GLYX-13) |
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Authors: | Krishnaprasad Madica Krishna Chaitanya Nadimpally Gangadhar J. Sanjayan |
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Affiliation: | 1. Division of Organic Chemistry, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India;2. Academy of Scientific and Innovative Research (AcSIR), CSIR, Pune 411008, India |
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Abstract: | Rapastinel (GLYX-13) is a C-amidated tetrapeptide drug under clinical development for adjunctive treatment of major depressive disorder (MDD). Rapastinel features two consecutive proline residues centered at the peptide sequence (Thr-Pro-Pro-Thr-NH2), which are detrimental to its biological activity. In this communication, we report the synthesis of very close structural analogues of rapastinel comprising silaproline (Sip) as proline surrogate. By virtue of its enhanced lipophilicity and metabolic stability, Sip introduction in the native rapastinel sequence is expected to improve its pharmacokinetic profiles. |
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Keywords: | Rapastinel Apimostinel Silaproline Peptide |
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