Solid and solution phase syntheses of the 2-cyanopyrrolidide DPP-IV inhibitor NVP-DPP728

Willand, Nicolas; Joossens, Jurgen; Gesquière, Jean‐Claude; Tartar, André; Evans, D. Michael; Roe, Michael B.

doi:10.1016/s0040-4020(02)00536-7

Cited by 7 publications

(7 citation statements)

References 7 publications

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“…70 (saxagliptin)164 was recently launched under the name Onglyza, and the structurally related 1 165 is licensed in Europe. The dinitrile 71 (NVP-DPP728)166 is in phase II clinical development.…”

Section: α-Amino Nitrile Drugs and Drug Leadsmentioning

confidence: 99%

Nitrile-Containing Pharmaceuticals: Efficacious Roles of the Nitrile Pharmacophore

et al. 2010

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Section: α-Amino Nitrile Drugs and Drug Leadsmentioning

confidence: 99%

Nitrile-Containing Pharmaceuticals: Efficacious Roles of the Nitrile Pharmacophore

et al. 2010

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“…In addition, the in vitro specificity was profiled in over 100 receptor and enzyme assays and no significant binding was observed (10 µM) [113]. A solid phase procedure for the synthesis of analogues of 17 has been reported [113,114].…”

mentioning

confidence: 99%

The Therapeutic Potential of Inhibitors of Dipeptidyl Peptidase IV (DPP IV) and Related Proline-Specific Dipeptidyl Aminopeptidases

Augustyns¹,

Veken²,

Senten³

et al. 2005

CMC

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In this review the structural and functional aspects of dipeptidyl peptidase IV (DPP IV) will be described, and the therapeutic potential of DPP IV inhibitors will be highlighted. DPP IV will be situated in clan SC, a group of serine proteases that contains several proline specific peptidases. Structural aspects of DPP IV and its interaction with different types of inhibitors are recently revealed by the publication of several crystal structures. Especially the design and development of new DPP IV inhibitors based on the three-dimensional structure, substrate specificity and catalytic mechanism will be discussed. In the last years there was an important development of new pyrrolidine-2-nitriles with very promising therapeutic properties for the treatment of type 2 diabetes. The role of DPP IV in peptide metabolism of members of the PACAP/glucagon peptide family, neuropeptides and chemokines has been thoroughly investigated during recent years. This is directly related to the promising therapeutic potential of DPP IV inhibitors in the treatment of type 2 diabetes and in the treatment of immunological disorders. Several inhibitors are currently under investigation in clinical trials for the treatment of type 2 diabetes and represent a new class of drugs for the treatment of this disease.

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“…The adduct 139 was dissolved in 10%TFA solution to afford the target compound NVP‐DPP728 140 in 50% yield (Scheme ) . On the other hand, compound NVP‐DPP728 140 was prepared in 75% yield via stirring of solution of adduct 139 in 10%TFA/90%CH 2 Cl 2 in the presence of excess 3‐(4‐(hydrazinosulfonyl)phenyl)propyl AM resin room temperature (RT) for 1 h (Scheme ) .…”

Section: Nvp‐dpp‐iv and Nvp‐dpp728 Inhibitorsmentioning

confidence: 99%

“…Condensation of 145 with ethylenediamine in DMSO afforded N ‐(2‐aminoethyl)‐Gly‐ l ‐Pro‐resin 146 . Treatment of 146 with 2‐acetyldimedone 147 in DMF afforded N ‐( N ‐[1‐{4,4‐dimethl‐2,6‐dioxo‐cyclohexyidene}‐ethylamino]‐2‐aminoethyl‐Gly‐ l ‐Pro‐resin 148 (Scheme ) .…”

Section: Nvp‐dpp‐iv and Nvp‐dpp728 Inhibitorsmentioning

confidence: 99%

“…The resin 150 was stirred in trifluoroacetic acid in CH 2 Cl 2 at RT for 2 h to afford the N ‐[2‐(5‐cyanopyridin‐2‐ylamino)ethyl]‐ N ‐[2‐(2‐S‐cyanopyrrolidin‐1‐yl)‐2‐oxoethyl]‐acetamide 151 . Removal of trifluoroacetyl group from 151 was carried out via stirring of 151 with aqueous ammonia in methanol for 3 h to achieve the desired compound NVP‐DPP728 140 in 80% yield (Scheme ) .…”

Section: Nvp‐dpp‐iv and Nvp‐dpp728 Inhibitorsmentioning

confidence: 99%

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A Review: Synthesis and Medicinal Importance of Nicotinonitriles and Their Analogous

Gouda

Hussein

Helal

et al. 2018

Journal of Heterocyclic Chem

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Solid and solution phase syntheses of the 2-cyanopyrrolidide DPP-IV inhibitor NVP-DPP728

Cited by 7 publications

References 7 publications

Nitrile-Containing Pharmaceuticals: Efficacious Roles of the Nitrile Pharmacophore

Nitrile-Containing Pharmaceuticals: Efficacious Roles of the Nitrile Pharmacophore

The Therapeutic Potential of Inhibitors of Dipeptidyl Peptidase IV (DPP IV) and Related Proline-Specific Dipeptidyl Aminopeptidases

A Review: Synthesis and Medicinal Importance of Nicotinonitriles and Their Analogous

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