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Current Medicinal Chemistry

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Review Article

Recent Medicinal Chemistry Approach for the Development of Dipeptidyl Peptidase IV Inhibitors

Author(s): Bhumi M. Shah, Palmi Modi and Priti Trivedi*

Volume 28, Issue 18, 2021

Published on: 12 October, 2020

Page: [3595 - 3621] Pages: 27

DOI: 10.2174/0929867327666201012153255

Price: $65

Abstract

Background: Diabetes, a metabolic disease, occurs due to a decreased or no effect of insulin on the blood glucose level. The current oral medications stimulate insulin release, increase glucose absorption and its utilization, and decrease hepatic glucose output. Two major incretin hormones like Glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide - 1 (GLP-1) stimulate insulin release after a meal, but their action is inhibited by enzyme dipeptidyl peptidase- IV.

Objective: The activity of endogenous GLP-1 and GIP prolongs and extends with DPP IV inhibitors, which are responsible for the stimulation of insulin secretion and regulation of blood glucose level. DPP IV inhibitors have shown effectiveness and endurability with a neutral effect on weight as well as less chances of hypoglycemia in the management of type 2 diabetes. These journeys started from Sitagliptin (marketed in 2006) to Evogliptin (marketed in 2015, Korea).

Conclusion: Treatment of type 2 diabetes includes lifestyle changes, oral medications, and insulin. Newer and superior therapies are needed more than currently prescribed drugs. Various heterocyclic derivatives have been tried, but due to masking of DASH proteins, CYP enzymes, and hERG channel, they showed side effects. Based on these, the study has been focused on the development of safe, influential, selective, and long-lasting inhibitors of DPP IV.

Keywords: Diabetes, DPP IV inhibitors, GLP -1, Heterocyclic derivatives, Type-2 diabetes, CYP enzymes.

« Previous Next »
[1]
IDF DIABETES ATLAS. 9th edition 2019. Available at: https://www.diabetesatlas.org/en/ (accessed on Dec 12th, 2018).
[2]
Kaveeshwar, S.A.; Cornwall, J. The current state of diabetes mellitus in India. Australas. Med. J., 2014, 7(1), 45-48.
[http://dx.doi.org/10.4066/AMJ.2014.1979] [PMID: 24567766]
[3]
Zheng, Y.; Ley, S.H.; Hu, F.B. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat. Rev. Endocrinol., 2018, 14(2), 88-98.
[http://dx.doi.org/10.1038/nrendo.2017.151] [PMID: 29219149]
[4]
Pathak, R.; Bridgeman, M.B. Dipeptidyl peptidase-4 (DPP-4) inhibitors in the management of diabetes. P&T, 2010, 35(9), 509-513.
[PMID: 20975810]
[5]
Neumiller, J.J. Differential chemistry (structure), mechanism of action, and pharmacology of GLP-1 receptor agonists and DPP-4 inhibitors. J Am Pharm Assoc (2003), 2009, 49((Suppl. 1)), S16-S29.
[http://dx.doi.org/10.1331/JAPhA.2009.09078] [PMID: 19801361]
[6]
Nathan, D.M.; Buse, J.B.; Davidson, M.B.; Heine, R.J.; Holman, R.R.; Sherwin, R.; Zinman, B. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes association and the European association for the study of diabetes. Diabetes Care, 2006, 29(8), 1963-1972.
[http://dx.doi.org/10.2337/dc06-9912] [PMID: 16873813]
[7]
Barnett, A. DPP-4 inhibitors and their potential role in the management of type 2 diabetes. Int. J. Clin. Pract., 2006, 60(11), 1454-1470.
[http://dx.doi.org/10.1111/j.1742-1241.2006.01178.x] [PMID: 17073841]
[8]
Sebokova, E.; Christ, A.D.; Boehringer, M.; Mizrahi, J. Dipeptidyl peptidase IV inhibitors: the next generation of new promising therapies for the management of type 2 diabetes. Curr. Top. Med. Chem., 2007, 7(6), 547-555.
[http://dx.doi.org/10.2174/156802607780091019] [PMID: 17352676]
[9]
Green, B.D.; Flatt, P.R.; Bailey, C.J. Dipeptidyl peptidase IV (DPP IV) inhibitors: a newly emerging drug class for the treatment of type 2 diabetes. Diab. Vasc. Dis. Res., 2006, 3(3), 159-165.
[http://dx.doi.org/10.3132/dvdr.2006.024] [PMID: 17160910]
[10]
Hopsu-Havu, V.K.; Glenner, G.G. A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-β-naphthylamide. Histochemie, 1966, 7(3), 197-201.
[http://dx.doi.org/10.1007/BF00577838] [PMID: 5959122]
[11]
Wagner, L.; Klemann, C.; Stephan, M.; von Hörsten, S. Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins. Clin. Exp. Immunol., 2016, 184(3), 265-283.
[http://dx.doi.org/10.1111/cei.12757] [PMID: 26671446]
[12]
Omar, B.A.; Liehua, L.; Yamada, Y.; Seino, Y.; Marchetti, P.; Ahrén, B. Dipeptidyl peptidase 4 (DPP-4) is expressed in mouse and human islets and its activity is decreased in human islets from individuals with type 2 diabetes. Diabetologia, 2014, 57(9), 1876-1883.
[http://dx.doi.org/10.1007/s00125-014-3299-4] [PMID: 24939431]
[13]
Mulvihill, E.E.; Drucker, D.J. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr. Rev., 2014, 35(6), 992-1019.
[http://dx.doi.org/10.1210/er.2014-1035] [PMID: 25216328]
[14]
Thomas, L.; Eckhardt, M.; Langkopf, E.; Tadayyon, M.; Himmelsbach, F.; Mark, M. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J. Pharmacol. Exp. Ther., 2008, 325(1), 175-182.
[http://dx.doi.org/10.1124/jpet.107.135723] [PMID: 18223196]
[15]
Deacon, C.F. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes. Metab., 2011, 13(1), 7-18.
[http://dx.doi.org/10.1111/j.1463-1326.2010.01306.x] [PMID: 21114598]
[16]
DiaTribe Learn, making sense of diabetes. DPP-4 inhibitors. Available at: https://diatribe.org/dpp-4-inhibitors (accessed on Januray 12th, 2019).
[17]
Haffner, C.D.; McDougald, D.L.; Reister, S.M.; Thompson, B.D.; Conlee, C.; Fang, J.; Bass, J.; Lenhard, J.M.; Croom, D.; Secosky-Chang, M.B.; Tomaszek, T.; McConn, D.; Wells-Knecht, K.; Johnson, P.R. 2-Cyano-4-fluoro-1-thiovalylpyrrolidine analogues as potent inhibitors of DPP-IV. Bioorg. Med. Chem. Lett., 2005, 15(23), 5257-5261.
[http://dx.doi.org/10.1016/j.bmcl.2005.08.050] [PMID: 16168640]
[18]
Sakashita, H.; Kitajima, H.; Nakamura, M.; Akahoshi, F.; Hayashi, Y. 1-((S)-γ-substituted prolyl)-(S)-2-cyanopyrro-lidine as a novel series of highly potent DPP-IV inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(10), 2441-2445.
[http://dx.doi.org/10.1016/j.bmcl.2005.03.077] [PMID: 15863294]
[19]
Wright, S.W.; Ammirati, M.J.; Andrews, K.M.; Brodeur, A.M.; Danley, D.E.; Doran, S.D.; Lillquist, J.S.; McClure, L.D.; McPherson, R.K.; Orena, S.J.; Parker, J.C.; Polivkova, J.; Qiu, X.; Soeller, W.C.; Soglia, C.B.; Treadway, J.L.; VanVolkenburg, M.A.; Wang, H.; Wilder, D.C.; Olson, T.V. Cis-2,5-dicyanopyrrolidine inhibitors of dipeptidyl peptidase IV: synthesis and in vitro, in vivo, and X-ray crystallographic characterization. J. Med. Chem., 2006, 49(11), 3068-3076.
[http://dx.doi.org/10.1021/jm0600085] [PMID: 16722626]
[20]
Coumar, M.S.; Chang, C.N.; Chen, C.T.; Chen, X.; Chien, C.H.; Tsai, T.Y.; Cheng, J.H.; Wu, H.Y.; Han, C.H.; Wu, S.H.; Huang, Y.W.; Hsu, T.; Hsu, L.J.; Chao, Y.S.; Hsieh, H.P.; Jiaang, W.T. 3-[2-((2S)-2-cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramide analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes. Bioorg. Med. Chem. Lett., 2007, 17(5), 1274-1279.
[http://dx.doi.org/10.1016/j.bmcl.2006.12.019] [PMID: 17194587]
[21]
Corbett, J.W.; Dirico, K.; Song, W.; Boscoe, B.P.; Doran, S.D.; Boyer, D.; Qiu, X.; Ammirati, M.; Vanvolkenburg, M.A.; McPherson, R.K.; Parker, J.C.; Cox, E.D. Design and synthesis of potent amido- and benzyl-substituted cis-3-amino-4-(2-cyanopyrrolidide)pyrrolidinyl DPP-IV inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(24), 6707-6713.
[http://dx.doi.org/10.1016/j.bmcl.2007.10.063] [PMID: 17977724]
[22]
Fukushima, H.; Hiratate, A.; Takahashi, M.; Mikami, A.; Saito-Hori, M.; Munetomo, E.; Kitano, K.; Chonan, S.; Saito, H.; Suzuki, A.; Takaoka, Y.; Yamamoto, K. Synthesis and structure-activity relationships of potent 4-fluoro-2-cyanopyrrolidine dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem., 2008, 16(7), 4093-4106.
[http://dx.doi.org/10.1016/j.bmc.2008.01.016] [PMID: 18243000]
[23]
Kato, N.; Oka, M.; Murase, T.; Yoshida, M.; Sakairi, M.; Yamashita, S.; Yasuda, Y.; Yoshikawa, A.; Hayashi, Y.; Makino, M.; Takeda, M. Discovery and pharmacological characterization of N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl} amino)-2-methylpropyl]-2-methylpyrazolo [1, 5-a] pyrimidine-6-carboxamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective DPP-IV inhibitor. Bioorg. Med. Chem., 2011, 19(23), 7221-7227.
[http://dx.doi.org/10.1016/j.bmc.2011.09.043] [PMID: 22019046]
[24]
Zhao, G.; Kwon, C.; Wang, A.; Robertson, J.G.; Marcinkeviciene, J.; Parker, R.A.; Kirby, M.S.; Hamann, L.G. Substituted piperidinyl glycinyl 2-cyano-4,5-methano pyrrolidines as potent and stable dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(6), 1622-1625.
[http://dx.doi.org/10.1016/j.bmcl.2013.01.104] [PMID: 23416006]
[25]
Kuranov, S.O.; Tsypysheva, I.P.; Khvostov, M.V.; Zainullina, L.F.; Borisevich, S.S.; Vakhitova, Y.V.; Luzina, O.A.; Salakhutdinov, N.F. Synthesis and evaluation of camphor and cytisine-based cyanopyrrolidines as DPP-IV inhibitors for the treatment of type 2 diabetes mellitus. Bioorg. Med. Chem., 2018, 26(15), 4402-4409.
[http://dx.doi.org/10.1016/j.bmc.2018.07.018] [PMID: 30056037]
[26]
Caldwell, C.G.; Chen, P.; He, J.; Parmee, E.R.; Leiting, B.; Marsilio, F.; Patel, R.A.; Wu, J.K.; Eiermann, G.J.; Petrov, A.; He, H.; Lyons, K.A.; Thornberry, N.A.; Weber, A.E. Fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(5), 1265-1268.
[http://dx.doi.org/10.1016/j.bmcl.2003.12.040] [PMID: 14980678]
[27]
Hulin, B.; Cabral, S.; Lopaze, M.G.; Van Volkenburg, M.A.; Andrews, K.M.; Parker, J.C. New fluorinated pyrrolidine and azetidine amides as dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(21), 4770-4773.
[http://dx.doi.org/10.1016/j.bmcl.2005.07.026] [PMID: 16115768]
[28]
Yeh, T.K.; Tsai, T.Y.; Hsu, T.; Cheng, J.H.; Chen, X.; Song, J.S.; Shy, H.S.; Chiou, M.C.; Chien, C.H.; Tseng, Y.J.; Huang, C.Y.; Yeh, K.C.; Huang, Y.L.; Huang, C.H.; Huang, Y.W.; Wang, M.H.; Tang, H.K.; Chao, Y.S.; Chen, C.T.; Jiaang, W.T. (2S,4S)-1-[2-(1,1-dimethyl-3-oxo-3-pyrrolidin-1-yl-propylamino)acetyl]-4-fluoro-pyrrolidine-2-carbonitrile: a potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV. Bioorg. Med. Chem. Lett., 2010, 20(12), 3596-3600.
[http://dx.doi.org/10.1016/j.bmcl.2010.04.124] [PMID: 20483603]
[29]
Tajima, A.; Yamamoto, K.; Kozakai, A.; Okumura-Kitajima, L.; Mita, Y.; Kitano, K.; Jingu, S.; Nakaike, S. (2S,4S)-4-Fluoro-1-[(2-hydroxy-1,1-dimethylethyl)amino]acetyl-pyrrolidine-2-carbonitrile monobenzenesulfonate (TS-021) is a selective and reversible dipeptidyl peptidase IV inhibitor. Eur. J. Pharmacol., 2011, 655(1-3), 99-107.
[http://dx.doi.org/10.1016/j.ejphar.2011.01.010] [PMID: 21262219]
[30]
Sharma, M.; Gupta, M.; Singh, D.; Kumar, M.; Kaur, P. Synthesis, evaluation and molecular docking of prolyl-fluoropyrrolidine derivatives as dipeptidyl peptidase IV inhibitors. Chem. Biol. Drug Des., 2013, 82(2), 156-166.
[http://dx.doi.org/10.1111/cbdd.12142] [PMID: 23581745]
[31]
Ferraris, D.; Ko, Y.S.; Calvin, D.; Chiou, T.; Lautar, S.; Thomas, B.; Wozniak, K.; Rojas, C.; Kalish, V.; Belyakov, S. Ketopyrrolidines and ketoazetidines as potent dipeptidyl peptidase IV (DPP IV) inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(22), 5579-5583.
[http://dx.doi.org/10.1016/j.bmcl.2004.08.057] [PMID: 15482928]
[32]
Zhao, K.; Lim, D.S.; Funaki, T.; Welch, J.T. Inhibition of dipeptidyl peptidase IV (DPP IV) by 2-(2-amino-1-fluoro-propylidene)-cyclopentanecarbonitrile, a fluoroolefin containing peptidomimetic. Bioorg. Med. Chem., 2003, 11(2), 207-215.
[http://dx.doi.org/10.1016/S0968-0896(02)00384-X] [PMID: 12470715]
[33]
Van der Veken, P.; Senten, K.; Kertèsz, I.; De Meester, I.; Lambeir, A.M.; Maes, M.B.; Scharpé, S.; Haemers, A.; Augustyns, K. Fluoro-olefins as peptidomimetic inhibitors of dipeptidyl peptidases. J. Med. Chem., 2005, 48(6), 1768-1780.
[http://dx.doi.org/10.1021/jm0495982] [PMID: 15771423]
[34]
Edmondson, S.D.; Wei, L.; Xu, J.; Shang, J.; Xu, S.; Pang, J.; Chaudhary, A.; Dean, D.C.; He, H.; Leiting, B.; Lyons, K.A.; Patel, R.A.; Patel, S.B.; Scapin, G.; Wu, J.K.; Beconi, M.G.; Thornberry, N.A.; Weber, A.E. Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(7), 2409-2413.
[http://dx.doi.org/10.1016/j.bmcl.2008.02.050] [PMID: 18331795]
[35]
Edmondson, S.D.; Mastracchio, A.; Beconi, M.; Colwell, L.F., Jr; Habulihaz, B.; He, H.; Kumar, S.; Leiting, B.; Lyons, K.A.; Mao, A.; Marsilio, F.; Patel, R.A.; Wu, J.K.; Zhu, L.; Thornberry, N.A.; Weber, A.E.; Parmee, E.R. Potent and selective proline derived dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(20), 5151-5155.
[http://dx.doi.org/10.1016/j.bmcl.2004.07.056] [PMID: 15380217]
[36]
Backes, B.J.; Longenecker, K.; Hamilton, G.L.; Stewart, K.; Lai, C.; Kopecka, H.; von Geldern, T.W.; Madar, D.J.; Pei, Z.; Lubben, T.H.; Zinker, B.A.; Tian, Z.; Ballaron, S.J.; Stashko, M.A.; Mika, A.K.; Beno, D.W.; Kempf-Grote, A.J.; Black-Schaefer, C.; Sham, H.L.; Trevillyan, J.M. Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibitors from a lead-like screening hit. Bioorg. Med. Chem. Lett., 2007, 17(7), 2005-2012.
[http://dx.doi.org/10.1016/j.bmcl.2007.01.026] [PMID: 17276063]
[37]
Kondo, T.; Nekado, T.; Sugimoto, I.; Ochi, K.; Takai, S.; Kinoshita, A.; Hatayama, A.; Yamamoto, S.; Kishikawa, K.; Nakai, H.; Toda, M. Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group. Bioorg. Med. Chem., 2008, 16(4), 1613-1631.
[http://dx.doi.org/10.1016/j.bmc.2007.11.031] [PMID: 18039579]
[38]
Andrews, K.M.; Beebe, D.A.; Benbow, J.W.; Boyer, D.A.; Doran, S.D.; Hui, Y.; Liu, S.; McPherson, R.K.; Neagu, C.; Parker, J.C.; Piotrowski, D.W.; Schneider, S.R.; Treadway, J.L.; VanVolkenberg, M.A.; Zembrowski, W.J. 1-((3S,4S)-4-amino-1-(4-substituted-1,3,5-triazin-2-yl) pyrrolidin-3-yl)-5,5-difluoropiperidin-2-one inhibitors of DPP-4 for the treatment of type 2 diabetes. Bioorg. Med. Chem. Lett., 2011, 21(6), 1810-1814.
[http://dx.doi.org/10.1016/j.bmcl.2011.01.055] [PMID: 21324688]
[39]
Jiang, T.; Zhou, Y.; Zhu, J.; Chen, Z.; Sun, P.; Zhang, Q.; Wang, Z.; Shao, Q.; Jiang, X.; Li, B.; Wang, H.; Zhu, W.; Shen, J. Design, synthesis, and pharmacological evaluation of highly potent and selective dipeptidyl peptidase-4 inhibitors. Arch. Pharm. (Weinheim), 2015, 348(6), 399-407.
[http://dx.doi.org/10.1002/ardp.201500082] [PMID: 25871012]
[40]
Cox, J.M.; Chu, H.D.; Kuethe, J.T.; Gao, Y.D.; Scapin, G.; Eiermann, G.; He, H.; Li, X.; Lyons, K.A.; Metzger, J.; Petrov, A.; Wu, J.K.; Xu, S.; Sinha-Roy, R.; Weber, A.E.; Biftu, T. The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors. Bioorg. Med. Chem. Lett., 2016, 26(11), 2622-2626.
[http://dx.doi.org/10.1016/j.bmcl.2016.04.020] [PMID: 27106708]
[41]
Wu, D.; Jin, F.; Lu, W.; Zhu, J.; Li, C.; Wang, W.; Tang, Y.; Jiang, H.; Huang, J.; Liu, G.; Li, J. Synthesis, structure-activity relationship, and pharmacophore modeling studies of pyrazole-3-carbohydrazone derivatives as dipeptidyl peptidase IV inhibitors. Chem. Biol. Drug Des., 2012, 79(6), 897-906.
[http://dx.doi.org/10.1111/j.1747-0285.2012.01365.x] [PMID: 22381062]
[42]
Sagar, S.R.; Agarwal, J.K.; Pandya, D.H.; Dash, R.P.; Nivsarkar, M.; Vasu, K.K. Design, synthesis and biological evaluation of novel pyrazolo-pyrimidinones as DPP-IV inhibitors in diabetes. Bioorg. Med. Chem. Lett., 2015, 25(20), 4428-4433.
[http://dx.doi.org/10.1016/j.bmcl.2015.09.015] [PMID: 26372650]
[43]
Villhauer, E.B.; Novartis, A.G.N.N. N-(Substituted glycyl)-4-cyanothiazolidines, pharmaceutical compositions containingthem and their use in inhibiting dipeptidyl peptidase-IV. US Patent 6,110,949, 29 August;2000
[44]
Park, W.S.; Kang, S.K.; Jun, M.A.; Shin, M.S.; Kim, K.Y.; Rhee, S.D.; Bae, M.A.; Kim, M.S.; Kim, K.R.; Kang, N.S.; Yoo, S.E.; Lee, J.O.; Song, D.H.; Silinski, P.; Schneider, S.E.; Ahn, J.H.; Kim, S.S. Discovery of β-aminoacyl containing thiazolidine derivatives as potent and selective dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2011, 21(5), 1366-1370.
[http://dx.doi.org/10.1016/j.bmcl.2011.01.041] [PMID: 21306895]
[45]
Yoshida, T.; Akahoshi, F.; Sakashita, H.; Kitajima, H.; Nakamura, M.; Sonda, S.; Takeuchi, M.; Tanaka, Y.; Ueda, N.; Sekiguchi, S.; Ishige, T.; Shima, K.; Nabeno, M.; Abe, Y.; Anabuki, J.; Soejima, A.; Yoshida, K.; Takashina, Y.; Ishii, S.; Kiuchi, S.; Fukuda, S.; Tsutsumiuchi, R.; Kosaka, K.; Murozono, T.; Nakamaru, Y.; Utsumi, H.; Masutomi, N.; Kishida, H.; Miyaguchi, I.; Hayashi, Y. Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): a highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Bioorg. Med. Chem., 2012, 20(19), 5705-5719.
[http://dx.doi.org/10.1016/j.bmc.2012.08.012] [PMID: 22959556]
[46]
Yoshida, T.; Akahoshi, F.; Sakashita, H.; Sonda, S.; Takeuchi, M.; Tanaka, Y.; Nabeno, M.; Kishida, H.; Miyaguchi, I.; Hayashi, Y. Fused bicyclic heteroarylpiperazine-substituted L-prolylthiazolidines as highly potent DPP-4 inhibitors lacking the electrophilic nitrile group. Bioorg. Med. Chem., 2012, 20(16), 5033-5041.
[http://dx.doi.org/10.1016/j.bmc.2012.06.033] [PMID: 22824762]
[47]
Xu, J.; Ok, H.O.; Gonzalez, E.J.; Colwell, L.F., Jr; Habulihaz, B.; He, H.; Leiting, B.; Lyons, K.A.; Marsilio, F.; Patel, R.A.; Wu, J.K.; Thornberry, N.A.; Weber, A.E.; Parmee, E.R. Discovery of potent and selective β-homophenylalanine based dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(18), 4759-4762.
[http://dx.doi.org/10.1016/j.bmcl.2004.06.099] [PMID: 15324903]
[48]
Nitta, A.; Fujii, H.; Sakami, S.; Satoh, M.; Nakaki, J.; Satoh, S.; Kumagai, H.; Kawai, H. Novel series of 3-amino-N-(4-aryl-1,1-dioxothian-4-yl)butanamides as potent and selective dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(23), 7036-7040.
[http://dx.doi.org/10.1016/j.bmcl.2012.09.099] [PMID: 23072865]
[49]
Ali, Z.; Akhtar, M.J.; Siddiqui, A.A.; Khan, A.A.; Haider, M.R.; Yar, M.S. Design, synthesis, and biological evaluation of novel quinazoline clubbed thiazoline derivatives. Arch. Pharm. (Weinheim), 2017, 350(2), 1600298.
[http://dx.doi.org/10.1002/ardp.201600298] [PMID: 28093794]
[50]
Chen, P.; Caldwell, C.G.; Mathvink, R.J.; Leiting, B.; Marsilio, F.; Patel, R.A.; Wu, J.K.; He, H.; Lyons, K.A.; Thornberry, N.A.; Weber, A.E. Imidazopiperidine amides as dipeptidyl peptidase IV inhibitors for the treatment of diabetes. Bioorg. Med. Chem. Lett., 2007, 17(21), 5853-5857.
[http://dx.doi.org/10.1016/j.bmcl.2007.08.030] [PMID: 17869513]
[51]
Wallace, M.B.; Feng, J.; Zhang, Z.; Skene, R.J.; Shi, L.; Caster, C.L.; Kassel, D.B.; Xu, R.; Gwaltney, S.L. II. Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(7), 2362-2367.
[http://dx.doi.org/10.1016/j.bmcl.2008.02.071] [PMID: 18346892]
[52]
Wang, L.; Zhang, B.; Ji, J.; Li, B.; Yan, J.; Zhang, W.; Wu, Y.; Wang, X. Synthesis and evaluation of structurally constrained imidazolidin derivatives as potent dipeptidyl peptidase IV inhibitors. Eur. J. Med. Chem., 2009, 44(8), 3318-3322.
[http://dx.doi.org/10.1016/j.ejmech.2009.03.021] [PMID: 19375196]
[53]
O’Connor, S.P.; Wang, Y.; Simpkins, L.M.; Brigance, R.P.; Meng, W.; Wang, A.; Kirby, M.S.; Weigelt, C.A.; Hamann, L.G. Synthesis, SAR, and atropisomerism of imidazolopyrimidine DPP4 inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(21), 6273-6276.
[http://dx.doi.org/10.1016/j.bmcl.2010.08.090] [PMID: 20833042]
[54]
Ikuma, Y.; Hochigai, H.; Kimura, H.; Nunami, N.; Kobayashi, T.; Uchiyama, K.; Furuta, Y.; Sakai, M.; Horiguchi, M.; Masui, Y.; Okazaki, K.; Sato, Y.; Nakahira, H. Discovery of 3H-imidazo[4,5-c]quinolin-4(5H)-ones as potent and selective dipeptidyl peptidase IV (DPP-4) inhibitors. Bioorg. Med. Chem., 2012, 20(19), 5864-5883.
[http://dx.doi.org/10.1016/j.bmc.2012.07.046] [PMID: 22938786]
[55]
Li, Q.; Zhou, M.; Han, L.; Cao, Q.; Wang, X.; Zhao, L.; Zhou, J.; Zhang, H. Design, Synthesis and Biological Evaluation of Imidazo[1,2-a]pyridine Derivatives as Novel DPP-4 Inhibitors. Chem. Biol. Drug Des., 2015, 86(4), 849-856.
[http://dx.doi.org/10.1111/cbdd.12560] [PMID: 25787859]
[56]
Karandikar, S.; Soni, R.; Soman, S.S.; Umar, S.; Suresh, B. 1, 2-Benzisoxazole-3-acetamide derivatives as dual agents for DPP-IV inhibition and anticancer activity. Synth. Commun., 2018, 48(22), 2877-2887.
[http://dx.doi.org/10.1080/00397911.2018.1508723]
[57]
Gao, Y.D.; Feng, D.; Sheridan, R.P.; Scapin, G.; Patel, S.B.; Wu, J.K.; Zhang, X.; Sinha-Roy, R.; Thornberry, N.A.; Weber, A.E.; Biftu, T. Modeling assisted rational design of novel, potent, and selective pyrrolopyrimidine DPP-4 inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(14), 3877-3879.
[http://dx.doi.org/10.1016/j.bmcl.2007.04.106] [PMID: 17502141]
[58]
Wang, W.; Devasthale, P.; Wang, A.; Harrity, T.; Egan, D.; Morgan, N.; Cap, M.; Fura, A.; Klei, H.E.; Kish, K.; Weigelt, C.; Sun, L.; Levesque, P.; Li, Y.X.; Zahler, R.; Kirby, M.S.; Hamann, L.G. 7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site. Bioorg. Med. Chem. Lett., 2011, 21(22), 6646-6651.
[http://dx.doi.org/10.1016/j.bmcl.2011.09.074] [PMID: 21996520]
[59]
Xie, H.; Zeng, L.; Zeng, S.; Lu, X.; Zhang, G.; Zhao, X.; Cheng, N.; Tu, Z.; Li, Z.; Xu, H.; Yang, L.; Zhang, X.; Huang, M.; Zhao, J.; Hu, W. Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization. Eur. J. Med. Chem., 2012, 52, 205-212.
[http://dx.doi.org/10.1016/j.ejmech.2012.03.015] [PMID: 22475866]
[60]
Kim, D.; Wang, L.; Beconi, M.; Eiermann, G.J.; Fisher, M.H.; He, H.; Hickey, G.J.; Kowalchick, J.E.; Leiting, B.; Lyons, K.; Marsilio, F.; McCann, M.E.; Patel, R.A.; Petrov, A.; Scapin, G.; Patel, S.B.; Roy, R.S.; Wu, J.K.; Wyvratt, M.J.; Zhang, B.B.; Zhu, L.; Thornberry, N.A.; Weber, A.E. (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4] triazolo [4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl) butan- 2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J. Med. Chem., 2005, 48(1), 141-151.
[http://dx.doi.org/10.1021/jm0493156] [PMID: 15634008]
[61]
Kowalchick, J.E.; Leiting, B.; Pryor, K.D.; Marsilio, F.; Wu, J.K.; He, H.; Lyons, K.A.; Eiermann, G.J.; Petrov, A.; Scapin, G.; Patel, R.A.; Thornberry, N.A.; Weber, A.E.; Kim, D. Design, synthesis, and biological evaluation of triazolopiperazine-based β-amino amides as potent, orally active dipeptidyl peptidase IV (DPP-4) inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(21), 5934-5939.
[http://dx.doi.org/10.1016/j.bmcl.2007.07.100] [PMID: 17827003]
[62]
Sharma, M.; Gupta, M.; Singh, D.; Kumar, M.; Kaur, P. Synthesis, evaluation and molecular docking of thiazolopyrimidine derivatives as dipeptidyl peptidase IV inhibitors. Chem. Biol. Drug Des., 2012, 80(6), 918-928.
[http://dx.doi.org/10.1111/cbdd.12041] [PMID: 22943413]
[63]
Gomha, S.M.; Eldebss, T.M.; Badrey, M.G.; Abdulla, M.M.; Mayhoub, A.S. Novel 4-heteroaryl-antipyrines as DPP-IV inhibitors. Chem. Biol. Drug Des., 2015, 86(5), 1292-1303.
[http://dx.doi.org/10.1111/cbdd.12593] [PMID: 26032047]
[64]
Schwehm, C.; Li, J.; Song, H.; Hu, X.; Kellam, B.; Stocks, M.J. Synthesis of new DPP-4 inhibitors based on a novel tricyclic scaffold. ACS Med. Chem. Lett., 2015, 6(3), 324-328.
[http://dx.doi.org/10.1021/ml500503n] [PMID: 25815154]
[65]
Deng, X.; Han, L.; Zhou, J.; Zhang, H.; Li, Q. Discovery of triazole-based uracil derivatives bearing amide moieties as novel dipeptidyl peptidase-IV inhibitors. Bioorg. Chem., 2017, 75, 357-367.
[http://dx.doi.org/10.1016/j.bioorg.2017.10.010] [PMID: 29096096]
[66]
Li, Q.; Han, L.; Zhang, B.; Zhou, J.; Zhang, H. Synthesis and biological evaluation of triazole based uracil derivatives as novel DPP-4 inhibitors. Org. Biomol. Chem., 2016, 14(40), 9598-9611.
[http://dx.doi.org/10.1039/C6OB01818A] [PMID: 27714283]
[67]
Zhang, Z.; Wallace, M.B.; Feng, J.; Stafford, J.A.; Skene, R.J.; Shi, L.; Lee, B.; Aertgeerts, K.; Jennings, A.; Xu, R.; Kassel, D.B.; Kaldor, S.W.; Navre, M.; Webb, D.R.; Gwaltney, S.L. Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV. J. Med. Chem., 2011, 54(2), 510-524.
[http://dx.doi.org/10.1021/jm101016w] [PMID: 21186796]
[68]
Meng, W.; Brigance, R.P.; Chao, H.J.; Fura, A.; Harrity, T.; Marcinkeviciene, J.; O’Connor, S.P.; Tamura, J.K.; Xie, D.; Zhang, Y.; Klei, H.E.; Kish, K.; Weigelt, C.A.; Turdi, H.; Wang, A.; Zahler, R.; Kirby, M.S.; Hamann, L.G. Discovery of 6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamides as potent, selective dipeptidyl peptidase-4 (DPP4) inhibitors. J. Med. Chem., 2010, 53(15), 5620-5628.
[http://dx.doi.org/10.1021/jm100634a] [PMID: 20684603]
[69]
Nishio, Y.; Kimura, H.; Sawada, N.; Sugaru, E.; Horiguchi, M.; Ono, M.; Furuta, Y.; Sakai, M.; Masui, Y.; Otani, M.; Hashizuka, T.; Honda, Y.; Deguchi, J.; Nakagawa, T.; Nakahira, H. 2-(6-[(3R)-3-amino-3-methylpiperidine-1-yl]-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-5H-pyrrolo[3,2-d]pyrimidine-5-ylmethyl)-4-fluorobenzonitrile (DSR-12727): a potent, orally active dipeptidyl peptidase IV inhibitor without mechanism-based inactivation of CYP3A. Bioorg. Med. Chem., 2011, 19(18), 5490-5499.
[http://dx.doi.org/10.1016/j.bmc.2011.07.042] [PMID: 21865048]
[70]
Deng, J.; Peng, L.; Zhang, G.; Lan, X.; Li, C.; Chen, F.; Zhou, Y.; Lin, Z.; Chen, L.; Dai, R.; Xu, H.; Yang, L.; Zhang, X.; Hu, W. The highly potent and selective dipeptidyl peptidase IV inhibitors bearing a thienopyrimidine scaffold effectively treat type 2 diabetes. Eur. J. Med. Chem., 2011, 46(1), 71-76.
[http://dx.doi.org/10.1016/j.ejmech.2010.10.016] [PMID: 21106276]
[71]
Tomovic, K.; Ilic, B.S.; Miljkovic, M.; Dimov, S.; Yancheva, D.; Kojic, M.; Mavrova, A.T.; Kocic, G.; Smelcerovic, A. Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative, one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4. Arch. Pharm. (Weinheim), 2020, 353(1), e1900238.
[http://dx.doi.org/10.1002/ardp.201900238] [PMID: 31710123]
[72]
Lai, Z.W.; Li, C.; Liu, J.; Kong, L.; Wen, X.; Sun, H. Discovery of highly potent DPP-4 inhibitors by hybrid compound design based on linagliptin and alogliptin. Eur. J. Med. Chem., 2014, 83, 547-560.
[http://dx.doi.org/10.1016/j.ejmech.2014.06.044] [PMID: 24996141]
[73]
Jha, V.; Bhadoriya, K.S. Synthesis, pharmacological evaluation and molecular docking studies of pyrimidinedione based DPP-4 inhibitors as antidiabetic agents. J. Mol. Struct., 2018, 1158, 96-105.
[http://dx.doi.org/10.1016/j.molstruc.2018.01.014]
[74]
Huang, J.; Deng, X.; Zhou, S.; Wang, N.; Qin, Y.; Meng, L.; Li, G.; Xiong, Y.; Fan, Y.; Guo, L.; Lan, D.; Xing, J.; Jiang, W.; Li, Q. Identification of novel uracil derivatives incorporating benzoic acid moieties as highly potent dipeptidyl peptidase-IV inhibitors. Bioorg. Med. Chem., 2019, 27(4), 644-654.
[http://dx.doi.org/10.1016/j.bmc.2019.01.001] [PMID: 30642693]
[75]
Miyamoto, Y.; Banno, Y.; Yamashita, T.; Fujimoto, T.; Oi, S.; Moritoh, Y.; Asakawa, T.; Kataoka, O.; Takeuchi, K.; Suzuki, N.; Ikedo, K.; Kosaka, T.; Tsubotani, S.; Tani, A.; Funami, M.; Amano, M.; Yamamoto, Y.; Aertgeerts, K.; Yano, J.; Maezaki, H. Design and synthesis of 3-pyridylacetamide derivatives as dipeptidyl peptidase IV (DPP-4) inhibitors targeting a bidentate interaction with Arg125. Bioorg. Med. Chem., 2011, 19(1), 172-185.
[http://dx.doi.org/10.1016/j.bmc.2010.11.038] [PMID: 21163664]
[76]
Kaczanowska, K.; Wiesmüller, K.H.; Schaffner, A.P. Design, synthesis, and in vitro evaluation of novel aminomethyl-pyridines as DPP-4 inhibitors. ACS Med. Chem. Lett., 2010, 1(9), 530-535.
[http://dx.doi.org/10.1021/ml100200c] [PMID: 24900243]
[77]
Peters, J.U.; Weber, S.; Kritter, S.; Weiss, P.; Wallier, A.; Zimmerli, D.; Boehringer, M.; Steger, M.; Loeffler, B.M. Aminomethylpyridines as DPP-IV inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(13), 3579-3580.
[http://dx.doi.org/10.1016/j.bmcl.2004.04.049] [PMID: 15177478]
[78]
Eckhardt, M.; Hauel, N.; Himmelsbach, F.; Langkopf, E.; Nar, H.; Mark, M.; Tadayyon, M.; Thomas, L.; Guth, B.; Lotz, R. 3,5-Dihydro-imidazo[4,5-d]pyridazin-4-ones: a class of potent DPP-4 inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(11), 3158-3162.
[http://dx.doi.org/10.1016/j.bmcl.2008.04.075] [PMID: 18485703]
[79]
Namoto, K.; Sirockin, F.; Ostermann, N.; Gessier, F.; Flohr, S.; Sedrani, R.; Gerhartz, B.; Trappe, J.; Hassiepen, U.; Duttaroy, A.; Ferreira, S.; Sutton, J.M.; Clark, D.E.; Fenton, G.; Beswick, M.; Baeschlin, D.K. Discovery of C-(1-aryl-cyclohexyl)-methylamines as selective, orally available inhibitors of dipeptidyl peptidase IV. Bioorg. Med. Chem. Lett., 2014, 24(3), 731-736.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.118] [PMID: 24439847]
[80]
Kim, H.J.; Kwak, W.Y.; Min, J.P.; Lee, J.Y.; Yoon, T.H.; Kim, H.D.; Shin, C.Y.; Kim, M.K.; Choi, S.H.; Kim, H.S.; Yang, E.K.; Cheong, Y.H.; Chae, Y.N.; Park, K.J.; Jang, J.M.; Choi, S.J.; Son, M.H.; Kim, S.H.; Yoo, M.; Lee, B.J. Discovery of DA-1229: a potent, long acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. Bioorg. Med. Chem. Lett., 2011, 21(12), 3809-3812.
[http://dx.doi.org/10.1016/j.bmcl.2011.04.029] [PMID: 21570283]
[81]
Kushwaha, R.N.; Srivastava, R.; Mishra, A.; Rawat, A.K.; Srivastava, A.K.; Haq, W.; Katti, S.B. Design, synthesis, biological screening, and molecular docking studies of piperazine-derived constrained inhibitors of DPP-IV for the treatment of type 2 diabetes. Chem. Biol. Drug Des., 2015, 85(4), 439-446.
[http://dx.doi.org/10.1111/cbdd.12426] [PMID: 25216392]
[82]
Edmondson, S.D.; Mastracchio, A.; Cox, J.M.; Eiermann, G.J.; He, H.; Lyons, K.A.; Patel, R.A.; Patel, S.B.; Petrov, A.; Scapin, G.; Wu, J.K.; Xu, S.; Zhu, B.; Thornberry, N.A.; Roy, R.S.; Weber, A.E. Aminopiperidine-fused imidazoles as dipeptidyl peptidase-IV inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(15), 4097-4101.
[http://dx.doi.org/10.1016/j.bmcl.2009.06.011] [PMID: 19539471]
[83]
Gupta, R.C.; Chhipa, L.; Mandhare, A.B.; Zambad, S.P.; Chauthaiwale, V.; Nadkarni, S.S.; Dutt, C. Novel N-substituted 4-hydrazino piperidine derivative as a dipeptidyl peptidase IV inhibitor. Bioorg. Med. Chem. Lett., 2009, 19(17), 5021-5025.
[http://dx.doi.org/10.1016/j.bmcl.2009.07.058] [PMID: 19643608]
[84]
Benbow, J.W.; Andrews, K.A.; Aubrecht, J.; Beebe, D.; Boyer, D.; Doran, S.; Homiski, M.; Hui, Y.; McPherson, K.; Parker, J.C.; Treadway, J.; Vanvolkenberg, M.; Zembrowski, W.J. Piperidinyl-2-phenethylamino inhibitors of DPP-IV for the treatment of type 2 diabetes. Bioorg. Med. Chem. Lett., 2009, 19(8), 2220-2223.
[http://dx.doi.org/10.1016/j.bmcl.2009.02.099] [PMID: 19285862]
[85]
Nishio, Y.; Kimura, H.; Tosaki, S.; Sugaru, E.; Sakai, M.; Horiguchi, M.; Masui, Y.; Ono, M.; Nakagawa, T.; Nakahira, H. Discovery of new chemotype dipeptidyl peptidase IV inhibitors having (R)-3-amino-3-methyl piperidine as a pharmacophore. Bioorg. Med. Chem. Lett., 2010, 20(24), 7246-7249.
[http://dx.doi.org/10.1016/j.bmcl.2010.10.101] [PMID: 21074430]
[86]
Chen, P.; Caldwell, C.G.; Ashton, W.; Wu, J.K.; He, H.; Lyons, K.A.; Thornberry, N.A.; Weber, A.E. Synthesis and evaluation of [(1R)-1-amino-2-(2,5-difluorophenyl)ethyl]cyclohexanes and 4-[(1R)-1-amino-2-(2,5-difluorophenyl)ethyl]piperidines as DPP-4 inhibitors. Bioorg. Med. Chem. Lett., 2011, 21(6), 1880-1886.
[http://dx.doi.org/10.1016/j.bmcl.2010.12.060] [PMID: 21320777]
[87]
Xing, J.; Li, Q.; Zhang, S.; Liu, H.; Zhao, L.; Cheng, H.; Zhang, Y.; Zhou, J.; Zhang, H. Identification of dipeptidyl peptidase IV inhibitors: virtual screening, synthesis and biological evaluation. Chem. Biol. Drug Des., 2014, 84(3), 364-377.
[http://dx.doi.org/10.1111/cbdd.12327] [PMID: 24674599]
[88]
Jadav, P.; Bahekar, R.; Shah, S.R.; Patel, D.; Joharapurkar, A.; Jain, M.; Sairam, K.V.; Singh, P.K. Design, synthesis and biological evaluation of novel aminomethyl-piperidones based DPP-IV inhibitors. Bioorg. Med. Chem. Lett., 2014, 24(8), 1918-1922.
[http://dx.doi.org/10.1016/j.bmcl.2014.03.009] [PMID: 24675378]
[89]
Ran, Y.; Pei, H.; Shao, M.; Chen, L. Synthesis, biological evaluation, and molecular docking of (R)-2-((8-(3-aminopiperidin-1-yl)-3-methyl-7-(3-methylbut-2-en-1-yl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)methyl)benzonitrile as dipeptidyl peptidase IV inhibitors. Chem. Biol. Drug Des., 2016, 87(2), 290-295.
[http://dx.doi.org/10.1111/cbdd.12663] [PMID: 26426933]
[90]
Srivastava, J.K.; Dubey, P.; Singh, S.; Bhat, H.R.; Kumawat, M.K.; Singh, U.P. Discovery of novel 1, 3, 5-triazine-thiazolidine-2, 4-diones as dipeptidyl peptidase-4 inhibitors with antibacterial activity targeting the S1 pocket for the treatment of type 2 diabetes. RSC Advances, 2015, 5(19), 14095-14102.
[http://dx.doi.org/10.1039/C4RA16903D ]
[91]
Wang, Y.; Tang, X.; Yi, L. Design and discovery of novel 1,3,5-triazines as dipeptidyl peptidase-4 inhibitor against diabetes. Pharmacology, 2019, 103(5-6), 273-281.
[http://dx.doi.org/10.1159/000494060] [PMID: 30799431]
[92]
Patel, B.D.; Bhadada, S.V.; Ghate, M.D. Design, synthesis and anti-diabetic activity of triazolotriazine derivatives as dipeptidyl peptidase-4 (DPP-4) inhibitors. Bioorg. Chem., 2017, 72, 345-358.
[http://dx.doi.org/10.1016/j.bioorg.2017.03.004] [PMID: 28302310]
[93]
Ahn, J.H.; Shin, M.S.; Jun, M.A.; Jung, S.H.; Kang, S.K.; Kim, K.R.; Rhee, S.D.; Kang, N.S.; Kim, S.Y.; Sohn, S.K.; Kim, S.G.; Jin, M.S.; Lee, J.O.; Cheon, H.G.; Kim, S.S. Synthesis, biological evaluation and structural determination of β-aminoacyl-containing cyclic hydrazine derivatives as dipeptidyl peptidase IV (DPP-IV) inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(9), 2622-2628.
[http://dx.doi.org/10.1016/j.bmcl.2007.01.111] [PMID: 17331715]
[94]
Biftu, T.; Qian, X.; Chen, P.; Feng, D.; Scapin, G.; Gao, Y.D.; Cox, J.; Roy, R.S.; Eiermann, G.; He, H.; Lyons, K. Novel tetrahydropyran analogs as dipeptidyl peptidase IV inhibitors: profile of clinical candidate (2R, 3S, 5R)-2-(2, 5-difluorophenyl)-5-[2-(methylsulfonyl)-2, 6-dihydropyrrolo [3, 4-c] pyrazol-5 (4H)-yl] tetrahydro-2H-pyran-3-amine (23). Bioorg. Med. Chem. Lett., 2013, 23(19), 5361-5366.
[http://dx.doi.org/10.1016/j.bmcl.2013.07.061] [PMID: 23972441]
[95]
Han, B.; Liu, J.L.; Huan, Y.; Li, P.; Wu, Q.; Lin, Z.Y.; Shen, Z.F.; Huang, H.H. Design, synthesis and primary activity of thiomorpholine derivatives as DPP-IV inhibitors. Chin. Chem. Lett., 2012, 23(3), 297-300.
[http://dx.doi.org/10.1016/j.cclet.2011.12.007 ]
[96]
Jiaang, W.T.; Chen, Y.S.; Hsu, T.; Wu, S.H.; Chien, C.H.; Chang, C.N.; Chang, S.P.; Lee, S.J.; Chen, X. Novel isoindoline compounds for potent and selective inhibition of prolyl dipeptidase DPP8. Bioorg. Med. Chem. Lett., 2005, 15(3), 687-691.
[http://dx.doi.org/10.1016/j.bmcl.2004.11.023] [PMID: 15664838]
[97]
Kato, N.; Oka, M.; Murase, T.; Yoshida, M.; Sakairi, M.; Yakufu, M.; Yamashita, S.; Yasuda, Y.; Yoshikawa, A.; Hayashi, Y.; Shirai, M.; Mizuno, Y.; Takeuchi, M.; Makino, M.; Takeda, M.; Kakigami, T. Synthesis and pharmacological characterization of potent, selective, and orally bioavailable isoindoline class dipeptidyl peptidase IV inhibitors. Org. Med. Chem. Lett., 2011, 1(1), 7.
[http://dx.doi.org/10.1186/2191-2858-1-7] [PMID: 22373386]
[98]
Xiao, P.F.; Guo, R.; Huang, S.Q.; Cui, H.J.; Ye, S.; Zhang, Z. Discovery of dipeptidyl peptidase IV (DPP4) inhibitors based on a novel indole scaffold. Chin. Chem. Lett., 2014, 25(5), 673-676.
[http://dx.doi.org/10.1016/j.cclet.2014.03.047 ]
[99]
Wang, S.; Su, M.; Wang, J.; Li, Z.; Zhang, L.; Ji, X.; Li, J.; Li, J.; Liu, H. (R)-3-amino-1-((3aS,7aS)-octahydro-1H-indol-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-one derivatives as potent inhibitors of dipeptidyl peptidase-4: design, synthesis, biological evaluation, and molecular modeling. Bioorg. Med. Chem., 2014, 22(23), 6684-6693.
[http://dx.doi.org/10.1016/j.bmc.2014.09.051] [PMID: 25457126]
[100]
Lübbers, T.; Böhringer, M.; Gobbi, L.; Hennig, M.; Hunziker, D.; Kuhn, B.; Löffler, B.; Mattei, P.; Narquizian, R.; Peters, J.U.; Ruff, Y.; Wessel, H.P.; Wyss, P. 1,3-disubstituted 4-aminopiperidines as useful tools in the optimization of the 2-aminobenzo[a]quinolizine dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(11), 2966-2970.
[http://dx.doi.org/10.1016/j.bmcl.2007.03.072] [PMID: 17418568]
[101]
Boehringer, M.; Fischer, H.; Hennig, M.; Hunziker, D.; Huwyler, J.; Kuhn, B.; Loeffler, B.M.; Luebbers, T.; Mattei, P.; Narquizian, R.; Sebokova, E.; Sprecher, U.; Wessel, H.P. Aryl- and heteroaryl-substituted aminobenzo[a] quinolizines as dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(3), 1106-1108.
[http://dx.doi.org/10.1016/j.bmcl.2009.12.025] [PMID: 20031408]
[102]
Feng, J.; Zhang, Z.; Wallace, M.B.; Stafford, J.A.; Kaldor, S.W.; Kassel, D.B.; Navre, M.; Shi, L.; Skene, R.J.; Asakawa, T.; Takeuchi, K.; Xu, R.; Webb, D.R.; Gwaltney, S.L., 2nd Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV. J. Med. Chem., 2007, 50(10), 2297-2300.
[http://dx.doi.org/10.1021/jm070104l] [PMID: 17441705]
[103]
Ali, Z.; Akhtar, M.J.; Haider, M.R.; Khan, A.A.; Siddiqui, A.A.; Yar, M.S. Design and synthesis of quinazoline-3,4-(4H)-diamine endowed with thiazoline moiety as new class for DPP-4 and DPPH inhibitor. Bioorg. Chem., 2017, 71, 181-191.
[http://dx.doi.org/10.1016/j.bioorg.2017.02.004] [PMID: 28215601]
[104]
Coppola, G.M.; Zhang, Y.L.; Schuster, H.F.; Russell, M.E.; Hughes, T.E. 1-aminomethylisoquinoline-4-carboxylates as novel dipeptidylpeptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2000, 10(14), 1555-1558.
[http://dx.doi.org/10.1016/S0960-894X(00)00286-9] [PMID: 10915049]
[105]
Banno, Y.; Miyamoto, Y.; Sasaki, M.; Oi, S.; Asakawa, T.; Kataoka, O.; Takeuchi, K.; Suzuki, N.; Ikedo, K.; Kosaka, T.; Tsubotani, S.; Tani, A.; Funami, M.; Tawada, M.; Yamamoto, Y.; Aertgeerts, K.; Yano, J.; Maezaki, H. Identification of 3-aminomethyl-1,2-dihydro-4-phenyl-1-isoquinolones: a new class of potent, selective, and orally active non-peptide dipeptidyl peptidase IV inhibitors that form a unique interaction with Lys554. Bioorg. Med. Chem., 2011, 19(16), 4953-4970.
[http://dx.doi.org/10.1016/j.bmc.2011.06.059] [PMID: 21764322]
[106]
Sutton, J.M.; Clark, D.E.; Dunsdon, S.J.; Fenton, G.; Fillmore, A.; Harris, N.V.; Higgs, C.; Hurley, C.A.; Krintel, S.L.; MacKenzie, R.E.; Duttaroy, A.; Gangl, E.; Maniara, W.; Sedrani, R.; Namoto, K.; Ostermann, N.; Gerhartz, B.; Sirockin, F.; Trappe, J.; Hassiepen, U.; Baeschlin, D.K. Novel heterocyclic DPP-4 inhibitors for the treatment of type 2 diabetes. Bioorg. Med. Chem. Lett., 2012, 22(3), 1464-1468.
[http://dx.doi.org/10.1016/j.bmcl.2011.11.054] [PMID: 22177783]
[107]
Lin, K.; Cai, Z.; Wang, F.; Zhang, W.; Zhou, W. Synthesis and biological evaluation of xanthine derivatives on dipeptidyl peptidase 4. Chem. Pharm. Bull. (Tokyo), 2013, 61(4), 477-482.
[http://dx.doi.org/10.1248/cpb.c12-01046] [PMID: 23358258]
[108]
Mo, D.W.; Dong, S.; Sun, H.; Chen, J.S.; Pang, J.X.; Xi, B.M.; Chen, W.H. Synthesis and potent inhibitory activities of carboxybenzyl-substituted 8-(3-(R)-aminopiperidin-1-yl)-7-(2-chloro/cyanobenzyl)-3-methyl-3,7-dihydro-purine-2,6-diones as dipeptidyl peptidase IV (DPP-IV) inhibitors. Bioorg. Med. Chem. Lett., 2015, 25(9), 1872-1875.
[http://dx.doi.org/10.1016/j.bmcl.2015.03.048] [PMID: 25838146]
[109]
Li, G.; Huan, Y.; Yuan, B.; Wang, J.; Jiang, Q.; Lin, Z.; Shen, Z.; Huang, H. Discovery of novel xanthine compounds targeting DPP-IV and GPR119 as anti-diabetic agents. Eur. J. Med. Chem., 2016, 124, 103-116.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.023] [PMID: 27560285]
[110]
Soni, R.; Soman, S.S. Design and synthesis of aminocoumarin derivatives as DPP-IV inhibitors and anticancer agents. Bioorg. Chem., 2018, 79, 277-284.
[http://dx.doi.org/10.1016/j.bioorg.2018.05.008] [PMID: 29783098]
[111]
Li, S.; Xu, H.; Cui, S.; Wu, F.; Zhang, Y.; Su, M.; Gong, Y.; Qiu, S.; Jiao, Q.; Qin, C.; Shan, J.; Zhang, M.; Wang, J.; Yin, Q.; Xu, M.; Liu, X.; Wang, R.; Zhu, L.; Li, J.; Xu, Y.; Jiang, H.; Zhao, Z.; Li, J.; Li, H. Discovery and rational design of natural-product-derived 2-phenyl-3, 4-dihydro-2 H-benzo [f] chromen-3-amine analogs as novel and potent dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes. J. Med. Chem., 2016, 59(14), 6772-6790.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00505] [PMID: 27396490]
[112]
Abu Khalaf, R.; Jarekji, Z.; Al-Qirim, T.; Sabbah, D.; Shattat, G. Pharmacophore modeling and molecular docking studies of acridines as potential DPP-IV inhibitors. Can. J. Chem., 2015, 93(7), 721-729.
[http://dx.doi.org/10.1139/cjc-2015-0039]
[113]
Park, W.S.; Jun, M.A.; Shin, M.S.; Kwon, S.W.; Kang, S.K.; Kim, K.Y.; Dal Rhee, S.; Bae, M.A.; Narsaiah, B.; Lee, D.H.; Cheon, H.G. Synthesis and biological evaluation of triazepane derivatives as DPP-IV inhibitors. J. Fluor. Chem., 2009, 130(11), 1001-1010.
[http://dx.doi.org/10.1016/j.jfluchem.2009.08.001]
[114]
Tsai, H.J.; Chou, S.Y.; Chuang, S.H.; Chen, C.C.; Hsu, F.L. D‐420720, A novel orally active sulfonamide compound dipeptidyl peptidase IV inhibitor: structure and activity relationship of arylsulfonamide to dipeptidyl peptidase IV inhibition. Drug Dev. Res., 2008, 69(8), 514-519.
[http://dx.doi.org/10.1002/ddr.20278 ]
[115]
Sharma, R.; Soman, S.S. Design and synthesis of sulfonamide derivatives of pyrrolidine and piperidine as anti-diabetic agents. Eur. J. Med. Chem., 2015, 90, 342-350.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.041] [PMID: 25437620]
[116]
Gao, H.D.; Liu, P.; Yang, Y.; Gao, F. Sulfonamide-1, 3, 5-triazine–thiazoles: discovery of a novel class of antidiabetic agents via inhibition of DPP-4. RSC Advances, 2016, 6(86), 83438-83447.
[http://dx.doi.org/10.1039/C6RA15948F]
[117]
Khalaf, R.A.; Sabbah, D.; Al-Shalabi, E.; Al-Sheikh, I.; Albadawi, G.; Abu Sheikha, G. Synthesis, structural characterization and docking studies of sulfamoyl- phenyl acid esters as dipeptidyl peptidase-iv inhibitors. Curr Comput Aided Drug Des, 2018, 14(2), 142-151.
[http://dx.doi.org/10.2174/1573409914666180308164013] [PMID: 29521244]
[118]
Abd El-Karim, S.S.; Anwar, M.M.; Syam, Y.M.; Nael, M.A.; Ali, H.F.; Motaleb, M.A. Rational design and synthesis of new tetralin-sulfonamide derivatives as potent anti-diabetics and DPP-4 inhibitors: 2D & 3D QSAR, in vivo radiolabeling and bio distribution studies. Bioorg. Chem., 2018, 81, 481-493.
[http://dx.doi.org/10.1016/j.bioorg.2018.09.021] [PMID: 30243239]
[119]
Nordhoff, S.; Cerezo-Gálvez, S.; Deppe, H.; Hill, O.; López-Canet, M.; Rummey, C.; Thiemann, M.; Matassa, V.G.; Edwards, P.J.; Feurer, A. Discovery of β-homophenylalanine based pyrrolidin-2-ylmethyl amides and sulfonamides as highly potent and selective inhibitors of dipeptidyl peptidase IV. Bioorg. Med. Chem. Lett., 2009, 19(15), 4201-4203.
[http://dx.doi.org/10.1016/j.bmcl.2009.05.109] [PMID: 19515557]
[120]
Liu, Y.; Si, M.; Tang, L.; Shangguan, S.; Wu, H.; Li, J.; Wu, P.; Ma, X.; Liu, T.; Hu, Y. Synthesis and biological evaluation of novel benzyl-substituted (S)-phenylalanine derivatives as potent dipeptidyl peptidase 4 inhibitors. Bioorg. Med. Chem., 2013, 21(18), 5679-5687.
[http://dx.doi.org/10.1016/j.bmc.2013.07.034] [PMID: 23938053]
[121]
Jiang, T.; Zhou, Y.; Chen, Z.; Sun, P.; Zhu, J.; Zhang, Q.; Wang, Z.; Shao, Q.; Jiang, X.; Li, B.; Chen, K.; Jiang, H.; Wang, H.; Zhu, W.; Shen, J. Design, synthesis, and pharmacological evaluation of fused β-homophenylalanine derivatives as potent DPP-4 inhibitors. ACS Med. Chem. Lett., 2015, 6(5), 602-606.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00074] [PMID: 26005541]
[122]
Boduszek, B.; Oleksyszyn, J.; Kam, C.M.; Selzler, J.; Smith, R.E.; Powers, J.C. Dipeptide phosphonates as inhibitors of dipeptidyl peptidase IV. J. Med. Chem., 1994, 37(23), 3969-3976.
[http://dx.doi.org/10.1021/jm00049a016] [PMID: 7966157]
[123]
Belyaev, A.; Zhang, X.; Augustyns, K.; Lambeir, A.M.; De Meester, I.; Vedernikova, I.; Scharpé, S.; Haemers, A. Structure-activity relationship of diaryl phosphonate esters as potent irreversible dipeptidyl peptidase IV inhibitors. J. Med. Chem., 1999, 42(6), 1041-1052.
[http://dx.doi.org/10.1021/jm981033g] [PMID: 10090787]
[124]
Gilmore, B.F.; Carson, L.; McShane, L.L.; Quinn, D.; Coulter, W.A.; Walker, B. Synthesis, kinetic evaluation, and utilization of a biotinylated dipeptide proline diphenyl phosphonate for the disclosure of dipeptidyl peptidase IV-like serine proteases. Biochem. Biophys. Res. Commun., 2006, 347(1), 373-379.
[http://dx.doi.org/10.1016/j.bbrc.2006.06.113] [PMID: 16824486]

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