Synthesis and biological evaluation of pyrazoline analogues with β-amino acyl group as dipeptidyl peptidase IV inhibitors

Jun, Mi Ae; Park, Woul Seong; Kang, Seung Kyu; Kim, Ki Young; Kim, Kwang-Rok; Rhee, Sang Dal; Bae, Myung Ae; Kang, Nam Sook; Sohn, Sang-Kwon; Kim, Sung Gyu; Lee, Jie‐Oh; Lee, Duck‐Hyung; Cheon, Hyae Gyeong; Kim, Sung Soo; Ahn, Jin Hee

doi:10.1016/j.ejmech.2007.11.029

Cited by 30 publications

(3 citation statements)

References 23 publications

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“…29 Many inhibitors of DPP-4 (Figure 1) possess five-membered heterocyclic rings (e.g., pyrrolidine, thiazolidine) as proline mimics at the P1 position. 30 Vildagliptin (2), saxagliptin (3), anagliptin (4), gosogliptin (5), and teneligliptin (6) (Figure 2) are approved DPP-4 inhibitors with pyrrolidine or analogs as P1 fragment with an α-aminoacyl linker. 31−33 P1 Fragment.…”

Section: ■ Dpp-4 Inhibitors With Pyrrolidine or Analogs As P1 Fragmen...mentioning

confidence: 99%

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Structure–Activity Relationship Analysis of Cocrystallized Gliptin-like Pyrrolidine, Trifluorophenyl, and Pyrimidine-2,4-Dione Dipeptidyl Peptidase-4 Inhibitors

2021

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Approved and potent reported dipeptidyl peptidase-4 (DPP-4) inhibitors with gliptin-like structures are classified here according to their structures and mechanisms of the inhibition in three groups: (i) those with pyrrolidine or analogs as P1 fragment with α-aminoacyl linker, (ii) structures with trifluorophenyl moiety or analogs as P1 fragment with β-aminobutanoyl linker, and (iii) DPP-4 inhibitors with pyrimidine-2,4-dione or analogs as P1′ fragment. The structure−activity relationship analysis was performed for those whose cocrystallized structures with the enzyme were published. While inhibitors with pyrrolidine and trifluorophenyl moiety or analogs as P1 fragment bind in a similar way in S1, S2 and S2 extensive domains of the enzyme, the binding mode of pyrimidine-2,4-dione derivatives/analogs differs with additional interactions in S1′ and S2′ pockets. Three general schemes of fragmented gliptins and gliptin-like structures with the enzyme and protein−ligand interaction fingerprints were made, which might be useful in the creation of DPP-4 inhibitor's design strategies.

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Section: ■ Dpp-4 Inhibitors With Pyrrolidine or Analogs As P1 Fragmen...mentioning

confidence: 99%

“…The S1 domain is considered a decisive site for binding of DPP-4 inhibitors . Many inhibitors of DPP-4 (Figure ) possess five-membered heterocyclic rings (e.g., pyrrolidine, thiazolidine) as proline mimics at the P1 position …”

Section: Dpp-4 Inhibitors With Pyrrolidine or Analogs As P1 Fragment ...mentioning

confidence: 99%

Structure–Activity Relationship Analysis of Cocrystallized Gliptin-like Pyrrolidine, Trifluorophenyl, and Pyrimidine-2,4-Dione Dipeptidyl Peptidase-4 Inhibitors

2021

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“…They have been found to possess antimicrobial, antidiabetic, antidepressant, anticancer, hypotensive, antiamoebic, anti-inflammatory and antitubercular activity [2][3][4][5][6][7][8][9][10]. As a part of our research programme on pyrazoline derivatives [11], we report herein the synthesis of [5-(1,3-diphenyl-1H-pyrazol-4-yl)-3-phenyl-4,5-dihydropyrazol-1-yl](pyridin-4-yl)methanone (2).…”

Section: Introductionmentioning

confidence: 98%

[5-(1,3-Diphenyl-1H-pyrazol-4-yl)-3-phenyl-4,5-dihydropyrazol-1-yl](pyridin-4-yl)methanone

Kaushik¹,

Nagpal²,

Verma³

et al. 2011

Molbank

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Dipeptidyl Peptidase 4 Inhibitors

Weber

Thornberry

2010

Burger's Medicinal Chemistry and Drug Discovery

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Defective insulin secretion is a hallmark of type 2 diabetes (T2DM), and agents that increase the concentration of circulating insulin have proven beneficial in the treatment of diabetes. Dipeptidyl peptidase 4 (DPP‐4) inhibitors are a new oral approach to T2DM that lower glucose via stabilization of the incretin hormone glucagon‐like peptide 1 (GLP‐1), which has clearly established roles in insulin secretion and inhibition of glucagon production. These agents have been shown to produce clinically meaningful glucose control in a range of patients with type 2 diabetes without many of the liabilities that are associated with other oral therapies, including weight gain, edema, GI intolerability, and hypoglycemia. Accordingly, DPP‐4 inhibitors have excellent potential for use in both monotherapy and combination with established agents. Extensive structure–activity relationship (SAR) studies in many different laboratories have resulted in the identification of a number of clinical candidates. The most advanced of these have recently been approved for the treatment of T2DM, representing the first new oral therapy for treatment of this disease since the introduction of troglitazone in 1998.

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Synthesis and biological evaluation of pyrazoline analogues with β-amino acyl group as dipeptidyl peptidase IV inhibitors

Cited by 30 publications

References 23 publications

Structure–Activity Relationship Analysis of Cocrystallized Gliptin-like Pyrrolidine, Trifluorophenyl, and Pyrimidine-2,4-Dione Dipeptidyl Peptidase-4 Inhibitors

Structure–Activity Relationship Analysis of Cocrystallized Gliptin-like Pyrrolidine, Trifluorophenyl, and Pyrimidine-2,4-Dione Dipeptidyl Peptidase-4 Inhibitors

[5-(1,3-Diphenyl-1H-pyrazol-4-yl)-3-phenyl-4,5-dihydropyrazol-1-yl](pyridin-4-yl)methanone

Dipeptidyl Peptidase 4 Inhibitors

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