Design, synthesis, and evaluation of 3,4-disubstituted pyrazole analogues as anti-tumor CDK inhibitors

Lin, Ronghui; Chiu, G.; Yu, Yongmei; Connolly, Peter J.; Li, Shengjian; Lü, Yanhua; Adams, Mary; Fuentes‐Pesquera, Angel R.; Emanuel, Stuart L.; Greenberger, Lee M.

doi:10.1016/j.bmcl.2007.05.092

Cited by 114 publications

(57 citation statements)

References 18 publications

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“…Diazoles, such as pyrazoles and pyrazolines are small molecules that have also been found to exhibit remarkable anticancer activities and have been identified as inhibitors of CDKs [162], VEGF [163] and P-gp [164]. These observations led Lesyk and colleagues to synthesise new isatin-pyrazoline hybrids (75a-d, Fig.…”

Section: Dual Action/ Hybrid Agentsmentioning

confidence: 99%

Recent Highlights in the Development of Isatin-Based Anticancer Agents

Vine¹,

Matesic²,

Locke³

et al. 2013

Advances in Anticancer Agents in Medicinal Chemistry

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Isatin (1H-indole-2,3-dione) and its derivatives are responsible for a broad spectrum of biological activities. Among these the cytotoxic and antineoplastic properties have been the most widely reported. The synthetic versatility of the isatin, due to its privileged scaffold, has led to the generation of a large number of structurally diverse derivatives which include analogues derived from either mono-, di-, and trisubstitution of the aryl ring A, and/or those obtained by derivatisation of the isatin nitrogen and C2/C3 carbonyl moieties. These compounds inhibit cancer cell proliferation and tumour growth via interaction with a variety of intracellular targets such as DNA, telomerase, tubulin, P-glycoprotein, protein kinases and phosphatases. Herein we review recent highlights in the development of isatin-based compounds as anticancer agents with a particular focus on the cytotoxicity and structure activity relationships. Abstract:Isatin (1H-indole-2,3-dione) and its derivatives are responsible for a broad spectrum of biological activities. Among these the cytotoxic and antineoplastic properties have been the most widely reported. The synthetic versatility of the isatin, due to its privileged scaffold, has led to the generation of a large number of structurally diverse derivatives which include analogues derived from either mono-, di-, and tri-substitution of the aryl ring A, and/or those obtained by derivatisation of the isatin nitrogen and C2/C3 carbonyl moieties. These compounds inhibit cancer cell proliferation and tumour growth via interaction with a variety of intracellular targets such as DNA, telomerase, tubulin, Pglycoprotein, protein kinases and phosphatases. Herein we review recent highlights in the development of isatin-based compounds as anticancer agents with a particular focus on the cytotoxicity and structure activity relationships.

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Section: Dual Action/ Hybrid Agentsmentioning

confidence: 99%

Recent Highlights in the Development of Isatin-Based Anticancer Agents

Vine¹,

Matesic²,

Locke³

et al. 2013

Advances in Anticancer Agents in Medicinal Chemistry

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“…(1) and (E)-1,4-dibromobut-2-ene (8). Compounds (6) and (9), when reacted separately with different heterocyclic secondary amines, gave the corresponding desired products, (7a-d) and (10a-d), respectively, in good yields (Scheme 2). The treatment of ethyl 4-amino-3-(4-chlorophenyl)-1H-pyrazol-5-carboxylate (1) with thiophosgene gave the corresponding 3-isothiocyanat derivatives (11).…”

Section: Chemistrymentioning

confidence: 99%

“…The treatment of ethylcarboxylate (1) with an excess of 1,4-dibromobutane (5) in the presence of K2CO3 in DMF at 25 °C for 5 h obtained crude ethyl-4-amino-1-(4-bromobutyl)-3-(4-chloro-phenyl)-1H-pyrazole-5-carboxylate (6). Similarly, ethyl 4-amino-1-[(2E)-(4-bromobut-2-en-1-yl)-3-(4-chlorophenyl)-1H-pyrazole-5-carboxylate (9) was prepared from (1) and (E)-1,4-dibromobut-2-ene (8).…”

Section: Chemistrymentioning

confidence: 99%

“…Similarly, ethyl 4-amino-1-[(2E)-(4-bromobut-2-en-1-yl)-3-(4-chlorophenyl)-1H-pyrazole-5-carboxylate (9) was prepared from (1) and (E)-1,4-dibromobut-2-ene (8). Compounds (6) and (9), when reacted separately with different heterocyclic secondary amines, gave the corresponding desired products, (7a-d) and (10a-d), respectively, in good yields (Scheme 2). (1) and (E)-1,4-dibromobut-2-ene (8).…”

Section: Chemistrymentioning

confidence: 99%

“…Pyrazoles are one of the most common pharmaceutically active compounds, and have attracted much attention due to their broad spectrum of biological activities such as anti-inflammatory [2,3], COX inhibitory [4], hypoglycemic [5], CDK2/Cyclin A [6], p38 MAP kinase [7], and antidepressive activities [8], and have been widely used in biopharmaceutical and pesticides. Pyrazole plays a unique role in drug discovery programs.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis and Biological Evaluation of N- Pyrazolyl Derivatives and Pyrazolopyrimidine Bearing a Biologically Active Sulfonamide Moiety as Potential Antimicrobial Agent

Hafez

El‐Gazzar

2016

Molecules

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Abstract:A series of novel pyrazole-5-carboxylate containing N-triazole derivatives 3,4; different heterocyclic amines 7a-b and 10a-b; pyrazolo [4,3-d]pyrimidine containing sulfa drugs 14a,b; and oxypyrazolo [4,3-d]pyrimidine derivatives 17, 19, 21 has been synthesized. The structure of the newly synthesized compounds was elucidated on the basis of analytical and spectral analyses. All compounds have been screened for their in vitro antimicrobial activity against three gram-positive and gram-negative bacteria as well as three fungi. The results revealed that compounds 14b and 17 had more potent antibacterial activity against all bacterial strains than reference drug Cefotaxime. Moreover compounds 4, 7b, and 12b showed excellent antifungal activities against Aspergillus niger and Candida albicans in low inhibitory concentrations but slightly less than the reference drug miconazole against Aspergillus flavus.

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First Copper‐Catalyzed Intramolecular Amidation in Substituted 4‐Iodopyrazoles Leading to the Synthesis of Pyrazolo[4,3‐b]‐ pyridin‐5‐ones

2009

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An unprecedented copper-catalyzed intramolecular amidation of substituted 4-iodopyrazoles generated either via Baylis-Hillman or Horner-Wadsworth-Emmons chemistry for the synthesis of pyrazoloA C H T U N G T R E N N U N G [4,3-b]pyridine-5-ones is described. In addition, the effect of the stereochemistry of the acrylamide on the cross-coupling reaction has been investigated and it is demonstrated that only the Z-isomer is favoured to undergo the intramolecular cyclization.

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Design, synthesis, and evaluation of 3,4-disubstituted pyrazole analogues as anti-tumor CDK inhibitors

Cited by 114 publications

References 18 publications

Recent Highlights in the Development of Isatin-Based Anticancer Agents

Recent Highlights in the Development of Isatin-Based Anticancer Agents

Synthesis and Biological Evaluation of N- Pyrazolyl Derivatives and Pyrazolopyrimidine Bearing a Biologically Active Sulfonamide Moiety as Potential Antimicrobial Agent

First Copper‐Catalyzed Intramolecular Amidation in Substituted 4‐Iodopyrazoles Leading to the Synthesis of Pyrazolo[4,3‐b]‐ pyridin‐5‐ones

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