Pyrazole is a five membered and two-nitrogen containing heterocyclic ring. These structures have been investigated in the development of novel compounds with hypoglycemic, analgesic, anti-inflammatory, antimicrobial, anticonvulsant, antidepressant, antimycobacterial, antioxidant, antiviral, insecticidal and antitumor activities. Therefore, these compounds have been synthesized as target structures by many researchers and were evaluated for their biological activities. We hope that the bioactivity of pyrazole derivatives will be beneficial for the rational design of new generation of small molecule drugs. In this review, we report the structures of 1 -pyrazoles with their corresponding biological activities for 21st (in 2000–2014 years) century.
A large number of structurally diverse natural compounds containing azole nucleus constitute an important class of biologically active heterocycles that are gaining more attention in the field of medicinal chemistry. Among azoles, pyrazoles are rarely found in nature probably due to difficulty in the formation of N–N bond by living organisms. However, they exhibit numerous biological activities, including anti-diabetic, antiviral, anticancer, anti-inflammatory, antibacterial and antifungal activities. The present review is an attempt to understand the chemistry along with medicinal importance of pyrazole containing natural products reported till date which would certainly help the scientific community to bring further developments in the isolation and synthetic methodologies for pyrazole based novel bioactive compounds. Pyrazole containing natural products exhibit important biological properties. The present review describes the medicinal importance and different strategies used for isolation and total synthesis of pyrazole containing natural products.
The pyrazole nucleus is an aromatic azole heterocycle with two adjacent nitrogen atoms. Pyrazole derivatives have exhibited a broad spectrum of biological activities, and approved pyrazole-containing drugs include celecoxib, antipyrine, phenylbutazone, rimonabant, and dipyrone. Many research groups have synthesized and evaluated pyrazoles against several biological agents. This review examines recent publications relating the structures of pyrazoles with their corresponding biological activities.
Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.
In this work, twenty-seven novel steroidal pyrazole derivatives were designed and effectively synthesized with two different commercially available staring material, Isopregnanolone and 5,16-Pregnadienolone , via the key intermediates, 17β-(4′-formyl)pyrazolylandrost-3β-yl formate and 17-(4′-formyl)pyrazolylandrost- 5,16-dienes-3β-yl formate, which were obtained from the cyclization of steroidal phenylhydrazone with Vilsmeier reagent catalyzed by phosphorous oxychloride followed by hydrolysis, then Borch reduction to afford the target derivatives under mild conditions. Structures of these compounds were identified by H NMR, C NMR and high resolution mass spectrometry. Based on our previous work, the cytotoxicity of these derivatives were evaluated by the SRB method against 293T cell lines and three cancer cell lines: A549, Hela and MCF-7. The results indicated that compounds , and exhibited moderate to high cytotoxic activities with IC values ranging from 0.62 to 7.51 μM. Among the eight hybrids, compound , with an ethyl amino and a dien-pregn moieties showed the highest potency, with an IC values of 0.87 μM and 0.53 μM for 293T cell lines and Hela cell lines, respectively. Some structure-activity relationships among the groups of the twenty-seven derivatives are discussed and identify several determinants important for the activity of these compounds. What's more, further molecular mechanism studies suggested that one of the most potent derivatives caused Hela cell lines apoptosis and arrested the cell cycle at S phase in a concentration dependent manner.
A new series of –substituted 2–pyrazolines , , , and were obtained from the cyclocondensation reaction of [(7–chloroquinolin–4–yl)amino]chalcones with hydrazine hydrate and its derivatives. Fourteen of the synthesized compounds including the starting chalcones were selected by US National Cancer Institute (NCI) for testing their anticancer activity against 60 different human cancer cell lines, with the most important GI values ranging from 0.28 to 11.7 μM (0.13–6.05 μg/mL) and LC values ranging from 2.6 to > 100 μM (1.2 to > 51.7 μg/mL), for chalcones , and pyrazolines , . All compounds were assessed for antibacterial activity against wild type and multidrug resistant gram negative and gram positive bacteria, with MIC values ranging from 31.25 to 500 μg/mL. Additionally, the novel compounds were tested for antifungal and antiparasitic properties. Although these compounds showed mild activity against , chalcones and showed high activity against with MIC = 7.8 μg/mL. For anti– activity the 2–pyrazoline was the most active with EC = 5.54 μg/mL. Regarding the activity against , compound was highly active with EC = 0.70 μg/mL. Chalcone had good activity against amastigotes with EC = 0.79 μg/mL.
Ibrutinib inhibits Bruton's tyrosine kinase, a component of normal B-cell activation pathways. Ibrutinib produced responses in 71% of patients with refractory chronic lymphocytic leukemia. Chronic lymphocytic leukemia (Cll) is the most common leukemia in adults. Therapy for symptomatic CLL has consisted predominantly of chemotherapeutic agents, including chlorambucil, cyclophosphamide, fludarabine, and combinations of these agents that are effective for palliation but do not improve survival. 1 The addition of the anti-CD20 antibody rituximab to chemotherapy (fludarabine 2 alone or in combination with cyclophosphamide 3 ) results in higher response rates, extended remissions, and improved overall survival. 4 However, a subgroup of patients with deletion of 17p13.1 have a poor response to chemoimmunotherapy, and patients with tumors expressing unmutated immunoglobulin variable-region heavy-chain genes have shorter remissions than those with mutated . . .
One-third of the world's population infected tuberculosis (TB), and more than 1 million deaths annually. The co-infection between the mainly pathogen (MTB) and HIV, and the incidence of drug-resistant TB, multi-drug resistant TB, extensively drug-resistant TB as well as totally drug-resistant TB have further aggravated the mortality and spread of this disease. Thus, there is an urgent need to develop novel anti-TB agents against both drug-susceptible and drug-resistant TB. The wide spectrum of biological activities and successful utilization of pyrazole-containing drugs in clinic have inspired more and more attention towards this kind of heterocycles. Numerous of pyrazole-containing derivatives have been synthesized for searching new anti-TB agents, and some of them showed promising potency and may have novel mechanism of action. This review aims to outline the recent achievements in pyrazole-containing derivatives as anti-TB agents and their structure-activity relationship. This review aims to outline the recent advances in the discovery of pyrazole-containing derivatives as anti-TB agents and the SAR of these heterocycles.
In this work novel organic based compounds, acyl thiourea derivatives were synthesized and their anticancer activities were investigated. A new series of acyl thiourea derivatives containing pyrazole ring were prepared in good yield through one pot reaction of 4-benzoyl-1, 5-diphenyl-1 -pyrazole-3-carbonyl chloride with ammonium thiocyanate and various amines. The structures of the newly synthesized compounds were confirmed by IR, H NMR, C NMR and elemental analysis. Anticancer activities of synthesized compounds were evaluated on human colon, liver and leukemia cancer cell lines. Cell culture studies have demonstrated significant toxicity of the compounds on the cell lines, and the levels of toxicity have altered in the presence of various side groups. These results confirm that novel pyrazolyl acyl thioureas derived compounds may be utilized for cancer treatment. Furthermore, these compounds have a great potential and significance for further investigations.