Substituted 2-arylbenzothiazoles as kinase inhibitors: Hit-to-lead optimization

Tasler, Stefan; Müller, Oliver; Wieber, Tanja; Herz, Thomas; Pegoraro, Stefano; Saeb, Wael; Lang, Martin; Krauss, Rolf; Totzke, Frank; Zirrgiebel, Ute; Ehlert, Jan E.; Kubbutat, Michael H.G.; Schächtele, Christoph

doi:10.1016/j.bmc.2009.07.047

Cited by 39 publications

(14 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Serine/Threonine and tyrosine kinases Substituted 2-arylbenzothiazoles EC50 = 60 nM. Structure-based [45] class for which structure-activity relationships (SARs) exist across the different lead chemotypes or active sites [19]. These compound subsets, also known as focused screening (illustrated in the appendix), can provide sufficient hits in the drug discovery phase, without screening the whole molecular inventory.…”

Section: Discussionmentioning

confidence: 99%

Neccessasity of Bio-imaging Hybrid Approaches Accelerating Drug Discovery Process (Mini-Review)

Samardzhieva¹,

Khan²

2018

IJCA

View full text Add to dashboard Cite

Imaging technologies have made a significant improvement in the past few decades and their application made a great impact on accelerating the process of drug discovery and development. The ability to non-invasively image an animal model or co-cultured live cells and validate potential drug target, biomarkers of drug efficacy and assess a pharmacological drug interaction significantly contributes to the process of translating molecules into medicines. This paper summarizes current trends in bio-imaging technologies and their application on the process of drug discovery. In particular, High Content Screening (HCS) and Virtual Screening (VS) are reviewed, and their respective examples are discussed to gain insight into state-of-the-art bio-imaging methodologies used for extracting knowledge and its application to drug discovery. This paper argues the need to reduce the gap between experimental (e.g. HCS based assays) and theoretical (e.g. VS based assays) assays. Although HCS and VS are leading drug discovery choices for the pharmaceutical industry and such investigations have been carried out in their respective campaign, the potential effects of these approaches together to facilitate the process of drug discovery has rarely been reported. Further, the prevalent research trends on developing hybrid approaches such as VS complementing HCS implies substantial enhancement to the goal of reliable drug candidate identification.

show abstract

Section: Discussionmentioning

confidence: 99%

Neccessasity of Bio-imaging Hybrid Approaches Accelerating Drug Discovery Process (Mini-Review)

Samardzhieva¹,

Khan²

2018

IJCA

View full text Add to dashboard Cite

show abstract

“…3D‐QSAR studies were carried out on a structurally diverse set of 37 inhibitors covering a good range of Aurora‐A inhibitory activity (Table 2) (25,26), to which the in vitro inhibitory values (as measured by IC 50 ) were collected from the literature. For the QSAR analyses, the IC 50 values were expressed in negative logarithmic units, pIC 50 (‐log IC 50 ).…”

Section: Methodsmentioning

confidence: 99%

Multicomplex‐Based Pharmacophore‐Guided 3D‐QSAR Studies of N‐Substituted 2′‐(Aminoaryl)Benzothiazoles as Aurora‐A Inhibitors

Qiu

et al. 2012

Chem Biol Drug Des

View full text Add to dashboard Cite

Aurora‐A has been known as one of the most important targets for cancer therapy, and some Aurora‐A inhibitors have entered clinical trails. In this study, combination of the ligand‐based and structure‐based methods is used to clarify the essential quantitative structure–activity relationship of known Aurora‐A inhibitors, and multicomplex‐based pharmacophore‐guided method has been suggested to generate a comprehensive pharmacophore of Aurora‐A kinase based on a collection of crystal structures of Aurora‐A–inhibitor complex. This model has been successfully used to identify the bioactive conformation and align 37 structurally diverse N‐substituted 2′‐(aminoaryl)benzothiazoles derivatives. The quantitative structure–activity relationship analyses have been performed on these Aurora‐A inhibitors based on multicomplex‐based pharmacophore‐guided alignment. These results may provide important information for further design and virtual screening of novel Aurora‐A inhibitors.

show abstract

“…Benzothiazole is one of the classes of privileged fused heterocycles found in several marine and terrestrial bioactive natural products. In recent decades, it has been established as a promising pharmacophore possessing diverse biological properties such as anticonvulsant [1,2], antihelmintic [3], neuroprotective [4], antiglutamate [5], antimalarial [6], antitubercular [7], antimicrobial [8], analgesic, anti-inflammatory [9] and anticancer activities [10][11][12][13]. Interestingly, benzothiazoles are present in bioluminescent luciferin and are used as fluorophores for two photon excitation as well as absorption processes [14,15].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potential of benzothiazoles: a patent review (2010 – 2014)

Kamal

Syed

Mohammed

2015

Expert Opinion on Therapeutic Patents

116

View full text Add to dashboard Cite

Several molecules containing benzothiazole skeleton are agents of choice for the treatment of various human diseases/disorders. Its versatile character of being capable of serving as ligand to various biomolecules attracted the interest of medicinal chemists for the development of therapies for respective ailments, especially, the 2-arylbenzothiazole moiety which is under development for the treatment of cancer. This signifies the increasing importance of benzothiazole nucleus in the area of drug discovery. Its structural simplicity and ease of synthesis provides scope for the development of chemical libraries that could serve in the discovery of new chemical entities progressing towards the market.

show abstract

Substituted 2-arylbenzothiazoles as kinase inhibitors: Hit-to-lead optimization

Cited by 39 publications

References 47 publications

Neccessasity of Bio-imaging Hybrid Approaches Accelerating Drug Discovery Process (Mini-Review)

Neccessasity of Bio-imaging Hybrid Approaches Accelerating Drug Discovery Process (Mini-Review)

Multicomplex‐Based Pharmacophore‐Guided 3D‐QSAR Studies of N‐Substituted 2′‐(Aminoaryl)Benzothiazoles as Aurora‐A Inhibitors

Therapeutic potential of benzothiazoles: a patent review (2010 – 2014)

Contact Info

Product

Resources

About