One-pot synthesis and biological evaluation of 2-pyrrolidinyl-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole: a unique, highly active antimicrotubule agent.


:A wide variety of small molecules with diverse molecular scaffolds inhibit microtubule formation. In this article we report a one-pot procedure for the preparation of a novel 2-(N-pyrrolidinyl)-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole in which the size of the substituent at the C-2 position of the thiazole ring plays an essential role in compound activity. The most active agent (3f) inhibited at submicromolar concentrations the growth of tumor cell lines. It also inhibited tubulin polymerization with an activity quantitatively similar to that of CA-4, and treatment of HeLa cells resulted in their arrest at the G2-M phase of the cell cycle. Furthermore, 3f was effective against multidrug resistant cancer cells and inhibited the growth of the HT-29 xenograft in a nude mouse model. This indicated that 3f is a promising new antimitotic agent with encouraging preclinical potential.


Eur J Med Chem


Romagnoli R,Baraldi PG,Lopez Cara C,Kimatrai Salvador M,Bortolozzi R,Basso G,Viola G,Balzarini J,Brancale A,Fu XH,Li J,Zhang SZ,Hamel E




Has Abstract


2011-12-01 00:00:00














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    pub_type: 杂志文章


    authors: Datta C,Das D,Mondal P,Chakraborty B,Sengupta M,Bhattacharjee CR

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    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Dadiboyena S,Nefzi A

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    journal_title:European journal of medicinal chemistry

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    authors: Bellia F,Amorini AM,La Mendola D,Vecchio G,Tavazzi B,Giardina B,Di Pietro V,Lazzarino G,Rizzarelli E

    更新日期:2008-02-01 00:00:00

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    journal_title:European journal of medicinal chemistry

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    authors: Ullah H,Previtali V,Mihigo HB,Twamley B,Rauf MK,Javed F,Waseem A,Baker RJ,Rozas I

    更新日期:2019-11-01 00:00:00

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    journal_title:European journal of medicinal chemistry

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    authors: Ansari M,Shokrzadeh M,Karima S,Rajaei S,Fallah M,Ghassemi-Barghi N,Ghasemian M,Emami S

    更新日期:2020-01-01 00:00:00