Catalyst-free synthesis of quinazolin-4-ones from (hetero)aryl-guanidines: application to the synthesis of pyrazolo[4,3-f]quinazolin-9-ones, a new family of DYRK1A inhibitors

被引：16

作者：

Debray, Julien ^{[1
,2
]}

Bonte, Simon ^{[1
,2
]}

Lozach, Olivier ^{[3
]}

Meijer, Laurent ^{[3
]}

Demeunynck, Martine ^{[1
,2
]}

机构：

[1] Univ Grenoble 1, CNRS, Dept Pharmacochim Mol, UMR 5063, F-38041 Grenoble 9, France

[2] Univ Grenoble 1, CNRS, ICMG, FR 2607, F-38041 Grenoble 9, France

[3] Stn Biol Roscoff, USR 3151, Prot Phosphorylat & Human Dis Grp, F-29680 Roscoff, France

来源：

MOLECULAR DIVERSITY | 2012年 / 16卷 / 04期

关键词：

Kinase inhibition; Quinazoline; Nitrogen heterocycles; Cyclization; KINASE INHIBITORS; AFFINITY-CHROMATOGRAPHY; BIOLOGICAL EVALUATION; IMMOBILIZED AXIN; DERIVATIVES; ALKALOIDS; PHOSPHORYLATION; PURIFICATION; CYCLIZATION; CHEMISTRY;

D O I：

10.1007/s11030-012-9397-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A small library of heterocycle-fused quinazolin-4-ones was prepared and evaluated as kinase inhibitors. The key step of the two-step process involves the environmental friendly thermolysis of N-ethoxycarbonyl-N'-(hetero) arylguanidines at 130 A degrees C in water. The cyclization is fully regioselective. The most active molecules, 7-(2-hydroxyethylamino)- and 7-(3-hydroxypropylamino)-pyrazolo[4,3-f]quinazolin-9-ones, inhibit DYRK1A and CLK1 at submicromolar concentrations, indicating the potential interest of this new heterocycle in drug design.

引用

页码：659 / 667

页数：9

共 22 条

[1] Synthesis and biological activity of novel antibacterial quinazolines [J].

Bedi, PMS ;

Kumar, V ;

Mahajan, MP .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (20) :5211-5213

[2] Synthesis and SAR of new pyrazolo[4,3-h]quinazoline-3-carboxamide derivatives as potent and selective MPS1 kinase inhibitors [J].

Caldarelli, Marina ;

Angiolini, Mauro ;

Disingrini, Teresa ;

Donati, Daniele ;

Guanci, Marco ;

Nuvoloni, Stefano ;

Posteri, Helena ;

Quartieri, Francesca ;

Silvagni, Marco ;

Colombo, Riccardo .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (15) :4507-4511

[3] A rapid and versatile synthesis of novel pyrimido[5,4-b]carbazoles [J].

Caruso, Anna ;

Lancelot, Jean-Charles ;

El-Kashef, Hussein ;

Sinicropi, Maria Stefania ;

Legay, Remi ;

Lesnard, Aurelien ;

Rault, Sylvain .

TETRAHEDRON, 2009, 65 (50) :10400-10405

[4] Synthesis and biological evaluation of 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors [J].

Chioua, Mourad ;

Samadi, Abdelouahid ;

Soriano, Elena ;

Lozach, Olivier ;

Meijer, Laurent ;

Marco-Contelles, Jose .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (16) :4566-4569

[5] Synthesis of quinazolinones and quinazolines [J].

Connolly, DJ ;

Cusack, D ;

O'Sullivan, TP ;

Guiry, PJ .

TETRAHEDRON, 2005, 61 (43) :10153-10202

[6] Leucettines, a Class of Potent Inhibitors of cdc2-Like Kinases and Dual Specificity, Tyrosine Phosphorylation Regulated Kinases Derived from the Marine Sponge Leucettamine B: Modulation of Alternative Pre-RNA Splicing [J].

Debdab, Mansour ;

Carreaux, Francois ;

Renault, Steven ;

Soundararajan, Meera ;

Fedorov, Oleg ;

Filippakopoulos, Panagis ;

Lozach, Olivier ;

Babault, Lucie ;

Tahtouh, Tania ;

Baratte, Blandine ;

Ogawa, Yasushi ;

Hagiwara, Masatoshi ;

Eisenreich, Andreas ;

Rauch, Ursula ;

Knapp, Stefan ;

Meijer, Laurent ;

Bazureau, Jean-Pierre .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (12) :4172-4186

[7] Montmorillonite K-10 catalyzed cyclization of N-ethoxycarbonyl-N′-arylguanidines: Access to pyrimido[4,5-c]carbazole and pyrimido[5,4-b]indole derivatives [J].

Debray, Julien ;

Zeghida, Walid ;

Baldeyrou, Brigitte ;

Mahieu, Christine ;

Lansiaux, Amelie ;

Demeunynck, Martine .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (14) :4244-4247

[8] Swift and Efficient Synthesis of 4-Phenylquinazolines: Involvement of N-Heterocyclic Carbene in the Key Cyclization Step [J].

Debray, Julien ;

Leveque, Jean-Marc ;

Philouze, Christian ;

Draye, Micheline ;

Demeunynck, Martine .

JOURNAL OF ORGANIC CHEMISTRY, 2010, 75 (06) :2092-2095

[9] Synthesis and evaluation of fused bispyrimidinoacridines as novel pentacyclic analogues of quadruplex-binder BRACO-19 [J].

Debray, Julien ;

Zeghida, Walid ;

Jourdan, Muriel ;

Monchaud, David ;

Dheu-Andries, Marie-Louise ;

Dumy, Pascal ;

Teulade-Fichou, Marie-Paule ;

Demeunynck, Martine .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2009, 7 (24) :5219-5228

[10]

Eguchi S, 2006, TOP HETEROCYCL CHEM, V6, P113, DOI 10.1007/7081_022

← 1 2 3 →