Construction of a 3D-shaped, natural product like fragment library by fragmentation and diversification of natural products

被引：33

作者：

Prescher, Horst ^{[1
,3
]}

Koch, Guido ^{[1
]}

Schuhmann, Tim ^{[1
]}

Ertl, Peter ^{[1
]}

Bussenault, Alex ^{[1
]}

Glick, Meir ^{[2
,4
]}

Dix, Ina ^{[1
]}

Petersen, Frank ^{[1
]}

Lizos, Dimitrios E. ^{[1
]}

机构：

[1] Novartis Inst BioMed Res Inc, Basel, Switzerland

[2] Novartis Inst BioMed Res Inc, Cambridge, MA USA

[3] SialoTec GmbH, Mannheim, Germany

[4] Merck Res Labs, Boston, MA USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 03期

关键词：

Fragment based drug discovery; Natural products; Fragment library; Natural product likeness; Rearrangement; STREPTOMYCES SP A92-308110; DRUG DISCOVERY; CYTOCHALASINS E; DESIGN; SANGLIFEHRINS; FERMENTATION; METABOLITES; DIVERSITY; FK506;

D O I：

10.1016/j.bmc.2016.12.005

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 fragment library consisting of 3D-shaped, natural product-like fragments was assembled. Library construction was mainly performed by natural product degradation and natural product diversification reactions and was complemented by the identification of 3D-shaped, natural product like fragments available from commercial sources. In addition, during the course of these studies, novel rearrangements were discovered for Massarigenin C and Cytochalasin E. The obtained fragment library has an excellent 3D-shape and natural product likeness, covering a novel, unexplored and underrepresented chemical space in fragment based drug discovery (FBDD). (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：921 / 925

页数：5

共 35 条

[1] REVISED STRUCTURES FOR CYTOCHALASINS E AND F [J].

ALDRIDGE, DC ;

GREATBANKS, D ;

TURNER, WB .

JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1973, (15) :551-552

[2] STRUCTURES OF FUNGAL METABOLITES CYTOCHALASINS E AND F [J].

ALDRIDGE, DC ;

BURROWS, BF ;

TURNER, WB .

JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1972, (03) :148-&

[3] Fragment-based lead discovery grows up [J].

Baker, Monya .

NATURE REVIEWS DRUG DISCOVERY, 2013, 12 (01) :5-10

[4]

BUCHI G, 1973, J AM CHEM SOC, V95, P5423, DOI 10.1021/ja00797a060

[5] Evolutions in fragment-based drug design: the deconstruction-reconstruction approach [J].

Chen, Haijun ;

Zhou, Xiaobin ;

Wang, Ailan ;

Zheng, Yunquan ;

Gao, Yu ;

Zhou, Jia .

DRUG DISCOVERY TODAY, 2015, 20 (01) :105-113

[6] HIGHLY SELECTIVE REACTIONS OF FK506 WITH DIAZOMETHANE [J].

EDMUNDS, AJF ;

BAUMANN, K ;

GRASSBERGER, M ;

SCHULZ, G .

TETRAHEDRON LETTERS, 1991, 32 (48) :7039-7042

[7] Twenty years on: the impact of fragments on drug discovery [J].

Erlanson, Daniel A. ;

Fesik, Stephen W. ;

Hubbard, Roderick E. ;

Jahnke, Wolfgang ;

Jhoti, Harren .

NATURE REVIEWS DRUG DISCOVERY, 2016, 15 (09) :605-619

[8] Introduction to Fragment-Based Drug Discovery [J].

Erlanson, Daniel A. .

FRAGMENT-BASED DRUG DISCOVERY AND X-RAY CRYSTALLOGRAPHY, 2012, 317 :1-32

[9] Natural product-likeness score and its application for prioritization of compound libraries [J].

Ertl, Peter ;

Roggo, Silvio ;

Schuffenhauer, Ansgar .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2008, 48 (01) :68-74

[10]

Ertl Peter, 2008, V66

← 1 2 3 4 →