New and unusual scaffolds in medicinal chemistry

被引：352

作者：

Marson, Charles M. ^{[1
]}

机构：

[1] UCL, Dept Chem, Christopher Ingold Labs, London WC1H 0AJ, England

来源：

CHEMICAL SOCIETY REVIEWS | 2011年 / 40卷 / 11期

关键词：

BIOLOGICAL EVALUATION; IN-VIVO; RECEPTOR ANTAGONISTS; BINDING-AFFINITY; DRUG DISCOVERY; HIGHLY POTENT; INHIBITORS; DESIGN; DERIVATIVES; SERIES;

D O I：

10.1039/c1cs15119c

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Contemporary medicinal chemistry faces diverse challenges from several directions, including the need for both potency and specificity of any therapeutic agent; the increasingly demanding requirements of low toxicity shown across all patients treated; and the need for novelty in intellectual property, given the extensive use of benzenoid and heteroaromatic ring systems in numerous patents. Increasingly, such challenges are being met by a shift to new and/or unusual ring systems (scaffolds) that lie outside the field of (hetero)aromatic systems. This critical review surveys a necessarily limited selection of currently atypical scaffolds, chiefly drawn from the literature of the last three years, that have found application in medicinal chemistry, some being present in agents with therapeutic potential while others are found in agents already in clinical use (163 references).

引用

页码：5514 / 5533

页数：20

共 162 条

[141] 1-Sulfonyl-4-acylpiperazines as Selective Cannabinoid-1 Receptor (CB1R) Inverse Agonists for the Treatment of Obesity [J].

Vachal, Petr ;

Fletcher, Joan M. ;

Fong, Tung M. ;

Huang, Cathy C. R. -R. ;

Lao, Julie ;

Xiao, Jing C. ;

Shen, Chun-Pyn ;

Strack, Alison M. ;

Shearman, Lauren ;

Stribling, Sloan ;

Chen, Richard Z. ;

Frassetto, Andrea ;

Tong, Xinchun ;

Wang, Junying ;

Ball, Richard G. ;

Tsou, Nancy N. ;

Hickey, Gerard J. ;

Thompson, Donald F. ;

Faidley, Terry D. ;

Nicolich, Susan ;

Achanfuo-Yeboah, Joana ;

Hora, Donald F. ;

Hale, Jeffrey J. ;

Hagmann, William K. .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (08) :2550-2558

[142] Rigid Analogues of the α2-Adrenergic Blocker Atipamezole: Small Changes, Big Consequences [J].

Vacher, Bernard ;

Funes, Philippe ;

Chopin, Philippe ;

Cussac, Didier ;

Heusler, Peter ;

Tourette, Amelie ;

Marien, Marc .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (19) :6986-6995

[143] Cyclic Sulfones as Novel P3-Caps for Hepatitis C Virus NS3/4A (HCV NS3/4A) Protease Inhibitors: Synthesis and Evaluation of Inhibitors with Improved Potency and Pharmacokinetic Profiles [J].

Velazquez, Francisco ;

Sannigrahi, Mousumi ;

Bennett, Frank ;

Lovey, Raymond G. ;

Arasappan, Ashok ;

Bogen, Stephane ;

Nair, Latha ;

Venkatraman, Srikanth ;

Blackman, Melissa ;

Hendrata, Siska ;

Huang, Yuhua ;

Huelgas, Regina ;

Pinto, Patrick ;

Cheng, Kuo-Chi ;

Tong, Xiao ;

McPhail, Andrew T. ;

Njoroge, F. George .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (08) :3075-3085

[144] Discovery of a Potent, Orally Active 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor for Clinical Study: Identification of (S)-2-(1S,2S,4R)-Bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221) [J].

Veniant, Murielle M. ;

Hale, Clarence ;

Hungate, Randall W. ;

Gahm, Kyung ;

Emery, Maurice G. ;

Jona, Janan ;

Joseph, Smriti ;

Adams, Jeffrey ;

Hague, Andrew ;

Moniz, George ;

Zhang, Jiandong ;

Bartberger, Michael D. ;

Li, Vivian ;

Syed, Rashid ;

Jordan, Steven ;

Komorowski, Renee ;

Chen, Michelle M. ;

Cupples, Rod ;

Kim, Ki Won ;

St Jean, David J., Jr. ;

Johansson, Lars ;

Henriksson, Martin A. ;

Williams, Meredith ;

Vallgarda, Jerk ;

Fotsch, Christopher ;

Wang, Minghan .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (11) :4481-4487

[145] Potent ketoamide inhibitors of HCV NS3 protease derived from quaternized P1 groups [J].

Venkatraman, Srikanth ;

Velazquez, Francisco ;

Wu, Wanli ;

Blackman, Melissa ;

Madison, Vincent ;

Njoroge, F. George .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (07) :2151-2155

[146] Potent aza-peptide derived inhibitors of HCV NS3 protease [J].

Venkatraman, Srikanth ;

Wu, Wanli ;

Shih, Neng-Yang ;

Njoroge, F. George .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (16) :4760-4763

[147] 2-Arylureidophenyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)triazines as highly potent and selective ATP competitive mTOR inhibitors: Optimization of human microsomal stability [J].

Verheijen, Jeroen C. ;

Richard, David J. ;

Curran, Kevin ;

Kaplan, Joshua ;

Yu, Ker ;

Zask, Arie .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (08) :2648-2653

[148] Small Molecule Antagonist of Leukocyte Function Associated Antigen-1 (LFA-1): Structure-Activity Relationships Leading to the Identification of 6-((5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl)nicotinic Acid (BMS-688521) [J].

Watterson, Scott H. ;

Xiao, Zili ;

Dodd, Dharmpal S. ;

Tortolani, David R. ;

Vaccaro, Wayne ;

Potin, Dominique ;

Launay, Michele ;

Stetsko, Dawn K. ;

Skala, Stacey ;

Davis, Patric M. ;

Lee, Deborah ;

Yang, Xiaoxia ;

McIntyre, Kim W. ;

Balimane, Praveen ;

Patel, Karishma ;

Yang, Zheng ;

Marathe, Punk ;

Kadiyala, Pathanjali ;

Tebben, Andrew J. ;

Sheriff, Steven ;

Chang, ChiehYing Y. ;

Ziemba, Theresa ;

Zhang, Huiping ;

Chen, Bang-Chi ;

DelMonte, Albert J. ;

Aranibar, Nelly ;

McKinnon, Murray ;

Barrish, Joel C. ;

Suchard, Suzanne J. ;

Dhar, T. G. Murali .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (09) :3814-3830

[149] Oxetanes as promising modules in drug discovery [J].

Wuitschik, Georg ;

Rogers-Evans, Mark ;

Mueller, Klaus ;

Fischer, Holger ;

Wagner, Bjoern ;

Schuler, Franz ;

Polonchuk, Liudmila ;

Carreira, Erick M. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2006, 45 (46) :7736-7739

[150] Oxetanes in Drug Discovery: Structural and Synthetic Insights [J].

Wuitschik, Georg ;

Carreira, Erick M. ;

Wagner, Bjoern ;

Fischer, Holger ;

Parrilla, Isabelle ;

Schuler, Franz ;

Rogers-Evans, Mark ;

Mueller, Klaus .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (08) :3227-3246

← 8 9 10 11 12 13 14 15 16 17 →