Chemfiles Volume 4 Article 8

Privileged Structures: Indoles

Sigma-Aldrich is proud to offer a new series of ChemFiles—called Privileged Structures, to our Drug Discovery and Organic Synthesis customers. Each piece will highlight a specific motif, selected applications, and the range of products Sigma-Aldrich offers in this area. Our first installment focuses on the indole scaffold. In the future we will be highlighting other medicinally relevant cores and other selected drug-relevant building blocks. We trust you will find these pieces useful, and we welcome your comments for future installments. If you do not see a particular product or wish to have us synthesize one for you, please email us at

Privileged structures are described as a class of molecules capable of binding to multiple receptors with high affinity.1 Utilization of these molecules enables the medicinal chemist to rapidly determine biologically active compounds across a wide range of therapeutic areas. In practice, the medicinal chemist will often choose to synthesize one library based upon one core scaffold and screen it against a variety of receptors, yielding several active compounds. In order to be considered privileged, a substructure should represent a molecule’s core element and make up a significant portion of its total mass.

The privileged structure highlighted in this ChemFile is the indole scaffold. The indole substructure is a basic element for a number of biologically active natural and synthetic products. Since January 2003, there have been more than 400 drugs and 3000 patents in which the indole motif has been present. The range of applications for these therapeutically relevant compounds includes protein kinase C inhibitors, 5-HT agonists, melatonin agonists, and glucocorticoid receptor modulators.

Protein kinase C inhibitor shown to be useful treatment for cardiovascular diseases, diabetes, respiratory disorders, and autoimmune disease2

5-HT agonist useful for treatment of neurological and cognitive disorders3

Melatonin agonist useful treatment for strokes4

Glucocorticoid receptor modulator useful for treatment of hypertension, arrhythmias, and myocardial infarction5

(C4,780-9)(B 2761)Histamine H4 receptor antagonists6

(28,628-1)Potent Cyclin D1-CDK4 Inhibitor7

Listed on the following pages is a selection of indoles available from Sigma-Aldrich. For a complete list of indoles, please visit our Web site at under the Drug Discovery Product lines.

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  1. Chem. Rev. 2003, 103, 893–930
  2. Novartis AG., Patent number WO-2004072062
  3. Suven Life Sciences Limited, WO-2004048330
  4. The University of Hong Kong, Ultra Biotech Ltd., WO-2004066995
  5. Eli Lilly and Company, WO-2004067529
  6. Bioorganic & Medicinal Chemistry Letter 2004, 14, 5251–5256
  7. J. Med. Chem. 2003, 46, 2027–2030

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