Spirocyclic Scaffolds in Medicinal Chemistry

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Spirocyclic Scaffolds in Medicinal Chemistry. / Hiesinger, Kerstin; Dar'In, Dmitry; Proschak, Ewgenij; Krasavin, Mikhail.

In: Journal of Medicinal Chemistry, Vol. 64, No. 1, 14.01.2021, p. 150-183.

Research output: Contribution to journal › Article › peer-review

Author

Hiesinger, Kerstin ; Dar'In, Dmitry ; Proschak, Ewgenij ; Krasavin, Mikhail. / Spirocyclic Scaffolds in Medicinal Chemistry. In: Journal of Medicinal Chemistry. 2021 ; Vol. 64, No. 1. pp. 150-183.

BibTeX

@article{4980d6d625cf444c95bbc57945d13bd4,

title = "Spirocyclic Scaffolds in Medicinal Chemistry",

abstract = "Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest in less planar bioactive compounds has given rise to the development of synthetic methodologies for the preparation of spirocyclic scaffolds. In this Perspective, we summarize the diverse synthetic routes to obtain spirocyclic systems. The impact of spirocycles on potency and selectivity, including the aspect of stereochemistry, is discussed. Furthermore, we examine the changes in physicochemical properties as well as in in vitro and in vivo ADME using selected studies that compare spirocyclic compounds to their nonspirocyclic counterparts. In conclusion, the value of spirocyclic scaffolds in medicinal chemistry is discussed. ",

keywords = "SMALL-MOLECULE INHIBITORS, RECEPTOR ANTAGONISTS, GPR40 AGONISTS, HIGH-AFFINITY, DISCOVERY, POTENT, FENSPIRIDE, OPTIMIZATION, PROLINE, DESIGN",

author = "Kerstin Hiesinger and Dmitry Dar'In and Ewgenij Proschak and Mikhail Krasavin",

year = "2021",

month = jan,

day = "14",

doi = "10.1021/acs.jmedchem.0c01473",

language = "English",

volume = "64",

pages = "150--183",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "1",

}

RIS

TY - JOUR

T1 - Spirocyclic Scaffolds in Medicinal Chemistry

AU - Hiesinger, Kerstin

AU - Dar'In, Dmitry

AU - Proschak, Ewgenij

AU - Krasavin, Mikhail

PY - 2021/1/14

Y1 - 2021/1/14

N2 - Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest in less planar bioactive compounds has given rise to the development of synthetic methodologies for the preparation of spirocyclic scaffolds. In this Perspective, we summarize the diverse synthetic routes to obtain spirocyclic systems. The impact of spirocycles on potency and selectivity, including the aspect of stereochemistry, is discussed. Furthermore, we examine the changes in physicochemical properties as well as in in vitro and in vivo ADME using selected studies that compare spirocyclic compounds to their nonspirocyclic counterparts. In conclusion, the value of spirocyclic scaffolds in medicinal chemistry is discussed.

AB - Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest in less planar bioactive compounds has given rise to the development of synthetic methodologies for the preparation of spirocyclic scaffolds. In this Perspective, we summarize the diverse synthetic routes to obtain spirocyclic systems. The impact of spirocycles on potency and selectivity, including the aspect of stereochemistry, is discussed. Furthermore, we examine the changes in physicochemical properties as well as in in vitro and in vivo ADME using selected studies that compare spirocyclic compounds to their nonspirocyclic counterparts. In conclusion, the value of spirocyclic scaffolds in medicinal chemistry is discussed.

KW - SMALL-MOLECULE INHIBITORS

KW - RECEPTOR ANTAGONISTS

KW - GPR40 AGONISTS

KW - HIGH-AFFINITY

KW - DISCOVERY

KW - POTENT

KW - FENSPIRIDE

KW - OPTIMIZATION

KW - PROLINE

KW - DESIGN

UR - http://www.scopus.com/inward/record.url?scp=85100069361&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/0b869082-7145-3e69-900f-dc750dcdd82e/

U2 - 10.1021/acs.jmedchem.0c01473

DO - 10.1021/acs.jmedchem.0c01473

M3 - Article

C2 - 33381970

AN - SCOPUS:85100069361

VL - 64

SP - 150

EP - 183

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 1

ER -

ID: 73598376