New Spiro[cycloalkane-pyridazinone] Derivatives with Favorable Fsp3 Character

Csilla Sepsey Für,Hedvig Bölcskei

doi:10.3390/chemistry2040055

Csilla Sepsey Für, Hedvig Bölcskei

Open Access

https://doi.org/10.3390/chemistry2040055

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Journal: Chemistry	Publication Date: Oct 6, 2020
Citations: 3	License type: CC BY 4.0

Affiliation: Budapest University of Technology and Economics

Abstract

The large originator pharmaceutical companies need more and more new compounds for their molecule banks, because high throughput screening (HTS) is still a widely used method to find new hits in the course of the lead discovery. In the design and synthesis of a new compound library, important points are in focus nowadays: Lipinski’s rule of five (RO5); the high Fsp3 character; the use of bioisosteric heterocycles instead of aromatic rings. With said aim in mind, we have synthesized a small compound library of new spiro[cycloalkane-pyridazinones] with 36 members. The compounds with this new scaffold may be useful in various drug discovery projects.

Highlights

There are various methods used to find a hit that will later be a lead compound in the development of a new drug, a new chemical entity
High-throughput screening (HTS) [1,2] is a widely used method, which needs a large number of compounds
Pyridazinones were formed from isomeric γ-oxocarboxylic acids containing 1,1-disubstituted CcCyhheecmmloiissattrrlyyk22a00n22e00s, 22w, xxith hydrazine and hydrazine derivatives

Summary

Introduction

There are various methods used to find a hit that will later be a lead compound in the development of a new drug, a new chemical entity. Veber et al [6] suggested that the polar surface area should be smaller than 140 A2 and the number of rotatable bonds should be ten or less in an ideal case The fulfillment of these two criteria provides the opportunity for good oral bioavailability. Today these parameters are routinely studied to predict the drug candidates’ pharmacokinetics and ADME profiles [3]. Over the past decade there has been an increasing practice of creating structurally more complex molecules which are closer to natural materials and provide an opportunity to produce new types of compounds. Ppuubblliisshheedd aannootthheerr eexxaammppllee ffoorr tthhee ssyynntthheessiiss ooff ccoommppoouunnddss wwiitthh hhiigghh FFsspp cchhaarraacctteerr [[1100,,1111]]. Considering the advantages of compounds with high Fsp character, we have designed a compound library with a spiro[cycloalkane-pyridazinone] scaffold instead of the usual phenyl-pyridazinone derivatives

Synthesis of the Starting Materials

Formation of Pyridazinone Ring

N-Substituted Pyridazinone Derivatives

Conclusions