Synthesis of 3-phenylpyrazolo[4,3-b]pyridines via a convenient synthesis of 4-amino-3-arylpyrazoles and SAR of corticotropin-Releasing factor receptor type-1 antagonists

doi:10.1016/S0960-894X(03)00621-8

Bioorganic & Medicinal Chemistry Letters

Volume 13, Issue 19, 16 October 2003, Pages 3367-3370

https://doi.org/10.1016/S0960-894X(03)00621-8 Get rights and content

Abstract

3-Phenylpyrazolo[4,3-b]pyridines were synthesized via a cyclization of 4-amino-3-phenylpyrazoles 11–13 with ethyl acetoacetate. These compounds were found to be potent CRF₁ antagonists. The 2-alkylpyrazolo[4,3-b]pyridines were more polar but less active than the corresponding 1-alkyl-isomers.

Graphic

Section snippets

Acknowledgements

We like to thank Mr. Zhengyu Liu for technical supports of this work.

References (19)

D.J Wustrow et al.
Bioorg. Med. Chem. Lett.
(1998)
P.J Gilligan et al.
Bioorg. Med. Chem.
(2000)
C Keller et al.
Drug Metab. Dispos.
(2002)
S.J Angyal et al.
J. Chem. Soc
(1952)
A Albert et al.
J. Chem. Soc.
(1948)
D.W Schulz et al.
PNAS
(1996)
D.E Grigoriadis et al.
Curr. Med. Chem.
(2001)
Wilcoxen, K.; Chen, C.; Huang, C.; Haddach, M.; Xie, M.; Wing, L.; Grigoriadis, D. E.; De Souza, E. B.; McCarthy, J. R....
Chen, C.; Wilcoxen, K.; Bozigian, H.; Chen, T.; Cha, M.; McCarthy, J. R.; Huang, C. H.; Haddach, M.; Zhu, Y. F.;...
Huang, C. Q.; Haddach, M.; Chen, C.; Wilcoxen, K. M.; Xie, Y.; Grigoriadis, D. E.; McCarthy, J. R. Book of Abstracts,...

There are more references available in the full text version of this article.

Cited by (17)

Recent Progress in the Synthesis of Pyrazolopyridines and Their Derivatives
2019, Organic Preparations and Procedures International
3D-QSAR study of corticotropin-releasing factor 1 antagonists and pharmacophore-based drug design
2010, Neurochemistry International
Corticotropin-releasing factor (CRF) is a neuropeptide that falls into the broad spectrum of having neurotransmitter/neurohormonal/neuromodulator activities. The design and synthesis of low molecular weight non-peptide antagonists for the CRF receptors is a very important area of research as they can be employed in the treatment of a wide variety of disorders. To investigate the ligand–receptor binding mode and design novel CRF1 antagonists, both quantitative and qualitative 3D-QSAR analysis have been performed on a data set of CRF₁ antagonists by using HypoGen and HipHopRefine programs of Catalyst software. The training set of HypoGen study included twenty-five structurally diverse CRF₁ antagonists with Ki values ranging from 0.5 nM to 10 μM. The common feature-based 3D-QSAR study used eight highly potent CRF₁ antagonists and four poor antagonistic ligands to generate 3D-pharmacophore models with excluded volumes. The obtained 3D-pharmacophore models from each study served as queries for virtual screening with a ‘focused compound library’ for novel CRF₁ antagonist development. Pharmacophore models obtained for antagonist binding are useful for CRF related chemical biology and drug design. Strategies and methods employed in this paper are simple and practical for medicinal chemists in drug R&D.
Chapter 6.3 Triazines, tetrazines and fused ring polyaza systems
2005, Progress in Heterocyclic Chemistry
This chapter provides an overview on the synthesis and reactions of Triazines, Tetrazines, and Fused Ring Polyaza Systems. This chapter describes the synthesis and biological activity of triazines and pyrimido. A general protocol for the rapid and high yield synthesis of diverse triazines, by microwave-assisted technology, has been developed. The structure and the use of Triazines as a ligand in coordination chemistry have been studied. Triazine derivatives having styryl or higher oligo chains in the 2, 4, and 6 positions have been described as star-shaped push-pull compounds. Derivatives of thienotriazine, thienoimidazotriazine, thienotriazolotriazine, and thienotetrazolotriazine have been discussed in the chapter.
Straightforward and Efficient Protocol for the Synthesis of Pyrazolo [4,3-b]pyridines and Indazoles
2023, International Journal of Molecular Sciences
Synthesis of 5-amino-1H-pyrazolo[4,3-b]pyridine derivatives and annulation of imidazole and pyrimidine rings thereto
2020, Chemistry of Heterocyclic Compounds
SO<inf>3</inf>H-functionalized MCM-41 as an efficient catalyst for the combinatorial synthesis of 1H-pyrazolo-[3,4-b]pyridines and spiro-pyrazolo-[3,4-b]pyridines
2017, Journal of the Iranian Chemical Society

View all citing articles on Scopus

View full text

Synthesis of 3-phenylpyrazolo[4,3-b]pyridines via a convenient synthesis of 4-amino-3-arylpyrazoles and SAR of corticotropin-Releasing factor receptor type-1 antagonists

Abstract

Section snippets

Acknowledgements

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem.

Drug Metab. Dispos.

J. Chem. Soc

J. Chem. Soc.

PNAS

Curr. Med. Chem.