Discovery of 6-chloro-2-trifluoromethyl-7-aryl-7H-imidazo[1,2-a]imidazol-3-ylmethylamines, a novel class of corticotropin-releasing factor receptor type 1 (CRF1R) antagonists

Zuev, Dmitry; Vrudhula, Vivekananda M.; Michne, Jodi A.; Dasgupta, Bireshwar; Pin, Sokhom S.; Huang, Xiaohua; Wu, Dedong; Gao, Qi; Zhang, Jie; Taber, Matthew T.; Macor, John E.; Dubowchik, Gene M.

doi:10.1016/j.bmcl.2010.04.094

Cited by 7 publications

(3 citation statements)

References 18 publications

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“…Other conditions (base, solvents) were tested in order to change the selectivity of the reaction, which turned out to be unsuccessful 11. Without further separation, 5a and 5b were engaged in an intramolecular silver salt assisted cyclisation performed in tetramethylene sulfone at 150 °C during 12 h2c according to the conditions of Zuev and Dubowchik's group. Unfortunately, the totality of the starting material was recovered, leading us to develop a different and innovative strategy.…”

Section: Resultsmentioning

confidence: 99%

Access to Imidazo[1,2‐a]imidazolin‐2‐ones and Functionalization through Suzuki–Miyaura Cross‐Coupling Reactions

Grosse¹,

Pillard²,

Himbert³

et al. 2013

Eur J Org Chem

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We report herein a synthetic pathway to new 6(5)‐bromo‐5(6)‐methylimidazo[1,2‐a]imidazolin‐2‐ones. The synthetic potential of these scaffolds was demonstrated by displacing bromine by Suzuki–Miyaura cross‐coupling reactions. A large panel of boronic acids (aryl, heteroaryl or vinyl) could easily be introduced, giving access to a large and diversified library of 6(5)‐substituted 5(6)‐methylimidazo[1,2‐a]imidazolin‐2‐ones.

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Section: Resultsmentioning

confidence: 99%

Access to Imidazo[1,2‐a]imidazolin‐2‐ones and Functionalization through Suzuki–Miyaura Cross‐Coupling Reactions

Grosse¹,

Pillard²,

Himbert³

et al. 2013

Eur J Org Chem

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“…The imidazo-imidazole scaffolds hold a special place in this category, since they are found in compounds showing a wide range of pharmaceutical activities. In particular, they have been described as antifungal (Lila et al, 2003), antithrombotic (Imaeda et al, 2008; Fujimoto et al, 2009), anxiolytic and anti-depressive agents (Han et al, 2005; Tellew and Luo, 2008; Zuev et al, 2010). In addition, they have been reported as androgen receptor agonists and antagonists that are useful in the treatment of a variety of disorders (Zhang et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Development of Novel and Efficient Processes for the Synthesis of 5-Amino and 5-Iminoimidazo[1,2-a]imidazoles via Three-Component Reaction Catalyzed by Zirconium(IV) Chloride

et al. 2019

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General and efficient approaches for the synthesis of new 5-amino and 5-iminoimidazo[1,2- a ]imidazoles were developed through a three-component reaction of 1-unsubstituted 2-aminoimidazoles with various aldehydes and isocyanides mediated by zirconium(IV) chloride. The protocols were established considering the reactivity of the starting substrate, which varies depending on the presence of a substituent on the 2-aminoimidazole moiety. A library of new N-fused ring systems with wide structural diversification, novel synthetic, and potential pharmacological interest was obtained in moderate to good yields.

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“…Recently, our group made significant efforts to discover a new synthetic route and study the chemical reactivity of [5–5]fused ring systems . In particular, the imidazo[1,2- a ]imidazole unit has been studied as a CRF 1 R antagonist involved in diseases such as depression and anxiety …”

Section: Introductionmentioning

confidence: 99%

Ligandless Palladium-Catalyzed Regioselective Direct C–H Arylation of Imidazo[1,2-a]imidazole Derivatives

Grosse

Pillard²,

Massip

et al. 2015

J. Org. Chem.

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Herein a novel access to functionalizable 6-substituted imidazo[1,2-a]imidazole scaffolds is described. The reactivity of this heterobicyclic unit toward direct C-H arylation was studied, and conditions allowing regioselective arylation at position 3 were successfully developed. The practicability of this method is manifested by the ligandless conditions and low catalyst loading. The strategy is functional group tolerant and provides rapid access to a large variety of 3,6-di(hetero)arylated imidazo[1,2-a]imidazole derivatives. A second arylation at position 2 was then carried out, and a library of diversified 2,3,6-tri(hetero)arylated imidazo[1,2-a]imidazoles was generated in good yields. A one-pot, two-step procedure was finally developed.

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Discovery of 6-chloro-2-trifluoromethyl-7-aryl-7H-imidazo[1,2-a]imidazol-3-ylmethylamines, a novel class of corticotropin-releasing factor receptor type 1 (CRF1R) antagonists

Cited by 7 publications

References 18 publications

Access to Imidazo[1,2‐a]imidazolin‐2‐ones and Functionalization through Suzuki–Miyaura Cross‐Coupling Reactions

Access to Imidazo[1,2‐a]imidazolin‐2‐ones and Functionalization through Suzuki–Miyaura Cross‐Coupling Reactions

Development of Novel and Efficient Processes for the Synthesis of 5-Amino and 5-Iminoimidazo[1,2-a]imidazoles via Three-Component Reaction Catalyzed by Zirconium(IV) Chloride

Ligandless Palladium-Catalyzed Regioselective Direct C–H Arylation of Imidazo[1,2-a]imidazole Derivatives

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Discovery of 6-chloro-2-trifluoromethyl-7-aryl-7H-imidazo[1,2-a]imidazol-3-ylmethylamines, a novel class of corticotropin-releasing factor receptor type 1 (CRF1R) antagonists

Cited by 7 publications

References 18 publications

Access to Imidazo[1,2‐a]imidazolin‐2‐ones and Functionalization through Suzuki–­Miyaura Cross‐Coupling Reactions

Access to Imidazo[1,2‐a]imidazolin‐2‐ones and Functionalization through Suzuki–­Miyaura Cross‐Coupling Reactions

Development of Novel and Efficient Processes for the Synthesis of 5-Amino and 5-Iminoimidazo[1,2-a]imidazoles via Three-Component Reaction Catalyzed by Zirconium(IV) Chloride

Ligandless Palladium-Catalyzed Regioselective Direct C–H Arylation of Imidazo[1,2-a]imidazole Derivatives

Contact Info

Product

Resources

About

Access to Imidazo[1,2‐a]imidazolin‐2‐ones and Functionalization through Suzuki–Miyaura Cross‐Coupling Reactions

Access to Imidazo[1,2‐a]imidazolin‐2‐ones and Functionalization through Suzuki–Miyaura Cross‐Coupling Reactions