Novel pyrrole-containing progesterone receptor modulators

Collins, Matthew A.; Hudak, Valerie; Bender, Reinhold; Fensome, Andrew; Zhang, Puwen; Miller, Lori L.; Winneker, Richard C.; Zhang, Zhiming; Zhu, Yuan; Cohen, Jeffrey; Unwalla, Rayomond J.; Wrobel, Jay

doi:10.1016/j.bmcl.2004.02.054

Cited by 55 publications

(31 citation statements)

References 10 publications

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“…The methods include the CuCl-mediated reaction of aryl nitriles with (methylamino)acetaldehyde dimethyl acetal, [18] the van Leusen chemistry of a tosmic reagent, [8j] the Pd-catalyzed Suzuki reaction of arylboronic acids with 5-bromo-1-methyl-1H-imidazole, [19] and the Pd-catalyzed direct C-5 arylation of 1-methyl-1H-imidazole (7) with aryl halides. [20] The latter methodology offers a number of advantages over the other procedures, including convenience, simplicity, and the use of readily available starting materials, but the different protocols used thus far to perform the direct arylation reaction met with limited success because of modest yields, [20a,b,d] low regioselectivity, [20b,d] and the use of electrophiles represented exclusively by activated aryl halides.…”

Section: Synthesis Of 5-aryl-1-methyl-1h-imidazolesmentioning

confidence: 99%

Regioselective Synthesis of 4,5‐Diaryl‐1‐methyl‐1H‐imidazoles Including Highly Cytotoxic Derivatives by Pd‐Catalyzed Direct C‐5 Arylation of 1‐Methyl‐1H‐imidazole with Aryl Bromides

et al. 2008

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A general and efficient three-step procedure for the highly regioselective synthesis of 1-methyl-1H-imidazoles possessing electron-rich, electron-neutral and/or electron-deficient aryl moieties at their 4- and 5-position is described. The first step involves the Pd-catalyzed direct C-5 arylation of commercially available 1-methyl-1H-imidazole with aryl bromides and the second and third step of the sequence involve the selective C-4 bromination of the resulting 5-aryl-1-methyl-1H-imidazoles with NBS followed by a PdCl2(dppf)-catalyzed Suzuki-type reaction between 5-aryl-4-bromo-1-methyl-1H-imidazoles and arylboronic acids under phase-transfer conditions. Two so prepared 4,5-diaryl-1-methyl-1H-imidazoles, which can be regarded as Z-restricted analogues of naturally-occurring combretastatin A-4 (CA-4), have proven to be highly cytotoxic against a variety of human tumor cell lines and one of these derivatives has been shown to be more cytotoxic than CA-4 and all of the imidazole derivatives investigated in the literature so far

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Section: Synthesis Of 5-aryl-1-methyl-1h-imidazolesmentioning

confidence: 99%

Regioselective Synthesis of 4,5‐Diaryl‐1‐methyl‐1H‐imidazoles Including Highly Cytotoxic Derivatives by Pd‐Catalyzed Direct C‐5 Arylation of 1‐Methyl‐1H‐imidazole with Aryl Bromides

et al. 2008

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“…Three sesquiterpenoids (20)(21)(22) were isolated from the culture broth of Penicillium oblatum which showed to have in vitro affinity for the progesterone receptor. The compound with an acyl group on R2 (20; PF1092A) was the most active compound and showed an IC 50 of 18 nM on the porcine progesterone receptor.…”

Section: Medicinal Chemistrymentioning

confidence: 99%

Non-Steroidal Steroid Receptor Modulators

Buijsman¹,

Hermkens²,

Rijn³

et al. 2005

CMC

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The last ten years much attention has been focused on the finding of non-steroidal ligands for steroidal nuclear receptors for reasons such as diminishing cross-reactivity to eliminate side effect profiles, changing physicochemical properties which might cause different tissue distribution profiles and altering binding modes which influence the binding of cofactors. Compounds with a selective functionality profile are referred to as selective nuclear receptor modulators (e.g., SARMs or SPRMs). In the following paragraphs non-steroidal ligands which have full or partial agonistic activity will be described for the following receptors: PR, GR, AR, LXR and FXR.

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“…So far, nitrogen-containing heterocycles fused with an arylsubstituted benzene ring, such as compounds 3 and 4, have been widely studied. [43][44][45][46][47] Considering the structures of these non-steroidal PR ligands, we thought that bicyclic 6-arylcoumarin would be an alternative scaffold. Coumarin is one of widely used fluorophore, and the fluorescence properties of its derivatives are known to depend upon the nature and position of substituents.…”

Section: Fluorescent Progesterone Receptor Ligands Based On the Coumamentioning

confidence: 99%

Development of Functional Molecules for Elucidation of the Physiological Roles of Several Nuclear Receptors and Their Endogenous Ligands

Hirano

2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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Nuclear receptors and their endogenous ligands are involved in key biological functions, including development, homeostasis and metabolism, and functional molecules that can modulate receptor activities are of interest for basic research to elucidate the signaling pathways, as well as having potential therapeutic applications. Here, we summarize our recent work on the development of nuclear receptor ligands, focusing on thyroid hormone receptor (TR) antagonists, fluorescent ligands for progesterone receptors (PR), and inhibitors of histone methyltransferase (HMT). We have developed a series of potent TR antagonists bearing a thiazolidinedione group as a bioisoster of a polar amino acid group. Utilizing our library of fluorescent coumarin derivatives, we obtained a PR antagonist that exhibits fluorescence enhancement upon binding to PR. We also developed a series of HMT inhibitors based on the structure of adenosylmethionine (AdoMet), a cofactor in the methylation reaction, by introducing various alkylamino groups onto the nitrogen atom in place of the sulfur atom of AdoMet. Our compounds should be useful in functional analysis of these nuclear receptors and investigations of their signaling pathways.

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Novel pyrrole-containing progesterone receptor modulators

Cited by 55 publications

References 10 publications

Regioselective Synthesis of 4,5‐Diaryl‐1‐methyl‐1H‐imidazoles Including Highly Cytotoxic Derivatives by Pd‐Catalyzed Direct C‐5 Arylation of 1‐Methyl‐1H‐imidazole with Aryl Bromides

Regioselective Synthesis of 4,5‐Diaryl‐1‐methyl‐1H‐imidazoles Including Highly Cytotoxic Derivatives by Pd‐Catalyzed Direct C‐5 Arylation of 1‐Methyl‐1H‐imidazole with Aryl Bromides

Non-Steroidal Steroid Receptor Modulators

Development of Functional Molecules for Elucidation of the Physiological Roles of Several Nuclear Receptors and Their Endogenous Ligands

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