Synthesis, biological evaluation and molecular modelling studies of methyleneimidazole substituted biaryls as inhibitors of human 17α-hydroxylase-17,20-lyase (CYP17). Part I: Heterocyclic modifications of the core structure

Jagusch, Carsten; Negri, Matthias; Hille, Ursula; Hu, Qingzhong; Bartels, Marc; Jahn-Hoffmann, Kerstin; Mendieta, Mariano A.E. Pinto-Bazurco; Rodenwaldt, Barbara; Müller‐Vieira, Ursula; Schmidt, Dirk

doi:10.1016/j.bmc.2007.10.094

Cited by 80 publications

(45 citation statements)

References 28 publications

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“…Such phenylboronic acids bearing electron withdrawing or amino groups have already been coupled on thiophene or benzothiophene rings following this methodology. However, these aromatics were seldom tetrasubstituted or the thiophene ring was not as electrodeficient as our substrate [27][28][29][30][31] . Interestingly, there is no report on palladium-catalyzed thiophene arylation with 4-vinyl phenylboronic acid.…”

Section: Solid-phase Synthesismentioning

confidence: 81%

New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis

Lethu

Bosc

Mouray

et al. 2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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Section: Solid-phase Synthesismentioning

confidence: 81%

New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis

Lethu

Bosc

Mouray

et al. 2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…1). 42 The safety, efficacy, and tolerability of AA were demonstrated in phase ½ trials administered either alone or with oral prednisone, with significant antitumour activity being reported in mCRPC patients who had previously received chemotherapy, such as docetaxel, and in those patients who were chemotherapy-naïve. [43][44][45][46] This led to further phase 3 evaluation of AA plus prednisone in both the pre-and post-docetaxel treatment setting.…”

Section: Abirateronementioning

confidence: 99%

Contemporary agents in the management of metastatic castration-resistant prostate cancer

Kapoor

Shayegan³

et al. 2016

CUAJ

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Docetaxel-based chemotherapy has been the standard of care for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Over the past few years, there has been a significant paradigm shift in the treatment landscape of this disease. A deeper understanding of prostate cancer biology, along with the development of novel agents has created hope towards treating chemotherapy-naïve and resistant disease. Following the implementation of docetaxel as the first-line therapy for mCRPC, five novel therapies have demonstrated survival benefit in mCRPC. Cabazitaxel, abiraterone acetate, and enzalutamide are three agents recently approved for the treatment of mCRPC, having shown overall survival benefit in patients previously treated with docetaxel, while both abiraterone acetate and enzalutamide have also shown promise in the pre-docetaxel setting. Sipuleucel-T has shown overall survival benefit in asymptomatic mCRPC, while radium-223 provides survival benefit to patients with mCRPC who are symptomatic from their skeletal metastases in both docetaxel-naïve patients and post-docetaxel patients. Denosumab, an anti-RANKL antibody, has been approved for the prevention of skeletal-related events in patients with prostate cancer bone metastases. This review examines the phase 3 trials supporting the use of theses novel agents in the treatment of mCRPC. While these agents provide incremental increases in patient survival, further study to determine the best choice, combination, and/or sequencing of administration is still necessary.

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“…Several active and less active compounds (C-ring: 6 -11 (R, S); Aring: 13 (R, S), 16, 17, 19 (R, S) and 21) were docked by means of the GOLD v 3.0.1 software [20] in the active site of our homology model of CYP17 [12].…”

Section: Molecular Modelling Studiesmentioning

confidence: 99%

“…Very recently [12], we found new highly potent and selective compounds, which showed better pharmacokinetic and pharmacodynamic profiles than abiraterone, a CYP17 inhibitor currently undergoing clinical phase II [13], by replacing the A-ring-mimicking benzene nucleus with different heterocycles.…”

Section: Introductionmentioning

confidence: 99%

CYP17 Inhibitors. Annulations of Additional Rings in Methylene Imidazole Substituted Biphenyls: Synthesis, Biological Evaluation and Molecular Modelling

Mendieta

Negri

et al. 2008

Archiv der Pharmazie

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Twenty-one novel compounds originating from two classes of annulated biphenyls were synthesized as mimetics of the steroidal A- and C-rings and examined for their potency as inhibitors of human CYP17. Selected compounds were tested for inhibition of the hepatic CYP enzyme 3A4. Potent CYP17 inhibitors were found for each class, compound 9 (17 and 71% at 0.2 and 2 microM, respectively) and 21 (591 nM). Compound 21 showed only weak inhibition of CYP3A4 (32 and 64% at 2 and 10 microM, respectively). Both compounds, however, exhibited moderate to strong inhibition of the glucocorticoid-forming enzyme CYP11B1. The most interesting compounds were docked into our protein model. They bound into one of the modes which we have previously published. New interaction regions were identified.

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Synthesis, biological evaluation and molecular modelling studies of methyleneimidazole substituted biaryls as inhibitors of human 17α-hydroxylase-17,20-lyase (CYP17). Part I: Heterocyclic modifications of the core structure

Cited by 80 publications

References 28 publications

New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis

New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis

Contemporary agents in the management of metastatic castration-resistant prostate cancer

CYP17 Inhibitors. Annulations of Additional Rings in Methylene Imidazole Substituted Biphenyls: Synthesis, Biological Evaluation and Molecular Modelling

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