Qingzhong Hu

Summary

Affiliation: Saarland University
Country: Germany

Publications

  1. doi request reprint Selective dual inhibitors of CYP19 and CYP11B2: targeting cardiovascular diseases hiding in the shadow of breast cancer
    Qingzhong Hu
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, P O Box 151150, D 66123 Saarbrucken, Germany
    J Med Chem 55:7080-9. 2012
  2. doi request reprint CYP17 inhibitors. Annulations of additional rings in methylene imidazole substituted biphenyls: synthesis, biological evaluation and molecular modelling
    Mariano A E Pinto-Bazurco Mendieta
    Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrucken, Germany
    Arch Pharm (Weinheim) 341:597-609. 2008
  3. doi request reprint Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17)--part II: Core rigidification and influence of substituents at the methylene bridge
    Qingzhong Hu
    Pharmaceutical and Medicinal Chemistry, Saarland University, PO Box 151150, D 66041 Saarbrucken, Germany
    Bioorg Med Chem 16:7715-27. 2008
  4. doi request reprint Novel CYP17 inhibitors: synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls
    Ulrike E Hille
    Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrucken, Germany
    Eur J Med Chem 44:2765-75. 2009
  5. doi request reprint Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prostate cancer
    Qingzhong Hu
    Pharmaceutical and Medicinal Chemistry and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Saarland University, Saarbrucken, Germany
    J Med Chem 53:5749-58. 2010
  6. doi request reprint Novel imidazol-1-ylmethyl substituted 1,2,5,6-tetrahydropyrrolo[3,2,1-ij]quinolin-4-ones as potent and selective CYP11B1 inhibitors for the treatment of Cushing's syndrome
    Lina Yin
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, D 66123 Saarbrucken, Germany
    J Med Chem 55:6629-33. 2012
  7. doi request reprint Tetrahydropyrroloquinolinone type dual inhibitors of aromatase/aldosterone synthase as a novel strategy for breast cancer patients with elevated cardiovascular risks
    Lina Yin
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, D 66123 Saarbrucken, Germany
    J Med Chem 56:460-70. 2013
  8. pmc 3-Pyridyl substituted aliphatic cycles as CYP11B2 inhibitors: aromaticity abolishment of the core significantly increased selectivity over CYP1A2
    Lina Yin
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Saarbrucken, Germany
    PLoS ONE 7:e48048. 2012
  9. doi request reprint Highly potent and selective nonsteroidal dual inhibitors of CYP17/CYP11B2 for the treatment of prostate cancer to reduce risks of cardiovascular diseases
    Mariano A E Pinto-Bazurco Mendieta
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, D 66123 Saarbrucken, Germany
    J Med Chem 56:6101-7. 2013
  10. doi request reprint Novel pyridyl substituted 4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines as potent and selective aldosterone synthase inhibitors with improved in vitro metabolic stability
    Qingzhong Hu
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, D 66123, Saarbrucken, Germany
    J Med Chem 58:2530-7. 2015

Collaborators

  • Rolf W Hartmann
  • Sureyya Olgen
  • Andrea Cavalli
  • Uli Kazmaier
  • Maurizio Recanatini
  • Lina Yin
  • Mariano A E Pinto-Bazurco Mendieta
  • Cornelia M Grombein
  • Ulrike E Hille
  • Juliette Emmerich
  • Matthias Negri
  • Thomas Lauterbach
  • Ursula Müller-Vieira
  • Carsten Jagusch
  • Christina Zimmer
  • Sabrina Rau
  • Weixing Zhu
  • Nina Hanke
  • Sebastian J Krug
  • Marc Bartels
  • Dirk Schmidt
  • Kerstin Jahn-Hoffmann
  • Ralf Heim
  • Amjad Ali
  • Michael Man Chu Lo
  • Edward Metzger
  • Chris J van Koppen
  • Matthias Engel
  • Simon Lucas
  • Frauke Maurer
  • Carsten Vock
  • Barbara Rodenwaldt

Detail Information

Publications22

  1. doi request reprint Selective dual inhibitors of CYP19 and CYP11B2: targeting cardiovascular diseases hiding in the shadow of breast cancer
    Qingzhong Hu
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, P O Box 151150, D 66123 Saarbrucken, Germany
    J Med Chem 55:7080-9. 2012
    ..These compounds showed also good selectivity toward CYP11B1 (selectivity factors (IC(50 CYP11B1)/IC(50 CYP11B2)) around 50) and CYP17 (no inhibition)...
  2. doi request reprint CYP17 inhibitors. Annulations of additional rings in methylene imidazole substituted biphenyls: synthesis, biological evaluation and molecular modelling
    Mariano A E Pinto-Bazurco Mendieta
    Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrucken, Germany
    Arch Pharm (Weinheim) 341:597-609. 2008
    ..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...
  3. doi request reprint Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17)--part II: Core rigidification and influence of substituents at the methylene bridge
    Qingzhong Hu
    Pharmaceutical and Medicinal Chemistry, Saarland University, PO Box 151150, D 66041 Saarbrucken, Germany
    Bioorg Med Chem 16:7715-27. 2008
    ..Using our CYP17 homology protein model, docking studies with selected compounds were performed to study possible interactions between inhibitors and amino acid residues of the active site...
  4. doi request reprint Novel CYP17 inhibitors: synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls
    Ulrike E Hille
    Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrucken, Germany
    Eur J Med Chem 44:2765-75. 2009
    ..Docking studies using our CYP17 protein model were performed with selected compounds to study the interactions between the inhibitors and the amino acid residues of the active site...
  5. doi request reprint Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prostate cancer
    Qingzhong Hu
    Pharmaceutical and Medicinal Chemistry and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Saarland University, Saarbrucken, Germany
    J Med Chem 53:5749-58. 2010
    ....
  6. doi request reprint Novel imidazol-1-ylmethyl substituted 1,2,5,6-tetrahydropyrrolo[3,2,1-ij]quinolin-4-ones as potent and selective CYP11B1 inhibitors for the treatment of Cushing's syndrome
    Lina Yin
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, D 66123 Saarbrucken, Germany
    J Med Chem 55:6629-33. 2012
    ..2 nM) than leads and more selective (SF = 11) than I and metyrapone. Since it also showed potent inhibition of rat CYP11B1 and good selectivity over human CYP17 and CYP19, it is a promising candidate for further development...
  7. doi request reprint Tetrahydropyrroloquinolinone type dual inhibitors of aromatase/aldosterone synthase as a novel strategy for breast cancer patients with elevated cardiovascular risks
    Lina Yin
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, D 66123 Saarbrucken, Germany
    J Med Chem 56:460-70. 2013
    ..This compound is considered as a candidate for further evaluation in vivo...
  8. pmc 3-Pyridyl substituted aliphatic cycles as CYP11B2 inhibitors: aromaticity abolishment of the core significantly increased selectivity over CYP1A2
    Lina Yin
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Saarbrucken, Germany
    PLoS ONE 7:e48048. 2012
    ..The design conception demonstrated in this study can be helpful in the optimization of CYP inhibitor drugs regarding CYP1A2 selectivity...
  9. doi request reprint Highly potent and selective nonsteroidal dual inhibitors of CYP17/CYP11B2 for the treatment of prostate cancer to reduce risks of cardiovascular diseases
    Mariano A E Pinto-Bazurco Mendieta
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, D 66123 Saarbrucken, Germany
    J Med Chem 56:6101-7. 2013
    ..These compounds are considered as promising candidates for further in vivo evaluation. ..
  10. doi request reprint Novel pyridyl substituted 4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines as potent and selective aldosterone synthase inhibitors with improved in vitro metabolic stability
    Qingzhong Hu
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, D 66123, Saarbrucken, Germany
    J Med Chem 58:2530-7. 2015
    ..Compound 26 not only exhibited a much longer half-life (t1/2 ≫ 120 min), but also sustained inhibitory potency (IC50 = 4.2 nM) and selectivity over CYP11B1 (SF = 422), CYP17, CYP19, and a panel of hepatic CYP enzymes. ..
  11. doi request reprint The role of fluorine substitution in biphenyl methylene imidazole-type CYP17 inhibitors for the treatment of prostate carcinoma
    Qingzhong Hu
    Pharmaceutical and Medicinal Chemistry, Saarland University, PO Box 151150 and Helmholtz Institute for Pharmaceutical Research, Saarland HIPS, 66041 Saarbrucken, Germany
    ChemMedChem 5:899-910. 2010
    ..The SARs obtained confirm the reliability of the protein model; compound 9 (IC(50)=131 nM) was identified as a strong CYP17 inhibitor, showing potent activity in rat, high bioavailability, and a long plasma half-life: 12.8 h...
  12. doi request reprint Cushing's syndrome: development of highly potent and selective CYP11B1 inhibitors of the (pyridylmethyl)pyridine type
    Juliette Emmerich
    Pharmaceutical and Medicinal Chemistry, Saarland University, and Department of Drug Design and Optimization, Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, 66123 Saarbrucken, Germany
    J Med Chem 56:6022-32. 2013
    ..Investigation of cytotoxicity and inhibition of hepatic CYP2A6 and CYP3A4 showed that 44 fulfills first safety criteria and can be considered for further in vivo evaluation in rats. ..
  13. doi request reprint Heteroatom insertion into 3,4-dihydro-1H-quinolin-2-ones leads to potent and selective inhibitors of human and rat aldosterone synthase
    Cornelia M Grombein
    Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, D 66123 Saarbrucken, Germany
    Eur J Med Chem 90:788-96. 2015
    ..Thus, we discovered compounds 4 and 9 which show potent inhibition of hCYP11B2 (IC50 < 1 nM) and the corresponding rat enzyme (4: 64%, 9: 51% inhibition, at 2 μM)...
  14. doi request reprint Hits identified in library screening demonstrate selective CYP17A1 lyase inhibition
    Sebastian J Krug
    Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, 66123 Saarbrucken, Germany
    J Steroid Biochem Mol Biol 134:75-9. 2013
    ..Hits identified within this novel assay demonstrated selective inhibition of CYP17A1 lyase activity, and thus mark the basis for the development of selective C(17,20)-lyase inhibitors for the treatment of prostate cancer...
  15. doi request reprint Novel pyridyl- or isoquinolinyl-substituted indolines and indoles as potent and selective aldosterone synthase inhibitors
    Lina Yin
    Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, D 66123 Saarbrucken, Germany
    J Med Chem 57:5179-89. 2014
    ..Because of these advantageous profiles, compounds 14 and 23 are considered to be candidates for further in vivo evaluation...
  16. pmc Recent progress in pharmaceutical therapies for castration-resistant prostate cancer
    Lina Yin
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, Saarbrücken D 66123, Germany
    Int J Mol Sci 14:13958-78. 2013
    ....
  17. doi request reprint Potent 11β-hydroxylase inhibitors with inverse metabolic stability in human plasma and hepatic S9 fractions to promote wound healing
    Weixing Zhu
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, D 66123 Saarbrucken, Germany
    J Med Chem 57:7811-7. 2014
    ..It showed no inhibition of CYP17 and CYP19 and no mutagenic effects. It exhibited inverse metabolic stability in plasma (t1/2 ≫ 150 min), which is similar to wound fluid in composition, and in liver S9 fractions (t1/2 = 16 min). ..
  18. doi request reprint Aldosterone synthase inhibitors as promising treatments for mineralocorticoid dependent cardiovascular and renal diseases
    Qingzhong Hu
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Campus C2 3, D 66123 Saarbrucken, Germany
    J Med Chem 57:5011-22. 2014
    ..Recently, much more selective CYP11B2 inhibitors have been reported, which could be promising drug candidates for the treatment of aldosterone related diseases. ..
  19. doi request reprint 1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols: a new class of potent and selective aldosterone synthase inhibitors
    Cornelia M Grombein
    Pharmaceutical and Medicinal Chemistry, Saarland University and Helmholtz Institute for Pharmaceutical Research Saarland HIPS, Saarland University, Campus C2 3, D 66123 Saarbrucken, Germany
    Eur J Med Chem 89:597-605. 2015
    ..The most potent compound (IC50 = 14 nM) discovered was the meta-trifluoromethoxy derivative 11, which also exhibited excellent selectivity toward CYP11B1 (SF = 415), and showed no inhibition of CYP17 and CYP19...
  20. doi request reprint Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors
    Qingzhong Hu
    Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C23, D 66123 Saarbrucken, Germany
    J Med Chem 53:5049-53. 2010
    ....
  21. ncbi request reprint Synthesis, biological evaluation and molecular modelling studies of methyleneimidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17). Part I: Heterocyclic modifications of the core structure
    Carsten Jagusch
    Pharmaceutical and Medicinal Chemistry, Saarland University, PO Box 151150, D 66041 Saarbrucken, Germany
    Bioorg Med Chem 16:1992-2010. 2008
    ..5 h vs 1.6 h). Docking studies revealed two new binding modes different from the one of the substrates and steroidal inhibitors...
  22. doi request reprint CYP17 inhibitors--abiraterone, C17,20-lyase inhibitors and multi-targeting agents
    Lina Yin
    Department of Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, D 66123 Saarbrucken, Germany
    Nat Rev Urol 11:32-42. 2014
    ..Some of these strategies-including the drugs orteronel, VT-464 and galeterone--are supported by preclinical data and are being explored in the clinic...