Lanqi Jia

Publications (3)5.3 Total impact

• Article: Discovery of VTP-27999, an Alkyl Amine Renin Inhibitor with Potential for Clinical Utility

  Lanqi Jia, Robert D. Simpson, Jing Yuan, Zhenrong Xu, Wei Zhao, Salvacion Cacatian, Colin M. Tice, Joan Guo, Alexey Ishchenko, Suresh B. Singh, Zhongren Wu, Brian M. McKeever, Yuri Bukhtiyarov, Judith A. Johnson, Christopher P. Doe, Richard K. Harrison, Gerard M. McGeehan, Lawrence W. Dillard, John J. Baldwin, David A. Claremon
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  ABSTRACT: Structure guided optimization of a series of nonpeptidic alkyl amine renin inhibitors allowed the rational incorporation of additional polar functionality. Replacement of the cyclohexylmethyl group occupying the S1 pocket with a (R)-(tetrahydropyran-3-yl)methyl group and utilization of a different attachment point led to the identification of clinical candidate 9. This compound demonstrated excellent selectivity over related and unrelated off-targets, >15% oral bioavailability in three species, oral efficacy in a double transgenic rat model of hypertension, and good exposure in humans.Keywords: Renin; aspartyl protease; hypertension; structure-based drug design
  08/2011;
• Article: Biphenyl/diphenyl ether renin inhibitors: filling the S1 pocket of renin via the S3 pocket.

  Jing Yuan, Robert D Simpson, Wei Zhao, Colin M Tice, Zhenrong Xu, Salvacion Cacatian, Lanqi Jia, Patrick T Flaherty, Joan Guo, Alexey Ishchenko, [......], Jennifer Berbaum, Reshma Panemangalore, Ross Bentley, Christopher P Doe, Richard K Harrison, Gerard M McGeehan, Suresh B Singh, Lawrence W Dillard, John J Baldwin, David A Claremon
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  ABSTRACT: Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension.
  Bioorganic & medicinal chemistry letters 08/2011; 21(16):4836-43. · 2.65 Impact Factor
• Article: Optimization of orally bioavailable alkyl amine renin inhibitors.

  Zhenrong Xu, Salvacion Cacatian, Jing Yuan, Robert D Simpson, Lanqi Jia, Wei Zhao, Colin M Tice, Patrick T Flaherty, Joan Guo, Alexey Ishchenko, [......], Jennifer Mason, Reshma Panemangalore, Maria Grazia Cappiello, Ross Bentley, Christopher P Doe, Richard K Harrison, Gerard M McGeehan, Lawrence W Dillard, John J Baldwin, David A Claremon
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  ABSTRACT: Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC(50) of 0.83nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10mg/kg resulted in >20h reduction of blood pressure in a double transgenic rat model of hypertension.
  Bioorganic & medicinal chemistry letters 12/2009; 20(2):694-9. · 2.65 Impact Factor