Optimization of orally bioavailable alkyl amine renin inhibitors

Journal Article · Fri Sep 17 00:00:00 EDT 2010 · Bioorg. Med. Chem. Lett.

DOI:https://doi.org/10.1016/j.bmcl.2009.11.066· OSTI ID:1002629

Xu, Zhenrong; Cacatian, Salvacion; Yuan, Jing; Simpson, Robert D; Jia, Lanqi; Zhao, Wei; Tice, Colin M; Flaherty, Patrick T; Guo, Joan; Ishchenko, Alexey; Singh, Suresh B; Wu, Zhongren; McKeever, Brian M; Scott, Boyd B; Bukhtiyarov, Yuri; Berbaum, Jennifer; Mason, Jennifer; Panemangalore, Reshma; Cappiello, Maria Grazia; Bentley, Ross ; Doe, Christopher P; Harrison, Richard K; McGeehan, Gerard M; Dillard, Lawrence W; Baldwin, John J; Claremon, David A ^[1]

---

1. Vitae

Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC{sub 50} of 0.83 nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10 mg/kg resulted in >20 h reduction of blood pressure in a double transgenic rat model of hypertension.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002629
• Journal Information: Bioorg. Med. Chem. Lett., Journal Name: Bioorg. Med. Chem. Lett. Journal Issue: (2) ; 01, 2010 Vol. 20; ISSN 0960-894X
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
AMINES
BLOOD PRESSURE
DESIGN
HYPERTENSION
IN VITRO
IN VIVO
LEAD COMPOUNDS
OPTIMIZATION
ORAL ADMINISTRATION
PLASMA
RENIN