Sacubitril, also known as AHU377, is angiotensin receptor neprilysin inhibitor being studied for use in combination with valsartan for heart failure. Sacubitril is a prodrug that is activated to LBQ657 by de-ethylation via esterases. LBQ657 inhibits the enzyme neprilysin, which is responsible for the degradation of atrial and brain natriuretic peptide, two blood pressure lowering peptides that work mainly by reducing blood volume.
Zhang, Bo; Ding, Xiaohua; Dai, Dongcheng; Lei, Sijun; Liu, Xueming; Duan, Panpan; Chen, Yongkai; Wang, Chaodong. Preparation of crystal form and amorphous form of AHU-377 ammonium salt. WO 2018196860. (Wuhan Ll Science and Technology Development Co., Ltd., Peop. Rep. China; Wuhan Qr Pharmaceuticals Co., Ltd)
Thirumalai Rajan, Srinivasan; Eswaraiah, Sajja; Rajeshwar Reddy, Sagyam; Rajesham, Boge; Chakradhar, Nandigama; Srinivasa Rao, Ambati. Process for the preparation of trisodium sacubitril valsartan, its polymorphs, and solid dispersions thereof. WO 2017154017. (MSN Laboratories Private Limited, India)
Putapatri, Siddamal Reddy; Khairnar, Bhushan Balasaheb; Pandey, Gyanendra; Singh, Kaptan; Prasad, Mohan; Kumar, Ashok. Process for the preparation of sacubitril or salts thereof. WO 2017141193. (Sun Pharmaceutical Industries Limited, India)
Yan, Jie; Xu, Wenjie; Li, Song; Zheng, Yanxin; Zhi, Jianqiong. Process for preparation of angiotensin II receptor antagonist metabolite and nep inhibitor composite. WO 2017125031. (Process for preparation of angiotensin II receptor antagonist metabolite and nep inhibitor composite).
Halama, Ales; Zvatora, Pavel; Voslar, Michal; Stach, Jan; Zapadlo, Michal; Dammer, Ondrej; Krejcik, Lukas; Dvorakova, Lenka; Rezankova, Marketa; Vyslouzil, Rostislav. Preparation and characterization of sacubitril in crystal forms. WO 2017097275. (Zentiva, K.S., Czech Rep.)
Bodkhe, Arjun Rajaram; Maurya, Sadanand Hardeo; Samala, Rajamouli Srihari; Jagtap, Sunil Baburao; Joshi, Ashutosh Vijay; Luthra, Parven Kumar. Preparation of sacubitril and salt thereof and novel compounds used in the process. WO 2017033212. (Actavis Group Ptc Ehf., Iceland)
Halama, Ales; Zapadlo, Michal. Synthesis, Isolation, and Analysis of Stereoisomers of Sacubitril. Organic Process Research & Development. Volume 23. Issue 1. Pages 102-107. 2019.
Wang, Yun; Chen, Fen-Er; Shi, Yong; Tian, Wei-Sheng. Multigram scale, chiron-based synthesis of sacubitril. Tetrahedron Letters. Volume 57. Issue 52. Pages 5928-5930. 2016.
Yang, Fei; Wang, Chunjuan; Tong, Zhaolong; Yu, Hongping; Xu, Yaochang. Preparation of diaryl-substituted 4-amino-butyric acid derivatives as NEP inhibitors. Assignee Shanghai Hansoh Biomedical Co., Ltd., Peop. Rep. China; Jiangsu Hansoh Pharmaceutical Co., Ltd. WO 2014198195 A1. (2014).
Singh, Kumar Kamlesh; Diwakar, Santosh Devidas; Jadhav, Shankar Dada. Preparation of solid state forms of trisodium salt of valsartan/sacubitril complex and sacubitril sodium. Assignee Cadila Healthcare Limited, India. IN 2015MU02655 A. (2017).
