Neurokinin-1 receptor antagonists: a comprehensive patent survey.
BACKGROUND
Substance P is involved in mediating a number of biological effects such as emesis, pain, inflammation, bronchoconstriction, antitumor activity, and regulation of gastrointestinal and CNS function by binding to the neurokinin-1 (NK1) receptor. Antagonists of this receptor have the potential to be useful in the treatment of various disease conditions.


METHODS
More than 300 patents have been filed by nearly 20 companies and 2 academic institutions in the past 2 decades. This review provides an overview of the patenting activity in the NK1 antagonist field over the last 20 years.


RESULTS
Chemically diverse non-peptide NK1 receptor antagonists have been identified since the discovery of CP-96,345 by Pfizer in 1991. Representative examples of patented ligands and their biological activities are presented in a company-wise approach.


CONCLUSIONS
The NK1 receptor research has led to the clinical introduction of aprepitant in 2003 and its water soluble injectable form, fosaprepitant dimeglumine, in 2009 by Merck for the prevention of postoperative nausea and vomiting and for inhibiting chemotherapy-induced nausea and vomiting. In addition, maropitant citrate received approval in 2007 for veterinary use.
Millennium: The Takeda Oncology Company, Cambridge, MA 02139, USA.
Shih-Chung
SC
Huang
Vijaya L
VL
Korlipara
D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D006801:Humans; D008969:Molecular Sequence Data; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010330:Patents as Topic; D011487:Protein Conformation; D018040:Receptors, Neurokinin-1 / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D013373:Substance P / Q000378:metabolism
D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; D018040:Receptors, Neurokinin-1; D013373:Substance P