Important Compound Classes
Title
Antimalarial Hexahydropyrimidine Analogues
Patent Publication Number
WO 2021/032687 A1
Publication Date
February 25, 2021
Priority Application
GB 1911865.2 and GB 1913759.5
Priority Date
August 19, 2019 and September 24, 2019
Inventors
De Haro Garcia, T.; Lowe, M. A.; Maccoss, M.; Taylor, R. D.; Zhu, Z.
Assignee Company
UCB Biopharma SRL, Belgium
Disease Area
Malaria
Biological Target
Plasmodium falciparum
Summary
Malaria is a mosquito-borne infectious disease caused by a parasite of the genus Plasmodium, which has devastating consequences. In 2010, an estimated 225 million cases were reported with 610 000–971 000 deaths, approximately 80% of which occurred in sub-Saharan Africa, mostly in young children (aged 5 or less).
The present application describes a series of novel hexahydropyrimidine compounds as potent inhibitors of the growth and propagation of the Plasmodium falciparum parasite in human blood and therefore beneficial for the treatment of malaria. Further, the application discloses compounds, their preparation, use, pharmaceutical composition, and treatment.
Definitions
W = C(O) or S(O)2;
Z = aryl or heteroaryl, either of which groups may be optionally substituted by one or more substituents;
R1 = C3–7 cycloalkyl, aryl(C1–6)alkyl, C3–7 heterocycloalkyl, C3–7 heterocycloalkyl(C1–6)alkyl, C4–9 heterobicycloalkyl, C4–9 spiroheterocycloalkyl or heteroaryl(C1–6)alkyl, any of which groups may be optionally substituted by one or more substituents; and
R2, R3, and R4 = H, halogen, or trifluoromethyl.
Key Structures
Biological Assay
The 3D7 asexual blood stage assay was performed. The compounds described in this application were tested for their ability to inhibit growth and propagation of the Plasmodium falciparum parasite in human blood. The IC50 (nM) are shown in the following Table.
Biological Data
The Table below shows representative
compounds were tested for their ability to inhibit growth and propagation
of the Plasmodium falciparum parasite in human blood.
The biological data obtained from testing representative examples
are listed in the following Table.
Claims
Total claims: 15
Compound claims: 12
Pharmaceutical composition claims: 1
Method of treatment claims: 1
Use of compound claims: 1
Recent Review Articles
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1.
Patel O. P. S.; Beteck R. M.; Legoabe L. J.. Eur. J. Med. Chem. 2021, 210, 113084.
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2.
Okombo J.; Kanai M.; Deni I.; Fidock D. A.. Trends Parasitol 2021, in press.
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3.
Li J.; Sun X.; Li J.; Yu F.; Zhang Y.; Huang X.; Jiang F.. Arch. Pharm. 2020, 353, 2000131.
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4.
Patel O. P. S.; Beteck R. M.; Legoabe L. J.. Eur. J. Med. Chem. 2021, 213, 113193.
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5.
Qin H.; Zhang Z.; Lekkala R.; Alsulami H.; Rakesh K. P.. Eur. J. Med. Chem. 2020, 193, 112215.
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6.
Tibon N. S.; Ng C. H.; Cheong S. L.. Eur. J. Med. Chem. 2020, 188, 111983.
The author declares no competing financial interest.