64055-67-0Relevant academic research and scientific papers
Structure-Activity Relationship Studies of Tolfenpyrad Reveal Subnanomolar Inhibitors of Haemonchus contortus Development
Le, Thuy G.,Kundu, Abhijit,Ghoshal, Atanu,Nguyen, Nghi H.,Preston, Sarah,Jiao, Yaqing,Ruan, Banfeng,Xue, Lian,Huang, Fei,Keiser, Jennifer,Hofmann, Andreas,Chang, Bill C. H.,Garcia-Bustos, Jose,Wells, Timothy N. C.,Palmer, Michael J.,Jabbar, Abdul,Gasser, Robin B.,Baell, Jonathan B.
, p. 1036 - 1053 (2019/01/14)
Recently, we have discovered that the registered pesticide, tolfenpyrad, unexpectedly and potently inhibits the development of the L4 larval stage of the parasitic nematode Haemonchus contortus with an IC50 value of 0.03 μM while displaying good selectivity, with an IC50 of 37.9 μM for cytotoxicity. As a promising molecular template for medicinal chemistry optimization, we undertook anthelmintic structure-activity relationships for this chemical. Modifications of the left-hand side (LHS), right-hand side (RHS), and middle section of the scaffold were explored to produce a set of 57 analogues. Analogues 25, 29, and 33 were shown to be the most potent compounds of the series, with IC50 values at a subnanomolar level of potency against the chemotherapeutically relevant fourth larval (L4) stage of H. contortus. Selected compounds from the series also showed promising activity against a panel of other different parasitic nematodes, such as hookworms and whipworms.
5-HYDROXYPYRIMIDINE-4-CARBOXAMIDE COMPOUND
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, (2011/05/16)
The present invention provides compounds which promote erythropoietin production. Compounds represented by the following general formula (1) or pharmacologically acceptable salts thereof are provided: [wherein, R1 represents a group —X-Q1, X-Q1-Y-Q2 or X-Q1-Y-Q2-Z-Q3, X represents a single bond, —CH2— or the like, Q1 represents a monocyclic or bicyclic heterocyclic group which may have substituent(s), Y represents a single bond, —CH2—, or the like, Q2 represents a monocyclic or bicyclic hydrocarbon ring group which may have substituent(s) or a monocyclic or bicyclic heterocyclic group which may have substituent(s), Z represents a single bond, —CR11R12— or the like, R11 and R12 each independently represents a hydrogen atom, a halogen atom or the like, Q3 represents a phenyl group which may have substituent(s), a C3-C7 cycloalkyl group which may have substituent(s), a C3-C7 cycloalkenyl group which may have substituent(s) or a monocyclic or bicyclic heterocyclic group which may have substituent(s), R2 represents a C1-C3 alkyl group or the like, and R3 represents a hydrogen atom or a methyl group].
