(+)-SJ733   Click here for help

GtoPdb Ligand ID: 9723

Synonyms: (+)-SJ000557733 | (+)-SJ557733
Antimalarial Ligand
Compound class: Synthetic organic
Comment: (+)-SJ733 is the optimized lead for the dihydroisoquinolones (DHIQ), a novel chemotype with antimalarial activity [2].
The (+)-enantiomer, shown here, has a significantly higher antimalarial potency [2].

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 86.09
Molecular weight 468.12
XLogP 3.8
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES N#Cc1cc(ccc1F)NC(=O)C1c2ccccc2C(=O)N(C1c1cccnc1)CC(F)(F)F
Isomeric SMILES N#Cc1cc(ccc1F)NC(=O)[C@H]1c2ccccc2C(=O)N([C@@H]1c1cccnc1)CC(F)(F)F
InChI InChI=1S/C24H16F4N4O2/c25-19-8-7-16(10-15(19)11-29)31-22(33)20-17-5-1-2-6-18(17)23(34)32(13-24(26,27)28)21(20)14-4-3-9-30-12-14/h1-10,12,20-21H,13H2,(H,31,33)/t20-,21+/m0/s1
InChI Key VKCPFWKTFZAOTO-LEWJYISDSA-N
Guide to Malaria Pharmacology Comments
(+)-SJ733 is equally potent against all developmental forms of the asexual blood stage parasite and also has potential for transmission blockade [2]. The compound was under clinical development as the fast clearance component of a single-exposure radical cure and prophylaxis (SERCaP) antimalarial drug but is no longer in the Medicines for Malaria (MMV) portfolio after it was found to have lower concentrations in humans than expected [3]. A back-up series, that has been informed by (+)-SJ733, is being developed by the University of Kentucky.

Potential Target/Mechanism of Action: Evidence from genetic experiments indicates that Plasmodium non-SERCA-type Ca2+-transporting P-ATPase (PfATP4) may be the relevant molecular target [2]. Further information about possible mechanistic insights is provided under the Clinical data tab.
Target Candidate Profiles
Profile Intended Use Target Stage Comment References
TCP-5 transmission reduction gametocytes 2
TCP-1 reduce parasite burden asexual blood stages 2