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Details

Stereochemistry ABSOLUTE
Molecular Formula C47H54N6O3
Molecular Weight 750.9701
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of ACT-451840

SMILES

CC(=O)N1CCN(CC1)C2=CC=C(CN([C@@H](CC3=CC=CC=C3)C(=O)N4CCN(CC5=CC=C(C=C5)C#N)CC4)C(=O)\C=C\C6=CC=C(C=C6)C(C)(C)C)C=C2

InChI

InChIKey=BQZUYCCCNXOADJ-TVNMEPFQSA-N
InChI=1S/C47H54N6O3/c1-36(54)50-28-30-51(31-29-50)43-21-16-41(17-22-43)35-53(45(55)23-18-37-14-19-42(20-15-37)47(2,3)4)44(32-38-8-6-5-7-9-38)46(56)52-26-24-49(25-27-52)34-40-12-10-39(33-48)11-13-40/h5-23,44H,24-32,34-35H2,1-4H3/b23-18+/t44-/m0/s1

HIDE SMILES / InChI

Molecular Formula C47H54N6O3
Molecular Weight 750.9701
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 1
Optical Activity UNSPECIFIED

ACT-451840 is a new compound with potent activity against sensitive and resistant Plasmodium falciparum strains. ACT-451840 has been used in trials studying malaria. ACT-451840 appears to have a distinct mode of action that sets it apart from current antimalarial drugs, including artemisinins. It has a rapid onset of action as well as activity on all blood-borne (erythrocytic) stages, which is retained against multiple resistant parasites, including artemisinin-resistant strains. Unlike the majority of antimalarial agents, ACT-451840 has the potential to block disease transmission due to its activity on gametocytes. he antimalarial activity of ACT-451840 was studied in an experimental induced blood stage malaria clinical trial performed in collaboration with MMV Medicines for Malaria Ventures at the laboratories of Professor James McCarthy, MBBS, MD of the Royal Brisbane and Women's Hospital in Herston, Australia. In the trial, ACT-451840 was safe and well tolerated and showed clinical efficacy against the early stages of P. falciparum infections. The PK/PD model developed from this proof-of-concept study with eight healthy subjects enabled prediction of therapeutic effects, with cure rates following 1 week of therapy (single daily doses) predicted to be equivalent to artesunate monotherapy.

Approval Year

PubMed

PubMed

TitleDatePubMed
First-in-humans study of the safety, tolerability, and pharmacokinetics of ACT-451840, a new chemical entity with antimalarial activity.
2015 Feb
Discovery and Characterization of ACT-451840: an Antimalarial Drug with a Novel Mechanism of Action.
2016 Sep 20
Patents

Sample Use Guides

This was a first-in-humans single-ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of ACT-451840 across doses of 10, 50, 200, and 500 mg in healthy male subjects. In the 200- and 500-mg dose groups, the effect of food was investigated, and antimalarial activity was assessed using an ex vivo bioassay with P. falciparum.
Route of Administration: Oral
In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4 nM (standard deviation [SD]: ± 0.0 nM) against the drug-sensitive P. falciparum NF54 strain. ACT-451840 potently prevented male gamete formation from the gametocyte stage with a 50% inhibition concentration of 5.89 nM (SD: ± 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory concentration of 30 nM (range: 23-39).
Substance Class Chemical
Created
by admin
on Sat Dec 16 11:04:45 GMT 2023
Edited
by admin
on Sat Dec 16 11:04:45 GMT 2023
Record UNII
FO890BDO84
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ACT-451840
Common Name English
2-PROPENAMIDE, N-((4-(4-ACETYL-1-PIPERAZINYL)PHENYL)METHYL)-N-((1S)-2-(4-((4-CYANOPHENYL)METHYL)-1-PIPERAZINYL)-2-OXO-1-(PHENYLMETHYL)ETHYL)-3-(4-(1,1-DIMETHYLETHYL)PHENYL)-
Systematic Name English
(S,E)-N-(4-(4-ACETYLPIPERAZIN-1-YL)BENZYL)-3-(4-(TERT-BUTYL)PHENYL)-N-(1-(4-(4-CYANOBENZYL)PIPERAZIN-1-YL)-1-OXO-3-PHENYLPROPAN-2-YL)ACRYLAMIDE
Systematic Name English
Code System Code Type Description
CAS
1839508-99-4
Created by admin on Sat Dec 16 11:04:46 GMT 2023 , Edited by admin on Sat Dec 16 11:04:46 GMT 2023
PRIMARY
CAS
1314143-88-8
Created by admin on Sat Dec 16 11:04:46 GMT 2023 , Edited by admin on Sat Dec 16 11:04:46 GMT 2023
ALTERNATIVE
FDA UNII
FO890BDO84
Created by admin on Sat Dec 16 11:04:46 GMT 2023 , Edited by admin on Sat Dec 16 11:04:46 GMT 2023
PRIMARY
PUBCHEM
53303762
Created by admin on Sat Dec 16 11:04:46 GMT 2023 , Edited by admin on Sat Dec 16 11:04:46 GMT 2023
PRIMARY
SMS_ID
300000041384
Created by admin on Sat Dec 16 11:04:46 GMT 2023 , Edited by admin on Sat Dec 16 11:04:46 GMT 2023
PRIMARY
DRUG BANK
DB13054
Created by admin on Sat Dec 16 11:04:46 GMT 2023 , Edited by admin on Sat Dec 16 11:04:46 GMT 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY