147384-69-8

Usage

Uses

Used in Pharmaceutical Industry:
Kynostatin is used as an antimalarial agent for its ability to combat both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Its mechanism of action involves targeting the parasite's mitochondria, which disrupts energy production and results in the death of the parasite. This makes kynostatin a promising candidate for the development of new treatments for malaria, particularly in regions where conventional drugs have become less effective due to resistance.
Further research is necessary to explore the full potential of kynostatin in clinical settings, including its safety profile, optimal dosage, and possible synergistic effects with existing antimalarial drugs. The development of drug delivery systems for kynostatin may also enhance its bioavailability and therapeutic efficacy, making it a more viable option for malaria treatment.

InChI:InChI=1/C35H45N5O6S2/c1-34(2,3)39-32(44)30-35(4,5)48-21-40(30)33(45)29(42)25(17-22-11-8-7-9-12-22)38-31(43)26(20-47-6)37-28(41)19-46-27-14-10-13-23-18-36-16-15-24(23)27/h7-16,18,25-26,29-30,42H,17,19-21H2,1-6H3,(H,37,41)(H,38,43)(H,39,44)/t25-,26-,29-,30+/m0/s1

Upstream product

• 80278-25-7 5-isoquinolinyloxyacetic acid 
• 159000-72-3 (R)-N-tert-butyl-3-[(2S,3S)-3-[(S)-2-(tert-butoxycarbonyl)amino-3-methylthiopropionyl]amino-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 
• 130292-81-8 methyl 5-isoquinolyloxyacetate 
• 2439-04-5 5-hydroxyisoquinoline 
• 159000-71-2 Boc-Apns-Dmt-NHtBu 
• 184955-18-8 (R)-N-tert-butyl-3-<(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl>-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 
• 148983-13-5 (R)-4-tert-Butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carboxylic acid tert-butyl ester 
• 117918-23-7 (R)-3-tert-butoxycarbonyl-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid 
• 158941-58-3 (R)-N-tert-butyl-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 

Relevant academic research and scientific papers

New water-soluble prodrugs of HIV protease inhibitors based on O→N intramolecular acyl migration

To improve the low water-solubility of HIV protease inhibitors, we synthesized water-soluble prodrugs of KNI-272 and KNI-279 which are potent HIV-1 protease inhibitors consisting of an Apns-Thz core structure (Apns; allophenylnorstatine, Thz; thiazolidine-4-carboxylic acid) as an inhibitory machinery. The prodrugs, which contained an O-acyl peptidomimetic structure with an ionized amino group leading to the increase of water-solubility, were designed to regenerate the corresponding parent drugs based on the O→N intramolecular acyl migration reaction at the α-hydroxy-β-amino acid residue, that is allophenylnorstatine. The synthetic prodrugs 3, 4, 6, and 7 improved the water-solubility (>300 mg/mL) more than 4000-fold in comparison with the parent compounds, which is the practically acceptable value as water-soluble drugs. These prodrugs were stable as an HCl salt and in a strongly acidic solution corresponding to gastric juice (pH 2.0), and could be converted to the parent compounds promptly in the aqueous condition from slightly acidic to basic pH at 37°C, with the suitable migration rate, via a five-membered ring intermediate. Using a similar method, we synthesized a prodrug (12) of ritonavir, a clinically useful HIV-1 protease inhibitor as an anti-AIDS drug. In contrast to the prodrugs 3, 4, 6, and 7, the prodrug 12 was very slowly converted to ritonavir probably through a six-membered ring intermediate, with the t1/2 value of 32 h that may not be suitable for practical use.

Structure-activity relationship of orally potent tripeptide-based HIV protease inhibitors containing hydroxymethylcarbonyl isostere

We designed and synthesized a new class of peptidomimetic human immunodeficiency virus protease inhibitors containing a unique unnatural amino acid, allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid], with a hydroxymethylcarbonyl isostere as the active moiety. From a structure-activity relationship study of HIV-1 protease inhibition, enzyme selectivity for other aspartyl proteases, the antiviral activity and pharmacokinetics in rats, 24c (KNI-227) and 24d (KNI-272, our first clinical candidate) were found to be selective and orally potent HIV protease inhibitors. Moreover, an improvement of the pharmacokinetic features of KNI-272 provided two long-lasting and highly bioavailable compounds (24g: JE-2178,h: JE-2179).