Processing

Please wait...

Settings

Settings

Goto Application

1. WO2020068004 - ANTITUBERCULOSIS LANOSTANE TRITERPENOID AND METHOD OF MAKING THE COMPOUNDS

Publication Number WO/2020/068004
Publication Date 02.04.2020
International Application No. PCT/TH2019/000037
International Filing Date 30.08.2019
IPC
A61K 31/575 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
56Compounds containing cyclopentahydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
575substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
A61P 31/06 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
31Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
04Antibacterial agents
06for tuberculosis
C07J 9/00 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
JSTEROIDS
9Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
CPC
A61K 31/575
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives, e.g. steroids
575substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
Applicants
  • NATIONAL SCIENCE AND TECHNOLOGY DEVELOPMENT AGENCY [TH]/[TH]
  • THE THAI LAND RESEARCH FUND (TRF) [TH]/[TH]
Inventors
  • ISAKA, Masahiko
  • CHINTHANOM, Panida
  • VICHAI, Vanicha
  • DOKLADDA, Kanchana
  • SAPPAN, Malipan
  • THONGPANCHANG, Chawanee
Agents
  • RUANGSIN, Ratchada
  • CHAMCHAENG, Samornluk
Priority Data
180100602728.09.2018TH
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) ANTITUBERCULOSIS LANOSTANE TRITERPENOID AND METHOD OF MAKING THE COMPOUNDS
(FR) TRITERPÉNOÏDE DE TYPE LANOSTANE ANTITUBERCULEUX ET PROCÉDÉ DE PRÉPARATION DES COMPOSÉS
Abstract
(EN)
A new lanostane triterpenoid (24E)-3β-acetoxy-15α-propionyloxylanosta-7,9( 11 ),24-trien-26-oic acid (GA003), is synthesized by acylation reaction of a naturally occurring fungal metabolite, (24E)-3β-acetoxy-15α-hydroxylanosta-7,9( 11 ),24-trien-26-oic acid (ganoderic acid T-O). GA003 is identified as the most potent antimycobacterial against Mycobacterium tuberculosis H37Ra (MIC 0.0977 μg/ml) through a series of structural modifications (semi-synthesis) of a lead natural product, (24E)-3β,15α diacetoxylanosta-7,9(1 1),24-trien-26-oic acid. GA003 exhibits potent growth inhibitory activity against Mycobacterium tuberculosis strains H37Rv (virulent strain), THX-0001 (pre-XDR strain), THX-0002 (XDR strain), and THX-0003 (XDR strain), with MIC values of 0.3125, <0.156, 0.625, and 1.25 μg/ml, respectively, while showing very weak cytotoxicity to Vero cells (African green monkey kidney fibroblasts). Therefore, GA003 and pharmaceutical compositions containing GA003 may be useful for the treatment of tuberculosis.
(FR)
L'invention concerne un nouveau triterpénoïde de type lanostane, l'acide (24E)-3p-acétoxy-15α-propionyloxylanosta-7,9(11),24-trién-26-oïque (GA003), qui est synthétisé par une réaction d'acylation d'un métabolite fongique naturel, l'acide (24E)-3P-acétoxy-15α-hydroxylanosta-7,9(11),24-trién-26-oïque(acide ganodérique T-0). Le GA003 est identifié comme étant le plus puissant anti-mycobactérien contre Mycobacterium tuberculosis H37Ra (MIC 0,0977 µg/ml) à travers une série de modifications structurales (semi-synthèse) d'un important produit naturel, l'acide (24E)-3p,15α-diacetoxylanosta-7,9(1 l),24-trién-26-oïque. GA003 présente une puissante activité d'inhibition de la croissance contre Mycobacterium tuberculosis H37Rv (souche virulente), THX-0001 (souche pré-XDR), THX -0002 (souche XDR), et THX-0003 (souche XDR), avec des valeurs de MIC de 100,3125, <0,156, 0,625, et 1,25 μg/ml, respectivement, tout en présentant une cytotoxicité très faible envers les cellules Vero (fibroblastes rénaux de singes verts d'Afrique). Par conséquent, GA003 et les compositions pharmaceutiques contenant GA003 peuvent être utiles pour le traitement de la tuberculose.
Latest bibliographic data on file with the International Bureau