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1. WO2021057061 - SENOLYTIC AND ANTIINFLAMMATORY PRODRUGS AND METHODS OF USE THEREOF

Publication Number WO/2021/057061
Publication Date 01.04.2021
International Application No. PCT/CN2020/092933
International Filing Date 28.05.2020
IPC
C07H 19/073 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
19Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro derivatives thereof
02sharing nitrogen
04Heterocyclic radicals containing only nitrogen as ring hetero atom
06Pyrimidine radicals
073with 2-deoxyribosyl as the saccharide radical
A61K 31/7068 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
70Carbohydrates; Sugars; Derivatives thereof
7042Compounds having saccharide radicals and heterocyclic rings
7052having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
706containing six-membered rings with nitrogen as a ring hetero atom
7064containing condensed or non-condensed pyrimidines
7068having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
A61P 39/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
39General protective or antinoxious agents
A61P 29/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
29Non-central analgesic, antipyretic or antiinflammatory agents, e.g antirheumatic agents; Non-steroidal antiinflammatory drugs (NSAIDs)
CPC
A61K 31/7068
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
70Carbohydrates; Sugars; Derivatives thereof
7042Compounds having saccharide radicals and heterocyclic rings
7052having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
706containing six-membered rings with nitrogen as a ring hetero atom
7064containing condensed or non-condensed pyrimidines
7068having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
A61P 29/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
29Non-central analgesic, antipyretic or anti-inflammatory agents, e.g antirheumatic agents; Non-steroidal anti-inflammatory drugs (NSAIDs)
A61P 39/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
39General protective or antinoxious agents
C07H 19/06
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
19Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides ; Anhydro-derivatives thereof
02sharing nitrogen
04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
06Pyrimidine radicals
Applicants
  • PEKING UNIVERSITY [CN]/[CN]
Inventors
  • DENG, Hongkui
  • LUO, Tuoping
  • CAI, Yusheng
  • ZHOU, Huanhuan
  • ZHU, Yinhua
  • ZHAO, Jingjing
  • DONG, Jiebin
  • LI, Honggang
Agents
  • CHINA SCIENCE PATENT & TRADEMARK AGENT LTD.
Priority Data
PCT/CN2019/10788725.09.2019CN
PCT/CN2020/08113325.03.2020CN
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) SENOLYTIC AND ANTIINFLAMMATORY PRODRUGS AND METHODS OF USE THEREOF
(FR) PROMÉDICAMENTS SÉNOLYTIQUES ET ANTI-INFLAMMATOIRES ET PROCÉDÉS D'UTILISATION DE CES DERNIERS
Abstract
(EN)
Senolytic and anti-inflammatory prodrugs are provided, which are designed from a cytotoxic agent, by chemically modifying the cytotoxic agent to incorporate a site cleavable by SA-β-gal following delivery of the prodrug in vivo, to release the active parent drug. The prodrug includes a galactose-based moiety, which is preferably acetylated, and benzyl oxy carboxy group and a cytotoxic agent moiety. The selenolytic prodrug is used to selectivelv kill one or more senescent cells and/or reduce an acute or chronic inflammatory response in a subject in need thereof, by administering to the subject therapeutically effective amount of the senolytic prodrugs. The disclosed compositions can be used to reduce one or more symptoms associated with a Senescence-associated disease or disorder or an inflammatory disorder, for example, a virus-mediated inflammation, in a subject.
(FR)
L'invention concerne des promédicaments sénolytiques et anti-inflammatoires, qui sont conçus à partir d'un agent cytotoxique, par modification chimique de l'agent cytotoxique pour incorporer un site clivable par du SA-β-gal après administration du promédicament in vivo, afin de libérer le principe actif parent. Le promédicament comprend un fragment à base de galactose, qui est de préférence acétylé, et un groupe benzyloxy carboxy et un fragment agent cytotoxique. Le promédicament sénolytique est utilisé pour détruire sélectivement une ou plusieurs cellules sénescentes et/ou réduire une réponse inflammatoire aiguë ou chronique chez un sujet en ayant besoin, par administration au sujet d'une quantité thérapeutiquement efficace des promédicaments sénolytiques. Les compositions décrites peuvent être utilisées pour réduire un ou plusieurs symptômes associés à une maladie ou à un trouble ou à un trouble inflammatoire associé à la sénescence, par exemple une inflammation à médiation virale, chez un sujet.
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