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1. WO2004005310 - NEW COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATMENT OF INFLAMMATORY DISEASES AND CONDITIONS

Publication Number WO/2004/005310
Publication Date 15.01.2004
International Application No. PCT/HR2003/000037
International Filing Date 08.07.2003
Chapter 2 Demand Filed 06.02.2004
IPC
C07H 17/00 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
17Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
CPC
A61P 1/04
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
1Drugs for disorders of the alimentary tract or the digestive system
04for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 11/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
11Drugs for disorders of the respiratory system
A61P 11/06
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
11Drugs for disorders of the respiratory system
06Antiasthmatics
A61P 17/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
17Drugs for dermatological disorders
A61P 17/06
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
17Drugs for dermatological disorders
06Antipsoriatics
A61P 19/02
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
19Drugs for skeletal disorders
02for joint disorders, e.g. arthritis, arthrosis
Applicants
  • PLIVA-ISTRAZIVACKI INSTITUT D.O.O. [HR]/[HR] (AllExceptUS)
  • MERCEP, Mladen [HR]/[HR] (UsOnly)
  • MESIC, Milan [HR]/[HR] (UsOnly)
  • TOMASKOVIC, Linda [HR]/[HR] (UsOnly)
  • MARKOVIC, Stribor [HR]/[HR] (UsOnly)
  • MAKARUHA, Oresta [HR]/[HR] (UsOnly)
  • POLJAK, Visnja [HR]/[HR] (UsOnly)
Inventors
  • MERCEP, Mladen
  • MESIC, Milan
  • TOMASKOVIC, Linda
  • MARKOVIC, Stribor
  • MAKARUHA, Oresta
  • POLJAK, Visnja
Priority Data
60/394,67008.07.2002US
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) NEW COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATMENT OF INFLAMMATORY DISEASES AND CONDITIONS
(FR) NOUVEAUX COMPOSES, COMPOSITIONS ET PROCEDES POUR TRAITER LES MALADIES ET ETATS INFLAMMATOIRES
Abstract
(EN) The present invention relates (a) to new compounds represented by Formula (I): wherein M represents a macrolide subunit (macrolide moiety) derived from macrolide possessing the property of accumulation in inflammatory cells, S represents a steroid subunit (steroid moiety) derived from steroid drug with anti-inflammatory activity and L represents a linker molecule linking M and S, (b) to their pharmacologically acceptable salts, prodrugs and solvates, (c) to processes and intermediates for their preparation, and (d) to their use in the treatment of inflammatory diseases and conditions in humans and animals. Such compounds inhibit many cytokines and immune mediators involved in immune responses which cause inflammation, allergy, or alloimmunity, including without limitation IL-1, 2, 4, 5, 6, 10, 12, GMCSF, ICAM, and TNF-&agr;. Importantly, anti-inflammatory steroids exert a direct anti-inflammatory effect through binding to the glucocorticosteroid receptor.
(FR) Cette invention se rapporte : (a) à de nouveaux composés représentés par la formule (I), où M représente une sous-unité macrolide (fraction macrolide) dérivée d'un macrolide ayant la propriété de s'accumuler dans les cellules inflammatoires, S représente une sous-unité stéroïde (fraction stéroïde) dérivé d'un médicament aux stéroïdes ayant une action anti-inflammatoire, et L représente une molécule de liaison reliant M et S, (b) à leurs sels, promédicaments, et solvates pharmacologiquement acceptables, (c) à des procédés et à des intermédiaires servant à leur préparation et (d) à leur utilisation dans le traitement des maladies et états inflammatoires chez l'homme et chez les animaux. Ces composés inhibent un grand nombre de cytokines et de médiateurs immuns impliqués dans les réactions immunitaires qui causent l'inflammation, l'allergie ou l'allo-immunité y compris notamment IL-1, 2, 4, 5, 6, 10, 12, GMCSF, ICAM et TNF-$g(a). Observation importante, les stéroïdes anti-inflammatoires exercent un effet anti-inflammatoire direct par fixation au récepteur des glucocorticostéroïdes.
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