VITAMIN D DERIVATIVES ACTIVE ON THE VITAMIN D NUCLEAR RECEPTOR, PREPARATION AND USES THEREOF

• US 20090131378A1
• Filed: 09/28/2005
• Published: 05/21/2009
• Est. Priority Date: 09/28/2005
• Status: Active Grant

• Current Assignee: Centre National De La Recherche Scientifique, Universite De Strasbourg (Financière Meeschaert SA), Inserm (institut national de la sant et de la recherche mdicale
• Original Assignee: Centre National De La Recherche Scientifique, Inserm (institut national de la sant et de la recherche mdicale, Universidad De Santiago De Compostela (Tecnocontrol Servicios SA), Université Louis Pasteur
• Inventors: Rochel, Natacha, Moras, Dino, Mourino-Mosquera, Antonio, Wurtz, Jean-Marie, Rodrigues, Luis Cezar
• Granted Patent: US 8,198,263 B2
• Time in Patent Office: Days
• US Class Current: 514/167
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/18 Antioxidants, e.g. antiradicals preparations for protection against sunlight A61Q17/00
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07D 307/12 Radicals substituted by oxygen atoms

Abstract

The invention relates to vitamin D derivatives and their uses, particularly in the pharmaceutical industry. The invention discloses compounds having different interesting biological properties, including vitamin D nuclear receptor (VDR) agonist activity, as well as therapeutics methods by administering said compounds, in particular for treating cancer, psoriasis, autoimmune diseases, osteodistrophy and osteoporosis. It further relates to pharmaceutical compositions comprising said compounds and methods for preparing the same.

Claims

1. A compound presenting the following formula (I):

wherein R₁ represents a group selected from a hydrogen atom, a halogen atom, a linear or branched (C₁-C₁₀)alkyl, an (C₁-C₁₀)alkoxy, C₂-C₁₀ branched or linear alkenyl or C₂-C₁₀ branched or linear alkynyl, an (C₅-C₁₄)aryl, and an (C₅-C₁₄)aryloxy group, in which said group is optionally substituted by at least one halogen atom, hydroxyl or —

NH₂ group;

and wherein R represents

in which Z represents

wherein;

R₂ and R₃, identical or different, represent a group selected from H, halogen atom, a C₁-C₁₀ branched or linear alkyl, C₂-C₁₀ branched or linear alkenyl or C₂-C₁₀ branched or linear alkynyl group;

R₄ and R₅, identical or different, represent a group selected from H, halogen atom, a C₁-C₆ linear or branched alkyl, C₂-C₁₀ branched or linear alkenyl or C₂-C₁₀ branched or linear alkynyl group;

m represents an integer comprised between 0 and 5 inclusive; and

n represents an integer comprised between 0 and 5 inclusive.

2. The compound according to claim 1, wherein R₁ represents a group selected from H, halogen atom, CH₃, (CH₂)₃OH or O(CH₂)₃OH.

3. The compound according to claim 1, wherein R represents:

4. The compound according to claim 1, wherein m is 0 or 1.

5. The compound according to claim 1, wherein n is 0.

6. The compound according to claim 1, wherein R₂ and R₃, identical or different, represent a group selected from H, halogen atom and a C₁-C₄ branched or linear alkyl.

7. The compound according to claim 1, wherein R₄ and R₅, identical or different, represent a group selected from H, halogen atom and a C₁-C₄ linear or branched alkyl.

8. The compound according to claim 1, wherein said compound is the specific stereoisomer according to the following formula (IV):

wherein R₁ and R are as defined in claim 1.

9. The compound according to claim 8, wherein R represents

10. The compound according to claim 8, wherein R represents

11. A pharmaceutical composition comprising at least one compound according to claim 1 and a pharmaceutically acceptable support, optionally in association with another active agent.

12. A method of treating cancer, dermatological disorders, inflammation related disorders, autoimmune diseases, osteodistrophy or osteoporosis comprising administering a pharmaceutical composition comprising at least one compound according to claim 1 and a pharmaceutically acceptable support.

13. A method of treating breast cancer, prostate cancer, colon cancer, leukemia, rheumatoid arthritis, psoriatic arthritis, psoriasis, photoaging, multiple sclerosis, type I diabetes, low bone turnover osteoporosis, steroid induced osteoporosis, senile osteoporosis, postmenopausal osteoporosis, osteomalacia or renal osteodystrophy comprising administering a pharmaceutical composition comprising at least one compound according to claim 1 and a pharmaceutically acceptable support.