CA2505874A1 - Ccr1 antagonists for the treatment of i.a. demyelinating inflammatory disease - Google Patents

Ccr1 antagonists for the treatment of i.a. demyelinating inflammatory disease Download PDF

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Publication number
CA2505874A1
CA2505874A1 CA 2505874 CA2505874A CA2505874A1 CA 2505874 A1 CA2505874 A1 CA 2505874A1 CA 2505874 CA2505874 CA 2505874 CA 2505874 A CA2505874 A CA 2505874A CA 2505874 A1 CA2505874 A1 CA 2505874A1
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Prior art keywords
compound
disease
physiologically acceptable
inflammatory
chloro
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Granted
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CA 2505874
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French (fr)
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CA2505874C (en
Inventor
Kenneth G. Carson
Geraldine C. B. Harriman
Shomir Ghosh
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Millennium Pharmaceuticals Inc
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Individual
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems

Abstract

The invention provides compounds having the formula (I): wherein R1 is halogen. The invention also provides compositions comprising the compounds, and methods of treating diseases or disorders that comprise administering on e or more of the compounds to a subject in need thereof. The disclosed compoun ds have CCR1 antagonist activity.

Claims (20)

1. A compound having the formula:

or a physiologically acceptable salt thereof, wherein R1 is a halogen.
2. The compound of Claim 1 wherein R1 is selected from the group consisting of chloro, fluoro and bromo.
3. The compound of Claim 2 wherein R1 is chloro.
4. A pharmaceutical composition comprising the compound of Claim 1 and a physiologically acceptable Garner or excipient.
5. A method for treating a disease characterized by pathogenic leukocyte recruitment, pathogenic leukocyte activation or pathogenic leukocyte recruitment and activation, comprising administering to a subject in need thereof an effective amount of a compound of Claim 1.
6. A compound having the structure:

or a physiologically acceptable salt thereof, wherein R1 is a halogen.
7. The compound of Claim 6 wherein R1 is selected from the group consisting of chloro, fluoro and bromo.
8. The compound of Claim 7 wherein R1 is chloro.
9. A pharmaceutical composition comprising the compound of Claim 6 and a physiologically acceptable carrier or excipient.
10. A method for treating a disease characterized by pathogenic leukocyte recruitment, pathogenic leukocyte activation or pathogenic leukocyte recruitment and activation, comprising administering to a subject in need thereof an effective amount of a compound of Claim 6.
11. The method of Claim 10 wherein R1 chloro.
12. The method of Claim 10 wherein said disease is an acute or chronic inflammatory disease.
13. The method of Claim 10 wherein said disease is selected from the group consisting of inflammatory arthritis, inflammatory demyelinating disease, atherosclerosis, arteriosclerosis, restenosis, ischemia/reperfusion injury, diabetes mellitus, psoriasis, inflammatory bowel diseases, rejection of a transplanted graft, graft versus host disease, allergy and asthma.
14. The method of Claim 13 wherein said disease is inflammatory arthritis.
15. The method of Claim 14 wherein said inflammatory arthritis is rheumatoid arthritis.
16. The method of Claim 13 wherein said disease is inflammatory demyelinating disease.
17. The method of Claim 16 wherein said inflammatory demyelinating disease is multiple sclerosis.
18. A method of antagonizing a C-C Chemokine Receptor 1 in a subject, comprising administering to a subject in need thereof an effective amount of a compound of Claim 1.
19. A compound having the formula:

or a physiologically acceptable salt thereof, wherein R1 is a halogen.
20. A pharmaceutical composition comprising the compound of Claim 19 and a physiologically acceptable carrier or excipient.
CA 2505874 2002-11-13 2003-11-12 Ccr1 antagonists for the treatment of i.a. demyelinating inflammatory disease Expired - Fee Related CA2505874C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US42594702P 2002-11-13 2002-11-13
US60/425,947 2002-11-13
PCT/US2003/035817 WO2004043965A1 (en) 2002-11-13 2003-11-12 Ccr1 antagonists for the treatment of i.a. demyelinating inflammatory disease

Publications (2)

Publication Number Publication Date
CA2505874A1 true CA2505874A1 (en) 2004-05-27
CA2505874C CA2505874C (en) 2012-07-17

Family

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CA 2505874 Expired - Fee Related CA2505874C (en) 2002-11-13 2003-11-12 Ccr1 antagonists for the treatment of i.a. demyelinating inflammatory disease

Country Status (25)

Country Link
US (7) US20040106639A1 (en)
EP (2) EP1562954B1 (en)
JP (1) JP4644491B2 (en)
KR (1) KR101109348B1 (en)
CN (1) CN100343257C (en)
AR (1) AR041942A1 (en)
AT (2) ATE325124T1 (en)
AU (2) AU2003291452A1 (en)
BR (1) BR0316261A (en)
CA (1) CA2505874C (en)
CY (1) CY1107985T1 (en)
DE (2) DE60332663D1 (en)
DK (1) DK1562954T3 (en)
EA (1) EA007748B1 (en)
ES (2) ES2261979T3 (en)
HK (2) HK1074046A1 (en)
IL (2) IL168384A (en)
MX (1) MXPA05005105A (en)
NO (1) NO331855B1 (en)
PL (1) PL211022B1 (en)
PT (1) PT1562954E (en)
SI (1) SI1562954T1 (en)
TW (1) TWI291467B (en)
WO (1) WO2004043965A1 (en)
ZA (2) ZA200504144B (en)

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