CA2469625A1 - Use of pyridine-2,4-dicarboxylic acid diamides and of pyrimidine-4,6-dicarboxylic acid diamides for selective collagenase inhibition - Google Patents

Use of pyridine-2,4-dicarboxylic acid diamides and of pyrimidine-4,6-dicarboxylic acid diamides for selective collagenase inhibition Download PDF

Info

Publication number
CA2469625A1
CA2469625A1 CA002469625A CA2469625A CA2469625A1 CA 2469625 A1 CA2469625 A1 CA 2469625A1 CA 002469625 A CA002469625 A CA 002469625A CA 2469625 A CA2469625 A CA 2469625A CA 2469625 A1 CA2469625 A1 CA 2469625A1
Authority
CA
Canada
Prior art keywords
alkyl
hydrogen atom
halogen
formula
compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002469625A
Other languages
French (fr)
Other versions
CA2469625C (en
Inventor
Klaus-Ulrich Weithmann
Joerg Habermann
Herbert Kogler
Reinhard Kirsch
Volkmar Wehner
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi Aventis Deutschland GmbH
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2469625A1 publication Critical patent/CA2469625A1/en
Application granted granted Critical
Publication of CA2469625C publication Critical patent/CA2469625C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • 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
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • 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
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • 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
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • A61P35/00—Antineoplastic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention concerns pyridine-2,4-dicarboxylic acid diamides and pyrimidine- 4,6-dicarboxylic acid diamides of formula (I) for selective collagenase (MPP 13) inhibition. Said pyridine-2,4-dicarboxylic acid diamides and pyrimidine- 4,6-dicarboxylic acid diamides can therefore be used for treating degenerative joint diseases.

Claims (20)

1. ~A compound of the formula I, and/or all the stereoisomeric forms of the compound of the formula I
and/or mixtures of these forms in any ratio, and/or a physiologically tolerated salt of the compound of the formula I, wherein A is a nitrogen atom, R1 and R3 are identical or different and are, independently of each other 1. hydrogen atom,
2. halogen,
3. -(C1-C4)-alkyl, in which alkyl is unsubstituted or substituted once, twice or three times by halogen,
4. -O-(C1-C4)-alkyl, in which alkyl is unsubstituted or substituted once, twice or three times by halogen,
5. -C(O)-O-R4, in which R4 is hydrogen atom or -(C1-C4)-alkyl,
6. -CN,
7. -N(R5)(R6), in which R5 and R6 are identical or different and are, independently of each other, 1. hydrogen atom, 2. -(C1-C4)-alkyl, 3. -C(O)-(C1-C4)-alkyl or 4. -SO2-(C1-C4)-alkyl,
8. -OH,
9. -S-(C1-C4)-alkyl,
10. -S(O)-(C1-C4)-alkyl,
11. -S(O)2-R7, in which R7 is -(C1-C4)-alkyl, -OH or -NH2, R2 is 1. hydrogen atom, 2. halogen, 3. -(C1-C4)-alkyl, 4. -O-(C1-C4)-alkyl, 5. -C(O)-O-R4, in which R4 is hydrogen atom or -(C1-C4)-alkyl, 6. -CN, 7. -N(R5)(R6), in which R5 and R6 are identical or different and are, independently of each other, 1. hydrogen atom, 2. -(C1-C4)-alkyl, 3. -C(O)-(C1-C4)alkyl or 4. -SO2-(C1-C4)-alkyl, 8. -OH, 9. -S-(C1-C4)-alkyl, 10. -S(O)-(C1-C4)-alkyl, 11. -S(O)2-R7, in which R7 is -(C1-C4)-alkyl, -OH or -NH2, R1 and R2 or R2 and R3 form, together with the carbon atoms to which they are in each case bonded, a 5- or 6-membered ring which is aromatic or saturated and contains zero, one or two heteroatoms from the series oxygen, nitrogen or sulfur, and the other radical R1 or R3 has the abovementioned meaning of 1. to 11., with the exception of the case where a) the radicals R1, R2 and R3 are all simultaneously hydrogen atom, or b) all the radicals from R1, R2 and R3 are, independently of each other, only hydrogen atom, halogen, nitro, -(C1-C4)-alkyl or -(C1-C4)-alkoxy.
2. ~A compound of the formula I as claimed in claim 1; wherein A is a nitrogen atom, R1 and R3 are identical or different and are, independently of each other, 1. hydrogen atom, 2. -(C1-C4)-alkyl, in which alkyl is substituted once, twice or three times by halogen, or 3. -O-(C1-C4)-alkyl, in which alkyl is substituted once, twice or three times by halogen, 4. -OH, 5. -C(O)-O-R4, in which R4 is hydrogen atom or -(C1-C4)-alkyl, 6. -CN, 7. -N(R5)-R6, in which R5 and R6 are identical or different and are, independently of each other, 1. hydrogen atom, 2. -(C1-C4)-alkyl, 3. -C(O)-(C1-C4)-alkyl or 4. -SO2-(C1-C4)-alkyl, 8. -S-(C1-C4)-alkyl, 9. -S(O)-(C2-C4)-alkyl, or 10. -S(O)2-R7, in which R7 is -(C1-C4)-alkyl, -OH or -NH2, in which R1, R2 and R3 are not simultaneously hydrogen atom, and R2 is 1. hydrogen atom, 2. halogen, 3. -O-(C1-C4)-alkyl, 4. -(C1-C4)-alkyl, 5. -C(O)-O-R4, in which R4 is hydrogen atom or -(C1-C4)-alkyl, 6. -CN, 7. -N(R5)(R6), in which R5 and R6 are identical or different and are, independently of each other, 1. hydrogen atom, 2. -(C1-C4)-alkyl, 3. -C(O)-(C1-C4)-alkyl, or 4. -SO2-(C1-C4)-alkyl, 8. -OH, 9. -S-(C1-C4)-alkyl, 10. -S(O)-(C1-C4)-alkyl, or 11. -S(O)2-R7, in which R7 is -(C1-C4)-alkyl, -OH or -NH2, or.
R1 and R2 or R2 and R3 form, together with the carbon atoms to which they are in each case bonded, a 5- or 6-membered ring which is aromatic or saturated and contains zero, one or two heteroatoms from the series oxygen, nitrogen or sulfur, and the other radical R1 or R3 is 1. hydrogen atom, 2. halogen, 3. -(C1-C4)-alkyl, in which alkyl is unsubstituted or substituted once, twice or three times by halogen 4. -O-(C1-C4)-alkyl, in which alkyl is unsubstituted or substituted once, twice or three times by halogen 5. -C(O)-O-R4, in which R4 is hydrogen atom or -(C1-C4)-alkyl, 6. -CN, 7. -N(R5)(R6), in which R5 and R6 are identical or different and are, independently of each other, 1. hydrogen atom, 2. -(C1-C4)-alkyl, 3. -C(O)-(C1-C4)-alkyl, or 4. -SO2-(C1-C4)-alkyl, 8. -OH, 9. -S-(C1-C4)-alkyl, 10. -S(O)-(C1-C4)-alkyl, or 11. -S(O)2-R7, in which R7 is -(C1-C4)-alkyl, -OH or -NH2.

3. A compound of the formula I as claimed in claim 1 or 2, wherein A is a nitrogen atom, R1 and R3 are identical or different and are, independently of each other, 1. hydrogen atom, 2. chlorine, 3. fluorine, 4. trifluoromethyl, 5. methoxy, 6. methyl, 7. -C(O)-OH, 8. -C(O)-O-CH3, 9. -CN, 10. -N H2, 11. -NH-C(O)-CH3,
12. -NH-SO2-CH3,
13. -N-(CH3)2,
14. -SO2-NH2,
15. -OH,
16. -O-CH2-(CHF2),
17. -S-CH3,
18. -S(O)-CH3,
19. -S(O)2-CH3 or
20. bromine, in which R1, R2 and R3 are not simultaneously hydrogen atom, and R2 is 1. hydrogen atom, 2. chlorine, 3. fluorine, 4. methoxy, 5. methyl, 6. bromine, 7. -C(O)-OH, 8. -C(O)-O-CH3, 9. -CN, 10. -NH2, 11. -NH-C(O)-CH3, 12. -NH-SO2-CH3, 13. -N-(CH3)2, 14. -SO2-NH2, 15. -OH, 16. -O-CH2-(CHF2), 17. -S-CH3, 18. -S(O)-CH3, or 19. -S(O)2-CH3, or R1 and R2 or R2 and R3 form, together with the carbon atoms to which they are in each case bonded, a dioxolane, dihydrofuran or furan ring, and the other radical R1 or R3 has the abovementioned meaning of 1. to 20.

4. A compound of the formula I as claimed in one or more of claims 1 to 3, and/or all stereoisomeric forms of the compound of formula I
and/or mixtures of these forms in every ratio, and/or a physiologically tolerated salt of the compound of the formula I, wherein A is a nitrogen atom R1 and R3 are identical or different and are, independently of each other, 1. hydrogen atom, 2. -(C1-C4)-alkyl, in which alkyl is substituted once, twice or three times by halogen, or 3. -O-(C1-C4)-alkyl, in which alkyl is substituted once, twice or three times by halogen, in which R1, R2 and R3 are not simultaneously hydrogen atom, and R2 is 1. hydrogen atom, 2. halogen 3. -O-(C1-C4)-alkyl, or 4. -(C1-C4)-alkyl, or R1 and R2 or R2 and R3 form, together with the carbon atoms to which they are in each case bonded, a 5- or 6-membered ring which is aromatic or saturated and contains zero, one or two heteroatoms from the series oxygen, nitrogen or sulfur, and the other radical R1 or R3 is 1. hydrogen atom, 2. halogen, 3. -(C1-C4)-alkyl, in which alkyl is unsubstituted or substituted once, twice or three times by halogen, or 4. -O-(C1-C4)-alkyl, in which alkyl is unsubstituted or substituted once, twice or three times by halogen.

5. A compound of the formula I as claimed in one or more of claims 1 to 4, wherein A is a nitrogen atom, R1 and R3 are identical or different and are, independently of each other, 1. hydrogen atom, or 2. trifluoromethyl, in which R1, R2 and R3 are not simultaneously hydrogen atom, and R2 is 1. hydrogen atom, 2. chlorine, 3. fluorine, 4. methoxy or 5. methyl, or R1 and R2 or R2 and R3 form, together with the carbon atoms to which they are in each case bonded, a dioxolane, dihydrofuran or furan ring and the other radical R1 or R3 is 1. hydrogen atom, 2. chlorine, 3. fluorine, 4. trifluoromethyl, 5. methoxy, or 4. methyl.

6. A process for preparing the compound of the formula I as claimed in one or more of claims 1 to 5, which comprises reacting a compound of the formula II

a) with a compound of the formula III

where R1, R2 and R3 have the meanings given in formula I as claimed in claim 1 and Y is halogen, hydroxyl or C1-C4-alkoxy or, together with the carbonyl group, forms an active ester or a mixed anhydride, with a compound of the formula I being formed and the reaction products being converted, where appropriate, into their physiologically tolerated salts, or b) reacting a compound of the formula II with a compound of the formula III to give a compound of the formula IV

where R1, R2 and R3 have the meanings given in formula I as claimed in claim 1 and Y is halogen, hydroxy or C1-C4-alkoxy or, together with the carbonyl group, forms an active ester or a mixed anhydride, and then purifying the compound of the formula IV obtained, where appropriate, and then converting it, with a compound of the formula III, into a compound of the formula I.

7. A pharmaceutical which comprises an effective content of at least one compound of the formula I as claimed in one or more of claims 1 to 5 together with a pharmaceutically suitable and physiologically tolerated carrier substance, additive and/or other active compounds and auxiliary substances.

8. The use of the compound of the formula I

and/or all the stereoisomeric forms of the compound of the formula I
and/or mixtures of these forms in any ratio, and/or a physiologically tolerated salt of the compound of the formula I
for producing a pharmaceutical for the prophylaxis and therapy of diseases such as osteoarthroses, spondyloses, chondrolysis following joint trauma or a relatively long period of joint immobilization following injuries to the meniscus or patella or tearing of a ligament, diseases of the connective tissue such as collagenoses, periodontal diseases and wound healing disturbances, chronic diseases of the locomotor system, such as inflammatory, immunologically or metabolism-determined acute and chronic arthritides, arthropathies, myalgias and disturbances of bone metabolism or breast cancer, wherein A is a carbon atom or nitrogen atom, R1 and R3 are identical or different and are, independently of each other, 1. hydrogen atom, 2. halogen, 3. -(C1-C4)-alkyl, in which alkyl is unsubstituted or substituted once, twice or three times by halogen, 4. -O-(C1-C4)-alkyl, in which alkyl is unsubstituted or substituted once, twice or three times by halogen, 5. -C(O)-O-R4, in which R4 is hydrogen atom or -(C1-C4)-alkyl, 6. -CN, 7. -N(R5)(R6), in which R5 and R6 are identical or different and are, independently of each other, 1. hydrogen atom, 2. -(C1-C4)-alkyl, 3. -C(O)-(C1-C4)-alkyl or 4. -SO2-(C1-C4)-alkyl, 8. -OH, 9. -S-(C1-C4)-alkyl, 10. -S(O)-(C1-C4)-alkyl, 11. -S(O)2-R7, in which R7 is -(C1-C4)-alkyl, -OH or -NH2, R2 is 1. hydrogen atom, 2. halogen, 3. -O-(C1-C4)-alkyl, 4. -(C1-C4)-alkyl, 5. -C(O)-O-R4, in which R4 is hydrogen atom or -(C1-C4)-alkyl, 6. -CN, 7. -N(R5)(R6), in which R5 and R6 are identical or different and are, independently of each other, 1. hydrogen atom, 2. -(C1-C4)-alkyl, 3. -C(O)-(C1-C4)-alkyl or 4. -SO2-(C1-C4)-alkyl, 8. -OH, 9. -S-(C1-C4)-alkyl, 10. -S(O)-(C1-C4)-alkyl, 11. -S(O)2-R7, in which R7 is -(C1-C4)-alkyl, -OH or -NH2, or R1 and R2 or R2 and R3 form, together with the carbon atoms to which they are in each case bonded, a 5- or 6-membered ring which is aromatic or saturated and contains zero, one or two heteroatoms from the series oxygen, nitrogen or sulfur, and the other radical R1 or R3 has the abovementioned meaning of 1. to 11.

9. The use as claimed in claim 8, which comprises employing a compound of the formula I wherein A is a carbon atom or nitrogen atom, R1 and R3 are identical or different and are, independently of each other, 1. hydrogen atom, 2. halogen, 3. -(C1-C4)-alkyl, in which alkyl is unsubstituted or substituted once, twice or three times by halogen, 4. -O-(C1-C4)-alkyl, in which alkyl is unsubstituted or substituted once, twice or three times by halogen, R2 is 1. hydrogen atom, 2. halogen, 3. -O-(C1-C4)-alkyl, or 4. -(C1-C4)-alkyl, or R1 and R2 or R2 and R3 form, together with the carbon atoms to which they are in each case bonded, a 5- or 6-membered ring which is aromatic or saturated and contains zero, one or two heteroatoms from the series oxygen, nitrogen or sulfur, and the other radical R1 or R3 has the abovementioned meaning of 1. to 4.

10. The use as claimed in claims 8 and 9, which comprises employing a compound for the formula I wherein A is a carbon atom or nitrogen atom, R1 and R3 are identical or different and are, independently of each other, 1. hydrogen atom, 2. chlorine, 3. fluorine, 4. trifluoromethyl, 5. methoxy, 6. methyl, 7. -C(O)-OH, 8. -C(O)-O-CH3, 9. -CN, 10. -NH2, 11. -NH-C(O)-CH3, 12. -NH-SO2-CH3, 13. -N-(CH3)2, 14. -SO2-NH2, 15. -OH, 16. -O-CH2-(CHF2), 17. -S-CH3, 18. -S(O)-CH3, 19. -S(O)2-CH3 or 20. bromine, R2 is 1. hydrogen atom, 2. chlorine, 3. fluorine, 4. methoxy, 5. methyl, 6. bromine, 7. -C(O)-OH, 8. -C(O)-O-CH3, 9. -CN, 10. -NH2, 11. -NH-C(O)-CH3, 12. -NH-SO2-CH3, 13. -N-(CH3)2, 14. -SO2-NH2, 15. -OH, 16. -O-CH2-(CHF2), 17. -S-CH3, 18. -S(O)-CH3, or 19. -S(O)2-CH3, or R1 and R2 or R2 and R3 form, together with the carbon atoms to which they are in each case bonded, a dioxolane, dihydrofuran or furan ring, and the other radical R1 or R3 has the abovementioned meaning of 1. to 20.

11. The use as claimed in one or more of claims 8 to 10 which comprises employing a compound of the formula I wherein A is a carbon atom or nitrogen atom, R1 and R3 are identical or different and are, independently of each other, 1. hydrogen atom, 2. chlorine, 3. fluorine, 4. trifluoromethyl, 5. methoxy, or 6. methyl, R2 is 1. hydrogen atom, 2. chlorine, 3. fluorine, 4. methoxy, or 5. methyl, or R1 and R2 or R2 and R3 form together with the carbon atoms to which they are in each case bonded, a dioxolane, dihydrofuran or furan ring. einase 13 are the degenerative joint diseases.
CA2469625A 2001-12-08 2002-11-25 Use of pyridine-2,4-dicarboxylic acid diamides and of pyrimidine-4,6-dicarboxylic acid diamides for selective collagenase inhibition Expired - Fee Related CA2469625C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10160357A DE10160357A1 (en) 2001-12-08 2001-12-08 Use of pyridine-2,4-dicarboxylic acid diamides and pyrimidine-4,6-dicarboxylic acid diamides for the selective inhibition of collagenases
DE10160357.6 2001-12-08
PCT/EP2002/013240 WO2003049738A1 (en) 2001-12-08 2002-11-25 Use of pyridine-2,4-dicarboxylic acid diamides and of pyrimidine-4,6-dicarboxylic acid diamides for selective collagenase inhibition

Publications (2)

Publication Number Publication Date
CA2469625A1 true CA2469625A1 (en) 2003-06-19
CA2469625C CA2469625C (en) 2011-07-26

Family

ID=7708512

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2469625A Expired - Fee Related CA2469625C (en) 2001-12-08 2002-11-25 Use of pyridine-2,4-dicarboxylic acid diamides and of pyrimidine-4,6-dicarboxylic acid diamides for selective collagenase inhibition

Country Status (9)

Country Link
EP (1) EP1455790B1 (en)
JP (1) JP4527980B2 (en)
AT (1) ATE390137T1 (en)
AU (1) AU2002358535B2 (en)
CA (1) CA2469625C (en)
DE (2) DE10160357A1 (en)
IL (2) IL162314A0 (en)
MX (1) MXPA04005129A (en)
WO (1) WO2003049738A1 (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MXPA03004920A (en) 2001-02-14 2003-09-05 Warner Lambert Co Pyrimidine matrix metalloproteinase inhibitors.
DOP2002000333A (en) 2001-02-14 2002-09-30 Warner Lambert Co DERIVATIVES OF ISOFTALIC ACID AS INHIBITORS OF METALOPROTEINASES OF THE MATRIX
DOP2002000332A (en) 2001-02-14 2002-08-30 Warner Lambert Co MATRIX METALOPROTEINAS PYRIDINE INHIBITORS
US6924276B2 (en) 2001-09-10 2005-08-02 Warner-Lambert Company Diacid-substituted heteroaryl derivatives as matrix metalloproteinase inhibitors
CA2462442A1 (en) 2001-10-12 2003-04-24 Warner-Lambert Company Llc Alkyne matrix metalloproteinase inhibitors
BR0315055A (en) * 2002-11-02 2005-08-16 Aventis Pharma Gmbh Pyrimidin-4,6-dicarboxylic acid diacids for selective collagenase inhibition
DE10300017A1 (en) * 2003-01-03 2004-07-15 Aventis Pharma Deutschland Gmbh Selective MMP 13 inhibitors
US20060173183A1 (en) * 2004-12-31 2006-08-03 Alantos Pharmaceuticals, Inc., Multicyclic bis-amide MMP inhibitors
US20060293345A1 (en) * 2005-05-20 2006-12-28 Christoph Steeneck Heterobicyclic metalloprotease inhibitors
US20070155738A1 (en) 2005-05-20 2007-07-05 Alantos Pharmaceuticals, Inc. Heterobicyclic metalloprotease inhibitors
CA2658362A1 (en) * 2006-06-29 2008-01-03 Alantos Pharmaceuticals Holding, Inc. Metalloprotease inhibitors
WO2009140101A2 (en) * 2008-05-12 2009-11-19 Boehringer Ingelheim International Gmbh Imidazopyridine compounds useful as mmp-13 inhibitors
GB201908453D0 (en) * 2019-06-12 2019-07-24 Enterprise Therapeutics Ltd Compounds for treating respiratory disease

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3931432A1 (en) * 1989-09-21 1991-04-04 Hoechst Ag PYRIMIDIN-4,6-DICARBONSAEUREDIAMIDE, METHOD FOR THE PRODUCTION AND USE THEREOF AND MEDICINAL PRODUCTS BASED ON THESE COMPOUNDS
DE4020570A1 (en) * 1990-06-28 1992-01-02 Hoechst Ag 2,4- AND 2,5-SUBSTITUTED PYRIDINE-N-OXIDES, METHOD FOR THE PRODUCTION AND USE THEREOF
DOP2002000332A (en) * 2001-02-14 2002-08-30 Warner Lambert Co MATRIX METALOPROTEINAS PYRIDINE INHIBITORS
DOP2002000333A (en) * 2001-02-14 2002-09-30 Warner Lambert Co DERIVATIVES OF ISOFTALIC ACID AS INHIBITORS OF METALOPROTEINASES OF THE MATRIX
MXPA03004920A (en) * 2001-02-14 2003-09-05 Warner Lambert Co Pyrimidine matrix metalloproteinase inhibitors.

Also Published As

Publication number Publication date
AU2002358535A1 (en) 2003-06-23
ATE390137T1 (en) 2008-04-15
EP1455790B1 (en) 2008-03-26
WO2003049738A1 (en) 2003-06-19
EP1455790A1 (en) 2004-09-15
IL162314A (en) 2011-07-31
CA2469625C (en) 2011-07-26
IL162314A0 (en) 2005-11-20
MXPA04005129A (en) 2004-08-11
DE10160357A1 (en) 2003-06-18
DE50211985D1 (en) 2008-05-08
JP2005513049A (en) 2005-05-12
AU2002358535B2 (en) 2007-05-10
JP4527980B2 (en) 2010-08-18

Similar Documents

Publication Publication Date Title
CA2469625A1 (en) Use of pyridine-2,4-dicarboxylic acid diamides and of pyrimidine-4,6-dicarboxylic acid diamides for selective collagenase inhibition
ES473451A1 (en) Imidazole derivatives their synthesis and their pharmaceutical formulations.
ATE163923T1 (en) 25-CARBONIC ACID DERIVATIVES IN THE VITAMIN D SERIES, PHARMACEUTICAL PREPARATIONS CONTAINING THESE DERIVATIVES AND THEIR USE IN THE PRODUCTION OF MEDICINAL PRODUCTS
ES8707191A1 (en) Imidazole analogs of mevalonolactone and derivatives thereof.
PT83843B (en) PROCESS FOR THE PREPARATION OF RAPAMICINE AVERAGES
HUT57230A (en) Process for producing pyrimidine-nucleosides and pharmaceutical compositions containing them
TR200000837A2 (en) Process and intermediates to prepare anti-cancer compositions.
CA2304713A1 (en) Biphenyl-5-alkanoic acid derivatives and use thereof
ES8306119A1 (en) Trisubstituted imidazole derivatives, processes for preparing them, pharmaceutical compositions containing them, and their use.
ES2131207T3 (en) AMIDAS DERIVATIVES OF VALPROIC ACID AND 2-VALPROENOIC ACID AND ITS USE AS ANTICONVULSIVES.
ES8101068A1 (en) Amino-pyrimidine-carbanilides, process for their preparation, medicines containing them.
ES431307A1 (en) Tetrahydro-azepinoquinolines
MY105158A (en) Substituted 4-aminoquinoline derivatives as gastric acid secretion inhibutors.
BG104726A (en) Novel derivatives of the dihydroxyhexanoic acid
RU94038256A (en) Derivatives of pyrazolopyrimidine, method of their synthesis, pharmaceutical compositions based on thereof
ES2095080T3 (en) REGIOSELECTIVE SYNTHESIS OF ACID 4-CHLORO-2-THIOFENCARBOXILICO.
HU9200335D0 (en) Medical products with human interleukin-2 content
ES8502116A1 (en) Pyrazolopyridine compounds.
TR200101083T2 (en) High purity composition containing (7alfa, 17alfa) -17-hydroxy- 7-methyl-19-nor-17-pregn-5 (10) -en-20-in-3-one.
MX9204748A (en) SUBSTITUTED MANDELIC ACID DERIVATIVES AND PROCEDURES FOR ITS PREPARATION.
ITMI922742A1 (en) COMPOUNDS WITH THERAPEUTIC ACTIVITIES USEFUL FOR THE TREATMENT OF DISEASES CONNECTED WITH A GLUTATION DEFICIENCY, PROCEDURE FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM.
ES466493A1 (en) 4-phenylbutyric acid dervatives process for their preparation and pharmaceutical compostions containing them
ES399873A1 (en) 1-phenoxy-2-hydroxy-3-hydroxyalkylamino-propanes an processes for their preparation
IL115085A0 (en) Bicyclic carboxamide derivatives their preparation and pharmaceutical compositions containing them
DE3269505D1 (en) Substituted 1-benzoyl-2-phenylimino-imidazolidines, their acid addition salts, process for their preparation and pharmaceutical compositions containing them

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20181126