Biphenyl and biphenyl-analogous compounds as integrin antagonists

• US 6,420,396 B1
• Filed: 12/15/1999
• Issued: 07/16/2002
• Est. Priority Date: 12/16/1998
• Status: Expired due to Fees

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Beiersdorf AG (maxingvest GmbH & Co. KGaA)
• Inventors: Keldenich, Jörg, Urbahns, Klaus, Härter, Michael, Lustig, Klemens, Gerdes, Christoph, Vaupel, Andrea, Stahl, Elke, Schmidt, Delf, Albers, Markus, Stelte-Ludwig, Beatrix, Brueggemeier, Ulf
• Primary Examiner(s): Raymond, Richard L.
• Assistant Examiner(s): MCKENZIE, THOMAS C
• Application Number:
  US09/464,237
• Time in Patent Office: 944 Days
• Field of Search: 514/352, 546/312
• US Class Current: 514/352
• CPC Class Codes: C07C 237/36 having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/04 with a four-membered ring
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2601/18 with a ring being at least seven-membered
• CPC Class Codes: C07C 2602/42 the bicyclo ring system containing seven carbon atoms
• CPC Class Codes: C07C 271/22 to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07C 275/42 being further substituted by carboxyl groups
• CPC Class Codes: C07C 311/06 to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07C 311/09 the carbon skeleton being further substituted by at least two halogen atoms
• CPC Class Codes: C07C 311/10 of a saturated carbon skeleton containing rings
• CPC Class Codes: C07C 311/11 of an acyclic unsaturated carbon skeleton
• CPC Class Codes: C07C 311/13 the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 311/19 to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07C 311/29 having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 311/43 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 311/47 Y being a hetero atom
• CPC Class Codes: C07C 317/14 having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 323/44 X or Y being nitrogen atoms
• CPC Class Codes: C07D 207/34 : 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
• CPC Class Codes: C07D 213/38 : having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
• CPC Class Codes: C07D 213/40 : Acylated substituent nitrogen atom
• CPC Class Codes: C07D 213/55 : Acids; Esters
• CPC Class Codes: C07D 213/74 : Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 213/75 : Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 213/82 : in position 3
• CPC Class Codes: C07D 231/18 : One oxygen or sulfur atom
• CPC Class Codes: C07D 233/64 : with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
• CPC Class Codes: C07D 233/84 : Sulfur atoms
• CPC Class Codes: C07D 233/88 : Nitrogen atoms, e.g. allantoin
• CPC Class Codes: C07D 233/90 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 235/30 : Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 235/32 : Benzimidazole-2-carbamic acids, unsubstituted or substituted; Esters thereof; Thio-analogues thereof
• CPC Class Codes: C07D 261/10 : 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
• CPC Class Codes: C07D 263/58 : 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 in position 2
• CPC Class Codes: C07D 277/42 : Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 277/54 : Nitrogen and either oxygen or sulfur atoms
• CPC Class Codes: C07D 277/82 : Nitrogen atoms
• CPC Class Codes: C07D 285/10 : 1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles
• CPC Class Codes: C07D 285/135 : Nitrogen atoms
• CPC Class Codes: C07D 285/14 : condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 295/096 : with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/13 : to an acyclic saturated chain
• CPC Class Codes: C07D 295/15 : to an acyclic saturated chain
• CPC Class Codes: C07D 295/215 : Radicals derived from nitrogen analogues of carbonic acid
• CPC Class Codes: C07D 307/52 : Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 333/34 : Sulfur atoms
• CPC Class Codes: C07D 333/48 : by oxygen atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to 2-Mesitylsulfonylamino-3-{3′[(pyridinylamino)methyl][1,1-biphenyl]-4-yl}propanoic acid, pharmaceutical compositions thereof, their preparation, their use in the treatment of cancer, arteriosclerosis, restenosis, osteolytic disorders, ophthalmic disorders, and their use as integrin antagonists. The compounds according to the invention have the formula (I):

Claims

1. A compound of the formula:

wherein

R¹ is hydrogen or alkyl having 1-6 carbon atoms;

or a physiologically acceptable salt thereof.

2. The compound according to claim 4, which is in the form of a purified stereoisomer.

3. The compound according to claim 1, which is (2S)-2-mesitylsulfonylamino-3-{3′

-[(2-pyridinylamino)-methyl][1,1′

biphenyl]-4-yl}-propanoic acid of the formula;

or a physiologically acceptable salt thereof.

4. A pharmaceutical composition comprising at least one compound according to any one of claims 1-3 and an inert, non-toxic, pharmaceutically suitable excipient or solvent.

5. A method for inhibiting angiogenesis and/or for treating a disorder selected from the group consisting of osteolytic diseases, arteriosclerosis, restenosis after percutaneous transluminal angioplasty and/or stenting, rheumatoid arthritis and ophthalmia, said method comprising administering to said patient an effective amount therefor of at least one compound according to any one of claims 1-3.

6. The method according to claim 5, which is for inhibiting angiogenesis.

7. The method according to claim 5, which is for treating osteolytic diseases.

8. The method according to claim 5, which is for treating osteoporosis.

9. The method according to claim 5, which is for treating arteriosclerosis.

10. The method according to claim 5, which is for treating restenosis after percutaneous transluminal angioplasty and/or stenting.

11. The method according to claim 5, which is for treating rheumatoid arthritis.

12. The method according to claim 5, which is for treating ophthalmia.