HRP980443A2 - Novel inhibitors of aggrecanase and matrix metalloproteinases for the treatment of arthritis - Google Patents
Novel inhibitors of aggrecanase and matrix metalloproteinases for the treatment of arthritisInfo
- Publication number
- HRP980443A2 HRP980443A2 HR60/068,335A HRP980443A HRP980443A2 HR P980443 A2 HRP980443 A2 HR P980443A2 HR P980443 A HRP980443 A HR P980443A HR P980443 A2 HRP980443 A2 HR P980443A2
- Authority
- HR
- Croatia
- Prior art keywords
- hydroxy
- phenyl
- nra
- indanyl
- methyl
- Prior art date
Links
- 108010003059 aggrecanase Proteins 0.000 title claims description 21
- 239000003112 inhibitor Substances 0.000 title description 14
- 206010003246 arthritis Diseases 0.000 title description 13
- 102000002274 Matrix Metalloproteinases Human genes 0.000 title description 6
- 108010000684 Matrix Metalloproteinases Proteins 0.000 title description 6
- 229910020008 S(O) Inorganic materials 0.000 claims description 444
- 229910052760 oxygen Inorganic materials 0.000 claims description 428
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 311
- 229910003813 NRa Inorganic materials 0.000 claims description 273
- 229910052757 nitrogen Inorganic materials 0.000 claims description 229
- 229910052717 sulfur Inorganic materials 0.000 claims description 197
- 238000000034 method Methods 0.000 claims description 193
- 125000005842 heteroatom Chemical group 0.000 claims description 186
- 125000000623 heterocyclic group Chemical group 0.000 claims description 153
- 229910052739 hydrogen Inorganic materials 0.000 claims description 150
- 101150073096 NRAS gene Proteins 0.000 claims description 126
- 150000001875 compounds Chemical class 0.000 claims description 126
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 120
- 125000002837 carbocyclic group Chemical group 0.000 claims description 99
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 86
- 229910052799 carbon Inorganic materials 0.000 claims description 86
- 125000004450 alkenylene group Chemical group 0.000 claims description 85
- 125000002947 alkylene group Chemical group 0.000 claims description 85
- 125000004419 alkynylene group Chemical group 0.000 claims description 85
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 84
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 84
- 229910052794 bromium Inorganic materials 0.000 claims description 84
- 229910052801 chlorine Inorganic materials 0.000 claims description 84
- 229910052731 fluorine Inorganic materials 0.000 claims description 84
- 229910052740 iodine Inorganic materials 0.000 claims description 84
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 84
- 241000124008 Mammalia Species 0.000 claims description 74
- SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical compound NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 claims description 64
- 201000010099 disease Diseases 0.000 claims description 52
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 52
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
- -1 C1-C8 alkyl-NR10 Chemical group 0.000 claims description 43
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 42
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 41
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 34
- 238000006243 chemical reaction Methods 0.000 claims description 32
- 239000000651 prodrug Substances 0.000 claims description 29
- 229940002612 prodrug Drugs 0.000 claims description 29
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 28
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 208000027866 inflammatory disease Diseases 0.000 claims description 15
- 230000001404 mediated effect Effects 0.000 claims description 15
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
- 201000008482 osteoarthritis Diseases 0.000 claims description 12
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 11
- 208000023275 Autoimmune disease Diseases 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 230000035939 shock Effects 0.000 claims description 11
- 206010048998 Acute phase reaction Diseases 0.000 claims description 10
- 206010006895 Cachexia Diseases 0.000 claims description 10
- 206010027476 Metastases Diseases 0.000 claims description 10
- 201000004681 Psoriasis Diseases 0.000 claims description 10
- 206010037660 Pyrexia Diseases 0.000 claims description 10
- 230000001154 acute effect Effects 0.000 claims description 10
- 230000004658 acute-phase response Effects 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 208000015181 infectious disease Diseases 0.000 claims description 10
- 201000006417 multiple sclerosis Diseases 0.000 claims description 10
- 208000007848 Alcoholism Diseases 0.000 claims description 9
- 208000010412 Glaucoma Diseases 0.000 claims description 9
- 208000031886 HIV Infections Diseases 0.000 claims description 9
- 208000037357 HIV infectious disease Diseases 0.000 claims description 9
- 206010064390 Tumour invasion Diseases 0.000 claims description 9
- 201000007930 alcohol dependence Diseases 0.000 claims description 9
- 208000022531 anorexia Diseases 0.000 claims description 9
- 230000000740 bleeding effect Effects 0.000 claims description 9
- 230000023555 blood coagulation Effects 0.000 claims description 9
- 230000009400 cancer invasion Effects 0.000 claims description 9
- 201000007717 corneal ulcer Diseases 0.000 claims description 9
- 206010061428 decreased appetite Diseases 0.000 claims description 9
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 9
- 208000007565 gingivitis Diseases 0.000 claims description 9
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 9
- 201000003142 neovascular glaucoma Diseases 0.000 claims description 9
- 201000001245 periodontitis Diseases 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 230000004614 tumor growth Effects 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- ZYIMYAJZHPOFQU-XPKDYRNWSA-N (2r)-n'-hydroxy-n-[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]-2-(2-methylpropyl)butanediamide Chemical compound C1=CC=C2[C@H](NC(=O)[C@@H](CC(=O)NO)CC(C)C)[C@H](O)CC2=C1 ZYIMYAJZHPOFQU-XPKDYRNWSA-N 0.000 claims description 5
- AQLJBZWVCZCQCY-MQVPCNEGSA-N (2r)-2-[[4-(2,4-dichlorophenyl)phenyl]methyl]-n'-hydroxy-n-[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]butanediamide Chemical compound C([C@H](CC(=O)NO)C(=O)N[C@H]1C2=CC=CC=C2C[C@H]1O)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1Cl AQLJBZWVCZCQCY-MQVPCNEGSA-N 0.000 claims description 4
- VETZHHOGSHSDQI-SGGJORCASA-N (2r)-2-[[4-(2,4-dimethoxyphenyl)phenyl]methyl]-n'-hydroxy-n-[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]butanediamide Chemical compound COC1=CC(OC)=CC=C1C(C=C1)=CC=C1C[C@H](CC(=O)NO)C(=O)N[C@H]1C2=CC=CC=C2C[C@H]1O VETZHHOGSHSDQI-SGGJORCASA-N 0.000 claims description 4
- TZHSKYKMJBHKLJ-NIDLKEISSA-N (2r)-2-[[4-(2-chlorophenyl)phenyl]methyl]-n'-hydroxy-n-[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]butanediamide Chemical compound C([C@H](CC(=O)NO)C(=O)N[C@H]1C2=CC=CC=C2C[C@H]1O)C(C=C1)=CC=C1C1=CC=CC=C1Cl TZHSKYKMJBHKLJ-NIDLKEISSA-N 0.000 claims description 4
- DPYKIUQVCIUGEL-NIDLKEISSA-N (2r)-2-[[4-(3,5-dichlorophenyl)phenyl]methyl]-n'-hydroxy-n-[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]butanediamide Chemical compound C([C@H](CC(=O)NO)C(=O)N[C@H]1C2=CC=CC=C2C[C@H]1O)C(C=C1)=CC=C1C1=CC(Cl)=CC(Cl)=C1 DPYKIUQVCIUGEL-NIDLKEISSA-N 0.000 claims description 4
- KKEGVCYPTAVMIQ-NIDLKEISSA-N (2r)-2-[[4-(3-chloro-4-fluorophenyl)phenyl]methyl]-n'-hydroxy-n-[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]butanediamide Chemical compound C([C@H](CC(=O)NO)C(=O)N[C@H]1C2=CC=CC=C2C[C@H]1O)C(C=C1)=CC=C1C1=CC=C(F)C(Cl)=C1 KKEGVCYPTAVMIQ-NIDLKEISSA-N 0.000 claims description 4
- KLPLOGXKUWGLSE-XRODADMRSA-N (2r)-2-[[4-(3-fluorophenyl)phenyl]methyl]-n'-hydroxy-n-[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]butanediamide Chemical compound C([C@H](CC(=O)NO)C(=O)N[C@H]1C2=CC=CC=C2C[C@H]1O)C(C=C1)=CC=C1C1=CC=CC(F)=C1 KLPLOGXKUWGLSE-XRODADMRSA-N 0.000 claims description 4
- SBQLOBWDHMXOHB-OKEQGEBHSA-N (2r)-2-[[4-[2-(tert-butylsulfamoyl)phenyl]phenyl]methyl]-n'-hydroxy-n-[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]butanediamide Chemical compound CC(C)(C)NS(=O)(=O)C1=CC=CC=C1C(C=C1)=CC=C1C[C@H](CC(=O)NO)C(=O)N[C@H]1C2=CC=CC=C2C[C@H]1O SBQLOBWDHMXOHB-OKEQGEBHSA-N 0.000 claims description 4
- LCLCZPQXAUSLQC-QFUCXCTJSA-N (2r)-n'-hydroxy-n-[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]-2-(3-phenylpropyl)butanediamide Chemical compound C([C@H](CC(=O)NO)C(=O)N[C@H]1C2=CC=CC=C2C[C@H]1O)CCC1=CC=CC=C1 LCLCZPQXAUSLQC-QFUCXCTJSA-N 0.000 claims description 4
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- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- FDBYIYFVSAHJLY-UHFFFAOYSA-N resmetirom Chemical compound N1C(=O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)N2C(NC(=O)C(C#N)=N2)=O)Cl)=N1 FDBYIYFVSAHJLY-UHFFFAOYSA-N 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- NPDBDJFLKKQMCM-UHFFFAOYSA-N tert-butylglycine Chemical compound CC(C)(C)C(N)C(O)=O NPDBDJFLKKQMCM-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 230000008354 tissue degradation Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/06—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US5594497P | 1997-08-18 | 1997-08-18 | |
US6833597P | 1997-12-19 | 1997-12-19 |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP980443A2 true HRP980443A2 (en) | 1999-10-31 |
Family
ID=26734798
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR60/068,335A HRP980443A2 (en) | 1997-08-18 | 1998-08-14 | Novel inhibitors of aggrecanase and matrix metalloproteinases for the treatment of arthritis |
Country Status (15)
Country | Link |
---|---|
US (1) | US6576664B1 (et) |
EP (1) | EP1005448A2 (et) |
KR (1) | KR20010023001A (et) |
CN (1) | CN1268117A (et) |
AR (1) | AR016134A1 (et) |
AU (1) | AU9021498A (et) |
BR (1) | BR9815596A (et) |
CA (1) | CA2301038A1 (et) |
EE (1) | EE200000093A (et) |
HR (1) | HRP980443A2 (et) |
IL (1) | IL133952A0 (et) |
NO (1) | NO20000784L (et) |
PL (1) | PL339006A1 (et) |
SK (1) | SK1602000A3 (et) |
WO (1) | WO1999009000A2 (et) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
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US6747027B1 (en) | 1996-07-22 | 2004-06-08 | Pharmacia Corporation | Thiol sulfonamide metalloprotease inhibitors |
US6794511B2 (en) | 1997-03-04 | 2004-09-21 | G. D. Searle | Sulfonyl aryl or heteroaryl hydroxamic acid compounds |
US7115632B1 (en) | 1999-05-12 | 2006-10-03 | G. D. Searle & Co. | Sulfonyl aryl or heteroaryl hydroxamic acid compounds |
US6696449B2 (en) | 1997-03-04 | 2004-02-24 | Pharmacia Corporation | Sulfonyl aryl hydroxamates and their use as matrix metalloprotease inhibitors |
WO1999025687A1 (en) | 1997-11-14 | 1999-05-27 | G.D. Searle & Co. | Aromatic sulfone hydroxamic acid metalloprotease inhibitor |
US20010039287A1 (en) | 1997-11-14 | 2001-11-08 | Thomas E Barta | Aromatic sulfone hydroxamic acid metalloprotease inhibitor |
US6750228B1 (en) | 1997-11-14 | 2004-06-15 | Pharmacia Corporation | Aromatic sulfone hydroxamic acid metalloprotease inhibitor |
US6800646B1 (en) | 1999-02-08 | 2004-10-05 | Pharmacia Corporation | Sulfamato hydroxamic acid metalloprotease inhibitor |
AU4181000A (en) | 1999-04-02 | 2000-10-23 | Du Pont Pharmaceuticals Company | Novel lactam inhibitors of matrix metalloproteinases, tnf-alpha, and aggrecanase |
US6649377B1 (en) | 1999-05-10 | 2003-11-18 | Syntex (U.S.A.) Llc | Human aggrecanase and nucleic acid compositions encoding the same |
US6656448B1 (en) | 2000-02-15 | 2003-12-02 | Bristol-Myers Squibb Pharma Company | Matrix metalloproteinase inhibitors |
US6683093B2 (en) | 2000-05-12 | 2004-01-27 | Pharmacia Corporation | Aromatic sulfone hydroxamic acids and their use as protease inhibitors |
YU85403A (sh) | 2001-05-11 | 2006-03-03 | Pharmacia Corporation | Aromatični sulfonski hidroksamati i njihova upotreba kao proteaznih inhibitora |
US6683078B2 (en) | 2001-07-19 | 2004-01-27 | Pharmacia Corporation | Use of sulfonyl aryl or heteroaryl hydroxamic acids and derivatives thereof as aggrecanase inhibitors |
AU2003221786A1 (en) | 2002-04-25 | 2003-11-10 | Pharmacia Corporation | Piperidinyl-and piperazinyl-sulfonylmethyl hydroxamic acids and their use as protease inhibitors |
AU2003297062A1 (en) * | 2002-12-11 | 2004-06-30 | University Of Massachusetts | METHOD OF INTRODUCING siRNA INTO ADIPOCYTES |
ZA200605248B (en) | 2003-12-15 | 2007-10-31 | Japan Tobacco Inc | Cyclopropane compounds and pharmaceutical use thereof |
WO2005109001A2 (en) * | 2004-05-12 | 2005-11-17 | Galapagos N.V. | Methods, compositions and compound assays for inhibiting amyloid-beta protein production |
CN101426499A (zh) * | 2006-02-22 | 2009-05-06 | 弗特克斯药品有限公司 | 毒蕈碱受体调节剂 |
US8987252B2 (en) * | 2007-05-10 | 2015-03-24 | Albany Molecular Research, Inc. | Aryloxy- and heteroaryloxy-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
EP2594557B1 (en) * | 2009-05-28 | 2016-08-10 | Novartis AG | Substituted aminopropionic derivatives as neprilysin inhibitors |
ES2748940T3 (es) | 2011-11-11 | 2020-03-18 | Univ Yale | Evaluación de la presencia de una fibrilación auricular y de la vulnerabilidad a ésta, y otras indicaciones sobre la base de la toma de imágenes basada en metaloproteinasas de matriz |
MX2017007874A (es) | 2014-12-24 | 2018-01-24 | Lg Chemical Ltd | Derivado de biarilo como agonista de gpr120. |
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GB8827308D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
GB9102635D0 (en) | 1991-02-07 | 1991-03-27 | British Bio Technology | Compounds |
CA2102890A1 (en) | 1991-05-28 | 1992-11-29 | Soumya P. Sahoo | Substituted n-carboxyalkylpeptidyl derivatives as antidegenerative active agents |
US5413999A (en) * | 1991-11-08 | 1995-05-09 | Merck & Co., Inc. | HIV protease inhibitors useful for the treatment of AIDS |
US5318964A (en) | 1992-06-11 | 1994-06-07 | Hoffmann-La Roche Inc. | Hydroxamic derivatives and pharmaceutical compositions |
GB2268935B (en) | 1992-06-24 | 1996-10-23 | Nat Heart & Lung Inst | Diagnosis of rejection of transplanted organs |
GB9215665D0 (en) * | 1992-07-23 | 1992-09-09 | British Bio Technology | Compounds |
GB9307956D0 (en) | 1993-04-17 | 1993-06-02 | Walls Alan J | Hydroxamic acid derivatives |
GB9320660D0 (en) | 1993-10-07 | 1993-11-24 | British Bio Technology | Inhibition of cytokine production |
US5508404A (en) * | 1995-03-15 | 1996-04-16 | Merck & Co., Inc. | Reductive amination process |
US6008243A (en) | 1996-10-24 | 1999-12-28 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use |
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1998
- 1998-08-14 HR HR60/068,335A patent/HRP980443A2/hr not_active Application Discontinuation
- 1998-08-14 US US09/134,484 patent/US6576664B1/en not_active Expired - Lifetime
- 1998-08-18 IL IL13395298A patent/IL133952A0/xx unknown
- 1998-08-18 CA CA002301038A patent/CA2301038A1/en not_active Abandoned
- 1998-08-18 BR BR9815596-2A patent/BR9815596A/pt not_active IP Right Cessation
- 1998-08-18 AU AU90214/98A patent/AU9021498A/en not_active Abandoned
- 1998-08-18 SK SK160-2000A patent/SK1602000A3/sk unknown
- 1998-08-18 EE EEP200000093A patent/EE200000093A/et unknown
- 1998-08-18 AR ARP980104071A patent/AR016134A1/es not_active Application Discontinuation
- 1998-08-18 CN CN98807928A patent/CN1268117A/zh active Pending
- 1998-08-18 KR KR1020007001609A patent/KR20010023001A/ko not_active Application Discontinuation
- 1998-08-18 EP EP98942083A patent/EP1005448A2/en not_active Withdrawn
- 1998-08-18 PL PL98339006A patent/PL339006A1/xx unknown
- 1998-08-18 WO PCT/US1998/017048 patent/WO1999009000A2/en not_active Application Discontinuation
-
2000
- 2000-02-17 NO NO20000784A patent/NO20000784L/no unknown
Also Published As
Publication number | Publication date |
---|---|
NO20000784D0 (no) | 2000-02-17 |
AR016134A1 (es) | 2001-06-20 |
WO1999009000A3 (en) | 1999-09-10 |
WO1999009000A2 (en) | 1999-02-25 |
EP1005448A2 (en) | 2000-06-07 |
NO20000784L (no) | 2000-04-07 |
PL339006A1 (en) | 2000-12-04 |
US6576664B1 (en) | 2003-06-10 |
KR20010023001A (ko) | 2001-03-26 |
EE200000093A (et) | 2000-12-15 |
CA2301038A1 (en) | 1999-02-25 |
AU9021498A (en) | 1999-03-08 |
SK1602000A3 (en) | 2000-09-12 |
CN1268117A (zh) | 2000-09-27 |
IL133952A0 (en) | 2001-04-30 |
BR9815596A (pt) | 2001-01-02 |
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