HRP20050137A2 - Hetero biaryl derivatives as matrix metalloproteinase inhibitors - Google Patents
Hetero biaryl derivatives as matrix metalloproteinase inhibitors Download PDFInfo
- Publication number
- HRP20050137A2 HRP20050137A2 HR20050137A HRP20050137A HRP20050137A2 HR P20050137 A2 HRP20050137 A2 HR P20050137A2 HR 20050137 A HR20050137 A HR 20050137A HR P20050137 A HRP20050137 A HR P20050137A HR P20050137 A2 HRP20050137 A2 HR P20050137A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- alkylenyl
- substituted
- phenyl
- tetrazol
- Prior art date
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- 150000005363 heterobiaryls Chemical class 0.000 title claims description 12
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 title description 2
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 492
- 150000003839 salts Chemical class 0.000 claims description 204
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 190
- -1 4-Methoxybenzylamide 4-[2-(4-methanesulfonylbenzyl)-2H-tetrazol-5-yl]pyridine-2-carboxylic acid Chemical compound 0.000 claims description 190
- 125000005466 alkylenyl group Chemical group 0.000 claims description 188
- 238000000034 method Methods 0.000 claims description 126
- 239000000203 mixture Substances 0.000 claims description 85
- 125000001424 substituent group Chemical group 0.000 claims description 72
- 125000001072 heteroaryl group Chemical group 0.000 claims description 70
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 63
- 125000004432 carbon atom Chemical group C* 0.000 claims description 60
- 229910052760 oxygen Inorganic materials 0.000 claims description 59
- 125000004434 sulfur atom Chemical group 0.000 claims description 47
- 229910020008 S(O) Inorganic materials 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 36
- 125000005842 heteroatom Chemical group 0.000 claims description 35
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 34
- 229910052721 tungsten Inorganic materials 0.000 claims description 34
- 229910052770 Uranium Inorganic materials 0.000 claims description 33
- 125000002619 bicyclic group Chemical group 0.000 claims description 31
- 231100000252 nontoxic Toxicity 0.000 claims description 29
- 230000003000 nontoxic effect Effects 0.000 claims description 29
- 125000001624 naphthyl group Chemical group 0.000 claims description 26
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 201000008482 osteoarthritis Diseases 0.000 claims description 23
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 22
- 125000002950 monocyclic group Chemical group 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 239000002585 base Substances 0.000 claims description 18
- 229910052731 fluorine Inorganic materials 0.000 claims description 17
- 150000001721 carbon Chemical group 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 13
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 12
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 12
- 239000011737 fluorine Substances 0.000 claims description 12
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000006237 oxymethylenoxy group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
- RMVDOOXVUHLPPR-UHFFFAOYSA-N 4-[[5-[3-[3-(4-fluorophenyl)prop-1-ynyl]phenyl]tetrazol-2-yl]methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CN1N=C(C=2C=C(C=CC=2)C#CCC=2C=CC(F)=CC=2)N=N1 RMVDOOXVUHLPPR-UHFFFAOYSA-N 0.000 claims description 5
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 5
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 4
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 4
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 4
- MSDHNDJEIXVNCL-UHFFFAOYSA-N 1-[4-[[5-[3-[3-(4-fluorophenyl)prop-1-ynyl]phenyl]tetrazol-2-yl]methyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(CN2N=C(N=N2)C=2C=C(C=CC=2)C#CCC=2C=CC(F)=CC=2)C=CC=1C1(C(=O)O)CC1 MSDHNDJEIXVNCL-UHFFFAOYSA-N 0.000 claims description 3
- XULFQWXPGBLAMD-UHFFFAOYSA-N 2-[4-[[5-[3-[3-(4-fluorophenyl)prop-1-ynyl]phenyl]tetrazol-2-yl]methyl]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1CN1N=C(C=2C=C(C=CC=2)C#CCC=2C=CC(F)=CC=2)N=N1 XULFQWXPGBLAMD-UHFFFAOYSA-N 0.000 claims description 3
- NFLAZYMFUQNYQY-UHFFFAOYSA-N 4-[2-[(4-cyanophenyl)methyl]tetrazol-5-yl]-n-(pyridin-4-ylmethyl)pyridine-2-carboxamide Chemical compound C=1C(C2=NN(CC=3C=CC(=CC=3)C#N)N=N2)=CC=NC=1C(=O)NCC1=CC=NC=C1 NFLAZYMFUQNYQY-UHFFFAOYSA-N 0.000 claims description 3
- OFBZVPFOXMSFJR-UHFFFAOYSA-N 4-[2-[(4-methylsulfonylphenyl)methyl]tetrazol-5-yl]-n-(pyridin-3-ylmethyl)pyridine-2-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1N=C(C=2C=C(N=CC=2)C(=O)NCC=2C=NC=CC=2)N=N1 OFBZVPFOXMSFJR-UHFFFAOYSA-N 0.000 claims description 3
- YGDLBUDIDLQOAU-UHFFFAOYSA-N 4-[2-[(4-methylsulfonylphenyl)methyl]tetrazol-5-yl]-n-(pyridin-4-ylmethyl)pyridine-2-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1N=C(C=2C=C(N=CC=2)C(=O)NCC=2C=CN=CC=2)N=N1 YGDLBUDIDLQOAU-UHFFFAOYSA-N 0.000 claims description 3
- YDYYREKOXLIKCA-UHFFFAOYSA-N 4-[2-[(4-methylsulfonylphenyl)methyl]tetrazol-5-yl]-n-(pyrimidin-5-ylmethyl)pyridine-2-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1N=C(C=2C=C(N=CC=2)C(=O)NCC=2C=NC=NC=2)N=N1 YDYYREKOXLIKCA-UHFFFAOYSA-N 0.000 claims description 3
- HYCDSMAFYDBXIZ-UHFFFAOYSA-N 4-[[5-[2-[(4-fluorophenyl)methylcarbamoyl]-6-methylpyridin-4-yl]tetrazol-2-yl]methyl]benzoic acid Chemical compound N=1C(C)=CC(C2=NN(CC=3C=CC(=CC=3)C(O)=O)N=N2)=CC=1C(=O)NCC1=CC=C(F)C=C1 HYCDSMAFYDBXIZ-UHFFFAOYSA-N 0.000 claims description 3
- ZXJYHWUCDSTYKD-UHFFFAOYSA-N 4-[[5-[2-[(4-fluorophenyl)methylcarbamoyl]pyridin-4-yl]tetrazol-2-yl]methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CN1N=C(C=2C=C(N=CC=2)C(=O)NCC=2C=CC(F)=CC=2)N=N1 ZXJYHWUCDSTYKD-UHFFFAOYSA-N 0.000 claims description 3
- VMKVNFPIDQWPRL-UHFFFAOYSA-N 4-[[5-[3-[3-(4-fluorophenyl)prop-1-ynyl]phenyl]-1,3,4-thiadiazol-2-yl]methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CC1=NN=C(C=2C=C(C=CC=2)C#CCC=2C=CC(F)=CC=2)S1 VMKVNFPIDQWPRL-UHFFFAOYSA-N 0.000 claims description 3
- RUFRYPKUYGNNEJ-UHFFFAOYSA-N 4-[[5-[3-[3-(4-fluorophenyl)prop-1-ynyl]phenyl]tetrazol-2-yl]methyl]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1CN1N=C(C=2C=C(C=CC=2)C#CCC=2C=CC(F)=CC=2)N=N1 RUFRYPKUYGNNEJ-UHFFFAOYSA-N 0.000 claims description 3
- UHJMJRJLDIOKOH-UHFFFAOYSA-N 2-[[5-[3-[3-(4-fluorophenyl)prop-1-ynyl]phenyl]tetrazol-2-yl]methyl]-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC(CN2N=C(N=N2)C=2C=C(C=CC=2)C#CCC=2C=CC(F)=CC=2)=N1 UHJMJRJLDIOKOH-UHFFFAOYSA-N 0.000 claims description 2
- JFVKCKJSGDZGIV-UHFFFAOYSA-N 3-[[5-[3-[3-(4-fluorophenyl)prop-1-ynyl]phenyl]tetrazol-2-yl]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CN2N=C(N=N2)C=2C=C(C=CC=2)C#CCC=2C=CC(F)=CC=2)=C1 JFVKCKJSGDZGIV-UHFFFAOYSA-N 0.000 claims description 2
- OTGUOURICNZALL-UHFFFAOYSA-N 4-[[5-[5-[3-(4-methoxyphenyl)prop-1-ynyl]pyridin-3-yl]tetrazol-2-yl]methyl]benzoic acid Chemical compound C1=CC(OC)=CC=C1CC#CC1=CN=CC(C2=NN(CC=3C=CC(=CC=3)C(O)=O)N=N2)=C1 OTGUOURICNZALL-UHFFFAOYSA-N 0.000 claims description 2
- IQGZKYQSUCITMB-UHFFFAOYSA-N n-[(3,4-dichlorophenyl)methyl]-4-[2-[(4-methylsulfonylphenyl)methyl]tetrazol-5-yl]pyridine-2-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1N=C(C=2C=C(N=CC=2)C(=O)NCC=2C=C(Cl)C(Cl)=CC=2)N=N1 IQGZKYQSUCITMB-UHFFFAOYSA-N 0.000 claims description 2
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- SOEGIVLPHZHKDC-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-1-yl)-4-[2-[(4-methylsulfonylphenyl)methyl]tetrazol-5-yl]pyridine-2-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CN1N=C(C=2C=C(N=CC=2)C(=O)NC2C3=CC=CC=C3CC2)N=N1 SOEGIVLPHZHKDC-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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PCT/IB2003/003616 WO2004014366A1 (en) | 2002-08-13 | 2003-08-03 | Hetero biaryl derivatives as matrix metalloproteinase inhibitors |
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