CA2651762A1 - Compounds and compositions as channel activating protease inhibitors - Google Patents
Compounds and compositions as channel activating protease inhibitors Download PDFInfo
- Publication number
- CA2651762A1 CA2651762A1 CA002651762A CA2651762A CA2651762A1 CA 2651762 A1 CA2651762 A1 CA 2651762A1 CA 002651762 A CA002651762 A CA 002651762A CA 2651762 A CA2651762 A CA 2651762A CA 2651762 A1 CA2651762 A1 CA 2651762A1
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- Prior art keywords
- compound
- reference compound
- alkyl
- optionally substituted
- mmol
- 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.)
- Abandoned
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 277
- 230000003213 activating effect Effects 0.000 title claims abstract description 45
- 239000000203 mixture Substances 0.000 title description 49
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title description 16
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title description 4
- 238000000034 method Methods 0.000 claims abstract description 117
- 108091005804 Peptidases Proteins 0.000 claims abstract description 33
- 239000004365 Protease Substances 0.000 claims abstract description 33
- 102000035195 Peptidases Human genes 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 108010031970 prostasin Proteins 0.000 claims abstract description 24
- 102100029500 Prostasin Human genes 0.000 claims abstract description 23
- 101000798702 Homo sapiens Transmembrane protease serine 4 Proteins 0.000 claims abstract description 19
- 102100032471 Transmembrane protease serine 4 Human genes 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 102100037942 Suppressor of tumorigenicity 14 protein Human genes 0.000 claims abstract description 15
- 101000661807 Homo sapiens Suppressor of tumorigenicity 14 protein Proteins 0.000 claims abstract description 8
- 102100022046 Brain-specific serine protease 4 Human genes 0.000 claims abstract description 7
- 108010059081 Cathepsin A Proteins 0.000 claims abstract description 7
- 102000005572 Cathepsin A Human genes 0.000 claims abstract description 7
- 101000897856 Homo sapiens Adenylyl cyclase-associated protein 2 Proteins 0.000 claims abstract description 7
- 101000896891 Homo sapiens Brain-specific serine protease 4 Proteins 0.000 claims abstract description 7
- 101000836079 Homo sapiens Serpin B8 Proteins 0.000 claims abstract description 7
- 101000836075 Homo sapiens Serpin B9 Proteins 0.000 claims abstract description 7
- 108010028275 Leukocyte Elastase Proteins 0.000 claims abstract description 7
- 108010091175 Matriptase Proteins 0.000 claims abstract description 7
- 102100033174 Neutrophil elastase Human genes 0.000 claims abstract description 7
- 102000004142 Trypsin Human genes 0.000 claims abstract description 7
- 108090000631 Trypsin Proteins 0.000 claims abstract description 7
- 239000012453 solvate Substances 0.000 claims abstract description 7
- 239000012588 trypsin Substances 0.000 claims abstract description 7
- 101000638154 Homo sapiens Transmembrane protease serine 2 Proteins 0.000 claims abstract description 6
- 101000798700 Homo sapiens Transmembrane protease serine 3 Proteins 0.000 claims abstract description 6
- 101100069392 Mus musculus Gzma gene Proteins 0.000 claims abstract description 6
- 102100031989 Transmembrane protease serine 2 Human genes 0.000 claims abstract description 6
- 150000004677 hydrates Chemical class 0.000 claims abstract description 6
- 101000598054 Homo sapiens Transmembrane protease serine 11B Proteins 0.000 claims abstract 3
- 101000637855 Homo sapiens Transmembrane protease serine 11E Proteins 0.000 claims abstract 3
- 101000798707 Homo sapiens Transmembrane protease serine 13 Proteins 0.000 claims abstract 3
- 102100037023 Transmembrane protease serine 11B Human genes 0.000 claims abstract 3
- 102100032001 Transmembrane protease serine 11E Human genes 0.000 claims abstract 3
- 102100032467 Transmembrane protease serine 13 Human genes 0.000 claims abstract 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- -1 methylenecyclohexyl Chemical group 0.000 claims description 29
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000003386 piperidinyl group Chemical group 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 19
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- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 18
- 208000006673 asthma Diseases 0.000 claims description 14
- 125000001544 thienyl group Chemical group 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 125000001475 halogen functional group Chemical group 0.000 claims description 11
- 230000001404 mediated effect Effects 0.000 claims description 11
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 11
- 125000002837 carbocyclic group Chemical group 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 8
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 230000003182 bronchodilatating effect Effects 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
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- 229910052799 carbon Inorganic materials 0.000 claims description 5
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- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
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- 206010036790 Productive cough Diseases 0.000 claims description 4
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 4
- 238000009825 accumulation Methods 0.000 claims description 4
- 230000001387 anti-histamine Effects 0.000 claims description 4
- 229940124584 antitussives Drugs 0.000 claims description 4
- 208000007451 chronic bronchitis Diseases 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
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- 210000003802 sputum Anatomy 0.000 claims description 4
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- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
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- 206010057190 Respiratory tract infections Diseases 0.000 claims description 3
- 230000000954 anitussive effect Effects 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 230000003115 biocidal effect Effects 0.000 claims description 3
- 210000000424 bronchial epithelial cell Anatomy 0.000 claims description 3
- 125000005959 diazepanyl group Chemical group 0.000 claims description 3
- 201000005296 lung carcinoma Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 201000009266 primary ciliary dyskinesia Diseases 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical group C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 229910017852 NH2NH2 Inorganic materials 0.000 claims 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 claims 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 228
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 195
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 167
- 238000005481 NMR spectroscopy Methods 0.000 description 130
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 122
- 229910001868 water Inorganic materials 0.000 description 103
- 238000006243 chemical reaction Methods 0.000 description 91
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 91
- 239000000243 solution Substances 0.000 description 91
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 87
- 239000000543 intermediate Substances 0.000 description 85
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- 235000019439 ethyl acetate Nutrition 0.000 description 84
- 239000002904 solvent Substances 0.000 description 77
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 55
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
- 239000011541 reaction mixture Substances 0.000 description 52
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 49
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 47
- 238000002360 preparation method Methods 0.000 description 47
- 239000012267 brine Substances 0.000 description 45
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 45
- 239000003153 chemical reaction reagent Substances 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 37
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- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000000926 separation method Methods 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
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
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- 239000011593 sulfur Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- WDPWEXWMQDRXAL-UHFFFAOYSA-N tert-butyl 1,4-diazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCNCC1 WDPWEXWMQDRXAL-UHFFFAOYSA-N 0.000 description 1
- LBQDLHPFISVBRU-UHFFFAOYSA-N tert-butyl 4-(2-aminoethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CCN)CC1 LBQDLHPFISVBRU-UHFFFAOYSA-N 0.000 description 1
- KLKBCNDBOVRQIJ-UHFFFAOYSA-N tert-butyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CN)CC1 KLKBCNDBOVRQIJ-UHFFFAOYSA-N 0.000 description 1
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
- YWSXTMBDIBZHBB-UHFFFAOYSA-N tert-butyl n-but-3-enylcarbamate Chemical compound CC(C)(C)OC(=O)NCCC=C YWSXTMBDIBZHBB-UHFFFAOYSA-N 0.000 description 1
- DJJOYDXRUBOZON-UHFFFAOYSA-N tert-butyl n-methyl-n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)C1CCNCC1 DJJOYDXRUBOZON-UHFFFAOYSA-N 0.000 description 1
- CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- FKKJJPMGAWGYPN-UHFFFAOYSA-N thiophen-2-ylmethanamine Chemical compound NCC1=CC=CS1 FKKJJPMGAWGYPN-UHFFFAOYSA-N 0.000 description 1
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical class O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 1
- 229960000707 tobramycin Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- 229960004764 zafirlukast Drugs 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
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- 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
- C07D413/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
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- Oncology (AREA)
- Communicable Diseases (AREA)
- Ophthalmology & Optometry (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
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| US80298306P | 2006-05-23 | 2006-05-23 | |
| US60/802,983 | 2006-05-23 | ||
| US86060406P | 2006-11-22 | 2006-11-22 | |
| US60/860,604 | 2006-11-22 | ||
| PCT/US2007/069059 WO2007137080A2 (en) | 2006-05-23 | 2007-05-16 | Compounds and compositions as channel activating protease inhibitors |
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| CA2651762A1 true CA2651762A1 (en) | 2007-11-29 |
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| CA002651762A Abandoned CA2651762A1 (en) | 2006-05-23 | 2007-05-16 | Compounds and compositions as channel activating protease inhibitors |
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| GB0507577D0 (en) * | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
| WO2007140117A1 (en) * | 2006-05-23 | 2007-12-06 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| US7951823B2 (en) * | 2006-05-23 | 2011-05-31 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| CN101600428A (zh) * | 2007-02-09 | 2009-12-09 | Irm责任有限公司 | 作为通道活化蛋白酶抑制剂的化合物和组合物 |
| CA2677485A1 (en) * | 2007-02-09 | 2008-08-14 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| IE20070935A1 (en) * | 2007-12-21 | 2009-06-24 | Trinity College Dublin | Guanidine based compounds and their use in the treatment of mental and neurological disorders. |
| PL2421826T3 (pl) * | 2009-04-20 | 2014-03-31 | Hoffmann La Roche | Pochodne proliny jako inhibitory katepsyn |
| CA2826623A1 (en) * | 2010-02-03 | 2011-08-11 | Meh Associates, Inc | Multiple substituted fluoromethanes as selective and bioactive isosteres |
| MX2014006211A (es) | 2011-11-25 | 2014-08-08 | Hoffmann La Roche | Nuevos derivados de pirrolidina como inhibidores de catepsina. |
| RU2728785C2 (ru) | 2014-10-06 | 2020-07-31 | Кортексим, Инк. | Ингибиторы лизинспецифичного гингипаина |
| CN105001131A (zh) * | 2015-07-31 | 2015-10-28 | 吉尔生化(上海)有限公司 | 一种医药中间体nα-z-s-苄基-l-半胱氨酸-4-硝基苯酯的合成方法 |
| CA3004095A1 (en) | 2015-11-09 | 2017-05-18 | Cortexyme, Inc. | Inhibitors of arginine gingipain |
| CN109983012B (zh) | 2016-09-16 | 2023-12-01 | 莱特豪斯制药公司 | 赖氨酸牙龈蛋白酶的酮抑制剂 |
| CN110483437B (zh) * | 2018-05-14 | 2022-12-06 | 嘉兴维眸生物科技有限公司 | 一种含五元环的化合物及其制备和应用 |
| CA3154761A1 (en) | 2019-09-17 | 2021-03-25 | Mereo Biopharma 4 Limited | Alvelestat for use in the treatment of graft rejection, bronchiolitis obliterans syndrome and graft versus host disease |
| SI4106757T1 (sl) | 2020-04-16 | 2023-11-30 | Mereo Biopharma 4 Limited | Postopki, ki vključujejo zaviralec nevtrofilne elastaze alvelestat, za zdravljenje bolezni dihal, ki jo sproži pomanjkanje antitripsina alfa-1 |
| WO2023067103A1 (en) | 2021-10-20 | 2023-04-27 | Mereo Biopharma 4 Limited | Neutrophil elastase inhibitors for use in the treatment of fibrosis |
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| GB8809316D0 (en) * | 1987-05-11 | 1988-05-25 | Ici America Inc | Heterocyclic ketones |
| US5672582A (en) | 1993-04-30 | 1997-09-30 | Merck & Co., Inc. | Thrombin inhibitors |
| IL112795A (en) | 1994-03-04 | 2001-01-28 | Astrazeneca Ab | Peptide derivatives as antithrombic agents their preparation and pharmaceutical compositions containing them |
| US5726159A (en) * | 1994-03-04 | 1998-03-10 | Eli Lilly And Company | Antithrombotic agents |
| US5705487A (en) * | 1994-03-04 | 1998-01-06 | Eli Lilly And Company | Antithrombotic agents |
| ZA951618B (en) | 1994-03-04 | 1996-08-27 | Lilly Co Eli | Antithrombotic agents |
| US5707966A (en) * | 1994-03-04 | 1998-01-13 | Eli Lilly And Company | Antithrombotic agents |
| HU221197B1 (en) | 1994-06-02 | 2002-08-28 | Aventis Pharma Inc | Elastase inhibitor tripeptides and pharmaceutical compositions comprising thereof |
| JPH0820597A (ja) | 1994-07-07 | 1996-01-23 | Meiji Seika Kaisha Ltd | トロンビン阻害作用を有する複素環カルボニル化合物 |
| US5618792A (en) * | 1994-11-21 | 1997-04-08 | Cortech, Inc. | Substituted heterocyclic compounds useful as inhibitors of (serine proteases) human neutrophil elastase |
| US5710130A (en) * | 1995-02-27 | 1998-01-20 | Eli Lilly And Company | Antithrombotic agents |
| US5914319A (en) * | 1995-02-27 | 1999-06-22 | Eli Lilly And Company | Antithrombotic agents |
| CA2176414A1 (en) | 1995-05-18 | 1996-11-19 | S. David Kimball | Acyl guanidine and amidine prodrugs |
| US5827860A (en) | 1995-06-07 | 1998-10-27 | Ortho Pharmaceutical Corporation | Peptidyl heterocycles useful in the treatment of thrombin related disorders |
| US5523308A (en) | 1995-06-07 | 1996-06-04 | Costanzo; Michael J. | Peptidyl heterocycles useful in the treatment of thrombin related disorders |
| US6211154B1 (en) * | 1995-06-07 | 2001-04-03 | Cor Therapeutics, Inc. | Ketoheterocyclic inhibitors of factor Xa |
| US6022861A (en) * | 1995-06-07 | 2000-02-08 | Cor Therapeutics, Inc. | Ketoheterocyclic inhibitors of factor Xa |
| US6069130A (en) | 1995-06-07 | 2000-05-30 | Cor Therapeutics, Inc. | Ketoheterocyclic inhibitors of factor Xa |
| US5827866A (en) | 1995-06-07 | 1998-10-27 | Ortho Pharmaceutical Corporation | Peptidyl heterocycles useful in the treatment of thrombin related disorders |
| IL119466A (en) | 1995-11-03 | 2001-08-26 | Akzo Nobel Nv | Thrombin inhibitors, their preparation and pharmaceutical compositions containing them |
| IL120311A (en) | 1996-03-01 | 2001-10-31 | Akzo Nobel Nv | Serine protease inhibitors and pharmaceuticals containing them |
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-
2007
- 2007-05-16 US US11/749,430 patent/US7951823B2/en not_active Expired - Fee Related
- 2007-05-16 CA CA002651762A patent/CA2651762A1/en not_active Abandoned
- 2007-05-16 EP EP07783835A patent/EP2027143A2/en not_active Withdrawn
- 2007-05-16 AU AU2007253819A patent/AU2007253819B2/en not_active Ceased
- 2007-05-16 RU RU2008150615/04A patent/RU2419626C2/ru not_active IP Right Cessation
- 2007-05-16 BR BRPI0712021-4A patent/BRPI0712021A2/pt not_active IP Right Cessation
- 2007-05-16 WO PCT/US2007/069059 patent/WO2007137080A2/en not_active Ceased
- 2007-05-16 MX MX2008014839A patent/MX2008014839A/es active IP Right Grant
- 2007-05-16 JP JP2009512222A patent/JP2009538327A/ja active Pending
- 2007-05-16 KR KR1020087031129A patent/KR101069051B1/ko not_active Expired - Fee Related
- 2007-05-23 AR ARP070102231A patent/AR061109A1/es not_active Application Discontinuation
- 2007-05-23 CL CL200701481A patent/CL2007001481A1/es unknown
- 2007-05-23 TW TW096118422A patent/TW200813094A/zh unknown
- 2007-05-23 PE PE2007000642A patent/PE20080708A1/es not_active Application Discontinuation
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2011
- 2011-04-19 US US13/089,973 patent/US8338469B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| TW200813094A (en) | 2008-03-16 |
| KR20090014217A (ko) | 2009-02-06 |
| KR101069051B1 (ko) | 2011-09-29 |
| US8338469B2 (en) | 2012-12-25 |
| JP2009538327A (ja) | 2009-11-05 |
| EP2027143A2 (en) | 2009-02-25 |
| AU2007253819A1 (en) | 2007-11-29 |
| CL2007001481A1 (es) | 2008-05-09 |
| US20070275906A1 (en) | 2007-11-29 |
| BRPI0712021A2 (pt) | 2012-01-03 |
| WO2007137080A3 (en) | 2008-01-24 |
| US20110257077A1 (en) | 2011-10-20 |
| US7951823B2 (en) | 2011-05-31 |
| AR061109A1 (es) | 2008-08-06 |
| RU2419626C2 (ru) | 2011-05-27 |
| MX2008014839A (es) | 2008-12-05 |
| PE20080708A1 (es) | 2008-07-30 |
| WO2007137080A2 (en) | 2007-11-29 |
| AU2007253819B2 (en) | 2011-02-17 |
| RU2008150615A (ru) | 2010-06-27 |
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| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20130927 |