TW534905B - Heterocyclic compounds, intermediates therefor, and elastase inhibitors - Google Patents
Heterocyclic compounds, intermediates therefor, and elastase inhibitors Download PDFInfo
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- TW534905B TW534905B TW089103336A TW89103336A TW534905B TW 534905 B TW534905 B TW 534905B TW 089103336 A TW089103336 A TW 089103336A TW 89103336 A TW89103336 A TW 89103336A TW 534905 B TW534905 B TW 534905B
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- isopropyl
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- 150000002391 heterocyclic compounds Chemical class 0.000 title claims abstract description 8
- 239000003602 elastase inhibitor Substances 0.000 title abstract description 11
- 239000000543 intermediate Substances 0.000 title description 5
- -1 2-benzoxazolyl Chemical group 0.000 claims abstract description 92
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 24
- 150000002148 esters Chemical class 0.000 claims abstract description 13
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 7
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims abstract description 5
- 239000004480 active ingredient Substances 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims description 192
- 229960002429 proline Drugs 0.000 claims description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 102000016387 Pancreatic elastase Human genes 0.000 claims description 12
- 108010067372 Pancreatic elastase Proteins 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 claims description 7
- 102000052502 human ELANE Human genes 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
- 229930182821 L-proline Natural products 0.000 claims description 5
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 4
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 claims description 4
- 229940125904 compound 1 Drugs 0.000 claims description 4
- 229940125782 compound 2 Drugs 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 229940125898 compound 5 Drugs 0.000 claims description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 2
- 239000003591 leukocyte elastase inhibitor Substances 0.000 claims description 2
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 claims 1
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 150000001923 cyclic compounds Chemical class 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 abstract description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 abstract description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 4
- 125000000638 benzylaminocarbonyl group Chemical group C(C1=CC=CC=C1)NC(=O)* 0.000 abstract description 2
- 230000003448 neutrophilic effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 51
- 238000011049 filling Methods 0.000 description 48
- 238000005481 NMR spectroscopy Methods 0.000 description 43
- 238000000034 method Methods 0.000 description 38
- 101150041968 CDC13 gene Proteins 0.000 description 31
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 31
- 238000004519 manufacturing process Methods 0.000 description 30
- 230000002079 cooperative effect Effects 0.000 description 29
- 239000000243 solution Substances 0.000 description 29
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- 238000006243 chemical reaction Methods 0.000 description 24
- 230000002829 reductive effect Effects 0.000 description 24
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 11
- 239000013078 crystal Substances 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 210000000440 neutrophil Anatomy 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 241000699800 Cricetinae Species 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 235000011054 acetic acid Nutrition 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 238000009434 installation Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 239000002504 physiological saline solution Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 125000004434 sulfur atom Chemical group 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 230000002849 elastaseinhibitory effect Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- FATAVLOOLIRUNA-UHFFFAOYSA-N formylmethyl Chemical group [CH2]C=O FATAVLOOLIRUNA-UHFFFAOYSA-N 0.000 description 5
- BMFVGAAISNGQNM-UHFFFAOYSA-N isopentylamine Chemical compound CC(C)CCN BMFVGAAISNGQNM-UHFFFAOYSA-N 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 229940122858 Elastase inhibitor Drugs 0.000 description 4
- 102000001554 Hemoglobins Human genes 0.000 description 4
- 108010054147 Hemoglobins Proteins 0.000 description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
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- 150000002440 hydroxy compounds Chemical class 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
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- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
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- 229910052717 sulfur Inorganic materials 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 3
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 description 3
- 108010028275 Leukocyte Elastase Proteins 0.000 description 3
- 102000016799 Leukocyte elastase Human genes 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
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- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 3
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- 238000000354 decomposition reaction Methods 0.000 description 3
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- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- 125000005702 oxyalkylene group Chemical group 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229910052704 radon Inorganic materials 0.000 description 1
- SYUHGPGVQRZVTB-UHFFFAOYSA-N radon atom Chemical compound [Rn] SYUHGPGVQRZVTB-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000002940 repellent Effects 0.000 description 1
- 239000005871 repellent Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical class [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 238000009941 weaving Methods 0.000 description 1
- 101150008351 ycf3 gene Proteins 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. 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
- 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
- C07K5/0821—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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11056052A JP2000256396A (ja) | 1999-03-03 | 1999-03-03 | 複素環式化合物およびその中間体ならびにエラスターゼ阻害剤 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW534905B true TW534905B (en) | 2003-06-01 |
Family
ID=13016323
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW089103336A TW534905B (en) | 1999-03-03 | 2000-02-25 | Heterocyclic compounds, intermediates therefor, and elastase inhibitors |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6835714B1 (enExample) |
| EP (1) | EP1157998B1 (enExample) |
| JP (1) | JP2000256396A (enExample) |
| KR (1) | KR100622709B1 (enExample) |
| CN (1) | CN1183156C (enExample) |
| AT (1) | ATE259376T1 (enExample) |
| AU (1) | AU758739B2 (enExample) |
| CA (1) | CA2362911A1 (enExample) |
| DE (1) | DE60008218T2 (enExample) |
| DK (1) | DK1157998T3 (enExample) |
| ES (1) | ES2215608T3 (enExample) |
| HK (1) | HK1044955B (enExample) |
| HU (1) | HUP0200608A3 (enExample) |
| IL (2) | IL144813A0 (enExample) |
| MX (1) | MXPA01008836A (enExample) |
| NZ (1) | NZ513594A (enExample) |
| PL (1) | PL199136B1 (enExample) |
| PT (1) | PT1157998E (enExample) |
| RU (1) | RU2222539C2 (enExample) |
| TR (1) | TR200102540T2 (enExample) |
| TW (1) | TW534905B (enExample) |
| WO (1) | WO2000052032A1 (enExample) |
| ZA (1) | ZA200106514B (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2289887A3 (en) | 2000-06-30 | 2011-07-06 | Seikagaku Corporation | Epoxycarboxylic acid amides, azides and amino alcohols and processes for preparation of alpha-keto amides by using them |
| AR029851A1 (es) | 2000-07-21 | 2003-07-16 | Dendreon Corp | Nuevos peptidos como inhibidores de ns3-serina proteasa del virus de hepatitis c |
| SK742003A3 (en) | 2000-07-21 | 2003-06-03 | Schering Corp | Novel peptides as NS3-serine protease inhibitors of hepatitis C virus |
| US7244721B2 (en) | 2000-07-21 | 2007-07-17 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
| US7012066B2 (en) * | 2000-07-21 | 2006-03-14 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
| GB0021315D0 (en) | 2000-08-30 | 2000-10-18 | Dainippon Pharmaceutical Co | Heterocyclic compounds and intermediates thereof |
| WO2002026229A1 (en) * | 2000-09-29 | 2002-04-04 | Ono Pharmaceutical Co., Ltd. | Airway mucus secretion inhibitors |
| PL371539A1 (en) * | 2002-02-05 | 2005-06-27 | Dainippon Pharmaceutical Co, Ltd. | Heterocyclic compounds having elastase-inhibiting activity and intermediates thereof |
| ATE438622T1 (de) * | 2004-02-27 | 2009-08-15 | Schering Corp | 3,4-(cyclopentyl)kondensierte prolinverbindungen als inhibitoren der ns3-serinprotease des hepatitis-c-virus |
| EP2019837B1 (en) * | 2006-05-23 | 2011-03-23 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| EP2027143A2 (en) * | 2006-05-23 | 2009-02-25 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| WO2008032331A1 (en) * | 2006-09-12 | 2008-03-20 | Himalaya Global Holdings Ltd. | Herbal composition for the prevention of wrinkles and skin disorders, methods of preparing the same and uses thereof |
| CA2677485A1 (en) * | 2007-02-09 | 2008-08-14 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| CA2677487A1 (en) * | 2007-02-09 | 2008-08-14 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| US9353113B2 (en) | 2011-03-18 | 2016-05-31 | Ono Pharmaceutical Co., Ltd. | Tetrahydrocarboline derivative |
| CN104031014B (zh) * | 2013-03-08 | 2016-05-11 | 华中师范大学 | 香豆素衍生物及其制备方法以及弹性蛋白酶活性检测方法和检测试剂盒 |
| CN104165869B (zh) * | 2013-05-17 | 2016-12-28 | 华中师范大学 | 一种检测蛋白水解酶活性的方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS231228B1 (en) | 1982-10-01 | 1984-10-15 | Evzen Kasafirek | Biologically effective tri and tetrapeptide alkylamide derivatives and their processing method |
| GB8600263D0 (en) | 1985-01-22 | 1986-02-12 | Ici America Inc | Peptide derivatives |
| GB8809316D0 (en) | 1987-05-11 | 1988-05-25 | Ici America Inc | Heterocyclic ketones |
| CA1340191C (en) | 1988-06-13 | 1998-12-15 | Katsuhiro Imaki | Derivatives of p-substituted phenyl ester of pivalic acid |
| IT1245712B (it) * | 1991-04-09 | 1994-10-14 | Boehringer Mannheim Italia | Ammine eterocicliche utili terapia dell'asma e dell'infiammazione delle vie aeree |
| IT1255704B (it) * | 1992-09-30 | 1995-11-10 | Boehringer Mannheim Italia | Ammine eterocicliche utili nella terapia dell'asma e dell'infiammazione delle vie aeree |
| US5565568A (en) * | 1995-04-06 | 1996-10-15 | Eli Lilly And Company | 2-acylaminopropanamides as tachykinin receptor antagonists |
-
1999
- 1999-03-03 JP JP11056052A patent/JP2000256396A/ja active Pending
-
2000
- 2000-02-23 CA CA002362911A patent/CA2362911A1/en not_active Abandoned
- 2000-02-23 IL IL14481300A patent/IL144813A0/xx active IP Right Grant
- 2000-02-23 TR TR2001/02540T patent/TR200102540T2/xx unknown
- 2000-02-23 HU HU0200608A patent/HUP0200608A3/hu unknown
- 2000-02-23 WO PCT/JP2000/001022 patent/WO2000052032A1/ja not_active Ceased
- 2000-02-23 ES ES00905282T patent/ES2215608T3/es not_active Expired - Lifetime
- 2000-02-23 CN CNB008070636A patent/CN1183156C/zh not_active Expired - Fee Related
- 2000-02-23 EP EP00905282A patent/EP1157998B1/en not_active Expired - Lifetime
- 2000-02-23 AT AT00905282T patent/ATE259376T1/de not_active IP Right Cessation
- 2000-02-23 DE DE60008218T patent/DE60008218T2/de not_active Expired - Fee Related
- 2000-02-23 AU AU26902/00A patent/AU758739B2/en not_active Ceased
- 2000-02-23 MX MXPA01008836A patent/MXPA01008836A/es active IP Right Grant
- 2000-02-23 NZ NZ513594A patent/NZ513594A/xx unknown
- 2000-02-23 HK HK02106283.1A patent/HK1044955B/zh not_active IP Right Cessation
- 2000-02-23 KR KR1020017011031A patent/KR100622709B1/ko not_active Expired - Fee Related
- 2000-02-23 DK DK00905282T patent/DK1157998T3/da active
- 2000-02-23 PT PT00905282T patent/PT1157998E/pt unknown
- 2000-02-23 RU RU2001126725/04A patent/RU2222539C2/ru not_active IP Right Cessation
- 2000-02-23 PL PL349709A patent/PL199136B1/pl not_active IP Right Cessation
- 2000-02-23 US US09/913,538 patent/US6835714B1/en not_active Expired - Fee Related
- 2000-02-25 TW TW089103336A patent/TW534905B/zh not_active IP Right Cessation
-
2001
- 2001-08-08 IL IL144813A patent/IL144813A/en not_active IP Right Cessation
- 2001-08-08 ZA ZA200106514A patent/ZA200106514B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HK1044955B (zh) | 2005-07-08 |
| CN1183156C (zh) | 2005-01-05 |
| KR100622709B1 (ko) | 2006-09-13 |
| RU2222539C2 (ru) | 2004-01-27 |
| PT1157998E (pt) | 2004-06-30 |
| EP1157998B1 (en) | 2004-02-11 |
| AU758739B2 (en) | 2003-03-27 |
| EP1157998A4 (en) | 2003-01-29 |
| IL144813A (en) | 2006-12-10 |
| KR20020002396A (ko) | 2002-01-09 |
| JP2000256396A (ja) | 2000-09-19 |
| CA2362911A1 (en) | 2000-09-08 |
| US6835714B1 (en) | 2004-12-28 |
| ES2215608T3 (es) | 2004-10-16 |
| HK1044955A1 (en) | 2002-11-08 |
| DE60008218T2 (de) | 2004-12-09 |
| TR200102540T2 (tr) | 2002-01-21 |
| MXPA01008836A (es) | 2002-05-14 |
| NZ513594A (en) | 2003-04-29 |
| HUP0200608A3 (en) | 2002-09-30 |
| IL144813A0 (en) | 2002-06-30 |
| DK1157998T3 (da) | 2004-06-14 |
| EP1157998A1 (en) | 2001-11-28 |
| ZA200106514B (en) | 2002-05-10 |
| HUP0200608A2 (en) | 2002-08-28 |
| CN1349542A (zh) | 2002-05-15 |
| ATE259376T1 (de) | 2004-02-15 |
| AU2690200A (en) | 2000-09-21 |
| WO2000052032A1 (en) | 2000-09-08 |
| DE60008218D1 (de) | 2004-03-18 |
| PL199136B1 (pl) | 2008-08-29 |
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