KR930010015A - 단백질 분해효소 억제제인 2-치환된 사카린 유도체 - Google Patents
단백질 분해효소 억제제인 2-치환된 사카린 유도체 Download PDFInfo
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- KR930010015A KR930010015A KR1019920021437A KR920021437A KR930010015A KR 930010015 A KR930010015 A KR 930010015A KR 1019920021437 A KR1019920021437 A KR 1019920021437A KR 920021437 A KR920021437 A KR 920021437A KR 930010015 A KR930010015 A KR 930010015A
- Authority
- KR
- South Korea
- Prior art keywords
- phenyl
- alkyl
- oxadiazol
- alkoxy
- substituted
- Prior art date
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical class C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 title abstract 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 19
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 16
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 9
- 239000001257 hydrogen Substances 0.000 claims abstract 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract 5
- 150000002431 hydrogen Chemical class 0.000 claims abstract 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 4
- 108091005804 Peptidases Proteins 0.000 claims abstract 3
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract 3
- -1 lower-alkoxycarbonyl Chemical group 0.000 claims 124
- 150000001875 compounds Chemical class 0.000 claims 13
- 125000005843 halogen group Chemical group 0.000 claims 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 3
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- 125000004518 1,2,5-thiadiazol-3-yl group Chemical group S1N=C(C=N1)* 0.000 claims 2
- 239000004365 Protease Substances 0.000 claims 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 2
- 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 claims 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims 1
- 125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 claims 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims 1
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 claims 1
- LYTMVABTDYMBQK-UHFFFAOYSA-N 2-benzothiophene Chemical compound C1=CC=CC2=CSC=C21 LYTMVABTDYMBQK-UHFFFAOYSA-N 0.000 claims 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 claims 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims 1
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims 1
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims 1
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 claims 1
- 102000035195 Peptidases Human genes 0.000 abstract 1
- 230000002255 enzymatic effect Effects 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 208000015122 neurodegenerative disease Diseases 0.000 abstract 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 abstract 1
- 229940081974 saccharin Drugs 0.000 abstract 1
- 235000019204 saccharin Nutrition 0.000 abstract 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
-
- 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
- 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
- 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
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
- C07F9/6539—Five-membered rings
- C07F9/6541—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
본 발명은 퇴행성 질환의 치료에 유용하며 하기 일반식을 갖는, 단백질분해 효소의 효소 활성을 억제하는 신규한 2-치환된 사카린, 및 그의 제조방법 및 약학 조성물 및 사용방법을 개시한다.
상기식에서, L은 -O-, -S-, -SO-또는 -SO2이고; m 및 n은 각각 독립적으로 0또는 1이고; R1은 할로, 저급-알카노일, 1-옥소페날레닐, 페닐 또는 치환된 페닐, 헤테로사이클릴 또는 치환된 헤테로 사이클리이거나, 또는 L이 -O-이고, n이 1일 때 사이클로헵타트리에논-2-일이거나, 또는 L이 -S-이고 n이 1일 때, 시아노 또는 저급-알콕시티오 카보닐이거나, 또는 L이 -SO2이고 n이 1일 때, 저급-알킬 또는 트리플루오로메틸이고; R2는 수소, 저급-알콕시카보닐, 페닐 또는 페닐티오이고; R3및 R4는 각각 수소 또는 다양한 치환체이다.
Description
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Claims (13)
- 하기 일반식(I)의 화합물:상기식에서, L은 -O-, -S-, -SO-또는 -SO2이고; m 및 n은 각각 독립적으로 0또는 1이고; R1은 1-(4-저급-알킬피페라진-1-일)카보닐, 포르밀, 저급-알콕시카보닐, 4-티아모르폴리닐설포닐 또는 그의 S-디옥사이드, 하이드록시-저급-알킬, 할로-저급-알킬, 4-모르폴리닐-저급-알킬아미노카보닐, 4-모르폴리닐-저급-알콕시카보닐, 1-(4-저급-알킬피페라진-1-일)설포닐, 4-모르폴리닐-저급-알콕시, 디-저급-알킬아미노-저급-알킬아미노설포닐 또는 그이 N-저급-알킬 유도체, 저급-알킬-설포닐, 4,5-디하이드로옥사졸-2-일, 저급-알킬테트라졸-5-일, 4-모르폴리닐카보닐, 니트로 페닐아조, 카복실 또는 디-저급-알킬포스포닐에 의해 치환된 페닐, 또는 피리다진-3-일, 4-피론-3-일, 퀴놀린-8-일, 1,3,4-옥사디아졸-2-일, 쿠마린-7-일, 사카린-6-일, 이미다졸-1-일, 1.3.4-트리아졸-2-일, 티아졸-2-일, 2-티옥소-2,3-디하이드로-1,3,4-옥사디아졸-3-일, 1,2,5-티아디아졸-3-일, 2-티옥소-2,3-디하이드로-1,3,4-티아디아졸-3-일, 2-티옥소-2,3-디하이드로-1,3,4-티아디아졸-5-일, 1,2,3-트리아졸-2-일 1,2,4-트리아진-5-일, 5-옥소-6-하이드록시-4,5-디하이드로-1,24-트리아진-5-일, 이속사졸-5-일, 이속사졸-3-일, 4,5-디하이드로-5-옥소-1,2,4-옥사디아졸-4-일, 피리딜, 1,1,3-트리옥소-테트라하이드로-1,25-티아디아졸-2-일, 6,7-디하이드로-1H-1,2,4-트리아졸로[3,4-b][1,3]티아진-3-일, 4,5-디하이드로-5-옥소-1,2,4-옥사디아졸-4-일, 2,5-디옥소피롤리딘-1-일, 2,3--디하이드로-2-일, 티아졸-4-일, 2,3-디하이드로-2-옥소-5-페닐-1,3,4,-티아디아졸-3-일, 2,3-디하이드로-2-옥소-5-페닐-1,3,4-옥사디아졸-3-일, 6-옥소-1,2-디하이드로-1,2,4-트리아진-1-일, 1,2,3-트리아진-1-일 및 1-인돌릴로부터 선택된 헤테로사이클릴, 또는 임의의 이용가능한 질소 원자에서 저급-알킬, 하이드록시-저급-알킬, 사이클로알킬, 2-,3- 또는 4-피리디닐, 카복시-저급-알킬, 저급-알콕시카보닐-저급-알킬, 아미노카보닐-저급-알킬, 저급-알킬아미노-카보닐-저급-알킬, 디-저급-알킬아미노-카보닐-저급-알킬, 아미노-저급-알킬, 저급-알킬아미노-저급-알킬, 디-저급-알킬-아미노-저급-알킬, 4-모르폴리닐-저급-알킬, 1-피페리디닐-저급-알킬, 1-피롤리디닐-저급-알킬, 또는 페닐, 또는 아미, 저급-알킬-아미노, 디-저급-알킬아미노, 저급-알칸아미도, N-저급-알킬-저급-알카아미도, 카복시-저급-알칸아미도, 카복시, 저급-알콕시카보닐, 저급-알콕시 또는 할로에 의해 치환된 페닐에 의해 치환된 상기 헤테로사이클릴, 또는 임의의 이용가능한 질소 원자에서 니트로, 저급-알킬-아미노, 저급-알킬아미노, 디-저급-알킬아미노, 사이클로 알킬아미노, 머캅토, 저급-알킬티오, 아미노-저급-알킬티오, 저급-알킬아미노-저급-알킬아미노-저급-알킬티오, 저급-알콕시카보닐, 디-저급-알킬아미노-저급-알킬, 4-모르폴리닐-저급-알킬아미노, 시아노, 1-피페리디닐-저급-알킬, 하이드록시-저급-알콕시, 피라지닐, 저급-알콕시카보닐-저급-알킬, 또는 벤조일, 또는 저급-알콕시 또는 할로에 의해 치환된 벤조일, 또는 페닐, 또는 아미노, 저급-알킬아미노, 디-저급-알킬아미노, 저급-알칸아미도, -N-저급-알킬-저급-알칸아미도, 저급-알킬, 저급-알콕시, 할로, 트리플루오로메틸, 저급-알콕시-폴리-저급-알콕시, 메틸렌디옥시 또는 저급알콕시카보닐에 의해 치환된 페닐에 의해 치환된 상기 헤테로사이클리, 또는 1H-(5-테트라졸릴), 5-옥소-1-테트라졸리닐, 5-티옥소-1-테트라졸리닐(하기 정의된 R2가 페닐티오이외의 것일 때), 피리미디닐, 2-벤조옥사졸릴, 2-벤조티아졸릴 것일 때), 피리미디닐, 2-벤조옥사졸릴, 2-벤조티아졸릴, 2-프탈이미딜, 2-(1,3,4-티아디아졸릴), 5-(1,2,4-티아디아졸릴), 5-티옥소-3-(1,2,4-티아디졸릴)4-(5-티옥소-1,34-티아디아졸릴) 3-(1,24-트리아졸릴), 4-(1,2,4-틀리아졸릴), 1,2,3-트리아졸-1-일, 2-이미다졸릴 및 임의의 이용가능한 탄소원자에서 디-저급-알킬아미노-저급-알킬, 4-모르폴리닐-저급-알킬아미노, 시아노, 1-피페리디닐-저급-알킬, 하이드록시-저급-알킬, 페닐설포닐, 톨루엔설포닐, 할로, 트리-저급-알킬실릴, 카복시 또는 그의 알칼리 금속염, 푸릴, 트리플루오로메틸, 2-벤조티아졸릴, 저급-알킬설포닐, 아미노카보닐, 벤질, 4-모르폴리닐, 피리디닐, 저급-알콕시, 피라지닐, 저급-알콕시카보닐-저급-알킬, 벤조일, 또는 저급-알콕시 또는 할로에 의해 치환된 벤조일, 또는 트리플루오로메틸, 저급-알콕시-폴리-저급-알콕시, 메틸렌디옥시 또는 저급알콕시카보닐에 의해 치환된 벤조일, 또는 트리플루오로메틸, 저급-알콕시-폴리-저급-알콕시 메틸렌디옥시 또는 저급알콕시카보닐에 의해 치환된 페닐에 의해 치환된 3-(1,2,4-트리아졸로[4,3-a]피리디닐)로부터 선택된 헤테로사이클리이거나, 또는 R4가 카복시-저급-알콕시, 적 Q-알콕시카보닐-저급-알콕시 또는 디-저급-아릴아미노카보닐옥시일 때 헤테로사이클릴은 1-페닐테트라졸-5-일이거나, 또는 L이 -O-이고 n이 1일 때, 사이클로헵타트리에논-2-일 이거나, 또는 L이 -S-이고 n이 1일 때, 시아노 또는 저급-알콕시카보닐, 페닐 또는 페닐티오이고; R3는 수소, 할로, 1차 또는 2차 저급-알킬, 저급-알콕시, 저급-알콕시카보닐, 페닐, 플루오로-저급-알킬, 저급-알케닐, 시아노 또는 디-저급-알킬아미노이고; R4는 수소, 또는 할로, 시아노, 니트로, 아미노, 저급-알칸아미도, 페닐-저급-알칸아미노, 디페닐-저급-알칸아미도, 저급-알킬설포닐아미노, 폴리플루오로-저급-알킬설포닐아미노, 아미노설포닐, 저급-알킬폴리할로-저급-알킬, 사이클로알킬, 폴리할로-저급-알콕시, 하이드록시, 저급-알콜콕시, 카복시, 하이드록시메틸, 포르밀, 아미노메틸, 저급-알킬설포닐, 폴리할로-저급-알킬설포닐, 저급-알킬설포닐-아미노설포닐, 저급-알콕시-저급-알콕시, 저급-알콕시-폴리-저급-알킬렌오기시, 카복시-저급-알코시, 저급-알콕시카보닐-저급 알콕시 또는 디-저급-알킬아니노카보닐옥시로부터 선택된 1 내지 3개의 치환제이고; 단, (1)n이 0일 때 R1은 단지 헤테로사이클릴일 수 있고, CHR2는 단지 R1의 고리 질소 원자에 결합될 수 있고, (2) m이 0이고, n이 1이고, L이 -O-, -S- 또는 -SO-이고, R2, R3및 R4가 모두 소소이거나, 또는 m이 0이고, n이 1이고, L이 -S-이고, R2및 R4가 수소이고, R3및 R4가 둘다 수소일 때 R1은 치환된 페닐인 수 없다.
- 제1항에 있어서, L이 -O- 또는 -S-이고, m이 0이고, n이 0또는1이고, R2가 수소인 화합물.
- 제2항에 있어서, R3가 수소, 클로로, 브로모, 메틸, 에틸, 프로필, 이소프로필, 2급-부틸, 메톡시, 에톡시, 이소프로폭시 또는 페닐이고, R4가 수소, 7-클로로, 5-니트로, 6-니트로, 5-아미노, 5-아세틸아미노, 5-(3,3-디페닐-프로피온아미도), 5-(1,1,3,3-테트라메틸부틸), 6-하이드록시, 7-하이드록시, 5-메톡시, 6-메톡시, 7-메톡시, 5,6-디메톡시, 5,7-디메톡시, 6,7-디메톡시, 6-[2-(2-메톡시에톡시)에톡시], 7-[2-(2-메톡시에톡시)에톡시], 7-카복시메톡시, 7-(t-부톡시카보닐)-메톡시, 7-디메틸아미노카보닐옥시, 6-프로필-7-메톡시, 5,7-디메톡시-6-메틸 또는 5-하이드록시-6-메톡시인 화합물.
- 제3항에 있어서, L이 -O-이고, n이 1이고, R1이 페닐 또는 치환된 페닐이고, 치환된 페닐이 2-포르밀-4-니트로페닐, 2-하이드록시메틸-4-니트로페닐, 2-클로로메틸-4-니트로페닐, 4-클로로메틸-2-니트로페닐, 4-(4-니트로페닐아조)페닐, 2,4-디콜로로-6-(4-모르폴리닐설포닐)페닐, 2-클로로-4-(4-모르폴리닐설포닐)페닐, 2-메톡시카보닐-5-메톡시페닐, 2-플루오로-4-(4-모르폴리닐설포닐)페닐, 2-클로로-4-(1,1-디옥소-4-티아모르폴리닐설포닐)페닐, 2,6-디플루오로-4-(4-모르폴리닐설포닐)페닐, 4-플루오로-2-(4-모르폴리닐설포닐)페닐, 3-[(4-모르폴리닐)에톡시]페닐, 3-[2-(4-모로폴리닐)에톡시카보닐]페닐, 3-[2-(4-메틸피페라진-1-일)설포닐]페닐, 3-[(4-모르폴리닐)에톡시]페닐, 4-(4-모르폴리닐설포닐)-3-트리프루오로메틸페닐, 2,5-디플루오로-4-(4-모르폴리닐설포닐)페닐, 2,6-디클로로-4-(4,5-디하이드로옥사졸-2-일)페닐, 2,6-디클로로-4-(2-메틸테트라졸-5-일)페닐, 2,6-디클로로-4-에톡시카보닐페닐, 2,4-디클로로-3-[2-(4-모르폴리닐)에틸아미노카보닐]페닐, 2-디에틸포스닐페닐, 2,5-디플루오로-4-(4-메틸-1-피페라지닐설포닐)페닐, 2,6-디플루오로-4-(4-메틸-1-피페라지닐설포닐)페닐 또는 2,3,5-틀리플루오로-4-(4-모르폴리설포닐)페닐인 화합물.
- 제4항에 있어서, R1이 플루우로 및 4-모르폴리닐설포닐에 의해 치환된 페닐인 화합물.
- 제5항에 있어서, R1이 2,3,5-트리플루오로-4-(4-모르폴리닐설포닐)페닐이고, R3가 이소프로필이고, R4가 6-메톡시인 화합물.
- 제3항에 있어서, L이 -O-이고, n이 1이고, R1이 헤테로사이클릴 또는 치환된 헤테로사이클릴이고, 헤테로사이클릴 또는 치환된 헤테로사이클릴이 5,7-디클로로퀴놀린-8-일, 2-메틸-4-피론-3-일, 6-하이드록시메틸-4-피론-3-일, 4,5=디클로로피리다진-3-일, 2-에틸-4-피론-3-일, 3-페닐쿠마린-7-일, 4-페닐쿠마린-7-일, 6-클로로-4-트리플루오로메틸쿠마린-7-일, 4-메틸쿠마린-7-일, 3-(벤조티아졸-2-일)쿠마린-7-일, 사카린-6-일, 4-(4-모르폴리닐)-1,2,5-티아디아졸-3-일, 3-메틸티오-6-메틸-1,24-트리아짐-5-일, 4-에톡시카보닐이속사졸-5-일, 2,5-디옥소피롤리딘-1-일, 2-메틸-4,5-디(하이드록시메틸)-3--피리딜, 5-메톡시카보닐이속사졸-3-일, 1-메틸-2-에톡시카보닐인돌-3-일, 2-페닐-5-메틸티아졸-4-일 또는 2-메틸-5-페닐티아졸-4-일인 화합물.
- 제3항에 있어서, L이 -S-이고, N이 1이고, R1이 헤테로사이클릴 또는 치환된 헤테로사이클릴이고 헤테로사이클로릴 또는 치환된 헤테로사이클릴이 5-(2-디에틸아미노에틸)-1,3,4-티아디아졸-2-일, 5-[2-(1-피페리디닐)에틸]1,3,4-티아디아졸-2-일, 5-펜ㄹ-1,3,4-옥사디아졸-2-일, 4-(에톡시카보닐메틸)티아졸-2-일, 5-(2-푸릴)-1.3.4.-옥사디아졸-2-일, 5-벤질-1,3,4-옥사디아졸-2-일, 5-하이드록시-6-메틸-6,7-디하이드로-1H-1,2,4-틀리아졸로 [3,4-b][1,3]티아존진-3-일, 5-(3-피리딜)-1,3,4,-옥사디아졸-2-일, 5-(4-비페닐릴)-1,3,4-옥사디아졸-2-일, 5-(피라지닐)-1,3,4-옥사디아졸-2-일, 5-(2-피리딜)-1,3,4-티아디아졸-2-일, 5-(3-푸릴)-1,3,4-옥사디아졸-2-일, 4-메틸-5-에톡시카보닐티아졸-2-, 4-페닐티아졸-2-일, 4,5-디메틸티아졸-2-일, 4-(4-모르폴리닐)-1,2,5-티아디아졸-3-일, 5-(2-피리딜)1.3,4-옥사디아졸-2-일, 5-{4-[2-(2-메톡시에톡시)에톡시]페닐}-1,3,4-옥사디아졸-2-일, 5-(3,4-메틸렌디옥시페닐)-1,3,4,-옥사디아졸-2-일, 5-(2,5-디메톡시페닐)-1,3,4,-옥사디아졸-2-일, 5-(2-메톡시페닐)-1,3,4-옥사디아졸-2-일 또는 5-페닐옥사졸-2-일인 화합물.
- 제3항에 있어서, n이 0이고, R1이 헤테로사이클릴 또는 치환된 헤테로 사이클릴이고, 헤테로사이클릴 또는 치환된 헤테로사이클릴이 4,5-디시아노이미다졸-1-일, 1,1,3-트리옥소테트라하이드로-1,2,5-티아디아졸-2-일, 4,5-디(메톡시카보닐)-1,2,3-트리아진-1-일, 5-페닐설포닐-1,2,3-트리아졸-1-일, 4-트리메틸실릴-5-페닐설포닐-1,2,3-트리아졸-1-일,, 4-메톡시카보닐-1,2,3-트리아졸-1-일, 5-메톡시카보닐-1,2,3-트리아졸-1-일, 4-에톡시카보닐-5-페닐-1,2,3-트리아진-1-일, 4-페닐-5-에톡시카보닐-1,2,3-트리아졸-1-일, 4-카복시-1,2,3-트리아졸-1-일, 4-페닐-5-(4-메틸페닐설포닐)-1,2,3-트리아졸-1-일, 4-(4-메틸페닐설포닐)-5-페닐-1,2,3-트리아졸-1-일, 4-페닐설포닐-1,2,3-트리아졸-1-일, 4-에틸설포닐-5-이소프로필-1,2,3-트리아진-1-일, 4-이소프로필-5-에틸설포닐)-1,2,3-트리아진-1-일, 4,5-디(아미노카보닐)-1,2,3-트리아진-1-일, 4,5-디카복시-1,2,3-트리아진-1-일, 4-트리메틸실릴-5-디메틸아미노설포닐-1,2,3-트리아졸-1-일, 4-(1,1-디메틸에틸-5-디메틸아미노설포닐-1,2,3-트리아졸-1-일, 4-디메틸아미노설포닐-5--(1,1-디메틸)에틸-1,2,3-트리아졸-1-일, 4-페닐설포닐-5-트리메틸실릴-1,2,3-트리아졸-1-일, 2-벤조일-4,5-디브로모이미다졸-1-일, 2-티옥소-2,3-디하이드로-1,3,4-옥사디아졸-3-일, 2-티옥소-2,3-디하이드로-5-(2-피리딜)-1,3,4-옥사디아졸-3-일, 2,3-디하이드로-2-옥소-5-페닐-1,3,4-옥사디아졸-3-일,2,3-디하이드로-2-옥소-5-페닐-1,3,4-옥사디아졸-3-일, 4,5-디시아노-1,2,3-트리아졸-1-일, 4,5-디시아노-1,2,3-트리아졸-2-일, 4,5-디(t-부틸설포닐)-1,2,3-트리아졸-1-일, 4,5-디(트리플루오로메틸)-1,2,3-트리아졸-1-일, 4,5-디(1-피페리디닐카보닐)-1,2,3-트리아졸-2-일, 2-메틸티오-5-메틸-6-옥소-1,2-디하이드로-1,3,4-트리아진-1-일, 3-벤질록시-4,5-디하이드로-5-옥소-1,2,4-옥사디아졸-4-일, 1,2,5-티아디아졸-3-일, 2-(4-메톡시벤조일)인돌-1-일 또는 2-메틸-3-(2,6-디클로로벤조일)인돌-1-일인 화합물.
- 단백질분해 효소 억제 농도의 제1항에 따른 일반식(I)화합물 및 약학적 담체를 포함하는 약학적 조성물.
- 단백질분해 효소 억제 농도의 제2항 내지 제9항중 어느 한 항에 따른 일반식(I)화합물 및 약학적 담체를 포함하는 약학 저조성물.
- 퇴행성 질환의 치료가 필요한 환자에게 상기 질혼을 치료하기 위한 약제의 제조를 위한 제1항에 따른 일반식(I)화합물의 용도.
- 퇴행성 질환의 치료가 필요한 환자에게 상기 질환을 치료하기 위한 약제의 제조를 위한 제2항 내지 제9항중 어느 한 항에 따른 화합물의 용도.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
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| Application Number | Priority Date | Filing Date | Title |
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| US07/793,033 US5236917A (en) | 1989-05-04 | 1991-11-15 | Saccharin derivatives useful as proteolytic enzyme inhibitors and compositions and method of use thereof |
| US793,033 | 1991-11-15 |
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| KR930010015A true KR930010015A (ko) | 1993-06-21 |
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| KR1019920021437A KR930010015A (ko) | 1991-11-15 | 1992-11-14 | 단백질 분해효소 억제제인 2-치환된 사카린 유도체 |
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- 1992-09-25 AU AU25340/92A patent/AU654581B2/en not_active Ceased
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- 1992-10-19 MX MX9206008A patent/MX9206008A/es unknown
- 1992-11-12 EP EP92203469A patent/EP0542372A1/en not_active Withdrawn
- 1992-11-13 NO NO924401A patent/NO303119B1/no unknown
- 1992-11-13 IL IL10374892A patent/IL103748A/xx not_active IP Right Cessation
- 1992-11-13 FI FI925167A patent/FI925167A/fi unknown
- 1992-11-13 NZ NZ244446A patent/NZ244446A/en unknown
- 1992-11-13 HU HU9203566A patent/HUT66873A/hu unknown
- 1992-11-13 CZ CS923390A patent/CZ339092A3/cs unknown
- 1992-11-13 RU RU92004381A patent/RU2101281C1/ru active
- 1992-11-14 KR KR1019920021437A patent/KR930010015A/ko not_active Application Discontinuation
- 1992-11-14 MY MYPI92002080A patent/MY107740A/en unknown
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1995
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- 1995-06-30 HU HU95P/P00637P patent/HU211663A9/hu unknown
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1997
- 1997-02-20 US US08/803,297 patent/US5874432A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US5596012A (en) | 1997-01-21 |
| RU2101281C1 (ru) | 1998-01-10 |
| US5236917A (en) | 1993-08-17 |
| US5371074A (en) | 1994-12-06 |
| AU654581B2 (en) | 1994-11-10 |
| CA2079822A1 (en) | 1993-05-16 |
| FI925167A0 (fi) | 1992-11-13 |
| SG55181A1 (en) | 1998-12-21 |
| HU211663A9 (en) | 1995-12-28 |
| US5650422A (en) | 1997-07-22 |
| NZ244446A (en) | 1994-09-27 |
| HUT66873A (en) | 1995-01-30 |
| EP0542372A1 (en) | 1993-05-19 |
| IL103748A0 (en) | 1993-04-04 |
| NO303119B1 (no) | 1998-06-02 |
| CZ339092A3 (en) | 1993-06-16 |
| NO924401L (no) | 1993-05-18 |
| FI925167A (fi) | 1993-05-16 |
| NO924401D0 (no) | 1992-11-13 |
| TW221433B (ko) | 1994-03-01 |
| JPH05194444A (ja) | 1993-08-03 |
| US5874432A (en) | 1999-02-23 |
| MY107740A (en) | 1996-05-30 |
| IL103748A (en) | 1997-02-18 |
| HU9203566D0 (en) | 1993-01-28 |
| MX9206008A (es) | 1993-11-01 |
| AU2534092A (en) | 1993-05-20 |
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