JP2001506614A - カルパインインヒビターとしてのケトベンズアミド - Google Patents
カルパインインヒビターとしてのケトベンズアミドInfo
- Publication number
- JP2001506614A JP2001506614A JP52615698A JP52615698A JP2001506614A JP 2001506614 A JP2001506614 A JP 2001506614A JP 52615698 A JP52615698 A JP 52615698A JP 52615698 A JP52615698 A JP 52615698A JP 2001506614 A JP2001506614 A JP 2001506614A
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- alkyl
- formula
- mmol
- propani
- 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.)
- Granted
Links
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- 229940121926 Calpain inhibitor Drugs 0.000 title description 6
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- 150000001875 compounds Chemical class 0.000 claims abstract description 41
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
- -1 Phenyl ring Chemical group 0.000 claims description 32
- 108010032088 Calpain Proteins 0.000 claims description 28
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
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- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 4
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- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 4
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 102000000589 Interleukin-1 Human genes 0.000 claims description 2
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- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 206010008129 cerebral palsy Diseases 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 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 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000005412 pyrazyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
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- 125000001544 thienyl group Chemical group 0.000 claims description 2
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- 208000030886 Traumatic Brain injury Diseases 0.000 claims 1
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- 230000000740 bleeding effect Effects 0.000 claims 1
- 230000004663 cell proliferation Effects 0.000 claims 1
- 208000021090 palsy Diseases 0.000 claims 1
- 125000005495 pyridazyl group Chemical group 0.000 claims 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 5
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
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- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
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- KSQVGVMZECCPAT-AEFFLSMTSA-N [(1R)-4-phenyl-1-[[(2R)-2-(pyrazine-2-carbonylamino)pentanoyl]amino]butyl]boronic acid Chemical compound B([C@H](CCCC1=CC=CC=C1)NC(=O)[C@@H](CCC)NC(=O)C2=NC=CN=C2)(O)O KSQVGVMZECCPAT-AEFFLSMTSA-N 0.000 description 6
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/82—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/87—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/36—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.式I: [式中、 R1は、フェニル、ナフチル、キノリル、ピリジル、ピリミジル、ピラジル、 ピリダジル、キナゾリル、キノキサリル、チエニル、ベンゾチエニル、ベンゾフ リル、ベンズイミダゾリル、フラニル、インドリル、イソキノリン、テトラヒド ロイソキノリンまたはテトラヒドロキノリンであり、その際、芳香環およびヘテ ロ芳香環は、更に、1、2または3個のR5基によって置換されていてもよい、 R2は、塩素、臭素、フッ素、C1〜C6−アルキル、C2〜C6−アルケニル、 C2〜C6−アルキニル、C1〜C6−アルキルフェニル、C2〜C6−アルケニルフ ェニル、C2〜C6−アルキニルフェニル、フェニル、NHCO−C1〜C4−アル キル、−NHCO−フェニル、−NHCO−ナフチル、H2N−SO2−C1〜C4 −アルキル−、COOH、−COO−C1〜C4−アルキル、−CONH−C1〜 C4−アルキル、C1〜C4−アルコキシ、NO2またはNH2であ り、 R3は、部分的に1または2個のR5基によって置換されていてもよいフェニル環 、シクロプロピル環、シクロブチル環、シクロペンチル環、シクロヘキシル環、 シクロヘプチル環、インドリル環、ピリジル環またはナフチル環を有していても よいC1〜C6−アルキルであり、 Xは、結合、−(CH2)m−、−(CH2)m−O−(CH2)o−、−(CH2)n −S−(CH2)m−、−(CH2)n−SO−(CH2)m−、−(CH2)n−SO2 −(CH2)m−、−CH=CH−、−C≡C−、−CO−CH=CH−、CO −(CH2)m−、−(CH2)m−NHCO−(CH2)o−、−(CH2)m−CO NH−(CH2)o−、− (CH2)m−NHSO2−(CH2)o−、−NH−CO −CH=CH−、−CH=CH−CO−NH−、−(CH2)m−SO2NH−( CH2)o−または であり、 R4は、OR6、NR7R8 であり、 R5は、水素、C1〜C4−アルキル、−O−C1〜C4−アルキル、OH、Cl、 F、Br、I、CF3、 NO2、NH2、CN、COOH、COO−C1〜C4−アルキル、−NHCO−C1 〜C4−アルキル、−NHCO−フェニル、−NHSO2−C1〜C4−アルキル 、−NHSO2−フェニル、−SO2−C1〜C4−アルキルまたは−SO2−フェ ニルであり、 R6は、水素、1または2個のR9基によって置換されていてもよいフェニル環に よって置換されていてもよいC1〜C6−アルキルであり、 R7は、水素またはC1〜C6−アルキルであり、 R8は、水素または、1もしくは2個のR9基を有していてもよいフェニル環また は基: の1個によって置換されていてもよいC1〜C6−アルキル基であり、 R9は、水素、C1〜C4−アルキル、−O−C1〜C4−アルキル、OH、Cl、 F、Br、I、CF3、NO2、NH2、CN、COOH、COO−C1〜C4−ア ルキル、−NHCO−C1〜C4−アルキル、−NHCO−フェニル、−NHSO2 −C1〜C4−アルキル、−NHSO2−フェニル、−SO2−C1〜C4−アルキ ルまたは−SO2−フェニルであり、 R10は、水素または、1もしくは2個のR9基によ って置換されていてもよいフェニル環によって置換されていてもよいC1〜C6− アルキルであり、 nは、0、1または2であり、 mは、0、1、2、3または4であり、 oは、0、1、2、3または4である]のケトベンズアミドならびにその互変 異性形および異性形、ならびに場合によりその生理学的に認容性の塩。 2.R2が、水素、C1〜C4−アルキル、フッ素または塩素であり、 R3は、R5基によってそれぞれ置換されていてもよい−CH2−フェニル、− CH2−シクロヘキシル、n−ブタニルまたはn−ペンタニルであり、 R4は、−NR8であり、 R1、Xおよびnは請求項1記載のものである、請求項1記載の式Iのケトベ ンズアミド。 3.疾患の抑制に使用するための、請求項1記載の式Iのケトベンズアミド。 4.システインプロテアーゼのインヒビターとして使用される薬剤を製造するた めの、請求項1記載の式Iのケトベンズアミドの使用。 5.高められたカルパイン活性が生じる疾患を治療するための薬剤を製造するた めの、請求項1記載の式Iのケトベンズアミドの使用。 6.神経変性疾患および神経障害を治療するための薬剤を製造するための、請求 項1記載の式Iのケトベ ンズアミドの使用。 7.虚血、外傷または激しい出血によって誘発される疾患およびニューロンの損 傷を治療するための薬剤を製造するための、請求項1記載の式Iのケトベンズア ミドの使用。 8.脳卒中および頭蓋/脳の外傷を治療するための薬剤を製造するための、請求 項1記載の式Iのケトベンズアミドの使用。 9.アルツハイマー病およびハンチントン病を治療するための薬剤を製造するた めの、請求項1記載の式Iのケトベンズアミドの使用。 10.てんかんを治療するための薬剤を製造するための、請求項1記載の式Iの ケトベンズアミドの使用。 11.心臓の虚血後の心臓への損傷、腎臓の虚血後の腎臓への損傷、骨格筋の損 傷、筋ジストロフィー、平滑筋細胞の増殖のために起こる損傷、冠状血管麻痺、 脳血管麻痺、眼の白内障および血管形成後の血管の再狭窄を治療するための薬剤 を製造するための、請求項1記載の式Iのケトベンズアミドの使用。 12.腫瘍およびその転移を治療するための薬剤を製造するための請求項1記載 の式Iのケトベンズアミドの使用。 13.高められたインターロイキン1濃度が生じる疾患の治療のための薬剤を製 造するための、請求項1 記載の式Iのケトベンズアミドの使用。 14.少なくとも1種の請求項1記載の式Iのケトベンズアミドを含有する薬物 調剤。
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DE19651316.2 | 1996-12-11 | ||
DE19651316 | 1996-12-11 | ||
PCT/EP1997/006655 WO1998025883A1 (de) | 1996-12-11 | 1997-11-28 | Ketobenzamide als calpain-inhibitoren |
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CA3038331A1 (en) | 2016-09-28 | 2018-04-05 | Blade Therapeutics, Inc. | Calpain modulators and therapeutic uses thereof |
AU2018289434A1 (en) * | 2017-06-23 | 2020-01-16 | Blade Therapeutics, Inc. | Calpain modulators and therapeutic uses thereof |
US20220257570A1 (en) * | 2019-07-31 | 2022-08-18 | Blade Therapeutics, Inc. | Calpain inhibitors and uses thereof for treating neurological disorders |
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US5496927A (en) * | 1985-02-04 | 1996-03-05 | Merrell Pharmaceuticals Inc. | Peptidase inhibitors |
EP0672648B1 (en) * | 1989-04-15 | 1998-09-23 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai | Threo (2R,3S)-3-amino-2-hydroxypentanoic acid and threo (2R,3S)-3-(p-methoxy-benzyloxycarbonyl/FMOC) amino-2-hydroxy-pentanoic acid |
DE4000204A1 (de) * | 1990-01-05 | 1991-07-11 | Steag Ag | Vorrichtung zum dosierten austragen von schuettfaehigem feststoff |
CA2097815C (en) * | 1990-12-28 | 2001-04-17 | Fumio Suzuki | Quinoline derivative |
EP0564552A1 (en) * | 1990-12-28 | 1993-10-13 | Cortex Pharmaceuticals, Inc. | Use of calpain inhibitors in the inhibition and treatment of neurodegeneration |
CA2071621C (en) * | 1991-06-19 | 1996-08-06 | Ahihiko Hosoda | Aldehyde derivatives |
JPH09500087A (ja) * | 1992-06-24 | 1997-01-07 | コーテックス ファーマシューティカルズ インコーポレイテッド | カルパイン活性の増大に関連した健康障害の抑制及び処置におけるカルパイン阻害剤の使用法 |
US5541290A (en) * | 1993-06-24 | 1996-07-30 | Harbeson; Scott L. | Optically pure calpain inhibitor compounds |
US6150378A (en) * | 1997-10-07 | 2000-11-21 | Cephalon, Inc. | Peptidyl-containing α-ketoamide cysteine and serine protease inhibitors |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012518616A (ja) * | 2009-02-20 | 2012-08-16 | アボット ゲーエムベーハー ウント カンパニー カーゲー | カルボキサミド化合物及びカルパイン阻害剤としてのその使用 |
JP2019533007A (ja) * | 2016-09-13 | 2019-11-14 | ハプロゲン・ゲーエムベーハー | 抗ウイルス化合物 |
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ZA9711141B (en) | 1999-06-11 |
JP4099237B2 (ja) | 2008-06-11 |
NZ335981A (en) | 2000-04-28 |
AU5752398A (en) | 1998-07-03 |
BG103485A (en) | 2000-01-31 |
HUP0000475A3 (en) | 2002-11-28 |
ATE244216T1 (de) | 2003-07-15 |
EP0944582B1 (de) | 2003-07-02 |
TR199901305T2 (xx) | 1999-08-23 |
CN1245486A (zh) | 2000-02-23 |
NO992821D0 (no) | 1999-06-10 |
IL130124A0 (en) | 2000-06-01 |
BG63382B1 (bg) | 2001-12-29 |
AR010348A1 (es) | 2000-06-07 |
SK74599A3 (en) | 1999-12-10 |
ID22426A (id) | 1999-10-14 |
CO4910159A1 (es) | 2000-04-24 |
HRP970680B1 (en) | 2002-08-31 |
PL334059A1 (en) | 2000-01-31 |
AU721620B2 (en) | 2000-07-13 |
CA2274464C (en) | 2007-01-02 |
HRP970680A2 (en) | 1998-10-31 |
US6103720A (en) | 2000-08-15 |
DE59710384D1 (de) | 2003-08-07 |
HUP0000475A2 (hu) | 2000-05-28 |
RU2190599C2 (ru) | 2002-10-10 |
WO1998025883A1 (de) | 1998-06-18 |
SK282680B6 (sk) | 2002-11-06 |
BR9713704A (pt) | 2000-05-09 |
EP0944582A1 (de) | 1999-09-29 |
TW536530B (en) | 2003-06-11 |
CA2274464A1 (en) | 1998-06-18 |
ES2202663T3 (es) | 2004-04-01 |
KR20000057495A (ko) | 2000-09-15 |
NO992821L (no) | 1999-06-11 |
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