HUP0202508A2 - Method of inhibiting amyloid protein aggregation and imaging amyloid deposits - Google Patents

Method of inhibiting amyloid protein aggregation and imaging amyloid deposits

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Publication number
HUP0202508A2
HUP0202508A2 HU0202508A HUP0202508A HUP0202508A2 HU P0202508 A2 HUP0202508 A2 HU P0202508A2 HU 0202508 A HU0202508 A HU 0202508A HU P0202508 A HUP0202508 A HU P0202508A HU P0202508 A2 HUP0202508 A2 HU P0202508A2
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Hungary
Prior art keywords
group
alkyl
atom
protein aggregation
phenyl
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HU0202508A
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Hungarian (hu)
Inventor
Corinne Elizabeth Augelliszafran
Mark Robert Barvian
Christopher Franklin Bigge
Shelly Ann Glase
Shunichiro Hachiya
John Steven Keily
Takenori Kimura
Yingjie Lai
Annette Theresa Sakkab
Mark James Suto
Lary Craswell Walker
Tomoyuki Yasunaga
Nian Zhuang
Original Assignee
Warner-Lambert Company
Yamanouchi Pharmaceutical Co., Ltd.
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Application filed by Warner-Lambert Company, Yamanouchi Pharmaceutical Co., Ltd. filed Critical Warner-Lambert Company
Publication of HUP0202508A2 publication Critical patent/HUP0202508A2/en
Publication of HUP0202508A3 publication Critical patent/HUP0202508A3/en

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    • C07C233/42—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/43—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
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Abstract

A találmány amiloid protein aggregáció gátlására és amiloidlerakódások kimutatására szolgáló eljárásokra, az eljárásokbanalkalmazható (I) általános képletű vegyületek - amelyeknek képletébenRa jelentése hidrogénatom, 1-6 szénatomos alkilcsoport vagy (1-6szénatomos alkil)-karbonil-csoport; n értéke 0, 1, 2, 3, 4 vagy 5; R1,R2, R3, R4, R5, R6 és R7 jelentése egymástól függetlenül hidrogén-,halogénatom, hidroxi-, aminocsoport, -NRbRc általános képletű csoport,karboxicsoport, (1-6 szénatomos alkoxi)-karbonil-csoport,nitrocsoport, 1-12 szénatomos alkoxicsoport, 1-8 szénatomosalkilcsoport, trifluor-metil-, ciano-, adott esetben szubsztituáltbenzil-oxi-csoport, fenil-(CH2)m- általános képletű csoport, adottesetben szubsztituált fenoxicsoport, sztirilcsoport, -O(CH2)p-NRbRc, -CONRbRc, -NHCORb, -NH(CH2)pNRbRc, -N(1-6 szénatomos alkil) (CH2)pNRbRcáltalános képletű csoport vagy 1,3-bisz(1-6 szénatomos alkoxi)-2-propil-csoport; R8 jelentése karboxi-, tetrazolilcsoport, -SO2Rd vagy-CONH-SO2Rd általános képletű csoport; Rb és Rc jelentése egymástólfüggetlenül hidrogénatom, 1-6 szénatomos alkilcsoport, fenil-(CH2)m-általános képletű csoport, vagy Rb és Rc azzal a nitrogénatommalegyütt, amelyhez a két szubsztituens kapcsolódik, egy ciklusospiperidil-, pirrolil-, imidazolil-, piperazinil-, 4-(1-6 szénatomosalkil)-piperazinil-, morfolino-, tiomorfolino-,dekahidroizokinolilvagy pirazolilcsoportot képez; Rd jelentésehidrogénatom, 1-6 szénatomos alkilcsoport, trifluor-metil- vagyfenilcsoport; m értéke 0, 1, 2, 3, 4 vagy 5; p értéke 1, 2, 3, 4 vagy5; A jelentése metincsoport vagy nitrogénatom; valamint R1 és R2metilén-dioxi-csoportot is jelenthet, ha a két szubsztituens egymássalszomszédos helyzetben van < és gyógyászatilag elfogadható sóikra,valamint a vegyületeket tartalmazó gyógyszerkészítményekre vonatkozik.A találmány szerinti, az amiloid protein aggregáció gátlására szolgálóeljárást az Alzheimer-kór kezelésére alkalmazzák. ÓFor the methods of inhibiting amyloid protein aggregation and detecting amyloid deposits of the invention, the compounds of general formula (I) can be used in the methods - in the formula Ra is a hydrogen atom, a C1-C6 alkyl group or (C1-C6 alkyl)-carbonyl group; n is 0, 1, 2, 3, 4 or 5; R1, R2, R3, R4, R5, R6 and R7 are independently hydrogen, halogen atom, hydroxy, amino group, -NRbRc group, carboxyl group, (C1-C6 alkoxy)carbonyl group, nitro group, 1- 12-carbon alkoxy group, 1-8 carbon-atom alkyl group, trifluoromethyl-, cyano-, optionally substituted benzyloxy group, phenyl(CH2)m- group, optionally substituted phenoxy group, styryl group, -O(CH2)p-NRbRc , -CONRbRc, -NHCORb, -NH(CH2)pNRbRc, -N(C1-C6 alkyl) (CH2)pNRbR group of general formula or 1,3-bis(C1-C6 alkoxy)-2-propyl group; R8 is carboxy, tetrazolyl, -SO2Rd or -CONH-SO2Rd; Rb and Rc independently represent a hydrogen atom, an alkyl group with 1-6 carbon atoms, a group of the general formula phenyl-(CH2)m-, or Rb and Rc together with the nitrogen atom to which the two substituents are attached, a cyclic piperidyl-, pyrrolyl-, imidazolyl-, piperazinyl- , forms a 4-(C1-C6 alkyl)piperazinyl, morpholino, thiomorpholino, decahydroisoquinolyl or pyrazolyl group; Rd represents a hydrogen atom, an alkyl group with 1 to 6 carbon atoms, a trifluoromethyl or a phenyl group; m is 0, 1, 2, 3, 4 or 5; p is 1, 2, 3, 4 or 5; A is a methine group or a nitrogen atom; and R1 and R2 can also be methylenedioxy groups if the two substituents are in adjacent positions < and applies to their medicinally acceptable salts as well as pharmaceutical preparations containing the compounds. The method for inhibiting amyloid protein aggregation according to the invention is used for the treatment of Alzheimer's disease. HE

HU0202508A 1999-06-10 2000-05-31 Method of inhibiting amyloid protein aggregation and imaging amyloid deposits HUP0202508A3 (en)

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US13855099P 1999-06-10 1999-06-10
PCT/US2000/015071 WO2000076489A2 (en) 1999-06-10 2000-05-31 Method of inhibiting amyloid protein aggregation and imaging amyloid deposits

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HUP0202508A2 true HUP0202508A2 (en) 2002-12-28
HUP0202508A3 HUP0202508A3 (en) 2003-03-28

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CA2357450A1 (en) * 2000-09-29 2002-03-29 Warner-Lambert Company Phenoxazine analogs useful as amyloid aggregation inhibitors and treatment of alzheimer's disease and disorders related to amyloidosis
GB0225548D0 (en) 2002-11-01 2002-12-11 Glaxo Group Ltd Compounds
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