RU97103565A - AMINO ALKYL AND ACYLAMINO ALKYL ETHERS, METHOD FOR THEIR RECOVERY AND THEIR USE AS ANTAGONISTS OF BRADIKININ RECEPTOR - Google Patents

AMINO ALKYL AND ACYLAMINO ALKYL ETHERS, METHOD FOR THEIR RECOVERY AND THEIR USE AS ANTAGONISTS OF BRADIKININ RECEPTOR

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RU97103565A
RU97103565A RU97103565/04A RU97103565A RU97103565A RU 97103565 A RU97103565 A RU 97103565A RU 97103565/04 A RU97103565/04 A RU 97103565/04A RU 97103565 A RU97103565 A RU 97103565A RU 97103565 A RU97103565 A RU 97103565A
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Prior art keywords
aryl
alkenoyl
formula
hydrogen
alkyl
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RU97103565/04A
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Russian (ru)
Inventor
Хайч Хольгер
Вагнер Адальберт
Вирт Клаус
Шелкенс Бернвард
Нелкен Герхард
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Хехст АГ
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Claims (7)

1. Соединения общей формулы I
Figure 00000001

где R1, R2, R3 одинаковы или различны (C1 - C5)-алкил, (C6 - C10)-арил, (C1 - C3)-алкил-(C6 - C10)-арил, галоген, водород, (C3 - C8)-циклоалкил, CHO, CO-O-(C1 - C3)-алкил, COOH;
R4, R5 одинаковы или различны водород, галоген, (C1 - C3)-алкокси, нитро, циано, S-(C1 - C3)-алкил;
n число от 1 до 8;
R6 водород, (C1 - C3)-алкил, (C3 - C5)-алкилалкенил, (C1 - C3)-алкил-(C6 - C10)-арил;
R7 водород и следующие замещенные или незамещенные ацильные остатки: (C1 - C6)-алканоил, (C1 - C3)-алкокси-(C2 - C6)-алканоил, (C1 - C6)-алкилкарбамоил-(C2 - C6)-алканоил, (C6 - C12)-арил-(C2 - C6)-алканоил, (C3 - C7)-алкеноил, (C3 - C8)-циклоалкилкарбонил, (C5 - C7)-циклоалкенилкарбонил, (C1 - C3)-алкоксикарбонил, (C6 - C12)-арилоксикарбонил, (C6 - C12)-ароил, (C1 - C3)-алкокси-(C6 - C12)-ароил, галоген-(C6 - C12)-ароил, (C6 - C12)-арил-(C3 - C6)-алкеноил, (C1 - C3)-алкокси-(C6 - C12)-арил-(C3 - C6)-алкеноил, (C1 - C3)-алкилен диокси-(C6 - C12)-арил-(C3 - C6)-алкеноил, нитро-(C6 - C12)-арил-(C3 - C6)-алкеноил, циано-(C6 - C12)-арил-(C3 - C6)-алкеноил, галоген-(C6 - C12)-арил-(C3 - C6)-алкеноил, галоген-(C1 - C3)-алкил-(C6 - C12)-арил-(C3 - C6)-алкеноил; гетеро-(C3 - C8)-циклоалкил-(C6 - C12)-арил-(C3 - C6)-алкеноил, амино-(C6 - C12)-арил-(C3 - C6)-алкеноил, (C1 - C4)-алкиламино-(C6 - C12)-арил-(C3 - C6-алкеноил, C2 - C5)- ациламино-(C6 - C12)-арилциннамоил, (C1 - C3)-алкоксикарбониламино-(C6 - C12)-арилциннамоил, (C1 - C4)-алкиламинокарбониламиноциннамоил, гетеро-(C6 - C12)-арил-(C2 - C6)-алканоиламино-(C6 - C12)-арил-(C3 - C6)-алкеноил, (C6 - C12)-ароиламино-(C6 - C12)-арил-(C3 - C6)-алкеноил, гетеро-(C6 - C12)-арилкарбониламино-(C6 - C12)-арил-(C3 - C6)-алкеноил, (C1 - C5)-алкилсульфониламино-(C6 - C12)-арил-(C3 - C6)-алкеноил, (C1 - C5)-алкилуреидо-(C6 - C12)-арил-(C3 - C6)-алкеноил, (C2 - C6)-алканоил-(C6 - C12)-арил-(C3 - C6)-алкеноил, (C1 - C5)-алкоксикарбонил-(C6 - C12)-арил-(C3 - C6)-алкеноил, (C1 - C5)-алкилкарбамоил-(C6 - C12)-арил-(C3 - C6)-алкеноил, (C6 - C12)-арилкарбамоил-(C6 - C12)-арил-(C3 - C6)-алкеноксил, (C6 - C12)-арил-(C1 - C5)-алкоксикарбонил, (C1 - C5)-алкилкарбамоил, (C6 - C12)-арилкарбамоил, (C6-C12)-ароилкарбамоил, (C1 - C6)-алкилсульфонил, (C6-C12)-арилсульфонил (C6 - C12)-арил-(C1 - C6)-алкилсульфонил и фталоил (для R6 = R7),
а также их физиологически приемлемые соли.1. Compounds of General Formula I
Figure 00000001

where R 1 , R 2 , R 3 are the same or different (C 1 - C 5 ) -alkyl, (C 6 - C 10 ) -aryl, (C 1 - C 3 ) -alkyl- (C 6 - C 10 ) - aryl, halogen, hydrogen, (C 3 –C 8 ) cycloalkyl, CHO, CO — O- (C 1 –C 3 ) alkyl, COOH;
R 4 , R 5 identical or different hydrogen, halogen, (C 1 - C 3 ) -alkoxy, nitro, cyano, S- (C 1 - C 3 ) -alkyl;
n is a number from 1 to 8;
R 6 is hydrogen, (C 1 - C 3 ) alkyl, (C 3 - C 5 ) alkylalkenyl, (C 1 - C 3 ) alkyl- (C 6 - C 10 ) -aryl;
R 7 hydrogen and the following substituted or unsubstituted acyl residues: (C 1 - C 6 ) alkanoyl, (C 1 - C 3 ) alkoxy (C 2 - C 6 ) alkanoyl, (C 1 - C 6 ) alkylcarbamoyl - (C 2 - C 6 ) -alkanoyl, (C 6 - C 12 ) -aryl- (C 2 - C 6 ) -alkanoyl, (C 3 - C 7 ) -alkoyl, (C 3 - C 8 ) -cycloalkylcarbonyl , (C 5 - C 7 ) -cycloalkenylcarbonyl, (C 1 - C 3 ) alkoxycarbonyl, (C 6 - C 12 ) aryloxycarbonyl, (C 6 - C 12 ) -aroyl, (C 1 - C 3 ) alkoxy - (C 6 - C 12 ) -aroyl, halo- (C 6 - C 12 ) -aroyl, (C 6 - C 12 ) -aryl- (C 3 - C 6 ) -alkenoyl, (C 1 - C 3 ) -alkoxy- (C 6 - C 12 ) -aryl- (C 3 - C 6 ) -alkenoyl, (C 1 - C 3 ) -alkylene dioxy- (C 6 - C 12 ) -aryl- (C 3 - C 6 ) alkenoyl, nitro, (C 6 - C 12) -aryl- (C 3 - C 6) alkenoyl, cyano - (C 6 - C 12) -aryl- (C 3 - C 6) alkenoyl, halo- (C 6 - C 12) -aryl- (C 3 - C 6) alkenoyl, halo- (C 1 - C 3 ) -alkyl- (C 6 - C 12 ) -aryl- (C 3 - C 6 ) -alkoyl; hetero- (C 3 - C 8 ) -cycloalkyl- (C 6 - C 12 ) -aryl- (C 3 - C 6 ) -alkenoyl, amino- (C 6 - C 12 ) -aryl- (C 3 - C 6 ) -alkenoyl, (C 1 - C 4 ) -alkylamino- (C 6 - C 12 ) -aryl- (C 3 - C 6 -alkenoyl, C 2 - C 5 ) - acylamino- (C 6 - C 12 ) - aryl cinnamoyl, (C 1 -C 3 ) -alkoxycarbonylamino- (C 6 -C 12 ) -arylcinnamoyl, (C 1 -C 4 ) alkylaminocarbonylamino-cinnamoyl, hetero- (C 6 -C 12 ) aryl- (C 2 -C 6 ) -alkanoylamino- (C 6 - C 12 ) -aryl- (C 3 - C 6 ) -alkenoyl, (C 6 - C 12 ) -aryoylamino- (C 6 - C 12 ) -aryl- (C 3 - C 6 ) alkenoyl, hetero- (C 6 - C 12) -arilkarbonilamino- (C 6 - C 12) -aryl- (C 3 - C 6) alkenoyl, (C 1 - C 5) -alkilsulfonilamino- (C 6 - C 12) -aryl- (C 3 - C 6) alkenoyl, (C 1 - C 5) -alkilureido- (C 6 - C 12) -ari - (C 3 - C 6) alkenoyl, (C 2 - C 6) -alkanoil- (C 6 - C 12) -aryl- (C 3 - C 6) alkenoyl, (C 1 - C 5) -alkoxycarbonyl - (C 6 - C 12 ) -aryl- (C 3 - C 6 ) -alkenoyl, (C 1 - C 5 ) -alkylcarbamoyl- (C 6 - C 12 ) -aryl- (C 3 - C 6 ) -alkenoyl , (C 6 - C 12 ) -arylcarbamoyl- (C 6 - C 12 ) -aryl- (C 3 - C 6 ) -alkenoxyl, (C 6 - C 12 ) -aryl- (C 1 - C 5 ) -alkoxycarbonyl , (C 1 - C 5 ) -alkylcarbamoyl, (C 6 - C 12 ) -arylcarbamoyl, (C 6 -C 12 ) -aroylcarbamoyl, (C 1 - C 6 ) alkylsulfonyl, (C 6 -C 12 ) -arylsulfonyl (C 6 - C 12 ) -aryl- (C 1 - C 6 ) -alkylsulfonyl and phthaloyl (for R 6 = R 7 ),
and their physiologically acceptable salts. 2. Соединения формулы I по п.1, где R1, R2, R3 одинаковы или различны водород, (C1 - C3)-алкил, R4, R5 галоген; R6 водород, метил, этил, бензил.2. The compounds of formula I according to claim 1, where R 1 , R 2 , R 3 are the same or different hydrogen, (C 1 - C 3 ) -alkyl, R 4 , R 5 is halogen; R 6 hydrogen, methyl, ethyl, benzyl. 3. Соединения формулы I по п.1 или 2, в которой R7 обозначает: водород или ацильный остаток.3. The compounds of formula I according to claim 1 or 2, in which R 7 denotes: hydrogen or acyl residue. 4. Соединения формулы I по пп.1 - 3, в которой R1, R2, R3 одинаковы или различны водород, метил, этил, пропил; R4, R5 хлор; n от 1 до 4; R6 водород; R7 водород, (C2 - C5)-алканоил, (C3 - C5)-алкеноил, (C1 - C5)-алкиламинокарбонил, (C6 - C10)-арил-(C2 - C3)-алкиламинокарбонил, (C1 - C5)-алкоксикарбонил, (C6 - C10)-арил-(C1 - C3)-алкилоксикарбонил, (C6 - C10)-арил-(C3 - C7)-циклоалкилкарбонил, остаток транс-коричной кислоты, фенильное кольцо которого замещено одним или двумя одинаковыми или различными остатками из ряда а) водород, b) (C1 - C3)-алкил, с) амино, d) (C1 - C3)-моно- и диалкиламино, е) галоген, f) (C1 - C3)-галогеналкил, g) (C2 - C5)-ациламино и h) (C1 - C3)-алкокси.4. The compounds of formula I in PP.1 - 3, in which R 1 , R 2 , R 3 the same or different hydrogen, methyl, ethyl, propyl; R 4 , R 5 is chlorine; n from 1 to 4; R 6 is hydrogen; R 7 is hydrogen, (C 2 - C 5 ) alkanoyl, (C 3 - C 5 ) alkenoyl, (C 1 - C 5 ) alkylaminocarbonyl, (C 6 - C 10 ) aryl- (C 2 - C 3 ) -alkylaminocarbonyl, (C 1 - C 5 ) -alkoxycarbonyl, (C 6 - C 10 ) -aryl- (C 1 - C 3 ) -alkyloxycarbonyl, (C 6 - C 10 ) -aryl- (C 3 - C 7 ) -cycloalkylcarbonyl, the residue of trans-cinnamic acid, the phenyl ring of which is substituted by one or two identical or different residues from the series a) hydrogen, b) (C 1 - C 3 ) -alkyl, c) amino, d) (C 1 - C 3 ) mono- and dialkylamino, e) halogen, f) (C 1 -C 3 ) -haloalkyl, g) (C 2 -C 5 ) acylamino and h) (C 1 -C 3 ) -alkoxy. 5. Способ получения соединений формулы I по пп.1 - 4, отличающийся тем, что
а) соединение формулы II
Figure 00000002

где R1, R2 и R3 имеют вышеуказанные значения,
приводят во взаимодействие с соединением формулы III
Figure 00000003

где R4, R5 и n имеют вышеуказанное значение, в присутствии гидридов металлов, таких, как гидриды лития, калия или натрия, или карбонатов щелочных металлов, таких, как карбонаты натрия, калия или цезия, в инертном растворителе, таком, как N, N-диметилформамид (DMF) или диметилсульфоксид (DMSO), при температурах от 0oС до 60oС с получением соединения формулы IV
Figure 00000004

в котором заместители и переменные имеют вышеуказанное значение;
b) соединение формулы IV переводят гидразинолизом в этаноле с обратным холодильником в соединение формулы Ia
Figure 00000005

где R1, R2, R3, R4, R5 и n имеют вышеуказанное значение;
с) соединения формулы Ia при необходимости ацилируют и/или алкилируют известными способами и
d) получение соединения формулы I при необходимости переводят известными способами в физиологически приемлемые соли.5. The method of obtaining compounds of the formula I in PP.1 to 4, characterized in that
a) a compound of formula II
Figure 00000002

where R 1 , R 2 and R 3 have the above values,
interact with the compound of formula III
Figure 00000003

where R 4 , R 5 and n have the above meaning, in the presence of metal hydrides, such as lithium, potassium or sodium hydrides, or alkali metal carbonates, such as sodium, potassium or cesium carbonates, in an inert solvent, such as N , N-dimethylformamide (DMF) or dimethyl sulfoxide (DMSO), at temperatures from 0 o C to 60 o C to obtain the compounds of formula IV
Figure 00000004

in which the substituents and variables have the above meaning;
b) a compound of formula IV is converted by hydrazinolysis in ethanol under reflux to a compound of formula Ia
Figure 00000005

where R 1 , R 2 , R 3 , R 4 , R 5 and n have the above meaning;
c) compounds of formula Ia are acylated if necessary and / or alkylated by known methods, and
d) The preparation of a compound of formula I, if necessary, is converted into physiologically acceptable salts if necessary by known methods. 6. Соединения формулы I по пп.1 - 4 в качестве лечебного средства. 6. The compounds of formula I in PP.1 - 4 as a therapeutic agent. 7. Лечебное средство, содержащее, по меньшей мере, одно соединение формулы I по пп.1 - 4. 7. Therapeutic agent containing at least one compound of formula I in PP.1 - 4.
RU97103565/04A 1996-03-13 1997-03-12 AMINO ALKYL AND ACYLAMINO ALKYL ETHERS, METHOD FOR THEIR RECOVERY AND THEIR USE AS ANTAGONISTS OF BRADIKININ RECEPTOR RU97103565A (en)

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DE19609827.0 1996-03-13

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