RU96113091A - NEW ESSENTIAL DERIVATIVES 9-HYDROXY-PYRIDO [1,2-A] PYRIMIDIN-4-SHE - Google Patents

NEW ESSENTIAL DERIVATIVES 9-HYDROXY-PYRIDO [1,2-A] PYRIMIDIN-4-SHE

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Publication number
RU96113091A
RU96113091A RU96113091/04A RU96113091A RU96113091A RU 96113091 A RU96113091 A RU 96113091A RU 96113091/04 A RU96113091/04 A RU 96113091/04A RU 96113091 A RU96113091 A RU 96113091A RU 96113091 A RU96113091 A RU 96113091A
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Russia
Prior art keywords
formula
compound according
pyrimidin
pyrido
alkanediyl
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Application number
RU96113091/04A
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Russian (ru)
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RU2126406C1 (en
Inventor
Ванденберк Ян
Эдмон Жозефин Кенни Людо
Original Assignee
Жансен Фармасетика Н.В.
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Application filed by Жансен Фармасетика Н.В. filed Critical Жансен Фармасетика Н.В.
Priority claimed from PCT/EP1994/003804 external-priority patent/WO1995014691A1/en
Publication of RU96113091A publication Critical patent/RU96113091A/en
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Publication of RU2126406C1 publication Critical patent/RU2126406C1/en

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Claims (12)

1. Эфирные производные 9-гидрокси-пиридо[1,2-а]пиримидин-4-она общей формулы I
Figure 00000001

его фармацевтически приемлемая аддитивная соль кислоты и стереоизомеры,
где Alk представляет собой С1-4 алкандиил;
D представляет собой гетероцикл формулы
Figure 00000002

где каждый из R1 независимо представляет собой С2-6 алкенил; С2-6 алкинил; С3-6 циклоалкил, возможно замещенный С1-4 алкилом, С1-19 алкил, возможно замещенный С3-6 циклоалкилом, галогеном, С1-6 алкокси или циано;
каждый из R2 независимо представляет собой водород или С1-4 алкил.1. Ester derivatives of 9-hydroxy-pyrido [1,2-a] pyrimidin-4-one of the general formula I
Figure 00000001

its pharmaceutically acceptable acid addition salt and stereoisomers,
where Alk is C 1-4 alkanediyl;
D is a heterocycle of the formula
Figure 00000002

where each of R 1 independently represents a C 2-6 alkenyl; C 2-6 alkynyl; C 3-6 cycloalkyl, possibly substituted with C 1-4 alkyl, C 1-19 alkyl, possibly substituted with C 3-6 cycloalkyl, halogen, C 1-6 alkoxy or cyano;
each of R 2 independently represents hydrogen or C 1-4 alkyl. 2. Соединение по п.1, где R2 представляет собой метил.2. The compound according to claim 1, where R 2 represents methyl. 3. Соединение по п. 2, где Alk представляет собой С1-3 алкандиил, R1 представляет собой С1-12 алкил или С1-4 алкил, замещенный С1-4 алкокси или циано.3. The compound according to claim 2, wherein Alk is C 1-3 alkanediyl, R 1 is C 1-12 alkyl or C 1-4 alkyl, substituted with C 1-4 alkoxy or cyano. 4. Соединение по п.3, где Alk представляет собой С1-2 алкандиил.4. The compound according to claim 3, wherein Alk is C 1-2 alkanediyl. 5. Соединение по п. 2, где Alk представляет собой С1-3 алкандиил, R1 представляет собой С2-4 алкенил или С2-4 алкинил.5. The compound according to claim 2, wherein Alk is C 1-3 alkanediyl, R 1 is C 2-4 alkenyl or C 2-4 alkynyl. 6. Соединение по п.5, где Alk представляет собой С1-2 алкандиил.6. The compound according to claim 5, wherein Alk is C 1-2 alkanediyl. 7. Соединение по п.1, где соединение представляет собой:
3-[2-[4-(6-фтор-1,2-бензизоксазол-3-ил)-1-пиперидинил] этил] -6,7,8,9-тетрагидро-9-метокси-2-метил
Figure 00000003
пиридо[1,2-а] пиримидин-4-он;
3-[2-[4-(6-фтор-1,2-бензизоксазол-3-ил)-1-пепиридинил] этил] -6,7,8,9-тетрагидро-2-метил-9-пропокси
Figure 00000004
пиридо[1,2-а]пиримидин-4-он;
3-[2-[4-(6-фтор-1,2-бензизоксазол-3-ил)-1-пиперидинил] этил] -9-метокси- -2-метил
Figure 00000005
пиридо[1,2-а]пиримидин-4-он;
3-[2-[4-(6-фтор-1,2-бензизоксазол-3-ил)-1-пиперидинил] этил] -2-метил-9- (2-пропенил-окси)
Figure 00000006
пиридо[1,2-а]пиримидин-4-он;
3-[2-[4-(6-фтор-1,2-бензизоксазол-3-ил)-1-пиперидинил] этил] -2-метил-9- (2-пропинил-окси)
Figure 00000007
пиридо[1,2-а]пиримидин-4-он;
его фармацевтически-приемлемую аддитивную соль кислоты или стереоизомер.7. The compound according to claim 1, where the compound is:
3- [2- [4- (6-fluoro-1,2-benzisoxazol-3-yl) -1-piperidinyl] ethyl] -6,7,8,9-tetrahydro-9-methoxy-2-methyl
Figure 00000003
pyrido [1,2-a] pyrimidin-4-one;
3- [2- [4- (6-fluoro-1,2-benzisoxazol-3-yl) -1-pepyridinyl] ethyl] -6,7,8,9-tetrahydro-2-methyl-9-propoxy
Figure 00000004
pyrido [1,2-a] pyrimidin-4-one;
3- [2- [4- (6-fluoro-1,2-benzisoxazol-3-yl) -1-piperidinyl] ethyl] -9-methoxy--2-methyl
Figure 00000005
pyrido [1,2-a] pyrimidin-4-one;
3- [2- [4- (6-fluoro-1,2-benzisoxazol-3-yl) -1-piperidinyl] ethyl] -2-methyl-9- (2-propenyl-oxy)
Figure 00000006
pyrido [1,2-a] pyrimidin-4-one;
3- [2- [4- (6-fluoro-1,2-benzisoxazol-3-yl) -1-piperidinyl] ethyl] -2-methyl-9- (2-propynyl oxy)
Figure 00000007
pyrido [1,2-a] pyrimidin-4-one;
its pharmaceutically acceptable acid addition salt or stereoisomer. 8. Композиция, включающая в себя фармацевтически приемлемый носитель и активный ингредиент, отличающаяся тем, что в качестве активного ингредиента используют эффективное антипсихотическое количество соединения по любому из пп.1-7. 8. A composition comprising a pharmaceutically acceptable carrier and active ingredient, characterized in that an effective antipsychotic amount of the compound according to any one of claims 1 to 7 is used as an active ingredient. 9. Способ получения композиции по п.8, отличающийся тем, что фармацевтически приемлемый носитель смешивают с эффективным антипсихотическим количеством соединения по любому из пп.1-7 до получения однородной смеси. 9. The method of obtaining the composition of claim 8, wherein the pharmaceutically acceptable carrier is mixed with an effective antipsychotic amount of a compound according to any one of claims 1 to 7 to obtain a homogeneous mixture. 10. Соединения по любому из пп.1-7, обладающие фармакологическими свойствами. 10. Compounds according to any one of claims 1 to 7, with pharmacological properties. 11. Промежуточное соединение формулы
Figure 00000008

где Alk представляет собой С1-4 алкандиил;
R2 представляет собой водород или С1-4 алкил,
где фармацевтически приемлемая аддитивная соль кислоты или стереоизомер.11. Intermediate compound of formula
Figure 00000008

where Alk is C 1-4 alkanediyl;
R 2 is hydrogen or C 1-4 alkyl,
where the pharmaceutically acceptable acid addition salt or stereoisomer. 12. Способ получения соединения по п.1, отличающийся тем, что а) проводят N-алкилирование 3-пиперидинил-1,2-бензизоксазол формулы (II) алкилирующим агентом формулы (III) , где W представляет собой реакционноспособную уходящую группу, а D имеет значения, указанные в п.1,
Figure 00000009

б) проводят циклизацию оксима формулы (IV), где Y представляет собой реакционноспособную уходящую группу,
Figure 00000010

в) проводят
Figure 00000011
алкилирование промежуточного соединения формулы (IV-a) или (V-b) с алкилирующим агентом формулы
R'-W (VI),
где W представляет собой реакционноспособную уходящую группу,
получая соответственно соединения формулы (I-a) и (I-b)
Figure 00000012

Figure 00000013

г) проводят взаимопреобразование соединений формулы (I) одно в другое, используя известные способы, и далее, при желании, преобразуют соединения формулы (I) в терапевтически активную нетоксичную аддитивную соль кислоты, производя обработку кислотой, или, наоборот, преобразуя соль в свободное основание, производят обработку щелочью; и/или получают стереоизомеры этих соединений.12. The method of obtaining the compound according to claim 1, characterized in that a) N-alkylation of 3-piperidinyl-1,2-benzisoxazole of formula (II) is performed with an alkylating agent of formula (III), where W is a reactive leaving group, and D has the values specified in paragraph 1,
Figure 00000009

b) cyclization of the oxime of the formula (IV) is carried out, where Y is a reactive leaving group,
Figure 00000010

c) conduct
Figure 00000011
alkylation of an intermediate of formula (IV-a) or (Vb) with an alkylating agent of formula
R'-W (VI),
where W is a reactive leaving group,
receiving respectively the compounds of formula (Ia) and (Ib)
Figure 00000012

Figure 00000013

d) carry out the interconversion of the compounds of formula (I) into one another, using known methods, and then, if desired, convert the compounds of formula (I) into a therapeutically active non-toxic additive salt of the acid, processing the acid, or, conversely, converting the salt into the free base , make processing by alkali; and / or get stereoisomers of these compounds.
RU96113091A 1993-11-23 1994-11-16 Ester derivatives of 9-hydroxy-pyrido[1,2-a]pyrimidine-4-one, a method of their synthesis, a composition showing antipsychotic activity and a method of its preparing RU2126406C1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP93203270 1993-11-23
EP93203270.9 1993-11-23
PCT/EP1994/003804 WO1995014691A1 (en) 1993-11-23 1994-11-16 NOVEL 9-HYDROXY-PYRIDO[1,2-a]PYRIMIDIN-4-ONE ETHER DERIVATIVES

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RU2126406C1 RU2126406C1 (en) 1999-02-20

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EP (1) EP0730594B1 (en)
JP (1) JP3553951B2 (en)
AT (1) ATE184281T1 (en)
AU (1) AU687940B2 (en)
CA (1) CA2175372C (en)
DE (1) DE69420579T2 (en)
DK (1) DK0730594T3 (en)
ES (1) ES2137486T3 (en)
FI (1) FI112483B (en)
GR (1) GR3031500T3 (en)
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SI (1) SI0730594T1 (en)
WO (1) WO1995014691A1 (en)

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