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RU2345996C1 - Annelated azaheterocyclic amides, which include pyrimidine fragment, method of obtaining and their application - Google Patents

Annelated azaheterocyclic amides, which include pyrimidine fragment, method of obtaining and their applicationDownload PDF

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RU2345996C1
RU2345996C1RU2007127192/04ARU2007127192ARU2345996C1RU 2345996 C1RU2345996 C1RU 2345996C1RU 2007127192/04 ARU2007127192/04 ARU 2007127192/04ARU 2007127192 ARU2007127192 ARU 2007127192ARU 2345996 C1RU2345996 C1RU 2345996C1
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optionally substituted
substituted
alkyl
atom
general formula
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RU2007127192/04A
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Александр Васильевич Иващенко (US)
Александр Васильевич Иващенко
Сергей Евгеньевич Ткаченко (RU)
Сергей Евгеньевич Ткаченко
Иль Матусович Окунь (US)
Илья Матусович Окунь
Николай Филиппович Савчук (RU)
Николай Филиппович Савчук
Андрей Александрович Иващенко (RU)
Андрей Александрович Иващенко
Дмитрий Владимирович Кравченко (RU)
Дмитрий Владимирович Кравченко
Елена Александровна Рыжова (RU)
Елена Александровна Рыжова
бьев Сергей Борисович Ал (RU)
Сергей Борисович Алябьев
Александр Викторович Хват (US)
Александр Викторович Хват
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Андрей Александрович Иващенко
Алла Хем, Ллс
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Priority to PCT/IB2008/052846prioritypatent/WO2009010925A2/en
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Abstract

FIELD: chemistry.
SUBSTANCE: present invention relates to new annelated azaheterocyclic amides, including a pyrimidine fragment, with the general formula 1, method of obtaining them and their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of P13K kinase, in compounds with the general formula 1:
Figure 00000130
, where: X represents an oxygen atom, sulphur atom or not necessarily substituted at the nitrogen NH group, where the substitute is selected from lower alkyls and possibly a substituted aryl; Y represents an atom of nitrogen or substituted at the carbon atom CH group, where the substitute is selected from lower alkyls; Z represents an oxygen atom; R1 represents a hydrogen atom or not necessarily substituted C1-C6alkyl, or Z represents a nitrogen atom, which is together with a carbon atom, with which it is joined, form through Z and R1 annelated imidazole cycle; R2 and R3 independently from each other represent hydrogen, not necessarily substituted with C1-C6alkyl, C3-C6cycloalkyl, not necessarily substituted with phenyl, not necessarily substituted with 6-member aza-heteroaryl, under the condition, when Y represents a nitrogen atom, or R2 and R3 independently from each other represent not necessarily substituted C1-C6alkyl, not necessarily substituted with phenyl, not necessarily substituted with 5-7-member heterocycle with 1-2 heteroatoms, selected from nitrogen and oxygen, and possibly annelated with a phenyl ring, under the condition, when Y does not necessarily represent a substituted carbon atom at the CH group, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents a substituted aminoC1-C6alkyl and not necessarily substituted 5-6-member aza-heterocycloalkyl, under the condition, when Y represents a group which is substituted at the CH atom, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents phenyl which is not necessarily substituted, pyridyl which is not necessarily substituted, pyrimidinyl which is not necessarily substituted, under the conditions, when R1 represents a substituted aminoC1-C6alkyl, substituted C2-C3hydroxyalkyl and aza-heterocycloalkyl not necessarily substituted, Y represents a group with CH substituted, and X represents an oxygen atom, sulphur, and the substitute of the above indicated substituted alkyl, phenyl, heterocycle, pyridyl, pyrimidyl are selected from groups of hydroxyl-, cyano-groups, hydrogen, lower alkyls, possibly mono- or di-substituted lower alkyl sulfamoyl, carbamoyl, C1-C6alkoxycarbonyl, amino, mono- or di-lower alkyl-amine, N-(lower alkyl), N-(phenylC1-C6alkyl)amine, phenyl, possibly substituted with a halogen atom, C1-C6alkyl, haloid-C1-C6alkyl; phenylC1-C6alkyl, saturated or non-saturated 5-6-member heterocycle containing 1-2-heteroatoms, selected from nitrogen, oxygen and sulphur, and possible condensation with a benzene ring R4 represents hydrogen or a lower alkyl.
EFFECT: obtaining new annelated aza-heterocyclic amides, including a pyrimidine fragment, with the general formula with the possibility of their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of PI3K kinase.
16 cl, 5 tbl, 5 ex

Description

Translated fromRussian

Текст описания приведен в факсимильном виде.

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The text of the description is given in facsimile form.
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Claims (16)

Translated fromRussian
1. Аннелированные азагетероциклы, включающие пиримидиновый фрагмент, общей формулы 1 в форме свободных оснований или фармацевтически приемлемых солей
Figure 00000110

где Х представляет собой атом кислорода, атом серы или необязательно замещенную по азоту NH группу, где заместитель выбирается из низшего алкила или возможно замещенного арила;
Y представляет собой атом азота или замещенную по атому углерода СН группу, где заместитель выбирается из низшего алкила;
Z представляет собой атом кислорода;
R1 представляет собой атом водорода или необязательно замещенный C1-С6 алкил, или
Z представляет собой атом азота, который вместе с атомом углерода, с которым он связан, образуют через Z и R1 аннелированный имидазолиновый цикл;
R2 и R3 независимо друг от друга представляют собой водород, необязательно замещенный C1-С6алкил, С3-С6ациклоалкил, необязательно замещенный фенил, необязательно замещенный 6-членный азагетероарил, при условии, когда Y представляет собой атом азота, или
R2 и R3 независимо друг от друга представляют собой необязательно замещенный C1-С6алкил, необязательно замещенный фенил, необязательно замещенный 5-7-членный гетероциклил с 1-2 гетероатомами, выбираемыми из азота и кислорода, и возможно аннелированный с фенильным кольцом, или R2 и R3 вместе с атомом азота, с которым они связаны, образуют необязательно замещенный 5-7-членный азагетероциклил, возможно конденсированный с бензольным кольцом или спироконденсированный с диоксаланом, при условии, когда Y представляет собой необязательно замещенную по атому углерода СН группу, а Х представляет собой атом кислорода, атом серы, или
R2 представляет собой водород, a R3 представляет собой замещенный аминоС1-С6алкил или необязательно замещенный 5-6-членный азагетероциклилалкил, при условии, когда Y представляет собой необязательно замещенную по атому углерода СН группу, а Х представляет собой атом кислорода, атом серы, или
R2 представляет собой водород, а R3 представляет собой необязательно замещенный фенил, необязательно замещенный пиридил, необязательно замещенный пиримидинил, при условии, когда R1 представляет собой замещенный аминоС1-С6алкил, замещенный С2-С3 гидроксиалкил или необязательно замещенный азагетероциклилалкил, Y представляет необязательно замещенную по атому углерода СН группу, а Х представляет атом кислорода, атом серы;
при этом заместители в указанных выше замещенных алкиле, фениле, гетероциклиле, пиридиле, пиримидиле выбираются из группы гидрокси, цианогруппы, галогена, низшего алкила, возможно моно- или дизамещенного низшим алкилом сульфамоила, карбамоила, С1-С6алкоксикарбонила, амино, моно- или ди-низшего алкиламина, N-(низший алкил), N-(фенилС1-С6алкил)амина, фенила, возможно замещенного атомом галогена, C1-С6алкилом, галоид-С1-С6алкилом; фенилС1-С6алкила, насыщенного или ненасыщенного 5-6-членного гетероциклила, содержащего 1-2-гетероатома, выбранных из азота, кислорода и серы, и возможно конденсированного с бензольным кольцом,
R4 представляет собой водород или низший алкил;
исключая 4,5-дигидро-6-метил-4-оксо-1-(2,4,6-трихлорфенил)-1Н-пиразоло[3,4-d]пиримидин-3-карбоксамид; 4,5-дигидро-4-оксо-1-дифенил-1Н-пиразоло[3,4-d]пиримидин-3-карбоксамид; 4,5-дигидро-4-оксо-1β-D-рибофуранозил-1Н-пиразоло3,4-пиримидин-3-карбоксамид.1. Annelated azaheterocycles comprising the pyrimidine moiety of general formula 1 in the form of free bases or pharmaceutically acceptable salts
Figure 00000110

where X represents an oxygen atom, a sulfur atom or an optionally nitrogen-substituted NH group, where the substituent is selected from lower alkyl or optionally substituted aryl;
Y represents a nitrogen atom or a CH group substituted on a carbon atom, wherein the substituent is selected from lower alkyl;
Z represents an oxygen atom;
R1 represents a hydrogen atom or optionally substituted C1 -C6 alkyl, or
Z represents a nitrogen atom, which, together with the carbon atom to which it is bonded, form an annelated imidazoline ring through Z and R1;
R 2 and R 3 independently of one another are hydrogen, optionally substituted C1 -C6 alkyl, C3 -C6 acycloalkyl, optionally substituted phenyl, optionally substituted 6-membered azaheteroaryl, provided that Y represents a nitrogen atom, or
R2 and R3 independently from each other are optionally substituted C1 -C6 alkyl, optionally substituted phenyl, optionally substituted 5-7 membered heterocyclyl with 1-2 heteroatoms selected from nitrogen and oxygen, and optionally annelated with a phenyl ring, or R 2 and R 3 together with the nitrogen atom to which they are bonded form an optionally substituted 5-7 membered azaheterocyclyl, possibly fused to a benzene ring or spirocondensed with dioxalan, provided that Y is an optionally substituted p carbon atom of the CH group and X represents an oxygen atom, a sulfur atom, or
R2 is hydrogen, and R3 is substituted aminoC1 -C6 alkyl or optionally substituted 5-6 membered azaheterocyclylalkyl, provided that Y is an optionally substituted carbon atom CH group, and X represents an oxygen atom, a sulfur atom , or
R2 is hydrogen, and R3 is optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, provided that R1 is substituted aminoC1 -C6 alkyl, substituted C2 -C3 hydroxyalkyl or optionally substituted azaheterocyclylalkyl, Y is optionally substituted at the carbon atom of the CH group, and X represents an oxygen atom, a sulfur atom;
while the substituents in the above substituted alkyl, phenyl, heterocyclyl, pyridyl, pyrimidyl are selected from the group of hydroxy, cyano, halogen, lower alkyl, possibly mono- or disubstituted by lower alkyl sulfamoyl, carbamoyl, C1 -C6 alkoxycarbonyl, amino, mono or di-lower alkylamine, N- (lower alkyl), N- (phenylC1 -C6 alkyl) amine, phenyl optionally substituted with a halogen atom, C1 -C6 alkyl, halogen-C1 -C6 alkyl; phenylC1 -C6 alkyl, saturated or unsaturated 5-6 membered heterocyclyl containing 1-2 heteroatoms selected from nitrogen, oxygen and sulfur, and possibly fused to a benzene ring,
R4 represents hydrogen or lower alkyl;
excluding 4,5-dihydro-6-methyl-4-oxo-1- (2,4,6-trichlorophenyl) -1H-pyrazolo [3,4-d] pyrimidine-3-carboxamide; 4,5-dihydro-4-oxo-1-diphenyl-1H-pyrazolo [3,4-d] pyrimidine-3-carboxamide; 4,5-dihydro-4-oxo-1β-D-ribofuranosyl-1H-pyrazolo-3,4-pyrimidine-3-carboxamide.2. Соединения по п.1, представляющие собой замещенные амиды 4-оксо-3,4-дигидрофуро(или тиено)[2,3-b]пиримидин-5-карбоновых кислот общей формулы 1.1 или их фармацевтически приемлемые соли
Figure 00000111

где R1 и Z имеют вышеуказанные значения; X1 представляет собой атом кислорода, атом серы; R2 и R3 независимо друг от друга представляют собой необязательно замещенный алкил, необязательно замещенный фенил, необязательно замещенный гетероциклил, или R2 и R3 вместе с атомом азота, с которым они связаны, образуют необязательно замещенный 5-7-членный азагетероциклил, возможно конденсированный с бензольным кольцом, или
R2 представляет собой водород, а R3 представляет собой замещенный амино C1-С6алкил или необязательно замещенный азагетероциклилалкил, или
R2 представляет собой водород, а R3 представляет собой необязательно замещенный фенил, необязательно замещенный пиридил, необязательно замещенный пиримидинил, при условии, когда R1 представляет собой замещенный аминоалкил или необязательно замещенный азагетероциклилалкил;
R5 представляет собой водород или низший алкил.2. The compounds according to claim 1, which are substituted amides of 4-oxo-3,4-dihydrofuro (or thieno) [2,3-b] pyrimidine-5-carboxylic acids of the general formula 1.1 or their pharmaceutically acceptable salts
Figure 00000111

where R1 and Z have the above meanings; X1 represents an oxygen atom, a sulfur atom; R2 and R3 independently from each other are optionally substituted alkyl, optionally substituted phenyl, optionally substituted heterocyclyl, or R2 and R3 together with the nitrogen atom to which they are attached form an optionally substituted 5-7 membered azaheterocyclyl, possibly fused to a benzene ring , or
R2 is hydrogen, and R3 is substituted amino C1 -C6 alkyl or optionally substituted azaheterocyclylalkyl, or
R2 is hydrogen, and R3 is optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, provided that R1 is substituted aminoalkyl or optionally substituted azaheterocyclylalkyl;
R5 represents hydrogen or lower alkyl.3. Соединения по п.2, представляющие собой замещенные амиды 4-оксо-3,4-дигидрофуро[2,3-b]пиримидин-5-карбоновых кислот общей формулы 1.1.1, замещенные амиды 4-оксо-3,4-дигидротиено[2,3-b]пиримидин-5-карбоновых кислот общей формулы 1.1.2, замещенные амиды 2,3-дигидрофуро[3,2-е]имидазо[1,2-с]пиримидин-9-карбоновых кислот 1.1.3 и замещенные амиды 2,3-дигидротиено[3,2-е]имидазо[1,2-с]пиримидин-9-карбоновых кислот 1.1.4 или их фармацевтически приемлемые соли
Figure 00000112
Figure 00000113
Figure 00000114
Figure 00000115

где R1 и R5 имеют вышеуказанное значение;
R2 и R3 независимо друг от друга представляют собой необязательно замещенный C1-С6алкил, необязательно замещенный фенил, необязательно замещенный гетероциклил, или R2 и R3 вместе с атомом азота, с которым они связаны, образуют необязательно замещенный 5-7-членный азагетероциклил, возможно конденсированный с бензольным кольцом, или
R2 представляет собой водород, а R3 представляет собой замещенный амино C1-С6алкил или необязательно замещенный азагетероциклилалкил, или
R2 представляет собой водород, а R3 представляет собой необязательно замещенный фенил, необязательно замещенный пиридил, необязательно замещенный пиримидинил, при условии, когда R1 представляет собой замещенный аминоС1-С6алкил или необязательно замещенный азагетероциклилалкил;
R6 и R7 независимо друг от друга представляют собой водород.3. The compounds according to claim 2, which are substituted amides of 4-oxo-3,4-dihydrofuro [2,3-b] pyrimidine-5-carboxylic acids of the general formula 1.1.1, substituted amides of 4-oxo-3,4- dihydrothieno [2,3-b] pyrimidine-5-carboxylic acids of the general formula 1.1.2, substituted amides of 2,3-dihydrofuro [3,2-e] imidazo [1,2-c] pyrimidine-9-carboxylic acids 1.1. 3 and substituted amides of 2,3-dihydrothieno [3,2-e] imidazo [1,2-c] pyrimidine-9-carboxylic acids 1.1.4 or their pharmaceutically acceptable salts
Figure 00000112
Figure 00000113
Figure 00000114
Figure 00000115

where R1 and R5 have the above meaning;
R2 and R3, independently of one another, are optionally substituted C1 -C6 alkyl, optionally substituted phenyl, optionally substituted heterocyclyl, or R2 and R3 together with the nitrogen atom to which they are attached form an optionally substituted 5-7 membered azaheterocyclyl, possibly condensed with a benzene ring, or
R2 is hydrogen, and R3 is substituted amino C1 -C6 alkyl or optionally substituted azaheterocyclylalkyl, or
R2 is hydrogen, and R3 is optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, provided that R1 is substituted aminoC1 -C6 alkyl or optionally substituted azaheterocyclylalkyl;
R6 and R7 are independently hydrogen.4. Соединения по п.3, представляющие собой замещенные амиды 3-аминоалкил-6-метил-4-оксо-3,4-дигидрофуро[2,3-b]пиримидин-5-карбоновых кислот общей формулы 1.1.1.1, 1.1.1.2 и 1.1.1.3, замещенные амиды 3-аминоалкил-6-метил-4-оксо-3,4-дигидротиено[2,3-b]пиримидин-5-карбоновых кислот общей формулы 1.1.1.4, 1.1.1.5 и 1.1.1.6, замещенные амиды 3-гидроксиалкил-6-метил-4-оксо-3,4-дигидро-фуро[2,3-b]пиримидин-5-карбоновых кислот общей формулы 1.1.1.7 и 1.1.1.8 и замещенные амиды 3-гидроксиалкил-6-метил-4-оксо-3,4-дигидротиено[2,3-b]пиримидин-5-карбоновых кислот общей формулы 1.1.1.9 и 1.1.1.10 или их фармацевтически приемлемые соли
Figure 00000116
Figure 00000117
Figure 00000118

Figure 00000119
Figure 00000120
Figure 00000121

Figure 00000122
Figure 00000123
Figure 00000124
Figure 00000125

где R3 представляет собой необязательно замещенный фенил, необязательно замещенный пиридил, необязательно замещенный пиримидинил;
R1a и R1b независимо друг от друга представляют собой атом водорода, необязательно замещенный низший алкил или вместе с атомом углерода, с которым они связаны, образуют 5-7 членный азагетероциклил;
R1c, R1d и R1e представляют собой атом водорода или необязательно замещенный низший алкил или один из R1c, R1d и R1e вместе с атомом углерода, с которым он связан, и R1a вместе с атомом азота, с которым он связан, образуют 5-6-членный насыщенный гетероциклил с 1-2 гетероатомами, выбранными из азота и кислорода, при условии, когда два других из R1c, R1b и R1e и R1d являются водородом.4. The compounds according to claim 3, which are substituted amides of 3-aminoalkyl-6-methyl-4-oxo-3,4-dihydrofuro [2,3-b] pyrimidine-5-carboxylic acids of the general formula 1.1.1.1, 1.1. 1.2 and 1.1.1.3, substituted amides of 3-aminoalkyl-6-methyl-4-oxo-3,4-dihydrothieno [2,3-b] pyrimidine-5-carboxylic acids of the general formulas 1.1.1.4, 1.1.1.5 and 1.1. 1.6, substituted amides of 3-hydroxyalkyl-6-methyl-4-oxo-3,4-dihydro-furo [2,3-b] pyrimidine-5-carboxylic acids of the general formula 1.1.1.7 and 1.1.1.8 and substituted amides 3- hydroxyalkyl-6-methyl-4-oxo-3,4-dihydrothieno [2,3-b] pyrimidine-5-carboxylic acids of the general formulas 1.1.1.9 and 1.1.1.10 or their pharmaceutical ski acceptable salts
Figure 00000116
Figure 00000117
Figure 00000118

Figure 00000119
Figure 00000120
Figure 00000121

Figure 00000122
Figure 00000123
Figure 00000124
Figure 00000125

where R3 is optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyrimidinyl;
R1 a and R1 b independently represent a hydrogen atom, an optionally substituted lower alkyl, or together with the carbon atom to which they are attached form 5-7 membered azaheterocyclyl;
R1 c, R1 d and R1 e represent a hydrogen atom or an optionally substituted lower alkyl or one of R1 c, R1 d and R1 e together with the carbon atom to which it is bonded, and R1 a together with the nitrogen atom to which it is bonded forms a 5-6 membered saturated heterocyclyl with 1-2 heteroatoms selected from nitrogen and oxygen, provided that the other two of R1 c, R1 b and R1 e and R1 d are hydrogen.5. Соединения по п.1, представляющие собой замещенные амиды 4-оксо-4,5-дигидро-азолопиримидин-3-карбоновых кислот общей формулы 1.2 или их фармацевтически приемлемые соли:
Figure 00000126

где R1, R4, X и Z имеют вышеуказанные значения; R2 и R3 независимо друг от друга представляют собой водород, необязательно замещенный C1-С6алкил, необязательно замещенный фенил, необязательно замещенный 6-членный азотсодержащий гетероциклил или R2 и R3 вместе с атомом азота, с которым они связаны, образуют необязательно замещенный 5-7-членный азагетероциклил.5. The compounds according to claim 1, which are substituted amides of 4-oxo-4,5-dihydro-azolopyrimidin-3-carboxylic acids of the general formula 1.2 or their pharmaceutically acceptable salts:
Figure 00000126

where R1, R4, X and Z have the above meanings; R2 and R3 independently from each other are hydrogen, optionally substituted C1 -C6 alkyl, optionally substituted phenyl, optionally substituted 6-membered nitrogen-containing heterocyclyl, or R2 and R3 together with the nitrogen atom to which they are attached form an optionally substituted 5- 7 membered azaheterocyclyl.6. Способ получения соединений общей формулы 1 по любому из пп.1-5 взаимодействием соответствующих кислот общей формулы F1 с аминами общей формулы F2 в присутствии конденсирующих реагентов
Figure 00000127
Figure 00000128

где X, Y, Z, R1, R2, R3 и R4 имеют вышеуказанные для соединений общей формулы 1 значения.6. A method for producing compounds of general formula 1 according to any one of claims 1 to 5 by reacting the corresponding acids of general formula F1 with amines of general formula F2 in the presence of condensing agents
Figure 00000127
Figure 00000128

where X, Y, Z, R1, R2, R3 and R4 have the above meanings for compounds of general formula 1.7. Ингибиторы PI3 киназ, представляющие собой соединения общей формулы 1 по п.1.7. Inhibitors of PI3 kinases, which are compounds of General formula 1 according to claim 1.8. Селективные ингибиторы изоформы р110-альфа PI3 киназ по п.7, представляющие собой соединения общей формулы 1 по п.1.8. Selective inhibitors of the isoform p110-alpha PI3 kinases according to claim 7, which are compounds of General formula 1 according to claim 1.9. Селективные ингибиторы изоформы р110-бета PI3 киназ по п.7, представляющие собой соединения общей формулы 1 по п.1.9. Selective inhibitors of the isoform of p110-beta PI3 kinases according to claim 7, which are compounds of the general formula 1 according to claim 1.10. Селективные ингибиторы изоформы р110-гамма PI3 киназ по п.7, представляющие собой соединения общей формулы 1 по п.1.10. Selective inhibitors of the isoform p110-gamma PI3 kinases according to claim 7, which are compounds of general formula 1 according to claim 1.11. Селективные ингибиторы изоформы р110-дельта PI3 киназ по п.7, представляющие собой соединения общей формулы 1 по п.1.11. Selective inhibitors of the isoform p110-delta PI3 kinases according to claim 7, which are compounds of the general formula 1 according to claim 1.12. Селективные ингибиторы изоформы р110-альфа PI3 киназ с мутацией в эксоне 20(H1047R) по п.7, представляющие собой соединения общей формулы 1 по п.1.12. Selective inhibitors of the isoform p110-alpha PI3 kinases with mutation in exon 20 (H1047R) according to claim 7, which are compounds of the general formula 1 according to claim 1.13. Соединения общей формулы 1 по п.1, в качестве биологически активных ингредиентов для получения лекарственных средств для лечения онкологических заболеваний.13. The compounds of General formula 1 according to claim 1, as biologically active ingredients for the manufacture of medicines for the treatment of cancer.14. Фармацевтическая композиция, обладающая свойствами ингибитора PI3 киназ, содержащая в качестве активного ингредиента, по крайней мере, одно соединение общей формулы 1 по п.1 или соединение по любому из пп.2-5 или его фармацевтически приемлемую соль в эффективном количестве.14. A pharmaceutical composition having the properties of a PI3 kinase inhibitor, containing as an active ingredient at least one compound of general formula 1 according to claim 1 or a compound according to any one of claims 2-5 or a pharmaceutically acceptable salt thereof in an effective amount.15. Способ получения фармацевтической композиции по п.14 смешением биологически активного ингредиента по п.13 с инертным наполнителем и/или растворителем.15. The method of obtaining the pharmaceutical composition according to p. 14 by mixing the biologically active ingredient according to p. 13 with an inert filler and / or solvent.16. Лекарственное средство в форме таблеток, капсул или инъекций, помещенных в фармацевтически приемлемую упаковку, включающее ингибитор Р13 киназ по любому из пп.7-12 или фармацевтическую композицию по п.14 в эффективном количестве.16. A drug in the form of tablets, capsules, or injections in a pharmaceutically acceptable package, comprising the P13 kinase inhibitor according to any one of claims 7-12 or the pharmaceutical composition of claim 14 in an effective amount.
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