RU2318818C1 - Azaheterocycles, combinatory library, focused library, pharmaceutical composition and method for preparing (variants) - Google Patents

Azaheterocycles, combinatory library, focused library, pharmaceutical composition and method for preparing (variants) Download PDF

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RU2318818C1
RU2318818C1 RU2006111951/04A RU2006111951A RU2318818C1 RU 2318818 C1 RU2318818 C1 RU 2318818C1 RU 2006111951/04 A RU2006111951/04 A RU 2006111951/04A RU 2006111951 A RU2006111951 A RU 2006111951A RU 2318818 C1 RU2318818 C1 RU 2318818C1
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RU2006111951A (en
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Александр Васильевич Иващенко
Алексей Петрович Ильин
Владимир Михайлович Кисель
Андрей Сергеевич Трифиленков
Сергей Александрович Цырульников
Александр Михайлович Шкирандо
Марина Васильевна Чуракова
Ирина Олеговна Ломакина
Виктор Владимирович Потапов
Анастасия Ильясовна Замалетдинова
Сергей Евгеньевич Ткаченко
Дмитрий Владимирович Кравченко
Александр Викторович Хват
Илья Матусович Окунь
Александр Сергеевич Киселев
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Общество С Ограниченной Ответственностью "Исследовательский Институт Химического Разнообразия"
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Priority to RU2006111951/04A priority Critical patent/RU2318818C1/en
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    • C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
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Abstract

FIELD: organic chemistry, medicine, biochemistry, pharmacy.
SUBSTANCE: invention relates to novel azaheterocycles of the general formula (I):
Figure 00000002
possessing inhibitory effect on activity of tyrosine kinase and can be used in treatment of different diseases mediated by these receptors. In compound of the general formula (1) W represents azaheterocycle comprising 6-13 atoms that can be optionally annelated with at least one (C5-C7)-carbocycle and/or possibly annelated with heterocycle comprising 4-10 atoms in ring and comprising at least one heteroatom chosen from oxygen (O), sulfur (S) or nitrogen (N) atom; Ra 1 represents a substitute of amino group but not hydrogen atom, such as substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-10-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; Rb represents carbamoyl group -C(O)NHRa wherein Ra represents a substitute of amino group but not hydrogen atom, such as possibly substituted alkyl, possibly substituted aryl, possibly substituted 5-10-membered heterocyclyc comprising at least one heteroatom chosen from O, S or N; Rc represents a substitute of cyclic system, such as possibly substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-6-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; or Rb and Rc form in common aminocyanomethylene group [(=C(NH2)CN], or their pharmaceutically acceptable salts. Also, invention relates to methods for synthesis of these compounds (variants), a pharmaceutical composition, combinatory and focused libraries.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods for synthesis and preparing.
35 cl, 16 sch, 13 tbl, 43 ex

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Figure 00000257
The text of the description is given in facsimile form.
Figure 00000003
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Figure 00000257

Claims (35)

1. Азагетероциклы общей формулы 11. Azaheterocycles of the general formula 1
Figure 00000258
Figure 00000258
 где W представляет собой азагетероцикл, включающий 6-13 атомов, необязательно аннелированный, по крайней мере, с одним C5-C7 карбоциклом и/или возможно аннелированным гетероциклом с 4-10 атомами в кольце, и включающим, по крайней мере, один из гетероатомов, выбранный из группы О, S или N;where W is an azaheterocycle comprising 6 to 13 atoms, optionally annelated with at least one C 5 -C 7 carbocycle and / or possibly annelated heterocycle with 4-10 atoms in the ring, and including at least one of heteroatoms selected from the group O, S or N; R1 a представляет собой заместитель аминогруппы, исключая водород, такой как, возможно замещенный C1-С6 алкил, возможно замещенный арил или возможно замещенный 5-10-членный гетероциклил, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N; Rb представляют собой карбамоильную группу -C(O)NHRa, в которой Ra представляет собой заместитель аминогруппы, исключая водород, такой как возможно замещенный алкил, возможно замещенный арил, возможно замещенный 5-10-членный гетероциклил, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N; Rc представляют собой заместитель циклической системы, такой как возможно замещенный C1-С6 алкил, возможно замещенный арил или возможно замещенный 5-6-членный гетероциклил, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или Rb и Rc вместе образуют амино-циано-метиленовую группу [(=C(NH2)CN]; или их фармацевтически приемлемые соли, включающие темплейты Т-1.1-Т-1.41; Т-2.1-Т.2.4; Т-3.1, Т-3.2:R 1 a represents an amino group substituent, excluding hydrogen, such as optionally substituted C 1 -C 6 alkyl, optionally substituted aryl or optionally substituted 5-10 membered heterocyclyl, including at least one of the heteroatoms selected from group O S or N; R b represents a carbamoyl group —C (O) NHR a , in which R a represents a substituent of an amino group, excluding hydrogen, such as optionally substituted alkyl, optionally substituted aryl, optionally substituted 5-10 membered heterocyclyl, including at least one of the heteroatoms selected from the group O, S or N; R c represent a cyclic system substituent, such as a possibly substituted C 1 -C 6 alkyl, a possibly substituted aryl or a possibly substituted 5-6 membered heterocyclyl, including at least one of the heteroatoms selected from the group O, S or N , or R b and R c together form an amino-cyano-methylene group [(= C (NH 2 ) CN]; or their pharmaceutically acceptable salts, including templates T-1.1-T-1.41; T-2.1-T.2.4; T-3.1, T-3.2:
Figure 00000259
Figure 00000260
Figure 00000261
Figure 00000262
Figure 00000263
Figure 00000259
Figure 00000260
Figure 00000261
Figure 00000262
Figure 00000263
Figure 00000264
Figure 00000265
Figure 00000266
Figure 00000267
Figure 00000268
Figure 00000264
Figure 00000265
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Figure 00000267
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Figure 00000269
Figure 00000270
Figure 00000271
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Figure 00000273
Figure 00000269
Figure 00000270
Figure 00000271
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Figure 00000273
Figure 00000274
Figure 00000275
Figure 00000276
Figure 00000277
Figure 00000278
Figure 00000274
Figure 00000275
Figure 00000276
Figure 00000277
Figure 00000278
Figure 00000279
Figure 00000280
Figure 00000281
Figure 00000282
Figure 00000283
Figure 00000284
Figure 00000279
Figure 00000280
Figure 00000281
Figure 00000282
Figure 00000283
Figure 00000284
Figure 00000285
Figure 00000286
Figure 00000287
Figure 00000288
Figure 00000289
Figure 00000290
Figure 00000285
Figure 00000286
Figure 00000287
Figure 00000288
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Figure 00000290
Figure 00000291
Figure 00000292
Figure 00000293
Figure 00000294
Figure 00000295
Figure 00000291
Figure 00000292
Figure 00000293
Figure 00000294
Figure 00000295
Figure 00000296
Figure 00000297
Figure 00000298
Figure 00000299
Figure 00000300
Figure 00000301
Figure 00000296
Figure 00000297
Figure 00000298
Figure 00000299
Figure 00000300
Figure 00000301
 в которых пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000302
) представляет одинарную или двойную связь, и исключая азагетероциклы, включающие фрагменты В(1-29), азагетероциклы С1(1-6) и С2(1-17)in which the dotted line with the solid line accompanying it (
Figure 00000302
) represents a single or double bond, and excluding azaheterocycles, including fragments B (1-29), azaheterocycles C1 (1-6) and C2 (1-17)
Figure 00000303
Figure 00000304
Figure 00000305
Figure 00000306
Figure 00000307
Figure 00000303
Figure 00000304
Figure 00000305
Figure 00000306
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Figure 00000309
Figure 00000310
Figure 00000311
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Figure 00000309
Figure 00000310
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Figure 00000315
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Figure 00000313
Figure 00000314
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Figure 00000316
Figure 00000317
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Figure 00000317
Figure 00000318
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Figure 00000320
Figure 00000321
Figure 00000322
Figure 00000323
Figure 00000320
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Figure 00000322
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Figure 00000324
Figure 00000325
Figure 00000326
Figure 00000327
Figure 00000324
Figure 00000325
Figure 00000326
Figure 00000327
Figure 00000328
Figure 00000329
Figure 00000330
Figure 00000331
Figure 00000328
Figure 00000329
Figure 00000330
Figure 00000331
Figure 00000332
Figure 00000333
Figure 00000334
Figure 00000332
Figure 00000333
Figure 00000334
Figure 00000335
Figure 00000336
Figure 00000337
Figure 00000338
Figure 00000335
Figure 00000336
Figure 00000337
Figure 00000338
Figure 00000339
Figure 00000340
Figure 00000341
Figure 00000342
Figure 00000339
Figure 00000340
Figure 00000341
Figure 00000342
Figure 00000343
Figure 00000344
Figure 00000345
Figure 00000346
Figure 00000343
Figure 00000344
Figure 00000345
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Figure 00000347
Figure 00000348
Figure 00000349
Figure 00000350
Figure 00000347
Figure 00000348
Figure 00000349
Figure 00000350
Figure 00000351
Figure 00000352
Figure 00000353
Figure 00000354
Figure 00000351
Figure 00000352
Figure 00000353
Figure 00000354
 2. Соединения по п.1, представляющие собой замещенные азагетероциклы общей формулы 1.1-1.52. The compounds according to claim 1, which are substituted azaheterocycles of the general formula 1.1-1.5
Figure 00000355
Figure 00000356
Figure 00000357
Figure 00000355
Figure 00000356
Figure 00000357
Figure 00000358
Figure 00000359
Figure 00000358
Figure 00000359
 где пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000360
) представляет одинарную или двойную связь; R1 a, Rb и Rc имеют вышеуказанное значение; R2 a представляет собой заместитель аминогруппы, такой как атом водорода, возможно замещенный C1-С6 алкил, каждый из R1 d и R2 d, R3 d и R4 d независимо друг от друга представляют заместитель циклической системы, выбранный из водорода, возможно замещенного C1-С6 алкила, возможно замещенного арила, илиwhere the dashed line with the solid line accompanying it (
Figure 00000360
) represents a single or double bond; R 1 a , R b and R c have the above meaning; R 2 a represents an amino group substituent, such as a hydrogen atom, optionally substituted C 1 -C 6 alkyl, each of R 1 d and R 2 d , R 3 d and R 4 d independently represent a cyclic system substituent selected from hydrogen, possibly substituted C 1 -C 6 alkyl, optionally substituted aryl, or R1 d и R2 a для соединений 1.1, 1.2 и 1.3 и R2 d и R2 a для соединений 1.4 и 1.5 могут образовывать вместе с атомами, с которыми они связаны, возможно замещенный 4-10-членный азагетероцикл, возможно содержащий дополнительно гетероатомы, выбранные из азота, кислорода или серы, и возможно конденсированный с бензольным кольцом или с другим 5-6-членным гетероциклом, в котором гетероатомы выбраны из азота, кислорода или серы, аR 1 d and R 2 a for compounds 1.1, 1.2 and 1.3, and R 2 d and R 2 a for compounds 1.4 and 1.5 can form, together with the atoms to which they are attached, a possibly substituted 4-10 membered azaheterocycle, possibly containing additional heteroatoms selected from nitrogen, oxygen or sulfur, and possibly fused to a benzene ring or another 5-6 membered heterocycle in which the heteroatoms are selected from nitrogen, oxygen or sulfur, and R3 d и R2 d для соединений 1.3, R1 d и R2 d для соединений 1.4 и 1.5 и R4 d и R3 d для соединений 1.5 вместе с атомами, с которыми они связаны, могут образовывать возможно замещенный алифатический цикл, содержащий 4-12 атомов углерода, возможно замещенный моно- или конденсированный биароматический цикл или возможно замещенный 5-6-членный гетероцикл, в котором гетероатомы выбраны из азота, кислорода или серы, и который может быть конденсирован с другим возможно замещенным 5-6-членным гетероциклом, содержащим в качестве гетероатомов азот, кислород или серу, илиR 3 d and R 2 d for compounds 1.3, R 1 d and R 2 d for compounds 1.4 and 1.5, and R 4 d and R 3 d for compounds 1.5, together with the atoms to which they are bonded, can form a possibly substituted aliphatic ring, containing 4-12 carbon atoms, a possibly substituted mono- or fused biaromatic ring, or a possibly substituted 5-6 membered heterocycle in which heteroatoms are selected from nitrogen, oxygen or sulfur, and which may be fused to another possibly substituted 5-6 membered a heterocycle containing nitrogen, oxygen or sulfur as heteroatoms, or Rc и R2 d для соединений 1.2, или Rc и R3 d для соединений 1.3 и 1.4, или Rc и R4 d для соединений 1.5 вместе с атомами, с которыми они связаны, могут образовывать возможно замещенный алифатический цикл, содержащий 4-12 атомов углерода или возможно замещенный 5-6-членный гетероцикл, в котором гетероатомы выбраны из азота, кислорода или серы, и который может быть конденсирован с другим возможно замещенным 5-6-членным гетероциклом, содержащим в качестве гетероатомов азот, кислород или серу.R c and R 2 d for compounds 1.2, or R c and R 3 d for compounds 1.3 and 1.4, or R c and R 4 d for compounds 1.5, together with the atoms to which they are bonded, can form a possibly substituted aliphatic ring containing 4-12 carbon atoms or a possibly substituted 5-6 membered heterocycle in which the heteroatoms are selected from nitrogen, oxygen or sulfur, and which can be condensed with another possibly substituted 5-6 membered heterocycle containing nitrogen, oxygen as heteroatoms sulfur. 3. Соединения по п.1, представляющие собой замещенные диазепины общей формулы 1.63. The compounds according to claim 1, which are substituted diazepines of General formula 1.6
Figure 00000361
Figure 00000361
 где пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000360
) представляет одинарную или двойную связь, R1 a, R2 a, Rb и Rc имеют вышеуказанное значение, каждый из R1 d, R2 d и R3 d независимо друг от друга представляют заместитель циклической системы, выбранный из водорода, возможно замещенного C1-C6 алкила, возможно замещенного арила, илиwhere the dashed line with the solid line accompanying it (
Figure 00000360
) represents a single or double bond, R 1 a , R 2 a , R b and R c have the above meaning, each of R 1 d , R 2 d and R 3 d independently represent a cyclic system substituent selected from hydrogen, optionally substituted C 1 -C 6 alkyl; optionally substituted aryl; or R3 d и R2 d вместе с атомами, с которыми они связаны, могут образовывать возможно замещенный моно- или конденсированный биароматический цикл, возможно замещенный 5-6-членный гетероцикл, в котором гетероатомы выбраны из азота, кислорода или серы, и который может быть конденсирован с другим возможно замещенным 5-6-членным гетероциклом, содержащим в качестве гетероатомов азот, кислород или серу, или возможно замещенный алифатический цикл, содержащий 4-12 атомов углерода, аR 3 d and R 2 d together with the atoms to which they are bonded can form a possibly substituted mono- or fused biaromatic ring, possibly a substituted 5-6 membered heterocycle in which the heteroatoms are selected from nitrogen, oxygen or sulfur, and which can be condensed with another possibly substituted 5-6 membered heterocycle containing nitrogen, oxygen or sulfur as heteroatoms, or a possibly substituted aliphatic ring containing 4-12 carbon atoms, and R1 d и R2 a могут образовывать вместе с атомами, с которыми они связаны, возможно замещенный 4-6-членный азагетероцикл, возможно содержащий дополнительно гетероатомы, выбранные из азота, кислорода или серы, и возможно конденсированный с возможно замещенным бензольным кольцом или с другим возможно замещенным 5-6-членным гетероциклом, в котором гетероатомы выбраны из азота, кислорода или серы.R 1 d and R 2 a can form, together with the atoms to which they are bonded, a possibly substituted 4-6 membered azaheterocycle, optionally containing additional heteroatoms selected from nitrogen, oxygen or sulfur, and possibly condensed with a possibly substituted benzene ring or another possibly substituted 5-6 membered heterocycle in which the heteroatoms are selected from nitrogen, oxygen or sulfur. 4. Соединения по п.3, представляющие собой 3-оксо-2,3,4,5-тетрагидро-1Н-бензо[е][1,4]диазепины, общей формулы 1.6.14. The compounds according to claim 3, which are 3-oxo-2,3,4,5-tetrahydro-1H-benzo [e] [1,4] diazepines, of the general formula 1.6.1
Figure 00000362
Figure 00000362
 где R1 a, R2 a, Rb, Rc и R1 d имеют вышеуказанное для 1.6 значение; Rn d представляет собой один или два заместителя циклической системы, выбранных из водорода, возможно замещенного C1-C6-алкила, нитро, галогена, амино, C1-С6 ациламино, арилсульфонил-амино, ариламинокарбониламино, возможно замещенного 5-6-членного азагетероциклила.where R 1 a , R 2 a , R b , R c and R 1 d have the above meaning for 1.6; R n d represents one or two substituents of the cyclic system selected from hydrogen, optionally substituted C 1 -C 6 alkyl, nitro, halogen, amino, C 1 -C 6 acylamino, arylsulfonyl amino, arylaminocarbonylamino, optionally substituted 5-6 -membered azaheterocyclyl. 5. Соединения по п.3 или 4, представляющие собой 3-оксо-2,3,4,5-тетрагидро-1Н-бензо[е][1,4]диазепины, включающие темплейт общей формулы 1.6.1.1-1.6.1.165. The compounds according to claim 3 or 4, which are 3-oxo-2,3,4,5-tetrahydro-1H-benzo [e] [1,4] diazepines, including a template of the general formula 1.6.1.1-1.6.1.16
Figure 00000363
Figure 00000364
Figure 00000365
Figure 00000366
Figure 00000363
Figure 00000364
Figure 00000365
Figure 00000366
Figure 00000367
Figure 00000368
Figure 00000369
Figure 00000370
Figure 00000367
Figure 00000368
Figure 00000369
Figure 00000370
Figure 00000371
Figure 00000372
Figure 00000373
Figure 00000374
Figure 00000371
Figure 00000372
Figure 00000373
Figure 00000374
Figure 00000375
Figure 00000376
Figure 00000377
Figure 00000378
Figure 00000375
Figure 00000376
Figure 00000377
Figure 00000378
 где Rb и Rc имеют вышеуказанное значение.where R b and R c have the above meaning. 6. Соединения по п.1, представляющие собой 7-оксоазепаны общей формулы 1.76. The compounds according to claim 1, which are 7-oxoazepanes of the general formula 1.7
Figure 00000379
Figure 00000379
 где пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000380
) представляет одинарную или двойную связь; R1 a, Rb и Rc имеют вышеуказанное значение; R1 d и R2 d вместе с атомами, с которыми они связаны, и R3 d и R4 d вместе с атомами, с которыми они связаны, образуют соответственно возможно замещенный ароматический цикл или возможно замещенный 5-6-членный азагетероцикл, возможно содержащий дополнительно гетероатомы, выбранные из азота, кислорода или серы, и возможно конденсированный с бензольным кольцом или с другим 5-6-членным гетероциклом, в котором гетероатомы выбраны из азота, кислорода или серы, или возможно замещенный алифатический цикл, содержащий 4-12 атомов углерода.where the dashed line with the solid line accompanying it (
Figure 00000380
) represents a single or double bond; R 1 a , R b and R c have the above meaning; R 1 d and R 2 d together with the atoms to which they are bonded, and R 3 d and R 4 d, together with the atoms to which they are bonded, form a correspondingly possibly substituted aromatic ring or a possibly substituted 5-6 membered azaheterocycle, possibly additionally containing heteroatoms selected from nitrogen, oxygen or sulfur, and optionally fused to a benzene ring or another 5-6 membered heterocycle in which heteroatoms are selected from nitrogen, oxygen or sulfur, or a possibly substituted aliphatic ring containing 4-12 atoms carbon. 7. Соединения по п.6, представляющие собой аннелированные 7-оксоазепаны, включающие темплейт общей формулы 1.7.1-1.7.747. The compounds according to claim 6, which are annelated 7-oxoazepanes, including a template of the general formula 1.7.1-1.7.74
Figure 00000381
Figure 00000382
Figure 00000383
Figure 00000384
Figure 00000385
Figure 00000386
Figure 00000381
Figure 00000382
Figure 00000383
Figure 00000384
Figure 00000385
Figure 00000386
Figure 00000387
Figure 00000388
Figure 00000389
Figure 00000390
Figure 00000391
Figure 00000392
Figure 00000387
Figure 00000388
Figure 00000389
Figure 00000390
Figure 00000391
Figure 00000392
Figure 00000393
Figure 00000394
Figure 00000395
Figure 00000396
Figure 00000397
Figure 00000398
Figure 00000393
Figure 00000394
Figure 00000395
Figure 00000396
Figure 00000397
Figure 00000398
Figure 00000399
Figure 00000400
Figure 00000401
Figure 00000402
Figure 00000403
Figure 00000404
Figure 00000399
Figure 00000400
Figure 00000401
Figure 00000402
Figure 00000403
Figure 00000404
Figure 00000405
Figure 00000406
Figure 00000407
Figure 00000408
Figure 00000409
Figure 00000410
Figure 00000405
Figure 00000406
Figure 00000407
Figure 00000408
Figure 00000409
Figure 00000410
Figure 00000411
Figure 00000412
Figure 00000413
Figure 00000414
Figure 00000415
Figure 00000416
Figure 00000411
Figure 00000412
Figure 00000413
Figure 00000414
Figure 00000415
Figure 00000416
Figure 00000417
Figure 00000418
Figure 00000419
Figure 00000420
Figure 00000421
Figure 00000422
Figure 00000417
Figure 00000418
Figure 00000419
Figure 00000420
Figure 00000421
Figure 00000422
Figure 00000423
Figure 00000424
Figure 00000425
Figure 00000426
Figure 00000427
Figure 00000428
Figure 00000423
Figure 00000424
Figure 00000425
Figure 00000426
Figure 00000427
Figure 00000428
Figure 00000429
Figure 00000430
Figure 00000431
Figure 00000432
Figure 00000433
Figure 00000434
Figure 00000429
Figure 00000430
Figure 00000431
Figure 00000432
Figure 00000433
Figure 00000434
Figure 00000435
Figure 00000436
Figure 00000437
Figure 00000438
Figure 00000439
Figure 00000440
Figure 00000435
Figure 00000436
Figure 00000437
Figure 00000438
Figure 00000439
Figure 00000440
Figure 00000441
Figure 00000442
Figure 00000443
Figure 00000444
Figure 00000445
Figure 00000446
Figure 00000441
Figure 00000442
Figure 00000443
Figure 00000444
Figure 00000445
Figure 00000446
Figure 00000447
Figure 00000448
Figure 00000449
Figure 00000450
Figure 00000451
Figure 00000452
Figure 00000447
Figure 00000448
Figure 00000449
Figure 00000450
Figure 00000451
Figure 00000452
 где Rb и Rc имеют вышеуказанное значение.where R b and R c have the above meaning. 8. Соединения по п.1, представляющие собой замещенные азагетероциклы общей формулы 1.8-1.158. The compounds according to claim 1, which are substituted azaheterocycles of the general formula 1.8-1.15
Figure 00000453
Figure 00000454
Figure 00000455
Figure 00000456
Figure 00000453
Figure 00000454
Figure 00000455
Figure 00000456
Figure 00000457
Figure 00000458
Figure 00000459
Figure 00000460
Figure 00000457
Figure 00000458
Figure 00000459
Figure 00000460
 где пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000461
) представляет одинарную или двойную связь, R1 a, Rb и Rc имеют вышеуказанное значение; R2 a представляет собой заместитель аминогруппы, такой как атом водорода, возможно замещенный C1-С6 алкил, каждый из R1 d, R2 d, R3 d, R4 d и R5 d независимо друг от друга представляют заместитель циклической системы, выбранный из водорода, возможно замещенного C1-С6 алкила, возможно замещенного арила, илиwhere the dashed line with the solid line accompanying it (
Figure 00000461
) represents a single or double bond, R 1 a , R b and R c have the above meaning; R 2 a represents an amino group substituent, such as a hydrogen atom, optionally substituted C 1 -C 6 alkyl, each of R 1 d , R 2 d , R 3 d , R 4 d and R 5 d independently represent a cyclic substituent a system selected from hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted aryl, or R1 d и R2 a, для соединений 1.8, 1.9, R2 a и R2 d для соединений 1.10, 1.11, R2 a и R3 d для соединений 1.12 и 1.13, R2 a и R4 d для соединений 1.14, 1.15 могут образовывать вместе с атомами, с которыми они связаны, возможно замещенный 4-6-членный азагетероцикл, возможно содержащий дополнительно гетероатомы, выбранные из азота, кислорода или серы, и возможно конденсированный с возможно замещенным бензольным кольцом или с другим возможно замещенным 5-6-членным гетероциклом, в котором гетероатомы выбраны из азота, кислорода или серы, аR 1 d and R 2 a , for compounds 1.8, 1.9, R 2 a and R 2 d for compounds 1.10, 1.11, R 2 a and R 3 d for compounds 1.12 and 1.13, R 2 a and R 4 d for compounds 1.14 1.15 can form, together with the atoms with which they are bonded, a possibly substituted 4-6 membered azaheterocycle, optionally containing additional heteroatoms selected from nitrogen, oxygen or sulfur, and possibly condensed with a possibly substituted benzene ring or with another possibly substituted 5- A 6-membered heterocycle in which heteroatoms are selected from nitrogen, oxygen or sulfur, and R1 d и R2 d для соединений 1.9, 1.12, 1.13, 1.14, 1.15, R2 d и R3 d для соединений 1.11, 1.14, 1.15, R4 d и R3 d для соединений 1.13, R4 d и R5 d для соединений 1.15 вместе с атомами, с которыми они связаны, могут образовывать возможно замещенный алифатический цикл, включающий 4-12 атомов углерода, возможно замещенный моно- или конденсированный биароматический цикл или возможно замещенный 5-6-членный гетероцикл, в котором гетероатомы выбраны из азота, кислорода или серы, и который может быть конденсирован с другим возможно замещенным 5-6-членным гетероциклом, содержащим в качестве гетероатомов азот, кислород или серу.R 1 d and R 2 d for compounds 1.9, 1.12, 1.13, 1.14, 1.15, R 2 d and R 3 d for compounds 1.11, 1.14, 1.15, R 4 d and R 3 d for compounds 1.13, R 4 d and R 5 d for compounds 1.15, together with the atoms to which they are bonded, can form a possibly substituted aliphatic ring comprising 4-12 carbon atoms, possibly a substituted mono- or condensed biaromatic ring, or a possibly substituted 5-6 membered heterocycle in which heteroatoms are selected from nitrogen, oxygen or sulfur, and which may be condensed with another possibly substituted 5-6 membered heterocycle containing as heteroatoms nitrogen, oxygen or sulfur. 9. Соединения по п.1, представляющие собой замещенные азагетероциклы общей формулы 1.16 -1.189. The compounds according to claim 1, which are substituted azaheterocycles of the general formula 1.16 -1.18
Figure 00000462
Figure 00000463
Figure 00000464
Figure 00000462
Figure 00000463
Figure 00000464
 где пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000465
) представляет одинарную или двойную связь, R1 a, R2 a, Rb и Rc имеют вышеуказанное значение; R3 a представляет собой заместитель аминогруппы, выбранный из группы водород, возможно замещенный алкил, возможно замещенный циклоалкил, возможно замещенный арил; R1 d, R2 d, R3 d и R4 d независимо друг от друга представляют собой заместители циклической системы, выбранные из водорода, возможно замещенного C1-С6 алкила, возможно замещенного арила, или для соединений 1.16 R2 d и R3 a вместе с атомами, с которыми они связаны, могут образовывать через R2 d и R3 a возможно замещенный азагетероцикл; или для соединений 1.17 независимо R3 d и R3 a вместе с атомами, с которыми они связаны, могут образовывать через R3 d и R3 a возможно замещенный 4-6-членный азагетероцикл, a R1 d и R2 d вместе с атомами, с которыми они связаны, могут образовывать через R1 d и R2 d возможно замещенный ароматический цикл, 5-6-членный возможно замещенный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или алифатический цикл, включающий от 4 до 12 атомов углерода; или для соединений 1.18 независимо R1 d и R2 d вместе с атомами, с которыми они связаны, могут образовывать через R1 d и R2 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода, а R3 a и R3 d вместе с атомами, с которыми они связаны, могут образовывать через R3 a и R3 d возможно замещенный 4-6-членный азагетероцикл, a R3 d и R4 d вместе с атомами, с которыми они связаны, могут образовывать через R3 d и R4 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода.where the dashed line with the solid line accompanying it (
Figure 00000465
) represents a single or double bond, R 1 a , R 2 a , R b and R c have the above meaning; R 3 a represents an amino substituent selected from the group of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl; R 1 d , R 2 d , R 3 d and R 4 d independently represent cyclic system substituents selected from hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted aryl, or for compounds 1.16 R 2 d and R 3 a together with the atoms to which they are bonded can form a possibly substituted azaheterocycle through R 2 d and R 3 a ; or for compounds 1.17, independently R 3 d and R 3 a, together with the atoms to which they are bonded, can form a possibly substituted 4-6 membered azaheterocycle through R 3 d and R 3 a , R 1 d and R 2 d together with the atoms to which they are bonded can form a possibly substituted aromatic ring through R 1 d and R 2 d , a 5-6 membered possibly substituted heterocycle comprising at least one of the heteroatoms selected from the group O, S or N, or an aliphatic cycle comprising from 4 to 12 carbon atoms; or for compounds 1.18, independently of R 1 d and R 2 d, together with the atoms to which they are bonded, can form through R 1 d and R 2 d a possibly substituted aromatic ring, possibly a 5-6 membered heterocycle including at least , one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring comprising from 4 to 12 carbon atoms, and R 3 a and R 3 d together with the atoms to which they are bonded can form through R 3 a and R 3 d is a possibly substituted 4-6 membered azaheterocycle, and R 3 d and R 4 d together with the atoms to which they are bonded can t form through R 3 d and R 4 d a possibly substituted aromatic ring, possibly a substituted 5-6 membered heterocycle comprising at least one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring including from 4 to 12 carbon atoms. 10. Соединения по п.1, представляющие собой замещенные азагетероциклы общей формулы 1.19 или 1.2010. The compounds according to claim 1, which are substituted azaheterocycles of the general formula 1.19 or 1.20
Figure 00000466
Figure 00000467
Figure 00000466
Figure 00000467
 где пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000465
) представляет одинарную или двойную связь, R1 a, R2 a, Rb и Rc имеют вышеуказанное значение; R1 d, R2 d, R3 d и R4 d независимо друг от друга представляют собой заместитель циклической системы, выбранный из водорода, возможно замещенного C1-C6 алкила или для соединений 1.19 независимо R1 d и R2 d вместе с атомами, с которыми они связаны, могут образовывать через R1 d и R2 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода, a R2 a и R3 d вместе с атомами, с которыми они связаны, могут образовывать через R2 a и R3 d возможно замещенный 4-6-членный азагетероцикл; или для соединений 1.20 независимо R1 d и R2 d вместе с атомами, с которыми они связаны, могут образовывать через R1 d и R2 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода, R2 a и R3 d вместе с атомами, с которыми они связаны, могут образовывать через R2 a и R3 d возможно замещенный 4-6-членный азагетероцикл, а R3 d и R4 d вместе с атомами, с которыми они связаны, могут образовывать через R3 d и R4 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода.where the dashed line with the solid line accompanying it (
Figure 00000465
) represents a single or double bond, R 1 a , R 2 a , R b and R c have the above meaning; R 1 d , R 2 d , R 3 d and R 4 d independently represent a cyclic system substituent selected from hydrogen, optionally substituted C 1 -C 6 alkyl, or for compounds 1.19 independently R 1 d and R 2 d together with the atoms to which they are bonded, they can form through R 1 d and R 2 d a possibly substituted aromatic ring, possibly a substituted 5-6 membered heterocycle, including at least one of the heteroatoms selected from the group O, S or N , or a possibly substituted aliphatic cycle comprising from 4 to 12 carbon atoms, a R 2 a and R 3 d together with the atoms with which they are connected by eye, can form through R 2 a and R 3 d a possibly substituted 4-6 membered azaheterocycle; or for compounds 1.20, independently of R 1 d and R 2 d, together with the atoms to which they are bonded, can form through R 1 d and R 2 d a possibly substituted aromatic ring, possibly a substituted 5-6 membered heterocycle, including at least , one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring comprising from 4 to 12 carbon atoms, R 2 a and R 3 d together with the atoms to which they are bonded, can form through R 2 a R 3 d and optionally substituted 4-6-membered azaheterocycle, and R 3 d and R 4 d together with the atoms to which they are attached, can forming a through d R 3 d and R 4 optionally substituted aromatic ring, optionally substituted 5-6-membered heterocycle comprising at least one heteroatom selected from O, S or N, or an optionally substituted aliphatic ring comprising 4 to 12 carbon atoms. 11. Соединения по п.10, представляющие собой замещенные азагетероциклы общей формулы 1.19.1 или 1.20.111. The compounds of claim 10, which are substituted azaheterocycles of the general formula 1.19.1 or 1.20.1
Figure 00000468
Figure 00000469
Figure 00000468
Figure 00000469
 где пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000465
) представляет одинарную или двойную связь, R1 a, R2 a, Rb, Rc, R3 d и R4 d имеют вышеуказанное для 1.19 и 1.20 значение, Rn d представляет собой один или два заместителя циклической системы, выбранные из водорода, возможно замещенного С1-С4-алкила.where the dashed line with the solid line accompanying it (
Figure 00000465
) represents a single or double bond, R 1 a , R 2 a , R b , R c , R 3 d and R 4 d are as defined above for 1.19 and 1.20, R n d is one or two substituents of the cyclic system selected from hydrogen, possibly substituted C 1 -C 4 -alkyl. 12. Соединения по п.1, представляющие собой замещенные азагетероциклы общей формулы 1.21 или 1.2212. The compounds according to claim 1, which are substituted azaheterocycles of the general formula 1.21 or 1.22
Figure 00000470
Figure 00000471
Figure 00000470
Figure 00000471
 где пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000465
) представляет одинарную или двойную связь, R1 a, R2 a, Rb и Rc имеют вышеуказанное значение; R1 d, R2 d, R3 d и R4 d независимо друг от друга представляют собой заместитель циклической системы, выбранный из водорода, возможно замещенного C1-С6-алкила, или для соединений 1.21 независимо R1 d и R2 d вместе с атомом, с которым они связаны, могут образовывать через R1 d и R2 d возможно замещенный С3-С6-циклоалкил, R2 a и R2 d вместе с атомами, с которыми они связаны, могут образовывать через R2 a и R2 d возможно замещенный 5-6-членный азагетероцикл, возможно содержащий дополнительные гетероатомы, выбранные из азота, кислорода или серы, a R3 d и R4 d вместе с атомами, с которыми они связаны, могут образовывать через R3 d и R4 d возможно замещенный 5-6-членный азагетероцикл; или для соединений 1.22 независимо R1 d и R2 d вместе с атомами, с которьми они связаны, могут образовывать через R1 d и R2 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода; R2 a и R2 d вместе с атомами, с которыми они связаны, могут образовывать через R2 a и R2 d возможно замещенный 5-6-членный азагетероцикл, возможно содержащий дополнительный гетероатом, выбранный из азота, кислорода или серы, а R3 d и R4 d вместе с атомами, с которыми они связаны, могут образовывать через R3 d и R4 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода.where the dashed line with the solid line accompanying it (
Figure 00000465
) represents a single or double bond, R 1 a , R 2 a , R b and R c have the above meaning; R 1 d , R 2 d , R 3 d and R 4 d independently represent a cyclic system substituent selected from hydrogen, optionally substituted C 1 -C 6 alkyl, or for compounds 1.21 independently R 1 d and R 2 d together with the atom to which they are bonded, can form through R 1 d and R 2 d optionally substituted C 3 -C 6 -cycloalkyl, R 2 a and R 2 d together with the atoms to which they are bonded can form via R 2 a and R 2 d optionally substituted 5-6 membered azaheterocycle, possibly containing additional heteroatoms selected from nitrogen, oxygen or sulfur, a R 3 d and R 4 d together with at the ohms to which they are connected can form, via R 3 d and R 4 d, a possibly substituted 5-6 membered azaheterocycle; or for compounds 1.22, independently of R 1 d and R 2 d, together with the atoms to which they are bonded, can form through R 1 d and R 2 d a possibly substituted aromatic ring, possibly a substituted 5-6 membered heterocycle, including at least one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring comprising from 4 to 12 carbon atoms; R 2 a and R 2 d together with the atoms to which they are bonded can form, via R 2 a and R 2 d, a possibly substituted 5-6 membered azaheterocycle, possibly containing an additional heteroatom selected from nitrogen, oxygen or sulfur, and R 3 d and R 4 d together with the atoms to which they are bonded can form, via R 3 d and R 4 d, a possibly substituted aromatic ring, possibly a substituted 5-6 membered heterocycle, including at least one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring comprising from 4 to 12 carbon atoms. 13. Соединения по п.12, представляющие собой замещенные азагетероциклы общей формулы 1.21.1 или 1.22.113. The compounds of claim 12, which are substituted azaheterocycles of the general formula 1.21.1 or 1.22.1
Figure 00000472
Figure 00000473
Figure 00000472
Figure 00000473
 где пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000465
) представляет одинарную или двойную связь, R1 a, R2 a, Rb, Rc, R1 d и R2 d имеют вышеуказанное для 1.21 и 1.22 значение, Rn d представляет собой один или два заместителя циклической системы, выбранные из водорода или возможно замещенного C1-С6-алкила.where the dashed line with the solid line accompanying it (
Figure 00000465
) represents a single or double bond, R 1 a , R 2 a , R b , R c , R 1 d and R 2 d are as defined above for 1.21 and 1.22, R n d is one or two cyclic substituents selected from hydrogen or optionally substituted C 1 -C 6 alkyl. 14. Соединения по п.1, представляющие собой замещенные азагетероциклы общей формулы 1.23-1.3314. The compounds according to claim 1, which are substituted azaheterocycles of the general formula 1.23-1.33
Figure 00000474
Figure 00000475
Figure 00000476
Figure 00000477
Figure 00000474
Figure 00000475
Figure 00000476
Figure 00000477
Figure 00000478
Figure 00000479
Figure 00000480
Figure 00000481
Figure 00000478
Figure 00000479
Figure 00000480
Figure 00000481
Figure 00000482
Figure 00000483
Figure 00000484
Figure 00000482
Figure 00000483
Figure 00000484
 где А представляет собой атом С, О, S или NR2 a; пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000465
) представляет одинарную или двойную связь; R1 a, Rb и Rc имеют вышеуказанное значение; R2 a представляет собой заместитель аминогруппы, такой как атом водорода, возможно замещенный C1-С6 алкил, каждый из R1 d, R2 d, R3 d, R4 d, R5 d и R6 d независимо друг от друга представляют заместитель циклической системы, выбранный из водорода, возможно замещенного C1-C6 алкила, возможно замещенного арила, или для соединений 1.23 и 1.27 R1 d и R2 d вместе с атомом, с которым они связаны, могут образовывать через R1 d и R2 d возможно замещенный С5-С6 циклоалкил; для соединений 1.23, 1.25, 1.27, 1.28, 1.30, 1.31, 1.33 R3 d и R4 d вместе с атомами, с которыми они связаны, могут образовывать через R3 d и R4 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода, а для соединений 1.23, 1.24, 1.25, 1.26 Rc и R4 d вместе с атомами, с которыми они связаны, могут образовывать через Rc и R4 d возможно замещенный циклоалкил или возможно замещенный 5-6-членный гетероцикл; или для соединений 1.24, 1.25, 1.26, 1.28, 1.29, 1.30, 1.31, 1.32, 1.33 независимо R1 d и R2 d вместе с атомами, с которыми они связаны, могут образовывать через R1 d и R2 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода; для соединений 1.24 R3 d и R4 d вместе с атомом, с которым они связаны, могут образовывать через R3 d и R4 d возможно замещенный С5-С6 циклоалкил, a Rc и R4 d вместе с атомами, с которыми они связаны, могут образовывать через Rc и R4 d возможно замещенный С5-С6 циклоалкил; или для соединений 1.26 R2 d и R3 d вместе с атомами, с которыми они связаны, могут образовывать соответственно через R2 d и R3 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода; для соединений 1.27, 1.29, 1.30, 1.31 и 1.32 R4 d и R5 d вместе с атомами, с которыми они связаны, могут образовывать через R4 d и R5 d возможно замещенный циклоалкил; для соединений 1.26,1.27, 1.29, 1.30 Rc и R5 d вместе с атомами, с которыми они связаны, могут образовывать через Rc и R5 d возможно замещенный С5-С6 циклоалкил; для соединений 1.28 R5 d и R6 d вместе с атомом, с которым они связаны, могут образовывать через R5 d и R6 d возможно замещенный С5-С6 циклоалкил, a Rc и R6 d вместе с атомами, с которыми они связаны, могут образовывать через Rc и R6 d возможно замещенный С5-С6 циклоалкил; для соединений 1.31, 1.32, 1.33 R5 d и R6 d вместе с атомами, с которыми они связаны, могут образовывать через R5 d и R6 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода, a Rc и R6 d вместе с атомами, с которыми они связаны, могут образовывать через Rc и R6 d возможно замещенный С5-С6 циклоалкил или возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N; или для соединений 1.32, 1.33 R2 d и R3 d вместе с атомами, с которьми они связаны, могут образовывать через R2 d и R3 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода.where A represents an atom of C, O, S or NR 2 a ; dashed line with the solid line accompanying it (
Figure 00000465
) represents a single or double bond; R 1 a , R b and R c have the above meaning; R 2 a represents an amino group substituent, such as a hydrogen atom, optionally substituted C 1 -C 6 alkyl, each of R 1 d , R 2 d , R 3 d , R 4 d , R 5 d and R 6 d independently each other is represented by a cyclic system substituent selected from hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted aryl, or for compounds 1.23 and 1.27, R 1 d and R 2 d together with the atom to which they are bonded can form via R 1 d and R 2 d optionally substituted C 5 -C 6 cycloalkyl; for compounds 1.23, 1.25, 1.27, 1.28, 1.30, 1.31, 1.33, R 3 d and R 4 d together with the atoms to which they are bonded can form a possibly substituted aromatic ring through R 3 d and R 4 d , possibly substituted 5- A 6-membered heterocycle comprising at least one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring containing from 4 to 12 carbon atoms, and for compounds 1.23, 1.24, 1.25, 1.26 R c and R 4 d, together with the atoms to which they are bonded, can form, via R c and R 4 d, a possibly substituted cycloalkyl or a possibly substituted 5-6 membered get erocycle; or for compounds 1.24, 1.25, 1.26, 1.28, 1.29, 1.30, 1.31, 1.32, 1.33 independently R 1 d and R 2 d together with the atoms to which they are bonded can form a possibly substituted aromatic via R 1 d and R 2 d a cycle, an optionally substituted 5-6 membered heterocycle comprising at least one of heteroatoms selected from the group O, S or N, or an optionally substituted aliphatic ring comprising from 4 to 12 carbon atoms; for compounds 1.24, R 3 d and R 4 d together with the atom to which they are bonded can form a possibly substituted C 5 -C 6 cycloalkyl via R 3 d and R 4 d , a R c and R 4 d together with atoms, with by which they are bonded, they can form, via R c and R 4 d, a possibly substituted C 5 -C 6 cycloalkyl; or for compounds 1.26, R 2 d and R 3 d together with the atoms to which they are bonded can form, respectively, through R 2 d and R 3 d a possibly substituted aromatic ring, possibly a substituted 5-6 membered heterocycle including at least one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring comprising from 4 to 12 carbon atoms; for compounds 1.27, 1.29, 1.30, 1.31 and 1.32, R 4 d and R 5 d together with the atoms to which they are bonded can form a possibly substituted cycloalkyl through R 4 d and R 5 d ; for compounds 1.26, 1.27, 1.29, 1.30, R c and R 5 d together with the atoms to which they are bonded can form a possibly substituted C 5 -C 6 cycloalkyl through R c and R 5 d ; for compounds 1.28, R 5 d and R 6 d together with the atom to which they are bonded can form optionally substituted C 5 -C 6 cycloalkyl via R 5 d and R 6 d , and R c and R 6 d together with atoms, with by which they are bonded, they can form, via R c and R 6 d, a possibly substituted C 5 -C 6 cycloalkyl; for compounds 1.31, 1.32, 1.33, R 5 d and R 6 d together with the atoms to which they are bonded can form, via R 5 d and R 6 d, a possibly substituted aromatic ring, possibly a substituted 5-6 membered heterocycle, including at least one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring containing from 4 to 12 carbon atoms, a R c and R 6 d together with the atoms to which they are bonded, can form through R c R 6 d and optionally substituted C 5 -C 6 cycloalkyl or optionally substituted 5-6-membered heterocycle comprising at steps , One of the heteroatoms selected from O, S or N; or for compounds 1.32, 1.33, R 2 d and R 3 d, together with the atoms to which they are bonded, can form through R 2 d and R 3 d a possibly substituted aromatic ring, possibly a 5-6 membered heterocycle including at least at least one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring containing from 4 to 12 carbon atoms. 15. Соединения по п.1, представляющие собой замещенные азагетероциклы общей формулы 1.37-1.4015. The compounds according to claim 1, which are substituted azaheterocycles of the general formula 1.37-1.40
Figure 00000485
Figure 00000486
Figure 00000487
Figure 00000488
Figure 00000485
Figure 00000486
Figure 00000487
Figure 00000488
 где пунктирная линия с сопровождающей ее сплошной линией (
Figure 00000465
) представляет одинарную или двойную связь, R1 a, R2 a, Rb и Rc имеют вышеуказанное значение; R4 a представляет собой заместитель аминогруппы, выбранный из возможно замещенного C1-С6 алкила; каждый из R1 d, R2 d, R4 d и R5 d независимо друг от друга представляют собой заместитель циклической системы, выбранный из водорода, возможно замещенного C1-C6 алкила, возможно замещенного арила, или для соединений 1.37 R1 d и R2 d вместе с атомом, с которым они связаны, могут образовывать через R1 d и R2 d возможно замещенный С5-С6 циклоалкил, R2 a и R4 a вместе с атомами, с которыми они связаны, могут образовывать через R2 a и R4 a возможно замещенный 5-6-членный азагетероцикл, a Rc и R4 d вместе с атомами, с которыми они связаны, могут образовывать через Rc и R4 d возможно замещенный С5-С6 циклоалкил или возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N; или для соединений 1.38 независимо R1 d и R2 d вместе с атомом, с которым они связаны, могут образовывать через R1 d и R2 d возможно замещенный С5-С6 циклоалкил или возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, R2 a и R4 a вместе с атомом, с которым они связаны, могут образовывать через R2 a и R4 a возможно замещенный азагетероцикл, a Rc и R4 d вместе с атомами, с которыми они связаны, могут образовывать через Rc и R4 d возможно замещенный C5-6циклоалкил или возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N; или для соединений 1.39 независимо R1 d и R2 d вместе с атомом, с которым они связаны, могут образовывать через R1 d и R2 d возможно замещенный С5-6 циклоалкил или возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, R2 a и R4 a вместе с атомами, с которыми они связаны, могут образовывать через R2 a и R4 a возможно замещенный 5-6-членный азагетероцикл, независимо R4 d и R5 d вместе с атомами, с которыми они связаны, могут образовывать через R4 d и R5 d возможно замещенный ароматический цикл, возможно аннелированный возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода, a Rc и R5 d вместе с атомами, с которыми они связаны, могут образовывать через Rc и R5 d возможно замещенный C5-6циклоалкил или возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N; или для соединений 1.40 независимо R1 d и R2 d вместе с атомом, с которым они связаны, могут образовывать через R1 d и R2 d возможно замещенный циклоалкил или возможно замещенный гетероцикл, R2 a и R4 a вместе с атомом, с которым они связаны, могут образовывать через R2 a и R4 a возможно замещенный 5-6-членный азагетероцикл, R4 d и R5 d вместе с атомами, с которыми они связаны, могут образовывать через R4 d и R5 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода, a Rc и R5 d вместе с атомами, с которыми они связаны, могут образовывать через Rc и R5 d возможно замещенный циклоалкил или возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N.where the dashed line with the solid line accompanying it (
Figure 00000465
) represents a single or double bond, R 1 a , R 2 a , R b and R c have the above meaning; R 4 a represents an amino group substituent selected from optionally substituted C 1 -C 6 alkyl; each of R 1 d , R 2 d , R 4 d and R 5 d independently represent a cyclic system substituent selected from hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted aryl, or for compounds 1.37 R 1 d and R 2 d together with the atom to which they are bonded can form a possibly substituted C 5 -C 6 cycloalkyl through R 1 d and R 2 d , R 2 a and R 4 a together with the atoms to which they are bonded can to form through R 2 a and R 4 a a possibly substituted 5-6 membered azaheterocycle, a R c and R 4 d together with the atoms to which they are bonded can form through R c and R 4 d a possibly substituted C 5 -C 6 cycloalkyl or a possibly substituted 5-6 membered heterocycle comprising at least one of heteroatoms selected from the group O, S or N; or for compounds 1.38, independently of R 1 d and R 2 d, together with the atom to which they are bonded, can form, via R 1 d and R 2 d, a possibly substituted C 5 -C 6 cycloalkyl or a possibly substituted 5-6 membered heterocycle including at least one of the heteroatoms selected from the group O, S or N, R 2 a and R 4 a together with the atom to which they are bonded can form a possibly substituted azaheterocycle through R 2 a and R 4 a , a R c and R 4 d, together with the atoms to which they are bonded, can form, via R c and R 4 d, a possibly substituted C 5-6 cycloalkyl or a possibly substituted 5-6 membered th heterocycle comprising at least one of heteroatoms selected from the group O, S or N; or for compounds 1.39 are independently R 1 d and R 2 d together with the atom to which they are attached, may form through R 1 d and R 2 d optionally substituted C 5-6 cycloalkyl or optionally substituted 5-6-membered heterocycle comprising at least one of the heteroatoms selected from the group O, S or N, R 2 a and R 4 a together with the atoms to which they are bonded can form a possibly substituted 5-6 membered via R 2 a and R 4 a azaheterocycle independently R 4 d and R 5 d together with the atoms to which they are attached, may form through R 4 d and R 5 d optionally substituted aromatic ring poss zhno annelated optionally substituted 5-6-membered heterocycle comprising at least one heteroatom selected from O, S or N, or an optionally substituted aliphatic ring comprising from 4 to 12 carbon atoms, a R c, and R 5 d, together with the atoms to which they are bonded, can form, via R c and R 5, d a possibly substituted C 5-6 cycloalkyl or a possibly substituted 5-6 membered heterocycle comprising at least one of the heteroatoms selected from group O S or N; or for compounds 1.40, independently of R 1 d and R 2 d, together with the atom to which they are bonded, can form, via R 1 d and R 2 d, a possibly substituted cycloalkyl or possibly substituted heterocycle, R 2 a and R 4 a together with the atom, to which they are bonded, they can form through R 2 a and R 4 a a possibly substituted 5-6 membered azaheterocycle, R 4 d and R 5 d together with the atoms to which they are bonded can form via R 4 d and R 5 d optionally substituted aromatic ring; optionally substituted 5-6 membered heterocycle comprising at least one of heteroatoms selected from the groups s O, S or N, or a possibly substituted aliphatic ring comprising from 4 to 12 carbon atoms, and R c and R 5 d, together with the atoms to which they are bonded, can form a possibly substituted cycloalkyl through R c and R 5 d or optionally substituted 5-6 membered heterocycle comprising at least one of the heteroatoms selected from the group O, S or N. 16. Азагетероциклы общей формулы 2.1-2.4 и их фармацевтически приемлемые кислотно-аддитивные соли16. Azaheterocycles of the general formula 2.1-2.4 and their pharmaceutically acceptable acid addition salts
Figure 00000489
Figure 00000490
Figure 00000491
Figure 00000492
Figure 00000489
Figure 00000490
Figure 00000491
Figure 00000492
 где R1 a представляет собой заместитель аминогруппы, предпочтительно возможно замещенный C1-С6 алкил, возможно замещенный арил или возможно замещенный 5-6-членный гетероциклил, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N; R2 a и R3 a независимо друг от друга представляют собой заместители аминогруппы, выбранные из группы водород, возможно замещенный алкил, возможно замещенный арил; R1 d, R2 d, R3 d, R4 d, R5 d, R6 d, R7 d и R8 d независимо друг от друга представляют собой заместитель циклической системы, выбранный из водорода, возможно замещенного C1-С6 алкила, возможно замещенного арила или возможно замещенного 5-6-членного гетероциклила, включающего, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенного С3-6 циклоалкила; или R1 d и R2 d вместе с атомом углерода, с которым они связаны, могут образовывать через R1 d и R2 d возможно замещенный С3-6 циклоалкил; или для соединений 2.1 и 2.2 R3 d, R4 d, R5 d, R6 d вместе с атомами, с которыми они связаны, могут образовывать через R4 d и R5 d возможно замещенный ароматический цикл или возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода; или R2 a вместе с атомом, с которыми он связан, и R3 d и R4 d вместе с атомами, с которыми они связаны, образуют через R2 a и R3 d и R4 d возможно замещенный 5-6-членный азагетероцикл; или R3 a вместе с атомом, с которыми он связан, и R5 d и R6 d вместе с атомами, с которыми они связаны, образуют через R3 a и R5 d и R6 d возможно замещенный 5-6-членный азагетероцикл; или R2 a вместе с атомом, с которым он связан, и R3 d, R4 d, R5 d и R6 d вместе с атомами, с которыми они связаны, образуют через R2 a, R4 d и R5 d возможно замещенный 5-6-членный азагетероцикл; или R3 a вместе с атомом, с которым он связан, и R3 d, R4 d, R5 d и R6 d вместе с атомами, с которыми они связаны, образуют через R3 a, R4 d или через R5 d и R6 d возможно замещенный 5-6-членный азагетероцикл; или для соединений 2.3 и 2.4 R3 d, R4 d, R5 d и R6 d вместе с атомами, с которыми они связаны, образуют через R4 d и R5 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный гетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода; или R5 d, R6 d, R7 d и R8 d вместе с атомами, с которыми они связаны, образуют через R7 d и R5 d возможно замещенный ароматический цикл, возможно замещенный 5-6-членный азагетероцикл, включающий, по крайней мере, один из гетероатомов, выбранных из группы О, S или N, или возможно замещенный алифатический цикл, включающий от 4 до 12 атомов углерода, исключая пиперазин Еwhere R 1 a represents an amino group substituent, preferably optionally substituted C 1 -C 6 alkyl, optionally substituted aryl or optionally substituted 5-6 membered heterocyclyl, comprising at least one of heteroatoms selected from the group O, S or N ; R 2 a and R 3 a independently represent amino substituents selected from the group hydrogen, optionally substituted alkyl, optionally substituted aryl; R 1 d , R 2 d , R 3 d , R 4 d , R 5 d , R 6 d , R 7 d and R 8 d independently represent a cyclic system substituent selected from hydrogen, optionally substituted with C 1 - C 6 alkyl, optionally substituted aryl or optionally substituted 5-6 membered heterocyclyl, comprising at least one of the heteroatoms selected from the group O, S or N, or optionally substituted C 3-6 cycloalkyl; or R 1 d and R 2 d, together with the carbon atom to which they are bonded, can form, via R 1 d and R 2 d, a possibly substituted C 3-6 cycloalkyl; or for compounds 2.1 and 2.2, R 3 d , R 4 d , R 5 d , R 6 d together with the atoms to which they are bonded can form a possibly substituted aromatic ring or possibly substituted 5-6 through R 4 d and R 5 d a membered heterocycle comprising at least one of heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring comprising from 4 to 12 carbon atoms; or R 2 a together with the atom with which it is bonded, and R 3 d and R 4 d together with the atoms with which they are bonded, form through R 2 a and R 3 d and R 4 d a possibly substituted 5-6 membered azaheterocycle; or R 3 a together with the atom with which it is bonded and R 5 d and R 6 d together with the atoms with which they are bonded form through R 3 a and R 5 d and R 6 d a possibly substituted 5-6 membered azaheterocycle; or R 2 a together with the atom with which it is bonded and R 3 d , R 4 d , R 5 d and R 6 d together with the atoms with which they are bonded, form through R 2 a , R 4 d and R 5 d optionally substituted 5-6 membered azaheterocycle; or R 3 a together with the atom with which it is bonded, and R 3 d , R 4 d , R 5 d and R 6 d together with the atoms with which they are bonded, form through R 3 a , R 4 d or through R 5 d and R 6 d optionally substituted 5-6 membered azaheterocycle; or for compounds 2.3 and 2.4, R 3 d , R 4 d , R 5 d and R 6 d together with the atoms to which they are bonded form a possibly substituted aromatic ring through R 4 d and R 5 d , possibly substituted 5-6- a member heterocycle comprising at least one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring comprising from 4 to 12 carbon atoms; or R 5 d , R 6 d , R 7 d and R 8 d together with the atoms to which they are bonded, form through R 7 d and R 5 d a possibly substituted aromatic ring, possibly a substituted 5-6 membered azaheterocycle, including at least one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic ring comprising from 4 to 12 carbon atoms, excluding piperazine E
Figure 00000493
Figure 00000493
 17. Азагетероциклы общей формулы 3.1 или 3.217. Azaheterocycles of the general formula 3.1 or 3.2
Figure 00000494
Figure 00000495
Figure 00000494
Figure 00000495
 где для соединений 3.1 R1 a и R2 a независимо друг от друга представляют собой заместитель аминогруппы, выбранный из возможно замещенного C1-6алкила, возможно замещенного циклоалкила, возможно замещенного арила; R1 d представляет собой арил; R2 d представляет собой атом водорода или C1-С6 алкил, или R1 d и R2 d вместе с атомом, с которым они связаны, образуют через R1 d и R2 d циклоалкил или 5-6-членный гетероциклил; R3 d и R4 d независимо друг от друга представляют собой заместитель циклической системы, выбранный из C1-С6 алкила, или R3 d и R4 d вместе с атомом углерода, с которым они связаны, образуют через R3 d и R4 d циклоалкил или возможно замещенный 5-6-членный азагетероцикл; для соединений 3.2 R1 a представляет собой заместитель аминогруппы; R1 d представляет собой арил или гетероциклил; R2 d представляет собой атом водорода или C1-С6 алкил, или R1 d и R2 d вместе с атомом, с которым они связаны, образуют через R1 d и R2 d C5-C6 циклоалкил или 5-6-членный гетероцикл; R2 a вместе с атомом, с которым он связан, и R3 d вместе с атомом, с которым он связан, образуют через R2 a и R3 d 5-6-членный азагетероцикл, исключая пиперазиндионы общей формулы Dwhere for compounds 3.1, R 1 a and R 2 a independently represent an amino group substituent selected from optionally substituted C 1-6 alkyl, optionally substituted cycloalkyl, optionally substituted aryl; R 1 d represents aryl; R 2 d represents a hydrogen atom or C 1 -C 6 alkyl, or R 1 d and R 2 d together with the atom to which they are bonded, form R 1 d and R 2 d cycloalkyl or 5-6 membered heterocyclyl; R 3 d and R 4 d independently from each other represent a substituent of the cyclic system selected from C 1 -C 6 alkyl, or R 3 d and R 4 d together with the carbon atom to which they are attached form through R 3 d and R 4 d cycloalkyl or optionally substituted 5-6 membered azaheterocycle; for compounds 3.2, R 1 a represents an amino group substituent; R 1 d represents aryl or heterocyclyl; R 2 d represents a hydrogen atom or C 1 -C 6 alkyl, or R 1 d and R 2 d together with the atom to which they are bonded, form R 1 d and R 2 d C 5 -C 6 cycloalkyl or 5- 6 membered heterocycle; R 2 a together with the atom with which it is bonded and R 3 d together with the atom with which it is bonded form a 5-6 membered azaheterocycle through R 2 a and R 3 d , excluding piperazinedions of the general formula D
Figure 00000496
Figure 00000496
 где R1 a=Н, СН3; R2 a = необязательно замещенный алкил; R1 d - арил или необязательно замещенный алкил; R2 d и R3 d = необязательно замещенный алкил или R2 d и R3 d вместе с атомом углерода, с которым они соединены, образуют через R2 d и R3 d циклопропан.where R 1 a = H, CH 3 ; R 2 a = optionally substituted alkyl; R 1 d is aryl or optionally substituted alkyl; R 2 d and R 3 d = optionally substituted alkyl or R 2 d and R 3 d, together with the carbon atom to which they are attached, form cyclopropane via R 2 d and R 3 d . 18. Соединения по п.17, представляющие собой азагетероциклы, включающие фрагмент формулы 3.1.1-3.1.718. The compounds of claim 17, which are azaheterocycles comprising a fragment of the formula 3.1.1-3.1.7
Figure 00000497
Figure 00000498
Figure 00000499
Figure 00000500
Figure 00000497
Figure 00000498
Figure 00000499
Figure 00000500
Figure 00000501
Figure 00000502
Figure 00000503
Figure 00000501
Figure 00000502
Figure 00000503
 19. Способ получения азагетероциклов общей формулы 1.1-1.5 по п.2 взаимодействием бифункционального реагента общей формулы 4.5(1-5), выбранного из группы, указанной ниже, либо необязательно N-защищенной аминокислоты общей формулы 4.1(1-3), выбранной из группы, указанной ниже, и эфира оксо-карбоновой кислоты общей формулы 4.2(1-3), выбранного из группы, указанной ниже, с изонитрилом общей формулы В2 и первичным амином общей формулы В3 в среде органического растворителя, при этом, в случае получения соединений, в которых Rb и Rc вместе представляют собой аминоцианометилен =C(NHR3 a)CN, реакции ведут в присутствии кислотного катализатора19. The method for producing azaheterocycles of general formula 1.1-1.5 according to claim 2 by reacting a bifunctional reagent of general formula 4.5 (1-5) selected from the group indicated below, or optionally an N-protected amino acid of general formula 4.1 (1-3) selected from a group indicated below and an oxo-carboxylic acid ester of the general formula 4.2 (1-3) selected from the group indicated below with isonitrile of the general formula B 2 and a primary amine of the general formula B 3 in an organic solvent, in this case for preparing compounds in which R b and R c together represent an amine cyanomethylene = C (NHR 3 a ) CN, reactions are carried out in the presence of an acid catalyst
Figure 00000504
Figure 00000505
Figure 00000506
Figure 00000507
Figure 00000508
Figure 00000509
Figure 00000504
Figure 00000505
Figure 00000506
Figure 00000507
Figure 00000508
Figure 00000509
Figure 00000510
Figure 00000511
Figure 00000512
Figure 00000513
Figure 00000514
Figure 00000510
Figure 00000511
Figure 00000512
Figure 00000513
Figure 00000514
 где R' представляет собой водород или (СН3)3СОС(О);where R 'represents hydrogen or (CH 3 ) 3 COC (O); R" представляет собой алкил или арил;R "represents alkyl or aryl; R1 a, R2 a, R3 a, Rc, R1 d, R2 d, R3 d и R4 d имеют значения, указанное выше для соединений общей формулы 1.1-1.5.R 1 a , R 2 a , R 3 a , R c , R 1 d , R 2 d , R 3 d and R 4 d are as defined above for compounds of the general formula 1.1-1.5. 20. Способ получения азогетероциклов общей формулы 1.6 по п.3 взаимодействием в среде органического растворителя изонитрила общей формулы В2, первичного амина общей формулы В3 и бифункционального реагента общей формулы 4.7, либо необязательно N-защищенной аминокислоты общей формулы 4.1 и галогенкарбонильных соединений общей формулы 4.6 с последующей циклизацией образующихся аддуктов, причем для получения соединений общей формулы 1.6, в которых Rb и Rc вместе представляют собой аминоцианометилен =C(NHR3 a)CN, реакции проводят в присутствии кислотного катализатора20. The method for producing azaheterocycles of general formula 1.6 according to claim 3 by reacting in an organic solvent an isonitrile of general formula B 2 , a primary amine of general formula B 3 and a bifunctional reagent of general formula 4.7, or an optionally N-protected amino acid of general formula 4.1 and halogen-carbonyl compounds of general formula 4.6 followed by cyclization of the resulting adducts, moreover, to obtain compounds of the general formula 1.6, in which R b and R c together are amino cyanomethylene = C (NHR 3 a ) CN, the reactions are carried out in the presence of acid go catalyst
Figure 00000515
Figure 00000516
Figure 00000517
Figure 00000518
Figure 00000519
Figure 00000515
Figure 00000516
Figure 00000517
Figure 00000518
Figure 00000519
 где R1 a, R2 a, R3 a, Rc, R1 d, R2 d и R3 d имеют значение, указанное выше для азагетероциклов общей формулы 1.6; R' представляет собой водород или (СН3)3СОС(О).where R 1 a , R 2 a , R 3 a , R c , R 1 d , R 2 d and R 3 d have the meaning indicated above for azaheterocycles of the general formula 1.6; R 'represents hydrogen or (CH 3 ) 3 COC (O). 21. Способ получения азепанов общей формулы 1.7 по п.6 взаимодействием бифункционального реагента общей формулы 4.8, изонитрила общей формулы В2 и первичного амина общей формулы В3 в среде органического растворителя, причем для получения соединений общей формулы 1.7, в которых Rb и Rc вместе представляют собой аминоцианометилен C(NHR3 a)CN, реакции проводят в присутствии кислотного катализатора21. The method of producing azepanes of general formula 1.7 according to claim 6 by reacting a bifunctional reagent of general formula 4.8, isonitrile of general formula B 2 and a primary amine of general formula B 3 in an organic solvent, moreover, to obtain compounds of general formula 1.7, in which R b and R c together represent aminocyanomethylene C (NHR 3 a ) CN, the reactions are carried out in the presence of an acid catalyst
Figure 00000520
Figure 00000515
Figure 00000516
Figure 00000520
Figure 00000515
Figure 00000516
 где R1 a, R3 a, Rc, R1 d, R2 d, R3 d и R4 d имеют значение, указанное выше для азагетероциклов общей формулы 1.7.where R 1 a , R 3 a , R c , R 1 d , R 2 d , R 3 d and R 4 d have the meaning indicated above for azaheterocycles of the general formula 1.7. 22. Способ получения азагетероциклов общей формулы 1.8-1.15 по п.8 взаимодействием изонитрила общей формулы B2, первичного амина общей формулы В3 в среде органического растворителя и моноэфира дикарбоновой кислоты общей формулы 4.9(1-4) и необязательно защищенного амино-карбонильного соединения общей формулы 4.10(1-3) с последующей циклизацией образующихся аддуктов или бифункционального реагента общей формулы 4.11(1-8), причем для получения соединений общей формулы 1.8-1.15, в которых Rb и Rc вместе представляют собой аминоцианометилен C(NHR3 a)CN, реакции проводят в присутствии кислотного катализатора22. The method for producing azaheterocycles of general formula 1.8-1.15 according to claim 8 by reacting isonitrile of general formula B 2 , a primary amine of general formula B 3 in an organic solvent and a dicarboxylic acid monoester of general formula 4.9 (1-4), and an optionally protected amino-carbonyl compound general formula 4.10 (1-3) followed by cyclization of the resulting adducts or bifunctional reagent of general formula 4.11 (1-8), and to obtain compounds of General formula 1.8-1.15, in which R b and R c together are aminocyanomethylene C (NHR 3 a ) CN, reaction pr bred in the presence of an acid catalyst
Figure 00000521
Figure 00000522
Figure 00000523
Figure 00000524
Figure 00000521
Figure 00000522
Figure 00000523
Figure 00000524
Figure 00000525
Figure 00000526
Figure 00000527
Figure 00000525
Figure 00000526
Figure 00000527
Figure 00000528
Figure 00000529
Figure 00000530
Figure 00000531
Figure 00000528
Figure 00000529
Figure 00000530
Figure 00000531
Figure 00000532
Figure 00000533
Figure 00000534
Figure 00000535
Figure 00000532
Figure 00000533
Figure 00000534
Figure 00000535
 где R1 a, R2 a, R3 a, Rc, R1 d, R2 d, R3 d, R4 d и R5 d имеют значение, указанное выше для азагетероциклов общей формулы 1.8-1.15.where R 1 a , R 2 a , R 3 a , R c , R 1 d , R 2 d , R 3 d , R 4 d and R 5 d have the meaning indicated above for azaheterocycles of the general formula 1.8-1.15. 23. Способ получения азогетероциклов общей формулы 1.16-1.18 по п.9 взаимодействием в среде органического растворителя изонитрила общей формулы В2, первичного амина общей формулы В3 и бифункционального реагента общей формулы 4.12(1-3), причем для получения соединений общей формулы 1.16-1.18, в которых Rb и Rc вместе представляют собой аминоцианометилен C(NHR3 a)CN, реакции проводят в присутствии кислотного катализатора23. The method of producing azoheterocycles of the general formula 1.16-1.18 according to claim 9 by reacting in an organic solvent an isonitrile of the general formula B 2 , a primary amine of the general formula B 3 and a bifunctional reagent of the general formula 4.12 (1-3), moreover, to obtain compounds of the general formula 1.16 -1.18, in which R b and R c together represent aminocyanomethylene C (NHR 3 a ) CN, the reactions are carried out in the presence of an acid catalyst
Figure 00000536
Figure 00000537
Figure 00000538
Figure 00000515
Figure 00000516
Figure 00000536
Figure 00000537
Figure 00000538
Figure 00000515
Figure 00000516
 где R1 a, R2 a, R3 a, Rc, R1 d, R2 d, R3 d и R4 d имеют значение, указанное выше для азагетероциклов общей формулы 1.16-1.18.where R 1 a , R 2 a , R 3 a , R c , R 1 d , R 2 d , R 3 d and R 4 d have the meaning given above for azaheterocycles of the general formula 1.16-1.18. 24. Способ получения азогетероциклов общей формулы 1.19, 1.20 по п.10 взаимодействием в среде органического растворителя изонитрила общей формулы В2, первичного амина общей формулы В3 и бифункционального реагента общей формулы 4.13(1,2), причем для получения соединений общей формулы 1.19, 1.20, в которых Rb и Rc вместе представляют собой аминоцианометилен C(NHR3 a)CN, реакции проводят в присутствии кислотного катализатора24. The method of producing azoheterocycles of the general formula 1.19, 1.20 of claim 10 by reacting in an organic solvent an isonitrile of the general formula B 2 , a primary amine of the general formula B 3 and a bifunctional reagent of the general formula 4.13 (1,2), moreover, to obtain compounds of the general formula 1.19 , 1.20, in which R b and R c together represent aminocyanomethylene C (NHR 3 a ) CN, the reactions are carried out in the presence of an acid catalyst
Figure 00000539
Figure 00000540
Figure 00000515
Figure 00000516
Figure 00000539
Figure 00000540
Figure 00000515
Figure 00000516
 где R1 a, R2 a, R3 a, Rc, R1 d, R2 d, R3 d и R4 d имеют значение, указанное выше для азагетероциклов общей формулы 1.19,1.20.where R 1 a , R 2 a , R 3 a , R c , R 1 d , R 2 d , R 3 d and R 4 d are as defined above for azaheterocycles of the general formula 1.19.1.20. 25. Способ получения азогетероциклов общей формулы 1.21, 1.22 по п.12 взаимодействием в среде органического растворителя изонитрила общей формулы В2, первичного амина общей формулы В3 и бифункционального реагента общей формулы 4.14(1,2), причем для получения соединений общей формулы 1.21, 1.22, в которых Rb и Rc вместе представляют собой аминоцианометилен C(NHR3 a)CN, реакции проводят в присутствии кислотного катализатора25. The method of producing azoheterocycles of the general formula 1.21, 1.22 according to claim 12 by reacting in an organic solvent an isonitrile of the general formula B 2 , a primary amine of the general formula B 3 and a bifunctional reagent of the general formula 4.14 (1,2), moreover, to obtain compounds of the general formula 1.21 , 1.22 in which R b and R c together are amino cyanomethylene C (NHR 3 a ) CN, the reactions are carried out in the presence of an acid catalyst
Figure 00000541
Figure 00000542
Figure 00000515
Figure 00000516
Figure 00000541
Figure 00000542
Figure 00000515
Figure 00000516
 где R1 a, R2 a, R3 a, Rc, R1 d, R2 d, R3 d и R4 d имеют значение, указанное выше для азагетероциклов общей формулы 1.21, 1.22.where R 1 a , R 2 a , R 3 a , R c , R 1 d , R 2 d , R 3 d and R 4 d have the meaning indicated above for azaheterocycles of the general formula 1.21, 1.22. 26. Способ получения азагетероциклов общей формулы 1.23-1.33 по п.14 взаимодействием изонитрила общей формулы B2, первичного амина общей формулы В3, замещенной кислоты общей формулы 4.15(1-4) и галоген-карбонильного соединения общей формулы 4.16(1-4) в среде органического растворителя с последующей циклизацией образующихся аддуктов, причем для получения соединений общей формулы 1.23-1.33, в которых Rb и Rc вместе представляют собой аминоцианометилен C(NHR3 a)CN, реакции проводят в присутствии кислотного катализатора26. The method of producing azaheterocycles of the general formula 1.23-1.33 according to claim 14, by reacting isonitrile of the general formula B 2 , a primary amine of the general formula B 3 , a substituted acid of the general formula 4.15 (1-4) and a halogen-carbonyl compound of the general formula 4.16 (1-4 ) in an organic solvent medium followed by cyclization of the formed adducts, moreover, to obtain compounds of the general formula 1.23-1.33, in which R b and R c together are amino cyanomethylene C (NHR 3 a ) CN, the reactions are carried out in the presence of an acid catalyst
Figure 00000543
Figure 00000544
Figure 00000545
Figure 00000546
Figure 00000547
Figure 00000548
Figure 00000549
Figure 00000550
Figure 00000543
Figure 00000544
Figure 00000545
Figure 00000546
Figure 00000547
Figure 00000548
Figure 00000549
Figure 00000550
 где R1 a, R3 a, Rc, R1 d, R2 d, R3 d, R4 d, R5 d, R6 d и А имеют значение, указанное выше для азагетероциклов общей формулы 1.23-1.33.where R 1 a , R 3 a , R c , R 1 d , R 2 d , R 3 d , R 4 d , R 5 d , R 6 d and A have the meaning indicated above for azaheterocycles of the general formula 1.23-1.33. 27. Способ получения азагетероциклов общей формулы 1.23-1.33 по п.14 взаимодействием изонитрила общей формулы В2, первичного амина общей формулы В3, соответствующей галогензамещенной кислоты общей формулы 4.17(1-4) и соответствующего замещенного карбонильного соединения общей формулы 4.18(1-4) в среде органического растворителя с последующей циклизацией образующихся аддуктов, причем для получения соединений общей формулы 1.23-1.33, в которых Rb и Rc вместе представляют собой аминоцианометилен C(NHR3 a)CN, реакции проводят в присутствии кислотного катализатора27. The method for producing azaheterocycles of general formula 1.23-1.33 according to claim 14 by reacting isonitrile of general formula B 2 , a primary amine of general formula B 3 , the corresponding halogen-substituted acid of general formula 4.17 (1-4), and the corresponding substituted carbonyl compound of general formula 4.18 (1- 4) in an organic solvent medium followed by cyclization of the formed adducts, moreover, to obtain compounds of the general formula 1.23-1.33, in which R b and R c together are amino cyanomethylene C (NHR 3 a ) CN, the reactions are carried out in the presence of acid catalysis atora
Figure 00000551
Figure 00000552
Figure 00000553
Figure 00000554
Figure 00000551
Figure 00000552
Figure 00000553
Figure 00000554
Figure 00000555
Figure 00000556
Figure 00000557
Figure 00000558
Figure 00000555
Figure 00000556
Figure 00000557
Figure 00000558
 где R1 a, R3 a, Rc, R1 d, R2 d, R3 d, R4 d, R5 d, R6 d и А имеют значение, указанное выше для азагетероциклов общей формулы 1.23-1.33.where R 1 a , R 3 a , R c , R 1 d , R 2 d , R 3 d , R 4 d , R 5 d , R 6 d and A have the meaning indicated above for azaheterocycles of the general formula 1.23-1.33. 28.Способ получения азагетероциклов общей формулы 1.23-1.33 по п.14 взаимодействием изонитрила общей формулы В2, первичного амина общей формулы В3 и соответствующего бифункционального реагента общей формулы 4.19.1-4.19.11 в среде органического растворителя, причем для получения соединений общей формулы 1.23-1.33, в которых Rb и Rc вместе представляют собой аминоцианометилен C(NHR3 a)CN, реакции проводят в присутствии кислотного катализатора28. A method of producing azaheterocycles of general formula 1.23-1.33 according to claim 14, by reacting isonitrile of general formula B 2 , a primary amine of general formula B 3 and the corresponding bifunctional reagent of general formula 4.19.1-4.19.11 in an organic solvent, moreover, formula 1.23-1.33, in which R b and R c together represent aminocyanomethylene C (NHR 3 a ) CN, the reaction is carried out in the presence of an acid catalyst
Figure 00000559
Figure 00000560
Figure 00000561
Figure 00000562
Figure 00000559
Figure 00000560
Figure 00000561
Figure 00000562
Figure 00000563
Figure 00000564
Figure 00000565
Figure 00000566
Figure 00000563
Figure 00000564
Figure 00000565
Figure 00000566
Figure 00000567
Figure 00000568
Figure 00000569
Figure 00000567
Figure 00000568
Figure 00000569
 где R1 a, R3 a, Rc, R1 d, R2 d, R3 d, R4 d, R5 d, R6 d и А имеют значение, указанное выше для азагетероциклов общей формулы 1.23-1.33.where R 1 a , R 3 a , R c , R 1 d , R 2 d , R 3 d , R 4 d , R 5 d , R 6 d and A have the meaning indicated above for azaheterocycles of the general formula 1.23-1.33. 29. Способ получения азагетероциклов общей формулы 1.37, 1.39 по п.15 взаимодействием изонитрила общей формулы В2, первичного амина общей формулы В3, (2,3-дизамещенной-тиоуреидо)-уксусной кислоты общей формулы 4.20 и галоген-карбонильного соединения общей формулы 4.21.1 или 4.21.2 в среде органического растворителя с последующей циклизацией образующихся аддуктов, или бифункционального реагента общей формулы 4.22.1 или 4.22.2 в среде органического растворителя, причем для получения соединений общей формулы 1.37, 1.39, в которых Rb и Rc вместе представляют собой аминоцианометилен C(NHR4 a)CN, реакции проводят в присутствии кислотного катализатора29. The method of producing azaheterocycles of the general formula 1.37, 1.39 according to claim 15 by reacting isonitrile of the general formula B 2 , a primary amine of the general formula B 3 , (2,3-disubstituted-thioureido) -acetic acid of the general formula 4.20 and a halogen-carbonyl compound of the general formula 4.21.1 or 4.21.2 in an organic solvent, followed by cyclization of the resulting adducts, or a bifunctional reagent of general formula 4.22.1 or 4.22.2 in an organic solvent, to obtain compounds of general formula 1.37, 1.39, in which R b and R c together represent a minocyanomethylene C (NHR 4 a ) CN, reactions are carried out in the presence of an acid catalyst
Figure 00000570
Figure 00000571
Figure 00000572
Figure 00000570
Figure 00000571
Figure 00000572
Figure 00000573
Figure 00000574
Figure 00000573
Figure 00000574
 где R1 a, R2 a, R3 a, R4 a, Rc, R1 d, R2 d, R3 d, R4 d и R5 d имеют значение, указанное выше для азагетероциклов общей формулы 1.37, 1.39.wherein R 1 a, R 2 a, R 3 a, R 4 a, R c, R 1 d, R 2 d, R 3 d, R 4 d and R 5 d are as defined above for azaheterocycles general formula 1.37, 1.39. 30. Способ получения азагетероциклов общей формулы 1.38, 1.40 по п.15 взаимодействием изонитрила общей формулы В2, первичного амина общей формулы В3 и галоген-карбонильного соединения общей формулы 4.21.1 или 4.21.2 и (3,3-дизамещенной-тиоуреидо)-уксусной кислоты общей формулы 4.23 в среде органического растворителя с последующей циклизацией образующихся аддуктов или бифункционального реагента общей формулы 4.24.1 или 4.24.2, причем для получения соединений общей формулы 1.38, 1.40, в которых Rb и Rc вместе представляют собой аминоцианометилен C(NHR4 a)CN, реакции проводят в присутствии кислотного катализатора30. The method of producing azaheterocycles of the general formula 1.38, 1.40 according to claim 15 by reacting isonitrile of the general formula B 2 , a primary amine of the general formula B 3 and a halogen-carbonyl compound of the general formula 4.21.1 or 4.21.2 and (3,3-disubstituted-thioureido ) -acetic acid of general formula 4.23 in an organic solvent, followed by cyclization of the resulting adducts or bifunctional reagent of general formula 4.24.1 or 4.24.2, moreover, to obtain compounds of general formula 1.38, 1.40, in which R b and R c together are aminocyanomethylene C (NHR 4 a) CN, the reaction n oestriasis in the presence of an acid catalyst
Figure 00000575
Figure 00000571
Figure 00000572
Figure 00000575
Figure 00000571
Figure 00000572
Figure 00000576
Figure 00000577
Figure 00000576
Figure 00000577
 где R1 a, R2 a, R3 a, R4 a, Rc, R1 d, R2 d, R3 d, R4 d и R5 d имеют значение, указанное выше для азагетероциклов общей формулы 1.38, 1.40.where R 1 a , R 2 a , R 3 a , R 4 a , R c , R 1 d , R 2 d , R 3 d , R 4 d and R 5 d have the meaning given above for azaheterocycles of the general formula 1.38, 1.40. 31. Способ получения азагетероциклов общей формулы 2.1-2.4 по п.16 взаимодействием карбонильного соединения общей формулы 4.26, изонитрила общей формулы В2 и бифункционального реагента общей формулы 4.27.1 или 4.27.2 в среде органического растворителя31. A method for producing azaheterocycles of general formula 2.1-2.4 according to claim 16 by reacting a carbonyl compound of general formula 4.26, isonitrile of general formula B 2 and a bifunctional reagent of general formula 4.27.1 or 4.27.2 in an organic solvent
Figure 00000578
Figure 00000579
Figure 00000578
Figure 00000579
Figure 00000580
Figure 00000581
Figure 00000580
Figure 00000581
 где R1 a, R2 a, R3 a, R1 d, R2 d, R3 d, R4 d, R5 d, R6 d, R7 d и R8 d имеют значение, указанное выше для азагетероциклов общей формулы 2.1-2.4.where R 1 a , R 2 a , R 3 a , R 1 d , R 2 d , R 3 d , R 4 d , R 5 d , R 6 d , R 7 d and R 8 d are as defined above for azaheterocycles of the general formula 2.1-2.4. 32. Способ получения азагетероциклов общей формулы 3.1, 3.2 по п.17 взаимодействием в среде органического растворителя изонитрила общей формулы B2, первичного амина общей формулы В3, карбонильного соединения общей формулы 4.26 и необязательно N-защищенной аминокислоты общей формулы 4.2832. The method for producing azaheterocycles of general formula 3.1, 3.2 according to 17, reacting in an organic solvent an isonitrile of general formula B 2 , a primary amine of general formula B 3 , a carbonyl compound of general formula 4.26 and optionally an N-protected amino acid of general formula 4.28
Figure 00000582
Figure 00000583
Figure 00000515
Figure 00000516
Figure 00000582
Figure 00000583
Figure 00000515
Figure 00000516
 где R1 a, R2 a, R3 a, R1 d, R2 d, R3 d и R4 d имеют значение, указанное выше для азагетероциклов общей формулы 3.1, 3.2; R представляет собой атом водорода или (СН3)3СОС(О).where R 1 a , R 2 a , R 3 a , R 1 d , R 2 d , R 3 d and R 4 d have the meaning indicated above for azaheterocycles of the general formula 3.1, 3.2; R represents a hydrogen atom or (CH 3 ) 3 COC (O). 33. Комбинаторная библиотека для определения соединений-лидеров, состоящая из азагетероциклических соединений общей формулы 1 по п.1, и/или азагетероциклических соединений общей формулы 2.1, 2.2, 2.3 и 2.4 по п.16, и/или азагетероциклических соединений общей формулы 3.1 и 3.2 по п.17.33. A combinatorial library for determining leader compounds, consisting of azaheterocyclic compounds of the general formula 1 according to claim 1, and / or azaheterocyclic compounds of the general formula 2.1, 2.2, 2.3 and 2.4 according to clause 16, and / or azaheterocyclic compounds of the general formula 3.1 and 3.2 according to claim 17. 34. Фокусированная библиотека для определения соединений-лидеров, содержащая, по крайней мере, одно азагетероциклическое соединение общей формулы 1 по п.1, и/или азагетероциклическое соединение общей формулы 2.1, 2.2, 2.3 и 2.4 по п.16, и/или азагетероциклическое соединение общей формулы 3.1 и 3.2 по п.17.34. A focused library for determining leader compounds, containing at least one azaheterocyclic compound of the general formula 1 according to claim 1, and / or an azaheterocyclic compound of the general formula 2.1, 2.2, 2.3 and 2.4 according to clause 16, and / or azaheterocyclic the compound of General formula 3.1 and 3.2 according to 17. 35. Фармацевтическая композиция, обладающая антиканцерогенной активностью и предназначенная для получения лекарственных средств для лечения и предупреждения развития различных заболеваний животных и людей в форме таблеток, капсул или инъекций, помещенных в фармацевтически приемлемую упаковку, содержащая в качестве активной субстанции фармацевтически эффективное количество, по крайней мере, одного азагетероциклического соединения общей формулы 1 по п.1, и/или азагетероциклического соединения общей формулы 2.1, 2.2, 2.3 и 2.4 по п.16, и/или азагетероциклического соединения общей формулы 3.1 и 3.2 по п.17, или его фармацевтически приемлемой соли.35. A pharmaceutical composition having anticarcinogenic activity and intended for the manufacture of medicines for the treatment and prevention of various diseases of animals and humans in the form of tablets, capsules or injections, placed in a pharmaceutically acceptable package containing a pharmaceutically effective amount as an active substance, at least , one azaheterocyclic compound of the general formula 1 according to claim 1, and / or an azaheterocyclic compound of the general formula 2.1, 2.2, 2.3 and 2.4 according to clause 16, and / or aza a heterocyclic compound of general formula 3.1 and 3.2 according to claim 17, or a pharmaceutically acceptable salt thereof.
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