UA73913C2 - Azolo triazines and pyrimidines - Google Patents

Abstract

Corticotropin releasing factor (CRF) antagonists of formula (I) or (II) and their use in treating anxiety, depression, and other psychiatric, neurological disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress.

Description

Description of the invention

This invention relates to the treatment of psychiatric disorders and neurological diseases, including 2 major depression, anxiety disorders, post-traumatic stress disorders, supranuclear palsy and eating disorders, in addition to immunological, cardiovascular disorders or disorders, associated with disturbances in the work of the heart, and hypersensitivity of the large intestine associated with psychopathological disturbance and stress, with the help of the introduction of known (1, 5-a|-pyrazolo-1, C, 5-triazines, 1, 5-a |-1, 2, Z-triazolo-1, Z, 5-triazines, (1, 5-α|-pyrazolo-pyrimidines and (1, 5-α|-1, 2, Z-triazolo-pyrimidines. 70 Factor , promoting the release of adrenocortisotropic hormone (here it is referred to as SKE), a peptide consisting of 41 amino acids, is the primary physiological regulator of proopiomelanocortin (ROM) - obtained by isolating the peptide from the adenohypophysis. O5A) 80:4851 (1983); MU. to its endocrine role in the pituitary gland, immunohistological localization of SKE demonstrates that the hormone has a wide extrahypothamic distribution in the 12 central nervous system and produces a wide range of functionally independent, electrophysiological components and effects that influence behavior and play the role of a neurotransmitter and neuromodulator in the brain of MU. MaiYe ei aYi., Kes. Year Nail Kev. 39:245 (1983); S.G. Koor, Reger. Wepamu May 2:39 (1985); E.V. YuOe 5Botsla ei ai., U. Metsygovsi. 5:3189 (1985)). This is also evidence that SKE plays a significant role in the integration of the appropriate response of the immune system to physiological, psychological and immunological stress factors |U.E. ViaiosK, RpuzioIodisa! Chemiemus 69:1 (1989); U.E. Mopeau, I be Zsi. 41:527 (1987)).

Clinical evidence provides evidence that SCE plays a role in psychiatric disorders and neurological diseases, including depression, anxiety disorders, and eating disorders.

The role of SKE, also postulated in the etiology and pathophysiology of Alzheimer's disease, Parkinson's disease,

Huntington's disease, progressive supranuclear palsy and amyotrophic lateral sclerosis, that is, from the point of view of how they relate to the disruption of the function of SKE neurons in the central nervous system (E.V. Oe Zotsga, Nozr. Ge)

Rgasiise 23:59 (1988).

With an affective disorder or deep depression, the concentration of SKE in the cerebrospinal fluid (C5E) of individuals who did not take medication significantly increases |S.V. Metegoii Zsiepse 226:1342 (1984); SM. Vapki eyi am, At. in. Rev. 144:873 (1987); K.O. Egapse ei ai., VioYi. Resuspiaiu 28:86 (1988); M. Agayo ei ai., Fr

Vio). Resuspiaiu 25:355 (19853). In addition, the density of SKE receptors significantly decreases in the frontal cortical layer of suicide victims due to hypersecretion of SKE |S.V. Metegoii ei aI.Agsy. Sept. Rzuspiainu 45:577 (1988)). In addition, there is a direct response of adrenocorticotropin (ASTN) to SKE (when administered intravenously), which is observed in patients who are in a state of depression (R.MU. boiYi ei aI,, At .. so

Resuspiaiu 141:619 (1984); R. Noivroeg ei ai.,, Revuspopetsygoepdosgipoirsdu 9:147 (1984); R.MU. boiy ei ai., 3o MemzhEpa. U. Mea. 314:1129 (1986)). Preclinical studies on rats and non-human primates provided additional support for the hypothesis, which proves that hypersecretion of SKE can be included in the symptoms observed in human depression |K.M. ZaroizKu, Agsy. (Zep. Reuspiaiu 46:1047 (1989)). There is preliminary evidence that tricyclic antidepressants can alter SCE levels and thus modulate SCE receptors in the brain. WITH

Also, the role of SKE is postulated in the etiology of disorders associated with anxiety. SKE causes in animals anxiogenic effects and antagonism between benzodiazepine antiphobic sedative agents or

With" antiphobic sedative agents without benzodiazepine and SKE, which is demonstrated in various models associated with anxiety behavior (O.K. VgShhop ei ai., I iye Bei 31:363 (1982); S.MU. Vegptidde apa A .).

Oypp of Kedia. Review 16:83 (1986)). Previous studies, using the surface antagonist of receptors 49 SVE α-helical ovoid SKE (9-41) demonstrate on various variants of behavior (paradigms) that it is. the antagonist causes sedative-like effects, qualitatively similar to benzodiazepine effects (S.M. Vegidde apa A.Yu). Juippus lake Nopt. Vepahm. 21:393 (1987); Vgaiip Kezeagsp Kemiemuv 15:71 (1990)). Neurochemical, endocrine, and receptor binding studies have all demonstrated antagonism between SCEs and benzodiazepine and anxiolytics, providing further evidence for involvement in the pathological process in these SERE disorders. -k 70 Chlordiazeroxide weakens the "anxiogenic" effects of SKE, in both tests conducted on rats: in the conflict test of IK.T. Vgyop ei ai., Rzusporpaptasiodu 88:170 (1985); K.T. VgShop ei ai., Rvusporpaptasyodu 94:306 p" (1988) and in the acoustic test for fear |M.K. Zuegaiom/ei aiYi,, Resusporpagtasiodu 88:147 (1986).

A benzodiazepine receptor antagonist (Ko 15-1788), the only one that did not affect operant behavior in the conflict test, reversed the aversive effects of SCE in a dose-dependent manner, while the inversion of the benzodiazepine agonist (BE057142) increased the range actions of SKE (|K.T. Vgiyop ei ai.,

GF) Razusporpagtasiodu 94:306 (1988).

It remains to clarify the mechanisms and sites of action through which standard antiphobic sedative agents and antidepressants cause their therapeutic effects. However, it was likely that they are included in the process of suppressing the hypersecretion of SKE, which is observed in these disorders. Of particular interest is that 60 previous studies examining the effects of an SKE receptor antagonist (α-helical SKE 944) in various behavioral paradigms demonstrate that the SKE antagonist causes sedative-like effects qualitatively similar to those of benzodiazepines | for review, see S. G. Koob apa K.T. Vhiyop, Ip: Factor contributing to the release of adrenocorticotropic hormone: Basic and Clinical Studies of Neuropeptides, E.V. Zoyiga apa S.V. Metegoii edz., SKS Rhevzv p221 (1991). for Some publications describe compounds of the antagonist of the factor promoting the release of adrenocorticotropic hormone and their use in the treatment of mental disorders and neurological diseases. Examples of such publications include the United States of America application |biropy Metzk PCT arrisaiop 0O594/11050)Y, PCT application DuPont Merck OB/11050, Pfitzer (Riegge) International Applications MO 95/34563, UMO 95/33727 and European

Pfitzer patent ER 0778 277 A1.

As far as is known about the compounds |1, 5-a|-pyrazolo-1, C, 5-triazines, |1, 5-a|-1, 2, C- triazolo-1, C, 5- triazines, (1, 5 -α|-pyrazolo-pyrimidines and (1, 5-α|-pyrazolo-1, 2, 3-triazolo-pyrimidine) have not been previously reported as adrenocorticotropic hormone antagonist compounds useful in the treatment of psychiatric disorders and neurological diseases However, there are publications that 7/0 study some of these compounds with a view to use for other purposes.

For example, European Patent EP 0 269 859 (Oviyka, 1988) discloses pyrazolotriazine compounds according to the formula: vi. ры вз х сч in which B is OH or alkanoyl, B? represents hydrogen, OH, or 5H, and BZ represents an unsaturated heterocyclic group, naphthyl, or substituted phenyl and designates that the compounds have xanthine oxidase inhibitory activity and are useful in the treatment of gout.

European Patent EP 0 594 149 (OvishKa, 1994) discloses compounds of pyrazolotriazine and pyrazolopyrimidine according to the formula: so on - (22) i zh chi ke Ky

And have a son. гий у -|е . - n - y - - in which A is CH or nitrogen, B 9 is hydrogen or acyl, and B' is alkyl, alkoxyl, and alkylthio, nitro, and the like, and specifies that the compounds inhibit androgen and are useful for the treatment of mild prostatic hypertrophy and mild prostate cancer.

United States Patent 5 3, 910, 907 (Imperial Chemical Industries, 1975) discloses -I pyrazolotriazines of the formula:

Mom and dad

Ah! s ' schu-- y

In M

F) x. ime) in which K" is CH, SoN or SeN, X is hydrogen, C 6H or t-SNaSeNu, CM, SOOBEI, chlorine, iodine or bromine, U is hydrogen, C Hn, o-CHnSeN»a , or p-CHzSeH,, and 7 is OH, CHz, CoNBv, SeNB, p-CzH»7, i- CzH7, ЗН, ЗН3, МНС)Нае, M(СоНб)», and determines that the compounds are phosphodiesterase 3, 5-cyclic adenosine monophosphate (c-AMP) inhibitors are useful as bronchodilators.

United States Patent 05 C, 995, 039 discloses pyrazolotriazines of the formula: b5

Magician

and wherein KW" is hydrogen or alkyl, B 2 is hydrogen or alkyl, B C is hydrogen, alkyl, alkanoyl, carbamoyl, or lower carbamoyl, and K is pyridyl, pyrimidyl, or pyrazinyl, and determines that the compounds are useful as bronchodilators.

United States Patent 05 5,137,887 discloses pyrazolotriazines of the formula: wherein K is lower alkoxy, it

I

Izha Em x V. (ba) determines that the compounds are inhibitors of xanthine oxidase and are useful for the treatment of gout.

United States Patent 05 4,892,576 discloses pyrazolotriazines of the formula: (o) wherein X is oxygen or sulfur, Ag is x co

X and -

M b oyu lu "

Sha in -- SHHA | | - with ve" ti 0 c. and E

And" nya, , , oh, , . Di-1 is a phenyl, naphthyl, pyridyl or thienyl group, Co-Ka is hydrogen, alkyl and the like, and Co is hydrogen, alkyl, phenyl and the like. The patent specifies that the compounds are useful as herbicides and as plant growth regulators. o United States Patent 05 5, 484, 760 and International Application MO 92/10098 disclose herbicidal compositions containing, among other things, a herbicidal composition according to the formula: shk : . tire B, Institute of Technology

IN.

HF) in which A can be nitrogen, B can be SKz, Kz can be phenyl or substituted phenyl, and so on, K kyu is -M(K.)502K5 or -50O2M(K)K", and Ki and Ko can be taken together to form . o Shchi de xX, U 60 --neO sonya or 000 NA Xiang and 7 represent hydrogen, alkyl, acyl, and so on, and O represents oxygen or sulfur. for United States Patent OZ Z, 910, 907 and the article by Seng et al. IZepda ei ai., U. Med. Spet.,

1982, 25, 243-249). reveal triazolotriazines - inhibitors of phosphodiesterase 3, 5-cyclic adenosine monophosphate according to the formula: 2

GK tu, 70 V tya t ; in which 7 is hydrogen, OH, CH 5, СоН5в, СеНбв, п-СзН», ivo- СзиН7, ЗН, ЗСН», МН(п-С.Ное), or М(СоН)», К is hydrogen or CH with, K;. is CH" or CoH5. The package contains eight therapeutic areas in which 19 phosphodiesterase 3,5-cyclic adenosine monophosphate inhibitors may be useful: asthma, diabetes, female fertility control, male infertility, psoriasis, thrombosis, anxiety, and hypertension.

International Application UMUO 95/35298 (Oivyka, 1995) discloses pyrazolopyrimidines and states that they are useful as analgesics. Compounds are presented according to the formula: in which O is carbonyl or sulfonyl, n has 7y-Щ- (МН) дн дня melon VI -- с

And: NO! an i o

Z - nya - xx zo vi i td - x or: value 0 or 1, A represents a simple bond, alkylene or alkenylene, K represents hydrogen, alkyl, and so on) in the future, B? represents naphthyl, cycloalkyl, heteroaryl, substituted phenyl or phenoxy, KZ represents hydrogen, - alkyl or phenyl, KE represents hydrogen, alkyl, alkoxycarbonyl, phenylalkyl, optionally phenylthio-substituted phenyl, or halogen, E? and B? are hydrogen or alkyl.

European Patent EP 0 591 528 (Oivyka, 1991) discloses the anti-inflammatory use of "pyrazolopyrimidines, which are presented according to the formula:

And" OH also and their 45th dream of Wu. syu y : se) and ayu Kz in which K. Ko, Kz and K. represent hydrogen, carboxyl, alkoxycarbonyl, optionally substituted alkyl, c» cycloalkyl or phenyl, K5 represents KM Ka, Ko represents pyridyl or optionally substituted phenyl,

KU and Kv are hydrogen or optionally substituted phenyl.

In Springer's article (|Zrgipdeg ei aY., 9. May. Spets., 1976, my. 19, Mo. 2, 291-296)| and 22 United States Patents (Springer) 4,021,556 and 3,920,652 disclose pyrazolopyrimidines for

Gee! by the formula: name) 60 b5

He vyb 70 I in which K can be phenyl, substituted phenyl or pyridyl, while pyrazolopyrimidines are used for the treatment of gout, the basis for this being their ability to inhibit xanthine oxidase 75.

In the article by Joshi Yuovpi ei ai., 9. Rgaki. Spetie, 321, 2, 1979, 341-344) reveal compounds according to the formula: t

Sene in which B is SEz, SoEv or SeNaE, and B? is SEz, SoEv, SEz or SeNaE. at

In the article Makvestia | Madievziats ef ai., Vy. boss. Veid., my. 101, p. 2, 1992, lines 131-136) "- pyrazolo is revealed|1, 5-а| pyrimidine according to the formula: F

SAM sha and Zh. -

Sene shi s z" In the article of Ibrahim (Ibgapit ei aiYi., Agsy. RNagt. (meippeiit) 320, 487-491 (1987) pyrazolo|1, 5-a| pyrimidines are disclosed according to the formula: sn: -i . i 50 | .run in sb" sn: Also where in which K represents MH" or OH, and Ag represents 4-phenyl-3-cyano-2-aminopyrid-2-yl.

GF) Other references that disclose azolopyrimidines include European Patent EP 0 511 528 (Oizika, Ky 1992), United States Patent 5 4,997,940 (Oomu, 1991), European Patent EP 0 374 448 (Mizzap, 1990) , United States Patent 5 4, 621, 556 (ISM, 1997), European Patent EP 0 531 901 (Etsiizauma, 1993), United States Patent 5 4, 567, 263 (VAZE, 1986), European Patent EP 60 o 662 477 (Izadgo, 1995), German Patent OE 4 243 279 (Waueg, 1994), United States Patent 5 5, 397, 774 (Oriopp, 1994), European Patent EP 0 521 662 (Oriopp, 1993), International Application UUO 94/109017 (Oriopp, 1994), 3. Med. Spet., 24, 610-613 (1981), and 9. Her. Spet., 22, 601 (1985).

According to one aspect, the present invention provides novel compounds, pharmaceutical compositions and methods that can be used to treat affective disorders, anxiety disorders, depression, irritable bowel syndrome, post-traumatic stress disorders ,

supranuclear palsy, immunodeficiency, Alzheimer's disease, gastrointestinal disease, anorexia nervosa or other eating disorders, drug or alcohol withdrawal symptoms, drug addiction, inflammatory disorders or reproductive problems in mammals, i.e. disorders, treatment which may be effective or ameliorated by antagonizing SCEs, which include, but are not limited to, disorders that are caused by or alleviated by SCEs, or disorders selected from inflammatory disorders such as rheumatoid arthritis and osteoarthritis, pain, asthma , psoriasis and allergies; generalized anxiety disorders; panic, intractable fear, disorders related to intractable neurosis; disorders associated with 7/0 post-traumatic stress; sleep disorders caused by stress; pain disorders such as fibromyalgia; mood disorders such as depression, including major depression, isolated episodes of depression, child seduction associated with depression, and postpartum depression; dystemia; bipolar disorders; cyclothymia; fatigue syndrome; headache caused by stress; human immunodeficiency virus (HIV) infection; neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease 7/5; gastrointestinal diseases such as ulcers, mucoid colitis, Crohn's disease, spasms of the colon, diarrhea, postoperative hypersensitivity of the iliac bone and colon, associated with psychopathological disorders or stress; eating disorders such as anorexia and bulimia nervosa; hemorrhagic stress; transient psychoses caused by stress; thyroid disease syndrome; antidiuretic hormone (ADH) mismatch syndrome; infertility; head injuries; spinal cord injury; ischemic neuronal damage (for example, cerebral ischemia such as cerebral hippocampal ischemia); neuronal damage caused by a toxic stimulant; epilepsy; cardiovascular and cardiac disorders, including hypertension, tachycardia, and congestive heart failure; attack; immune dysfunctions, including stress caused by immune dysfunctions (e.g. stress caused by nervous excitement, stress syndrome in pigs, bulimia, which promotes the spread of fever, equine paroxysmal fibrillation and dysfunctions caused by restriction of movement in chickens, stress associated with sudden movements in sheep, or human-animal resistance, relative to stress in dogs); muscle spasms; incontinence i) urine; senile dementia of the Alzheimer type; multi-infarct dementia; amyotrophic lateral sclerosis; chemical dependencies and excessive substance use (for example, addictions to alcohol, cocaine, heroin, benzodiazepines or other drugs and drugs); symptoms of drug and alcohol withdrawal; osteoporosis; c zo psychosocial microsomia and hypoglycemia in mammals.

The present invention provides new compositions that bind to the receptors of the factor promoting the release of adrenocorticotropic hormone, thus reducing the anxiogenic effects of SKE secretion. The compounds of this invention are useful for the treatment of psychiatric disorders and neurological diseases, disorders associated with anxiety, post-traumatic stress disorder, supranuclear palsy and related disorders associated with nutrition, and in addition, immunological, cardiovascular diseases or i- diseases associated with disturbances in the work of the heart and hypersensitivity of the large intestine associated with psychopathological disorders and stress in mammals.

In accordance with another aspect, the present invention provides new compositions according to Formulas (1) and (2) (described below), which are useful as antagonists of the factor promoting the release of "adrenocorticotropic hormone". The compounds of this invention show activity as antagonists of the factor promoting the release of adrenocorticotropic hormone and show a reduction in the hypersecretion of SKE. Given. the invention also includes pharmaceutical compositions containing such compounds according to Formulas (1) and (2), and methods and use of such compounds to reduce hypersecretion of SCE, and/or treat anxiety disorders.

In accordance with another aspect of the invention, the compounds provided by the present invention (and -I specifically marked as compounds of the present invention) are also useful as standards and reagents for determining the possibility of connection of pharmaceutical potential with the SKE receptor. o The present invention includes a method of treating an affective disorder, an anxiety disorder,

Ge) depression headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, weakened immunity, Alzheimer's disease, - gastrointestinal diseases, anorexia nervosa or other food-related diseases, symptoms 4) withdrawal from drugs or alcohol, addiction to excessive drug consumption, inflammatory disorders, cardiovascular diseases or diseases associated with heart problems, reproductive problems in mammals, human immunodeficiency virus infection, hemorrhagic stress, obesity, infertility, head injuries and spinal cord, epilepsy, seizure, ulcer, amyotrophic lateral sclerosis, hypoglycemia, or disorders that may be treated effectively or alleviated with an SERE antagonist that

Ф) include, but are not limited to, disorders in mammals that are caused by SCE or alleviated by SCE, which involves administering to the mammal a therapeutically effective amount of a compound according to Formulas (1) or (2): 60 b5

. . and their isomers.

A is nitrogen or SC; 7 represents nitrogen or CB2;

Ag is phenyl, naphthyl, pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, benzothienyl, benzofuranyl, 2, 3-dihydrobenzofuranyl, 2, 3-dihydrobenzothienyl, indanyl, 1, 2-benzopyranyl, 3, 4-dihydro-1, 2 -benzopyranyl, tetralinyl, each Ag is optionally substituted by groups from 1 to 5, and each Ag is attached to an unsaturated carbon atom; with

K is independently chosen in each implementation from the group: hydrogen, C.4-Su; alkyl, Co-C; alkenyl, Co-C, alkynyl, Ca-Cv cycloalkyl, C.-C7 cycloalkylalkyl, halo, CM, C.4-C haloalkyl;

B" is independently selected in each implementation from the group: hydrogen, C--Ci alkyl, Co-C. alkenyl, C.-C; alkynyl, halo, CM, C.4-C haloalkyl, C4-C42 hydroxyalkyl, Co-C4o Alkoxyalkyl, Co-C4o cyanoalkyl, C3-Cv cycloalkyl, Su/-C7 cycloalkylalkyl, -MEUV 9, C.-Sul alkyl-ME?B"9, MV?SOV U, -OB", ЗН or-В(О) 0B 2; o

IN? choose from the group: hydrogen, C.-C4 alkyl, Co-C. alkenyl, Co-Si alkynyl, Ca-Cv cycloalkyl, Su-C10 "- cycloalkylalkyl, C4Su hydroxyalkyl, halo, SM, - MAUV", MmaesoOv o, - Meb5(0)087, (OMA B, C, Su haloalkyl, o -O8 7, 8H or -5(0)0872;

VZ is chosen from the group: hydrogen, OK", 5H, 5(O)p"Z, sov" sov, os(OvV, MAZSOoV", MshSOK o, i. z5 MAZSOMEV - or from the group:

C4-C30 alkyl, C0-C40 alkenyl, C0-C40 alkynyl, C3--Ca cycloalkyl, C5-C6 cycloalkenyl, C1-C40 cycloalkylalkyl or C6-C30 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents which independently choose "in each realization from the group: C--Cv alkyl, Xa-Cv cycloalkyl, halo, C.-C4 haloalkyl, cyano, OK"? . alkynyl, C3-Cv cycloalkyl, C4-C1" cycloalkylalkyl, MO"; halo, SM, SS haloalkyl, MAbB", MAZSOV", MASOVI, CO, OB", 15 som", CO(MOKU) VK", CO or 5(0)02 7, in which each such C.4-Cu alkyl . -Su alkyl, MO". halo, SM, MAYA", MAZSOV", MAZSOV,

СО, ОВ", СО(MOVU) В", or (ОВ 7; со 25 and 27, 92 and Kg are independently selected in each implementation from the group: -оУу 70 - hydrogen, -С41-Су, alkyl, С3-С4о alkenyl . from 1 to 3, which are independently selected in each implementation from the group: C.-Cv alkyl, C.-C.10 cycloalkyl, halo, C.4-C. haloalkyl, cyano, ОВ", ЗН, Б(О)08 3, СО" .

HF) alkyl), heteroaryl, heteroaryl (C.-C alkyl), heterocyclyl or heterocyclyl (C.4-C, alkyl); t alternatively, ME OB", Me bar a are independently piperidine, pyrrolidine, piperazine, M-methylpiperazine, morpholine or thiomorpholine, each optionally substituted 1-3 in S.-Salkilu groups;

VZs are independently selected in each realization from the group: hydrogen, S.-Sualkil;

IN? and KE" are independently selected in each implementation from the group: hydrogen, C-C-C alkyl or C-C-C cycloalkyl; 2" are selected from the group: hydrogen, C-C-C alkyl, C--Sul haloalkyl, or C-C-C cycloalkyl;

B" is a C.-C, alkyl or C.C,y haloalkyl; because B"C is selected from the group: hydrogen, C.4-Cα alkyl, C4--C1 haloalkyl, C-Cv alkoxyalkyl, C.-Cv cycloalkyl, Su-C12 cycloalkylalkyl, aryl, aryl (C. Su alkyl)-, heteroaryl or heteroaryl (C.C, alkyl);

B" is selected from the group: C.4-C4 alkyl, Ca-Cio alkenyl, Ca-Cio alkynyl, Ca-Cv cycloalkyl or Cu-C125 cycloalkylalkyl, each optionally substituted with substituents from 1 to 3, which are independently selected in each implementation from the group: C-Cv alkyl, Xa-Cv cycloalkyl, halo, C4-C. haloalkyl, cyano, OK", 5H, 5(0)08 7, СО", sov, ОоС(ОвВ, Me8СОovВ", Mm(сСОov ', MAZSOoMe' 9", Me8SOov'?, MeV, sSOMA'YAV5 and

C.-C, alkylthio, C--Cv alkylsulfinyl and C.Ce alkylsulfonyl;

B"5 and KZ are independently selected in each implementation from the group: hydrogen, C.4-Cv alkyl, Xa-C10 cycloalkyl, Su-C16 cycloalkylalkyl, except that for 5(O)0B 77, BZ cannot be hydrogen ; 70 aryl is phenyl or naphthyl, each optionally substituted with substituents from 1 to 5, which are independently selected in each implementation from the group: Ci-Cv alkyl, C3-Cv cycloalkyl, halo, Ci-C4 haloalkyl, cyano, OB" ?, 5H, (Ov, Sov" sov" OosS(OvV, MAZSOoV" M(SOovV', MeZsOoMme 975, MAZSOoV'Z, MeV and

SOM br 15; heteroaryl is pyridyl, pyrimidinyl, triazinyl, furanyl, pyranyl, quinolinyl, isoquinolinyl, 75thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, isoxazolyl, pyrazolyl, 2,3-dihydrobenzothienyl, or 2,3- dihydrobenzofuranyl, each optionally substituted with substituents from 1 to 5, which are independently selected in each implementation from the group: C4-C6 alkyl, C3-C6 cycloalkyl, halo, C4-C4 haloalkyl, cyano, OB", 8H, (008, - SOV, sov", os(Ov', MeZsOoV", sh(SOvV",

MAeZSSSOOME 15875, MvZSO»V 5, MVY9VY5 and SOM bV 75; heterocyclyl is a saturated or partially saturated heteroaryl, optionally substituted with 1 to 5 substituents, which are independently selected in each implementation from the group: C.4-Cv alkyl, C3--Cv cycloalkyl, halo, CC, haloalkyl, cyano, OB ", ЗН, 5(0)08?, СО", sov, os(ОВ"?, MeZSOov", mov, MAZsOoMme 9875, MmeZsOoov", MA ZV and SOM JAV 5; src p represents independently in each realization 0 , 1 or 2; (2) The best methods of this invention are methods in which in compounds according to Formulas (1) or (2), Ag (o) represents phenyl, pyridyl or 2,3-dihydrobenzofuranyl, each of which is necessarily replaced by substitutes from 1 to 4 V.

Further, the best methods of the above-mentioned invention are methods in which, in the compounds according to Formulas (1) or (2), A represents hydrogen, 7 represents SC 2, Ag represents 2,4-dihydrophenyl, 2,4-dimethylphenyl or 2 , 4, b-trimethylphenyl, VK! Yes? represent CH", and EZ represents MAV 79, - 4) This invention includes compounds according to Formulas (1) or (2): (He) and their isomers, their or U a a c) " KE KE

B. (13 (2) and 95) stereoisomeric forms or mixtures of their stereoisomeric forms and forms of their pharmaceutically acceptable salts or co-prodrugs, in which: A is nitrogen or SC; 7 represents nitrogen or CB2; - Ag represents phenyl, naphthyl, pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, benzothienyl, and benzofuranyl, 2, 3-dihydrobenzofuranyl, 2, 3-dihydrobenzothienyl, indanyl, 1, 2-benzopyranyl, 3, 4-dihydro-1 , 2-benzopyranyl, tetralinyl, each Ag optionally substituted by groups from 1 to 5 EC? and each Ag is attached to an unsaturated carbon atom;

K is independently chosen in each implementation from the group: hydrogen,

C.4-C alkyl, Co-C, alkenyl, C-C alkynyl, C--Ce cycloalkyl, C.-C7 cycloalkylalkyl, halo, CM, CC haloalkyl; o B" is independently selected in each implementation from the group: hydrogen, C--Ci alkyl, Co-C. alkenyl, Co-C; alkynyl, halo, CM, C.4-C haloalkyl, C4-C42 hydroxyalkyl, Co- C4o alkoxyalkyl, Co-C4o cyanoalkyl, C3-C8 cycloalkyl, C3-C7 cycloalkylalkyl, MEUV 9, C.-C4 apKkt-MeE?B79, ME?SOV I, OB", ZN or (03082; 6o B? is chosen from groups: hydrogen, C.-C4 alkyl, Co-C. alkenyl, Co-Ci alkynyl, Ca-Cv cycloalkyl, Su-C10 cycloalkylalkyl, C4-Cu hydroxyalkyl, halo, SM, -"MEZUV", MASOVO, - Me b5 (0)087, (OMA, SS, haloalkyl, -O8 7, 8H or -5(0)0872;

VZ is chosen from the group: 65 - hydrogen, OK", ZN, (Op Z, Sov, sov, oOS(OV Z, MAZSOV,

Mm(сОов7», MAZсоомеов", mmeZсооме"Z, MAV", Mesavya, MOVO? СОМеЗВ", aryl, heteroaryl and heterocyclyl, or from the group: -Сб4-С3о alkyl, Со-С4о alkenyl, Со-С3о alkynyl, C3-C6 cycloalkyl, C5-C6 cycloalkenyl, C1-C40 cycloalkylalkyl or C3-C30 cycloalkenylalkyl, each optionally substituted with substituents from 1 to 3, which are independently selected in each implementation from the group: C3-C6 alkyl, C3-C6 cycloalkyl , halo, Ci-Su haloalkyl, cyano, OV"Z, ZN, (Op U,

СО 15, сов", ос(ОВЗ, MвЗсОвВ"5, ШСОв5, MeZсОвМе 19875, MeЗСОов"З, Me б875, СОМ 985, aryl, heteroaryl or heterocyclyl;

B" is independently selected in each implementation from the group: hydrogen,

C4-C30 alkyl, C0-C10 alkenyl, C0-C10 alkynyl, C3-C1 cycloalkyl, C1-C2 cycloalkylalkyl, MO". halo, SM, C4-C4 70 haloalkyl, ME9B", MeAZSOV", MeZSOoV", Sov", OV", SOMAbV", CO(MOVU) B", CO or 5(0)087, in which each such C.4 -C.o alkyl, Co-C4o alkenyl, Co-Cio alkynyl, C--Ci cycloalkyl and C.-C4o» cycloalkylalkyl is optionally substituted by substituents from 1 to 3, which are independently selected in each implementation from the group: C 4 -C/ alkyl, MO", halo, SM, MAU", MeEZSOvB 7, Mme8SOov, Sov, OB", COM, CO, CO(MOKU) B", or (OB 7;

II 2? and B", vda and Ka are independently selected in each implementation from the group: -hydrogen, -C41-Su, alkyl, C3-C4o alkenyl, C3-C3o alkynyl, C4-C4o haloalkyl with 1-10 halogens, Co-Cv alkoxyalkyl, C3-C10 cycloalkyl, C1-C10 cycloalkylalkyl, C1-C10 cycloalkenyl or C1-C14 cycloalkenylalkyl, each optionally substituted with substituents from 1 to 3, which are independently selected in each implementation from the group: C1-C10 alkyl, C3-C10 or Cycloalkyl, halo, S.-Su haloalkyl, cyano, OB, vn, (0083, SO, Sov, oOS(OV Z, MAZSOV 5, SOVI,

MeZsOoMme 9875, MeZsOov Z, Me bv"5, COM B", aryl, heteroaryl or heterocyclyl, -aryl, aryl (C.-C, alkyl), heteroaryl, heteroaryl (C.-Salkyl), heterocyclyl or heterocyclyl (C. -Su,alkyl); alternatively, ME OB", Me bar and are independently piperidine, pyrrolidine, piperazine, M-methylpiperazine, morpholine or thiomorpholine, each optionally substituted 1-3 with 25 C.-C,u alkyl groups ; at

VZ is independently selected in each implementation from the group: hydrogen or C.4-C6 alkyl;

BZ and KO are independently selected in each implementation from the group: hydrogen, C4-C6 alkyl or C3-C6 cycloalkyl;

B" is selected from the group: hydrogen, C1-C6 alkyl, C4-C6 haloalkyl, or C3-C6 cycloalkyl;

K represents C.-C, alkyl or C.-C, haloalkyl; and. 30 BZ are selected from the group: hydrogen, C.-Ci alkyl, C.4-C. haloalkyl, C.-C. "- alkoxyalkyl, C.-C. cycloalkyl, C.-C." cycloalkylalkyl, aryl, aryl (C.-C, alkyl)- , heteroaryl or heteroaryl (C.-C, alkyl)-; b

B" is selected from the group: C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C3-C10 cycloalkyl or C1-C12-C35 cycloalkylalkyl, each optionally substituted with substituents from 1 to 3, which independently are selected in each implementation from the group: C.4-Cv alkyl, C.3-Cb cycloalkyl, halo, C.i-C4 haloalkyl, cyano, OK"? ZN, (0)? CO,

SOY, os(oOvV", MeYASOoV"Y, Mm(СсОovV'Z, MeZsOoMv' Zv", MmeZSOoV'?, MAV! СсОМАбВ75 and

C.-C, alkylthio, C.-Cv alkylsulfinyl and C.-Ce alkylsulfonyl; "

B"5 and KZ are independently selected in each implementation from the group: hydrogen, C.4-Cv alkyl, Xia-C10 cycloalkyl, Su-C16 40 cycloalkylalkyl, except that for (030272, B"? cannot be hydrogen; c) aryl is phenyl or naphthyl, each optionally substituted "with substituents from 1 to 5, which are independently selected in each implementation from the group: C1-C5 alkyl, C3--Ce cycloalkyl, halo, C.i -WITH. haloalkyl, cyano, OK", 5Н, 5(0)08"?, СО, sov», ОоСс(ОВ', MeЗСОоВ", shСОВ,

MeZsOoMme 9875, MAZSOov 5, MAV Yav5 and SOM V 5; - heteroaryl is pyridyl, pyrimidinyl, triazinyl, furanyl, pyranyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, (95) isoxazolyl, pyrazolyl, 2,3-dihydrobenzothienyl, or 2 ... . necessarily substituted by substituents from 1 to 5, which are independently selected in each realization from the group: C4-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C haloalkyl, cyano, OK", 5H, 5(0)08" ?, СО, сов», ООСс(ОВ', MeЗСОоВ", щСОВ, MAZSOME v, MeEZSOov o, MAV and СОМ В 75; o p represents independently in each implementation 0, 1 or 2; under the conditions that: (1 ) when A represents nitrogen, 7 represents itself SV 7, B? represents hydrogen, B Z represents -OB 0 or di -OSOK Z, and B" represents hydrogen, then B! does not represent hydrogen, OH or 5H; (2) when A represents nitrogen, 7 represents CE 7 , B" represents CHnaz or CoH5, B represents hydrogen, and B 60 represents OH, hydrogen, CoHv, p-Czin7, II-CzNU, ZN, ZCH3, МНОС4HO, or M(CoHv/)", then Ag does not represent is phenyl or t-CH3-phenyl; (3) when A represents nitrogen, 7 represents SV, B? is hydrogen, and A is pyridyl, pyrimidyl, or pyrazinyl, and BZ is MAV 72, then K92 and Ka are not hydrogen or alkyl; 65 (4) when A represents nitrogen, 7 represents SV 2, and VC? represents ZOM, then KZ does not represent ОН or 5Н;

(5) when A represents nitrogen and 7 represents SC, then B? is not -ME? 80287 or -BO2MAZV 7; (6) when A represents nitrogen, 7 represents CE 2 and K? represents -ME 550258 or -ZO2MA SV, then VZ does not represent OH or 5H; (7) when A is nitrogen, 7 is SC, K is methyl or ethyl, K is hydrogen, and K is hydrogen, OH, CH3, C Hv, SeHv, p-C3H»7, iso-C3NU , ЗН, МН(п-САНо) or М(СоНб)", then Ag is not an unsubstituted methyl or t-methylphenyl; (8) when A represents CE, 7 represents SK, B? is hydrogen, phenyl or alkyl, B is MW.

SOBK ii Ag represents phenyl or phenyl substituted with methylthio, then KE " does not represent aryl, arnp(C-C alkyl), 70 tetraaryl, heteroaryl (C-C, alkyl), heterocyclyl, heterocycles (C-C alkyl); ( 9) when A is CE, 7 is CE 2, BE! is hydrogen or alkyl, and B C is ZB 73 or Mar a, then BZ is not aryl or heteroaryl, but B 922 and B"? are not hydrogen or aryl; or /5 (10) when A represents CH, 7 represents SV 2, E! represents OB", B? represents hydrogen, B Z represents OK", and K'" and BC"! both are hydrogen, then Ag is not phenyl, p-H-phenyl, p-MNHSOCH,-phenyl, p-CH3-phenyl, pyridyl or naphthyl; (11) when A represents CH, 7 represents SK, B? is hydrogen, Ag is unsubstituted phenyl,

VZ represents SNU, SoN, SEz or SeNaE, then Vi does not represent SEz or SoNB; (12) when A is CH, B is hydrogen, 7 is CE. 2, B is OH, and B and B are hydrogen, then Ag is not phenyl; (13) when A represents CH, VK represents hydrogen, 7 represents SV 7, B? is OH or MH", and in! and EZ are CH with, then Ag is not 4-phenyl-3-cyano-2-aminopyrid-2-yl.

I) The best compounds of the above invention are the compounds according to Formulas (1) and (2) and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and the forms of their pharmaceutically acceptable salts or (U prodrugs, under additional conditions that: (1 ) when A is nitrogen, K 1 is hydrogen, C 1-C, alkyl, halo,

CM, C4-C4" hydroxyalkyl, C4-C4 alkoxyalkyl or 505 (C.4-Cu alkyl), KZ is МЕСevВ 72 and Vba is unsubstituted C.-C, alkyl, then Ka is not phenyl, naphthyl, thienyl , benzothienyl, pyridyl, quinolyl, co pyrazinyl, furanyl, benzofuranyl, benzothiazolyl, indolyl or Ca-Cv cycloalkyl; (2) A is nitrogen, B is hydrogen, C.--Csu alkyl, halo, CM, C.4-C.4o hydroxyalkyl, C.4--C, alkoxyalkyl or 505(C.4-C.sub.alkyl), KZ is MKbav a and Kg is unsubstituted C-C/alkyl, then Ka is not phenyl, naphthyl, thienyl, (22) benzothienyl, pyridyl, quinolyl, pyrazinyl, furanyl, benzofuranyl, benzothiazolyl, indolyl or C3-Cv cycloalkyl. with

The preferred compounds of the above invention also include compounds of Formulas (1) and (2) and their isomers,

Of their stereoisomeric forms or mixtures of their stereoisomeric forms, and forms of their pharmaceutically acceptable salts or prodrugs, in which A is phenyl, pyridyl, or 2,3-dihydrobenzofuranyl, each optionally substituted with substituents from 1 to 4 B.

I/Y The best compounds of the above invention also include compounds according to Formulas (1) and (2) and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or forms - 70 prodrugs, in which A is nitrogen , 7 represents SK 2, Ag represents 2, 4-dichlorophenyl, 2, 4-dimethylphenyl c or 2, 4, b-trimethylphenyl, VK! Yes? represent CH", and EZ represents MAV 79, :z" 11) The best compounds of the above-mentioned invention are the compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and the forms of their pharmaceutically acceptable salts or prodrugs, in which 415 A represents itself nitrogen. - (121 The best compounds of the above invention also include the compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and the forms of their pharmaceutically acceptable salts or prodrugs. o (13) The best compounds of the above invention also include the compounds and their isomers, their stereoisomeric o forms or mixtures of their stereoisomeric forms, and forms of their pharmaceutically acceptable salts or prodrugs in which

Ag is phenyl, pyridyl, or 2,3-dihydrobenzofuranyl, and each Ag is optionally substituted with 1 to 4 B substituents. 4) (141) Preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms or mixtures thereof their stereoisomeric forms, and forms of their pharmaceutically acceptable salts or prodrugs, in which

E represents MAV 72 or OV. (15) Preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or prodrug forms thereof, in which iF) Ag is phenyl, pyridyl, or 2,3-dihydrobenzofuranyl, and each Ag is optionally substituted with substituents from 1 to 4 B, and VZ is ME Sar 72 or OB. (16) The best compounds of the above invention also include the compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms, in which 7 is SKZ. (17) The best compounds of the above invention also include the compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and forms of their pharmaceutically acceptable salts or prodrugs in which

Ag is phenyl, pyridyl, or 2,3-dihydrobenzofuranyl, and each Ag is optionally substituted with 1 to 4 B substituents.

(181) The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms in which

VZ is Mar 72 or OV. (19) The preferred compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms in which

K 2 is independently chosen from the group: - hydrogen; -Сб41-С3о alkyl, С3-С4о alkenyl, Са-С3о alkynyl, С4-С4о haloalkyl with 1-10 halogens, Со-Св alkoxyalkyl, С3-Св cycloalkyl, С/-С1о cycloalkylalkyl, Св-Сию cycloalkenyl or Се-С44 cycloalkenylalkyl, each optionally 70 substituted by substituents from 1 to 3, which are independently selected in each implementation from the group: ОВ З, СОВ "У, сОо285, осС(ОВ З, MAZSOV"», СО», МAZсОомме 9875, MmeZsov З, MA bv7"5, СОМ eV, aryl, heteroaryl or heterocyclyl, -aryl, aryl (С.-С . alkyl)-, heteroaryl, heteroaryl (C.-C, alkyl)-, heterocyclyl or heterocyclyl (C.-C. alkyl)-, and K/2 are independently selected in each implementation from the group: -hydrogen; -C5-C1o alkyl, C3-C10 alkenyl, C3-C0 alkynyl, C4--C30 haloalkyl with 1-10 halogens, C0-C10 alkoxyalkyl, C3-C10 cycloalkyl, C1-C10 cycloalkylalkyl, C1-C10 cycloalkenyl or Ce-C14 cycloalkenylalkyl, each optionally replaced by substitutes from 1 to 3, which are independently selected in each implementation from the group: Sy.-Sv al circle, C3-C10 cycloalkyl, halo, C.4-Cu haloalkyl, cyano, OBU, ZN, (0083, SO, SOVI, oS(OV Z, MAZSOV "V, SOVI, 720 MeZsOoMme 9875, MeZSOov Z, Me bv5, COM UV 5, aryl, heteroaryl or heterocyclyl, -aryl, aryl (C.4-C alkyl), heteroaryl, heteroaryl (C.4-C alkyl), heterocyclyl or heterocyclyl (C.4-C alkyl); alternatively, MAO", mebav'a are independently piperidine, pyrrolidine, piperazine,

M-methylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C.-C, alkyl groups; (20) The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms, in which i) dose and K 72 are identical and are selected from the group: - C.-C, alkyl or C3-C5 cycloalkyl, each optionally substituted with substituents from 1 to 3, which are independently selected in each implementation from the group: C4-C6 alkyl, C3-C5 cycloalkyl, halo, C.4-C5 haloalkyl .

COM "in 75, aryl, heteroaryl or heterocyclyl, and -aryl or heteroaryl. (21) The preferred compounds of the above invention also include the compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms , in which c va is selected from the group: -hydrogen; - -Cb41-C3o alkyl, C3-C4o alkenyl, Ca-C3o alkynyl, C4-C4o haloalkyl with 1-10 halogens, Co-Cv alkoxyalkyl, C3-Cv cycloalkyl, Su -C12 cyclocycloalkyl, C1-C10 cycloalkenyl or C1-C44 cycloalkenylalkyl, each optionally substituted with substituents from 1 to 3, which are independently selected in each implementation from the group: C 4-C8 alkyl, C3-C8 cycloalkyl, halo, C. 4-Su haloalkyl, cyano, ОВ", ЗН, Б(О)08 3, СО", sov, ос(ОВ З, MAZSOvV 5, СОУ», Z с 70 MeZsOoMme 9875, MeZsSOov"Z, MA'9v75, SOM 9B75, aryl, heteroaryl or heterocyclyl, -aryl, aryl (C4-C1 alkyl), heteroaryl, heteroaryl (C1-C6 alkyl), heterocyclyl or heterocyclyl (C4-C6 alkyl); K/"2 is selected from groups: a - C.-C, alkyl and any and S.-S. alkyl is substituted by substituents from 1 to 3, which are independently selected in each implementation from the group: C-Cv alkyl, C3-Cv cycloalkyl, halo, C-C4 haloalkyl, cyano, ОБ?, 5Н, (Ов sov sov, Оос( ov Me8cOovV" Mm(cSOovV'Z, MeZcOoMe'9v"?, Mme8cOov'Z, Me in, - COM B 5, aryl, heteroaryl or heterocyclyl. o (22) The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and the forms of their pharmaceutically acceptable salts or prodrugs, in which one of Ka and K "2 is selected from the group: -o 70 -C3-Cv cycloalkyl, each such C3-Cv cycloalkyl is substituted by substituents from 1 to 3, which are independently selected in each implementation from the group: C1-Ce alkyl, C3-Cv cycloalkyl, halo, C4i-Su; haloalkyl, cyano, c" OM 5, vn, 5(0)083, Sov", Sov, oS(OVZ, MeZSOvV 5, Sov)", MeEZsSOME 9875, Me8SOo8v 3, Me ov 5,

COM in 75, aryl, heteroaryl or heterocyclyl. -aryl, -heteroaryl or (F)-heterocyclyl, and the other of K92 and K8 is unsubstituted C4-C6 alkyl. (23) The preferred compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms, in which vva and vva are independently hydrogen or C 1-C.o alkyl, each such C.4-C.o alkyl is substituted with substituents from 1 to 3, which are independently selected in each implementation from the group: C.4-C.alkyl, C.sub.3-C.cycloalkyl, halo, C.i.-C. haloalkyl, cyano, OK", 5Н, 5(0)083, Сов, сов ос(ОВ, Me8СОоВ", shСОВ,

MeZsOoMme 9875, MeZSOov Z, Me bv5, COM UV5, aryl, heteroaryl or heterocyclyl. (24) Preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or prodrug forms thereof in which

Ag is phenyl, pyridyl, or 2,3-dihydrobenzofuranyl, and each Ag is optionally substituted with 1 to 4 B substituents, and BZ is ME. 28 72 or OV. (25) The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms in which

And independently choose from the group: - hydrogen; -C.A-C10 alkyl, C3-C10 alkenyl, C3-C0 alkynyl, C4--C30 haloalkyl with 1-10 halogens, C3-C10 alkoxyalkyl, C3-C10 cycloalkyl, C1-C10 cycloalkylalkyl, C1-C10 cycloalkenyl or Ce-Ci4 cycloalkenylalkyl, each optionally substituted with substituents from 1 to 3, which are independently selected in each implementation from the group: C 4-C; alkyl, Ca-Cv cycloalkyl, halo, C4-Su haloalkyl, cyano, OK», ЗН, (0) 3, СО», Сов», оС(ОВЗ, MAZSOV 5, СОУ», 70. chav8сОоМеЕ в", MeЗСсоов З , Me! 9v75, COM in 5, aryl, heteroaryl or heterocyclyl, -aryl, aryl (C.-C. alkyl)-, heteroaryl, heteroaryl (C.4-C, alkyl), heterocyclyl or heterocyclyl (C.4 -Cu alkyl); K/2 is independently selected in each implementation from the group: -C5-Clo alkyl, C3-C4o alkenyl, Ca-C3o alkynyl, C4-C4o haloalkyl with 1-10 halogens, Co-Cv alkoxyalkyl, C3-Cv cycloalkyl, C1-C10 cycloalkylalkyl, C1-C10 cycloalkenyl or C1-C14 cycloalkenylalkyl, each optionally substituted with substituents from 1 to C, which are independently selected in each implementation from the group: C4-C; alkyl, C3-C8 cycloalkyl , halo, C.4-Su haloalkyl, cyano, OBU, ZN, (0083, SO, SOVI, oS(OV Z, MAZSOV "V, SOVI,

MeZsOoMme 9875, MeZsOov Z, Me bv"5, COM B", aryl, heteroaryl or heterocyclyl, -aryl, aryl (C.-C, alkyl), heteroaryl, heteroaryl (C.-C,. alkyl), heterocyclyl or heterocyclyl (C.4-Cu alkyl); alternatively, MAV", Mesbav'a are independently piperidine, pyrrolidine, piperazine,

M-methylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C.-C, alkyl groups; (26) The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and the forms of their pharmaceutically acceptable salts or prodrugs, in which Va and VK 72 are identical and are selected from the group: Ha - C. -Su; alkyl or C3-C8 cycloalkyl, each optionally substituted with 1 to 3 substituents independently selected in each implementation from the group: C8-C8 alkyl, C3-C8 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OB"?, 5H, o (00, -sSOV, sov", osv, MAZSOov" Mm(СсОov'ya", MeZsOoMmv' v", MmAZSOV"Z, MeV",

COM "in 75, aryl, heteroaryl or heterocyclyl, and -aryl or heteroaryl. (27| Preferred compounds of the above invention also include the compounds and their isomers, their stereoisomeric forms and, forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms , in which "-ba and Kk 72 are identical and represent - C.-C, alkyl, each such C.4-C, alkyl is optionally substituted by substituents from 1 to 3, which are independently selected in each realization from the group : Ci-Cv alkyl, C3-Cv cycloalkyl, halo, Ci-Su4 haloalkyl, cyano, ОВК", 5Н, "о (Ов, -сСОВ"?, sov", osv, Me8сОov" Mm(сОov'", MeZсОоМе' in, MeZsOov"Z, MeV, m

COM B 5, aryl, heteroaryl or heterocyclyl. (28) The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms, in which la is selected from the group: "-hydrogen; 8 c -Cb41-C3o alkyl, C3-C4o alkenyl, Ca-C3o alkynyl, C4-C4o haloalkyl with 1-10 halogens, Co-Cv alkoxyalkyl, C3-Cv c cycloalkyl, Su-c12 cyclocycloalkylalkyl, Cv-Cio cycloalkenyl or Ce -Si4 cycloalkenylalkyl, each optionally "» substituted with 1 to 3 substituents, which are independently selected in each implementation from the group:

C.-Cv alkyl, C3-Cv cycloalkyl, halo, C.-Cv haloalkyl, cyano, OK"5, ЗН, (0083, СО, ОВЯ, осС(OK З,

MASOVE, Sov), MAZSOME bv5, MeZcOov З, MA b8B75, СОМ bv 5, aryl, heteroaryl or heterocyclyl, β- -aryl, aryl (Ci-C, alkyl), heteroaryl, heteroaryl (C.-C. alkyl), heterocyclyl or heterocyclyl (C.4-C,; alkyl); p'a oo represents -C,.-C, alkyl and each such C.-C, alkyl is substituted by substituents from 1 to 3, which are independently selected in each implementation from the group: C-Cv alkyl, C3-Cv cycloalkyl , halo, C4-Su haloalkyl, cyano, UVK "З, 5Н, -о 70 (00, sov sov osv Me8СОovВ", Mm(СсОov'ya, MAZsСОоМе 975, Me8сОov'З, Meev, с» СОМ in 75, aryl, heteroaryl, or heterocyclyl.(29) The best compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or prodrug forms thereof, wherein in one of the CCC g and Ka is selected from the group: -C3-C; cycloalkyl, each such C3-Ce cycloalkyl is substituted with substituents from 1 to 3, which

F) independently choose in each implementation from the group: C4--C; alkyl, C3-Ce cycloalkyl, halo, C--C4 haloalkyl, cyano, co OM 5, vn, 5(0)083, Sov", Sov, oS(OVZ, MeZSOvB 5, Sov)", MeEZsSOME 9875, Ме8СОо8в 3, Ме ов 5,

COM "in 75, aryl, heteroaryl or heterocyclyl. -aryl, because -heteroaryl or -heterocyclyl, and the other from K92 and K"2 is an unsubstituted C-C6 alkyl.

ISOs Preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or prodrug forms thereof, wherein vba and va are independently hydrogen or C 4 -C 10 alkyl, each such C.4-C40 alkyl is optionally substituted with substituents from 1 to 3, which are independently selected in each implementation from the group: C 4-C 62 adalkyl, Ca-Cb cycloalkyl, halo, C.-C. haloalkyl, cyano, OB", NN, 5(0)083, Sov sov", os(OK Z,

MAZsOov"?, ShsOv, MeZsOoMe vo, MeZsOov Z, Me 9875, СОМ yav", aryl, heteroaryl or heterocyclyl.

Preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or prodrug forms thereof, in which: - Ag is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ag is optionally substituted by substituents 1 to 4 27; -EZ is MAV Zabo OB and -B! and B? independently selected from the group: C.-C. alkyl, C.-C. cycloalkyl, C.-C.sub.4 cycloalkylalkyl.

The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and forms of their pharmaceutically acceptable salts or prodrugs, in which 70 wt 2 are independently selected from the group: -hydrogen; -Сб41-С3о alkyl, С3-С4о alkenyl, Са-С3о alkynyl, С4-С4о haloalkyl with 1-10 halogens, Со-Св alkoxyalkyl, С3-Св cycloalkyl, С/-С1о cycloalkylalkyl, Св-Сиу cycloalkenyl or Се-Си4 cycloalkenylalkyl, each optionally substituted with substituents from 1 to 3, which are independently selected in each implementation from the group: C 4-Cv alkyl, C3-Cv cycloalkyl, halo, C4-Cv haloalkyl, cyano, OK", ZN, (0) 3, СО", Сов", оС(ОВЗ, MAZSOV 5, СОУ», t MeZsoOoMme 9875, MeZSOov Z, Me bv5, СОМ УВВ 5, aryl, heteroaryl or heterocyclyl, -aryl, aryl (C.-C.u alkyl )-, heteroaryl, heteroaryl (C.4-C, alkyl), heterocyclyl or heterocyclyl (C4-C6 alkyl); K 2 is independently selected in each implementation from the group: -C5-C30 alkyl, C3-C6 alkenyl, C3-C .o alkynyl, C--C40 haloalkyl with 1-10 halogens, C0-C0 alkoxyalkyl, C3-C0 cycloalkyl, C1-C10 cycloalkylalkyl, C1-C20 cycloalkenyl or Ce-C4 cycloalkenylalkyl, each optionally substituted with substituents from 1 to C, which are independently selected in each implementation from the group: C 4-C; alkyl, C3-Cv cycloalkyl, halo, C4-Su haloalkyl, cyano, OK», ЗН, (0) 3, СО», Сов», оС(OVZ, MAZSOV 5, СОУ»,

MeZsOoMme 9875, MeZsOov Z, Me bv"5, COM B", aryl, heteroaryl or heterocyclyl, -aryl, aryl (C--C; alkyl), heteroaryl, heteroaryl (C4-C, alkyl), heterocyclyl or heterocyclyl (C .-S. su alkyl), alternatively, Mb", Mmesbav'a are independently piperidine, pyrrolidine, piperazine, o

M-methylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C.-C, alkyl groups;

The preferred compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms, in which va and VK 72 are identical and are selected from the group: co - C.-C , alkyl or C3-C5 cycloalkyl, each optionally substituted with substituents from 1 to 3, which are independently selected in each implementation from the group: C3-C5 alkyl, C3-C5 cycloalkyl, halo, Ci-C4 haloalkyl, cyano, OB 5H

COM "in 75, aryl, heteroaryl or heterocyclyl, and -aryl or heteroaryl. so

The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and the forms of their pharmaceutically acceptable salts or prodrugs, in which - ba and Kk 72 are identical and represent - C.-C, alkyl, each such C.4-C, alkyl is optionally substituted by substituents from 1 to 3, which are independently selected in each implementation from the group: C-C alkyl, C3-C cycloalkyl, halo, C4-C haloalkyl, cyano, OVC "Z . The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms, in which la is selected from the group: -hydrogen; - -Cb4-C3o alkyl, С3-С4о alkenyl, Са-С3о alkynyl, С4-С4о haloalkyl with 1-10 halogens, Со-Сд alkoxyalkyl, С3-С8о cycloalkyl, С/-С1о cycloalkylalkyl . Su haloalkyl, cyano, OK", ZN, (0208, SO", OWL? ос(ОВ З, МАЗСОВ 5, СО, - 20 Мв8ЗсСОоМА В, МВ8СОovZ, Me Ev, СОМ Вб, aryl, heteroaryl or heterocyclyl, -aryl, aryl (CgC/alkyl), heteroaryl, heteroaryl (C.-C, alkyl) , c» heterocyclyl or heterocyclyl (C.4-C alkyl); K/2 represents - C.-C., alkyl and each such C.-C. alkyl is substituted by substituents from 1 to 3, which are independently selected in each realization from the group: C-Cv alkyl, C3-Cv cycloalkyl, halo, C4-Cv haloalkyl, cyano, ОВК "З, 5Н, (ОЗ, СО, СОовя, оОС(ОВ З, MAZSOov "5, SCHO, MAZSOME 9875, MAZSOoV C, MA 9875, COM B, (F, aryl, heteroaryl or heterocyclyl. ka IZBI) Preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof or mixtures of stereoisomeric forms thereof, and forms of pharmaceutically acceptable salts or prodrugs thereof, in which because one of 92 and K"2 is selected from the group: -C3-C; cycloalkyl, each such C3-Ce cycloalkyl is substituted by substituents from 1 to 3, which are independently selected in each implementation from the group: C4-C8 alkyl, C3-- St. cycloalkyl, halo, S.- WITH; haloalkyl, cyano,

OM 5, vn, 5(0)083, Sov", Sov, oS(OVZ, MeZSOvV 5, Sov)", MeEZsSOME 9875, Me8SOo8v 3, Me ov 5,

COM "in 75, aryl, heteroaryl or heterocyclyl. -aryl, because -heteroaryl or -heterocyclyl, and the other from K92 and K"2 is an unsubstituted C-C6 alkyl.

Preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or prodrug forms thereof, wherein vba and va are independently hydrogen or C 4 -C 10 alkyl, each such C.4-C4o alkyl is optionally substituted by substituents from 1 to 3, which are independently selected in each implementation from the group: C 4-C/ alkyl, C.-Cv cycloalkyl, halo, C.4-C4 haloalkyl, cyano, OB ", 5H, (008, sov"? sov"? осС(ОВ У,

MAZsOov"?, ShsOv, MeZsOoMe vo, MeZsOov Z, Me 9875, SOM yav", aryl, heteroaryl or heterocyclyl.

Especially preferred compounds of the above invention are compounds according to Formula (50): 715 ier | . that sat down 487 Ff dyaj uche.

Formula (50). c and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and forms of their pharmaceutically acceptable salts or prolines, which are selected from the group containing: a compound according to the Formula (50), in which KZ is -МНСН(п-Рг )", K72 is chlorine, B 7? represents hydrogen, VU represents chlorine, BZ represents hydrogen and B"e represents hydrogen; a compound according to Formula (50), in which BZ represents -M(EO (p-Vy), B 2 represents chlorine, B ? represents 6 hydrogen, BC" represents chlorine, KZ represents hydrogen and VC": represents hydrogen; "- a compound according to Formula (50), in which KZ represents -M(СНСНООМе)", Б72 represents chlorine, B" is hydrogen, B. 77 is chlorine, KZ is hydrogen and Be is hydrogen; so is a compound according to Formula (50), in which BZ is -MNSN (ЕХО (п-Вы), B72 cha represents chlorine, B" represents hydrogen, VK 77 represents chlorine, VK 79 represents hydrogen and K"e represents hydrogen; a compound according to Formula (50), in which KZ represents -МНСН (EO (СНоОМе) , Ba « represents chlorine, K "7? represents hydrogen, VK 72 represents chlorine, B 79 represents hydrogen and BK 72 represents hydrogen; - c compound according to Formula (50), in which KZ represents -MNSN ( СНоОМе)", 72 represents chlorine, BC" represents

Is" hydrogen, VU represents chlorine, BZ represents hydrogen and B"e represents hydrogen; a compound according to Formula (50), in which B C represents -M (EO 5", B72 represents chlorine, B "7? represents hydrogen, Ks represents chlorine, KZ represents hydrogen and K": represents hydrogen; - and a compound according to Formula (50), in which KZ represents -MNCHN (СНоОЕО", 72 represents chlorine, B" represents is hydrogen, B. 77 is chlorine, KZ is hydrogen and Be is hydrogen; se) a compound according to Formula (50), in which KZ is -MNSN (ED ", B72 is shu 20 chlorine, B? represents hydrogen, 72 represents chlorine, 79 represents hydrogen and B" represents hydrogen; a compound according to Formula (50), in which EZ represents -M (Me) (RI), K72 represents c" chlorine, B ? represents hydrogen, 72 represents chlorine, 79 represents hydrogen and B" represents hydrogen; a compound according to Formula (50), in which KZ represents -M (p-Pg)", K72 represents chlorine, BK" is hydrogen,

B": represents chlorine, BZ represents hydrogen and B"e represents hydrogen; compound according to Formula (50), in which 2? is -MNON (EO (p-Pg), B 72 is chlorine, B" is hydrogen, VK 77 is chlorine, VK 79 is hydrogen and K"e is hydrogen; a compound according to the Formula ( 50), in which KZ is -MHNH (CH OMe)", K72 is methyl, B7? is hydrogen, B" is methyl, BZ is hydrogen and Be is methyl; a compound according to the Formula (50 ), in which KZ is -MNCH (CH OMe)", K72 is methyl, B7? is hydrogen, VU is methyl, BZ is hydrogen and B" is hydrogen; a compound according to Formula (50) , in which EZ is -MNCH (CHNoCHNoOMe)", la is methyl, B" is hydrogen, B" is methyl, BZ is hydrogen and Be is hydrogen; a compound according to Formula (50), in in which KZ is -MNCH (EO (CHNoOMEe), 272 is methyl, B7? is hydrogen, VU is methyl, BZ is hydrogen and B" is hydrogen; a compound according to Formula (50) in which BZ represents -MNSON (EbO 5", B72 represents methyl, VK 7? represents is hydrogen, B is methyl, KZ is hydrogen and Be is hydrogen; a compound of Formula (50), in which BZ is -OEI, 72 is chlorine, B" is hydrogen, B 72 is chlorine, KZ is hydrogen and K7e is hydrogen; a compound of Formula (50), in which KZ is -M (EO 5", K72 is methyl, K7? is hydrogen, Ks is methyl, BZ is hydrogen and Be is hydrogen; 70 a compound according to Formula (50) in which KZ is -M (CH CM)", K72 is methyl, K7? is hydrogen, B is methyl, KZ is hydrogen and Be is hydrogen; a compound according to Formula (50), in which EZ is - МНСН (Ме) (СНоОМе), 72 is methyl, EC" is hydrogen, B" is methyl, BZ is hydrogen and Be is hydrogen; a compound of Formula (50) in which BZ is -ОСН (EO (СНоОМе), 72 is methyl, B? is 19 hydrogen, VU is methyl, BZ is hydrogen and B? is hydrogen; a compound according to Formula (50), in which BZ is -M ( n-P) (CHocRg), B" represents methyl, B" represents is hydrogen, B is methyl, KZ is hydrogen and Be is hydrogen; a compound according to Formula (50), in which BZ is -MNOH (Me) (CH M (Me)", 72 is methyl, B 79 is hydrogen, B" is methyl, B is hydrogen and Be is hydrogen; a compound according to Formula (50), in which K3 is -M (cPg) (CHNoCHHCM), K72 is methyl, K7? is hydrogen, B" is methyl, B is hydrogen and Be is is hydrogen; a compound according to Formula (50), in which KZ is -M (p-Pg) (СНСНОСМ), 272 is methyl, B 7? is hydrogen, VU is methyl, B. is hydrogen and B" is hydrogen; c is a compound according to Formula (50), in which BZ is -M (p-Vy) (CH CM), 2 is methyl , B? represents -:(C) is hydrogen, B" represents methyl, B represents hydrogen and Be represents hydrogen; a compound according to the Formula (50), in which KZ is -MNCH (EO (CHNoOMEe), 272 is methyl, B 7? is hydrogen, B" is methyl, BZ is hydrogen and Be is methyl; so the compound according to Formula (50), in which KZ is -MNSN (ED 2, K72 is methyl, B? is hydrogen, VU is methyl, BZ is hydrogen and B" is methyl; a compound according to the Formula ( 50), in which BZ is -M (СНОСНоОМе)", B2 is methyl, B? is hydrogen, B is methyl, B is hydrogen and B"e is methyl; it is a compound according to the Formula (50 ), in which KZ is -MNSN (SNoOMe)", 72 is m bromine, B" is hydrogen, B. 77 is OMe, B 79 is hydrogen and Be is hydrogen; the compound according to the Formula (50 ), in which KZ is -MNSN (EO (СНОМ е)), VL is bromine, B 7" is hydrogen, B 797 is OMe, B 79 is hydrogen and Be is "470 hydrogen; - c compound according to Formula (50), in which KZ is -M (EO 5", K72 yav is methyl, K 7? is "» hydrogen, Ks is methyl, BZ is hydrogen and Be is methyl; " a compound according to Formula (50) in which BZ is -MNOH (СНоОЕО», B? is methyl, B? represents hydrogen, VU represents methyl, BZ represents hydrogen and B" represents methyl; -1 that the compound according to Formula (50), in which ЕZ represents -МНСН (СНоСНоОМе)», К72 represents methyl, EC" ? represents hydrogen, B" represents methyl, BZ represents hydrogen and Be represents methyl; o a compound according to Formula (50), in which KZ represents morpholine, B 72 represents methyl, B 7? represents (co) hydrogen, B is methyl, B is hydrogen and B"e is methyl; -l 20 is a compound according to Formula (50), in which ECZ is -"M (CHNSNoOMe)", B72 is bromine, KK? is is hydrogen, VK 77 is OMe, VK 7 is hydrogen and K "2 is hydrogen; the compound according to Formula (50), in which KZ is -MNSN (EO 5, K72 is bromine, B? is is hydrogen, VS is OMe, VZ is hydrogen, and Be is pure emits hydrogen; a compound according to Formula (50), in which KZ is -M (ЕОЯ 5, Ka is bromine, B 7? is

Ф) hydrogen, Ks represents OMe, BZ represents hydrogen and B" represents hydrogen; k is a compound according to Formula (50), in which KZ represents -MH (c-Pg), VK 72 represents methyl, K 7 ? represents hydrogen, B represents methyl, KZ represents hydrogen and Be represents hydrogen; for the compound according to Formula (50), in which KZ represents -MNCHN (SNoOMe)", B: represents CM, B"? represents hydrogen, BC represents OMe, BZ represents hydrogen and Be represents hydrogen; a compound according to Formula (50), in which KZ is -M (c-Pg) (СНСНСНСМ), К72 is methyl, К7? represents hydrogen, VU represents methyl, KZ represents hydrogen and B" represents methyl; to a compound of Formula (50) in which 2? represents -MSH (CHNoOMe)", B72 represents methyl, B" represents represents hydrogen, VU represents bromine, VU represents hydrogen and BC" represents hydrogen;

a compound according to the Formula (50), in which BZ is -MNH (CHNoOMe) (CHNOCHNoOMe), Ba is methyl, B "7? is hydrogen, VB.7- is bromine, K M is hydrogen and KB" : represents hydrogen; a compound according to Formula (50), in which KZ is -MHNH (CH OMe)", K72 is methyl, B 7? represents hydrogen, VU represents OMe, BZ represents methyl and Be represents hydrogen; a compound according to the Formula (50), in which KZ is -"M (СНСНООМе)", 272 is methyl, B" is hydrogen, B is OMe, B is methyl and Be is hydrogen; 70 a compound of Formula (50), in which BZ is -MNSON (EbO 5 ", B72 is methyl, BK 7? is hydrogen, B: is OMe, 279 is methyl and B" is hydrogen; a compound according to the Formula (50), in which KZ represents -M (EO 5", K72 represents methyl, K 7? represents hydrogen, Ks represents OMe, BZ represents methyl and Be represents hydrogen; the compound according to Formula (50), in which 2? is -MNCH (CHNoOMe)", 72 is chlorine, VE" is hydrogen, BC is methyl, KZ is hydrogen and VC" is hydrogen; a compound according to Formula (50), in in which C is -MNCH (EO (CHNoOMe)", BZ is chlorine, B" is hydrogen, B 72 is methyl, BZ is hydrogen and B" is hydrogen; a compound according to Formula (50), in which KZ is -"M (СНСНООМе)", 272 is chlorine, KE"? i is hydrogen, B is methyl, KZ is hydrogen, and Be is hydrogen; compound according to Formula (50), in which 2? represents -MNSN (СНоОМе) (СНоСНоОМе), 72 represents chlorine, B 7? represents hydrogen, B 77 represents methyl, B 79 represents hydrogen and KB": represents hydrogen; c 29 is a compound according to the Formula (50), in which KZ represents -M (c-Pg) (CHNoCNHCM), Ba represents itself methyl, BC"? is (In is hydrogen, VU is OMe, BZ is methyl and Be is hydrogen; a compound according to Formula (50), in which KZ is --M (c-Pg) (СНоСНЬСМ), Ba is chlorine, B" is hydrogen, B.7- is chlorine, B 79 is hydrogen, and BK" is hydrogen with itself; a compound according to Formula (50), in which KZ is (5)-MHNH (СНоОМе) - (СНоСНоОМе), 72 represents chlorine, ВК 7? represents hydrogen, В 77 represents chlorine, БК 79 represents Ф hydrogen and КБ": represents hydrogen; so a compound according to Formula (50), in which КЗ is -MNSN (SNoOMe)

Zo (СНоСНоОМе), 72 is chlorine, ВК 7? represents hydrogen, B 77 represents chlorine, BK 79 represents - hydrogen and KB": represents hydrogen; a compound according to Formula (50), in which BZ represents -MNSON (EO 2, 272 represents methyl, B? represents is hydrogen, VU is bromine, VU is hydrogen and BK" is hydrogen; " a compound according to Formula (50), in which EZ is -"M (СНоСНоМе)", 272 is methyl, B? is ("Od c is hydrogen, 77 is bromine, 79 is hydrogen, and VK" is hydrogen; "" a compound according to Formula (50), in which VZ is -MNHN (CH OMe) (CH»-iRg), K72 represents methyl, B 79 " represents hydrogen, BC represents methyl, B represents hydrogen and Be represents hydrogen; a compound according to Formula (50), in which KZ represents -"M (СНСНООМе)", 272 represents methyl , B" is hydrogen, KS is hydrogen, BZ is hydrogen and K"e is hydrogen; a compound according to Formula (50), in which EZ is -M (СНоСНоМе)», В" is is methyl, B" is hydrogen, B: is MMe", B is sob o hydrogen and B"? is hydrogen;

Ge) a compound according to the Formula (50), in which KZ is -MNCHN (CHNoOMe) (p-Pg), B72 is methyl, EC" is shu 20 is hydrogen, B": is methyl, 79 is hydrogen and B: represents hydrogen; a compound according to the Formula (50), in which KZ is -MNCH (CHNoOEU (ED, K72 is methyl, K7? is hydrogen, B" is methyl, BZ is hydrogen and Be is hydrogen; the compound according to Formula (50), in which KZ is -MNHN (SNoOMe) ria (SNoSNoOMe), 72 is methyl, B "7? is hydrogen, B 7-7 is MMe", BZ is hydrogen and B" is hydrogen;

F) a compound according to Formula (50), in which KZ is -M (EO", K72 is methyl, KB" is hydrogen, B: is chlorine, BZ is hydrogen and B": is hydrogen ; a compound according to Formula (50), in which KZ is -MNCHN (EX 5, K72 is methyl, K 7? is 60 hydrogen, B" is chlorine, KZ is hydrogen and Be is hydrogen; a compound of Formula (50), in which KZ is -"M (СНСНООМе)", 272 is methyl, B" is hydrogen, KS is chlorine, BZ is hydrogen and Be is hydrogen; the compound of Formula (50 ), in which EZ is -M (СНоСНоОМе)", В" is methyl, В" is б5 Hydrogen, В: is chlorine, КЗ is hydrogen and "2 is hydrogen; a compound according to the Formula ( 50), in which KZ is -M (SNoOMe)", K72 is methyl, K7? is hydrogen, KS is chlorine, BZ is hydrogen and Be is hydrogen; the compound according to Formula (50), in in which B C represents -M (EO 5", BZ represents methyl, B 7? represents is hydrogen, Ks is bromine, KZ is hydrogen and K": is hydrogen; a compound according to Formula (50), in which KZ is -M (EO 5", B" is chlorine, B 7? is hydrogen, Ks is methyl, BZ is hydrogen and Be is hydrogen; a compound of Formula (50), in which KZ is -MNSN (EO 5, K72 is chlorine, K7? is hydrogen, B is methyl, KZ is hydrogen and Be is hydrogen; 70 compound according to Formula (50) , in which KZ represents -MNSN (ED 2, K72 represents methyl, B? represents hydrogen, B represents MMe", BZ represents hydrogen and KK": represents hydrogen; a compound according to Formula (50) in which BZ is (5)-MNCH (SNoOMe) (SNoCNoOMe), 72 is methyl, B "7? is hydrogen, B 79 is methyl, B. 79 is hydrogen and KB": is hydrogen; t compound according to the Formula (50), in which B Z is MNON (CH OMe) (СНСНОООМе), Cl is methyl, K 15 is hydrogen, B 77 is methyl, BZ is hydrogen and ВК" is hydrogen; a compound according to Formula (50), in which KZ is (5)-MHNH (СНоОМ f) (СНоСНоМе), 72 is methyl, B 7? represents hydrogen, B 77 represents chlorine, B 79 represents 20 hydrogen and B": represents hydrogen; a compound of Formula (50) in which KZ is -MNH(CHNoOMe) (CHNOCHNoOMe), 72 is methyl, B 7? represents hydrogen, B 77 represents chlorine, B 79 represents hydrogen and KB": represents hydrogen; 25 a compound according to the Formula (50), in which EKZ is -M (c-Pg) (СНСННСМ), 72 сх is methyl, ВК" is hydrogen, ВК 77 is chlorine, B 79 is hydrogen and B "? represents (o) hydrogen; compound according to the Formula (50), in which KZ is -MH (EO (СНСМ), 272 is methyl, KB" is hydrogen, 77 is chlorine, KZ is hydrogen and Be is hydrogen; so 30 compound according to Formula (50), in which KZ represents -M (ЕЯ 5, Ka represents methyl, B 7? represents - methyl, K4c represents OMe, BZ represents hydrogen and BK" represents hydrogen; a compound according to the Formula (50), in which ЕЗ is -M (СНоСНоОМе) (СНоСН-ОН), Б 2 is chlorine, ВК 79 ia is hydrogen, B" is chlorine, BZ is hydrogen and ВК" is hydrogen; so 35 is a compound according to Formula (50), in which ECZ is -"M (CHNSNoOMe)", B72 is methyl, B" is methyl, B7c is OMe, B79 is hydrogen, and B. " represents hydrogen; a compound according to Formula (50), in which BZ represents -MNSON (EbO 5 ", B72 represents methyl, VK 7? represents methyl, B: represents OMe, 279 represents hydrogen and B? represents is hydrogen; « 40 a compound according to Formula (50), in which VZ is -M (CH os-Pg ) (p-Pg), Ba is methyl, B? represents (-- c is hydrogen, BC is chlorine, KZ is hydrogen and Be is hydrogen; c" is a compound according to Formula (50), in which KZ is -M (c-Pg) (СНСНСНСМ), К72 is is methyl, K 7? is methyl, Bc is OMe, BZ is hydrogen and Be is hydrogen; a compound according to Formula (50), in which KZ is -MNCHN (ED", B72 is -1 chlorine, B? represents hydrogen, KU represents OMe, BZ represents hydrogen and Be represents hydrogen; a compound according to Formula (50), in which B C represents -M (EO 5", B72 represents chlorine, B "7? o is hydrogen, Ks is OMe, BZ is hydrogen and Be is hydrogen; is), a compound according to Formula (50), in which KZ is -"M (СНСНООМЕе) 5, B72 is шу 70 is chlorine, B" represents hydrogen, B 77 represents OMe, VK 7 represents hydrogen and K 7? represents hydrogen; c" is a compound according to Formula (50), in which KZ represents -MNSN (EO (СНоОМе)), Ba represents is chlorine, B" is hydrogen, B.77 is OMe, B 79 is hydrogen t and Be represents hydrogen; a compound according to Formula (50), in which KZ represents -M (EO 5", B" represents chlorine, B 7? represents

F) hydrogen, Ks represents CM, VZ represents hydrogen and Be represents hydrogen; to the compound according to Formula (50), in which KZ is -M (c-Pg) (СНСНСНСМ), К72 is chlorine, B? represents hydrogen, VU represents OMe, VZ represents hydrogen and Be represents hydrogen; for a compound according to Formula (50), in which KZ is -MNCHN (CHNOOH)", B72 is chlorine, B" is hydrogen, B. 77 is chlorine, KZ is hydrogen and Be is hydrogen; the compound according to Formula (50), in which EZ is -M (СНоСНоМе)», В? represents methyl, B" represents hydrogen, 77 represents Shyu, BZ represents hydrogen, and Be represents hydrogen. 65 HER Especially the best compounds are 4-(bis-(2-methoxyethyl)amino)- 2,

7-dimethyl-8-(2-methyl-4-methoxyphenyl)-(1,5-α|-pyrazolo-1,3,β-triazines and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutical forms permissible salts or prodrugs. |-pyrazolo-1, C, Bb-triazines and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and the forms of their pharmaceutically acceptable salts or prodrugs. 41) The best compounds of the above invention are compounds and their isomers, their stereoisomeric forms or mixtures their stereoisomeric forms, and forms of their pharmaceutically acceptable salts or prodrugs, in which

A is a SC. 70 42) Preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or prodrug forms thereof.

The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms in which

Ag is phenyl, pyridyl, or 2,3-dihydrobenzofuranyl, and each Ag is optionally substituted with substituents from!Ido AK.

I44| Preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or prodrug forms thereof in which

VZ is Mar 72 or OV. (45) The preferred compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms, in which

Ag is phenyl, pyridyl, or 2,3-dihydrobenzofuranyl, and each Ag is optionally substituted with 1 to 4 substituents B" and EZ is MAV, 2, or OB 7.

І46І The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and the forms of their pharmaceutically acceptable salts or prodrugs, in which CM 7 is CB, о 47 The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and forms of their pharmaceutically acceptable salts or prodrugs in which

Ag is phenyl, pyridyl, or 2,3-dihydrobenzofuranyl, and each Ag is optionally substituted with 1 to 4 substituents 7. and

I48| Preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or prodrug forms thereof in which

VE is MAV 72 or OB. b (49) The best compounds of the above invention also include compounds and their isomers, their stereoisomeric c forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms in which

Ag is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ag is optionally substituted with 1 to 4 substituents B" and EZ is MAZav "a or OB 7. (BOY The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and the forms of their pharmaceutically acceptable salts or prodrugs, in which "20 ba and vya is independently hydrogen or C 4-C 40 alkyl and each such C 4-C 40 alkyl is -in with optionally substituted substituents from 1 to 3, which are independently selected in each implementation from the group: C 4-Cv alkyl, Ca-Cv cycloalkyl, halo, C-C haloalkyl, cyano, ОБ", 5Н, (008, -СОВ", сов" осС(ОВУ, и"? Me8сОov 5, щСОв 5, MeЗСОоМе 9в75, Me8сОov З, Me 9в"5, СОМ ev 5, aryl, heteroaryl or heterocyclyl. (01) The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and their pharmaceutically acceptable salt or prodrug forms, in which: - And -Ag is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ag is optionally substituted with substituents from 1 to 4 7, -KZ is MAV 72 or OK", and -B is independently selected from the group: hydrogen , C4-C6 alkyl, C3-C8 cycloalkyl, C1-C40 cycloalkylalkyl. is), (52) The best compounds of the above invention also include compounds and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and the forms of their pharmaceutically acceptable salts or prodrugs, in which Ba and Vya independently represent hydrogen or C 4-C 40 alkyl and each such C 4-C 40 alkyl is optionally substituted with substituents from 1 to 3, which are independently selected in each implementation from the group: C 4-C 4 alkyl, C 4-C 4 cycloalkyl, halo, C .-C4 haloalkyl, cyano, OK", 5H, 5(0)083, -СОВ"5, sov", oso,

Me8sOov 5, shSOv 5, MeZSOoMe 9v75, Me8sOov Z, Me 9v"5, СОМ ev 5, aryl, heteroaryl or heterocyclyl.

Especially preferred compounds of the above-mentioned invention are compounds according to Formula (51):

Ф) име) 60 b5 zer, DR da chav and dyaj de

Formula-(51). and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and the forms of their pharmaceutically acceptable salts or prodrugs, which are selected from the group containing: 20 a compound according to Formula (51), in which KZ is -MNSN (p-Pg) ", K72 is methyl, K 7? represents hydrogen, B represents methyl, KZ represents hydrogen and Be represents hydrogen; a compound according to Formula (51), in which KZ is -MHNH (CH 2OMe)", K72 is methyl, B 7? represents hydrogen, B" represents methyl, B" represents hydrogen and Be represents hydrogen; compound according to Formula (51), in which BZ is -M(СНоСНоОМе)", Б72 is methyl, B? is /-: CM 25 is hydrogen, VU is methyl, BZ is hydrogen and B" is hydrogen; Ho) a compound according to Formula (51), in which KZ is -M (c-Pg) (СНоСНЬСМ) , 72 represents methyl, K 7? represents hydrogen, VU represents methyl, BZ represents hydrogen and B"? is hydrogen; a compound according to Formula (51), in which KZ is -"M (СНаСНоМе)", В" is chlorine, BC" is (c 30 is hydrogen, BC is methyl, BZ is hydrogen and B": is hydrogen; a compound according to Formula (51), in which KZ is -MNCHN (SNoOMe)", 72 is chlorine, BC" ? is hydrogen, B is methyl, KZ is hydrogen and Be is hydrogen; (22) a compound according to Formula (51), in which KZ is -MNSN (EO 5, K72 is chlorine, K 7? represents CO 35 hydrogen, VU represents methyl, BZ represents hydrogen and B" represents hydrogen; m a compound according to Formula (51), in which B C represents -M (EO 5", BZ represents methyl, B 7? is hydrogen, Ks is methyl, BZ is hydrogen and Be is hydrogen; a compound of Formula (51) in which EZ is -M(p-Pg) (CHNoCHNoCM)", 272 is methyl, VK" is hydrogen, VU is methyl, BZ is hydrogen, and B" is hydrogen; 40 a compound according to Formula (51), in which EZ is -M (p-Vy) (CHNoCNHSM), la represents methyl, B" represents C with hydrogen, VU represents methyl, BZ represents hydrogen and B"? is hydrogen; "c is a compound according to Formula (51), in which KZ is -MNCHN (p-Pg) (CH OMe)", 72 is methyl, B 79 is hydrogen, BC is methyl, B is hydrogen and Be is is hydrogen; a compound according to Formula (51), in which KZ is -MNSN (ED 2, K72 is methyl, B? is -and hydrogen, BC is OMe, BZ is hydrogen and Be is hydrogen; the compound according to Formula (51), in which KZ is -MNCH (CH OMe)", K72 is methyl, B 7? is hydrogen, B" is OMe, BZ is hydrogen and B" is hydrogen; so a compound according to the Formula (51), in which ЕZ is (5) -МНСН (СНоСНоОМе) -о 70 СНоОМе, 272 is methyl, КЕ" is hydrogen, KS is methyl, КУ is hydrogen (c and 72 is hydrogen, a compound according to Formula (51) in which KZ is -MH(СНоСНоОМе) СНоОМе, 72 is methyl, B is hydrogen, BC is methyl, B is hydrogen and Be is hydrogen ; a compound according to Formula (51), in which IVF represents - "M (СНСНоОМе)", 272 represents methyl, B"? represents hydrogen, VU represents chlorine, BZ represents hydrogen and B"e represents hydrogen; o a compound according to Formula (51), in which B represents -MH (EO, 72 represents methyl, B" represents hydrogen , where Bc is methyl, BZ is hydrogen and Be is hydrogen, a compound of Formula (51) in which KZ is -MH (EO, K72 is methyl, KE" is hydrogen, 60 gives is methyl, BZ is hydrogen and Be is hydrogen; a compound according to Formula (51), in which KZ is -MNH(p-Pg)", K72 is methyl, K"9? is hydrogen, 77 is chlorine , KZ is hydrogen and Be is hydrogen, a compound according to Formula (51), in which BZ is -MNSON (CH OMe)", 72 is methyl, B 7? is 65 hydrogen, VU is chlorine, BZ is hydrogen and B" is hydrogen; a compound according to Formula (51), in which BZ is (5) -MH (СНоСНоОМе) СНоОМе, 72 is methyl, оо is hydrogen, КУ is chlorine, BZ is is hydrogen and VC" is water Yen; a compound according to Formula (51), in which KZ is -MH (СНоСНоОМе) СНоОМе, La is methyl, B is hydrogen, B" is chlorine, BZ is hydrogen and Be is hydrogen; a compound of Formula ( 51), in which KZ is -M (p-Pg) (СНСНОСМ), K72 is methyl, K7? is hydrogen, VU is OMe, BZ is hydrogen and Be is hydrogen; the compound according to the Formula ( 51), in which KZ is -M (EO 5", K72 is methyl, KB" is hydrogen,

Bs is OMe, BZ is hydrogen, and Be is hydrogen; 70 a compound according to Formula (51), in which ЕZ is (5) -МН (СНоСНоОМе) СНоОМе, B" is chlorine, P is hydrogen, KU is methyl, B" is hydrogen and B" : represents hydrogen; a compound according to Formula (51) in which BZ is -MH (CH oSNoOMe) СNoOMe, 72 is chlorine, B is hydrogen, BC is methyl, B is hydrogen and Be is hydrogen ; a compound according to Formula (51), in which KZ represents -M (EO 5, Ka represents chlorine, B 7? represents 75 hydrogen, K4c represents methyl, BZ represents hydrogen and B? represents hydrogen; a compound of Formula (51), in which KZ is -M (c-Pg) (CHNoCHHCM), 72 is methyl, K 7 is hydrogen, VU is OMe, BZ is hydrogen and Be is hydrogen; the compound is Formula (51), in which KZ is -M (c-Pg) (CHNoCHHCM), K72 is chlorine, B? is hydrogen, B- is methyl, KZ is hydrogen and BK" is hydrogen; the compound according to Formula (51), in which KZ is -M (p-Pr) (CH OMe), Kg is methyl, K 7? represents hydrogen, VU represents OMe, VZ represents hydrogen and Be represents hydrogen; a compound according to Formula (51), in which C is -MNCH (p-Pg) (CHNoOMe), 72 is chlorine, B" is hydrogen, B 77 is methyl, B" is hydrogen and B" is c 29 is hydrogen; Ge) a compound according to Formula (51), in which KZ is -MNSN (EO 5, K72 is bromine, B? is hydrogen, BC is OMe, BZ is hydrogen and Be is hydrogen; a compound according to Formula (51), in which VK is -MNON (ED 2, B" is bromine, BK" is hydrogen, B: is OMe, 279 is hydrogen and B" is is hydrogen; a compound according to Formula (51), in which BZ is -M (СНаСНоОМе)", В" is bromine, КЕ" is hydrogen, ВК 77 is ОМе, КЗ is hydrogen and B? is -: 0 hydrogen; c is a compound according to Formula (51), in which KZ is -MNCHN (СНоОМе)", 72 represents

Z is bromine, B" is hydrogen, B. 77 is OMe, B 79 is hydrogen and Be is hydrogen; a compound according to Formula (51), in which B C is -M (EO 5", BZ represents methyl, B7? represents hydrogen, Ks represents chlorine, KZ represents hydrogen and K": represents hydrogen; " a compound according to Formula (51), in which KZ represents -M (EO 5", B "? represents chlorine, B 7? represents sh-v c hydrogen, Ks represents OMe, BZ represents OMe and VK" represents hydrogen; "c is a compound according to Formula (51), in which KZ represents -MNSN (EYUO 5, K72 represents chlorine, K7? represents "hydrogen, BC represents OMe, BZ represents OMe and Be represents hydrogen; a compound according to Formula (51), in which KZ represents -"M (СНСНООМЕе) 5, B72 represents - 395 is chlorine, B" is hydrogen, B. 77 is chlorine, KZ is hydrogen and Be is hydrogen; o a compound according to Formula (51), in which C is -MNHN (СНоОМе )", B72 represents chlorine, B" represents

Ge) is hydrogen, 77 is chlorine, KZ is hydrogen and Be is hydrogen; pub compound according to Formula (51), in which KZ represents -M (Рг) (СН -СНоСМ), Be represents chlorine, B 7? represents hydrogen, BC represents chlorine, KZ represents hydrogen and Be represents hydrogen; c» a compound according to Formula (51), in which BZ is -M (Vy) (E)U, B72 is chlorine, B? is hydrogen, 72 is chlorine, 79 is hydrogen and B" is hydrogen; a compound of Formula (51) in which BZ is -MNON (EO CH oOMe, B is chlorine, B 7? is hydrogen, VU is chlorine, BZ is hydrogen and B"e is hydrogen; (F) a compound according to Formula (51), in which C is -MNCHN (E)O », B" is

GI chlorine, B? is hydrogen, 72 is chlorine, 79 is hydrogen and B" is hydrogen; a compound according to Formula (51), in which KZ is -MNSN (ED 2, K72 is methyl, B? is 6o hydrogen , B" represents methyl, BZ represents hydrogen and B": represents hydrogen; a compound according to Formula (51), in which KZ represents -MNSN (EO 5, K72 represents chlorine, K 7? represents hydrogen, VU represents methyl, BZ represents hydrogen and B" represents hydrogen; a compound according to Formula (51), in which BZ represents -MNSON (EbO 5", B72 represents methyl, VK 7? represents de Hydrogen, B" : represents chlorine, BZ represents hydrogen and B"e represents hydrogen; a compound according to Formula (51), in which KZ represents -M (EO 5", K72 represents methyl, K 7? represents hydrogen, Ks represents is OMe, BZ is hydrogen and Be is hydrogen, and the compound according to Formula (51), in which KZ is -M (Pg) (CH»СНоСМ), 72 is methyl, B is hydrogen, VU is is OMe, BZ is hydrogen and Be is hydrogen; ( 54 Especially best are 7-(3-pentylamino)-2, 5-dimethyl-3-(2-methyl-4-methoxyphenyl)-(1, 5-a) pyrazolopyrimidines and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms , and forms of their pharmaceutically acceptable salts or prodrugs.

І55І Particularly best are 7-(diethylamino)-2, 5-dimethyl-3-(2-methyl-4-methoxyphenyl)-(1, 5-a) 70 pyrazolopyrimidines and their isomers, their stereoisomeric forms or mixtures of their stereoisomeric forms, and forms of their pharmaceutically acceptable salts or prodrugs.

Especially best are 7-(M-cyanopropyl)-M-propylamino)-2, 5-dimethyl-3-(2, 4-dimethylphenyl)-(1, 5-a| pyrazolopyrimidines and their isomers, their stereoisomeric forms or mixtures their stereoisomeric forms, and the form of their pharmaceutically acceptable salts or prodrugs.

The present invention also provides pharmaceutical compositions comprising compounds of Formulas (1) and (2) and a pharmaceutically acceptable carrier.

Most of the compounds according to this invention have one or more asymmetric centers or planes. Unless otherwise stated, all chiral (enantiomeric and diastereomeric) and racemic forms are included in the present invention. A large number of geometric isomers of olefins, C-M double bonds and the like may be present in the compounds described herein, and all such stable isomers are contemplated by the present invention. The compounds of this invention can be isolated in optically active or racemic forms. Those skilled in the art are well aware of how to prepare optically active forms, either by decomposition of racemic forms or by synthesis of optically active starting materials. All chiral (enantiomeric and diastereomeric) and racemic forms and all geometrically isomeric forms of the structure are assumed unless the specific stereochemical form or isomeric form is not specifically indicated. at

The term "alkyl" includes both branched and straight chain alkyl having a specific number of carbon atoms. Commonly used abbreviations have the following meanings: Me is methyl, Ej is ethyl, Pg is propyl, and B is butyl. The prefix "n" means straight-chain alkyl. The prefix "c" means cycloalkyl. The prefix "5" means the C enantiomer, and the prefix "B" means the B enantiomer. "Alkenyl" includes hydrocarbon chains in both straight and branched configurations and one or more unsaturated carbon-carbon bonds that may occur at any stable point along the chain, such as ethenyl, propenyl, and the like. "Alkynyl" includes hydrocarbon chains of both straight and branched (2) configuration and one or more carbon-carbon triple bonds which may occur at any stable point along the chain, such as ethynyl, propynyl and the like . "Haloalkyl" is intended to include both branched and straight-chain alkyl having a particular c. the number of carbon atoms replaced by one or more halogens; "Alkoxy" represents an alkyl group of the indicated number of carbon atoms connected by an oxygen bridge; "cycloalkyl" is intended to include saturated ring groups, including mono-, bi-, or polycyclic ring systems such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. "Halo" or "halogen" includes fluorine, chlorine, bromine and iodine. t c The term "substituted" as used herein means that any one or more hydrogen atoms "" on the indicated atom are replaced by one selected from the group shown, while ensuring that the normal " valency of the indicated atom is not exceeded, and that as a result of substitution, a stable compound is obtained.

When the substituent is keto (ie, -0), then 2 hydrogen atoms are substituted on the atom.

Combinations of substituents and variables or only variables are permissible only if such combinations result in stable compounds. The term "stable compound" or "stable structure" as used herein means a compound which is sufficiently stable to maintain a useful degree of purity of the reaction mixture upon isolation and which is formulated on the basis of an effective therapeutic agent. The term "appropriate protecting amino acid group" means any group known to those skilled in the art of organic synthesis to protect amine groups or carboxylic acid groups. Such amine protecting groups include those listed in Sgeepe apa UUtsiv, "Protecting Groups in Organic Synthesis" ("Rgoyesiime OSgocrz ip Ogdapisv s" Zupipeviv") dopyp UUieu apa bop5, Mem Hogg (1991) and "Peptides: Analysis, Synthesis , Biology", Vol. 3, Academic Edition, New York (1981), the disclosures of which are incorporated herein by reference. Any amine protecting groups known to those skilled in the art can be used. Examples of amine protecting groups include, but are not limited to, the following: 1) acyl types such as formyl, trifluoroacetyl, phthalyl, and p-toluenesulfonyl; 2) types

GF! aromatic carbamates, such as benzyloxycarbonyl (Сб7) and substituted benzyloxycarbonyls, i-(p-biphenyl)-1-methylethoxycarbonyl and 9-fluorenylmethyloxycarbonyl (Etos); types of aliphatic carbamates such as tert-butyloxycarbonyl (Boc), ethoxycarbonyl, diisopropylmethoxycarbonyl and allyloxycarbonyl; 4) types of cyclic alkyl carbamates, such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; 5) types of 60 alkyl, such as triphenylmethyl and benzyl; 6) trialkylsilane, such as trimethylsilane; and 7) thio-containing types such as phenylthiocarbonyl and dithiasuccinoyl.

The term "pharmaceutically acceptable salts" includes acidic or basic salts of compounds of formulas (1) and (2).

Examples of pharmaceutically acceptable salts include, but are not limited to, salts of basic residues of mineral and organic acids, such as amines; alkali, or organic salts of acid residues, such as carboxylic acids and the like.

Pharmaceutically acceptable salts of the compounds of the invention can be made using the free acidic and basic forms of these compounds with a stoichiometric amount of the appropriate base or acid, respectively, in an aqueous or organic solution, or in a mixture of the two; in general, preferred non-aqueous agents are ether-like, ethyl acetic acid, ethyl alcohol, isopropyl alcohol, or acetonitrile alcohol. A list of suitable salts can be found in Ketipdiopye RpagtaseciisaIz Zsiepsev, 17, ed., Mask Ryviyivpipd Sotrapu,

Eazyup, RA, 1985, p. 1418, the disclosure of which is incorporated herein by reference. "Prodrugs" are considered to be any covalently bound carriers that deliver active parent drug agents according to Formulas (I) or (II) when such prodrugs are administered to a mammalian subject. Prodrugs of compounds according to Formulas (I) and (II) are made by modifying the functional groups existing in the compounds in such a way that the modifications remain, either with the help of established manipulations or immemorial, faithful to the original compounds. Prodrugs include compounds in which hydroxyl groups, amino groups, sulfhydryl groups, or carboxyl groups are linked by any group such that when administered to a mammalian subject, they are cleaved to form, respectively, free hydroxyl groups, amino groups, sulfhydryl groups or carboxyl groups. Examples of prodrugs include, but are not limited to, alcohol derivatives of acetates, formates and benzoates and amine functional groups in compounds of Formulas (I) and (II), and the like.

The term "therapeutically effective amount" of a compound of this invention means an amount that can effectively counteract a pathological level of SKE or treat symptoms of affective disorders, disorders related to anxiety or depression in the body.

Synthesis.

Certain compounds of Formula (1) can be prepared from intermediates of Formula (7) using the procedures shown in Scheme 1:

Compounds for

Scheme 1 of their thalloid agent or other. Sulfonylating agent Ж со зо 0000 жро /сонования, -/-solvent 00 как" t, ! ke tav Y -

Ak yh i - (1) 7 vo (8x « ny Z s v :» sh ry

VN, zh /- basis, nor 4-7 "solvent ii and Z ' (95) E- | ba ke) de - 50 a) Am syu"

Formula (7) (wherein M is oxygen) can be introduced with a halogenating agent or a sulfonylating agent in the presence or absence of a base in the presence or absence of a neutral solvent at a reaction temperature in the range of -80 degrees Celsius to 250 degrees Celsius, which gives products for

Formula (8) (in which X is halogen, alkanesulfonyloxy, arylsulfonyloxy, or

IF) haloalkane-sulfonyloxy). Halogenating Agents include, but are not limited to, 5OS15, ROSI1z, RS15, RS15, РОВГгз, РВгз or РВг», etc. Sulfonylating Agents include alkanesulfonyl halides or alkanesulfonyl anhydrides (such as methanesulfonyl chloride or methanesulfonyl anhydride), arylsulfonyl halides or arylsulfonyl anhydrides (such as p-toluenesulfonyl chloride or p-toluenesulfonyl anhydride) or haloalkylsulfonyl halides or haloalkylsulfonyl anhydrides (preferably . Bases may include, but are not limited to the following, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (with the number of carbon atoms from 1 to b) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal 65 hydrides, alkali metal dialkylamides (preferably lithium diisopropylamide), alkali metal bis(trialkylsilyl)amides (preferably sodium bis(trimethylsilyl)amide), trialkylamines (preferably M, M-diisopropyl-M-ethyl amine or triethylamine ) or aromatic amines (it is better when it is pyridine). Neutral solvents may include, but are not limited to, lower alkanitriles (having 1 to 6 carbon atoms, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4 -dioxane), M, M-dialkylformamides (it is better when they are dimethylformamides), M,

M-dialkylacetamides (better when it is dimethylacetamide), cyclic amides (better when it is M-methylpyrrolidin-2-one), dialkyl sulfoxides (better when it is dimethyl sulfoxide), aromatic hydrocarbons (better when it is benzene or toluene) or haloalkanes with the number of carbon atoms from 1 to 10 and the number of halogens from 1 to 10 (it is better when it is dichloromethane). The best reaction temperature range is from -20 to 100 degrees Celsius. 70 Compounds of Formula (8) can react with compounds of Formula BZN (in which BZ is defined as above, except that BZ is not ZN, SOK", CO»B", aryl or heteroaryl) in the presence or in the absence of the presence of a base or in the absence of a neutral solvent, in the range of reaction temperatures from -802C to 2502C, which makes it possible to generate compounds according to Formula (1). Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (having 1 to 6 carbon atoms) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium diisopropylamide), alkali metal carbonates, alkali metal bicarbonates, alkali metal bis(trialkylsilyl)amides (preferably sodium bis(trimethylsilyl)amide), trialkylamines (preferably M, M-di- isopropyl-M-ethylamine or triethylamine) or aromatic amines (it is better when it is pyridine). Neutral solvents may include, but are not limited to, alkyl alcohols (C1 to C8, preferably methyl alcohol or ethyl alcohol), lower alkanitriles (C1 to C6, preferably acetonitrile) , dialkyl ethers (it is better when it is diethyl ether), cyclic ethers (it is better when it is tetrahydrofuran or 1, 4-dioxane), M, M-dialkylformamides (it is better when it is dimethylformamide), M,

M-dialkylacetamides (better when it is dimethylacetamide), cyclic amides (better when it is M-methylpyrrolidin-2-one), CM dialkyl sulfoxides (better when it is dimethyl sulfoxide), aromatic hydrocarbons (better when it is benzene or o toluene) or haloalkanes with an amount carbon atoms from 1 to 10 and the number of halogens from 1 to 10 (it is better when it is dichloromethane). The best reaction temperature range is from 02C to 14020C.

Scheme 2 describes procedures for the conversion of intermediates of Formula (7) (wherein U is sulfur) to certain compounds of Formula (1). so z-d. Compounds according to Formula (7) (y

Scheme 2. - (22) so z5 x pe, zve ze

ВХ, ж/- base; sieve OI 0 solvent sa ; Y M, shi poko rukh OO "

Sha and slia u ts ; ! ! h. 415 oxidizing agent: 27 their solvent. ВН, Ж/- оспования and svi solvent Ж

Mami xx tiu zhk /«- solvent. with Ba in "Zh. and then, ! and 7 pi solvent vd

(13) (2) and in which M is sulfur) can be introduced with the alkylating agent К ХХ (in which КЗ is defined as 60 above, except that ЕК "З is not an aryl or heteroaryl) in the presence or absence of a base in the presence or absence of a neutral solvent at reaction temperatures ranging from -80°C to 250°C. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali alkoxides metals (with the number of carbon atoms from 1 to 6) (it is better when it is sodium methoxide or sodium ethoxide), hydrides of alkaline earth metals, dialkylamides of alkali 62 metals (it is better when it is lithium diisopropylamide), bis(trilkylsilylamides of alkali metals (it is better when it is bis sodium (trimethylsilyl)amide), trialkylamines (preferably M, M-di-isopropyl-M-ethyl amine or triethylamine) or aromatic amines (preferably pyridine). Neutral solvents may include, but are not limited to, the following and, low alkanitriles (with the number of carbon atoms from 71 to b, it is better when it is acetonitrile), dialkyl ethers (it is better when it is diethyl ether), cyclic ethers (it is better when it is tetrahydrofuran or 1, 4-dioxane), M, M-dialkylformamides (better when it is dimethylformamides), M,M-dialkylacetamides (better when it is dimethylacetamide), cyclic amides (better when it is M-methylpyrrolidin-2-one), dialkyl sulfoxides (better when it is dimethyl sulfoxide), aromatic hydrocarbons (better when it is benzene or toluene) or haloalkanes with the number of carbon atoms from 1 to 10 and the number of halogens from 1 to 10 (it is better when it is dichloromethane). The best range of reaction temperatures is from -80 to 1002C,

Compounds of Formula (12) (Formula (1), in which K is ZK ) can then react with compounds of Formula KOH, using conditions and reagents identical to those used to convert compounds of Formula (8) to compounds of Formula (1) as given above for Scheme 1, giving compounds of

Formula (1). Alternatively, compounds of Formula (12) (Formula (1) in which KZ is 5 73) can be oxidized to compounds of Formula (13) (Formula (1) in which KZ is 5(O) B Y , H has a value of 1, 2) by introducing an oxidizing agent in the presence of a neutral solvent at a temperature range from -802C to 25020,

Oxidizing agents include, but are not limited to, hydrogen peroxide, alkane or aryl peracids (preferably peracetic acid or t-chloroperbenzoic acid), dioxirane, oxone, or sodium periodate. Neutral solvents may include, but are not limited to, those listed above

Agents are alkanones (with the number of carbon atoms from 3 to 10, it is better when it is acetone), water, alkyl alcohols (with the number of carbon atoms from 1 to 6), aromatic hydrocarbons (it is better when it is benzene or toluene) or haloalkanes with the number of carbon atoms from 1 to 10 and with the number of halogens from 1 to 10 (preferably dichloromethane) or their combinations. The choice of oxidant and solvent is well left to experienced specialists in this field (cit. Oetiga, p. 8., Oxidation of Sulfur, Selenium and Tellurium, in Complete Organic Synthesis, edited by B. M. Trost (V. M. Tgovi), Ge) (Eivyoga, MU: Regdatop Rgezvz, 1991), 7, 762-769). It is better when the range of reaction temperatures is from -20 degrees Celsius to 100 degrees Celsius. Compounds according to Formula (13) (Formula (1), in which KZ is 5(О)08 73, p has a value of 1, 2) can be introduced with compounds according to Formula KE ZN, using the same conditions and reagents as those used to convert compounds of Formula (8) to compounds of Formula (1) as shown above for Scheme 1, giving compounds of Formula (1). -

Compounds according to Formula (1), in which KZ can be -"MAZSOV 7, -ЩСОв 75, -"CHE SOM be 7, -MA Sov 3, -ME VT, b -М285028 7, can be made from compounds according to the Formula ( 7), in which M is MH, using the procedures given in Scheme 3. o

The reaction of compounds h-

Scheme C "in the w sleepers come on with s ry alkylating; sulfonylating or te ch Sha CHINES: acylating agents. J NN

ОО, х7-bsnovation, solvent and sites Х ш 45 я ; syaketsi ra u se) 7) We are the same.

With a. - maidens; c" Kz same nav; nAbSOYU, mi(SsOov")o, NESOMACHK?. and MeeSoOgkz

HF) according to Formula (7), in which M is MH, with alkylating agents, sulfonylating agents or acylating agents or successive reactions with their combinations in the presence or absence of a base in a neutral solvent at a reaction temperature range of -80 degrees Celsius up to 250 degrees

Celsius can give compounds according to Formula (1), in which В З can be -МАЗСОВ", -Ш(СОК 7", -"МА СОМ в, -МЕ8сОоовЗ, "МАВ, -MAZ8028 7. Alkylating agents can include, however, they are not limited to the following, C4-C10 alkyl halides, -tosylates, -mesylates or - triflates, C4-C10 haloalkyl (with the number of halogens from 1 to 10) -halides, -tosylates, -mesylates or - triflates, Co-Cv alkoxyalkyl -halides, -tosylates, -mesylates or -triflates, C3-Ce cycloalkyl halides, -tosylates, -mesylates or - triflates, C/-C12 65 cycloalkylalkyl halides, -tosylates, -mesylates or - triflates, aryl(C. --Cu alkyl)-halides, -tosylates, -mesylates or -triflates, heteroaryl(C.--C,.alkyl)-halides, -tosylates, -mesylates or -triflates,

heterocyclyl(C.-C.sub.6 alkyl)-halides, -tosylates, -mesylates or -triflates. Acylating Agents may include, but are not limited to, C-C alkanoyl halides or anhydrides, C 4-C 10 haloalkanoyl halides or anhydrides with 1 to 10 halogens, C 1-C 6a alkoxyalkanoyl halides or anhydrides, C 3-Cv cycloalkanoyl halides or anhydrides, C/-C4o cycloalkylalkanoyl halides or anhydrides, aroyl halides or anhydrides, aryl(Ci-C;) alkanoyl halides or anhydrides, heteroaryl halides or anhydrides, heteroaryl(C.-C.u) alkanoyl halides or anhydrides, halides or anhydrides heterocyclylcarboxylic acid or heterocyclyl(Ci-C;) alkanoyl halides or anhydrides. Sulfonylating agents may include, but are not limited to, C 4-C 0 alkylsulfonyl 70 halides or anhydrides, C 4-C 0 haloalkylsulfonyl halides or anhydrides with 1 to 10 halogens, Co-Ce alkoxyalkylsulfonyl halides or anhydrides, C3-Ce cycloalkylsulfonyl halides or anhydrides, C/-C4o cycloalkylalkylsulfonyl halides or anhydrides, arylsulfonyl halides or anhydrides, aryl(C.-C)/)-, heteroarylsulfonyl halides or anhydrides, heteroaryl(C.i-C;. alkyl) sulfonyl halides or anhydrides , heterocyclylsulfonyl halides or anhydrides, heterocyclyl(Ci--C. alkyl) sulfonyl /5 hapogenides or anhydrides. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (having 1 to 6 carbon atoms) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (better when lithium diisopropylamide), alkali metal carbonates, alkali metal bicarbonates, bis(trialkylsilylamides of alkali metals (better when it is sodium bis(trimethylsilyl)amide), trialkylamines (better when it is M, M-di-isopropyl -M-ethyl amine or triethylamine) or aromatic amines (it is better when it is pyridine).

Neutral solvents may include, but are not limited to, alkyl alcohols (C1 to C8, preferably methyl alcohol or ethyl alcohol), lower alkanitriles (C1 to C, preferably acetonitrile ), dialkyl ethers (it is better when it is diethyl ether), cyclic ethers (it is better when it is tetrahydrofuran or 1, 4-dioxane), M, M-dialkylformamides (it is better when it is dimethylformamide), M, M-dialkylacetamides (it is better when it is dimethylacetamide), cyclic amides (better when it is M-methylpyrrolidin-2-one), dialkyl sulfoxides (better when it is dimethyl sulfoxide) or i) aromatic hydrocarbons (better when it is benzene or toluene). The best reaction temperature range is from 02; to 10090.

Scheme 4 describes the procedures that can ensure the production of intermediate compounds according to Formula (7), in which co 30 M is oxygen, sulfur and 7 is Sv,

Compounds for 077

Scheme 4 so 35 m.

VSOV," base,. I Mimn;-nNyu, solvent MS. A 000 solvent and "

And Yana's internet pi sp nn pan -o s AJ zhh . and?

I

E p. Odessa Also, we are chic ZVU. se U DE 7 kispota; solvent Z Sho" from Shko k y ; syu" | . ; IN

F. K

SC, basis, roll, hu bo solvent: A she 65 Su yzh, 8; and in its formula AgСНоСМ react with compounds of the formula K?СОР, in which VK? defined above, and vo represents halogen, cyano, lower alkoxy (with the number of carbon atoms from 1 to 6) or lower alkanoyloxy (with the number of carbon atoms from 1 to 6) in the presence or absence of a base in a neutral solvent at a reaction temperature range from -782C, up to 20022; gives compounds according to Formula (3). Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (having 1 to 6 carbon atoms) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium diisopropylamide), alkali metal carbonates, alkali metal bicarbonates, bis(trialkylsilylamides of alkali metals (preferably sodium 70 bistrimethylsilyl)amide), trialkylamines (preferably M, M-diisopropyl -M-ethyl amine or triethylamine) or aromatic amines (it is better when it is pyridine). Neutral solvents may include, but are not limited to, alkyl alcohols (C1 to C8, preferably methyl alcohol or ethyl alcohol), lower alkanitriles (C1 to C6, preferably acetonitrile ), dialkyl ethers (it is better when it is diethyl ether), cyclic ethers (it is better when it is 75 tetrahydrofuran or 1,4-dioxane), M, M-dialkylformamides (it is better when it is dimethylformamide), M,

M-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably M-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), or aromatic hydrocarbons (preferably benzene or toluene). The best range of reaction temperatures is from 02C to 10020C.

Compounds of Formula (3) can be introduced with hydrazine hydrate in the presence of a neutral solvent in the temperature range from 02C to 2002C, preferably in the temperature range from 702C to 15023, thus obtaining compounds of Formula (4). Neutral solvents may include, but are not limited to, alkyl alcohols (C1 to C8, preferably methyl alcohol or ethyl alcohol), lower alkanitriles (C1 to C, preferably acetonitrile ), dialkyl ethers (better when it is diethyl ether), cyclic ethers (better when it is tetrahydrofuran or 1,C 4-dioxane), M,M-dialkylformamides (better when it is dimethylformamide), M,M-dialkylacetamides (better when it is about dimethylacetamide), cyclic amides (preferably M-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene). Compounds of Formula (4) can react with compounds of Formula (5) (in which KU is alkyl (with the number of carbon atoms from 1 to b) in the presence or absence of an acid in the presence of a neutral solvent at and in the temperature range from 09С to 2002C, thus obtaining compounds according to Formula (6). Acids can "- include, but they are not limited to the following, alkanoic acids with the number of carbon atoms from 2 to 10 (it is better when it is acetic acid), haloalkanoic acids (the number of carbon atoms from 2 to 10, the number of Me halogens is from 1 to 10, such as trifluoroacetic acid), arylsulfonic acids (preferably C-toluenesulfonic acid or benzenesulfonic acid), alkanesulfonic acids with a number of carbon atoms from 2 to 10 (preferably methanesulfonic acid), hydrochloric acid, sulfuric acid, or phosphoric acid. Stoichiometric or catalytic amounts of such acids may be used. Neutral solvents may include, but are not are limited only to the following, water, alkanitriles (the number of carbon atoms is from 1 to 6, it is better when it is acetonitrile), hydrocarbons with the number of carbon atoms from 1 to 6 and the number of halogens from 1 to 6 (it is better when it is dichloromethane or chloroform), alkyl alcohols with the number of carbon atoms from 1 to 10 (it is better when it is ethyl alcohol), dialkyl ethers (it is better when it is diethyl ether), but) c cyclic ethers (the number of carbon atoms is from 4 to 12, it is better when it is diethyl ether or di-isopropyl c" ether) or cyclic ethers such as dioxane or tetrahydrofuran. The best temperature range is from ambient temperature to 1090.

Compounds according to Formula (6) can be transformed into compounds according to Formula (7) by introducing - 15 compounds С-У(КЗ9)» (in which У represents oxygen or sulfur, and К9 represents a halogen (it is better when it chlorine), alkoxy (number of carbon atoms from 71 to 4) or alkylthio (number of carbon atoms from 1 to 4)) in (95) in the presence or absence of a base in a neutral solvent in the range of reaction temperatures from -7892С to 2002С gives the compounds Formula (3). Bases may include, but are not limited to, 5-reduced bases, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (with a number of carbon atoms from 1 to b) (preferably sodium methoxide or sodium ethoxide), alkaline earth hydrides c» metals, dialkylamides of alkali metals (it is better when it is di-isopropylamide lithium), carbonates of alkali metals, bicarbonates of alkali metals, bis(trialkylsilylamides of alkali metals (it is better when it is bistrimethylsilyl)amide sodium), trialkylamines (it is better when it is M, M-di- isopropyl-M-ethyl amine or triethylamine) or aromatic amines (preferably pyridine). Neutral solvents may include, but are not limited to, alkyl alcohols (C1 to C8, preferably methyl alcohol or (F) ethyl alcohol), lower alkanitriles (C1 to C, preferably when it is acetonitrile),

GI dialkyl ethers (better when it is diethyl ether), cyclic ethers (better when it is tetrahydrofuran or 1, 4-dioxane), M, M-dialkylformamides (better when it is dimethylformamide), M, M-dialkylacetamides (better when it is dimethylacetamide) , cyclic amides (preferably M-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene). The best temperature range is between 0 and 15026.

Intermediate compounds according to Formula (7), in which 7 represents nitrogen, can be synthesized according to the methods given in Scheme 5. b5

And And Compounds for

Scheme 5 also U

VEN M, base, 2-0 reducing agent, solvent sha 70 sho p m X and shshshsh shov ish (ear

ME i vo nn Iii i pu - acid, cha vnu

ОиЙбО00obyuzchinniakore "in no x vyli y (307 A o (11u and X "-

U-C(B3" base, nn u so solvent reg ! g

DI: « i 20, 85; and 2 s in s ! with the formula АгСНоОСМ react with compounds of the formula КУСНОМЗ, in which КУ represents phenyl;" a group optionally substituted by hydrogen, alkyl (number of carbon atoms from 1 to 6) or alkoxy (number of carbon atoms from 1 to b) in the presence or absence of a base in a neutral solvent in the temperature range from 0 to 2002C, which makes it possible to generate compounds according to Formula (9). Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (having 1 to 6 carbon atoms) (preferably sodium methoxide or sodium ethoxide), hydrides alkaline earth metals, dialkylamides of alkaline metals (it is better when diisopropylamide

Te) lithium), carbonates of alkali metals, bicarbonates of alkali metals, bis(trialkylsilyl)amides of alkali metals (better when it is sodium bis(trimethylsilyl)amide), trialkylamines (better when it is M, M-di-isopropyl-M- ethyl amine or - triethylamine) or aromatic amines (it is better when it is pyridine). Neutral solvents may include, but are not limited to, alkyl alcohols (C1 to C8, preferably methyl alcohol or ethyl alcohol), lower alkanitriles (C1 to C6, preferably is acetonitrile), dialkyl ethers (better when it is diethyl ether), cyclic ethers (better when it is tetrahydrofuran or 1, 4-dioxane), M, M-dialkylformamides (better when it is dimethylformamide), M,

M-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably M-methylpyrrolidin-2-one), iF) dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or co-toluene). The best reaction temperature range is from ambient temperature to 100290.

Compounds of Formula (9) can be introduced with a reducing agent in a neutral solvent at a temperature of -100 to 1002, giving products of Formula (10). Reducing agents include, but are not limited to, (a) hydrogen gas in combination with noble metal catalysts such as palladium-on-carbon, Ryu 5, platinum-on-carbon, rhodium-on-aluminum, or Raney nickel ( Capeu), (B) alkali metals (preferably sodium) in combination with liquid ammonium or (c) cerium ammonium nitrate.

Neutral solvents may include, but are not limited to, alkyl alcohols 65 (C1 to C8, preferably methyl alcohol or ethyl alcohol), lower alkanitriles (C1 to C, preferably acetonitrile), water, dialkyl ethers

(it is better when it is diethyl ether), cyclic ethers (it is better when it is tetrahydrofuran or 1, 4-dioxane), M,

M-dialkylformamides (preferably dimethylformamides), M,M-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably K-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), or aromatic hydrocarbons (preferably is benzene or toluene). The best reaction temperatures are temperatures from -50 to 6020.

Compounds of Formula (9) are then converted to compounds of Formula (7) (wherein is nitrogen) via intermediates of Formula (11) using the reagents and reaction conditions shown in Scheme 4 for the conversion of compounds of Formula (4) to compounds according to Formula (7) (in which U represents SEZ). 70 Compounds of Formula (1) can also be prepared from compounds of Formula (7) (in which XM represents oxygen, sulfur, and 7 is defined above) as shown in Scheme 6. Compounds of

Scheme 6 y y n t Zh, / - acid, Vk?

CHE I - dehydrating agent ra CHIA "solvent: re I ne tylu AS nik

And Ak and Nya and the same

Кк Не сч 7) и жо, 5; I that Mn, sv a) An o

Formula (7) can react with KZN compounds in the presence of a dehydrating agent in a neutral solvent in the range of reaction temperatures from 0 to 25022. Dehydrating agents include, "9 but are not limited to the following, P 2O5, molecular sieve or inorganic or organic acids . Acids may include, but are not limited to, alkanoic acids having 2 to 10 carbon atoms (preferably acetic acid), haloalkanoic acids (2 to 10 carbon atoms, 1 to 10 halogens, such as trifluoroacetic acid), arylsulfonic acids (preferably p-toluenesulfonic acid or benzenesulfonic acid), alkanesulfonic acids with the number of carbon atoms from 2 to 10 (preferably methanesulfonic acid), hydrochloric acid, sulfuric acid, or phosphoric acid. Neutral solvents may include, but are not limited to, alkyl alcohols (C1 to C8, preferably methyl alcohol or ethyl alcohol), lower alkanitriles (C1 to C, preferably acetonitrile ), " dialkyl ethers (better when it is diethyl ether), cyclic ethers (better when it is tetrahydrofuran or 1,

A4-dioxane), M, M-dialkylformamides (preferably dimethylformamides), M, M-dialkylacetamides (preferably C dimethylacetamide), cyclic amides (preferably M-methylpyrrolidin-2-one), dialkylsulfoxides (preferably this is dimethylsulfoxide), aromatic hydrocarbons (it is better when it is benzene or toluene) or hydrocarbons with the number of carbon atoms from 1 to 10 and the number of halogens from 1 to 10 (it is better when it is chloroform). The best reaction temperature range is from ambient temperature to 602C.

Some compounds according to Formula (1) (in which A is nitrogen) can also be obtained using the methods depicted in Scheme 7: s "Scheme 7 Intermediate compounds according to se) - still oyu in s" n kseov, i mno nnoXx -k/- acid, Ko

M; solvent ai ve zv | AND! r Z U bo (14) | sh. Ak (1 Az

The formula (14), in which 7 is defined above, can react with compounds of the formula В ZС(ОВ2)5, in which КК? can be an alkyl (1 to 6 carbon atoms) in the presence or absence of an acid in a neutral solvent dB at a temperature range of 0 to 2502. Acids may include, but are not limited to, alkanoic acids having 2 to 2 carbon atoms 10 (preferably acetic acid), haloalkanoic acids (2 to 10 carbon atoms, 1 to 10 halogens, such as trifluoroacetic acid), arylsulfonic acids (preferably p-toluenesulfonic acid or benzenesulfonic acid), alkanesulfonic acids with the number of carbon atoms from 2 to 10 (it is better when it is methanesulfonic acid), hydrochloric acid, sulfuric acid or phosphoric acid. Stoichiometric or catalytic amounts of such acids may be used. Neutral solvents may include, but are not limited to, alkyl alcohols (C1 to C8, preferably methyl alcohol or ethyl alcohol), lower alkanitriles (C1 to C6, preferably acetonitrile ), dialkyl ethers (it is better when it is diethyl ether), cyclic ethers (it is better when it is tetrahydrofuran or 1, 4-dioxane), M, M-dialkylformamides (it is better when it is dimethylformamide), M,

M-dialkylacetamides (better when it is dimethylacetamide), cyclic amides (better when it is K-methylpyrrolidin-2-one), dialkyl sulfoxides (better when it is dimethyl sulfoxide), aromatic hydrocarbons (better when it is benzene or toluene) or hydrocarbons with the number of carbon atoms from 1 to 10 and the number of halogens from 1 to 10 (it is better when it is dichloromethane). The best reaction temperature range is from 50 to 15020.

Intermediate compounds according to Formula (7) can also be synthesized using the reactions depicted in

Schemes 8. p. and Compounds for

Scheme 8:

IN

AI 00 AM I/- catalyst, fig. th p solvent k - ; "m in Shchi o (18u Zh z ON, 58 NASK"; Ah | -

By formula (15), (y represents OH, ЗН, ME ОВ 7; 7 is defined above, X represents bromine, chlorine, iodine, Oz5СЕ»z or

В(ОК")2, and КК" is hydrogen or alkyl (the number of carbon atoms from 1 to 6) can react with a compound according to the Formula AgHM (in which M is a halogen, an alkali metal, 7psSi, 2pVg, 7pi, MaosIi, Mai, Sesi 5, «

CeH or copper halide) in the presence or absence of an organometallic catalyst in the presence or in the absence of a base in a neutral solvent in the temperature range from -100 to 2002. Experienced specialists in this field can determine that AgM reagents can be generated at the location. "c Organometallic catalysts include, but are not limited to, palladium phosphine complexes (such as РО(РРЖ))), palladium halides or alkanoates (such as PaСХРРН3)" or Pa(Oas)"), or nickel complexes (such as MICI2( (PPH3)2) Bases may include, but are not limited to the following, -1 395 alkali metal carbonates or trialkylamines (preferably M,M-diisopropyl-M-ethylamine or triethylamine).

Neutral solvents may include, but are not limited to, dialkyl ethers (95) (preferably diethyl ether), cyclic ethers (preferable tetrahydrofuran or 1,4-dioxane), M,C-M-dialkylformamides (preferable dimethylformamide), M, M-dialkylacetamides (better when it is dimethylacetamide), cyclic amides (better when it is M-methylpyrrolidin-2-one), dialkyl sulfoxides (better when it is 70 dimethyl sulfoxide), aromatic hydrocarbons (better when it is benzene or toluene) or water The best range of reaction temperatures is from -80 to 1002C. The choices of values for M and X are known to experienced specialists in this field, (cf. Imamoto, T., Organocerium Reagents in Complete Organic Synthesis, edited by B.M. Trost, (EiIvioga, MU: Regdatop Rgevzv, 1991), 1, 231 -250). (see. Knochel, P., Organozinc Reagents, Organocadmium and

Organomercury in the Complete Organic Synthesis, edited by B. M. Trost, (Eivioga, MU: Regdatop Rgevzvz, 1991), 1, 211-230). (see. Knight, D, U., Combined Reactions between Carbon Centers in Total Organic Synthesis, edited by B. M. Trost, (Eivyoga, MU: Regdatop Rgezv, 1991), 3, 481- 520). Compounds of Formula (1) can also be prepared using the methods depicted in Scheme 9. 60 b5

The scheme of the 9th century

Жій х n У АгМ, х./- catalyst, ША ЧИНы и 0 1 и solvent ат не. B I di Ey y Sha x v y (16) xX with Vk, C1, Y; (and)

Compounds according to Formula (16), in which A, 7, VE! and BZ are defined above, and X represents bromine, chlorine, iodine, O35CE3 or

B(OK")", and K" represents hydrogen or alkyl (the number of carbon atoms from 1 to b) can react with a compound according to the Formula AgM (in which M is a halogen, an alkali metal, 2psSii, 2pVg, 7piI, MaoSi, Mai, Sesi 5,

CeHgO or copper halide) in the presence or absence of an organometallic catalyst in the presence or absence of a base in a neutral solvent in the temperature range from -100 to 2002. Those skilled in the art can determine that AgM reagents can be generated at the location of He (see above references in Total Organic Synthesis). Organometallic catalysts include, but are not limited to, palladium phosphine complexes (such as РО(РРИЗ) 4 ), palladium halides or alkanoates (such as РаСИДРРПН»)2 or Ра(Оас)»), or nickel complexes (such as MiSiZh( РРНз)». Bases may include, but are not limited to, alkali metal carbonates or trialkylamines (preferably M,M-diisopropyl-M-ethylamine or triethylamine). Neutral solvents may include, but are not limited to, dialkyl ethers (preferably diethyl ether), cyclic ethers (preferable tetrahydrofuran or 1,4-dioxane), M,M-dialkylformamides (preferable - dimethylformamide), M, M-dialkylacetamides (better when it is dimethylacetamide), cyclic amides (better when it is () )|H-methylpyrrolidin-2-one), dialkylsulfoxides (better when it is dimethylsulfoxide), aromatic hydrocarbons (better when it is benzene or toluene) or water. The best reaction temperature range is from -80 to 10020. 3 Intermediate compounds according to Formula (7) (in which U represents oxygen, sulfur, MH, 7 represents SK av? and its

Ag defined above) can be fabricated as shown in Scheme 10.

Scheme 10 Compounds for 40 I shi s i t МНЖНЯС-У) МН; And c still zhi - eunovation or: : b; р ne v acid, solvent: y Х 2: o nav" M y 50 13 chni - | : syu"

X yu z /- knelota, Mk a solvent Z | SAME 60 d n b5

Formula (3) can react with compounds according to the Formula NoMMN (С-М) МН», in which M is oxygen, sulfur or МН, in the presence or absence of a base or an acid in a neutral solvent at temperatures from 0 to 25020. Acids may include, but are not limited to, alkanoic acids having 2 to 10 carbon atoms (preferably acetic acid), aryl sulfonic acids

Acids (preferably p-toluenesulfonic acid or benzenesulfonic acid), alkanesulfonic acids having 2 to 10 carbon atoms (preferably methanesulfonic acid), hydrochloric acid, sulfuric acid or phosphoric acid. Stoichiometric or catalytic amounts of such acids may be used.

Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (having 1 to 6 carbon atoms) (preferably 7/0 sodium methoxide or sodium ethoxide), hydrides alkaline earth metals, dialkylamides of alkali metals (it is better when it is diisopropylamide lithium), carbonates of alkali metals, bicarbonates of alkali metals, bis(trialkylsilyl)amides of alkali metals (it is better when it is bis(trimethylsilyl)amide sodium), trialkylamines (it is better when it is M,

M-di-isopropyl-M-ethyl amine or triethylamine) or aromatic amines (it is better when it is pyridine). Neutral solvents may include, but are not limited to, alkyl alcohols (having 7/5 carbon atoms from 1 to 6), lower alkanitriles (having 1 to 6 carbon atoms, preferably acetonitrile), dialkyl ethers (preferably when it is diethyl ether), cyclic ethers (better when it is tetrahydrofuran or 1,4-dioxane), M,M-dialkylformamides (better when it is dimethylformamide), M,M-dialkylacetamides (better when it is dimethylacetamide), cyclic amides (better when is M-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes with the number of carbon atoms from 1 to 10 and the number of halogens from 1 to 10 (preferably dichloromethane ).

The best reaction temperature range is from 0 to 1502C. Compounds of Formula (17) can then react with compounds of formula KZS(OKZ)5, in which KU can be alkyl (number of carbon atoms from 1 to 6) in the presence or absence of an acid in a neutral solvent at a temperature range from 0 to 2502C. Acids may include, but are not limited to, alkanoic acids having 2 to 10 carbon atoms (preferably acetic acid), arylsulfonic acids (preferably o-p-toluenesulfonic acid or benzenesulfonic acid), alkanesulfonic acids having carbon atoms from 2 to 10 (it is better when it is methanesulfonic acid), hydrochloric acid, sulfuric acid or phosphoric acid. Stoichiometric or catalytic amounts of such acids may be used. Neutral solvents may include, but are not limited to the following, lower alkanitriles (having 1 to 6 carbon atoms, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), M,M-dialkylformamides (preferably dimethylformamides), M,M-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably F

M-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes with the number of carbon atoms from 1 to 10 and the number of halogens from 1 to 10 (preferably dichloromethane ). The best reaction temperature range is from 50 to 15020. and -

Scheme 11 shows the procedures that can be used to convert compounds of Formula (1) in which KZ is SOK 7, СО2", MAZSOV " and SOMESUV " to other compounds of Formula (1) in which VZ is CH( ОН)В", СНоОН, МВЯСНоВ' and СНОМ" by means of introduction with a reducing agent in "5 neutral solvent in the temperature range from -80 to 25096. З7З с 70 Scheme 1 Reducing agents;" in 3 | A. Dn, 00 reducing genes, xx MO Mu 0 solvent Dn tya sh ve M po u Kk M 25 a) sov"; Agents include, but are not limited to, alkali metal or alkaline earth metal borohydrides, borane, dialkylboranes (such as di-isoamylborane) , alkali metal aluminum hydrides (preferably lithium aluminum hydride), (trialkoxy) alkali metal aluminum hydrides or dialkyl aluminum hydrides (such as diisobutylaluminum hydride). Neutral solvents may include, but are not limited to, alkyl alcohols (1 to 6 carbon atoms), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferable tetrahydrofuran or 1,4-dioxane), aromatic hydrocarbons (it is better when it is benzene or toluene). The best reaction temperature range is from -80 to

Scheme 12 depicts procedures that can be used to convert compounds of Formula (1) in which the C is CO" or CO to other compounds of Formula (1) in which the C is C(IONXE 72) by introduction with the reagent of By the formula of KM in a neutral solvent in the temperature range from -80 to 25026.

Scheme 12 M represents 3 re Y t AY in m ХU / reducing agent, and yuky ra Do s-solvent. JSC Mrya v n u.

Ag and (i) 83 - sov", Sov, 1 VZ - siovusV 0) - o CO, (1 A - SIV. 12 s halogen, alkali metal, 2pSi, 2pVg, 2pi, MosSi, Moi, SeSi", SeVho or copper halide Neutral solvents may include, but are not limited to, dialkyl ethers (preferably diethyl ether), cyclic ethers (preferable tetrahydrofuran), or aromatic hydrocarbons (preferable benzene or toluene) Preferred reaction temperature range is from -80 to 10020.

Compounds according to Formula (1), in which the KZ can be -"MAZSOV 7, -ShSOvK 75, -"CHEZSOME 7, -MAZSOovZ,-MebV", and -MA85028 7 can be synthesized as shown in Scheme 13. "-- ( 22) so i - shi s;" -And (95) se) - 50 se»

F) name) 60 b5

Scheme 13 host and: part 8) V. same / "update,. V. shchi and ek poozhny V. I Cause: and I

I she yam x obu (19) zv (4) de osv, C (10) 5 - M. (8) :apkylating, sulfonylating 460: ех o atsnlyating agents ry - pt/ - base, solvent l Shchy: in shchy X Ge) sh s A Y vch chi | SHHA s is m i" s ASV. :" Vu zmvbv!, MV'SOV" 7 nvesOMVsV", oz MKaSOvz (Se) Using the reaction of compounds according to Formula (18), in which VE and B! are defined above, with compounds according to Formula (4) or Formula (10) in the presence or absence of a base in a neutral solvent, compounds of Formula (19) can be obtained in the temperature range from -50 to 25020. Bases may include, but are not limited to, the following, alkali metal hydrides (better when it is sodium hydride), alkali metal alkoxides (with the number of carbon atoms from 1 to 6) (better when it is sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (better when lithium diisopropylamide) , alkali metal carbonates, alkali metal bicarbonates, alkali metal bis(trialkylsilylamides (preferably sodium bis(trimethylsilyl)amide), trialkylamines (preferably M, M-diisopropyl-M-ethyl amine or triethylamine) or aromatic amines (preferably pyridine.) Neutral solvents may include , but they are not limited to the following, alkyl alcohols (with the number of carbon atoms from 1 to 8, it is better when it is methyl alcohol or ethyl alcohol), lower alkanitriles (with the number of carbon atoms from 1 to 6, it is better when 60 is acetonitrile), dialkyl ethers (better when it is diethyl ether), cyclic ethers (better when it is tetrahydrofuran or 1, 4-dioxane), M, M-dialkylformamides (better when it is dimethylformamide), M,

M-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably M-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), or aromatic hydrocarbons (preferably benzene or toluene). A preferred reaction temperature range is from 0 to 10020. bB Compounds of Formula (19) may then be reacted with alkylating agents, sulfonylating agents, or acylating agents or sequential reactions with combinations thereof in the presence or absence of a base in a neutral solvent at reaction temperatures in the range from -8402C to 250 tgg"C can give compounds according to Formula (1), in which the KZ can be -"ЧАЗСОВ 7, -Щ(СОкК lo, -"МЕЗСсОоМе в", -"МА СО, -MA В, -МВ835028 7. Alkylating agents may include, but are not limited to, the following, C1-C10 alkyl halides, -tosylates, -mesylates or -triflates, C1-C10 haloalkyl (number of halogens from 1 to 10)-halides, -tosylates, -mesylates or - triflates, Co-Cv alkoxyalkyl halides, -tosylates, -mesylates or -triflates, C3-Ce cycloalkyl halides, -tosylates, -mesylates or - triflates, C,A-C1o cycloalkylalkyl halides, -tosylates, -mesylates or - triflates, aryl(C.--C;4 alkyl)-halides, -tosylates, -mesylates or - triflates, he theroaryl (C.--C,. alkyl)-halides, -tosylates, -mesylates or -triflates, 70 heterocyclyl(C.4-Su. alkyl)-halides, -tosylates, -mesylates or -triflates. Acylating agents may include, but are not limited to, C 4 -C 10 alkanoyl halides or anhydrides, C 4 -C 49 haloalkanoyl halides or anhydrides with 1 to 10 halogens, C 4 -C 10 alkoxyalkanoyl halides or anhydrides, C 3 -C 4 cycloalkanoyl halides or anhydrides, C/-C4o cycloalkylalkanoyl halides or anhydrides, aroyl halides or anhydrides, aryl(Ci-C;) alkanoyl halides or anhydrides, heteroaryl halides or 75 anhydrides, heteroaryl(C.-C.u) alkanoyl halides or anhydrides, halides or anhydrides of heterocyclylcarboxylic acid or heterocyclyl(Ci-C;) alkanoyl halides or anhydrides. Sulfonylating agents may include, but are not limited to, the following, C.4-C; alkylsulfonyl halides or anhydrides, C4-C10 haloalkylsulfonyl halides or anhydrides with the number of halogens from 1 to 10, Co-C8 alkoxyalkylsulfonyl halides or anhydrides, C3-Ce cycloalkylsulfonyl halides or anhydrides, C/-C12 cycloalkylalkylsulfonyl halides or anhydrides, aryl or sulfonyl anhydrides aryl(C.-C,)-, heteroarylsulfonyl halides or anhydrides, heteroaryl(Ci-C; alkyl) sulfonyl halides or anhydrides, heterocyclylsulfonyl halides or anhydrides, heterocyclyl(C--C,. alkyl) sulfonyl halides or anhydrides. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (having 1 to 6 carbon atoms) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides , dialkylamides of alkali metals (it is better when diisopropylamide lithium), carbonates of alkali metals, bicarbonates of alkali metals, bis(trialkylsilylamides of alkali metals (it is better when it is bis(trimethylsilyl)amide sodium), trialkylamines (it is better when it is M, M-di- isopropyl-K-ethyl amine or triethylamine) or aromatic amines (pyridine is better).

Neutral solvents may include, but are not limited to the following, CO alkyl alcohols (with a number of carbon atoms from 1 to 8, preferably methyl alcohol or ethyl alcohol), low alkane nitriles (with a number of carbon atoms from 1 to b, preferably when is acetonitrile), dialkyl ethers (better when it is diethyl ether), cyclic ethers (better when it is tetrahydrofuran or 1, 4-dioxane), M, M-dialkylformamides F (better when it is dimethylformamide), M, M-dialkylacetamides (better when is dimethylacetamide), cyclic amides with (preferably M-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene). The best range of reaction temperatures is from BС to 10026. -

Compounds according to Formula (1), in which A represents SC, and K is defined above, can be synthesized using the methods given in Scheme 14. - . and? -i (95) se) - 70 syu» ime) 60 b5

"Scheme 14 Compounds for 5 . Mr. O

Who is that in | nya and sincere (29) sa

ХО n/«juning, solvent. and Yi g o popy "th milestone for" and 14; Same "sv, " 7 X (10) 2 same in (2) Ah

Hey | and ko dD -. : she U vn tsa sho VN, those 7 bases; It is a solvent. to her about (Fi) life, | 1. | s zo i «- on | х Ф and thalogenating; agent or | ! s ah r bulfonylating agent Zhim -M o ay k-t xx t l- basis; | and k. In and in Well, I have a solvent: : Ky

V I and V M; "day 423) 8 "" Formula (4) or Formula (10) can be introduced with compounds of Formula (20), in which B and BZ " are defined above, in the presence or absence of a base in a neutral solvent at a temperature range from ОО to 2502С, which gives compounds according to Formula (1), in which A is SK, and the value of K is defined above. 49 Bases may include, but are not limited to, alkali metal hydrides

She (it is better when it is sodium hydride), alkali metal alkoxides (with the number of carbon atoms from 1 to 6) (it is better when

Ge) is sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium diisopropylamide), alkali metal carbonates, alkali metal bicarbonates, alkali metal bis(trialkylsilyl)amides (preferably bis(trimethylsilyl sodium amide), trialkylamines (better when it is M, -o 70 M-di-isopropyl-M-ethyl amine or triethylamine) or aromatic amines (better when it is pyridine). Neutral solvents may include, but are not limited to, alkyl alcohols (C1 to C8, preferably methyl alcohol or ethyl alcohol), lower alkanitriles (C1 to C6, preferably is acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), M,M-dialkylformamides (preferably 29 dimethylformamides), M,M-dialkylacetamides (preferable is dimethylacetamide), cyclic amides (preferably (PI |CH-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene). The best reaction temperature range is from 09C to 1002C Alternatively, compounds of Formula (1), in which A is SC and the value of K is defined above, can be synthesized via intermediates (22) and (23). For Compounds of Formula (4) or Formula (10) can be administered with compounds of Formula (21), in which B! defined above, and MK? is an alkyl (number of carbon atoms from 1 to 6), in the presence or absence of a base in a neutral solvent at a temperature range from 0 to 2502C, which gives compounds of

By formula (1), in which A is a SC, and the value of K is defined above. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (having 1 to 6 carbon atoms) (preferably sodium methoxide or sodium ethoxide),

hydrides of alkaline earth metals, dialkylamides of alkali metals (preferably lithium diisopropylamide), carbonates of alkali metals, bicarbonates of alkali metals, bis(trialkylsilylamides of alkali metals (preferably sodium bis(trimethylsilyl)amide), trialkylamines (preferably M, M- di-isopropyl-M-ethyl amine or triethylamine) or aromatic amines (preferably pyridine). Neutral solvents may include, but are not limited to, alkyl alcohols (having 1 to 8 carbon atoms, preferably methyl alcohol or ethyl alcohol), low alkanitriles (with the number of carbon atoms from 1 to 6, it is better when it is acetonitrile), dialkyl ethers (it is better when it is diethyl ether), cyclic ethers (it is better when it is tetrahydrofuran or 1, 4-dioxane), M, M-dialkylformamides (preferably dimethylformamides), M, 7/0 M-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably M-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic carbon evodne (it is better when it is benzene or toluene). A preferred reaction temperature range is from 09C to 1002C. Compounds of Formula (22) may be introduced with a halogenating agent or sulfonylating agent in the presence or absence of a base in the presence or absence of a neutral solvent over a reaction temperature range of -80 to 250C, giving compounds of 75 Formula (23) (in which X is halogen, alkanesulfonyloxy, arylsulfonyloxy or haloalkanesulfonyloxy). Halogenating agents include, but are not limited to the following,

OSI», ROSI», RSIz, ROVGz, RVgz or RVg5. Sulfonylating agents include, but are not limited to, alkanesulfonyl halides or alkanesulfonyl anhydrides (such as methanesulfonyl chloride or methanesulfonyl anhydride), arylsulfonyl halides or arylsulfonyl anhydrides (such as p-toluenesulfonyl chloride or p-toluenesulfonyl anhydride), or haloalkylsulfonyl halides or haloalylsulfonyl anhydrides (it is better when it is trifluoromethanesulfonyl anhydride). Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (having 1 to 6 carbon atoms) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, dialkylamides alkali metals (it is better when diisopropylamide Ga

Lithium), alkali metal bis(trialkylsilylamides (preferably sodium bis(trimethylsilyl)amide), trialkylamines (preferably M, M-diisopropyl-M-ethyl amine or triethylamine) or aromatic amines (preferably pyridine). and)

Neutral solvents may include, but are not limited to, lower alkanitriles (having 1 to 6 carbon atoms, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4 -dioxane), M, M-dialkylformamides (better when it is "with dimethylformamide), M, M-dialkylacetamides (better when it is dimethylacetamide), cyclic amides (better when it

M-methylpyrrolidin-2-one), dialkyl sulfoxides (better if it is dimethyl sulfoxide), aromatic hydrocarbons -- (better if it is benzene or toluene) or haloalkanes with the number of carbon atoms from 1 to 10 and the number of Fd) halogens from 1 to 10 (better when it is dichloromethane). The best reaction temperature range is from -202C to 10026.

Compounds of Formula (23) can react with compounds of Formula EN (in which B? is defined as above, except that KZ is not НН, СОК "7, СООВ, aryl or heteroaryl) in the presence or in - in the absence of a base in the presence or absence of a neutral solvent in the reaction temperature range of -80 to 2502C, resulting in the generation of compounds of Formula (1). Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkoxides of alkali metals (with the number of carbon atoms from 1 to 6) (it is better when it is sodium methoxide or sodium ethoxide), hydrides of alkaline earth metals, dialkylamides of alkali metals (it is better when it is lithium diisopropylamide), but) with bis(trialkylsilylamides of alkali metals ( preferably sodium bis(trimethylsilyl)amide), trialkylamines (preferably M,M-diisopropyl-M-ethyl amine or triethylamine) or aromatic amines (preferably pyridine). "Neutral solvents may include, however don't limit only the following are used, alkyl alcohols (the number of carbon atoms from 1 to 8, it is better when it is methyl alcohol or ethyl alcohol), lower alkanitriles (with the number of carbon atoms from 1 to b, it is better when it is acetonitrile), dialkyl ethers (it is better when it is . diethyl ether), cyclic ethers (better when it is tetrahydrofuran or 1, 4-dioxane), M, M-dialkylformamides d) (better when it is dimethylformamide), M, M-dialkylacetamides (better when it is dimethylacetamide), cyclic amides (better when is M-methyltrirolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatics, hydrocarbons (preferably benzene or toluene) or haloalkanes with the number of carbon atoms from 1 to 10 and the number of halogens from 1 to 10 (it is better when it is dichloromethane). The best range of reaction temperatures is from 09C to 14026.

Certain compounds of Formula (1) can also be prepared using methods depicted in Scheme 15.

F) name) 60 b5

Scheme 15 Compound by | AND

MM. Ve IJ tyu kpitcheseky sukslota 02000500 koh 0 MNIMN(SEUUMN" o ay (24) i acid, solvent ut EXTRACT in (25) r - (26) zho, 8 1u-v'si«MNIoV, in A'(s»orsny (skukov, where is the solvent about zfosnovaniya or u

OK І : And eosnoranany rozannimk: KOT; рРозчнНННк и и All from Fr

M quadrisoluble 1. ! ry sh See the text: Ж с) - ak m приманка Ф

Ag E (gtikh that, 8 (4) .5 - St.

Formula (24) (Co is a lower alkyl group, and Ag is defined above) can react with -70 hydrazine in the presence or absence of a neutral solvent, yielding intermediate compound (25), in which Ag is defined above. The conditions used are similar to those used to prepare the intermediate of Formula (4) from the compound of Formula (3) in Scheme 4. Compounds of Formula (25) in which A is nitrogen can be reaction with reagents of the formula КС (-МН) ОК, in which BK" is defined above, and Ko is a lower alkyl group) in the presence or absence of an acid in a neutral - 15 solvent, followed by a reaction with a compound of the formula U-C ( Ka)" (in which X represents oxygen or sulfur and Ka represents halogen (preferably chlorine), alkoxy (number of carbon atoms from 1 to 4) or alkylthio (95) (number of carbon atoms from 1 to 4) in in the presence or absence of a base in a neutral solvent gives a compound of Formula (27) (wherein A is nitrogen and Y is oxygen or sulfur). The conditions for these transformations are similar to those used for the conversion of the compound of Formula (4) to compounds according to Formula (7) in : n y : - Scheme 4. Alternatively, compounds according to Formula (25), in which A is which is SC, can react with "with compounds according to the formula K"(С-О) СНЕ (С-У) OK», in which B! defined above and Co is a lower alkyl group) to give a compound of Formula (27) (wherein A is SC) using conditions similar to those used to convert a compound of Formula (21) to a compound of Formula (22) ) in Scheme 14. Intermediate compounds of Formula (27) (wherein M is oxygen) can be introduced with halogenating agents or sulfonylating agents in the presence or absence of a base in a neutral solvent, followed by

Ф) the reaction with the YK ZN compound or the KN compound in the presence or absence of a base in a neutral co-solvent gives compounds according to Formula (10) (in which 7 is an SVU).

Those skilled in the art know that various combinations of halogenating agents, sulfonylating 6o agents, KZN or KN can be used to obtain compounds of Formula (1), different reaction sequences in Scheme 15. For example, in some cases it is desirable that the reaction compounds with a stoichiometric amount of halogenating agents or sulfonylating agents entered, reacted with B2H (or

VZN), then repeat the reaction with halogenating agents or sulfonylating agents and react with EZN (or EN), which gives compounds according to Formula (1). The reaction conditions and reagents used for these conversions are similar to those used for the conversion of intermediates of Formulas (22) to compounds (23) to compounds (1) in Scheme 14 (when A is SC) or conversion of intermediate compounds of Formulas (7) to compounds (8) to compounds (1) in Scheme 1 (in which A is nitrogen).

Alternatively, compounds of Formula (27) (where X is sulfur) can be converted to compounds of Formula (1) in Scheme 15. Intermediates of Formula (27) can be alkylated with compound BX (where B is lower alkyl , and X is halogen, alkanesulfonyloxy, or haloalkanesulfonyloxy) in a neutral solvent (then optionally oxidized with an oxidizing agent in a neutral solvent), and then react with VZN in the presence or absence of a neutral solvent, giving the compound as

Formula (1). The conditions and reagents used are similar to those used to convert intermediate 70 compounds of Formulas (7) to (12) (or to compound (13)) to compounds of Formula (7) in Scheme 2.

Compounds of Formula (1) can be prepared from compounds of Formula (24) using an alternative route as shown in Scheme 15. Compounds of Formula (24) can be converted to compounds of Formula (27) by reaction with compounds of Formula MNUMN (С-МН) МН" in the presence or absence of an acid in a neutral solvent, followed by reaction with the compounds К 2С (ОК)з (in which Ke is a lower alkyl, КЕ" is defined above, using the conditions applied to the conversion of compounds by Formula (3) to compounds (17) to compounds (7) in Scheme 10.

Certain compounds of Formula (2) can be prepared by methods shown in Scheme 16.

Scheme 16 of OKU. or B

At the same time - the basics; Mr. Sashe and

And 1 dk 0 solvent. ! |! zo (o)

Ah kh o (22) u so . a IVIEB (GE Kk -5 chekst 70 z . khz Z ch a re Zh/- bsnovakny, A. Kg Vu i At k- Zh o VozchinNnyK Ai ny Zh.

A Ob EL D that o Ah KE o au 2 "son (2) - 50

Compounds of Formula (275) can be introduced with various alkylating agents BC YX (where QX is defined as above, and X is halogen, alkanesulfonyloxy or haloalkanesulfonyloxy) in the presence or absence of a base in a neutral solvent, giving structures of the Formula ( 28). Compounds of Formula (28) (XU is oxygen) can then be converted to compounds of Formula (2) by introducing halogenating agents or sulfonylating agents in the presence or absence of a base in a neutral solvent, followed by reaction with in the presence or absence of a base in a neutral solvent gives

F! and iya with VZN and ab and and Й compounds according to Formula (2). The reaction conditions used for these transformations are the same as those used for the conversion of intermediates (22) to compounds (23) and then to compounds (1) in Scheme 14) (for the case where A is SC) or for the conversion of intermediate compounds of Formulas (7) to compounds (8) and then to 60 compounds (1) in Scheme 1) (for the case where A is nitrogen). Alternatively, compounds of Formula (28) may be alkylated compounds BX (where B/X is lower alkyl and X is alkanesulfonyloxy or haloalkanesulfonyloxy) in a neutral solvent (then optionally oxidized with an oxidizing agent in a neutral solvent), and then to react with VZN in the presence or absence of a base in a neutral solvent, giving compounds of Formula (1). The conditions and reagents used were the same as those used in the conversion of intermediates of Formulas (7) to compounds (12) (or to compounds (13)) and then to compounds of Formula (1) in Scheme 2 .

Compounds of Formula (1) in which 7 is CHO can be converted to compounds of Formula (2) as depicted in Scheme 16. Introduction with various alkylating agents K X (where K"" is defined above and X is alkanesulfonyloxy or haloalkanesulfonyloxy) in the presence or absence of a base in a neutral solvent, gives structures (2). Those skilled in the art will recognize that the methods used in Scheme 16 can also be used to prepare compounds of Formula (1) wherein 7 is SOV."

For Scheme 16, the terms "base" and "neutral solvent" may have the following meanings. 70 Bases may include, but are not limited to the following, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (with the number of carbon atoms from 1 to b) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium diisopropylamide), alkali metal bis(trialkylsilylamides (preferably sodium bis(trimethylcetyl)amide), trialkylamines (preferably M, M-diisopropyl-M-ethylamine or triethylamine) or aromatic amines 75 (preferably pyridine).Neutral solvents may include, but are not limited to, lower alkanitriles (C1 to B, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (better when it is tetrahydrofuran or 1, 4-dioxane), M, M-dialkylformamides (better when it is dimethylformamides), M, M-dialkylacetamides (better when it is dimethylacetamide), cyclic amides (better when it is K-methylpyrrolidine- 2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes with the number of carbon atoms from 1 to 10 and the number of halogens from 1 to 10 (preferably dichloromethane). The best reaction temperature range is from -202C to 10020C.

Examples.

Analytical data for the compounds described below were recorded using the following general procedures. everything

Nuclear magnetic resonance spectra for protons were recorded on an IVM-VgyKeg ET-NMR spectrometer (300 o

MHz); chemical shifts were recorded in ppm (65) from an internal tetramethylsilane standard in deuterochloroform or deuterodimethylsulfoxide as indicated below. The mass spectrum (M5) or high-resolution mass spectrum (NKM5) was recorded on a Rippedap MAT 8230 spectrometer (using chemical ionization (CI) with MHe as carrier gas or chromatography gas (C) as indicated below) or on a spectrometer model o

Neuleiyi Raskaga 5988A. Melting points were recorded on an Island Modei melting point apparatus "-510" and were not corrected. Boiling points were not corrected. All measurements of the pH level during the research were made using litmus paper. (2)

Reagents were purchased from commercial sources and, if necessary, purified using the general procedures outlined in O. Reitip apa MU... Aptagedo, Purification of Laboratory Chemicals, 3rd edition, |Mem/

Woik: Regdatop Rgezz, 1988). Chromatography was performed on silica gel using the solvent systems described below. Volume ranges are given for mixed solvent systems. Unless otherwise stated, parts and percentages are by weight.

The following examples provide a more detailed description of the invention. These examples, which define the best way to carry out the present invention, are intended to illustrate it and not to limit the invention.

Example 1 - c Production of 2,7-dimethyl-8-(2,4-dimethylphenyl) (1,5-a)-pyrazolo-|1,3,5)triazine-4(3H)-one "» (Formula 7 , in which M represents oxygen, K" represents CH, 7 represents C-CH3, Ag represents 2, "4-dimethylphenyl)

A. 1 -Cyano-1 -2. 4-dimethylphens)propan-2-one

Sodium granules (9.8 grams, 0.43 mol) were added portionwise to a solution of dimethylphenylacetonitrile (48 grams, - 0.33) in ethyl acetate (150 milliliters) at ambient temperature. The reaction mixture was heated to the reflux temperature and stirred for 16 hours. The resulting suspension was cooled to room temperature and filtered. The selected precipitate was washed with a large amount of ether, and then re)dried with air. The solid substance was dissolved in water, and then IM NS was added until the -sh 20 pH level was equal to 5-6. The mixture was extracted with ethyl acetate (200 milliliters three times); the combined organic layers were dried over Moss and filtered. The solvent was removed by distillation, which gave a white solid (45.7 grams, yield 74965): NMR (SOCI3, ZOOMHz) :; SI-M5: 188 (M'-H).

B. 5-Amino-4-(2.4-dimethylphenyl)-3-methylpyrazole

A mixture of 1-Cyano-1-2,4-dimethylphenyl)propan-2-one (43.8 grams, 0.223 mol), hydrazine hydrate (22 milliliters, 0.46 mol), glacial acetic acid (45 milliliters, 0.78 mol) and toluene (500 milliliters) was stirred at the temperature of phlegm formation for 18 hours in the apparatus designed for this in the form of a Dean-Stark separator (Oegeap-Z(agk). The reaction mixture was cooled to ambient temperature and the solvent was removed by mass. The residue was dissolved in 6M NOS and the resulting solution was extracted three times with ether. Concentrated ammonium hydroxide solution was added to the aqueous layer until the pH 60 level was 11. The resulting half-solution was extracted three times with ethyl acetate. The combined organic layers were dried over Mo95O); and filtered. The solvent was removed from the mass, which gave a solid pale brown viscous oily substance (334.6 grams, yield 7595): NMR (SOS1 z, ZOOMGhzC): 7.10 (v, 1H), 7.05 (9, 2H, 9-1), 2.37 (8, ZN), 2.10 (c, ZN); SI-M8: 202 (M i N).

S. 5-Acetamidino-4-(2.4-dimethylphenyl)-3-methylpyrazole. acetic acid salt of ethyl acemidate hydrochloride (60 grams, 0.48 mol) was immediately added to a rapidly stirred mixture of potassium carbonate (69.5 grams, 0.50 mol), dichloromethane (120 milliliters), and water (350 milliliters). The layers were separated and the aqueous layer was extracted with dichloromethane (twice of 120 milliliters). The combined organic layers were dried over Mo5O and filtered. The solvent was removed by simple distillation, and the flask containing the residue, a clear pale yellow liquid (35.0 grams), was then used without further purification.

Glacial acetic acid (9.7 mL, 0.17 mol) was added to a stirred mixture of 5-amino-4-(2,4-dimethylphenyl)-3-methylpyrazole (34 grams, 0.17 mol), ethyl acetamidate (22 grams, 0.25 mol), and acetonitrile. (500 milliliters). The resulting mixture was stirred at room temperature for 3 days; at the end of this time, it was concentrated by mass to approximately one third of its initial volume.

The resulting suspension was filtered, and the selected substance was washed with a large amount of ether. /o The white solid substance was dried in ip masso (31.4 grams, yield 6195): NMR (0M50O-ydv, 300 MHz): 7.00 (85, 1H), 6.90 (ad, 2H, 9-71), 2.28 (8, ZN ), 2.08 (in, ZN), 2.00 (in, ZN), 1.90 (in, ZN), 1.81 (in, ZN); SI-M8: 243 (M i N). p. 2. 7-dimethyl-8-(2, 4-dimethylphenyl) |1. 5-a) -pyrazol- |1, Z. 5) -triazine-4 (ZN)-one

Sodium granules (23 grams, 1 mol) were added portionwise to ethyl alcohol (500 milliliters) with vigorous stirring. After the sodium was completely reacted, 5-acetamidino-4-(2,7/5 4-dimethylphenyl)-3-methylpyrazole, acetic acid salt (31.2 grams, 0.1 mol) and diethyl carbonate (97 milliliters , 0.8 mol). The resulting mixture was heated to the temperature of phlegm formation and stirred for 18 hours. The mixture was cooled to room temperature and the solvent was removed by vacuum. The residue was dissolved in water, and a solution of 1M HC1 was added slowly until the pH level was 5-6. The aqueous layer was extracted three times with ethyl acetate; the combined organic layers were dried over Mo95O and filtered.

The solvent was removed from the mass, which gave a pale yellowish-brown solid (26 grams, yield 9895): NMR (SOS15z, ZOOMHC): 7.15 (in, 1H), 7.09 (in, 2H), 2.45 (8, ЗН), 2.39 (in, ZN), 2.30 (8, ZN) ; СИ-М5: 269 (Мах Н).

Example 2

Production of 5-methyl-3-(2, 4,6-trimethylphenyl) (1, 5-a|-(1,2,3)-triazolo-(1,3,5)triazine-7(6H)-one ( Formula 7, in which M is oxygen, K 41 is CH with, 7 is nitrogen, Ag is 2, 4, 6 with 7 trimethylphenyl).

A. 1-Phenylmethyl -4-(2, 4, 6 - trimethylphenyl) -5-aminotriazole and)

A mixture of 2, 4, b-trimethylbenzyl cyanide (1.0 grams, 6.3 mol), benzyl azide (0.92 grams, 6.9 mol) and

Potassium 1-butoxide in tetrahydrofuran (10 mL) was stirred at ambient temperature for 2.5 days. The resulting suspension was extracted three times with ethyl acetate. The combined organic layers were dried over Mo5O. and filtered. The solvent was removed by distillation to give a brown oily substance. Trituration with ether and filtration yielded a yellow solid (1.12 grams, yield 6195): NMR (СОС13, ЗО0MHz): 7.60-7.30 (t, 5Н), 2.30 (8, ЗН), 2.10 (8, 6Н) . Phew; SI-M5: 293 (M.N).

B. 4-(2.4.6-trimethylphenyl)-5-aminotriazole. me)

Sodium (500 milligrams, 22 mol) was added with stirring to a mixture of liquid ammonium (30 milliliters) and 1-y-phenylmethyl-4-(2, 4, 6-trimethylphenyl)-5-aminotriazole (1.1 grams, 3.8 mol). The reaction mixture was stirred until a dark green color remained. Ammonium chloride was added and the mixture was stirred for over 16 hours while heating to ambient temperature continued. The remainder was injected with a solution of IM

NOTE She was filtered. The aqueous layer was alkalized with a concentrated solution of ammonium hydrochloride (pH - 9), and then extracted three times with ethyl acetate. The combined organic layers were dried over M4O95O and filtered. The solvent was removed by vacuum to give a yellow solid (520 milligrams), which . homogenized using thin-layer chromatography (ethyl acetate): a NMR (SOS153, ZOOMHCc): 6.97 (b, 2H), 3.68-3.50 (bg.8, 2H), 2.32 (8, 3H), 2.10 (b, 6H); SI-M8: 203 (M i N).

S. 4-(2.4. b-trimethylphenyl)-5-aceamidinotriazole, acetic acid salt.

A mixture of 4-2,4,b-trimethylphenyl)-5-aminotriazole (400 milliliters, 1.98 mol), ethylacetamide (261 -I milligrams, 3 mol), and glacial acetic acid (0.1 milliliter, 1.98 mol) in acetonitrile (6 milliliters) stirred at ambient temperature for 4 hours. The resulting suspension was filtered, and the selected substance was washed with a large amount of ether. Drying ip brought meat

He) white solid substance (490 milligrams, yield 82965): NMR (0M50-a5, ZOOMHz): 7.90-7.70 (rg in, 0.5N), 7.50-7.20 (rg 85, 0.5N), 6.90 (in, 2N ), 3.50-3.10 (rg 8, ZN), 2.30-2.20 (rg 8, ZN), 2.05 (0, 7TN, 9-7), 1.96 (v, - 6H), 1.87 (v, 6H); SI-M8: 244 (M i N). 4) p. 5-methyl-3- (2, 4. b-t-rimethylphenigO (1. 5-a) -/1.. 2. 3|- triazolo- |1. 3. 5) -triazine-7 (ZN)-on.

Sodium (368 milligrams, 16.2 mol) was added with stirring to ethyl alcohol (10 milliliters) at room temperature. After the sodium was completely reacted, 4-(2,4,6 dv trimethylphenyl)-5-acetamidotriazole, acetic acid salt (490 milligrams, 71.6 mol) and diethyl carbonate (1.6 milliliters, 13 mol) were added. ). The reaction mixture was stirred at the temperature of phlegm formation for 5

F) hours, then cooled to room temperature. The reaction mixture was dissolved in water, and a solution of IM HC1 was added until the pH level was 5-6, and extraction was carried out three times with ethyl acetate. The combined organic layers were dried over NaOH and filtered. The solvent was removed by mass, which gave a residue of yellow bo Color. Trituration with ether and filtration afforded a yellow solid (300 milligrams, yield 6995): NMR (SOS15, ZOOMHz): 6.98 (in, 2H), 2.55 (8, ZN), 2.35 (in, ZN), 2.10 ( in, 6H); SI-M5: 279(M nn).

Example C

Production of 4-(di(carbomethoxymethyl)-2, 7-dimethyl-8-(2, 4-dimethylphenyl) (1, 5-a|-pyrazolo-1,3, 5-65 triazine. (Formula 1, in which KZ represents CH(ISНСООСН»а)2, VI represents CH with, 7 represents С-CHaz, Ag represents 2, 4-dimethylphenyl).

A. 4-chloro-2.7-dimethyl-8-(2, 4-dichlorophenyl)-(1.5-α|- pyrazolotriazine

Mixture of 2,7-dimethyl-8-(2,44-dimethylphenyl)-(1,5-α|-pyrazolo-1,3,5-4-one (Example 1, 1.38 grams, 4.5 mmol), M, M -dimethylaniline (1 mL, 8 mol) and phosphorus oxychloride (10 mL) were stirred at reflux temperature for 48 hours. Excess phosphorus oxychloride was removed by weight. The residue was poured into ice water, stirred briefly, and quickly extracted three times with ethyl acetate. Combined Organic Layers washed with ice water, then dried over NaCl, and filtered. The solvent was removed by reflux to give a brown oily substance. Thin-layer column chromatography (ethyl acetate:hexanes ratio 1:4) gave one fraction (K/-0.5). The solvent was removed by reflux mass yielded 7/0 yellow oily substance (1.0 grams, yield 68965): NMR (SOS1 3, ZO0MHz): 7.55 (a, 1H, 9-1), 7.38 (aa, yin, 0-71), 7.30 (а, 1Н, 9-7), 2.68 (c, ЗН), 2.45 (c, ЗН); СИ-М58: 327 (М и Н).

B. 4-(di (carbomethoxy) methyl) -2. 7-dimethyl-8-(2.4-dimethylphenyl)-I(1,5-a|-pyrazolo-1.3,5-triazine.

Sodium hydride (6090 in oil, 80 milligrams, 2 mmol) was washed twice with hexane, decanted after each wash, and the moisture was removed with anhydrous tetrahydrofuran (THE, 1 milliliter). A solution of diethyl malonate in /5 tetrahydrofuran (2 milliliters) was added dropwise over 5 minutes, vigorous gas evolution was observed during the addition. A solution of 4-chloro-2,7-dimethyl-8-(2,4-dichlorophenyl)-1|1,5-a|-pyrazolotriazine (0.5 grams, 1.75 mmol) in tetrahydrofuran was added and then the reaction mixture was stirred for 48 hours under nitrogen atmosphere. The resulting suspension was poured into water and extracted three times with ethyl acetate. The combined organic layers were washed once with brine, dried over Mozo, and filtered. The solvent was removed by mass, which gave a brown oily substance.

Column chromatography (ethyl acetate-hexanes ratio 1:9) yielded, after extraction of the solvent and oil, a pale yellow solid (CI -0.2, 250 milligrams, yield 3595): melting point 50-52 degrees Celsius; NMR (SOSIz, ZOOMHz): 12.35 (rg.v5, SHU, 7.15-7.00 (t, ZN), 4.40 (d, 2H, 9-7), 4.30 (ad, 2H, 9-7), 2.4, 2.35, 2.3, 2.2, 2.1.

Example 6 (8)

Production of 4-(1,3-dimethoxy-2-propylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl) (1,5-a|-pyrazolo-1,3,5-triazine. (Formula 1, in which VZ is МНСН(СН оОСНа)», Ви is CH with, 7 is

С-СНЗ3, Ag is 2, 4-dichlorophenyl). co

A. 4-chloro-2.7-dimethyl-8-(2.4-dichlorophenyl)-|1. 5 - ai- pyrazolotriazine.

A mixture of 2, 7-dimethyl-8-(2, 4-dimethylphenyl)-(1,5-a|opyrazolo-1,3,5-4-one (Example 1, 1.38 grams, 4.5 mmol), M, M -dimethylaniline (1 milliliter, 8 mol) and phosphorus oxychloride (10 milliliters) F) were stirred at the temperature of phlegm formation for 48 hours. The excess of phosphorus oxychloride was removed from the fat. at

The residue was poured into ice water, stirred briefly and quickly extracted three times with ethyl acetate. Cha

The combined organic layers were washed with ice water, then dried over Mo5zoO; and filtered.

The solvent was removed by mass, which gave a brown oily substance. Thin-layer column chromatography (ethyl acetate:hexanes ratio 1:4) gave one fraction (K-0.5). The solvent was removed from the oil, which gave a yellow oily substance (1.0 grams, yield 68965): NMR (SOS15z, ZOOMHz): 7.55 (a, 70. H, 9-1), 7.38 (aa, 1H, 9-71) , 7.30 (y, 1H, 9-7), 2.68 (in, ЗН), 2.45 (in, ЗН) ; SI-M5: 327 (M i N). - with B. 4-(I. 3-dimethoxy-2-propylamino)-2. 7-dimethyl-8-(2, 4-dichlorophenyl)-1, 5-α|-pyrazolo-1. c Z. 5- triazine. "» Mixture of 4-chloro-2,7-dimethyl-8-(2,4-dimethylphenyl)-I1,5-a|pyrazolo-1,3,5-triazine (Part A, 570 milligrams, 1.74 mmol), 1 . over Mo5zo, and filtered. The solvent was removed by mass. Column chromatography (CH5Cl25:CH2OH, 50:1 ratio) afforded one fraction. Solvent extraction by mass gave a solid (250 milligrams, yield 35965): (Ce) mp 118- 120 degrees Celsius, NMR (SOS1 3, 300 MHz): 12.35 (rg.5, Sh), 7.50 (v, 1H), tsu 5 7.28 (aa, 2H, 2-8), 6.75 (a, 1H, 9 -8), 4.70-4.58 (t, 1Н), 3.70-3.55 (t, 4Н), 3.43 (в, 6Н), 2.50 (в, ЗН), 2.35 (в, ЗН)4.40 (4, 2Н, 9-7), 4.30 (4, 2Н, 9-7), 2.4, 2.35, 2.3, 2.2, 2.1, (5 85, 12Н), 1.4 (Б ЗН, 9-7), с» 1.35-1.25 (t , ZN); SI-NKM5 : Calculated data: 409.1072, found data: 409.1085. The analysis is calculated for

SivNa"Si2M5O"; carbon, 52.69, hydrogen, 5.17, nitrogen, 17.07, chlorine, 17.28; Found data: carbon, 52.82, hydrogen, 5.06, nitrogen, 16.77, chlorine, 17.50.

The following additional examples shown in Tables 1-4 can be prepared using the above procedures and modifications thereof, which are known to those skilled in the art of organic synthesis. and F) The examples described in Table 1 can be prepared using the methods given in Examples 1, 2, C or 6. In general, the following abbreviations are used: RP is phenyl, Pg is propyl, Me is methyl, Ei is is ethyl, Vi is butyl, Ex is the example number. 60 b5

"Table 1 in

M t X 70! 7

Where I 7 g. t - B; tent t Ag - temperature With app. . | Melting with it is MNeN(СНОМе; Goshcha | 118-120 t sm MNSNR" 2,4-С;-Ры 114-116 8 С-Me 0000 МЕС 2,4-С15-РЕ. oily liquid.

I 3 СМе МРСНо-с-СЗ 2.8 С15-Рв oily liquid:

Гм С-Ме МСНИСОМе)» 2.4 -С1,-РЬ oily liquid shsho| sme / MN-Zteptnya ma-stv 00009092 | sch 128 s-Me MNSNEYSNOMe zua -С-РЬ 6000 TYABIVI iz sme ME 2,4 - SI;-RV. 133-134 about her s.me МНСН(СН:ОЕВ» 2.4 сх-РВ. oily liquid 13 ЕсМе |. МН-З-pentyl 24-С-РЕ 139-140 bro cm ММерии 254 -СсБ-РЕ 60- 62 17 cMe | MR; 2 cb-Rii oily liquid about 187 some IMN-3-texnl 2,4-Cb-P. 130-132 19 c-Me morpholino: 2,4-Ci;-PE - 2: c- Me M(SNRIU SSO Me 254 C5-Pr Se) 21 CMe MNHN(STRYSNOMe | 2,3- B-P 22 | c-Me MH-4-tetrahydrofuranyl 2,4 SARI iz) 23. c-Me "MNecyclopentyl" 5 ,4 -С-РЭ! I scha | 24 С-Me. | 122;3-А-tetrahydroisoquinolinyl 254 -С-Ри 25 сМе | СсНИ234-: | 2,4- С-РА

I / tetrahydroisbinolinyl 26" С-Me ОБ ha -Си5-РЕ 141-143 « 2 | ЕМе ОСШЭВ СНОМе 2,4 С-Ри | 28 С-Me OSНРЕ 2,4 -С5-РЕ - с 29: с-Me O-Z-pentyl 2,4 - Siu-RV 30. S-Me ЗB z, si R -I (65) (se) tsu 5 sb" (F, ko bo 65

3 СМеЕ ЧО 2,4-СБ-РЕ 35; С-Ме 505 2,4-СЁ-РЕ 33. с-Ме ШНО"; 2, -сСС-РЕ:

For C-Me CEO(CO;EO; 2.4 -C-RE 35. C-Me CH(EOScTON 2,4- C-RE 36 c-Me CHO SNMe 2.45 C-PH 137 CMe SOMMe; 2.4 - St.-Rii

ZV cSMe cOSN; 2.4-С5-РЕ 39. О-Ме снсч(ОтшсН,; 2,4-С-БЙ. 40 С-Ме С(ОНУуРН-З-pyrides 5 а- си;-РІи и оф сМе phenyl. for -С- RI!

In S-Me 2-SE»RE 2, A-C5-RE 3. s-m 2-RY-RY 2, - Si-Ry

A c-Me 3-pentyl 2.45 С RE 35; C-Me cyclobutyl. -а-СБ-РН! 1 b СМе о00озепиридило 2,4 - СИ5-Ра 47 с-Ме СН(Ed ССОММе; 2,4 - С;-Р 48 с-Ме СН(ВО) СЕСНММЕ»: 2,4-сб-РЕ 492 С-Ме MneSNISNYUMeU with 2,4,6-Mez-Rii 125-127 50 s-Me MNSNRg; СН-СНИ 2,4,6-мМе-вб 532 | СМе. ЖеНСНюЮМЕ» 2,4, 6- Mez-REI: 1235124 54 С-Me "МН-Z-heptyl: 254, 6-.Mez АРИ. Her 555 | sMe. MNSN(E)SN»OMe: 2.4,5- Mech-Ri 145-146 ! c in 56 | sMe ME 2,4,6- Mez-RE 88-90. 57 S-Me. MNSN(SNOBO» 2,4,6-Me; -RIE. 132-134. i)

BV CMe MN-Z-pentyl 254,6-Mez-RA 134-135 bo c-Me MR 2,4, 6- Mez-Ri 61 c-Me MN-z-texyl 2, 4,5-Mez-RE: . at 62 b-me: morpholino! " MH-4-tetrahydrofuranyl 7.4.6-Me-PE. 56 CMe o MEnocyclopentyl 254, 65-Mezh-Pi and 67 C-Me: 1,2,3,4-tetrahydroisoquinolinyl 2,4,6-Mez-PE m i 58 C-Me Spooz. 2, 4, 6- Mez-PE and letrahydroisochicolinyl) 69 c-Me OB 2.46 - Mez-RV. lo 4 sme OSN(E) STOMEe: 2,4,6- Mez-P " those O-Me OSTI: 2,4,6-Me-RV. y2 C-Me. O-3-pentyl 24, 6.- Mez-RE. ' o) c 73 cMme | 5 2,4, 6- Me-Ri. 74. c-Me 5(O)E 2; 6-Me-RE 5 cMe BOB. 2:4,6-Mez-Ri 76 Cs-Me SNO EB 2,4,6-Mech-Rii 7 sSsMe C(EO(SOEO; 2,4; 6-Mech-RE; - 78. se "SNEDSNON 2,4,6--Mez-RE 79 eMe CE) SNMe 2,4, 6-Mez-RE oo "50 : cSMe: SOMMe" 254.6 -Me-RI: and 81 Csme cOosn; 2,4:6-Mezh-RE. o 82 c-Me. "SNI(OH) SNU 2,4,6- Mez-RE shu 20 83 | cS-Me C(OH).RE-Z-pyridyl 2,4,6-Mes-Rii

And in SMe phenyl, 2.456-Mez-R

F) ime) 60 b5 -4B-

85 cmMe 2 SERIES 254.6- Meu-Ri 86 cm | 2-RI-RE 2,4,6-Mez-Ri 87 C-Me Z-pentyl 2,4,6- Mez-RE. 88 c-Me cyclobutyl. ! 2,4,6- Mez-Rii 89 c-Me Z-pyridyl 2,4, 6- Mez-Riv and 90 C-Me EN(E)SNSOMMe», 24,6- Mez-Ri 91 CMe SNO STISNAMe» 2 , 4-AMez-Ri Even before | 0 sEMe MNSN(SNOMe)» 2,4- Mez Ri 44-45 955 | cSMe MSPSTOMe»» 25a- Me;-PE "oily liquid og. -194 96 S-Me: OIE. 2,4-Mez-Rii oily liquid t СМе. MSS" 2,4-Me-RE 148-150 987. C-Me: "MNeCH (Me) ЕОМе 2, - Mez-Rik 102-104 75 in gosemMe OSN(BO СНОМе 2,4- Mez-RI oily liquid 100 " C Me MRI-c-SZNe 2, 4- Me-Ri oily liquid ab | oEMe | 0 MNen(MeusSTMMe 2, 4 -Mech-Rp 47-48 1027 seme Men) sNnSNAeM 2.4- Me»-REi 117-116 1032 S-Me MmRUYENASNSM: 2.8 - Mez-Ry oily liquid with 104 SMe . MV Sen 24-Me:-RE oily native 20 105 S.Me MNSNE 2.4 - Me»-Ri yub Ss-Me MEVy 2.4 -- Mez-Rii 197 c-Me MR (SNI sn: 2,4 -Me-Ri 108 C-Me. MH:Z-tectyl 2, A- Mez-RE. 109 C-Me. ME 2,4-Me -Rii sc dv | 110 s-Me MNSN (AGAIN: 2,4 -Mech-Rii pi s-Me MN-Z-pentyl with -Mech-RA at 115. S-Me MMery 2,4- Mez-RE

With c-Me MV: 2,4- Me-Ri 4 CMe MY-Z-kexyl 2.4 - Mez-RE 115 C-Me morpholino 2,4-Mez-Rv. and. 30 16 c-Me MSH(SNRI)SNSNOMe 2,4-Me-RE - 117 c-Me MNSN(SNURV) COM 254-Me-Ri

In c-Me MHe4-tetrahydrofuranil 2,4-Mez-RE! (e) it C-Me "MH-cyclopetyl 2,4-Me-Riv 120. c-me 1,2,3,4-tetrahydroisoquinolinyl. 2;4-Me-RI; i. 35 1 C-Me SNY, 34» E 24 -Me-PE cha tetrahydroisoquinolivil); that | and 2 s-Me : OBs | 2,4-Me-Ri ! their s-me oOSSHCHE)SNYUMe 2,4-Meh-Ri.

OA: C-Me OSTR 2,4-Me»-P | « 125 c-Me O-Z-pentyl 2,4- Mez-Rig z ra | cm | 5Ei 2,4--Mech-Rv | n- c 127 C-Me (XE. 2,4-Mez-Ri c GG 2585 C-Me 505 B 2,4-Me5-Ri: » 5 C cMe cH(CO; Ed» 2,4-Me-P 50-52. 129 C-Me C(E)(CO" BO". 2,4-Me-Ri 130 C-Me YESCHEV SON. 2,74- Me» eri -I 131 Cs-Me SEU sNOMe 2,4 -Mez-Ri 132; C-Me CH(EOSN»OVI 2,4-Mez-RI. oo 133. | cMe SOMMez 2,4 -Mez-Ph 434 c-Me SOSsH 2.8-Me;-Rii that 135 | cMe in sn(on sn; 24-Me-Pe: shu 20 i36 | c me C(OH) Pb:3-pyridyl: 2,4 -Me»-Pi: E 137 "C-Me | " phenyl | 2, 4 -Mez- RI; 4 s" ;

F) 5) because b5 -D7-

1351 СМе 1 WED : 24- ME-RE 139 | ССМе | 2-RI-RI 254 --Mech-Rii 140 C-Me Z-pentyl. 2,4-Me-PE 9 141 cSMe cyclobutyl 2,4 Me-Rii 142 Me 3-pyridyl 2,4-Me-Rii 143 c-Me CH(EVSNKSOMMe: |. 2, - Me-RE 14 С Me CH ( EFSNIMMe» 2,4-Me;-PE ! 1455 c-me MySNISNOMe) 5. 2-Me-4-MeO:P 45-46 ! 70 114 c-Me MSNSTOMeE» 2-Me-4-MeO:RI: oily liquid 1472 c-me МНСН(ЕССНюЮМе 2-Me-4-MeО-Рии 86-88 td С-Ме M (RU STSNSM. 2-Ме-4-МеО-Рё oily liquid. 149: СМе OSН(ЕО СОМ. 2 -Me-4-MeosRi: Ш 1507 S-Me MNSN(SNOMe) » 2-Vi-a-MeO-RE! 85-90

Ko S-Me M (СССНОМе) » ! 2-Bi-4-MeO-Rii oily liquid; t 15928 S-Me MNN) SVOME I 2-Vi--MeO-Ry 95-97 153 S-Me M (P)SNeSNSM 2-Vi-4-MeO-RK 154; S-Me | OSNHEO SOME: 2-VIEA-MeO-P 155 C-Me MNSN(CH»OMe)» -2-Me-4-YAMEz-PE 156 C-Me MSNeNOMe) 2AMe-4-YAME-PE oily liquid 157 Same | 0 MNeN (EOSNOME- 2-Me-4 Me RE

Co. | oMe 100 (Rousseau 2Me-AMMeuR 159 C-Me OSN(EUSNIUMe. 2-Me-4-NMez-Rii 160. c-Me MNeN (SNOM) with 2 Vi A-MMe R ii | Me M (SSNNOMO)» 2« Vg-4-KMehstvv with yiv C-Me MNSN(EO SNOM. 2-Bi:4-KMe-Pb ! s 29 4 163 Me o: (ROSS 25Vi-4-MMe-Ri (5) (l C-Me OSN (EOHSNOMEe 2-Vg-4-MMe-Re - 165 s-Me. MNSN(SNOMe) 2-Vi-4--VI-Ri; 4 166. cmMe MmSnSNIME» 2-Vg-4-i-Ri-Rig 167 o Me MYSN(BEOSTYOMe VIR so z 168 C-Me M(RI) SPSNISM 2-AVe-4-i-ri-R her 169 c-Me- OSNO CsNIOMe 25Vg-4-i-Ri-Ri - 170 C-Me МНСН(СНЙЮМе) with 2-Вг-а-Ме-vy about t. С-ме: MaСНСН.ОМе) 2-Ви-4-Ме-Ра 172 с--ме MНеСНЧЕ)СНОМе 2-Ви-4-Ме- RE with 173 c-Me. M (Rg) SNISNSM 2-Vi-4-MesRE: ; 4 CMe. OSN(EO SNOM. 2-Via-MeRy 1 | - i75h "C-Me MNeN(STOMe)" 22Vi-4 -Me-R; | 108-109 176 | sMe MSNSNOMe)" 2-Vi-4-Me-RA ! to her S-Me: MiISN (BO SNOMe 2-Vita-MesRii « p o| sme M (Re) SNISTSM 2 -Vi-y-Me-Rv 20 179 C-Me OSN(EVSNOMe | 2-Vi:-4-Me-Rii | with c 180 CMe | MNeN(SOMg) 2 | 2-021-46-Mech-RE 4181 С -Me MISVSNOMe)". vva Me -P. z" 182 CE-Me: kNeSN(STOMe)" deVg-2 6 (Me); -RI. 4183 s-Me M(STSNOME)". 4-Vi-2,640 Mer Re 184 S-Me. MNN (SOM) 4-i-Ri-2-5Me-Ri 185 C-Me: M (СПСНИюЮМе)» a-i-сRi-2-5Me-Re - 1486 s-Mme MNSN (SOM 2-Vy-4- SEER: p 187 O-Me M(SNASN»Me» 2VgA-SEHRI 188 C-Me MNeN(SNIMe)» so 2-Vi-4,6-(Meb)-Ri

Ge) 139; EMe | M(TOLERABLE) 5 | 2-Vg46b-(MeO)-Ry Her 190 | c-Me MNSN(SNYUMe): 00002-01-4,6-(MeO)o-Rv - Yur O| s-Me. MeSNeNOMe) 5 2-21-4,6-"MeO)z-Rii (with 192 S-Me. MNSN (SNOM) » 2,6:-(Me)u"-4-5Me:-Rii

F) ho) bo b5

193: СМе СНО те) 2 26-(Mer--5MeRy 194. с-Ме кнснисноМе; 4-(СОМеу-2-VI-Рр 195. | С-Ме ZheTSNOМе» ASOM) -2-VI- RE.: 196 : C-Me MNeN(COMe) 2,4,6-Mespyride-Zyl | and 197 c-m SNOM); 2,4,6-Mespyrid-Znlo at 198: C-Me MNSN(SNOMe)" 254 (Hgu-Ri: 199. C-Me MSTSNOMe" 2, 8-(Hg)eRy 200 C-Me MYSN(SNYUMe )» a-i-RI2: Mer o OO сMe M(SNISNOMe)» es 5MeR, 202 с-Me MNeN (СН2ОМе» а-и-Ри-2-805М ERA 203: СМе | "ШчеНстТОМе)» 4--Рг -2-50; Me-Rii 204 o-Me MHC Me)" 25, 6b-(Me)"-4-5Me-Pb 205 C-Me: M(SNSTOME". 2, 6-(Me)"-4 -5Me-Ri. 206 Cs-Me: Mnen(snOmM g)" 2.6- (Me) 54-80; Me-Rii 207 cE-Me MSNeNOMe); 2,6-(Me) 2502 MeR 208 cMe | MNSN(SNOMer » 2-1-4-i-ri-RE 72095 S-Me MSVBSNYUMe)". 2-1-4-RIURY 210 S-Me- MNeSNISNOM ee)". 2-Vi-eM- (Mer-6-Mes- Riin cSme | MmsSnetOMe" 2-Vi-A-M. (Me)"-6-MeO-Ri : | 22 se-Me MNeCH(SNuMe); 2,.4-15Me) 2-Pn 213: E-Me MSNeNOMe) 5. 2, A-I5Me | 2-5 ma s-Me МNeNeSNYUMe)" 2, A-I1505Me1 2-RIi . sme m(sSpsNnyuMe): ! 2. A-1505Me) 2-Ri 216 O-Me: МНеСН(СНОМе); 4-Ри2-5МесРЕ: 2 Orosye-Me MshСНеНноМо)" | 4с1-Ри-2-5Ме-Ри with 25 218 ЕМе МНеН(ШОМе» D-isre-2-505 Met o 2193 СМЕ Mem)» 4-iVe-2-502Me-Ri 220 "Me MNeN(SNOMe)" 2-4 (Meu 2:4-Me-P: 221 exactly MISTSNIOMe) 5: 2-M (Me) A-Me-RE 222 cMe MNSN (STO Me)» 2-Meb-4, 65 (Me) 5-Ri c zo 223 C-Me: M(SNCHNOM a) 5 2-Meb5-4, 6-4Me) 2 Ri 224 cmMe NSS Me)» 2-4SNSO ) -4, 6- (Me) Rie! - 225 СМе МИСТОМ)» 2-(С85СО)-4; 6- (Me Vii F 226 CH MNSN(СНОМе); 2,А-Мез-Рв

I 227 sn M(eNeNuMe), 2,4-MehRE with 228 se, MNeEP"SNOME)" 2, 4-Me»-Rk 1 229 "SE. MSNISNOMe) 254-MehRE - 230 ot MNeN(SNO Me)" 2 ,4-Me»- RK 231 | sazog MNSNRe 2, 4, 6-MezRi: 232 goth /MeVy. 2,4, 6-Me»Ri " 233 nitrogen MRG (SNI-c-C3 NU 2, 5; 6- Meu RE. 234 zyut MSNIENUMe) 2, 4,6-MechR.; o) c 235 pot /.MNoZ-teptyl 2, 4, 6-Mez»Ri

Collected: aut: MNeN (BO SNOM: 2, 4, 6-Mez-P: ! z» 237 yot MB 2; A, 6-Met 238 nitrogen МНЕНИСНОБО with 2,4,6:Me:Ri 239 nitrogen: МНЗ- pentyl. 2, A,.6-Mez-Rii: 240 | ab MMeriai | 2, 4, 6-MechRi; - 241 nitrogen Mt» 24.6 Mez-RV. ! o | 4 | zho "MNEZ-hexnl 2, 4,6-MeR: 243 au Morpholino 2,4,6-Me-RI" -Pv 2Av: nitrogen MH-tetrahydrofuran | 2,4, 6-Mes-Ra s» 247 ato MH-cyclopentyl- 2,4, 6-Mes-Rii (F, ih) 60 b5

248 nitrogen: 152.3, Х-tetragylroisoquinolinyl 2,4, -Mez-Ri

What tetrahydroisoquinolinyl); more 250 nitrogen OB 2, 4,6-Mez-Rii 251 nitrogen OSNO СОМе 2,4, 6-Mez-Rii 252 nitrogen | OSNOR 254, 6-Mez-PE 253 nitrogen O-3-peptyl 2,5, 6-MeuRV 254 nitrogen ЭЭ 2,4, 6-Mez-PE o 1 2255 azoi 50) 2,8, 6-Mez-PE p 256 nitrogen 50" V 2.4; 6-Mez-Ri 2-1 nitrogen | sleep; EE) 2 A, 6-Mech-Ri; 58 nitrogen FEO(CO»Ed; 2, 4, 6-Mech Ri; 259 nitrogen of СОН 2; 4; 6-MechR 260 nitrogen | 000 СхШЧЭ)СНОМе 7,4, 5-Mech-RB 261 nitrogen СОММech 2, 4 . | nitrogen | 7 phenyl. | 2,4,0-Me-Rii -266 nitrogen 2-SEURY 2,4, 5-Mez-PRE 720 267 nitrogen 2-RISPRE. 2,4, 6. Mayor. 268 Nitrogen of Z-pentyl 2, 4, 6-Mes-Rii 269 Nitrogen of cyclobutnium: ! 274.6 Meri 2759 nitrogen Z-pyridyl 2, A, B-Mez-RE 2 nitrogen SV (EVSVSOMMech 2,4,6-Mech RE ch 272 aiot ХНО СНИСНоММЕ» 2,4, 6-MezRy. o 273; nitrogen. МНСН (СНОМ) » 2,А-МехРи гла; nitrogen МНеНРе 2, 4-Ме-Рии 275. nitrogen MEVy 2,4-Мез-Ри 216 nitrogen. Mр (СНус-СзН5) 2, А-МехРе : с 277 nitrogen M (SNISNYUMe 5. 2 A-MenRv 278: nitrogen MH-3-teptyl 2,4-Meh Ri; «- 279: nitrogen MNSN(EUSPUMe 2, AAMe:PE 280: nitrogen: ME 2, 4-Me-Re F 282 nitrogen MN-Z-pentyl 25A-Me»- RE

Gaia | obsv. MIMERA Ba Meriv m- 284 nitrogen MR; 2,8-Me»-RE 285 nitrogen МН-З-hexyl 2, 4-Me» RE 286 nitrogen morpholino 2,А-Me»-Ре ов nitrogen МСНРИ) SVIISNOMe 2,4-Mech Re « 288. nitrogen "МНЕН (SNIRI) SNOMe Z, a-Mez-Ri. - 70 289: nitrogen MA - tetrahydrofuranite 2, a: MechRy c 290 nitrogen - MH-yclopentyl 2, 4-MechRa. ! h» 29 nitrogen 155.3, A-tetrahydroisoquinolinyl . | 2, 4 MeR " . 295 nitrogen CH a- 274 Mech Pv hetrahydroisoquinolinyl): 295 nitrogen OO 2, A-Me»Ra -1 294 nitrogen OSN(E) CHOM 2, A-Me-Ry 295. nitrogen OSNORI: 2.4 MERE and 296 nitrogen " 0-3-pentyl 2, 4 Me»so 297 nitrogen ZE 2,4-Me»PE 298 1 agate | (0) E 2,4-MeRi - 70 299 1. nitrogen 50; EC 2, A-Me»P syu 300 And nitrogen sy(сО» EE» 72. 4-Me-PE

F) name) 60 b5

With nitrogen TOBBBSSOE 2,4-Me»Pb ! 302: azoi SPE SON 2; 4-Mez-PE 303 nitrogen STE) STOMe 2,4-MeRizo nitrogen "SOMMe; 2,4-Me»RV 305. nitrogen cOosn 2 A-Me-Ri 06 nitrogen CsH«OH) CH 2,4-Me- RE

A 307 nitrogen ХУН) PE-Z-pyridyl 2,4-Me»-Ry and 308 nitrogen "phenyl. 2,4-Me»-R 309 azo 2-SERY 2, 4-Mez-Ry 310 yaot" 2-PH -Pb 2, 4-Mez-Pb

C nitrogen 3-pentyl 2, A-MePE 312: nitrogen cyclobutyl 2,4-Me-PE. and 313. nitrogen Z-pyridyl 25 4 MehzRI

With nitrogen: sp(EussSOMMe 2, A-Mech PE, ' 315: nitrogen. CH(EUSNIENNoMM ee". 2,4-Mez-PE. 3167 Me. ME 2-Bi-4-MeO-P) oily liquid with?" exactly | MH-3-Ppentyl 27Vg-4-MeO-Rii oily liquid 318" E-Me o (NNSC(SNeN oOMe)ENOME 25 8,6-Meh»RH 101-103

ZI EMe: Mia-CH) 2uA-Mech Ri oily liquid - with C-Me merfolino 2, 4, 6-Mez-RE 139-140 according to CE-Me MNSN(SNYUMe) with 2-SM.A-MesRv 152-153 .

KUg b-Me | m(-SnaEnneNneM 2,4, 6-Me»Rii 6 MmolAi zd S-Me / |InNSneENeN homEU SNOM 2Me-4Vi-Ry 0 5chE 3257: s-Me MNeN(SNoOMe); 22 U-MenA-MeO-Riii 35 -57 call: C-Me M(SSTOMe) 2 2,5-Me»4-MeO-REi 72 4 sc

With C-Me MH-3-pentyl 2, 5-Me-MeO-Ri yakat z-Me ME 2,.5-Mez-4-MeO-Rii oily liquid. (8) 329" c-Me MNSN (СНОМе)" 2-С1-4-МеРЕ 80-81

With 00sMe Msn(vdsvoMe | 2ySi-4-MerRi T-9. 3 cS-Me . M(SSNNOMeu -2-С14АМеР oily liquid with З3ae С-Me (53-ЧНСН(СНСНОМеU -2-01-А-МеРи 139- 140 o | CH:OMe | | ! | "-- z" c-Me: M (en) ENSNSM 2, 5-Me»-4-MeoRi o l420-122 zzy -Me ME -2-Me-4-MeORI oily liquid. (22) 335 s-Me Ov 2-Me-4-MeoOrA: oily liquid with C-Me 6)-MNen (СССВОМа). 2-Me-4-MeORE oily liquid, snuMme і- 337310 0- Me Mis) SNSNeM 2-Me-MeORB 129 zach cS-Me her MNnenH(SNeNOVO) І 2-Me-4-MeRiv amorphous substance 339 E-Me M (с-СЗН;У СНИСНСМ 2, 4-С1Б5-РЕ 461 ! by C-Me (5) -MNSN(SNISNOMe) 2, A-C-Ri 93-94 « t0 By ME -"MH-Z-pentyl-2-Me-4-HgRE. 115-119 s 342 C-Me М(СНеНнюМе)., "2-Me-4-VIRI. oily liquid: h» for 3 СМе МНСН(ЕН»-иР) СИОМе 2-Ме-4-ВгРЕ oily liquid " 344 сСМе МНСН (Ри)СНОМе 2-Me -45 Versions and 94-95

Жх | S-Me MNSN (EOUSNE 2-Me-4-VIR 76-77

Zb 10 cS-Me / |NeN(SNOMeOSnenOMe 2-Me-4-MeMRi. oily liquid -I 347 c-Me. o MEb 2-Me-4-SULFUR oily liquid. 348 c-Me | -"MN-Zepentyl. 2-Me-4:Sulphur: 122-124 o 349 E-Me M(CH.CH»OMe) 2-Me-4-SUlphurous oily liquid: (Ce) Z | 0 EeMe MNSN(SNUMe) 5. 2Me-4 -SUR 122423 351 cE-Me MES 2-Me4-SIRa. oily liquid: - 70 352 c-Me ME 2-C1-A-MeORE: oily liquid c" 353 C-Me MN-Z-pectyl 2-SI-A -MeORi 120-121.

F) name) because b5

354 c-Me MNSN(SNOMe) 2 2-SIA-MeoORA 3557 C-Me M (SNSVOMEe) » 2-Si-4-MeORi oily liquid with C-Me MNSN (EE) COMe 2-C14-MeORA 108-110 357 c-Me M (с-РО) СИБСНСМ 2-С1-4-МеОРи 127-129 3587 С-Ме ME 2-С1-4-МеОРЬ oily liquid with с-Ме МН-3-pentyl 2-С1-44-МеОРи 77-79. 4-MeORB 363 C-Me МНСН (Me) СТСН»ОМе 2-Ви-4-МеОРа зб4 с-Ме МНСН (EO СТСНОМе 2-Me-4-Meory 365 С-Me МНСН (Me) СЙСН»ОМе 2-Me -4-MeoRy 366 c-Me MNSN (СНОМ) 2 2-СИ-4, 5- (MeО) RA 367 С-Me M(СНСТОМе) 2-С1И-4, 5- (MeO) P 368 С-Me MNSN (E) СНОМе 2-СИ-4, 5- (МеО) ории 369 с-Ме M (с-Р) СНСНСМ 2-С1-4, 5- (MeО) »Ри 370 С-Ме ME 2-СИ-4 . -Me MNSN (Me СНоСН»ОМе 2-С1-4, 5- (MeO) zRA ztam C-Me МНОСН(СНОМе) 5 2-Вг-4, 5- (MeO) 2Рии 137-138 375 s-Me M( SNASNOMe), 2-Vg-4, 5- (MeO) 2Rii 3767 c-Me MNSN (E) SNOME 2-Vg-4, 5- (MeO) P I 147-148 377 s-Me M (s-Ri) SSNISM 2-VI-4, 5- (MeO) RP 378 S-Me MES 2-Vi-4, 5- (MeO) Ri 52-58 sch 379 С -Me MH-3-pentyl 2-Vg-4, 5- (MeO) 2PE 380 C-Me MNSN (BO SIESTOMe 2-Vi-4, 5- (MeO) Ri i) 381 s-Me MNSN (Me) SNSNOME 2-Vg-4, 5- (MeO) RP 382 c-Me MNSN (E)O СОМе 2-C1-4, 6- (MeO) zP

383 c-Me MNSN (Me) СОMe 2-С1-4, 6- (MeO) 2Рии 384 С-Me МНСН (Ed СНОМе 2-С1-4, 6- (MeO) Ra o 385 Сс-Me M (с- Ри) СНСНЖСМ 2-С1-4, 6- (MeO) 2Р «- zve c-Me ME 2-С1-4, 6- (MeO) zr 387 с-Me МН-3-pentyl 2-С1-4, 6 - (MeO) Ri F 388 S-Me MNSN (BO CH»CH»OMe 2-C1-4, 6- (MeO) Ri d 389 S-Me MNSN (Me) SNASNOMe 2-С1-4, 6- (MeO ) P 390 S-Me MNSN (B) SNoOMe 2-Me-4, 6- (MeO) »Ri M 391 S-Me MNSN (Me) SNOMe 2-Me-4, 6- (MeO) Ri 392 s-Me МНСН (Ed) СОМе 2-Me-4, 6- (MeО) »РВ 393 с-Ме M (с-Р) SNASNSM 2-Me-4, 6- (MeО) 2РВ 395 с-Me MEБ 2-Me- 4, 6- (MeO) Ri « 396 cS-Me MH-3-pentyl 2-Me-4, 6- (MeO) Ri - 70 397 c-Me MNSN (EE) SNASNOMe 2-Me-4, 6- ( MeO) Ri c 398 c-Me MNeCH (Me) SSNYMe 2-Me-4, 6- (MeO) RI c» 399 C-Me M (c-P) СсНСМ 2-Me-4, 6- (MeO) zr . Vg-4, 6- (MeO) Pv -1 403 C-Me MNSN (Me) SNASNOMe 2-Vi-4, 6- (MeO) Pv 404 C-Me MNeCH (Ed SNCH»OMe 2-Vg-4, 6 - (MeO) Riio, 405 s-Me MNSN (Me) SNNOMe 2-Me-4-MeORI: so 40 6 s-Me MNSN (Ed CH»OMe 2-Me-4-MeoR 407 S-Me MNeSN (Me) SNOMe 2-Me0-4-MeR -sho 70 408 S-Me MNSN (BO SNOMe 2-MeO-4- Merrii so 409 c-Me M (s-Ri) SNSNSM 2-MeO-4-Merii (F) ko bo b5

. with. What . Notes to 40 C-Me | ME I I 2-MeO-4-Mery: Shchi z zhi S-Me ; /MNOZ-pentyl 2-MeO-4-Merv. ! AND

A C-Me MYSN(EOSNSTOME 2-MeO:-4-Merv. I 413 c-Me MNN (Me) CISS»OMe 2-MeO-4-Merv ! 414 C-Me MNSN(E)OSTYOMe 2-Me0-4 -MerRii 415 S-Me MNON (Me SNOME: 2-MeO-4-Merii 16. S-Me ! MNSN(E) STOOMe 2 Me0-A-MerRi 417 S-Me: Mer) SNSNSM 2-MeO-4-Mer 70 418. C-Me ME 2-Meb:4-Meriai 419. C-Me MN-Z-pentyl 2-Me0-4-MeRi 40 | cMe MNSN(BuUSSNNOMe 2-MeO-4-Meriai 421 | cMe MNSN (Me) SNNOMe 2-MeO-4-Mer 423y c Me MNSN (ED CHNOM 2-MeO-4-Mer. 44 cMe MNSN(Me) SNOME 2-MeO-4-Mer. 425: s--Mme | MNSN( EO SOME 2-MeO-4-SULFURE oily liquid 427 C-Me ME 72-MeO-A.SULFUR 428 seMme MN:3-pentyl 2-MeO-4-SULFURE 429 | c-Me | MNSN(BO)STSTOMe iMebasR 430 C-Me MNeNMe) snSNyuUMe 2-MeO-4-С1РН

Table 1: a) Analytical calculated data: carbon, 52.69, hydrogen, 5.17, nitrogen, 17.07, chlorine, 17.28; Found data: carbon, 52.82, hydrogen, 5.06, nitrogen, 16.77, chlorine, 17.50. with

B) SI-NKM5: Calculated data: 406.1565, Found data: 405.1573 (Men); Analytical calculated data: Ge) carbon: 59.11; hydrogen: 6.20; nitrogen: 17.23; chlorine: 17.45; Found data: carbon: 59.93; hydrogen: 6.34; nitrogen: 16.50; chlorine: 16.95; NMR (SOS13, ZOOMHz): 0.95 (B 9-8, 4H), 1.30-1.40 (t, 4H), 1.50-1.75 (t, 4H), 2.35 (in,

ЗН, 2.48 (в, ЗН, 4.30-4.45 (t, 1Н), 6.15 (а, 9-8, 1Н), 7.30 (5, 2Н), 7.50 (5, 1Н). c) SI-NKM5: Calculated data : 392.1409, Found data: 392.1388 (MAN); NMR (SOS13, ZOOMHz): 1.00 (i, U o -8, ZN, 1.35 ( 9-8, ZN, 1.41 (a, 9-8, 2H), 1.65-1.85 (t, 2H), 2.30 (85, ЗН), 2.40 (в, ЗН), 3.85-4.20 (t, --- 4Н), 7.30 (в, 2Н), 7.50 (в, 1Н). a) SI--КМ5: Calculated data: 404.1409, Found data : 404.1408 (MAN). NMR (SOS13, ZOOMHz): 0.35-0.45 (t, o 2H), 0.52-0.62 (t, 2H), 0.98 (5 9-8, ЗН), 1.70-1.90 (t, 2H) .

Zo e) SI-NKM5: Calculated data: 424.1307, Found data: 424.1307 (MAN). NMR (SOS13, ZOOMHCts): 2.28 (v, ZN), - 2.40 (v, ZN), 3.40 (5, 6H), 3.75 (Y, 9-8, AN), 4.20-4.45 (t, AN), 7.30 (5, 2H), 7.50 (in, 1H).

In SI-NKM5: Calculated data: 406.1565, Found data: 406.1578 (MAN); NMR (SOS13, ZOOMHz): 0.90 (i, 9-8,

ZN), 1.00 (Her, 9-8, ZN), 1.28-1.45 (t, 4H), 1.50-1.80 (t, 4H) , 2.35 (in, ZN), 2.50 (in, ZN) , 4.20-4.35 ( t, 1H) « ; 6.10-6.23 (t, 1H), 7.30 (in, 2H), 7.50 (in, 1H). From 70 9) SI-NKM5: Calculated data: 394.1201, Found data: 394.1209 (MAN); NMR (SOS13, ZOOMHz): 1.02 (6, 9-8, s ZN), 1.65-1.90 (t, 2H), 2.35 (v, ZN), 2.48 (v, ZN), 3.40 (v, ZN), 3.50 -3.60 (t, 2H), 4.35-4.45 (riv, 1H),

From" 6.50-6.60 (t, 1H), 7.30 (in, 2H), 7.50 (in, 1H).

R) SI-NKM5: Calculated data: 364.1096, Found data: 364.1093 (MN). Analytical calculated data: carbon: 56.05; hydrogen: 5.27; nitrogen: 19.23; chlorine: 19.46; Found data: carbon: 55.96; hydrogen: 5.24; nitrogen: 18.93; chlorine: 19.25; NMR (SOS13, ZOOMHz): 1.35 (Her, 9-8, 6H), 2.30 (3, ЗН), 2.40 (z, ЗН), 3.95-4.15 (t, 4Н), 7 7.30 (v, 2Н), 7.50 (y, 20-1.1Н). z i) SI-NKM5: Calculated data: 438.1464, Found data: 438.1454 (MAN); NMR (SOS13, ZOOMHz): 1.22 (y, 9-8, 6H), 2.35 (5, ЗН), 2.47 (в, ЗН), 3.39 (а, 9-8, 4Н), 3.65 (aa, 9-81 . , 1H). -k 70 Y) SI-NKM5: Calculated data: 378.1252, Found data: 378.1249 (MAN); Analytical calculated data: carbon: 57.15; hydrogen: 5.61; nitrogen; 18.51; chlorine: 18.74; Found data: carbon: 57.56; hydrogen: 5.65; nitrogen: p» 18.35; chlorine: 18.45; NMR (SOS13, ZOOMGhzC): 1.00 (6 9-8, 6H), 1.55-1.70 (t, 2H), 1.70-1.85 (t, 2H), 2.35 (in,

ЗН), 2.50 (in, ЗН), 4.15-4.25 (t, 1Н), 6.18 (j, 9-8, 1Н), 7.30 (в, 2Н), 7.50 (5, 1Н).

KU) SI-NKM5: Calculated data: 398.0939, Found data: 398.0922 (MN); Analytical calculated data: 29 carbon: 60.31; hydrogen: 4.30; nitrogen: 17.58; chlorine: 17.80; Found data: carbon: 60.29; hydrogen: 4.59; nitrogen:

GF) 17.09; chlorine: 17.57; NMR (SOS13, ZOOMHz): 2.05 (v, ZN), 2.50 (5, ZN), 3.78 (v, ZN), 7.20-7.45 (t, 7H), 7.50 (a, 9-1, 1Hn). o I) SI--KM5: Calculated data: 392.1409, Found data: 392.1391 (MAN); NMR (SOS13, ZOOMHz): 0.98 (i, 9-8, 6H), 1.70-1.85 (t, 4H), 2.30 (v, ЗН), 2.40 (v, ЗН), 3.80-4.10 (t, 4Н) , 7.30 (5, 2H), 7.50 (a, 9-1, 1H). 60 t) SI-NKM5: Calculated data: 392.1409, Found data: 392.1415 (MAN); Analysis: Calculated data: carbon: 58.17; hydrogen: 5.92; nitrogen: 17.85; chlorine: 18.07; Found data: carbon: 58.41; hydrogen: 5.85: nitrogen: 18.10; chlorine: 17.75; NMR (SOS13, ZOOMHz): 0.90-1.05 (t, 6H), 1.35-1.55 (t, 2H), 1.55-1.85 (t, 4H), 2.35 (v, ZN), 2.48 (5, ZN), 4.20- 4.35 (t, 1H), 6.15 (9, 9-8, 1H), 7.30 (in, 2H), 7.50 (y, 20-1.1H). n) SI-NKM5: Calculated data: 337.0623, Found data: 337.0689 (M.N); Analysis: Calculated data: carbon: bo 53.43; hydrogen: 4.18; nitrogen: 16.62; chlorine: 21.03, Found data: carbon: 53.56; hydrogen: 4.33; nitrogen: 16.56;

chlorine: 20.75; NMR (SOS13, ZOOMHz): 1.60 (B, 9-8, ZN), 2.40 (5, ZN), 2.55 (z, ZN), 4.80 (ad, 9-8, 2H), 7.30 (a, 3-8 ,1H), 7.35 (aa, 9-8,1,1H), 7.55 (a, 9-1, 1H). o) SI-NKM5: Calculated data: 383.2321, Found data: 383.2309 (MAN); NMR (SOS 13, ZOOMGhzC): 2.00 (in, 6H), 2.20 (85, ZN), 2.30 (5, ZN), 2.45 (in, ZN), 3.45 (in, 6H), 3.61 (aa, 9-8 , 8, 2H), 3.70 (aa, 9-8, 8, 2H), 4.60-4.70 (t, 1H), 6.70 (a, U-8,1H), 6.94 (c, 2H). r) SI-NKM5: Calculated data: 370.2243, Found data: 370.2246 (M.N); Analysis: Calculated data: carbon: 65.02; hydrogen: 7.38; nitrogen: 18.96; Found data: carbon: 65.22; hydrogen: 7.39; nitrogen: 18.71; NMR (SOS13,

ZOOMHz): 2.18 (5, ZN), 2.30 (v, ZN), 2.45 (5, ZN), 3.45 (v, 6H), 3.60 (aa, 9-8, 8, 2H), 3.69 (aa, 9- 8, 8, 70.2 H), 4.60-4.70 (t, 1H), 6.70 (a, 9-8, 1H), 7.05 (a, 9-8, 1H), 7.07 (a, 9-8, 1H), 7.10 (c, 1H). a) SI-NKM5: Calculated data: 384.2400, Found data: 384.2393 (MN); NMR (SOS13, ZOOMHCc): 2.16 (in, ZN), 2.25 (8, ZN), 2.35 (in, ZN), 2.39 (in, ZN), 3.40 (in, 6H), 3.77 (9-8, 4H) , 4.20-4.45 (t, 4H), 7.02 (a, 3-8,1H), 7.05 (c, 1H), 7.10 (a, 9-7, 1H). "In SI-NKM5: Calculated data: 354.2294, Found data: 354.2271 (MAN); Analysis: Calculated data: carbon: 67.96; hydrogen: 7.71; nitrogen: 19.81; Found data: carbon: 67.56; hydrogen: 7.37; nitrogen: 19.60 ; NMR (SOS13,

ZOOMHz): 1.03 (5 9-8, ZN), 1.65-1.88 (t, 2H), 2.17 (in, ZN), 2.30 (in, ZN), 2.35 (5, ZN), 2.45 (in, ZN), 3.40 (5, ZN), 3.50-3.62 (t, 2H), 4.30-4.45 (t, 1H), 6.51 (a, 9-8, 1H), 7.04 (a, 20-8,1H), 7.10 (a , 9 -8, 1H), 7.12 (c, 1H). 8) SI-NKM5: Calculated data: 338.2345, Found data: 338.2332 (M.N); Analysis: Calculated data: carbon: 71.18; hydrogen: 8.06; nitrogen: 20.75; Found data: carbon: 71.43; hydrogen: 7.80; nitrogen: 20.70; NMR (SOS13, 2o ZOOMHz): 1.00 (6 9-8, 6H), 1.55-1.70 (t, 2H), 1.70-1.85 (t, 2H), 2.19 (v, ZN), 2.30 (v, ZN), 2.35 (8, ЗН), 2.46 (в, ЗН), 4.15-4.26 (t, 1Н), 6.17 (а, 9-8, 1Н), 7.06 (а, 20-8,1Н), 7.10 (а, 9 -1, 1H), 7.13 (8, 1H). 9 SI-NKM5: Calculated data: 324.2188, Found data: 324.2188 (MAN); NMR (SOS13, ZOOMHz): 1.25 (i, 3-8, 6H), 2.16 (Z, ZN), 2.28 (5, ZN), 2.35 (v, ZN), 2.40 (v, ZN), 3.95-4.20 ( t, 4H), 7.05 (aa, 9-81, 1H), 7.07 (5, 1), 7.10 (a, 9-1, 1Hn) c and) SI-NKM5: Calculated data: 346.1780, Found data: 346.1785 ( M.N); Analysis: Calculated data: carbon: 66.07; hydrogen: 5.54; nitrogen: 28.39; Found data: carbon: 66.07; hydrogen: 5.60; nitrogen: 27.81; NMR (SOS13, (8)

ZOOMHz): 2.15 (in, ЗН), 2.32 (8, ЗН) 2.17 (in, ЗН), 2.52 (in, ЗН), 5.25-5.35 (t, 4Н), 7.08 (в, 2Н), 7.15 (в, 1H).

M) SI-NKM5: Calculated data: 340.2137, Found data: 340.2137 (M.N); Analysis: Calculated data: carbon: 67.23; hydrogen: 7.42; nitrogen: 20.63; Found data: C: 67.11; hydrogen: 7.39; nitrogen: 20.26; NMR (SOS13, ZOOMHz): c zo 1.40 (a, 9.-8, ZN), 2.16 (b, ZN), 2.32 (b, ZN), 2.35 (8, ZN), 2.47 (b, ZN), 3.42 (c, ЗН), 3.50-3.60 (t, 2Н), 4.50-4.15 (t, 1Н), 6.56 (a, 9-8, 1Н), 7.00-7.15 (t, ЗН). -- m) SI-NKM5: Calculated data: 355.2134, Found data: 355.2134 (MAN); NMR (SOS13, ZOOMHz): 1.05 (i, 9-8, Ge!

ЗН), 1.85-2.00 (t, 2Н), 2.17 (в, ЗН), 2.36 (з, 6Н), 2.50 (в, ЗН), 3.41 (в, ЗН), 3.45 ( aa, 9-8, З31Н) , 3.82 (a49, 9-8, 1, 1H), 5.70-5.80 (t, 1H), 7.00-7.20 (t, ZN). and x) SI-NKM5: Calculated data: 364.2501, Found data: 364.2501 (MAN); NMR (SOS 13, ZOOMHz): 0.35-0.43 u- (t, 2H), 0.50-0.60 (t, 2H), 0.98 (f 9-8, ЗН), 1.20-1.30 (t, 1H), 1.72-1.90 (t, 2H), 2.18 (in, ЗН) 2.28 (in,

ZN), 2.35 (in, ZN), 2.40 (in, ZN), 3.88-4.03 (t, 2H), 4.03-4.20 (t, 2H), 7.00-7.15 (t, ZN). y) SI-NKM5: Calculated data: 353.2454, Found data: 353.2454 (M.N); Analysis: Calculated data: carbon: 68.15; hydrogen: 8.02; nitrogen: 23.84; Found data: carbon: 67.43; hydrogen: 7.81; nitrogen: 23.45; NMR (SOS13, "

ZOOMHz): 1.38 (а, 9-8, ЗН), 2.18 (в, ЗН), 2.30-2.40 (t, 12Н), 2.47 93, ЗН), 2.60-2.75 (t, 2Н), 4.30-4.50 (t , Z s 1H), 6.60-6.70 (t, 1H), 7.00-7.15 (t, ZN). . 7) SI-NKM5: Calculated data: 361.2140, Found data: 361.2128 (MAN); NMR (SOS13, ZOOMHz): 0.75-0.83 (t, a 2H), 1.00-1.10 (t, 2H), 2.17 (in, ЗН), 2.30 (in, ЗН), 2.36 (in, ЗН), 2.47 (in . aa) SI--KM5: Calculated data: 363.2297, Found data: 363.2311 (MAN); NMR (SOS13, ZOOMHz): 1.01 (i, -I ZN, 8), 1.75-1.90 (t, 2H), 2.15 (v, 3H), 2.19 (v, ZN), 2.35 (v, ZN), 2.40 ( в, ЗН), 2.40 (в, ЗН), 2.98 (и, 2Н, 9-8), 3.97-4.15 (t, 2Н), 4.15-4.30 (t, 2Н), 7.03(4, 1Н, 1), 7.08 (a, 1H, 9-8), 7.10 (c, 1H). o ab) SI--KM5: Calculated data: 363.2297, Found data: 363.2295 (MAN); NMR (SOS, ZOOMHz): 1.01 (i, ZN, (Ce) 9-8), 1.35-1.55 (t, 2H), 1.75-1.90 (t, 2H), 2.15 (v, ZN), 2.30 (v, ЗН), 2.36 (в, ЗН), 2.46 (в, ЗН), 4.10-4.30 шу 20 (t, 2Н), 4.95-5.10 (Бг 5, 2Н), 7.05 (а, 1Н, 9-8), 7.10 (a, 1H, 9-8), 7.15 (c, 1H). as) SI-NKM5: Calculated data: 368.2450, Found data: 368.2436; Analysis: Calculated data: carbon, (45) 68.62, hydrogen, 7.95, nitrogen, 19.06; Found data: carbon, 68.73, hydrogen, 7.97, nitrogen, 19.09; NMR (SOS),

ZOOMHz): 1.05 (5 9-8, ЗН), 1.70-1.90 (t, 2Н), 2.01 (y, 9-3, 6Н), 2.20 (в, ЗН), 2.30 (в, ЗН), 2.46, 2 .А465 (v, 8, ЗН), 3.42, 3.48 (v, в, ЗН), 3.53-3.63 (t, 2Н), 4.35-4.45 (t, 1Н), 6.73 (а, 9-8,1Н), 6.97 (c, 2H). (a4th) SI-NKM5: Calculated data: 352.2501, Found data: 352.2500 (M "N); Analysis: Calculated data: carbon: 71.76; hydrogen: 8.33; nitrogen: 19.92, Found data: carbon: 71.55; hydrogen: 8.15; nitrogen: 19.28; NMR o (SOS13, ZOOMGhC): 1.01(, 9-8, 6H), 1.58-1.70 (t, 2H), 1.70-1.85 (t, 2H), 2.02 (v, 6H), 2.19 (v, ZN), 2.45 ko (5, ZN), 4.12-4.28 (t, 1H), 6.18 (a, 9-8, 1H), 6.95 (c, 2H). (ae) SI-NKM5: Calculated data: 398.2556, Found data: 398.2551 (MN); Analysis: Calculated data: 60 carbon: 66.47; hydrogen: 7.86; nitrogen: 17.62, Found data: carbon: 66.74; hydrogen: 7.79; nitrogen: 17.70; NMR (SOS13, ZOOMHz): 2.00 (5, 6H), 2.12 (5, ZN), 2.30 (in, ZN), 2.37 (in, ZN), 3.40 (5, 6H), 3.78 (Her, 9-8, 4H), 4.25-4.40 (t, AN), 6.93 (v, 2H). (au SI-NKM5: Calculated data: 450.1141, Found data: 450.1133 (MN); Analysis: Calculated data: carbon: 50.67; hydrogen: 5.37; nitrogen: 15.55; bromine: 17.74; Found data: carbon: 52.36; hydrogen: 5.84 ; nitrogen: 65 14.90; bromine: 17.44; NMR (SOS13, ZOOMHz): 2.32 (in, ЗН), 2.57 (8, ЗН), 3.42 (з, 6Н), 3.60 (ad, 9-8, 2Н), 3.69 (a, --8, 2H), 3.82 (z, ЗН), 4.60-4.70 (t, 1H), 6.73 (a, U -8,1H), 6.93 (ad, 9-8, 1,1H), 7.22 (a, 9-8, 1H). -B4-

ad) SI-NKM5: Calculated data: 434.1192, Found data: 434.1169 (MAN); Analysis: Calculated data: carbon: 52.54; hydrogen: 5.58; nitrogen: 16.12; bromine: 18.40; Found data: carbon: 52.57; hydrogen: 5.60; nitrogen: 15.98; bromine: 18.22; NMR (SOS13, ZOOMHz): 1.00-1.07 (t, ZN), 1.65-1.85 (t, 2H), 2.35 (in, ZN), 2.46, 2.47 (in, 8, ZN), 3.40, 3.45 (5, 5 . 2H). ap) SI-NKM5: Calculated data: 337.2266, Found data: 337.2251 (MAN); Analysis: Calculated data: carbon: 70.18; hydrogen: 8.06; nitrogen: 20.75; Found data: carbon: 70.69; hydrogen: 7.66; nitrogen: 20.34; NMR (SOS13, ZOOMHz): 1.35 (Her, 9-8, 6H), 2.01 (in, 6H), 2.15 (8, ZN), 2.30 (in, ZN), 2.38 (5, ZN), 4.07 (a, 9-8, 4H), 6.93 (5, 2H). ai)) SI-NKM5: Calculated data: 412.2713, Found data: 412.2687 (MN); Analysis: Calculated data: 7/0 Carbon: 67.13; hydrogen: 8.08; nitrogen: 17.02; Found data: carbon: 67.22; hydrogen: 7.85; nitrogen: 17.13; NMR (СОС13, ЗООМГцС): 1.24 (i, 9-8, 6Н), 2.00 (в, 6Н), 2.20 (в, ЗН), 2.30 (в, ЗН), 2.43 (з, ЗН), 3.60 (а, 9-8, 4H), 3.66 (aa, 9-8, 3, 2H), 3.75 (aa, 2-8, Z, 2H), 4.55-4.65 (t, 1H), 6.75 (a, 9-8, 1H), 6.95 (in, 2H). ai) SI-NKM5: Calculated data: 398.2556, Found data: 398.2545 (M.N); Analysis: Calculated data: carbon 166.47; hydrogen: 7.86; nitrogen: 17.62; Found data: carbon: 66.87; hydrogen: 7.62; nitrogen: 17.75; NMR (SOS13,

ZOOMHz): 1.95-2.10 (t, 8H), 2.20 (v, ZN), 2.32 (v, ZN, 2.44 (v, ZN, 3.38 (v, ZN, 3.42 (v, ZN), 3.50-3.70 (t, 4H ), 4.58-4.70 (t, 1H), 6.87 (j, 9-8, 1H), 6.95 (c, 2H). ac) SI-NKM5: Calculated data: 338.1981, Found data: 338.1971 (MAN); Analysis: Calculated data: carbon: 67.63; hydrogen: 6.87; nitrogen: 20.06; Found data: carbon: 67.67; hydrogen: 6.82; nitrogen: 20.31; NMR (SOC13, ZOOMHz): 2.15 (in, ZN, 2.29 (in, ZN, 2.35 (9, ZN, 2.43 (c, ZN, 3.90 (b, 9-8, 4H), 4.35-4.45 (t, 4H), 7.00-7.15 (t, ZN). a)) SI-NKM5: Calculated data: 464.1297, Found data: 464.1297 (MAN); NMR (SOS13, ZOOMHz): 2.28 (v, ZN, 2.40 (v, ZN, 3.40 (z, 6H), 3.75 (Yii, 9-8, 4H), 3.83 (5 . data: 418.1242, Found data: 418.1223 (M-А-Н); NMR (СОС13, ЗООМГhz): 1.00 (i, а, сч 3-8, 1, 6Н), 1.55-1.75 (t, 4Н), 2.34 ( 5, ZN), 2.49 (z, ZN), 2.84 (5, ZN), 4.15-4.27 (t, 1H), 6.19 (a, 2-8, 1H), 6.93 (da, 9-8, 1, 1H ), 7.21-7.30 (t, 2H). Fr ap) SI-NKM5: Calculated data: 404.1086, Found data: 404.10795М-Н); NMR (SOS13, ZOOMHz): 1.35 (i, 9-8, 6H), 2.28 (85, ZN, 2.40 (v, ZN, 3.83 (z, ZN, 3.90-4.08 (t, 2H), 4.08-4.20 (t . . t, 1), 6.50-6.55 7 (t, 1H), 7.00-7.15 (t, ZN). b ar) SI-NKM5: Calculated data: 397.1988, Found data: 397.1984 (M--H); NMR (SOS13 . z, ZN, 4.58-4.70 (t, 1H), 6.75 and (a, 9-8, 1H), 7.20 (aa, 9-8,1, 1), 7.25 (a, 9-1,1H), 7.40 (in, 1H). cha ad) SI-NKM5: Calculated data: 375.2297, Found data: 375.2286 (MAN); Analysis: Calculated data: carbon: 70.56; hydrogen: 7.01; nitrogen: 22.44; Found data: carbon: 70.49; hydrogen: 6.99; nitrogen: 22.45; NMR (SOS13, ZOOMHz): 0.79-0.85 (t, 2H), 1.00-1.05 (t, 71H), 2.00 (v, 6H), 2.19 (v, ZN, 2.32 (v, ZN, 2 .44 (in, ZN, 2.84 (Y, 9-8, 2H), 3.30-3.40 (t, 1H), 4.50 (i, 9-8, 2H), 6.95 (in, 2H). « ag) SI-NKM5: Calculated data: 434.1192, Found data: 434.1189 (MN); Analysis: Calculated data: pt) c carbon: 52.54; hydrogen: 5.58; nitrogen: 16.12; bromine: 18.40; Found data: carbon: 52.75; hydrogen: 5.59; nitrogen:

And 16.09; bromine: 18.67; NMR (SOS13, ZOOMHz): 2.19 (v, ZN, 2.30 (85, ZN, 2.47 (v, ZN, 3.43 (v, 6H), 3.60 (aa, 9-8, and 8, 2H), 3.70 (aa, 9-8.8, 2H), 4.58-4.70 (t, 1H), 6.71 (a, 9-8, tn), 7.08 (a, 0-8,1n), 7.37 (aa, 9-81, 1) , 7.45 (9, 0-1, 1Hn). az) SI-NKM5: Calculated data: 448.1348, Found data: 448.1332 (MAN); Analysis: Calculated data: -I carbon: 53.58; hydrogen: 5.85; nitrogen: 16.62; bromine: 17.82; Data found: carbon: 53.68; hydrogen: 5.74; nitrogen: 15.52; bromine: 13.03; NMR (SOS13, ZOOMHz): 1.95-2.10 (t, 2H), 2.20 (v, ZN, 2.30 (v, ZN) . (a, 9-81), 7.35 (aa, 9-8, so 1, 1H), 7.47 (a, 9-1, 1Hn). a) SI-NKM5: Calculated data: 400.2349, Found data: 400.2348 (МН ); Analysis: Calculated data: - carbon: carbon: 63.14; hydrogen: 7.32; nitrogen: 7.53; Found data: carbon: 63.40; hydrogen: 7.08; nitrogen: 17.14; XNMR (SOC13, ZOOMHz): 2.16 (in, ЗН . -8, 2H), 3.85 (5, ZN, 4.59-4.70 (t, 1H), 6.70 (a, 9-8,1H), 6.76 (c, 1H), 6.96 (c, 1H). ai) SI-NKM5: Calculated data: 414.2505, Found data: 414.2493 (М-А-Н); NMR (SOS13, ZOOMHz): 2.15 (v, ZN, 5B 2.19 (v, ZN, 2.25 (v, ZN, 2.40 (5, ZN, 3.40 (z, 6H), 3.76 (Her, 9-8, 4H), 3.84 (in, ZN, 4.20-4.45 (t, 4H), 6.77 (5, 1H), 6.93 (5, 1H).

F) am) SI-NKM5: Calculated data: 368.2450, Found data: 368.2447 (MN); NMR (SOS13, ZOOMHz): 1.00 (i, ka 3-8, 6H), 1.55-1.85 (t, 4H), 2.19 (v, ZN), 2.20 (z, ZN), 2.30 (v, ZN), 2.47 (c, ЗН), 3.88 (c, ЗН), 4.10-4.30 (t, 1Н), 6.15 (a, 9-8, 1Н), 6.78 (c, 1Н), 6.98 (c, 1Н). in am) SI-NKM5: Calculated data: 353.2216, Found data: 353.2197 (MAN); NMR (SOS13, ZOOMHz): 1.35 (her, 3-8, 6H), 2.17 (in, ZN, 2.19 (in, ZN, 2.28 (in, ZN, 2.40 (zv, ZN), 3.85 (5, ZN, 3.90- 4.20 (t, 4H), 6.78 (v, 1H), 6.95 (a, 1H). ah) SI-NKM5: Calculated data: 390.1697, Found data: 390.1688 (MAN); Analysis: Calculated data: carbon: 58.53; hydrogen : 6.20; nitrogen: 17.96; chlorine: 9.09; Data found: carbon: 58.95; hydrogen: 6.28; nitrogen: 17.73; chlorine: 9.155. z, ZN, 3.42 (c, 6H), 3.60 (aa, 9-8, 65 8, 2H) 3.68 (ad, 9-8, 8, 2H), 4.59-4.72 (t, 1H), 6.72 (j, 9-8, 1H), 7.12 (a, 9-8, 1H), 7.23 (y, 9-8, 1H), 7.32 (c, 1H). au) SI-NKM5: Calculated data: 374.1748, Found data: 374.1735 (MN); Analysis: Calculated data:

carbon: 61.04; hydrogen: 6.47; nitrogen: 18.73; chlorine: 9.48; Found data: carbon: 61.. 47; hydrogen: 6.54; nitrogen: 18.23; chlorine: 9.61; NMR (SOS15, ZOOMHC): 1.01 (5 9-8, ZN, 1.62-1.88 (t, 4H), 2.35 (8, ZN, 2.37 ( in, ZN, 2.48 (4, 9-1, ZN, 3.40, 3.45 (5, 85, ЗН), 3.50-3.64 (t, 2Н), 4.38-4.47 (t, 1Н), 6.53 (а, 9-8,1Н), 7.12 (а, -8,1Н), 7.07 (9 . (85, ZN, 2.40 (85, ZN, 3.40 (c, 6H), 3.76 (5 9-8, 4H), 4.20-4.45 (t, 4H), 7.11 (a, 9-81), 7.22 (a, 9-8, 1H)U, 7.31 (8, 1H). ra) SI-NKM5: Calculated data: 404.1853, Found data: 404.1859 (MAN); Analysis: carbon: 59.47; hydrogen: 70 6.50; nitrogen: 17.34; chlorine : 8.79; Found data: carbon: 59.73; hydrogen: 6.46; nitrogen: 17.10; chlorine: 8.73; NMR (SOS13, ZOOMHC): 1.95-2.08 (t, 2H), 2.35 (v, ZN, 2.38 (5, ZN, 2.46 (z, ZN, 3.38 (85, ZN, 3.41 (v, ZN, 3.50-3.65 (t, 4H), 4.56-4.70 (t, 1H), 6.85 (j, 9-8, 1H), 7.12 (a , 9-8, 1H), 7.45 (a, 9-8, 1H), 7.32 (8, 1H).

B) SI-NKM5: Calculated data: 391.2246, Found data: 391.2258 (MAN); Analysis: carbon: 67.67; hydrogen: 6.71; nitrogen: 21.52; Found data: carbon: 67.93; hydrogen: 6.70; nitrogen: 21.48; NMR (SOS13, ZOOMHz): 0.76-0.84 y75 (t, 2H), 0.84-0.91 (t, 2H), 1.00-1.08 (t, 2H), 2.15 (8, ZN, 2.20 (v, ZN, 2.29 (v .

Bs) SI-NKM5: Calculated data: 386.2192, Found data: 386.2181 (MN); Analysis: carbon: 62.32; hydrogen: 7.06; nitrogen: 18.17; Found data: carbon: 62.48; hydrogen: 6.83; nitrogen: 18.15: NMR (SOS13, ZOOMHz): 7.1 (a, 1H, 3-8), 6.9 (a, tn, 9-1), 6.8 (aa, YAN, 9-81), 6.7 (Bha, tn, 0-8), 4.7-4.6 (t, 1Н), 3.85 (5, ЗН), 3.70-3.55 (t, AN), 3.45 (5, 6Н), 2.5 (5, ЗН), 2.3 (8, ЗН) , 2.15 (8, ZN). ra) SI--KM5: Calculated data: 400.2349, Found data: 400.2336 (MAN); NMR (SOS13, ZOOMHz): 7.1 (a, 1H, 3-7), 6.85 (a, 1H, 0-.1), 6.75 (aa, yin, 0-71), 4.45-4.25 (rg.5, 4H ), 3.75 (Her, 4H, 2-7), 3.4 (in, 6H), 2.4 (in,

ZN), 2.25 (in, ZN), 2.15 (in, ZN). d) SI-NKM5: Calculated data: 370.2243, Found data: 370.2247 (MN); Analysis: carbon: 65.02; hydrogen: ch 7.38; nitrogen: 18.96; Found data: carbon: 65.28; hydrogen: 7.27; nitrogen: 18.71; NMR (SOS13, ZOOMHz): 7.1 (a, 1H, 3-8), 6.85 (a, MH, 2-1), 6.8 (aa, yin, 9-8,1), 6.5 (rg. a, yin, 0-1), 4.5-4.3 (t, 7H), 3.85 (5, ЗН), 3.65-3.5 o (t, 2Н), 3.4 (8, 2Н), 2.5 (z, ЗН), 2.3 (5 , ZN), 2.2 (8, ZN), 1.9-1.7 (t, 2H), 1.05 (i, ZN, 9-7).

BU) SI-NKM5: Calculated data: 379.2246, Found data: 379.2248 (MAN); NMR (SOS13, ZOOMHz): 7.1 (a, 1H, 3-8), 6.85 (a, TN, 9-1), 6.8 (aa, yn, 9-81), 4.3-4.0 (t, 4H), 3.85 ( 8, ЗН), 3.0 (B 2Н, 9-7), 2.45 (8, ЗН), «9 зо 2.3 (8, ЗН), 2.2 (в, ЗН), 1.9-1.8 ( t, 2Н), 1.0 (, ZN, 9-7). ra) SI-N-EM5: Calculated data: 340.2137, Found data: 340.2122 (MAN); NMR (SOS1z, ZOOMHC): 7.1 (a, NN, t 3-8), 6.85 (0, 1H, 9-1), 6.75 (aa, TN, 9-81), 4.2-4.0 (rt, 4H), 3.85 (5, ZN, 2.4 (in, ZN), 2.3 (8, Z). Fu 2.2 (5, ZN), 1.35 (Her, 6H, 9-7).

Vp) SI-NKM5: Calculated data: 313.1665, Found data: 313.6664 (M.N), Bi) SI-NKM5: Calculated data: i) 400.2349, Found data: 400.2346 (MAN); NMR (SOS13, ZOOMHz): 7.1 (d, 1H, 9-7), 6.9-5.75 (T, ZN, 4.7-4.55 (t, cha 1H), 3.8 (5, ZN, 3.7-3.5 (T, 4H), 3.45 (in, ZN, 3.35 (in, ZN, 2.5 (in, ZN, 2.3 (5, ZN), 2.2 (5, ZN), g. 1-1.98 (T, gn).

BI) SI-NKM5: Calculated data: 377.2090, Found data: 377.2092 (M.N); Analysis: carbon: 67.00; hydrogen: 6.44; nitrogen: 22.32; Found data: carbon: 67.35; hydrogen: 6.44; nitrogen: 22.23; NMR (SOS13, ZOO0MHz): 7.1 (d, 1H, 9U8), 6.9 (d, 1H, 9-1), 6.8 (dd, 1H, 9-81), 4.55-4.4 (T, 2H), 3.85 (in . t, 2H). in s BC) SI-NKM5: Calculated data: 413.2427, Found data: 413.2416 (MAN); NMR (SOS13, ZOOHCS): 7.1 (d, 1H,

Y 3-8), 6.85 (d, 1H, 9-1), 6.75 (adiIN, 9U-8,1), 4.6 (T, 7H), 3.85 (z, ЗН, 3.75-3.6 (T, 4H), 3.6 (а, 4Н, 9-7), а 2.5 (8, ЗН, 2.3 8, ЗН, 2.2 (8, ЗН, 1.25 (К6Н, 1-7).

BI) SI-NKM5 Calculated data 420.1802, Found data 420.1825(М-Н); rt) SI-NKM5 Calculated data 390.1697, Found data 390.1707(M'-H); -I n) SI--KM5 Calculated data 397.1465, Found data 397.1462(M'N); ro) SI--KM5 Calculated data 360.1513, Found data 360.1514(M'N); and rr) SI-NKM5 Calculated data 374.1748, Found data 374.1737(M'-H);

Ge) Ba) SI-NKM5 Calculated data 479.1155, Found data 479.1154(M.N);

Bg) SI-NKM5 Calculated data 463.1219, Found data 463.1211(М'-Н); Analysis: Calculated carbon data: - 51.96, hydrogen: 5.23, nitrogen, 15.15, bromine: 17.28; Found data: C 52.29, hydrogen: 5.62, nitrogen: 14.79, bromine: 17.47 c» re) SI-NKM5: Calculated data: 433.1113, Found data: 433.1114 (M, 79vHg); 69 MNZ-SI M5: Calculated data: 406, Found data: 406 (M-N)k; NMR (SOS13, ZOOGCs): 8 7.28 (d, U-10MhzC, ip), 7.03 (d, U-8MhzC, 1), 6.96 (v, 1H), 6.7 (d, 9-9, 1H), 4.63 ( T, 1), 3.79 (in, ЗН), 3.6 (T, 4Н), 3.42 (t,

BN), 2.47 (in, ZN, 2.32 (in, ZN).

Example 431

F, Production of 2,4,7-trimethyl-8-(4-methoxy-2-methylphenyl) (1, 5-a)-pyrazolo-1,3,5-triazine. ime) (Formula 1, in which BZ is CH with, B is CH 3, 7 is C-CH 53, Ag is 4-methoxy-2-methylphenyl)/ 60 5-Acetamidino-4- (4 -methoxy-2-methylphenyl)-3-methylpyrazole, acetic acid salt (602 milligrams, 22 mmol) was mixed with a saturated solution of ManHsSoO»z (10 milliliters). The aqueous mixture was extracted three times with ethyl acetate. The combined organic layers were dried over Ma 5 O), filtered and concentrated in vacuo. The residue was mixed with toluene (10 milliliters) and trimethyl orthoacetate (0.36 grams, 33 mmol) was added to form a suspension. The reaction mixture was heated to reflux temperature under a nitrogen atmosphere and stirred for 16 hours. After cooling to ambient temperature, the reaction mixture was concentrated to afford an oily substance. Column chromatography (SNSI with: meon, -58v-

ratio 9: 1) yielded, after removal of the solvent ip maszo, a viscous yellow oil (H-0.6, 210 milligrams, yield 3795): NMR (SOS13, ZOOMGhzC): 7.15 (d, 1 H, 9-8), 6.9 (d, 1 H, 2-1), 6.85 (aa, 1 H, 9-8, 1), 3.85 (c, ЗН), 2.95 (c, ЗН), 2.65 (c, ЗН), 2.4 (c , ZN), 2.15 (in, ZN) ; SI-NKM5: Calculated data: 283.1559,

Found data: 283.1554 (М--Н).

Example 432 7-Hydroxy-2,5-dimethyl-3-(2-chloro-4-methylphenyl)pyrazolo(1,5-a|-pyrimidine. (Formula 1, in which A is CH, K1 is methyl, KZ is OH, 7 is C-Me, Ag is 2-chloro-4-methylphenyl).70 5-Amino-4-(2-chloro-4-methylphenyl)-3-methylpyrazole (1.86 milligrams, 8.4 mmol ) was dissolved in glacial acetic acid (30 mL) with stirring. Then, ethyl acetate (1.18 mL, 9.2 mmol) was added dropwise to form the final solution. The reaction mixture was heated to reflux and stirred for 16 h, then cooled to room temperature . Ether was added and the resulting precipitate was separated by filtration. Drying and a mass of white substance 7/5 Color (1.0 grams, yield 42 70): NMR (SOC1-, 300 MHz): 8.70 (rhe I H), 7.29 (8, 1 H), 7.21-7.09 (T, 2H), 5.62 (8, 1H), 2.35 (v, 6H), 2.29 (v, ZN; SI-M5: 288 (MAN).

Example 433 7-chloro-2,5-dimethyl-3-(chloro-4-methylphenyl)pyrazolo(1,5-a|-pyrimidine. (Formula 1, in which A is CH, KI! is methyl, KZ is chlorine, 7 is C-Me, A is 2-chloro-4-methylphenyl).

A mixture of 7-hydroxy-5-methyl-3-(2-chloro-4-methylphenyl)-pyrazolo|1.534)|) pyrimidine (1.0 grams, 3.5 mmol), phosphorus oxychloride (2.7 grams, 1.64 milliliters, 17.4 mmol), M . (ethyl acetate:hexanes, ratio 1:2) on the residue gave 7-chloro-5-methyl-3(2-chloro-4-methylphenyl)-pyrazolo|1,5a|pyrimidine (90 milligrams, yield 8490) as and ) of a yellow oily substance: NMR (SOS with, ZOOMHc): 7.13 (v, 1H), 7.27-7.26 (t, 1H), 7.16 (d, 1H, y-7), 6.80 (v, 1H), 2.55 ( in, ZN), 2.45 (in, ZN), 2.40 (in, ZN), ; SI-M8: 306 (MAN).

Example 434 with 7-(pentyl-3-amino)-5-methyl-3-(2-chloro-4-methylphenyl)pyrazolo(1,5-a|-pyrimidine. (Formula 1, in which A is CH, K1 represents methyl, KZ represents pentyl-3-amino, 7 represents -

C-Me, A is 2-chloro-4-methylphenyl). Gee!

A solution of 3-pentiamine (394 milligrams, 6.5 mmol.) td 7-chloro-5-methyl-3 (2-chloro-4-methylphenyl)-pyrazolo|1, ba| pyrimidine (200 milligrams, 0.65 mmol) in dimethylsulfoxide (OM5O, 10 milliliters) was stirred at a temperature of 150 degrees Celsius for 2 hours; then it was cooled to ambient temperature. The reaction mixture was then poured into water (100 milliliters) and mixed. As a result of three extractions with dichloromethane, washing of the combined organic layers with brine, drying over

Mao, filtration and extraction of the solvent ip mazo, obtained a yellow solid. Thin-layer chromatography (ethyl acetate:hexanes, ratio 1:4) gave a white solid (140 milligrams, yield 60,965): mp 139-141 degrees Celsius; NMR (SOS153, 300 Hz): 7.32 (8, -shd s 13, 7.27 (a, yin, 0-8), 7.12 (a, tn, 2-7), 6.02 (y, MH, 2-9), 5.78 (8, 1H), 3.50 -3.39 (t, 1H), 2.45 (v, ЗН), c 2.36 (v, 6H), 1.82-1.60 (t, 4H), 1.01 (i, 6H, 9-8) ; Analysis: Calculated data for C2OH25BSIMA: carbon, 67.31, and" hydrogen, 7.06, nitrogen, 15.70, chlorine, 9.93 ; Found data: carbon, 67.32, hydrogen, 6.95, nitrogen, 15.50, chlorine, 9.93.

The examples described in Table 2 can be prepared using the methods given in the Examples

LA, 18, 432, 433, 434. In general, the following abbreviations are used: P is phenyl, Pg is propyl, -I Me is methyl, Ei is ethyl, B is butyl, Ex is the example number, ЕЯ is Ac is ethyl acetate. (95) se) - 50 se»

F) name) 60 b5

"Table 2 of

A m r dl s u,

M

Ag m | | ET | Аг "Temperature of application; sht in melting (C) 4357 Sme 7938 schen yuMe" 24-СБ-РЬ 71-73 43600 Me. ОМ 2.4 С-РВ "86-87 vp | EM". mNeNn(veOSvoOoMme | 2.4 Сб-РЬ lot 387 С-Ме M(РО СниСНЕМ 2.4 Сб-РЕ 83-85: az С-Ме: /LNOZ-pentnl in Sy-Rv 175-176 сч о со -

F so h- « - s;» - And oh

That; - 50 s"

Ф) t 60 b5 a С Me МНСн(СНЮМе) зас 407 чай Еме МНН» 2.4 Me -RI, oily liquid. and C-Me: MNSN(COMe) 2,4- Mez-Rii 103-105 443 C-Me M(STSNoOMe) with 2,4-Me-PE 87-89. ku s-Me kes-RO SSS 2,4 Mary. 133 (does) du «s-Me MEN TYOMe) 2,4 Me Ri; TV; two eMe MNeSN (СНОМ) » ; 2.4-.Mez-Ry. 131-133 zy sme MNASN (0 2.4-Mech-Ri» 139-141 70 4487 s-Mme o ME. 2.4 Mez-R 92-94 449 s-Me. MR SNSNSM IY 2.45 Mez- RE і43- 144 850 S:Me M(Vy) SNISNSM i 2.4. Mez-RI; 115-117 51 S-Me MNSN(EOSNOMe 2.54 Me»-RE. oily liquid 45 S-Me MNISN(BO» 2-Me ,; 4- MeORE. 104-106 453 cmMe MNen(sNOMe) with Z. 2-Me, 4- MeORi; 115-146. 454" C-Me M(SSNMe) » 2-Me; 4 - MeORI oily liquid and a5U S-Me. (53 - MNSN(SNeNUMEe) - 2-Me, 4 - MeORii oily liquid and C-Me | ("NOM I ia5e" S-Me (5) MNSNISNISNISNUMEe). - 2-Me, 4 "- MeORI oily liquid сНОМе) 457 с-Ме: МНСН (Ed СОМе 2-Ме, 4 - ШРЕ oily liquid. 4587. с-Ме M(СНеТОМе) » 2,4- Mez-RB oily liquid 459": С-Ме " MNE 2-Me; 4a--AUG 94-96

And in Me MNSN(EOz 2-Me,4-SULPH 113-114. 461 seme MAE 2,4--Me»-РЬ is a foamy liquid. 462 с-Me (5) - MNSN(SNSN»OMe).- 2- Me4- SULFUR oily liquid: c (sNOMe) ШХ What about 43 C-Me M(RINSNAETSM 2-Me, 4 - MEORIi 8-19 zba c-Me OMvB 2-Me, 4 - MeORi 97-99 ab C-Me ( 5)3-- MNSN (SNESNOMg)- 2s1,4- Mary 101-103 . o (bvoMe) so z 1 665 s-Me MES" 2-s1,4 Mary | 129-130 che" s-Me m (ek ) STSsNeM 2-Me, is - MeoRi 177-178 - ch68i | s Me M (s-bhuSNSTsM 201.4- Mer 162-163 or s-Me "MNSN(v) SNOM. 2-Me, 4.- MeORE oily liquid o dom S-Me MNS) SOM 2-0, 4- Mary pin. Go)

I CMe MNeCH(SNOMEe) with 2-C1, 4- MeORB 472. C-Me M (СВССНОМее) with 2-С1,4-MeORB: i- 43 C-Me "МНОСН«EO SEOMe 2-С1;4- MeORE 474 c-Me M (sr cTSNeM 2-C1, a MeORE: 475 c-Me o ME. 2-SI, 4 - MeORIi: ab | EMe - МН-Z-pentium 2-С1; 4- MeORV « iao| EMe | mNnecEsstome 2-c1,4- MEORb with 8 C-Me MNenNuMeu SSN»OMe 2-1, A--MeOri. with at | s-m MNSNHEOSNTSNOMe 2-Vi, 4- MeORI;

From" 450: S.Me MNSnuMe) SPOSTYOMe: devVt2- Meogv !

VI. СМе МНСНЕОСнеСНОМе 2-Ме, 4- МеОРій 485. с-Ме МНеНа«Ме)СТСНОМ- 2-Me, 4- МеОРій | 483 cme | MNSN(SNOMe) 2 250214; 5- (MeO) with -PE - 484 C-Me SHSTEENOME" 2-si4, 5-(MeO) with-P 85 c-Me MNON (BO SOME 2-14; 5: (MeOu5-PE:

Mn 486 c-Me M(cSRSNSNSM 2-C1-4, 5-(MeO) with -Rig (Ce) 487 C-Me ME; phoana 5- (MeOu 2 -RE. 999-105 88 CMe o MNozpentyl o 2АС1 -, 55 (MeO) 5 -RE 169-170 - 489 C-Me MNYSNCH«BO SNOM 2-C1-4; 5-(MeO) 5-RE c» 390 | c-e5me | chnon(m)snsnoOmMe. 2 -C1-4, 5- (MeO)5-RE. ! (F) ho) bo b5 with 1 cme 100 MNSNiNOMe; 10551 5-(Meb); -Pv 5053 adm. 497 С-Me MISSNOME). 2-VI-4, 5- (MeO) 5-RI 116: 493 S-Me MNSN(EO CH»OMe 2-Vi-4,5- (MeO)5-Ri che | sMe m(сRUSSNSNSM 2-B- 4, 5- (MeO) z-RA 495. C-Me MEE" 2:VI-4,5- (MeO)" 5-REA 496 cMe | "MNeZ-pentyl 25 Vi: 5- (MeO)" "Vi 497 SAMe MNSN(EO SNISN»OMe 2-VI:-4,5- (MeO)» -Rii 498 s:me Mnen(MeustsnMe 22 Vg-4,5-(MeO) 2 RE 500 s-Me MmSsNSOoMer 2-С14 ,6- (Meb)" -Ry z01 C-Me MNeN(EO SNOME 214, 6- (Meb)" -РІ 502 C-Me Mm(erosyusnuem What 214,6 (MeOu» -РІ 504 СMe МН-3-pentyl 2-C1-4, 6: (MeO);-REi 5 505 C-Me MYSN (B) SVSNiOMe: 2-C1-4, 5- (MeO) 5 -RE 506 C-Me: MNN (Me ETsSNOMe 2- C1-4,6- (MeO)35 -RE 507 СсМе МНеН (СНОМ); 2-Me-4,6-(MeO)2-РІ p

ZOV I c-Me MSS Me) 2-Me-4,6-(MeO)5-RB I 509 C-Me MNSN(E) CH.OMe 2-Me-4, 6-(MeO)2-Ry. 510 C-Me M(sePO SSNOSM 2-Meg4; b- (MeO) z-PE 5 c-Me shi 2-Me-4,6- (MeO)2-Rii 512 | sme MH-Z-yentyl 2-Me -4,6-(MeO)5-Ry ОЙ з3 | сСМе | МНСН(БУСВИСНУМе | /2-Me-4,6-(MeO)з-РВ 514 О-Ме чнен (Ме) ЕСНоСНОМе го 2-Me-4 ,6- (MeO)»-RE. vis S-Me VYERIUSTSTSM 2-Vi-4, 6-(MeO) z-P sc 516 S-Me. che 2-Vi-4, 6-"MeO) 5 -RE : o 517 C-Me MN-Zopentyl 2-Vha, 65 (Meb)-RE 5 C-Me MNSN(E) СНСНОМе 2-Ви-4,6-(МеО)у» -РВ. 819 с-Me МНеН ( Me) SNISNOMEe. 2-Vg-4, 65-(MeO)5-PE 520 | eMe | MNSN(EDSnSTOMe | 0/2-MeMeORh so 521 C-Me mchenen(Me CSO Me 2-Me-4-MeORH 7 522 | s-Me MNSN (SNOMEe) ». 2-MeO-4-Mer - 573 S-Me MSBO Me) 2-MeO-4-MeRb 1524 S-Me MNSN(EO SNOM. 2-Meb-4-MerMe)

З25 С-Ме Мм(с-РО) СІЕНСНСМ. 2-MeO-4-Merium with 1 526. cSMe MES 2-MeO-4-Merium 527 c-Me MN-Zopentyl 2-MeO-4-Merium y- 328 c-Me MNSI(EOSNSNOMe 2-MeO-4-Merium 529 S-Me MneNn (Me) SNeVOME Ii 2-MeO-4-MerRk; 530 c-Me MNSN (СНОМ) 5 2-Meb-4-MeR 1 531. S-Me MiSnSnOMe) 2-Meb-4-Mer « 70 4-MeRi h 5. C-Me MyN-3-pentyl :2-MeO-4-MerRi no 536. | C-Me MNSN(E) STSNOMe 2-Me0-4-MerE 537 C-Me MySNuMe) SNHSNOME 2- MeO:4-Mery z38 S-Me E MNSN(SOM ee)" 2-MeO-4-SULFUR: -I 539 S-Me MSNeSTOMe)"; 1 2-Meo-4-SURIi 1 540) sMe MNSn(voOsnyuMe | 00 2-MeO-i-SULFUR (95) 541 cMme M (se-ROUSTSTSM E 2-MeO-4-SULFUR, 542 cSMe 1 o ZhBx and 2-MeO-4-SURF. o | 543 CMe 00000 MNeZpentilo 2-MeO -4-SIV - 70 548 СМе МНСН(Е) СНСНОМе 2-МегО-а-СРЙ 545 сСМе МнеНН(Ме СТСНОМе 2-МмеО-4-СРЙ. | and

Fe ) to Table 2: 5) SI--KM5: Calculated data: 423.1355; Found data: 423.1337 (M.--N). 29 c) Analysis: Calculated data: carbon, 61.38, hydrogen, 6.18, nitrogen, 14.32: Found data: carbon, 61.54,

HF) hydrogen, 6.12, nitrogen, 14.37. a) Analysis: Calculated data: carbon: 58.02, hydrogen, 5.65, nitrogen, 14.24; Found data: carbon, 58.11, hydrogen, 5.52, nitrogen, 14.26. f) Analysis: Calculated data: carbon, 59.71, hydrogen, 5.26, nitrogen, 14.85; Found data: carbon, 59.94, for hydrogen, 5.09, nitrogen, 17.23.

C) Analysis: Calculated data: carbon 60.48, hydrogen, 5.89, nitrogen, 14.85, Found data: carbon, 60.62, hydrogen, 5.88, nitrogen, 14.82.

R) SI-NKM5: Calculated data: 337.2388; Found data: 337.2392 (M.-N). i) Analysis: Calculated data: carbon, 68.45, hydrogen, 7.669, nitrogen, 15.21, Found data: carbon, 68.35, because hydrogen, 7.49 nitrogen, 14.91.

І) Analysis: Calculated data: carbon, 69.08, hydrogen, 7.915, nitrogen, 14.65, Found data: carbon, 68.85, hydrogen, 7.83, nitrogen, 14.54.

K) Analysis: Calculated data: carbon, 73.51, hydrogen, 7.01, nitrogen, 19.48,

Found data: carbon, 71.57, hydrogen, 7.15, nitrogen, 19.12.

I) SI-NKM5: Calculated data: 403.1899; Data found: 403.1901 (MAN). t) Analysis: Calculated data: carbon, 61.77, hydrogen, 6.49, nitrogen, 14.41, chlorine, 9.13; Found data: carbon, 61.90, hydrogen, 6.66, nitrogen, 13.62, chlorine, 9.25. n) Analysis: Calculated data: carbon, 67.31, hydrogen, 7.06, nitrogen, 15.70, chlorine, 9.93; Data found: 7/0 Carbon, 67.32, hydrogen, 6.95, nitrogen, 15.50, chlorine, 9.93. o) Analysis: Calculated data: carbon, 74.50, hydrogen, 8.14, nitrogen, 17.38, Found data: carbon, 74.43, hydrogen, 7.59, nitrogen, 17.16. p) Analysis: Calculated data: carbon, 73.10, hydrogen, 7.54, nitrogen, 19.37, Found data: carbon, 73.18, hydrogen, 7.59, nitrogen, 18.81. a) Analysis: Calculated data: carbon, 73.57, hydrogen, 7.78, nitrogen, 18.65, Found data: carbon, 73.55, hydrogen, 7.79, nitrogen, 18.64. d) SI-NKM5: Calculated data: 353.2333; Found data: 353.2341 (M.--N). 85) Analysis: Calculated data: carbon, 71.56, hydrogen, 8.02, nitrogen, 15.90, Found data: carbon, 71.45,

N.-7.99, nitrogen, 15.88.

O Analysis: Calculated data: carbon, 65.60, hydrogen, 7.34, nitrogen, 14.57, Found data: carbon, 65.42, hydrogen, 7.24, nitrogen, 14.37. j) SI-NKM5: Calculated data: 399.2398; Found data: 399.2396 (М--Н). m) SI-NKM5: Calculated data: 399.2398; Found data: 399.2396 (М--Н). m) SI-NKM5: Calculated data: 383.2450; Found data: 383.2447 (MAN). ch x) SI--KM5: Calculated data: 403.1887; Found data: 403.1901 (М--Н). y) SI--KM5: Calculated data: 295.1919; Found data: 295.1923 (M.-N). i) 7) Analysis: Calculated data: carbon, 67.31, hydrogen, 7.06, nitrogen, 15.70, Found data: carbon, 67.12, hydrogen, 6.86, nitrogen, 15.53. aa) Analysis: Calculated data: carbon, 61.77, hydrogen, 6.49, nitrogen, 14.41, chlorine, 9.13; Found data: carbon, 62.06, hydrogen, 6.37, nitrogen, 14.25, chlorine, 9.12. ab) SI-NKM5: Calculated data: 337.2017; Found data: 337.2028 (M.--N). - ac) SI-NKM5: Calculated data: 403.1893; Data found: 403.1901 (MAN). Gee! ad) Analysis: Calculated data: carbon, 70.00, hydrogen, 7.22, nitrogen, 18.55, Found data: carbon, 70.05, hydrogen, 7.22, nitrogen, 18.36. i) ae) Analysis: Calculated data: carbon, 70.98, hydrogen, 7.74, nitrogen, 16.55, Found data: carbon, 71.15, i-

H.7.46, nitrogen, 16.56. ad) Analysis: Calculated data: carbon, 66.59, hydrogen, 6.76, nitrogen, 16.34, Found data: carbon, 66.69, hydrogen, 6b.82, nitrogen, 16.20. ap) Analysis: Calculated data: carbon, 70.38, hydrogen, 6.71, nitrogen, 18.65, Found data: carbon, 70.35, " hydrogen, 6b.82, nitrogen, 18.83. from c ai) Analysis: Calculated data: carbon, 66.39, hydrogen, 5.85, nitrogen, 18.44, chlorine, 9.33; Found data: . carbon, 66.29, hydrogen, 5.51, nitrogen, 18.36, chlorine, 9.31. and?" ai) SI-NKM5: Calculated data: 369.2278; Found data: 369.2291 (M.N). ak) Analysis: Calculated data: carbon, 64.42, hydrogen, 6.77, nitrogen, 15.02, Found data: carbon, 64.59,

H.6.51, nitrogen, 14.81. -I Examples described in Table 3 can be prepared using the methods given in Examples 1, 2, C or 6. In general, the following abbreviations are used: RP is phenyl, Pg is propyl, Me is also methyl, Ei is is ethyl, B is butyl, Ex is the example number, E(Ac is co-ethyl acetate. - 50

Fe (F. ko bo b5

Table 3

GC and 2

M.

IJ I that I le EX Ak: Temperature approx. | SHY AND AND | melting (C) 546: C-Me MNN (BO g 2-Me-A:Me MR 164-166 547" C-Me .(5)-MNSNYASNISNOMe) - 2, 4--Me2-Ri oily liquid - (сНОМе ) and - : zav -"E-Me (55 - МНСН (СНСНЮМЕ) - 2-Me-а-Си-РЕ: "oily liquid.

Sh pom, t na! for oMe "M(eti) CH,SNSM. 2-Mea Gray bo 415-116 55. "C-Me MNeN(EO) CNM 2-Me-4-C1-Ri; 131-132 551. C-Me OM VE 2,3-Me»-4-OMeRE | oily liquid with 5828: C-Me. MSTSNOMe) set n. with Х 2 4- СХ-Р and y oily liquid 85537 сСМе | МНеН (СОМ: 2,5-Me» -4-OMe-Ry oily liquid: i) 554 s Me MNSN (to 2,3- Mez-4-OMeR 128-124 55500 cme M(CHnoRy) Re 2-Me-4-SIS-RE. oily liquid. 5565 SEMe M(isRO STSTSV 2,3-Me;-4:. Meri. 158-160 со 557 СМе: MeV) -2-с1-4-OMERI 558 сме 1 Mem 2-с1-OoMerv - 559 С:Me MR Re 2--01-4-ОМей 560 сме Мс-Ри) Ve. 2-с1-4-ОМеРи ia сб С-Ме МБО» 2-21-4-СМ-РЬ 115-117. с 562 | ЕМе "М( sRi) 2-Si-koMe: 127-129 5637 s-Me MNSN(STPHON) maA-sSh-RI;: 128.129 I i- 564 s-Me: M (eri EI 2.- Vi-4, 5- (Me ) 2Pb 365 sesMe M(CRI)Me 2--Vi-A, 5-0MeOu2RE shk 1 5663 CMe Mar 2- Me-42-MeoRi; 125-128 567 s-Me MNSN(EO SON 2- Me-4-MeoRi 50-62 « 568 C-Me MMe 002-Vi-4,5-(MebOuAR Sh Z 70 569 C-Me: M(SSNNOMe)» 2« Me-4-MeORIi 103-105 s 579 c-Me. Mis) ! 2-Me-4-MeOR. 773-174. "from 572 c-Me MH-2-pentyl 2,4-Сб-Р. 41 84120: -I o (se; - 50 syu

F) ko) 60 b5

| SEMe MNONEOSNISM. 2,4- Owl 141l43 823 s Me. МНСН(РГУСНИОМе за - sr 87-88 574 | сМе МНСНИСНИАРОСНОИОМее | 2.4-СИ-РИ s amorphous liquid. 4 5 575 С-Me MIN-2-butyl 2,8-Me-Ri goily liquid: 35 | Me МН-2 -pentyl 2,3-Me»-Ri oily liquid 577 C-Me MH-o-hexyl | 2,4- Mez-Ri oily liquid

І 578 ЕМе | MNN (i-Ro) Me: 2,4--Mez-Rii oily liquid. 879 SiMe | /МНСН(MeuСНо-иРг дуж- Mez-RE oily liquid 70 580 C-Me MYSN (Me) -e Sen 2.4 Mech-RE oily liquid: -581 С-Me MH-2-indanyl 2.4 - Me- RIE oily liquid. 582 ЕMe 1 МН-1-indania 2,4-Meh-Ri- oily liquid 583 с-Ме МНСН(Меу РЕ 254 -Ме-В oily natives 584 С-Me. МНеНу(Ме) СНО: (4 -SULFURE) 2.4- Me;-PE: oily liquid: 585 c-me Mnon(MesNneOsSNI 01 2,4- Me-RI. oily liquid; 386 C-Me MNSN(RY)SNRI 2,4- Me" -Rii oily liquid 587 | С-Me МНСНИМЕСНОЗМЕЕ 2.3- Me;-Рий oily soil -588 bЕ-Ме | МН- (2-РЕ-с-С5Ни) 72, 4-.Мез-Рик oily liquid 589 с-Me МНеН(ВО СН : 2-Me-RI 119-120 590 C-MeE MH-z3-hexyl 2,a-Me-RE : oily native lo | 39 | cMe OMVO 2-MeO-a-SULPH 00 oily liquid 592 c-Me MNSN( EO 5 2-MeO-4-SIRN: oily liquid 59u E-Me LMNSN(EO SNOME 2-MeO-a-SULFURE: oily liquid 594. С-Me MMech 2-MeO-4-SIRV. oily liquid. 955 | 0сMe MNSN (BO 2-OMe-4-Mern. oily liquid 596 C-Me ME. | 2-OMe-4-Mery oily liquid with 5UK "sv MNeN(COMe) " 2, 4-SI-RE oil clear liquid: o 598. C-Me M(e-Rg) Be: 2u4-Mez-Ri 599| c Me "M (c-Ro) EE 2, 4-С-РЕ o C-Me M (ROB 254.6-MezRi; 601 c-Me M(cRO B 2-Me-4 - Gray c zo 502 C- Me I M(S-ROBE 2-01-4- Me-Ry va3: sme и MNN u(S-RI) » | 254 Me»Ry «- god s-Me MNN (s-Ri)2: Ou a- Сио:Ри Я 605. с-Ме МНН (с-Ргу". | 2 Ме-4- СИ-Рий b same bob 00 с-Ме МNN (СРО 2-с1- 4 - Ме-РЬ | со 507 Ме МNN ( s-Rg)" 2-Me-4-OMe-Ri 608. SEMme. MNSN(s-r 5 250154 -OMe-Rb - 609. s-Me МНСНУСНоМе) with 2-с1-5- BOMeRi byu s-Me: Mo: ZAS in - E-OMEVi 51 s-Me M (RO SNSNSM 2-s1-5- EOMer 812 S Me MNSNVV; 5-S1-5- EOMeRY. « du . 613 S-Me. ShcheNKNOMe); 2nd - 5-KE-Omerii from 514. "S-Me MB; ro0246-Me»-pyriduz-yl with 615: seme Her 0 m(eruYesneM 22,6-Me»-pyrid-3-yl Y "» 616 С- Me MNSNIEI". 276-Me» -pyrid-3-nl " 617 S-Me MSVSNOMe)» 2; 6-Mes -pyrid-3-yl 518 son. MNSN(SNOME)» 2,4 - Me: -RIi 519 s-on. MES 2uy- Me -R | ! -I 520 son Bridge SNSTSM 2A- Me-RI Y 621 son MNSN(E0". 2u54- Me -RE o 625 son. Mm(SSTOMe" : 23u4- Mez-R so ba S-Mee MNSN(SBOMe)" 2.54 -Me:-RI 25 S-MEv. MES" : 2.4 - Meu-Ri ! - 70 636 CM; M (c-RE'ENSTSM 2.4- Me -RE I St. 627 | SMEE MNSN(Ed» 1 .5»4-Me-R | shi! 628 S-MEB SHSNeTOMe; 2.4.- Me -Rii 630 S-Me. MISNI Me) 2-Me-4-SIM:RI .

F) shi de Notes to Table 3: a) SI-NKM5: Calculated data: 367.2610, Found data: 367.2607 (M.N); 60 5) SI-YAKM5: Calculated data: 384.2400, Found data: 384.2393 (MAN); c) SI--KM5: Calculated data: 404.1853, Found data: 404.1844 (M.N); a) SI-NKM5: Calculated data: 381.1594, Found data: 381.1596 (M.N); Analysis: Calculated data: carbon: 63.07, hydrogen, 5.57, nitrogen, 22.07, chlorine, 9.32; Found data: carbon: 63.40, hydrogen, 5.55, nitrogen, 21.96, chlorine: 9.15 e) СИ--КМ5 Found data: 369.1594, Found data: 369.1576 (М.Н); bo In SI-NKM5 Found data: 354.2216, Found data: 354.2211 (MAN);

49) SI-YANKM5 Found data: 410.1072, Found data: 410.1075 (MAN);

R) SI-NKM5 Found data: 414.2427, Found data: 414.2427(М-Н)

Y) SINKM5 Found data: 368.2372, Found data: 368.2372(М-Н)

І) SI-NKM5 Found data: 384.1955, Found data: 384.1947(М-Н)

K) SI-NKM5 Found data: 391.2168, Found data: 391.2160(M '-Н)

I) SINKMZ5 Found data: 335.1984, Found data: 335.196ЦМ -Н) t) SI-NKM5 Found data: 382.0759, Found data: 382.0765(М-Н) n) MNA-SI M5: Calculated data: 360, Found data: 360 (MAN) 70 o) MNA-SI M: Calculated data: 374, Found data: 374 (Ma-N)zh; MMK (SOS1z, ZOOMHz):5 7.29 (y, U-8.4Hz, 1), 7.04 (aa, 0-1.8,8Hz, 1), 6.96 (a, 9-1.8Hz, 1H), 6.15 (a, 9 -10, 1H), 4.19 (t, 7H), 3.81 (v, ЗН), 2.47 (5, ЗН), 2.32 (8, ЗН), 1.65 (t, 4Н), 0.99 (Her, U-7.32Hz, 6H) r) MNZ-SI M5: Calculated data: 390, Found data: 390 (MAN); MMK (SOS153, ZOOMHz):6 7.28 (a, U-8Hz, 1)", 7.03 (a, 9-8Hz, 1H), 6.96 (5, 1H), 6.52 (a, 9-9Hz, 1), 4.36 (t, 1Н), 3.8 (z, ЗН), 3.55 (t, 2Н), 3.39 755. (8, ЗН), 2.47 (в, ЗН), 2.32 (в, ЗН), 1.76 (t, 2Н), 1.01 (i, 9-7.32Hz, ZN. a) SI-NKM5: Calculated data: 354.2294, Found data: 354.2279 (MAN) d) SI-NKM5: Calculated data: 340.2137, Found data: 340.2138 (MAN) 8) SI -NKM5: Calculated data: 436.1307, Found data: 436.1296 (MAN)

The examples described in Table 4 can be prepared using the methods given in the Examples

LA, 18, 432, 433, 434. In general, the following abbreviations are used: РИ represents phenyl, Рg represents propyl,

Me is methyl, Ej is ethyl, B is butyl, Ex is an example number, EAc is ethyl acetate.

Table 4

And! 7 "-

Ah o -

Me and VE Ak Temperature approx. melting SS) 531 S-Me Mnen (Bu | 2-Viy, 5 (MeONIUZH 00000 1604361 « 632 | s-Me MNSN(B) 2-Be-DMeORE 10-11 - 70 633 K s-Me MSBO Me 2-Vk -4-MeORi 7a-76 s 534 C-Me MNSN(CH»OMe) ! 25Vg-4-MeOriv 128-130; z» 535 С:Me OVIEO» 2-Me-4«SIRE o z-la " 636 С -Me: Mer) B 2,4-Mer 637 C-Me M(s-Ro) B 2,4-MeRy. 638 E-Me M (sr Bi 2, 4; 6-MerRy - 639 c-Me (SR ) Bi 2-Me-4-MeORi 640. S-Me I M(s-Re) BI 2 l-a-MeORI o fa S-Me Mi(s-Ro In 2-Sii-Meria so 62 | sMe om( stiuV 2"Me-4-SIRV 643; s-Me "MNeSN (s-g. 2, 4-СРЬ ! - bai. sMe MNSN (sr 2, Mary 645 s-Me МНСНС-Ru with: 2-Me-4 -СИ:РЬ с» 646 C-Me MNN (с-Ри) with 2-С1-4-Ме-РЕ 647 Me MNN (с-Ри3 with and 2-СиА-ОМе-РЕ І 648 с-Me MNN "( c-Ri) with 2-C1-4-OM er 645 C-Me MNeN (SNOM: 2-C1-5--OMeER ! "650 C-Me OOMm (k 2-C1-5-2-O Mary iF) 651 c-Me misRvsnsNsM 2-С1-5-Е-ОМеРЬ

GI | 652 SeMe. "MNN (Ed: 2-01-5-Е-ОМеРІ 653. С-Ме M(СНСНОМе) g ! 2-С1-5-Б-ОМеРІ | : 654. С-Ме ME 2,0-Ме»-pyride -3-il bo 655 s-me M(isR)enzhneM 0100 256-Mech-niride-Z-yii 656 S-Me MNSN(VO) with 2, 6-Mech-pyride-Z3-kl b5 tt Me 1 3 MSBsBOoMe; 01 056 Messhodzia 1000331 658 -on MneN (SNO Me); 2,8-Me-Ri 659 s-on ME 2,4-.Mez-Rii "vbo son to the city of YensnM 2:4-Me:-РЬ bb1 | dream /"MNON(EO and 2,4-Mez-RE 662 s-m MSNSNOMe)" ! 2,4- Me-Ri 863 | ME MNSNISNOMe): | 2,4-Mes-Ri both SES ME; 2,4 - Mez-RE 70 665 C-MEe Mie-ROSSNeNSM | 2.4 A Mez-RIi bo C-ME in: mmNen: (E)0 2 2, a- Mez-Pb (657 C-MEB. M(SPSTOME) g 2,4 -Me-RI ov8 | сМе /"MNSN(VO 2-Me-4-СМ-РЕ ba сМе | SNOM euz 2 -Me-4-СМ-РА

The examples described in Tables 5 or 6 can be prepared using the methods given in

Examples 1A, 18, 2, 3, 6, 431, 432, 433, 434 or by means of their combinations, which are suitable for this. In general, the following abbreviations are used: PA is phenyl, Pg is propyl, Me is methyl, Ei is ethyl, B is butyl, Ex is an example number, EIIAc is ethyl acetate.

Table 5

Az. 14: сч » Х ця ц-Я о о и | u-o village x and

Ag «- le Ka 1 V I A p 67 | broom | МНСНСНОМе 2, СЬ-РЕ - 71. methyl МНеСНР 2, ас-РЕ от. methyl "MEvy 228 -5- RY 673 | Mmethy MRYSNS ZNA 2,4-С5-РВ " 674. methyl МСНСНОМеБ 2.43 Со -РА 20 675: methyl МН-З-heptyl 24 --Р -о 676 methyl. 4-0-Ra i- 677 | Mmeshl | MB 2,4-C-PE "» 678 methyl MNH(ISNOTC 2,4-C5-RIi " 89 metnia |. MIN-Z-pentyl. | 2,4-0 - R. - I (95) se) - 50 syu

Ф) име) 60 b5 s bo -Methyl MMerv 2.45-00-B: 681 methyl MR» ha -СБ-РЕ 682. "methyl МН-3-texyl 7,4 САББ 683 p methyl morpholino, 2,4 -СБ- RE vva "Metiya MESNIRI) СНСНИОМе gua-сб-АРН 85 methyl МНеН(ИСНРИ) СОМЕ 24 -Э-РЕ "be methyl МН-а-tetrahydrofuranil 2,4-С-АРЕ

Her 687 methyl o | MH-piclopentyl 2,4-Сб-РЭ 88 Methyl ОБ: 2,4-сб-РБ ! then 689 methyl OSNO SOME 2,4-C-P. 1 -690 methyl OSTI. 224-СрБ-ПЕ 591 methyl d-3-pentyl 2,4-С5-ПЕ 692 methyl 5 2,4-СБ-ПЕ 593 -methyl 5ОЕЕ 2,4-СБ-П5 694 | methyl 505 2,3-E5-P. ! 695 methyl ! pentide 2,4-c-PE 696 methyl 2SI-RY 2524-15 -PE.

And 697 methyl | 2-PI-P 2,a-C5-PE 598 methyl C-pentyl 2,4 - Si-P: 699 methcl cyclobutyl : 2.4 -cb-PI 70. methyl. | 3-Shridyl ' 2.4- B-P 701 methyl CH(EO STSOMMe» ! 2A-C-PE 78x methyl, CH(E)SNISNIMech 24-C-PE 703. methyl MNCH(SNYMe) 2,4,6-Me- RIi 704 methyl o MNN» 22,4, 6- Mez-Ri c 705 methyl MEVy 2,4, 6- Mez-PH. 1 706) metnl MPE(CHno ono) 2, 4,6-Mez-Ri o 707 methyl . M(SNSNYUM ee); 2,4,6- Mez-Rii 708 menya. MH-3-heptide: | 2,4,6- Me;-RI 709 methyl МНСН(Е) СНОМе | 2,4, 6- Mez-PE so so to methyl MB | 27456 Mez-RA

Coffee methyl МНСН(СНОЕО» 2,4,6-Mech-Ry I - 712 methyl MH-3-pentyl. 2,4,6- Mez-RA sho metnlo | MMeRy 2,4, 6- Mez-Ry; | b » k methyl. MR. xu4,6-Mez-Pb so ty. methyl "MY-3-hexyl . 2,4, 6-- Mez-PIi l methyl. morpholino 1 2,4,6- Mez-PE i- 77 methyl M(SnYu:SnisniumMe 2,4,6-Mez-Ri

B methyl: МНеСНС(СНВ) СОМе 2,4,6- Mez-PE 7 methyl: МН-а-tetrahydrofuranil 2,4,5- Mez-PE 229 methyl МН-cyclolentyl: 2,4,6-Mez-PE « 20 ti1 methyl. ОВ 2,4, 6- Me5-РІ -o 122 Methid OSN(vei STOMe. I 2,4,6-Mez-Ри с 723 methyl -OSNoRa 2, 4,6 Mez-RA "» tA methyl OZ: pentyl 2 ,4, 6--Mez-Ри " 725 methyl 5Е 2,456 -Me-РЕ shir methyl ОБ 2,4, 6- Mez-РЕ 9727 | methyl | 50. 2,4,6--Mech-РИ -И 728 methyl CH(CO Ex 2,456- Mech-PE 129 methyl | С(EO (CO; Br ! 2,456 -Mez-ARy o 730 methyl SNEVSNOUN 2,4, 6-Mez-PE c 731 | methyl. | CE) CHMe | 2, 4, 6--Mez-Ria 5 732 "methyl COMMe". 2,4;6-Me5-RiB - 133 methyl

F) name) 60 b5

735 methyl C(OH) RI-Z-pyridyl 2y74,0- Mez-RE 736 methyl "phenia 2,4,6- Mez-РЬ 737 methyl 2-РНЕР | 2,4,6- Mez-РІ; 738 1 methyl 3-pentyl | 2,4;6- Mez-RiV t methyl cyclobutyl 2; 4; 5- Mez-PE 740 5 methyl | 3-pyridyl 2,8,6-Mez-P 741 | methyl SNEVENSOMM 274,6- Mez-Pb 742. methyl ЭН«Е) SNISNUMMe» 2. 6- Mez-Pb 743 |. Metnl MNeH(SNOMe». 2.45. Mech-PE; then Tay | methyl MSTeNuMe); 2, 4- Mez-ri ; 7a5 methyl МНеН(Э) СОМе 2,4- Me-Rii 746 methyl МН-З-pentyl 254. Me:-Rii 747 methyl ME, 2,4 Mech-Ri 748 methyl МЕСНСМ)»: 2, 8- Mez- Ri: 749 methyl MNN (Me SNIOMe ! 254 Me; -Ri; 750 "metide OSN(VE)O STOMe 2.4: Mez-RE. 75 methyl o Mr. 2.45 Meri 752 methy MNSN (Me) ЕNoMMe": 2,4- Me -RI 753 methyl MZhesn)snensM 2,4. Me-RE 754 methyl (RU SNSNSM 2,4- Me; RE. 755 | meterl (Vy) SNIENSM 2.4 Me -RE 756: methyl "MHC 2; 4 Me; I 151 methyl MVVSH 254 -Me-RV and 758 | " methyl MR (CHNi-c-CH); I 2.8: Me" -PIx Y 759 methyl MH-3-tedtinl! 2.4 Me; -Pb c 760 methyl oMEB. I 254 - Me; -PI: lei methyl chVen«sNuvO) with 2, 4- Mez-PE o 762 methyl MH-3-pentyl: 2,4-Me-PE 763 methyl MMeRi 2,4 Mez-RI 765 methyl o. MR; 254- Me: -PE 965 methyl MH-3-texium 2.4 - Me» -RIi She 766 | methyl morirolino ! 2,4 - Me»-PE - 767 "methnl M(SNORYU) SNOSNOMe, I 24 Mech-Pv 7658 methyl. МНСН(СНИРУСНОМе 2,4 -Meхz-Ри b 789 methyl МН-4-tetrahydrofuranil: 2,4.- Me-Pe o methyl. MH-piclopentyl 2-Me-4-MeO-Pb o z t methyl MNCH(STOMe) 2 Me MeO:RA i- 772; methyl: MZhSTSNoOMe)" 2-Me-4-MeO-Rii 773 . | methyl MNSN (c) EBOMe. 2-Me-4-MeO-vA 714 methyl: М (Р) СНСНеМ 2-Me-4-MeО-Ра 775 methyl ОСН«ЕВсNOMe. 2-Mea-MeО-РЕ « 76 methyl МНеН(СНОМе) 2Ви-4-МеО-Рв 777. | metiz K(SNISNoOMe) »: 2-Ви-4-МеО-Рии не с ТОВ methyl МНеН(В) СОМ. | 2-Ви-А-МеО- Rii. 779 methyl MIR) STSNSM 2-Bi-4-MeO-P,» 780: methyl OSNIE) SNOME 2-Bi-4-MeO-RI. 781. methyl MNH(ISNYMe) with 2Me-A-MMe:-Ri 15 782 methyl. M(ССН»ОМе» "2-Me: 4-ММе; -РВ -1 783 methyl. МНСН(Е)СНоОМе 2-Ме- 4-ММех-Ри 784 methyl MR ССНеСМ 2-Ме-4- MMez-Rii c 785 methyl OSNO SNOME 2-Me-4-MMe-Ri 786 methyl MNeH(SNOME)» 2-Bi-alchMez-PE o 787 methyl: M(snISTOMe) with I 2-Bi- 4-MMe»- Rishu 788 1 methyl МНСН(Е):СНОМе 2-Ви-А-ММе-РЕ 789: methyl.

F) name) 6o 65

790). methyl t Osn сСНОМе 2-VI-AL Mez АРИ 791. | meimya MCHNSNISNOMe) from 2Vi- dr RA 792 | metnl mSnSNOM ee); 2-Vh- 4-i-Rg- R: and 793 | metnia MYSN(voO) ENOME 2-Bi-4-i-Be- Ri 794 methyl. М(Ри) СНоСТСМ, 25ВИ-а-иРи-РЬ. 795 methyl. OSNEO SOME 2-Bi-a-i-Pi:P 796. methyl МНСНеСН»ОМе) with "2-Bi-8-Me-P ! vig methid |. M(СТСНОМе) 2 2-Bi-4-Me-P 70 798 methyl МНСН(ЕО СНЮМе 2-Ви-4-Ме-Ри 799 methyl Ммеуснем 2-Ви-4-Ме-Рей

Vo methyl OSNO SOM 2-VI-ya-Me-Pv 801 methyl | МНеСНИСВОМе with: 2"Ви-4-Ме-РБ 802 methyl M(СНАСНИОМе); 2-Bi-4-Me-Pb 803 methyl MHCNEu CHOM 25Bi-a-Me-PE 804 000 methyl Mi(PO CHOM 2 Vi Me-Prii 805 methyl. OSH(E)OSNOMe o2-Bi-4-Me-Pb. 806 | methyl 1 MNHON(CHNOMe)" 2C4,0-Mez" Ri 507 methyl M(CHNOMe) 2-14, 6-Mez-PE; 808 methyl MNN (CHNOM) 5: 4-Bi2, 6- (Me) 2 -PA. 809 methyl MISTOM" - 4-Bg-2,.6-(Me)z- P 810 methyl MHCNISNOMe) z. 4-i-Pi-2-5Me-Rit 811 oi 00 methyl M (ІСНОМе) with 4--Р-5МеРИ 1 812 methyl МНеСНИСНОМе. 2-Bi-4-SERB 1 813 methyl M (CHOM) » 2-Bi-A-SE PE and 814 methyl MHC (SOME) with 2-BI-4, 6-(MeO)2-Pb 815 methyl M ( STSNOMe) with 2-Vi«4; 6-(MeO) Pb o 816 methyl МНеН(СНОМегУх 2-С14,6-(Mebu.Р1 1 817 methyl M(ССНУМе) 2 2-С1-4, 6-"МеО) РЕ 818. | methyl МНХН(СНУМе) )» 2, 6- (Meu»-4-5Me-Pb 819 methyl MCS Me)» 2, 0- (Me) x4-5Me:Pi c zo 820 methyl MNeH(CHNOMe) with 4-(cOoMe)-2- Vi-Rig vg1 methyl: MeSTSNIOMe) 5 Go I-"COMe)-2-VI-PE - 822. methyl MNH(CHNOMeH 002,45 6-Mes-pyrid-3-yl 1 893 methyl | M(CHNOMe)". 2, 4, 6-Mech-pyrid-3-yl Me. 824 methyl MNCH(CHNOMe)" 2 - (Br -RV co 825 methyl MeSSVOME) ". 2A-(BE-Pb 86 methyl MNHHeCHNOMe) with | d-Ri -2-5Me-Pb m- 827 methyl М(СНеНОМО)". Я-Риг2-5МеР 828. methyl МНСНаСНОМе) with dni-Вг-2-505Ме-ПЕ 829 methyl З M(СНеСНОМе) 5 4-рк-2 -505MeR 830. methyl 1. MNSNisvfOMe); 2,6-(Me)--4-5Me:Rii « 831 methyl M (сНЮМе» 00 3у6-(Me)-4-5Me-Рв З 532. methyl МНеН(СНОМе)». 2,.6- ( Me) 27-4-505Me-Rii c | 833. methyl. M(CSNOME) ». 2,6-(Me) 505 Mevy SI "» 534 methyl МНеНСНОМе) 24 ОРБ " 835 methyl МИСБНОМе) » osara-еРиР И 836 methyl MNH(STOMe) » 2-VI-4-M- (Me)z-6-MeO-PE: 837 methyl: M (CHCHNOMeu» 2-Via-M-(Me) Meo-Ry -I 838 | methyl 00 ME 2-Bi-4-MeO-P 839. methia MH-3-pentyl 2-Bi-4-MeO-Pi o 840 7 methyl MNeH(SNIOMe) z | 2-4 4-Me-P І so Va methyl . syu 844 methyl M(CHnSTOMe): 2 5-Mekha-MeO-RI I

F) at 60 b5 vav: methyl | MH-3-pentane. ' | 2, 2 Mez-4MeO-PE, 846 methyl MES: 2, 5-Mex4-MeO-Pb 847 methyl MNCH(CHNOMe).; 2-C1-4-City Hall and 848 | methyl МНЕ) СНОМе 2-sia-Meryi 849 methyl 000 M(СБСТОМе)z ! 2-C1-4 Mary

B50. methyl. HO. shi NI 2"Me-4-MeoRv for methyl (53-MnSn(SNSTOoMe) CHOM: 2-Me-4-MeOR 855 | Mmethyl M(e-OHnUsSSsnOM 2-Me-4-MeoRy 856 methyl МНСН (СНСНОВО with 2-Me-4-MeORy. 857 methyl M se-c»HnOSSNSM au v-ST-PE 858 methyl | MEb 2-Me-4-SIRE 859 methyl МН-3-pentyl 2-Me-4-SYRI» 860 methyl | M (SNSTOM ee). from 2-Me-4-SULFUR 861. methyl MNON(CHNOMe) » 2-Me-α-SULFUR 862 methyl MES 2-Me-α-SULFUR.

Vo methyl ME; 2-s1-4-MeRii 864 | 00 methyl MH-3-pentyl 2-C1-4-MerRi 865 | methyl ENN Ma g 2-C1-4-MeORB 866 methyl MNeH(SNIOMe) 2-C1-4-MeORE "867 methyl Men) СНОМе 2-си:а-МеОВЕ 1 вбЕ methyl M (с-Ру СЕБСНСМ 2-С1- 4-MeORB

I 869 methyl 00 MEB C 2-C1-4-MEOR with tto methyl 00 MH-3-pentyl : 2-c1-4-MeORE o 871 methyl MNH(EOSHSNOMe ' 2-Cr4-MeORy 82 methyl MHeN(MeO STCHNOMe 2- С1-4-MeORi 873 | methyl МНеСН(ЕССНИСНОМе 2-Ви-4-МеОРЕ 874 methyl МНЕН(Меу ССНОМе. 2-Ви-А-MeORБ со 875 Methyl МНСН(ЕОСНСНУМе 2-Me-4-MeORa 876 metnlo | МНСН( Me) SNSNOME. 2-Me-4-MeORI - 877 methyl -. MNN (SNOMEu» 2-C1-4, 5- (MeO) with F 878 "Methyl M(SNSTOMe) with 2-14; 5- (MeO) 879 methyl | : "MeO) ZR - 882 1 methyl MEEZ-pentyl 2-СИ-4, 5-("MeO) Ri 883 methyl: МНСН (EOSPZHSNYUMe 2-С1-4, 5-(MeO) zp 884 | methyl chnen(Me) СТСНОМе 2-14, 5- (MeО)5Р 885 methyl МНеН (СНоОМе)» 2-ВИ-4,5-»MeО) РЕ « 20 886. methyl MeESHSNOMe)» 22VI-A, 5- (MeO) Pv t 887 methyl МНСНа(Е) СТСН»ОМе. 2Ви-4, 5-(МеО) РА with 888 methyl Мс-ВО) СтиСНСМ 2-Вг-4, 5-(MeО) Р

I" 889. methyl | ME 2-B-4,5-(MeO) Ra 890; methyl МН-3-pentyl : 2-Ви:-4, 5- (Meb)оРА 891 methyl МНеН(СНОМе) 2 2-С1-4, 6:5МеОУ РЕ 35 892: | methy | М(СБСНОМе)» 2-с14,6-(MeОу РЕ - 893. methyl| at 895 meiy Mnen(sshOMe)" 2-Me-4; 6-(Meb) P

Ge) 596 Metnlo | M(SSNNOMe) with 2-Me-4, 6-"MeO) Ri. 897: methyl. MNSN (BO StOMe 27Me-4, 0 (MeO) zr - ov methyl. ME 2-Me-a, 6: (MeO) Rv. p. 899. methyl MH-Znents u. 00 2-Me-4,6- ( MEOSORI

F) at 60 b5

900: methyl МНСНИВОСТСНюМе And MeЯ-МеОРЕ 901 methyl: МНН (Ме) СНУСНОМе 2-Me-4A-MeORi 902 methyl МНеН(СТОМе)» 2-MeO-4-Mery. 903 methyl M(ССНОМе) » | 2-MeO-4-City Hall! 904 methyl, "MNONI(B) SnOMe 2-MeO-4-MeR 905 methyl M(сРО СНСНСМ 2-MeO-4-Mery: 906 methyl. ME 2-MeO-4-Mery. 907. methyl МН-З-pentyl 2-MeO-4-Merii 908 methyl MNSN (BO STISN»OMe 2-MeO-4-Mery 509 methyl MNSN (Me) SNISNOMe: 2-MeO-4-Merii: 910 methyl: MNSN(SNYMe) 2-MeO-4 - Mayor:

SIV vyvtil M(SSNNOMe) g 2-Meb-4-Mery: 912 methyl MNeNEUSNYUMe 2-MeO-4-Mery; 913 methyl M (sr) CHCHnCM 2-MeO-4-Mery. t 914 methyl MEe 2-MeO-4-Mer. 915 methyl MH-Z-pentyl 2-MeO-2Meria 96 methyl. MNSN (SOMe)" | 2-MeO-4-SULFUR 917 | methyl М(СНЕНОМе) 2-МеО-4-СИРв 918 | methyl МНСН(Э) СНюМе: 2-MeО-4-SUРЫ 919 methyl ME 2-MeО-8-СРЫ 920 methide MY Z-pechtyl | 2-MeO-4-SULFURE

Table 6 ch (8)

VZ

I" | in o "- m land : -/ b

Dt so ich- hA- stump in | a bar app. ; sh 95 1 metl 10333 МНСЩСВОМЕ» 24-С-РЙ « 922 mety MNSNRt» 2.4 -с5-ВЙ Z to 923 methyl MBIVy 2.4-САРЬ с 924 | methyl MRCH» OZNA) 24-С-РА z» 925. methyl МЖСВСНюЮМе» 2,8-С5-РЭ " 926 methyl МН-З-teptyl 2, 5-5-РЭ ! 927 methyl MiІСН(ЕОСТОМе 2.4-СБ-РІ 928 methyl ME. 2a-C-PE -1 929 methyl MNCH(SNOVO» 2,4-SAPH 93 | methyl MH-3-pentnl 2,4-C-PE (95) 931 methyl | MMeria dan P so 932 methyl I MR; bu Si -P 933 methyl MEEZ-texyl 2,a-cb-RI ayu | GG Me i be»

F) name) 60 b5

934 methyl omerfolino | 2,4-С15-РВ. 933 methyl М(СНОРИ) СНСНОМе and -Св-бБ 936 methyl. | MNSE(SNoRI) SN.OMe. 2,4-s;-PH 95 s 937 metnia.

MH-4-tetrahydrofuranium 28 -C15-Pb 938 methyl MNecyclopentnl 2/4 -Cb-Pb 939 methyl OB: 2 -C5-Bb 940 methyl.

OSP(Eu COMe 2-1, RA 941 metnl: BASE 2.4-С1;-Рн 70 942 methyl "О-3-pentyl 54-С5-РЬ 943 methyl ЕЕ 2,4-С-Рии 944 methyl | 5(ОУЕ 2 ,4-С1,-Ри 945 methido З 505 EI 204 С-РВ 946 methyl phenyl | 2,4-С-Пр 947. metnia 2-SEURB 2,4-05-Ри т5 AB methyl 2РСВБ 24 -С;-Ри 949: methyl ! 3-Pentyl ma- "-B - 950 methyl g cyclobutyl 2,4-С5-РЬ 951 methyl | 3-pyridyl 2,4-05-РЭ 957. methyl | CH(Е) СТСОММе» 2 а- СБ-Ф 953 methyl | СН(БЕ)ОСННММЕ» | 2,4-СБ-Ри 954 7 Methyl МНеН(СН»ОМе)»! 246-Мех-Ри 955 с methyl МНеНРИ» 2,456-Мез-ПЕ 950 1 methyl ME 2,5,6- Mez-Ri 957 methyl MRIXHSN»C-SZNU 2,A,6-Mez-RE 958 methyl MeneBOMe»: 2,4,6-Me-RI !c 959 methyl MY Z-gentyl 2,4 . ,4,5-Mez-Ri 965 -methyl o M 2,4,6-Mech-Ri - 966 "methyl МН-3-hexyl 2,4,5-Mez-Ri; 1967 methyl morpholino | 2,4.6- Mez-PE; b 968 methyl M(SNORE) SNISN»OMe! 25 8,6-Mech-PE. co 960 methyl MNH(ISRISNIOMe: 2,4,6- Mech-Pb 970 methyl MH-4-tetrahyde rofuranil 254.6 -Mez-RI; in. 9 mMethyl "MH-cyclopentnium 254,6-Mez-PE 972 | methyl OK : 2,4,6- Me5-Pe: 973 methyl OSPEOSTIOME 2,4, 6-Mez-PE: 974 | meyl OSNORB 2,4,6 - Mez-RE. " du 975 "methyl O-3-pentyl 2,4,6-Mez-RI. -o 976 methyl ZE 2,43,6-Mez-RE c 9770 | methyl (Ou: 2,4,6-Meh-PE "" 978 methyl 50; BI 2.4;6-Mez-PE " 979 methyl CHO, EO; 2,4,6-Me-PE. 986: methyl C( ЕВ(СО EF 2,4,6--Me-РЬ 1 981 methyl сСщЕуСсНОН | 2; 4,6 Mez-PE - 982 | methyl CE) STUMe 2,4, 6 Mez-RI 983 -methyl.

SOKMe; | 2,4,6-Me-P: c | 984 | methyl SOSNU 2u456-Mez-RB ovb methyl. | SON) PE-3-pyrylyl 2,4,6-Mez-RK. - 987: methyl. phenyl 2,4,6-Mes-Rii so - o88. Mmeinlo 2-rRB-Ri; 2.45 6-Mech-PE;

(F, ko 60 65

Г989 17 methyl " Z pentium | | yy, Me -PE ! 990 methia | cyclobutyl. 2.4,6- Me-PE 991 metnl | o 3-pyridnia 2. 4,6- Mez-Ri 2 992 methyl CH(EOSNSOMMe" 2 . Meh-Riya 9960 | methyl МНеН (БО СН»ОМе: ! 2,4-Me»-Рии 0 997 | methyl | МН-3-pentyl 2,4-Me-Рии 1 7998 methyl | MEb 2,4-Me-Рии

I 999 methyl 0 schem» with 2u4- Me -Rii 0 methyl chnen(MesNOMe 2,4 Me ARI 1001 | metnl OSN(EO CHOM: 2.А-Me:-РА 1002 methyl МПЕ-е-СзН» 2,4- Mez2Ri 15 1003. methyl МНОеН(Me) СНАММе» | 2,4-MeARE 1004 "methyl mee-СхН) СНСНСМ 2,8- Me;-РЕ 1005 methyl М(РОСНСНСМ 2,4- Me,-Ри 1006 methyl MV) SIENISM 2:4- Mech-Ry Y 1007 methyl "MNeHRg" 2,4- Mez-Ryy |! uch 1008 methyl MeV | 2,4-Me»-PE 1009 | methyl MR (CH»-o-CH) ! 254 -Mech-Rii methyl MH-Zegeptyl 2.A- Me -Rii yuYT1 methyl ME; 2, 4-Mez-Rii 1012 methyl. MHSN(ISNOVO 2,4 - Mez-RE 1013 methyl MH-3-pentyl 2,4- MeeRi s | 1014 | methyl MMeri 2,4-Me»-Pb o 1015 methyl MR. za - Me RI 11016 | methyl MH-3-hexyl. , 2.4- Me:-PE ' 1017 "methyl "morpholino | 2,4 Me -Ph 1018 1 methy MISNHRI) SNASNUMe 2,4-Mech-Ri so zo 1019 methyl: MHCH(SNORV)SNHOMe 2,4-Me:-PHE ! 7020 methyl MH-atetrahydrofuranil 2,4- Me;-PH. - 1021 меня ME пиклопентих | 254 --Mez-Ra 1022 methyl ЖНСН (СОМ) 2-Me-45MeО-Ри» 1023 methyl MSNISNOMe)x 2-Me-4-MeO-Ри» с 1024 | metii MNSNCHE)SNOME | 2-Me-4-MeO-Rii 11025 1 meinl (RI) SNSNISM 2-Me-4:MeO-Rii M. 026 | methyl OSN (EOSNYUMe 2-Me--Meo-Rii ! 2 methyl МНСН(СНОМе)» 2-Bg-4-MeO:Rii ov methyl: M(SSTOMe) U I 2-Bi-4-MeO-Rb 1029-| methite МНСН(Е) СНЮМе 0000 av Meo-Ri « du | 030 methyl MaРО) СНССНИСМ 2-Ви-4-МеО-Рии З7З 11031 |) meinl OSN (EO-СНоОМе 2-Ви-а-МеО-Ри ' s 1032 .| metd |i CHNSN(CH.OMe) with 2-Me- 4-MMez - RI; "from 1033 methyl MSTSNOMe)" and 2-Me-4-MMe»-Rii " 1054. metnl MNSN(BOSTOME and 2- Me-4-MMe»-Rii 1035: methyl. : 2-Vg-4-MMe:- RI 1038: methyl M«(СНСНОМе) with | 2-VIi-4-MMez-Ри о 1039. | methyl МНеН(ЕВ СТОМе 2;Ви- 2-КМег- Rv с 1040 . methy | М(РО) ЭШСНСМ | 2-Вг- 4-IMMe; -Рій 14 methyl |. ОСН(Е)СТОМе 2-Ві- 4-ММе-Рій - 7 1042. | metalo | МНСН(СНЮМе)" zeVi - ЕРЕРЖ sü 1043. | methyl | MCNeСНОМе» | 000 2Ви-4а-реРБ 1

Ф) име) бо b5 lo meti MNON (EE) EN»OMe 2-VI- A EBRER 1045 metkl. MR) SNISTSM Z-VI- 451-RI-RE 046; methyl o. OSNI(EO EN,.OMe 2-Wt-4-i-Ri-Ri: 25 | 1047 methyl MNeH(SNOMEu» 2-Bi-4-Me-Rii 1048 methid M(STSVOMe) 5. 2-Bi-4- Me-Pi 1049 methyl MASN(EOSNOMe 2-Bi-4-Me-PE 1050 | methyl M(RUSSNSNSM 2-Bi-4-Me-P

І 1051 | mail OSN(E) СНОМе 2"Ви-4-Ме-Ре у 1052. metnya: МНСН(СНОМе". 2-Ви-4-Ме-Рё 1053. methyl MSTSНУМе» 25Ви-4-Ме-Ри 1054 methyl | МНеН (BO СНОМе 25ВИ-4-Ме-Ре 1055 methyl M (РО ССНСМ 2«Ви-4-Ме-Ри 1056.| methyl OSN (ВО СНЮМе | Ва-Mesry. 1057 methyl. МНСН (СОМе)». 2- 14, 6-Me»-Ri 1058 methyl М(СНСНУМе) » 2701-84, 6-Meх РИ 1959 methyl МНСН(СНОМО» 4-Bi-2,6- (Me) Р 1060: methyl M(СНСТОМе» 4- Bi2, 6-Meo-v! 1061. Methyl | МНеН(СНОМе)» апсре2-5МеРБ 062 mail M(СНАСНОМе) »! аи-Ре-2-5Ме-РЕ. 1063 methyl KННСН(СН,ОМе) 2-Ви- 4-Xu-Pb 1064 methyl M(CHCH.OMe) » 2-Bi-4-CeE.-PB 1065 methyl: MNeH(SNIOMe) » 2-Bi-4,6-(MBO)-PE ! 1067 methyl МНСН (SOM) » 2-C1.4, 6- (MeO) 5-Rih /l068 methyl M(piSNuMe) with 2-C1-4, 6-(MeO) UR! c 1069. methyl MNHNuISNOMe) 5: HO 56- (Me»-5Me-Rie o 1070 methyl M(CHCHNYMe) o Y 5e(Me)»-4-5Me-Ri 1071. methyl MNHNSTOMe)» A-(COMeu-2-VI-Py 1072. methyl M (CHNYMe) with a- (SOMEu-2-VI-RI. 1073. | methyl MNHN (CHOM) » 2,4,6-Messhrid-Zsyl so zo 1074 methyl M(CSN»OMe)» 2,4, 6-Mes-pyride -3-yl 1075 methyl INN (CHOM) ». 2,4-(Hgr -Pb - 1076 methyl M«СНСНОМе) with 2,4 -"ВГ"-ПЕ 1077 | Methyl Ministry of Emergency Situations (SOM); 4-и-Ри-25Ме-РЕ Ф 1078 methyl M(СНХСН»ОМЕе) g | 4-i-ri-2-5MeR with 1079 methyl МНСН(СНОМе: d-и«Ри-2-505Ме:Ри: 1080. methyl M(СНСТОМеІ with 4-1-Рг-2-505Ме-Ри; - 1081 methyl MNH(CHNOMe)" | 2,6-(Me) x4-5Me-Pb 1082 methyl M(CHNOMe" 2, 6-(Me) 2--5Me-PA.

And 1083 | osmetilo | МНЕН (СОМ) 2» 12, 6-(MeuchA-505Me-Rit 1084 Her methyl M (СВБСНюМе)» 2. 6-(Me) z-4-505Me-РЕ « zo | 1085 | metchl MHC (СНОМе) z 2 i-ReRi 2

ИО86 methyl | М(СНСНОМе)» 2-1-4-и-Ри-Вв ше с 1087 methyl МНеН(ЕНОМе)» 2-Ви-4-- (Ме)»-6-МеО-Ри. "» (1088 methyl (sne Me)" 2-VI-A-M- (Mer-6-MeO-PE " 1089 | methyl MeV 2-Vg-2-MeO:-RA 1090. methyl MH-3-pentyl 25Vi -45MeO-P 1091 methyl MNH(CHNOMe)» 2-CM-4-Me-Ra - 1092 7 metny M(с-с3Н») SPTETSM 2,4, 6-Mez-Ri 1093 methyl MHC (CHNOMe) CHOMe 2 Me --Vi-Ri. o SHHU4 | methyl MNHNaSNOME) in 2,5-Me-MeOR with 1095. methyl Mm(SNHNOMe)" 27 5-Mez-4-MeO-PE 1096 methyl MH:3-pentyl 275-Me" 4-MeO:Rii I - 1097. methyl МЕС -255-Mez4-MeO-RIi with 1098 | metnya.

1095. methyl: MONE) SOME ! 2-SI-Y-MeRE

About O| blizzard | 000 M (SNSBOMO 5-S14-Mayor:

My methyl her 0 (535-МНСЯ(СНСПОМе СНОМе о 2СвBAМе?є |! 1102. methyl | Manu snnSM 2,5-Meh4-MeORi 1103 | methyl. MEB | 2-Me-A4-MeORI pd. methyl OB 2-Me -4-MeORi 1105 | methyl. (5)-CHNH (СНСНОМе) СНО Me 2-Me-4--MeORi 11061 00 methyl 0 mM (esnusnesnsm 2-Me-A-MeOrB. 1107 methyl МНН (СНСНОУВО» 2-Me -4-MeORB to 1108 | methyl M (сн СНСНСМ 2, 4-С1-В 4109 metnl MEb 2-Me-α-SULFUR pyu methyl: МН-3-pentyl 2-Me-α-SULFUR vi Methyl | K(ISTSTOMe ) about 2-Me-4-SULFUR

Pich methyl МНСН(СНОМе) 2 2-Me-4-SULFUR. pz methyl MES 2-Me-4-SsiRn la | -Metyh MVe! 2-sye-MerRe 115 methyl MH-3-pentyl 2-C1-4-Mery 16 methyl. | M(СНОМеу; 2-СІ-YAMEOR p17 methyl | МНСП(СНОМе) 2 2-С1-4-МеОРы 1118: methyl: МОСЭВСНОМе 2 sa MeОРЕ 1119. methyl M (ср) СНЕВСМ 2-С14-МеОРы 1120 methyl ME 2- C1A-MeOR 1121 methyl MH-3-pentych 2-si4-MeORE 1123 methyl МНСН (ЕВ СТСН»ОМе 2-с4:MeORy

And yes. methyl МАСН (Ме) СНСН»ОМе 2сИ1-4-МеОрв сч 1125 1 Metyp МНСН(Е) СНСОМе 2ВгА-МеОРЕ 1126 "methyl | MNSN(Me) SUSTYOMe 2-Vg-4-Meor He) but methyl | MNSN(E) SNSTOMe. 2-Me-4-MeORi 1128 methyl МНСН(Ме) СНСТОМе 2-Me-4-MeORi; 11294 methyl MNeNIStoMe) 2-C1-4, 5- (MeO) gri 1130 | methyl M (SPON Me) 5 zna, 5:(MeOu ar | o zI31 methyl MNN (EO'CHNOMe 102-014, 5-(MeO) oRii - 1132 | methyl M (se-P) СССНЕМ 0008-0145 5-( MeO) РЕ 1833 methyl o MEЬ 2-С1-4, 55 (MeО) 2РВ. Ф 1134 | methyl МН-3-pentyl 2-14, 5(MeO) ru

I mZv | methyl MNH(VO SNISNOMe 2-E1-4, 8-(MeO) RE o z M36 | methyl MNH (Me) СНСНОМе oo ВС 5-(Meo)rvo k 1137 | methyl. МНеН(СНОМеу» 0000 Ya Vi-4, 5-("MeO) or 1138 | meinl M (СНСНОМе)» 25ВИ-й,5- (MeO) Ри 1139 methyl. МНеОН(Е) СНСНОМе 2-Вг:4;5- (MeO) Ри; 1140 | metnia. M (sr) SNHSNOSM 2-Vi:a, 5- (MeO) ZR ! « la methyl OO MEbS 2-8i-4,5-(MeO) ori 1145 marks MH-3-pentyl 2-Vi-4, 5- 4MeO) RI - p 1145 | metnia МНСН(СНУМе)» 2-С14 6. (MeO) or . | 4144 methyl. М(СНСНОМе)»: 2-С1-4; 6-(Meb) «Рии», t 3145 Methyl ME. 2-C1-4,6- (MeO)2Pv is methyl. | / MH-3-pentyl 8-14, 6- (Meb) Re 15 Its pe Mmethylo MNSNISNOMe" 2-Me-4, 6-( MeO) ev -I pa methyl 1 M(SVENUME) x 2-Me-4,6- (MeO) Ri 1149 methyl МНСН (БЕ) СНОМе 2-Me-i, 6- (MeO) Pv 2) 1150 1 methyl OMEЕ : 2-Me-4, 6: (MebO)5RA (1151 methyl | LMNZ-penty. 2-Me-4, 6-(MeO) gri. o OM52 | o methyl | MNN (B) SNASNOMe 2-Me-4 -MeORi pz 1153 methide MNSN(Me) CCNOMe 2-Me-4-MeORE 1154 methyl.

F) ho) bo b5

- Yay Usefulness. 1155 methyl M (SnSNMe» 2-MeO-4-Mery: g 1156 methyl "MNCH(EO COM: 22Meb:4-Mery, 1157 methyl M (c-ROSNSTSCM 2-MeO-4-Mevy; 1158 methyl | ME | 2 -MeO-4-MeR. 1159 methyl / MH-3-pentium 2 Meo-4-Merium and 1160 methyl МНСН(ЕВСНИСН»ОМе 2 Mes-4-Mer: I 1161 | methyl | KNeH(Me) СНИСТОМе 2-MeO- 4-Mery. 1162 methyl MNN (CHOM) 2-MeO-4-Mery o 1183 | methyl M(СТСНЮМе) сМеО-еМеРЬ tva methyl МНСН (BO STOMe 2-MeO-4. Mary 1165 | methyl M (сРАУСНСНСМ 2-Meb : a Merii 1166 Her methyl ME 2-Mesk4-Mer. I 1 Pb7 methyl MH o pentyl 2-MeO-4-MeRiii 1168. methyl МНСН(СНОМе) » ! 2-MeО-а-СИРВ 169 methyl M (СНИНОМе) 5 2-MeO-4-SULFUR 1170 methyl MASN(E) SEOMeE 2-MeO-A-SULFUR 71 | methyl ME 2Meo-a-SULFUR 1172 methyl MH-3-pentyl 2-Meu-4-SULFUR , , , ,

Analysis of the SKE receptor (SKE-KT1), according to the degree of its binding for the Calculation of Biological Activity

Next, there is a description of the selection of cell membranes that contain cloned human SKE receptors, for use in the standard analysis of the substance according to the degree of its binding, as well as a description of the analysis of it itself. high school

Informational ribonucleic acid (RNA) was isolated from the human hippocampus. Informational ribonucleic acid was reverse transcribed using oligo (a) 12-18, and the coding region was extended using (o)

RSK from initiation codon to termination codon. The resulting RSC fragment was cloned into

EsoKkM site of pROEMMU, from where, using XpoiIXhai, the insert was corrected and cloned into Xpoi-Xvai sites of the rtZag vector (which contains the cytomegalovirus (CMV) stimulator, 5M40 t splice and precursor polysignals A, Epstein-Barr virus replicator (Erziep-Vaght) and a marker , hygromycin (pudgotusip), which may be selected). The resulting expression vector, named rispSKEK, was transfected into -- 293EVMA cells and cells that supported the episome were selected in the presence of 400 microM hygromycin. Selected Fo cells that maintained viability for 4 weeks were pooled in hygromycin, adapted for growth in suspension and used to generate membranes, which are required for the analysis according to the degree of co-binding, which is described below. Individual aliquots containing approximately 1x10 8 cells in suspension were then centrifuged to form pellets and then cooled.

To perform the binding assay, the chilled pellets described above containing RSEKI receptor-transfected 293EVMA cells were homogenized in 10 milliliters of ice-cold tissue containing buffer (50 millimoles NEREZ buffer, pH 7.0, which contains 10 millimoles of MosSi, 2 millimoles of ESTA, 1 microgram/liter of aprotinin, 7 micrograms/liter of leupeptin, and 1 s microgram/liter of pepstatin). The resulting homogenate was centrifuged at 40,000 rpm for 12 minutes. the pellets were resuspended to obtain a protein concentration of 360 micrograms/ml for use in a subsequent test.

Binding tests were performed on plates with 96 cups; each cup had a capacity of 300 microliters. To each cup was added 50 microliters of the diluted drug to be tested -I (final drug concentration in the range of 1079 to 1079 Mol), 100 microliters of 725I-omipe-SVE (I-o-SEE) (final concentration of 150 peakMol) and 150 microliters of homogeneous cells described above. The plates were then allowed to sit at room temperature for 2 hours before filtration, which was done on SR/E (Ce) filters (Rhezoakea with 0.395 polyethyleneimine) using an appropriate cell harvester. Filters were rinsed 2 times with ice-cold buffer before removing individual filters and evaluating them for radioactivity levels using a gamma counter. The curves of inhibition of 7251-o-SVE binding to cell membranes at different dilutions of the tested drug were analyzed in accordance with the curve obtained using the iterative Gizamo fitting program

IR.U. Mipsop and 0. Kodvaga, Apa!. Viospet. 107:220 (1980)), which provided Ki values for inhibition, which were then used to assess biological activity.

A compound is considered active if it has a Ki value of less than about 1,000 nanoMole for SKE inhibition. i.e.) Inhibition of SKE-stimulated adenylate cyclase activity.

Inhibition of SKE-stimulated adenylate cyclase activity was performed as described in b. Vaitsadiia 6o ek ai. Bouparzet 1:572 (1987). Briefly, assays were performed at 372 for 10 minutes in a 200-milliliter buffer containing 100 mmol of Ttiz-HCl (pH 7.4 at 37 degrees

Celsius), 10 milliMole Maosi", 0.4 milliMole ESTA, 0.1 95 B5A, 1 milliMole isobutylmethylxanthine (IVMH), 250 units/milliliter phosphocreatine kinase, 5 milliMole creatine phosphate, 100 milliMole guanosine 5-triphosphate, 100 nonaMole oSPE, peptide antagonist (concentration range from 109 to 1097 in 0.8 milligrams of the original by soaking a weight of tissue (approximately 40-60 milligrams of protein). Reactions were initiated by the addition of 1 mmol ATP/ZRI adenosine 5-triphosphate (ATPU (approximately 2-4 milliCuries/tube) and ended with the addition of 100 milliliters of 50 millimoles of Tgiv-HCl, 45 millimoles of ATP, and 295 sodium dodecyl sulfate. In order to monitor the reduction of 35-cyclic adenosine monophosphate (CAMP), 1 microliter of (-NISAMP (approximately 40,000 decays per minute) was added to each sample (drt)) before separation. Separation | Z2RISAMR with GZ2R)

ATP was carried out with the help of sequential washing over columns of aluminum oxide and ХОомжмех.

Recovery was agreed upon by more than 8,095.

Certain compounds of the present invention have been tested using this test and found to be active. 70 Biological Analysis ip mimo.

The IP MIMO activity of the compounds of this invention can be evaluated using any of the biological tests available and accepted in this field. Illustrative for such tests may include the Acoustic Startle Test (Association biape Azzau), the Stair Climbing Test (ziaig

Siitbripd Tez), Chronic administration test (SPpgopis Adtipivigayop Avzau). These and other similar 75 models are useful for testing compounds in accordance with the present invention and are seen in the work of SU.

Berridge and A.Y. Danna "Reviews of Brain Research" (SLU. Veigtidde apa A... Oipp Vgaip Kezeagsp Bemiemuv 15:71 (1990)).

Compounds can be tested on any type of rodent or small mammal. The disclosure of tests in this specification is not intended to limit the practice of the present invention.

The compounds of the present invention are useful in the treatment of disorders associated with abnormal levels of adrenocorticotropic hormone-releasing factor in patients suffering from depression, affective disorders and/or anxiety disorders.

Compounds of the present invention can be administered to treat these abnormalities by means of contacting the active agent with a site on the mammal's body to which the agent acts. Gee!

The compounds may be administered by any standard means available for use with pharmaceutical agents either as an individual therapeutic agent or in a combination of therapeutic agents.

They can be administered one at a time, but, of course, are used together with a pharmaceutical carrier, which is selected taking into account the selected course of treatment and standard pharmaceutical practice.

The dosage that is introduced also varies depending on the application of factors such as Geo) pharmacodynamic characteristics of a separate agent and its regimen and course of treatment; patient's age, weight, state of health; nature and degree of symptoms; type of parallel treatment; frequency of treatment; and the desired effect. --

For use in the treatment of the aforementioned diseases or conditions of their treatment, the compounds according to this (o) invention can be administered orally daily at a dosage of the active ingredient from 0.002 to 200 milligrams/kilogram of body weight. Of course, a dose of 0.01 to 10 milligrams/kilogram in divided doses from one to four times a day, or in a form that gives permanent pain relief, will be effective for obtaining the desired pharmacological effect.

Dosage forms (compositions) suitable for administration contain from about 1 milligram to about 100 milligrams of active ingredient per unit. In these pharmaceutical compositions, the active ingredient is usually present in an amount of from about 5 to 9595 wt. of the total weight of the composition.

The active ingredient can be administered orally in the form of solid dosage forms, such as capsules, tablets and powders; or in liquid forms such as elixirs, syrups, and/or suspensions. Compounds in accordance with the present invention can also be administered parenterally in sterile liquid dosage forms. ,” Gelatin capsules may be used to contain the active ingredient and a suitable carrier such as, but not limited to, lactose, starch, magnesium stearate, stearic acid, or cellulose derivatives. Similar fillers can be used to obtain compressed tablets. Both tablets and capsules can be obtained as a long-acting product in order to provide continuous drug therapy for some time. Compressed tablets may be coated with sugar or coated with a film to mask an unpleasant taste, or be used to (Se) protect the active ingredients from exposure to the atmosphere, or to allow selective crushing of the shu 20 tablet in the gastrointestinal tract.

Liquid dosage forms for oral administration may contain coloring agents or flavoring agents in order to increase the patient's willingness to accept the medication.

In general, water, pharmaceutically acceptable oils, saline, aqueous dextrose (glucose), and sugar-related solutions and glycols such as proplene glycol or poly ethylene glycol are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain the active ingredient in the form of a water-soluble salt, a suitable stabilizing agent and, if necessary, oily substances. Antioxidant agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or in combination, are stabilizing agents. Citric acid and its salts and ethylenediaminetetraacetic acid (EOTA) are also used. In addition, parenteral solutions may contain preservatives such as benzalkonium chloride 60, methyl or propyl para-aminobenzoic acid, and chlorobutanol.

Suitable pharmaceutical noses are described in the work "Pharmaceutical methods of Remington" (Ketipdiop's

Rpagtaseciisa! Zsiepsev), A. Ovoya, to which this is given. standard reference.

Useful pharmaceutical dosage forms for the administration of the compounds of the present invention may be illustrated as follows: 65 Capsules.

A large number of capsule units are produced by filling standard two-part hard gelatin capsules, each filled with 100 milligrams of the active ingredient in powder form, 150 milligrams of lactose, 50 milligrams of cellulose, and 6 milligrams of magnesium stearate.

Soft - gelatin capsules.

A mixture of the active ingredient in an easily digestible oil such as soybean oil, soybean oil, or olive oil, prepared and pumped using positive displacement, is pumped into gelatin to form soft gelatin capsules, the mixture containing 100 mg of the active ingredient. Capsules are washed and dried.

Tablets

A large number of tablets are manufactured using standard procedures so that a 7/0 dosage unit contains 100 milligrams of active ingredient, 0.2 milligrams of colloidal silicon dioxide, 10 mg of magnesium stearate, 275 milligrams of microcrystalline cellulose, 11 milligrams of starch, and 98.8 milligrams of lactose. Suitable coatings can be applied to increase wettability or delay adsorption.

Compounds of the present invention may also be used as reagents or standards in the biochemical investigation of neurological function, dysfunction, and disease.

Claims (1)

The formula of the invention 1. writes formulas (1): svchren to IDY Ot o and its pharmaceutically acceptable salts, where: Ag - phenyl or pyridyl, optionally substituted by groups from 1 to C 7; with VZ selected from: MNOO (S.-S. ralkil), -- OV, b S.-Siralkilu, optionally substituted by 1 or 2 substituents СО(S.-Svalkil) or СО5(S.-Svalkil), and i, me bara; M B" is independently selected in each implementation from: halogen, C41-C-alkyl, O(C4-Sialkyl), SM and Х(C4-C:o alkylC.4-C.o alkyl); B is C.4- Siralkyl or C0-Sulfoxyalkyl; " dose and K 72 are independently selected in each realization from: H, si with C.-Sioalkyl, optionally substituted by CM, 1 or 2 OH or (C.4-Siralkyl) groups or with" M (C.4-Siralalkyl, C.4-C.oalkyl), Co-Salkyloxyalkyl, optionally substituted by F(C.4-C.oralalkyl), C,-C.ocycloalkylalkyl, Ca-C.cycloalkyl and - phenyl or o ba and K 72 taken together with the nitrogen atom to which they are attached, form a morpholine ring. c 2. The compound according to claim 1, where Ag is 2,4-dichlorophenyl, 2,4-dimethylphenyl or 2,4,b-trimethylphenyl; EE tav: - SNuz, and 3 - me bara, - 3. Compound according to claim 1, where EZ is MAbar "a or OK". c" 4. The compound according to claim 3, where K92 and "2 in Me bar a are identical. 5. The compound according to claim 3, where KZ and K"2 in MEbar a is Ci-Secycloalkyl. b. The compound according to clause 3, where Ka and B'/2 in MKbar'a are independently H or C-Sialkyl, and each C-4-Sioalkyl is optionally substituted. o 7. The compound according to claim 1, where Kba and "2 in Mbav/a are identical and are S.-Sulalkil, and each S.-Sulalkil is optionally substituted. to 8. The compound according to claim 1, where K92 and K " 2 selected from C3-Seccycloalkyl. in 9. The compound according to claim 1, where both and Va are identical and are selected from C1-C4 alkyl, optionally substituted, and C.-C cycloalkyl. 10. Compound according to claim 1 of formula (50): b5 ЕВ: борн "Obvious: оопуйщий да ю Ж С зн He and its pharmaceutically suitable salts, which are selected from the group of compounds in which: 23 - МНСн(п-Рг)", 872 - СИ, В75 - Н, Бс - СИ, B - H and Be - H; t5 VZ - MNSN(Ed(p-Vy), Ba - SI, 826 - H, Bs - SI, B - H and Be - H; 23 - MNSN(EF(SNoOMe), B72 - SI, BB - H, Vs - SI, V - H and Ve - H; 23 - МНСН(СНЁОMe), Va - SI, vv - H, vs - SI, 794 - H and Ve - H; 23 - ЖЕО» . sh(MeKhRY), B72 - SI, B75 - H, Vis - SI, VZ - H and 72 - H; 23 - MNSN(ED(p-Rg), 872 - SI, B75 - H, vis - SI, Ba - H and Be - H; 23 - MNSN(SNoOMe)", 72 - Me, B5 - H, v/s - Me, 79 - H and B72 - Me; zv 23 - MNSN(SNoOMe)", Ba - Me, B ? - H, Vs - Me, B79 - H and Ve - H; ch 23 - MNSN(EF(SNoOMe), Ba - Me, 75 - H, Vis - Me, B79 - H and Ve - H; o VZ - MNSN (EO", 72 - Me, V? - H, v/s - Me, VZ - H and 72 - H; 23 - OB vla - SI, 75 - H, ve - SI, VZ - H and Ve - H; 23 - Sh(СНоСМ)», 872 - Me, E5 - H, B: - Me, VU - H and Ve - H; o 3 - Mnen(MehSsNoOMe), B72 - Me, 5 - H, Bs - Me, 79 N and Be - H; - 23 - mnen(mechSsNoM(Me)»), 272 - Me, B75 - H, Bs - Me, 79 - H and B72 - H; 23 - Msh(с-РГ(СНоСНоСМ), 72 - Me, V - H, Vs - Me, VZ - H and V72 - H; b 23 - МНСН(ЕС(СНоОМе), Va - Me, 75 - H, Vys - Me, 79 - H and Ve - Me; co Z - MNSN(EO», 72 - Me, K?5 - H, v/z - Me, VZ - H and Ve - Me; m 3 - ShSnNosnNoOMe)» 872 - Me, B? - H, v/s - Me, 79 - H and "2 - Me; Z - MNSN(SNoOMe)", B72 - Vg, B"? - H, Be - OMe, VZ - H and B72 - H; 23 - MNSN(EC(SNoOMe)", B72 - Vg, B? - H, Bs - OMe, B79- H and B72- H; " 23 - ZEO", 72 - Me, KE" - H, Bs - Me, V - H and v72 - Me; 23 - MNSN(СНООЕО», 872 - Me, V"? - H, v/s - Me, 79 - H and Kg - Me; With p 23 - MNSN(СНХСНоОоМе )z(SNoOMe), Va - Me, V - H, Vs - Me, VZ - H and v72 - Me; Is" 23 - MNSN(EO", Va - Vg, V" - H, Vs - OMe, V/ 9 - Н and Бе - Н; З - МНСН(СНоОМ ее)", 72 - SM, В - Н, v/s - Me, ВУ - Н and В72 - Н; 415 З - Msh(с-Рг(СНоСНоСМ) . Ve - H; o 23 - mMnSn(СНооМехсносНооМе), Va - Me, В? , Vs - OMe, VZ - Me and ve - H; is, 23 - ShCSNosSnNoOMe)», 872 - Me, V" - H, v/s - OMe, VZ - Me and "2 - H; - 70 23 - MNSN(EO", 872 - Me, 25 - H, v/s - Ome, VZ - Me and 72 - H; syu Z - MNSN(SNoOMe)", 72 - SI, B - H, B 72 - Me. ), Be - SI, V - H, v5- Me, VZ - H and B72 - H; 5B 23 - Msh(с-РГ(СНоСНоСМ), Be - Me, B - H, Vs - ОМе, 879 - Me and B72 - H; o 23 - MSH(c-RH(СНоСНоСМ), 872 - SI, VI - H, Vys - SI, 794 - H and Ve - H; 23 - (8X-YANSH(СНоМе)ХСНоСНоОМе), 872 - SI, V" - H, Vs - SI, V - H and Ve - H; di 23 - MNSN(EO", 72 - Me, 75 - H, v/s - Vg, B7Y - H and 72 - H; Z - MnSnH(SNoOMe(p-Rg), 272 - Me, 25 - H, B - Me, B79 - H and Be - H; because VZ - МНСН(СНооОЕО(EO, B72 - Me, B? - H, Be - Me, KZ - H and Be - H; Z - MNSN(EO", 72 - Me, 5 - H, 75 - SI, B79 - H and 72 - H; 23 - MNSN(SNoOMe)", 72 - Me, 75 - H, Vs - SI, V - H and Ve - H; 23 - MNSN(EO", Va - SI, V - H, Vs - Me, VZ - H and B72 - H; 65 23 - MNSN(EO", Ba - Me, 75 - H, all - MMe", B79 - H and Be - H; 23 - MSH(с-РГ(СНоСНоСМ), Ba - Me, B - H, Vs - SI, 794 - H and B72 - H; З - МН(ED(SNСМ), 872 - Me, В2 - Н, Вс - SI, В'Я - Н and Бе - Н; З - МНСН(ЕО», 72 - Me, В? - Н, в" - OMe, VZ - H and B72 - H; Z - M(с-РО(СНоСНоСМ), Va - Me, EK? - H, V"? - Me, Kg - Me, KZ - H and ve - H; 9 VZ - МНСН(ЕО», 72 - SI, В75 - Н, вс - ОМе, ВЗ - Н and ве - Н; 23 - МНСН(ЕС(СНоОМе), 72 - SI, 75 - Н, Вс - ОМе, 9 - Н and Бе - H; 23 - ЖЕО", Б72 - СИ, 75 - Н, Выс - СМ, Б9 - Н and Бе - Н; 23 - M(с-РО(СНоСНоСМ), Ба - СИ, 275 - Н, ВВ - H, Vs - OMe, VZ - H and Ve - H; 70 VZ - MNSN(SNYON)", 72 - SI, VV - H, Ve - SI, Vya. H and Ve - H; 3 - ShChNosSnNoOMe) », 872 - SI, B75 - H, Be - SI, B7Y - H and B" - H; 23 - МНСН(СНоОМе)», 72 - SI, B7b - H, Bs - SI, BZ - H and ve - H ; 11. The compound according to claim 1, which is 4-(bis-(2-methoxyethyl)amino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-(1,5-α|-pyrazolo- 1,3,5-triazine. 12. The compound according to claim 1, which is 4-(bis-(2-methoxyethyl)amino)-2,7-dimethyl-8-(2,5-dimethyl-4-methoxyphenyl)-I(1,5-a| -pyrazolo-1,3,5-triazine. 13. A compound according to any one of claims 1, 10, 11 or 12, suitable for the manufacture of a medicament for the treatment of an affective disorder, an anxiety disorder, depression, headache, irritable bowel syndrome, a disorder associated with with post-traumatic stress disorder, supranuclear palsy, immunosuppression, Alzheimer's disease, gastrointestinal disease, anorexia nervosa or other eating disorders, drug or alcohol withdrawal symptoms, drug addiction, inflammatory disorders, cardiovascular disease, or diseases associated with disorders of the heart, reproductive problems in mammals, human immunodeficiency virus infection, hemorrhagic stress, obesity, infertility, head and spinal cord injuries, epilepsy, seizures, ulcers, Gee! amyotrophic lateral sclerosis, hypoglycemia, or disorders that can be effectively treated or alleviated by an SERE antagonist, including, but not limited to, disorders in mammals caused by or alleviated by SCE. 14. The compound according to claim 10, where KZ is MNSN(EO"; 72 is chlorine, KZ is fluorine, B": is methoxy and VE? and B": is H. 15. The compound according to claim 14, which is suitable for the manufacture of a medicament for the treatment of an affective disorder, such as an anxiety disorder, depression, headache, irritable bowel syndrome, "- a disorder associated with post-traumatic stress, supranuclear palsy, weakened immunity, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other diseases related to (o) nutrition, drug or alcohol withdrawal symptoms, drug addiction, inflammatory disorders, cardiovascular diseases or diseases related to associated with cardiac disorders, mammalian reproductive problems, human immunodeficiency virus infection, hemorrhagic stress, and - obesity, infertility, head and spinal cord injuries, epilepsy, seizures, ulcers, amyotrophic lateral sclerosis, hypoglycemia, or disorders whose treatment may be effective or alleviated by an antagonizing SCE, which include, but are not limited to and them, disorders in mammals caused by SKE "or alleviated with the help of SERE. 16. A pharmaceutical composition containing a pharmaceutically acceptable carrier and a therapeutically effective ts amount of a compound according to any one of claims 1, 2, 10, 11, 12 or 14. » Official Bulletin "Industrial Property". Book 1 "Inventions, useful models, topographies of integrated microcircuits", 2005, M 10, 15.10.2005. State Department of Intellectual Property of the Ministry of Education and Science of Ukraine. -I (95) se) - 50 syu» F) ime) 60 b5