Personalsafety benzosulfimide or its pharmaceutically acceptable salt, pharmaceutical composition, method of treatment of inflammation or associated with inflammation disease

 

(57) Abstract:

Personalsafety benzosulfimide formula I, where R1is phenyl, which contains as a substituent in position, which may be substituted by one radical selected from a halogen atom, (C1-C10)alkyl, sulfamine group or group (a), R2is hydrogen, (C1-C10)alkyl, (C1-C6)halogenated, cyano, carboxyl, (C1-C6)alkoxycarbonyl, (C1-C6)carboxyethyl, (C1-C10)cianelli, (C1-C6)alkoxy-carbonylation(C2-C6)alkenyl, aminocarbonyl, (C1-C6)aminocarbonylmethyl, (C1-C6)-N-alkylaminocarbonyl, N-allumination, (C3-C7) cycloalkylcarbonyl, (C1-C6)carboxymethylaminomethyl, (C1-C6) arelaxation (C1-C6) alkylaminocarbonyl, (C1-C6) hydroxyalkyl (designation of other radicals, see p. 1 claims). The compounds of formula I are useful for the treatment of inflammation during vascular diseases, migraine, inflammation of the thyroid gland. 6 c. and 13 C.p. f-crystals, 12 tab.

The present invention relates to anti-inflammatory pharmacist what s disease, such as arthritis.

Background of the invention

Prostaglandins play an important role in the inflammatory process and the inhibition of production of prostaglandins, especially the production of prostaglandins P2 PH2 and PE2 is a common goal in the development of new anti-inflammatory drugs. However, conventional non-steroidal anti-inflammatory drugs, which are actively weaken caused by the action of prostaglandins pain and swelling associated with inflammation, also have active influence on other regulated by prostaglandins processes not associated with the inflammatory process. Thus, the use of large doses of the most common non-steroidal anti-inflammatory remedies can cause significant side effects, including life-threatening ulcers, which limits the potential therapeutic use of nonsteroidal anti-inflammatory drugs. An alternative to nonsteroidal anti-inflammatory drugs is the use of corticosteroids, which cause even more serious side effects, especially if used long-term therapy.

It was shown that the previously used non-steroidal protivostala the spins arachidonic acid/prostaglandin man, including cyclooxygenase enzyme. The recent opening of inducing enzyme associated with inflammation (he got the name "cyclooxygenase II" or "prostaglandin H synthase-II"), is the real target for inhibition, which leads to efficient reduction of inflammation and has less and less significant side effects.

Know the use of pyrazoles for the treatment of inflammation. In U.S. Patent 5134142 (Matsuo) indicated that the 1.5 - diarylpyrazole and, in particular, 1-(4-forfinal)-5-[4-(methylsulphonyl)phenyl] -3-cryptomaterial, have anti-inflammatory activity. In U.S. Patent 3940418 (R. Hamilton) as anti-inflammatory funds describes tricyclic 4,5-dihydrobenzo[g] indazols. In addition, R. Hamilton describes tricyclic 4,5-dihydrobenzo[g] indazols as anti-inflammatory drugs in publication I. Heterocyclic Chem., 13, 545 (1976). In U.S. Patent 5134155 as inhibitors HM-CoA reductase are condensed tricyclic pyrazoles containing saturated ring, which serves as a bridge connecting the pyrazole nucleus and phenyl radicals. In European application 477049 (published 25 March 1992) reported (4,5-dihydro-1-phenyl-1H-benzo[g] indazol-3-yl) amides of the region is-dihydro-1-phenyl-1H-benzo[g] indazol-3 - yl)propanamide are Immunostimulants. In the publication M. Hashem et al., J. Med.Chem., 19, 229 (1976) indicated that the condensed tricyclic pyrazoles containing saturated ring, which serves as a bridge connecting the pyrazole nucleus and phenyl radicals, are antibiotics.

In the literature some pyrazolinone benzosulfimide described as intermediate compounds used in conducting syntheses. In particular, 4-[5-(4-chloro-phenyl)-3-phenyl-1H - pyrazole-1-yl] benzosulfimide derived from pyrazole derivative as intermediate compounds for the synthesis of substances that have the ability to lower the blood sugar /R. Soliman et al., J. Pharm. Sci., 76, 626 (1987)/. From the derived pyrazoline get 4-[5- [2-(4-bromophenyl)-2H-1,2,3-triazole-4-yl]-3-methyl-1H-pyrazole - 1-yl] benzosulfimide, which, reportedly, is able to reduce the sugar content in the blood /H. Mokhtar, Pak. J. Sci. Ind. Res., 31, 762 (1988)/. Similarly receive 4- [4-bromo-5-[2-(4-chlorophenyl)-2H-1,2,3-triazole-4-yl]-3 - methyl-1H-pyrazole-1-yl]benzosulfimide /H. Mokhtar et al., Pak. J. Sci. Ind. Res., 34, 9 (1991)/.

Data on phytotoxicity derivatives of pyrazole, in particular 1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3,4 - dicarboxylic acid, see M. Cocco et. al., Il. Farmaco-Ed. Sci., 40, 272 (1985).

the -651 (1978)/. Use sterilisation carboxylic acids when getting medicines for diabetes described in article R. Soliman et al., Pharmazie, 33, 184-185 (1978). As antidiabetics on the basis of sulfonylurea describes the use of 4-[3,4,5-triple-substituted-pyrazolyl-1 - yl]benzosulfimide, in particular 1-[4-(aminosulfonyl) phenyl]-3-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid /R. Soliman et al. , J. Pharm. Sci., 72, 1004 (1983)/. As an intermediate connection upon receipt of antidiabetics synthesized a series of 4-[3-substituted methyl-5-phenyl-1H-pyrazole-1 - yl] benzosulfimide, in particular, 4-[3-methyl-5-phenyl-1H - pyrazole-1-yl]benzosulfimide /H. Feid-Allah, Pharmazie, 36, 754 (1981)/. Further, the above 4-[3-methyl-5-phenyl - 1H-pyrazole-1-yl]benzosulfimide get 1-[4- (aminosulfonyl)phenyl]-5-phenylpyrazol-3-carboxylic acid /R. Soliman et al., J. Pharm. Sci., 70, 602 (1981)/.

Description of the invention

The class of compounds, useful in the treatment associated with inflammatory diseases, is determined by the formula I

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where R1is selected from aryl and heteroaryl, where R1contains as a substituent in position, which may be substituted by one or more radicals selected from sulfonyloxy group, halogen atom, alkyl, al the dust, the halogen atom, alkyl, halogenoalkane, cyano group, nitro group, formyl group, carboxyl group, alkoxygroup, aminocarbonyl group, alkoxycarbonyl group, carboxyethyl, alkoxycarbonylmethyl, amidinopropane, cyanoimino group, cyanoalanine, alkoxycarbonylmethyl, aminocarbonylmethyl, N-alkylaminocarbonyl group, N-allamericanheroes group, N,N,-dialkylaminoalkyl group, N-alkyl-N - allamericanheroes group, cycloalkylcarbonyl group, heterocyclizations group, carboxymethylaminomethyl group, arylcarbamoylpyrazoles group, alkylcarboxylic group, alkylcarboxylic, hydroxyalkyl, halogenoalkane, carboxylphenyl, alkoxycarbonylmethyl, aminocarbonylmethyl, alkylaminocarbonyl, N-alkylamino group, N,N - dialkylamino group, N-arylamino group, N-aralkylamines group, N-alkyl-N-aralkylamines group, N-alkyl-N-arylamino group, aminoalkyl, N-acylaminoalkyl, N,N-dialkylaminoalkyl, N-alluminare, N-aralkylamines, N-alkyl-N - aralkylamines, N-alkyl-N-alluminare, aryloxy group, Alcoxy group, aaltio group, Uralkali group, Ala is aminosulfonyl group, arylsulfonyl group, N,N-dialkylaminoalkyl group, N - alkyl-N-allamericanheroes groups, heterocyclic groups, groups

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< / BR>
< / BR>
where R3choose from hydrido group, alkyl, halogen atom, halogenoalkane, cyano group, nitro group, formyl group, carboxyl group, alkoxycarbonyl group, carboxyethyl, alkoxycarbonylmethyl, amidino group, cyanoimino group, aminocarbonyl group, alkoxy group, N-alkylamino group, N,N-dialkylamino group, aminocarbonylmethyl, N - alkylaminocarbonyl group, N-allamericanheroes group, N,N-dialkylaminoalkyl group, N-alkyl-N - allamericanheroes group, alkylcarboxylic group, alkylcarboxylic, hydroxyalkyl, alkylthio group, alkylsulfonyl group, alkylsulfonyl group, N - alkylaminocarbonyl group, N-allamericanheroes group, arylsulfonyl group, N,N-dialkylaminomethyl group, N-alkyl-N-allamericanheroes group, cycloalkyl, heterocyclic group, geterotsiklicheskie and aralkyl;

where R4choose from aralkyl, aryl, cycloalkyl, cycloalkenyl and heterocyclic group, where R4optional contains as C is on, alkylthio group, alkylsulfonyl group, alkyl, alkenyl, alkylsulfonyl group, cyano group, carboxyl group, alkoxycarbonyl group, aminocarbonyl group, N - alkylaminocarbonyl group, N-aryl-aminocarbonyl group, N,N,-dialkylaminoalkyl group, N-alkyl-N - allamericanheroes group, halogenoalkane, hydroxyl group, alkoxy group, hydroxyalkyl, halogenoalkane group, sulfamine group, N-alkylaminocarbonyl group, amino group, N-alkylamino group, N,N - dialkylamino group, heterocyclic group, cycloalkenyl, nitro group, acylamino-group group

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or where R3and R4together form the fragment

< / BR>
where m is from 1 to 3 inclusive,

A is selected from phenyl and a five - or six-membered rings of heteroaryl,

R5denotes alkyl,

R6indicates one or more radicals selected from halogen atom, alkylthio group, alkylsulfonyl group, alkylsulfonyl group, cyano group, carboxyl group, alkoxycarbonyl group, aminocarbonyl group, N - alkylaminocarbonyl group, N-arylamino-bonalnoy group, alkyl, alkenyl, N,N-dialkylaminoalkyl group, N-adaxially, halogenoalkane group, sulfamine group, N - alkylaminocarbonyl group, amino group, N-alkylamino group, N,N-dialkylamino group, heterocyclic group, cycloalkenyl, nitro group, acylamino group, and

R7choose from hydrido groups, alkyl, aryl and aralkyl;

provided that R2and R3are not identical radicals selected from hydrido group, carboxyl group and ethoxycarbonyl group, further provided that R2is not a carboxyl group or stands, if R3indicates hydrido group, a R4denotes phenyl; further provided that R4is not triazolium, when R2denotes methyl; further provided that R4is not arukenimon, when R2denotes a carboxyl group, aminocarbonyl group or ethoxycarbonyl group; further provided that R4is not phenyl when R2denotes methyl, a R3denotes a carboxyl group; and further provided that R4is not unsubstituted tanila, when R2represents trifluoromethyl; and further provided that R4denotes aryl, substituted allfamilies group, and R6means selfamily ielemia salt.

It should be understood that the expression "next subject" as used above, means that the stated condition is not associated with any of the previously set condition.

The compounds of formula I can be useful, but their usefulness is not limited to, for treating inflammation in a patient, and the treatment of other associated with inflammatory diseases, for example, they can be used as analgesics in the treatment of pain or headaches, or as antipyretics in the treatment of fever. For example, the compounds of formula I may be useful in the treatment of arthritis, including, but not limited to, rheumatoid arthritis, spondyloarthropathies, gouty arthritis, osteoarthritis, systemic lupus erythematosus and juvenile arthritis. Such compounds of formula I may be useful in the treatment of asthma, bronchitis, menstrual colic, tendonitis, bursitis and such skin conditions as psoriasis, eczema, burns and dermatitis. The compounds of formula I may also be useful to treat gastrointestinal conditions such as inflammation of the colon, Crohn's disease, gastritis, mucous colitis and ulcerative colitis and for the prevention of colorectal cancer. Connection forini, periarteritis nodosa, inflammation of the thyroid gland, gipoplasticheskaya anemia, Hodgkin's disease, sclerodoma, rheumatic fever, type 1 diabetes type malignant male, benign Wegener, nephrotic syndrome, Behcet's disease, polymyositis, gingivitis, allergies, conjunctivitis, swelling occurring after injury, myocardial ischemia, etc., the Compounds are useful as anti-inflammatory drugs, such as tools that are used to treat arthritis, with the additional benefit is that these funds have significantly less harmful side effects.

The present invention mainly includes compounds which selectively inhibit cyclooxygenase 11 with respect to oxigenase 1. Mainly the value of the IC50these compounds against cyclooxygenase 11 is approximately not more than 0.2 μm, and the ratio of selectivity of inhibition of oxygenase 11 and inhibition of oxygenase 1 is at least 50, more preferably at least 100. Even more preferably the value of the IC50compounds according to the invention with respect to cyclooxygenase 1 is more than approximately 1 μm, and e is th according to the invention to reduce the number of side effects, caused by conventional nonsteroidal anti-inflammatory drugs.

A preferred class of compounds include compounds of formula 1, where R1denotes aryl selected from phenyl, naphthyl and biphenyl, and five - or six-membered rings of heteroaryl, where R1contains as a substituent in position, which may be substituted by one or more radicals selected from allfamilies group, halogen atom, lower alkyl, lower alkoxy group, hydroxyl group, lower halogenoalkane or group

< / BR>
where R2choose from hydrido group, halogen atom, lower alkyl, lower halogenoalkane, cyano group, nitro group, formyl group, carboxyl group, lower alkoxycarbonyl group, lower carboxyethyl, lower alkoxycarbonyl, amidino group, cyanoimino group, lower zainoulline, lower alkoxycarbonylmethyl, aminocarbonyl group, a lower alkoxy group, a lower aryloxy group, a lower Alcoxy group, lower aminocarbonyl, lower N-alkylaminocarbonyl group, N-allamericanheroes group, lower N,N-dialkylaminoalkyl group, the lower N-alkyl-N-allamericanheroes group, a lower cycloalkane group, lower arylcarbamoylpyrazoles group, lower halogenoalkane, lower carboxyglutamate, lower alkoxycarbonylmethyl, lower aminocarbonylmethyl, lower alkylaminocarbonyl, lower alkylcarboxylic group, lower alkylcarboxylic, lower alkylamino group, lower N,N-dialkylamino group, N - arylamino group, a lower N-aralkylamines group, lower N-alkyl-N - aralkylamines group, lower N-alkyl-N-arylamino group, lower aminoalkyl, lower N-acylaminoalkyl, lower N,N - dialkylaminoalkyl, lower N-alluminare, lower N - aralkylamines, the lower N-alkyl-N-aralkylamines, lower N-alkyl-N-alluminare, aaltio group, a lower Uralkali group, lower hydroxyalkyl, lower alkylthio group, lower alkylsulfonyl group, lower alkylsulfonyl group, a lower N-alkylaminocarbonyl group, a lower N-allamericanheroes group, arylsulfonyl group, lower N,N-dialkylaminoalkyl group, lower N - alkyl-N-allamericanheroes groups, heterocyclic groups, groups

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< / BR>
< / BR>
where R3choose from hydrido group, lower alkyl, halogen atom, lower halogenoalkane, CGO of carboxyethyl, lower alkoxycarbonylmethyl, amidino group, cyanoimino group, aminocarbonyl groups, lower alkoxy groups, lower N - alkylamino group, lower N,N-dialkylamino group, lower aminocarbonyl, lower N-alkylaminocarbonyl group, a lower N-allamericanheroes group, lower N, N-dialkylaminoalkyl group, lower N-alkyl-N-allamericanheroes group, lower alkylcarboxylic group, lower alkylcarboxylic, lower hydroxyalkyl, lower alkylthio group, lower alkylsulfonyl group, lower alkylsulfonyl group, a lower N-alkylaminocarbonyl group, N - allamericanheroes group, arylsulfonyl group, lower N,N-dialkylaminoalkyl group, lower N-alkyl-N - allamericanheroes group, lower cycloalkyl, heterocyclic group, lower geterotsiklicheskie and aralkyl;

R4choose from low aralkyl, aryl, lower cycloalkyl, lower cycloalkenyl and from five to deletechannel heterocyclic group, where R4not necessarily contain as substituents in position, which may be substituted by one or more radicals selected from halogen atom, lower alkylthio group, lower alkylsulfonyl group, lower alkoxycarbonyl group, aminocarbonyl group, a lower N-alkylaminocarbonyl group, N-allamericanheroes group, lower N, N - dialkylaminoalkyl group, lower N-alkyl-N - allamericanheroes group, lower halogenoalkane, hydroxyl group, lower alkoxy group, lower hydroxyalkyl, lower halogenoalkane group, sulfamine group, a lower N-alkylaminocarbonyl group, amino group, lower N-alkylamino group, lower N,N-dialkylamino-group, five - or six-membered heterocyclic group, lower cycloalkenyl, nitro group, acylamino-group group

< / BR>
or where R3and R4together form the fragment

< / BR>
where m is from 1 to 3 inclusive;

A is selected from phenyl and a five - or six-membered rings of heteroaryl;

R5denotes lower alkyl;

R6indicates one or more radicals selected from halogen atom, lower alkylthio group, lower alkylsulfonyl group, lower alkylsulfonyl group, cyano group, carboxyl group, lower alkoxycarbonyl group, aminocarbonyl group, a lower N-alkylaminocarbonyl group, N-allamericanheroes group, lower alkyl, lower alkene is the alkyl, hydrido group, hydroxyl group, lower alkoxy group, lower hydroxyalkyl, lower halogenoalkane group, a lower N - alkylaminocarbonyl group, sulfamyl, amino group, lower N-alkylamino group, lower N,N-dialkylamino-group, five - or six-membered heterocyclic group, lower cycloalkenyl, nitro group, acylamino group, and

R7choose from hydrido group, lower alkyl, aryl and lower aralkyl,

or their pharmaceutically acceptable salts.

A more preferred class of compounds include compounds of formula I, where R1denotes phenyl, where R1contains as a substituent in position, which may be substituted by one or more radicals selected from allfamilies group, halogen atom, lower alkyl, lower alkoxy group, hydroxyl group, lower halogenoalkane or group

< / BR>
where R2choose from hydrido group, lower alkyl, lower halogenoalkane, cyano group, carboxyl group, lower alkoxycarbonyl group, lower carboxyethyl, lower zainoulline, lower alkoxycarbonylmethyl, lower halogenoalkane, lower carboxyglutamate, lower alkoxycarbonyl the but - groups, lower N,N-dialkylamino group, N-arylamino group, a lower N-aralkylamines group, lower N-alkyl-N-aralkylamines group, lower N-alkyl-N-arylamino group, lower aminoalkyl, lower N-acylaminoalkyl, lower N,N-dialkylaminoalkyl, lower N - alluminare, lower N-aralkylamines, lower N-alkyl-N - aralkylamines, lower N-alkyl-N-alluminare, aryloxy group, a lower Alcoxy group, lower alkoxy group, a lower alkylthio group, aaltio group, a lower Uralkali group, aminocarbonyl group, lower aminocarbonyl, lower N - alkylaminocarbonyl group, N-arylamino-carbonyl group, lower N,N-dialkylaminoalkyl group, lower N-alkyl-N - allamericanheroes group, lower cycloalkylcarbonyl group, lower carboxymethylaminomethyl group, lower arylcarbamoylpyrazoles group, lower hydroxyalkyl, groups

< / BR>
< / BR>
< / BR>
where R3choose from hydrido group, lower alkyl, halogen atom, cyano group, lower hydroxyalkyl, lower alkylthio group, lower alkyl-sulfanilic group, lower alkylsulfonyl groups, lower alkoxy groups, lower N - alkylamino group, lower N,N-dialkylamino group, initialselectionvalue group, the lower N-alkyl-N-allamericanheroes group and lower cycloalkyl;

where R4choose from low aralkyl, aryl, lower cycloalkyl, lower cycloalkenyl and from five to deletechannel heterocyclic group; R4not necessarily contain as substituents in position, which may be substituted by one or more radicals selected from halogen atom, lower alkylthio group, lower alkylsulfonyl group, lower alkyl, lower alkenyl, lower alkylsulfonyl group, cyano group, carboxyl group, lower alkoxycarbonyl group, aminocarbonyl group, lower halogenoalkane, hydroxyl group, lower alkoxy group, lower hydroxyalkyl, lower halogenoalkane group, sulfamine group, a lower N-alkylaminocarbonyl group, amino group, lower N-alkylamino group, a lower N, N-dialkylamino-group, five - or six-membered heterocyclic group, lower cycloalkenyl, nitro-groups,

< / BR>
< / BR>
or where R3and R4together form the fragment

< / BR>
where m is 2,

A is selected from phenyl and a five - or six-membered rings of heteroaryl;

R5denotes lower alkyl;

R6means Odie who uppy, lower alkyl, lower alkenyl, lower alkylsulfonyl group, cyano group, carboxyl group, lower alkoxycarbonyl group, aminocarbonyl group, lower halogenoalkane, hydroxyl group, lower alkoxy group, lower hydroxyalkyl, lower halogenoalkane group, sulfamine group, amino group, lower N-alkylamino group, lower N,N-dialkylamino group, lower cycloalkenyl and nitro group, and

R7choose from hydrido group, lower alkyl, aryl and lower aralkyl,

or their pharmaceutically acceptable salts.

Even more preferred class of compounds include compounds of formula I, where R1denotes phenyl, where R1contains as a substituent in position, which may be substituted by one or more radicals selected from allfamilies group, halogen atom, lower alkyl, lower alkoxy groups and groups

< / BR>
where R2choose from hydrido group, lower alkyl, lower halogenoalkane, cyano group, carboxyl group, lower alkoxycarbonyl group, lower carboxyethyl, lower zainoulline, lower alkoxycarbonylmethyl, lower halogenoalkane, lower carboxylate is ganancia, the lower N-alkylamino group, lower N,N - dialkylamino group, N-arylamino group, a lower N-aralkylamines group, lower N-alkyl-N-aralkylamines group, lower N-alkyl-N-arylamino group, lower aminoalkyl, lower N-acylaminoalkyl, lower N,N-dialkylaminoalkyl, lower N-alluminare, lower N-aralkylamines - alkyl, lower N-alkyl-N-aralkylamines, lower N-alkyl-N - alluminare, lower alkoxy group, aryloxy group, a lower Alcoxy group, a lower alkylthio group, aaltio group, a lower Uralkali group, aminocarbonyl group, lower aminocarbonyl, lower N-alkylaminocarbonyl group, N - allamericanheroes group, lower N,N-dialkylaminoalkyl group, lower N-alkyl-N-allamericanheroes group, lower cycloalkylcarbonyl group, lower carboxymethylaminomethyl group, lower heterocyclizations group, lower arylcarbamoylpyrazoles group, lower hydroxyalkyl, groups

< / BR>
< / BR>
< / BR>
where R3choose from hydrido group, lower alkyl, halogen atom, cyano group, lower hydroxyalkyl, lower alkoxy groups, lower N-alkylamino group, lower N, N - dialkylamino group, a lower alkylthio-gr aryl, lower cycloalkyl, lower cycloalkenyl and from five to deletechannel heterocyclic group, where R4not necessarily contain as substituents in position, which may be substituted by one or more radicals selected from halogen atom, lower alkylthio group, lower alkylsulfonyl group, lower alkyl, lower alkenyl, lower alkylsulfonyl group, cyano group, carboxyl group, lower alkoxycarbonyl group, aminocarbonyl group, lower halogenoalkane, hydroxyl group, lower alkoxy group, lower hydroxyalkyl, lower halogenoalkane group, sulfamine group, amino group, lower N-alkylamino group, lower N,N-dialkylamino group, five - or six-membered heterocyclic group, lower cycloalkenyl, nitro groups, groups

< / BR>
< / BR>
or where R3and R4together form the fragment

< / BR>
where m is 2,

A is selected from phenyl and a five-membered heteroaryl,

R5denotes lower alkyl;

R6indicates one or more radicals selected from halogen atom, lower alkyl, lower alkylsulfonyl group, lower halogenoalkane, a lower alkoxy group, sulfamine group, Amin whom BR>
or their pharmaceutically acceptable salts.

Within formula I there is a subclass of compounds, which includes such compounds, where R1denotes phenyl, which contains as a substituent in position, which may be substituted by one or more radicals selected from halogen atom, lower alkyl, sulfamine group

< / BR>
where R2choose from hydrido group, lower alkyl, lower halogenoalkane, cyano group, carboxyl group, lower alkoxycarbonyl group, lower carboxyethyl, lower zainoulline, lower alkoxycarbonylmethyl, lower halogenoalkane, lower carboxyglutamate, lower alkoxycarbonylmethyl, lower aminocarbonylmethyl, lower alkylaminocarbonyl, lower N-alkylamino group, lower N,N-dialkylamino group, N-arylamino group, a lower N-aralkylamines group, lower N-alkyl-N-aralkylamines group, lower N-alkyl-N-arylamino group, lower aminoalkyl, lower N-acylaminoalkyl, lower N,N - dialkylaminoalkyl, lower N-alluminare, lower N - aralkylamines, lower N-alkyl-N-aralkylamines, lower N-alkyl-N-alluminare, a lower alkoxy group, enacarbil group, lower aminocarbonyl, lower N-alkylaminocarbonyl group, N - allamericanheroes group, lower N, N-dialkylaminoalkyl group, lower N-alkyl-N-allamericanheroes group, lower cycloalkylcarbonyl group, lower carboxymethylaminomethyl group, lower arylcarbamoylpyrazoles group, lower hydroxyalkyl, groups

< / BR>
< / BR>
< / BR>
where R3choose from hydrido group, lower alkyl, halogen atom, cyano group, lower hydroxyalkyl, lower alkoxy groups, lower alkylthio group, a lower N-alkylamino group, lower N,N-dialkylamino group, lower alkylsulfonyl group and lower cycloalkyl;

where R4choose from low aralkyl, aryl, lower cycloalkyl, lower cycloalkenyl and from five to deletechannel heterocyclic group, where R4not necessarily contain as substituents in position, which may be substituted by one or more radicals selected from halogen atom, lower alkylthio group, lower alkylsulfonyl group, lower alkyl, lower alkenyl, lower alkylsulfonyl group, cyano group, carboxyl group, lower alkoxycarbonyl group, aminocarbonyl halogenoalkane group, allfamilies group, lower alkylaminocarbonyl group, amino group, lower N-alkylamino group, lower N,N - dialkylamino-group, five - or six-membered heterocyclic group, lower cycloalkenyl, nitro groups, groups

< / BR>
where R5denotes lower alkyl, and

R7choose from hydrido group, lower alkyl, aryl and lower aralkyl,

or their pharmaceutically acceptable salts.

The class of compounds of special interest includes such compounds of formula I, where R1denotes phenyl, which contains as a substituent in position, which may be substituted by one or more radicals selected from fluorine atom, chlorine atom, methyl, sulfamine group

< / BR>
where R2choose from hydrido groups, methyl, ethyl, ISO-propyl, tert-butyl, ISO-butyl, hexyl, formatie, diformate, trifloromethyl, chlormethyl, dichloromethyl, trichloromethyl, pentaborate, heptafluoropropyl, diperchlorate, dichloromethyl, deperately, deferrable, dichlorethyl, dichloropropyl, cyano group, carboxyl group, methoxycarbonyl group, ethoxycarbonyl group, ISO-propoxycarbonyl group, tert-butoxycarbonyl oxycarbonyl group, acetyl, propionyl, butyryl, out-of butyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, TRIFLUOROACETYL, cyanomethyl, ethoxycarbonylmethyl, 1,1-debtor-1-phenylmethyl, 1,1-debtor - 1-phenylethyl, divorcethe, methoxycarbonylmethyl, divorcelegal, N,N-dimethylacetamide, N - phenyldiethanolamine, N-ethylamino group, N-methylamino group, N,N-dimethylamino group, N, N-diethylamino group, N-phenylamino group, N-benzylamino group, N-phenylethylamine group, N-methyl-N - benzylamino group, N-ethyl-N-phenylamino group, N-methyl-N - phenylamino group, aminomethyl, N-methylaminomethyl, N, N - dimethylaminomethyl, N-phenyliminomethyl, N-benzylaminopurine, N - methyl-N-benzylaminopurine, N-methyl-N-phenyliminomethyl, methoxy group, ethoxy group, phenoxy group, benzyloxy group, methylthio group, phenylthio group, benzylthio group, N-metalmachine, N-methylthymidine, N-methylacetamide, urea, machivenyika, thiourea, timecamera, acetamide, N-phenylthiocarbamyl, N - benzyldimethylamine, N-methylthiocarbamate, N-phenylacetylamino, N-benzylmethylamine, N-methylacetamide, N - phenylacetamide, N-benzylacrylamide, N-methylacetamide, aminocarbonyl groverneeley group, N-propylaminoethyl group, N-butylaminoethyl group, N-isobutyleneisoprene group, N-tert-butylaminoethyl group, N-intramyocardially group, N-phenylenecarbonyl group, N, N - dimethylaminocarbonylmethyl group, N-methyl-N-ethylaminomethyl group, N-(3-forfinal) aminocarbonyl group, N-(4-were) aminocarbonyl group, N-(3-chlorophenyl) aminocarbonyl group, N-methyl-N-(3-chlorophenyl)aminocarbonyl group, N-(4 - methoxyphenyl)aminocarbonyl group, N-methyl-N - phenylenecarbonyl group, cyclopentanecarbonyl group, cyclohexanecarbonyl group, carboxymethylaminomethyl group, benzyloxycarbonylamino group, hydroxypropyl, hydroxymethyl and hydroxyethyl;

where R3choose from hydrido groups, methyl, ethyl, ISO-propyl, tert-butyl, ISO-butyl, hexyl, fluorine atom, chlorine atom, bromine atom, cyano group, methoxy group, a methylthio group, methylsulfonyl group, N-methylamino group, N-ethylamino group, N,N-dimethylamino group, N,N-diethylamino group, cyclopropyl, cyclopentyl, hydroxypropyl, hydroxymethyl and hydroxyethyl, and

where R4choose from phenylethenyl, phenyl, NAF, -cyclohexenyl, 1-cyclopentenyl, 4 - cyclopentenyl, benzofuran, 2,3-dihydrobenzofuran, 1,2,3,4 - tetrahydronaphthyl, benzothiazyl, indenyl, indanyl, indolyl, dihydroindole, Romania, benzopyrane, tigermania, benzothiophene, benzodioxolyl, benzodioxane, pyridyl, teinila, thiazolyl, oxazolyl, purile and pyrazinyl, where R4optional contains as a substituent in position, which may be substituted by one or more radicals selected from fluorine atom, chlorine atom, bromine atom, methylthio group, methylsulfinyl group, methyl, ethyl, propyl, ISO-propyl, tert-butyl, ISO-butyl, hexyl, etilene, propenyl, methylsulfonyl, cyano group, carboxyl group, methoxycarbonyl group, ethoxycarbonyl group, ISO - propoxycarbonyl group, tert-butoxycarbonyl group, propoxycarbonyl group, butoxycarbonyl group, ISO - butoxycarbonyl group, phenoxycarbonyl group, aminocarbonyl group, formatie, diformate, trifloromethyl, chlormethyl, dichloromethyl, trichloromethyl, pentaborate, heptafluoropropyl, bromodifluoromethyl, diperchlorate, dichloromethyl, deperately, deferrable, dichlorethyl, dichloropropyl, , offamilies group, methylamino-sulfonyloxy group, hydroxypropyl, hydroxy-ISO-propyl, hydroxymethyl, hydroxyethyl, triptoreline group, amino group, N-methylamino group, N-ethylamino group, N-ethyl-N - methylamino group, N,N-dimethylamino group, N,N-diethylamino group, formylamino group, methylcobalamine group, triptorelin group, piperidinyl, piperazinil, morpholino group, cyclohexylmethyl, cyclopropylmethyl, cyclopentylmethyl, nitro group, groups

< / BR>
< / BR>
where R7choose from hydrido groups, methyl, ethyl, phenyl or benzyl,

or their pharmaceutically acceptable salts.

Within formula I there is a second subclass of compounds of special interest, where R1denotes phenyl, which contains as a substituent in position, which may be substituted, sulfamylon group; R2choose from lower halogenoalkane, cyano group, carboxyl group, lower alkoxycarbonyl group, lower carboxyethyl, aminocarbonyl group, a lower N-alkylaminocarbonyl group, N - allamericanheroes group, lower N,N-dialkylaminoalkyl group, lower N-alkyl-N-allamericanheroes group, lower cycloalkyl m is 2, where A is selected from phenyl and a five-membered heteroaryl, and where R6indicates one or more radicals selected from halogen atom, lower alkyl, lower alkylsulfonyl group, lower halogenoalkane, a lower alkoxy group, amino group and nitro group, or their pharmaceutically acceptable salts.

The class of compounds of special interest includes such compounds of formula I, where R2choose from formatie, diformate, trifloromethyl, chlormethyl, dichloromethyl, trichloromethyl, pentaborate, heptafluoropropyl, diperchlorate, dichloromethyl, deperately, deferrable, dichlorethyl, dichloropropyl, cyano group, carboxyl group, methoxycarbonyl group, ethoxycarbonyl group, ISO-propoxycarbonyl group, tert-butoxycarbonyl group, propoxycarbonyl group, butoxycarbonyl group, ISO-butoxycarbonyl group, phenoxycarbonyl group, acetyl, propionyl, butyryl, out-of butyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, TRIFLUOROACETYL, aminocarbonyl group, N - methylaminomethyl group, N-ethylaminomethyl group, N - isopropylaminocarbonyl group, N-propylaminosulfonyl group, N-butylaminoethyl group, N-phenylenecarbonyl group, N, N - dimethylaminocarbonylmethyl group, N-methyl-N - ethylaminomethyl group, N-(3-forfinal)aminocarbonyl group, N-(4-methyl-phenyl)aminocarbonyl group, N-(3 - chlorophenyl)aminocarbonyl group, N-methyl-N-(3-chlorophenyl) aminocarbonyl group, N-(4 - methoxyphenyl)aminocarbonyl group, N-methyl-N-phenyl - aminocarbonyl group, cyclohexanecarbonyl group, hydroxypropyl, hydroxymethyl and hydroxyethyl; where A is selected from phenyl, purile and tanila; and where R6indicates one or more radicals selected from fluorine atom, chlorine atom, bromine atom, methylsulfonyl group, methyl, ethyl, ISO-propyl, tert-butyl, ISO-butyl, formatie, diformate, trifloromethyl, chlormethyl, dichloromethyl, trichloromethyl, pentaborate, heptafluoropropyl, diperchlorate, dichloromethyl, deperately, deferrable, dichlorethyl, dichloropropyl, methoxy group, methylenedioxy group, ethoxy group, propoxy group, n-butoxy group, amino group and nitro group, or their pharmaceutically acceptable salts.

Within formula I there is a third subclass of compounds of special interest, where R1selected from phenyl, naphthyl, biphenyl't be substituted, one or more radicals selected from halogen atom, lower alkyl, lower alkoxy groups, hydroxyl groups and lower halogenoalkane; where R2choose from lower halogenoalkane; where R3indicates hydrido group, and where R4denotes aryl, which contains as a substituent in position, which may be substituted, sulfamylon group, or their pharmaceutically acceptable salts.

The class of compounds of special interest includes such compounds of formula I, where R1selected from phenyl, naphthyl, benzofuran, benzothiazyl, indolyl, benzodioxolyl, benzodioxane, pyridyl, teinila, thiazolyl, oxazolyl, purile and pyrazinyl, where R1contains as a substituent in position, which may be substituted by one or more radicals selected from fluorine atom, chlorine atom, bromine atom, formatie, diformate, trifloromethyl, chlormethyl, dichloromethyl, trichloromethyl, pentaborate, heptafluoropropyl, diperchlorate, dichloropropyl, dichloromethyl, deperately, deferrable, dichlorethyl, methyl, ethyl, propyl, hydroxyl group, methoxy group, ethoxy group, propoxy group and n-butoxy group; R2choose from Qtopia, diperchlorate, deperately, dichloromethyl, deferrable, dichlorethyl and dichloropropyl; where R3indicates hydrido group, and where R4denotes phenyl, which contains as a substituent in position, which may be substituted, sulfamylon group, or their pharmaceutically acceptable salts.

Within formula I there is a subclass of causing great interest compounds represented by formula II:

< / BR>
where R2choose from hydrido group, alkyl, halogenoalkane, alkoxycarbonyl group, cyano group, cyanoalanine, carboxyl group, aminocarbonyl group, alkylaminocarbonyl group, cycloalkylcarbonyl group, allamericanheroes group, carboxymethylaminomethyl group, carboxyethyl, arylcarbamoylpyrazoles group, aminocarbonylmethyl, alkoxycarbonylmethyl and hydroxyalkyl;

R3choose from hydrido group, alkyl, cyano group, hydroxyalkyl, cycloalkyl, alkylsulfonyl group and halogen atom, and

R4choose from aralkyl, aryl, cycloalkyl, cycloalkenyl and heterocyclic group, where R4optional contains as a substituent polizeischule group, cyano group, nitro group, halogenoalkane, alkyl, hydroxyl groups, alkenyl, hydroxyalkyl, carboxyl group, cycloalkyl, alkylamino group, dialkylamino group, alkoxycarbonyl group, aminocarbonyl group, alkoxy group, halogenoalkane group, sulfamine group, heterocyclic group and amino group;

provided that R2and R3both are not hydrido group; further provided that R2is not a carboxyl group or stands, if R3indicates hydrido group, a R4denotes phenyl; further provided that R4is not triazolines group, if R2denotes methyl; further provided that R4is not arukenimon, when R2denotes a carboxyl group, aminocarbonyl group or ethoxycarbonyl group; further provided that R4is not phenyl when R2denotes methyl, and R3denotes a carboxyl group, and further provided that R4is not unsubstituted tanila, if R2denotes trifluoromethyl,

or their pharmaceutically acceptable salts.

The class of compounds of special interest includes such compounds of formula II, happy, cyano group, lower zainoulline, carboxyl group, aminocarbonyl group, lower alkylaminocarbonyl group, lower cycloalkylcarbonyl group, allamericanheroes group, lower carboxymethylaminomethyl group, lower arylcarbamoylpyrazoles group, lower aminocarbonylmethyl, alkoxycarbonylmethyl, lower carboxyethyl, lower alkoxycarbonylmethyl and lower hydroxyalkyl;

where R3choose from hydrido group, lower alkyl, cyano group, lower hydroxyalkyl, lower cycloalkyl, lower alkylsulfonyl group and halogen atom, and

where R4choose from aralkyl, aryl, cycloalkyl, cycloalkenyl and heterocyclic group, where R4optional contains as a substituent in position, which may be substituted by one or more radicals selected from halogen atom, lower alkylthio group, lower alkylsulfonyl group, cyano group, nitro group, lower halogenoalkane, lower alkyl, hydroxyl group, lower alkenyl, lower hydroxyalkyl, carboxyl group, lower cycloalkyl, lower alkylamino group, a lower dialkylamino group, lower alkoxyl group, five - or six-membered heterocyclic group and amino group; or their pharmaceutically acceptable salts.

A family of specific compounds of formula I of particular interest include the following compounds and their pharmaceutically acceptable salts:

4-[5-(4-(N-ethylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-(N-ethyl-N-methylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole - 1-yl] benzosulfimide,

4-[5-(3-fluoro-4-(N-methylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl] benzosulfimide,

4-[5-(3-chloro-4-(N-methylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl] benzosulfimide,

4-[5-(3-methyl-4-(N-methylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole - 1-yl] benzosulfimide,

4-[5-(4-(N, N-dimethylamino)-3-forfinal)-3-(trifluoromethyl)-1H-pyrazole - 1-yl]benzosulfimide,

4-[5-(3-chloro-4-(N, N-dimethylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole - 1-yl]benzosulfimide,

4-[5-(4-(N, N-dimethylamino)-3-were)-3-(trifluoromethyl)-1H-pyrazole - 1-yl]benzosulfimide,

4-[5-(4-(N-ethyl-N-methylamino)-3-forfinal)-3-(trifluoromethyl)-1H-pyrazole - 1-yl]benzosulfimide,

4-[5-(3-chloro-4-(N-ethyl-N-methylamino)-3-forfinal)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-(N-ethyl-N-methylamino)-3-were)-3-(trifluoromethyl)-1H - lonamin,

4-[5-(4-(3-chloro-4-(N, N-diethylamino)phenyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-(N, N-diethylamino)-3-were)-3-(trifluoromethyl)-1H - pyrazole-1-yl]benzosulfimide,

N-[4-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H-pyrazole-5-yl] - 3-forfinal]-N-methylacetamide,

N-[4-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H - pyrazole-5-yl]-3-chlorophenyl]-N-methylacetamide,

N-[4-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H-pyrazole-5-yl] - 3-forfinal]-N-metalmachine,

N-[4-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H-pyrazole - 5-yl]-3-chlorophenyl]-N-metalmachine,

N-[4-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H-pyrazole - 5-yl]-3-were]-N-metalmachine,

N-[4-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H-pyrazole-5 - yl]-3-forfinal]-N-methylthymidine,

N-[4-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H-pyrazole - 5-yl]-3-chlorophenyl]-N-methylthymidine,

N-[4-[1-[4-(aminosulfonyl)phenyl-3-(trifluoromethyl)-1H-pyrazole - 5-yl]-3-were]-N-methylthymidine,

4-[5-(3-(N,N-dimethylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-(N-ethyl-N-methylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole - 1-yl] benzosulfimide,

4-[5-(4-chloro-3-(N-methylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl] benzosulfimide,
N-[3-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H-pyrazole - 5-yl]-4-forfinal]-N-methylacetamide,

N-[3-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H-pyrazole - 5-yl]-4-were]-N-metalmachine,

N-[3-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H-pyrazole - 5-yl]-4-forfinal]-N-methylthymidine,

4-[5-(2-(N-ethyl-N-methylamino)-4-were)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

N-[2-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H-pyrazole - 5-yl]-4-were]-N-metalmachine,

N-[2-[1-[4-(aminosulfonyl)phenyl] -3-(trifluoromethyl)-1H-pyrazole - 5-yl]-4-forfinal]-N-methylthymidine,

4-[5-(1H-indol-5-yl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(7-fluoro-1H-indol-5-yl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(1-ethyl-1H-indol-5-yl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(7-methyl-1H-indol-5-yl)-3-(trifluoromethyl)-1H-pyrazole - 1-yl] benzosulfimide,

4-[5-(7-chloro-1-methyl-1H-indol-5-yl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl] benzosulfimide,

4-[5-(2,3-dihydro-1H-indol-5-yl)-3-(trifluoromethyl) -1H-pyrazole-1-yl]benzosulfimide,

4-[5-(7-fluoro-1-methyl-2,3-dihydro-1H-indol-5-yl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

4-[3-aminomethyl-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-1-yl] benzosulfimide,

4-[5-phenyl-3-(N-phenylamino)methyl-1H-pyrazole-1-yl]lessonslearned,

4-[3-(N-benzylamino)methyl-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[3-(N-benzyl-N-methylamino) methyl-5-phenyl-1H-pyrazole-1-yl] benzosulfimide,

4-[3-(N-methyl-N-phenylamino)methyl-5-phenyl-1H-pyrazole-1-yl] benzosulfimide,

N-[[1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-yl]methyl]acetamide", she

N-[[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H-pyrazole-3-yl] methyl] -N-methylacetamide,

N-[[1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-yl]methyl]-N - phenylacetamide,

N-[[1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-yl]methyl] -N-benzylacetone,

N-[[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H - pyrazole-3-yl]methyl]-urea,

N-[[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H-pyrazole-3-yl]methyl] -N-metalmachine,

N-[[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H - pyrazole-3-yl]methyl]-N-phenylacetone,

N-[[1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-yl]methyl] -N-benzyladenine,

N-[[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H-pyrazole-3-yl]methyl] thiourea,

N-[[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H-pyrazole-3-yl] methyl]-N-methylthymidine,

N-[[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H-pyrazole-3-yl] methyl]-N-phenyltoloxamine,

N-[[1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-yl] METI is ltio-5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-(N-methylamino)-5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1 - yl] benzosulfimide,

4-[4-(N, N-dimethylamino)-5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[3-methoxy-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[3-ethoxy-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[3-phenoxy-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[3-benzyloxy-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[3-methylthio-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[3-benzylthio-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[3-(N-methylamino)-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[3-(N,N-dimethylamino)-5-phenyl-1H-pyrazole-1-yl] benzosulfimide,

4-[3-(N-benzyl-N-methylamino)-5-phenyl-1H - pyrazole-1-yl] benzosulfimide,

N-[1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-yl] acetamide", she

N-[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1 H-pyrazole-3-yl]-N - methylacetamide,

N-[1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-yl]-N - benzylacetone,

N-[1-[4-(aminosulfonyl) phenyl]-5-phenyl-1H-pyrazole-3-yl] urea,

N-[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H-pyrazole-3-yl] -N - metalmachine,

N-[1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-yl]- N-benzyladenine,

N-[1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3 - yl]-thiourea,

4-[5-phenyl-3-(1,1-debtor-1-phenylmethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-phenyl-3-(1,1-debtor-2-phenylethyl)-1H-pyrazole-1-yl] benzosulfimide,

1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-DIPEROXY acid,

methyl ester 1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H - pyrazole-3-DIPEROXY acid,

1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-deflorated,

N, N-dimethyl-1-[4-(aminosulfonyl)phenyl] -5 - phenyl-1H-pyrazole-3-deflorated,

N-phenyl-1-[4 (aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-deflorated,

1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-acetic acid,

1-[4-(aminosulfonyl)phenyl] -4-chloro-5-phenyl-1H - pyrazole-3-DIPEROXY acid,

1-[4-(aminosulfonyl)phenyl] -4-bromo-5-phenyl-1H-pyrazole-3-DIPEROXY acid,

1-[4-(aminosulfonyl)phenyl] -4-chloro-5-(4-chlorophenyl)-1H - pyrazole-3-acetic acid,

1-[4-(aminosulfonyl) phenyl] -4-bromo-5 - phenyl-1H-pyrazole-3-acetic acid,

(R)-2-[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H-pyrazole-3-yl] propanoic acid,

(S)-2-[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H - pyrazole-3-yl]propanoic acid,

(R)-2-[1-[4-(aminosulfonyl)phenyl] -4-chloro-5-phenyl-1H - pyrazole-3-yl] propanoic acid,

(S)-2-[1-[4-(aminosulfonyl)phenyl] -4-chloro-5-phenyl-1H-Isleta,

(S)-2-[1-[4-(aminosulfonyl) phenyl] -4-bromo-5-phenyl-1H-pyrazole-3-yl] propanoic acid,

2-[1-[4-(aminosulfonyl)phenyl] -5-phenyl-1H-pyrazole-3-yl] -2-methylpropanoate acid,

2-[1-[4-(aminosulfonyl)phenyl] -4-chloro-5-phenyl - 1H-pyrazole-3-yl] -2-methylpropanoate acid,

2-[1-[4-(aminosulfonyl)phenyl] -4-bromo-5-phenyl-1H-pyrazole-3-yl] - 2-methylpropanoate acid,

2-fluoro-4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

3-fluoro-4-[5-phenyl-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

2-methyl-4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

3-methyl-4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

ethyl ester 1-[4-(aminosulfonyl)phenyl]- 5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid,

ethyl ester 1-[4-(aminosulfonyl)phenyl] -5-(4-were)-1H - pyrazole-3-carboxylic acid,

ISO-propyl ester 1-[4-(aminosulfonyl)phenyl] -5-(4-chlorophenyl)- 1H-pyrazole-3-carboxylic acid,

methyl ester 1-[4-(aminosulfonyl)phenyl] -5-(4 - AMINOPHENYL)-1H-pyrazole-3-carboxylic acid,

1-[4-(aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid,

tert-butyl ester 1-[4-(aminosulfonyl)phenyl] -5- (4-chlorophenyl)-1H-pyrazole-3-carboxylic acid,

propyl ester 1-[4-(aminosulfonyl)-1H - pyrazole-3-carboxylic acid,

ISO-butyl ester 1-[4-(aminosulfonyl)phenyl]-5- (4-chlorophenyl)-1H-pyrazole-3-carboxylic acid,

pentalogy ester 1-[4-(aminosulfonyl)phenyl] -5-(4-chlorophenyl)-1H-pyrazole-3 - carboxylic acid,

methyl ester 1-[4-(aminosulfonyl)phenyl] -5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid,

methyl ester 1-[4-(aminosulfonyl)phenyl]-5-(4-were)-1H - pyrazole-3-carboxylic acid,

methyl ester 1-[4- (aminosulfonyl)phenyl]-5-(4-methoxyphenyl)-1H-pyrazole-3 - carboxylic acid,

methyl ester 1-[4- (aminosulfonyl)phenyl] -5-(4-bromophenyl)-1H-pyrazole-3-carboxylic acid,

methyl ester 1-[4-(aminosulfonyl)phenyl] -5-(4 - nitrophenyl)-1H-pyrazole-3-carboxylic acid,

methyl ester 1- [4-(aminosulfonyl)phenyl] -5-(4-forfinal)-1H-pyrazole-3 - carboxylic acid,

methyl ester 1-[4-(aminosulfonyl) phenyl]-5-(3,5-dichloro-4-methoxyphenyl)-1H-pyrazole-3-carboxylic acid,

methyl ester 1-[4-(aminosulfonyl)phenyl]-5-(3,5 - debtor-4-methoxyphenyl)-1H-pyrazole-3-carboxylic acid,

N-(4-were)-1-[4-(aminosulfonyl)phenyl]-5-(4-forfinal)- 1H-pyrazole-3-carboxamide,

N-(3-chlorophenyl)-1-[4- (aminosulfonyl)phenyl] -5-(4-forfinal)-1H-pyrazole-3 - carboxamide,

N-(3-forfinal)-1-[4-(aminosulfonyl)phenyl] -5-(4-forfinal)-1H-pyrazole-3-carboxy ester of N-[[1-[4- (aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazole-3 - yl]carbonyl]glycine acid,

1-[4-(aminosulfonyl)phenyl]-5-(4-bromophenyl)-1H-pyrazole-3-carboxamide,

1-[4-(aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazole-3 - carboxamide,

N-phenyl-1-[4-(aminosulfonyl)phenyl] -5-(4 - forfinal)-1H-pyrazole-3-carboxamide,

N-(4-methoxyphenyl)-1- [4-(aminosulfonyl)phenyl] -5-(4-forfinal)-1H-pyrazole-3 - carboxamide,

N-(4-were)-1-[4-(aminosulfonyl)phenyl] - 5-(4-chlorophenyl)-1H-pyrazole-3-carboxamide,

N, N-dimethyl-1- [4-(aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazole-3 - carboxamide,

N-methyl-1-[4-(aminosulfonyl)phenyl] -5-(4 - chlorophenyl)-1H-pyrazole-3-carboxamide,

N-methyl-N-ethyl-1-[4-(aminosulfonyl)phenyl] -5-(4-chlorophenyl)- 1H-pyrazole-3-carboxamide,

N-phenyl-1-[4-(aminosulfonyl)phenyl] -5-(4 - chlorophenyl)-1H-pyrazole-3-carboxamide,

N-methyl-N-phenyl-1-[4- (aminosulfonyl)phenyl] -5-(4-chlorophenyl)-1H-pyrazole-3 - carboxamide,

N-ethyl-1-[4-(aminosulfonyl)phenyl] -5-(4 - chlorophenyl)-1H-pyrazole-3-carboxamide,

N-ISO-propyl-1-[4- (aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazole-3 - carboxamide,

N-propyl-1-[4-(aminosulfonyl)phenyl] -5-(4 - chlorophenyl)-1H-pyrazole-3-carboxamide,

N-butyl-1-[4- (aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazole-3 - carboxamide,

N-ISO-butyl-1-[4-(aminosulfonyl)phenyl] -5- (4-chlorophenyl)-1H-pyrazole-3-carboxamide,

N-tert-] -5-(4 - chlorophenyl)-1H-pyrazole-3-carboxamide,

N-cyclohexyl-1-[4- (aminosulfonyl)phenyl]-5-(4-forfinal)-1H-pyrazole-3 - carboxamide,

N-cyclopentyl-1-[4-(aminosulfonyl)phenyl] -5- (4-chlorophenyl)-1H-pyrazole-3-carboxamide,

4-[5-(4-chlorophenyl)-3- (pyrrolidinecarboxamido)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(piperidinecarboxylic)-1H-pyrazole - 1-yl]benzosulfimide,

N-(3-chlorophenyl)-1-[4-(aminosulfonyl) phenyl] -5-(4-chlorophenyl)-1H-pyrazole-3-carboxamide,

N-(2 - pyridyl)-1-[4-(aminosulfonyl)phenyl] -5-(4-chlorophenyl)-1H - pyrazole-3-carboxamide,

N-methyl-N-(3-chlorophenyl)-1-[4- (aminosulfonyl)phenyl] -5-(4-chlorophenyl)-1H-pyrazole-3 - carboxamide,

1-[4-(aminosulfonyl)phenyl]-5-(4-nitrophenyl)- 1H-pyrazole-3-carboxamide,

1-[4-(aminosulfonyl)phenyl]-5- (4-forfinal)-1H-pyrazole-3-carboxamide,

1-[4-(aminosulfonyl) phenyl]-5-phenyl-1H-pyrazole-3-carboxamide,

1-[4- (aminosulfonyl)phenyl] -5-(3-chloro-4-methoxyphenyl)-1H-pyrazole-3 - carboxamide,

1-[4-(aminosulfonyl)phenyl] -5-(4 - methylthiophenyl)-1H-pyrazole-3-carboxamide,

1-[4-(aminosulfonyl)phenyl] -5-(4-methoxyphenyl)- 1H-pyrazole-3-carboxamide,

1-[4-(aminosulfonyl)phenyl]-5- (4-were)-1H-pyrazole-3-carboxamide,

N-methyl-1-[4- (aminosulfonyl)phenyl] -5-(4-methoxyphenyl)-1H-pyrazole-3 - carboxamide,

N-[[1-[4-(aminosulfonyl)panasol-3 - carboxamide,

1-[4-(aminosulfonyl)phenyl] -5-(3,5-dichloro-4 - methoxyphenyl)-1H-pyrazole-3-carboxamide,

4-[5-(4-bromophenyl)-3-cyano-1H-pyrazole-1-yl]benzosulfimide,

4-[3-cyano-3-(4-forfinal)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3-cyano-1H-pyrazole-1-yl]benzosulfimide,

4-[3-cyano-5-(4-methoxyphenyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[3-cyano-5-(4-were)-1H-pyrazole-1-yl]benzosulfimide,

4-[3-cyano-5-(4-methylthiophenyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-chloro-4-methoxyphenyl)-3-cyano-1H - pyrazole-1-yl] benzosulfimide,

4-[5-(3,5-dichloro-4 - methoxyphenyl)-3-cyano-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-bromo-4-methoxyphenyl]-3-cyano-1H-pyrazole-1-yl] benzosulfimide,

4-[3-cyano-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-nitrophenyl}-3-cyano-1H-pyrazole-1 - yl]benzosulfimide,

4-[4-chloro-5-(4-forfinal)-1H-pyrazole-1 - yl]benzosulfimide,

4-[4-chloro-5-(4-chlorophenyl)-1H-pyrazole - 1-yl]benzosulfimide,

4-[4-bromo-5-(4-chlorophenyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-chloro-5-phenyl-1H-pyrazole-1-yl] benzosulfimide,

4-[4-chloro-5-(3,5-dichloro-4-methoxyphenyl)-1H - pyrazole-1-yl]benzosulfimide,

4-[4-bromo-5-(4-were)- 1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-3-(4-were) -1H-pyrazole-1-yl]baxevanis)-1H-pyrazole-1-yl]benzosulfimide,

4-[4 - bromo-5-(4-methoxyphenyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-cyano-5-(4-methoxyphenyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-chloro-5-(3, 5-debtor-4-methoxyphenyl)-1H-pyrazole - 1-yl] benzosulfimide,

4-[4-methyl-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[4-fluoro-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-4-methylsulphonyl - 1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(4 - chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[-ethyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-methyl-5-phenyl-3-(trifluoromethyl)-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(4-methoxyphenyl)-4-methyl-3-(trifluoromethyl)-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-4-methyl-3-(trifluoromethyl)-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-4-ethyl - 3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-ethyl-5-(4-were)-3-(trifluoromethyl)-1H-pyrazole-1 - yl]benzosulfimide,

4-[4-ethyl-5-(4-methoxy-3-were)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-ethyl - 5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-cyclopropyl-5-phenyl-3-(trifluoromethyl)- 1H-pyrazole-1-yl] benzosulfimide,

4-[4-ethyl-5-(3-fluoro-4 - chlorophenyl)-3-(triptoreline,

4-[5-(4-forfinal)-4-methyl-3-(trifluoromethyl) -1H-pyrazole-1-yl]benzosulfimide,

4-[4-methyl-5-(4 - were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-fluoro-5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-bromo-5-(4-chlorophenyl)-3-(deformity)- 1H-pyrazole-1-yl] benzosulfimide,

4-[4-chloro-5-(3,5-dichloro-4 - methoxyphenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-3-(deformity)-5-phenyl-1H-pyrazole-1-yl] benzosulfimide,

4-[4-bromo-3-(deformity)-5-phenyl-1H - pyrazole-1-yl]benzosulfimide,

4-[4-chloro-3-(deformity)-5-(4-methoxyphenyl)-1H - pyrazole-1-yl]benzosulfimide,

4-[4-chloro-3-cyano-5-phenyl-1H - pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(4-chlorophenyl)-3 - cyano-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-3-cyano-5- (4-forfinal)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-bromo-3 - cyano-5-(4-forfinal)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-bromo-3-cyano-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

ethyl ester [1-(4-aminosulphonylphenyl)-4-bromo-5-(4-chlorophenyl) -1H-pyrazole-3-yl]carboxylic acid,

methyl ester [1-(4 - aminosulphonylphenyl)-4-chloro-5-phenyl-1H-pyrazole-3-yl]carboxylic acid,

methyl ester [1-(4-aminosulphonylphenyl)-4-chloro-5-(4 - chlorophenyl)-1H-Paramonovo acid,

methyl ester [1-(4 - aminosulphonylphenyl)-4-chloro-5-(4-forfinal)-1H-pyrazole-3 - yl]carboxylic acid,

methyl ester [1-(4 - aminosulphonylphenyl)-4-bromo-5-(4-forfinal)-1H-pyrazole-3 - yl]carboxylic acid,

methyl ester [1-(4 - aminosulphonylphenyl)-4-chloro-5-(3-chloro-4-methoxyphenyl)-1H-pyrazole - 3-yl]carboxylic acid,

methyl ester [1-(4 - aminosulphonylphenyl)-4-chloro-5-(3,5-dichloro-4-methoxyphenyl)-1H - pyrazole-3-yl]carboxylic acid,

methyl ester [1-(4 - aminosulphonylphenyl)-5-(3-bromo-4-methoxyphenyl)-4-chloro-1H - pyrazole-3-yl]carboxylic acid,

[1-(4-aminosulphonylphenyl)-4-chloro-5-phenyl-1H - pyrazole-3-yl]carboxamide,

[1-(4-aminosulphonylphenyl)-4-chloro-5- (4-chlorophenyl)-1H-pyrazole-3-yl]carboxamide,

[1-(4 - aminosulphonylphenyl)-4-chloro-5-(4-forfinal)-1H-pyrazole-3-yl] carboxamide,

[1-(4-aminosulphonylphenyl)-4-bromo-5-(4-chlorophenyl) -1H-pyrazole-3-yl]carboxamide,

[1-(4-aminosulphonylphenyl)-4 - bromo-5-phenyl-1H-pyrazole-3-yl]carboxamide,

[1-(4 - aminosulphonylphenyl)-4-chloro-5-(4-chlorophenyl)-1H-pyrazole-3-yl]carboxylic acid,

[1-(4-aminosulphonylphenyl)-4-chloro-5 - phenyl-1H-pyrazole-3-yl] carboxylic acid,

[1-(4 - aminosulphonylphenyl)-4-chloro-5-phenyl-1H-pyrazole-3-yl] carboxylic acid,

[1-(4-aminosulphonylphenyl)-4-chloro-5-(3, 5-dichloro-4-label the R>
4-[4-chloro-3-methyl - 5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-3 - hydroxymethyl-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(4-chlorophenyl)-3-hydroxymethyl-1H-pyrazole-1-yl] benzosulfimide,

[1-(4-aminosulphonylphenyl)-4-chloro-5-(4 - chlorophenyl)-1H-pyrazole-3-yl]propanoic acid,

4-[5-(4 - chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-forfinal)-3-(trifluoromethyl)-1H-pyrazole - 1-yl]benzosulfimide,

4-[5-(4-cyanophenyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2,4-differenl)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,6 - deformity)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H - pyrazole-1-yl] benzosulfimide,

4-[5-(3,4-dichlorophenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5- (4-bromophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2,4-dichlorophenyl)-3-(trifluoromethyl)-1H - pyrazole-1-yl] benzosulfimide,

4-[5-(3-chlorophenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4 - were)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-triptoreline)-3-(trifluoromethyl)- 1H-the Ministry of foreign Affairs,

4-[5-(4-nitrophenyl)-3-(trifluoromethyl)-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(2-chlorophenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-forfinal)-3-(trifluoromethyl)-1H-pyrazole - 1-yl]benzosulfimide,

4-[5-(4-AMINOPHENYL)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2 - were)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-fluoro-2-were)-3-(trifluoromethyl)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(3-were)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4 - ethoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3,5-dimethyl-4-methoxyphenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3 - forfinal)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3-fluoro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl] benzosulfimide,

4-[5-(4-methylthiophenyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chloro-3 - were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-ethylphenyl)-3-(trifluoromethyl)-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(2,4-dimetilfenil)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methomyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-hydroxy-3-were)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3 - chloro-4-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3,4-acid)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3 - chloro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-chloro-4-methoxy-5-were)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3 - ethyl-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-fluoro-2-methoxyphenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-hydroxymethylene)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4 - methoxy-3-(1-propenyl) phenyl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(3, 5-dichloro-4-methoxyphenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2, 4-acid)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-chloro-4-forfinal)-3-(trifluoromethyl)- 1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methoxy-3-propylphenyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3, 5-debtor-4 - methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-fluoro-4-methylthiophenyl)-3- (trifluoromethyl)-1H-pyrazole-Hamid,

4-[1-[4-(aminosulfonyl)phenyl]-3- (trifluoromethyl)-1H-pyrazole-5-yl]benzoic acid,

4-[5-(3 - methyl-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(3-chloro-4-methylthiophenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4- (N,N-dimethylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methyl-3-nitrophenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4- (N-methylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-amino-4-were)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

methyl ester of 4-[1-[4-(aminosulfonyl)phenyl]-3-(trifluoromethyl)-1H - pyrazole-5-yl]benzoic acid

4-[1-[4-(aminosulfonyl) phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-yl]benzamide,

4-[5-(3,5-differenl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,4,6-tryptophanyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2,6-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,4,6-trichlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3,4-dimetilfenil)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(1,methyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2-chloro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chloro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2-methylsulfinylphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-methylsulfinylphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methylsulfinylphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2-fluoro-4-were)-3-(trifluoromethyl)-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(4-fluoro-3 - were)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-chloro-4-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chloro-2-were)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-hydroxyphenyl)- 3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5- (3,4-dihydroxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-ISO-propylphenyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

N-[4-[[1-[4- (aminosulfonyl)phenyl]-3-trifluoromethyl-1H-pyrazole-5 - yl]phenyl]acetamide", she

N-[4-[1-[4-(aminosulfonyl the evil-5 - yl]phenyl]triptorelin,

4-[5-(4-[N - methylaminomethyl]phenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,5-dichlorophenyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-n-butoxyphenyl)- 3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5- (4-[aminosulfonyl] phenyl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(2,3-differenl)-3-(trifluoromethyl)-1H-pyrazole - 1-yl] benzosulfimide,

4-[5-(2,5-differenl)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,3,4 - tryptophanyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3,4,5-tryptophanyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,4,5-tryptophanyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2,5,6 - tryptophanyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,3,4,5-tetrafluorophenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5- (2,3,4,6-tetrafluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(2,3,5,6-tetrafluorophenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5- (pentafluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,3,4-trichlorophenyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3,4,5 - trichlorophenyl)-3-(trisulfonated,

4-[5-(2,5,6 - trichlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,3,4,5-tetrachlorophenyl)-3-(trifluoromethyl)-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(2,3,4, 6- tetrachlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,3,5,6-tetrachlorophenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5- (2,3,4,5,6-pentachlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-tert-butylphenyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-ISO-butylphenyl)- 3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5- (4-chlorophenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-triptoreline)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methylthiophenyl)-3-(deformity)- 1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-(1-morpholino) phenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-were)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-phenyl-3-(deformity)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(4-methoxyphenyl)-3- (deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3, 4-dimetilfenil)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-fluoro-4-methoxyphenyl)-3- (deformity)-1H-pyrazole-1-yl] benzols the ester 4-[1-[4- (aminosulfonyl) phenyl]-3-(deformity)-1H-pyrazole-1 - yl]benzoic acid

4-[1-[4-(aminosulfonyl)phenyl] -3- (deformity)-1H-pyrazole-1-yl]benzamide,

4-[5-(2-fluoro-4 - methoxyphenyl)-3-(deformity)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(4-cyanophenyl)-3-(deformity)-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(3-chloro-4-were) -3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5- (3-chloro-4-methoxyphenyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chloro-3-were)-3- (deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3, 4-acid)-3-(deformity)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(3, 5-dichloro-4-methoxyphenyl)-3- (deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3, 5-debtor-4-methoxyphenyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2-methoxyphenyl)-3-(deformity)- 1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-bromo-4 - methoxyphenyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methylsulfinylphenyl)-3- (deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(5-bromo-2-thienyl)-3-(deformity)-1H-pyrazole - 1-yl]benzosulfimide,

4-[5-(5-chloro-2-thienyl)-3- (deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(1-cyclohexenyl)-3-(deformity)-1H-pyrazole-1 - yl] benzosulfimide,

4-[5-(cyclohexyl)-3-(deformity)-1H-pyrazole-1 - Xen-6 - yl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[3-(deformity)-5-(4-methylcyclohexyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(methyl-1-cyclohexenyl)-3- (deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2-methyl-1-cyclopentenyl)-3-(deformity)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(benzofuran-2-yl)-3- (deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5- (1,3-benzodioxol-5-yl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2-pyrazinyl)-3-(deformity)-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(4-(morpholino) phenyl)- 3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5- (2,5-dimethyl-3-furyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(5-methyl-2-furyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(1-chloro-1-methyl-4-cyclohexyl)-3- (deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3,4 - dibromo-4-methylcyclohexyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2-methoxycyclohexyl)-3-(deformity)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-thienyl)-3- (deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2,4 - dimethyl-3-thienyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,5-dichloro-3-thienyl)-3-(deformity)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(benzofuran-5-yl)-3- (trifluoromethyl)-1H-PI is 4-[5-(5-chloro-2-thienyl)-3-(trifluoromethyl)-1H - pyrazole-1-yl] benzosulfimide,

4-[5-(5-indanyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(5 - methyl-2-thienyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2,3-dihydrobenzofuran-5-yl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

5-[5- (1-cyclohexenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(5-benzothiazyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3,4-dihydro-2H-1-benzopyran-6-yl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3, 4- dihydro-2H-1-benzothiophen-6-yl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(2-phenylethenyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methyl-1,3 - benzodioxol-6-yl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl] benzosulfimide,

4-[5-(4-methyl-1,3-benzodioxol-5-yl)- 3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2 - pyrazinyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(biphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(1,2,3,4-tetrahydronaphtyl-6-yl)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2 - naphthyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-thiazolyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(2-oxazolyl)-3-(trifluoromethyl
4-[5- (cyclopentyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(cycloheptyl)-3-(trifluoromethyl)-1H-pyrazole - 1-yl]benzosulfimide,

4-[5-(1-cyclopentenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2 - furyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-pyridyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-pyridyl)-3-(trifluoromethyl)-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(6-methyl-3-pyridyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4 - pyridyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3-cyclohexenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-cyclohexenyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methylcyclohex-4 - EN-1-yl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(5-chloro-2-furyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(5-bromo-2-furyl)-3-(trifluoromethyl)-1H - pyrazole-1-yl] benzosulfimide,

4-[5-(6-methoxy-2-naphthyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4 - chlorophenyl)-3-(heptafluoropropyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(chlorodifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(pentafluoroethyl)e,

4-[3-(chlorodifluoromethyl)-5-(3-fluoro-4-methoxyphenyl)-1H - pyrazole-1-yl] benzosulfimide,

4-[5-(phenyl)-3- (permitil)-1H-pyrazole-1-yl]benzosulfimide,

4-[3- (dichloromethyl)-5-(3-fluoro-4-methoxyphenyl))-1H-pyrazole-1-yl] benzosulfimide,

4-[3-(bromodifluoromethyl)-5-(3-fluoro-4 - methoxyphenyl))-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4 - chlorophenyl)-3-(permitil)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3-(chloromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(dichloromethyl)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3- (dichloromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5- (4-forfinal)-3-(trichloromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(1,1-dottorati)- 1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3- (1,1-deferror)-1H-pyrazole-1-yl]benzosulfimide,

4-[5- (4-chlorophenyl)-3-(1,1-dichloroethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(1,1-dichloropropyl)-1H-pyrazole - 1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3-nitro-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3- (amidino)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4 - chlorophenyl)-3-(methylsulphonyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(N - methylaminomethyl)-1H-pyrazole-1-Neil)-3-(2-pyridyl)-1H - pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3-(N - cyanoimino)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4 - chlorophenyl)-3-(tetrazolyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chloranil)-3-(phenylsulfonyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(N - phenylenesulfonyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5- (4-chlorophenyl)-3-(N,N-dimethylaminomethyl)-1H-pyrazole-1 - yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3-(N-methyl-N-phenylenesulfonyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(N-ethylaminomethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(N-ISO - propylaminosulfonyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3-(N-methyl-N - ethylaminomethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5- (4-chlorophenyl)-3-(N-methyl-N-(3-chlorophenyl) aminosulfonyl)- 1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3- (N-methyl-N-(2-pyridyl)aminosulfonyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[3-methyl-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[3-ISO-butyl-5-phenyl-1H-pyrazole-1-yl] benzosulfimide,

4-[3-(3-hydroxypropyl)-5-phenyl-1H-pyrazole - 1-yl]benzosulfimide,

4-[5-(4-forfinal)-3-(3 - hydroxypropyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5- (3,5-dichloro-4-methoxyphenyl)-3-(3-hydroxypropionate,

1-[4- (aminosulfonyl)phenyl] -5-(4-forfinal)-1H-pyrazole-3-propanoic acid,

1-[4-(aminosulfonyl)phenyl] -5-(4-chlorophenyl)-1H - pyrazole-3-propanoic acid,

1-[4-(aminosulfonyl)phenyl]- 5-(4-chlorophenyl)-1H-pyrazole-3-propanamide,

1-[4-(aminosulfonyl) phenyl] -5-(4-forfinal)-1H-pyrazole-3-propanoic acid methyl ester,

4-[3-(3-hydroxymethyl)-5-phenyl-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(3-hydroxymethyl)- 1H-pyrazole-1-yl] benzosulfimide,

4-[3-(3-hydroxymethyl)- 5-(4-methoxyphenyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3,5-dichloro-4-methoxyphenyl)-3-(3-hydroxymethyl)-1H - pyrazole-1-yl] benzosulfimide,

4-[5-(3-chloro-4-methoxyphenyl) -3-(3-hydroxymethyl)-1H-pyrazole-1-yl] benzosulfimide,

ethyl ester of 3-[1-[4-(aminosulfonyl)phenyl)-5-phenyl-1H - pyrazole-3-yl] -2-cyano-propanoic acid,

4-[5-(4-chlorophenyl)- 3-(chloro)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4 - chlorophenyl)-3-(bromo)-1H-pyrazole-1-yl]benzosulfimide,

4-[ 5-(4-chlorophenyl)-3-(fluoro)-1H-pyrazole-1-yl]benzosulfimide,

4-[3-(deformity)-4, 5-dihydro-7-methoxy-1H-benzo[g] indazol-1-yl]benzosulfimide,

4-[3-(deformity)-4,5-dihydro-7-methyl-1H-benzo[g] indazol - 1-yl]benzosulfimide,

4-[4,5-dihydro-7-methoxy-3-(trifluoromethyl)-1H-benzo[g] Indus is 4,5-dihydro - 7-methyl-3-(trifluoromethyl)-1H-benzo[g] -indazol-1 - yl]benzosulfimide,

4-[4,5-dihydro-6,8-dimethyl-3-(trifluoromethyl)-1H - benzo[g]indazol-1-yl]benzosulfimide,

4-[4,5-dihydro-6,8-dimethoxy-3- (trifluoromethyl)-1H-benzo[g] indazol-1-yl] benzosulfimide,

methyl ester [1-(4-aminosulphonylphenyl)-4,5-dihydro-7 - methoxy-1H-Ben[g]indazol-3-yl]carboxylic acid,

4-[4,5 - dihydro-3-(trifluoromethyl)-1H-thieno[3,2, g] indazol-1-yl] benzosulfimide,

4-[1-phenyl-3-(deformity)-1H-pyrazole-5-yl] benzosulfimide,

4-[1-(4-chlorophenyl)-3-(deformity)-1H - pyrazole-5-yl]benzosulfimide,

4-[1-(4-forfinal)-3- (deformity)-1H-pyrazole-5-yl]benzosulfimide,

4-[1-(4 - methoxyphenyl)-3-(deformity)-1H-pyrazole-5-yl] benzosulfimide,

4-[1-phenyl-3-(trifluoromethyl)-1H-pyrazole-5-yl] benzosulfimide,

4-[1-(4-chlorophenyl)-3-(trifluoromethyl)-1H - pyrazole-5-yl]benzosulfimide,

4-[1-(4-forfinal)-3- (trifluoromethyl)-1H-pyrazole-5-yl]benzosulfimide,

4-[1-(4 - methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl] benzosulfimide.

A family of specific compounds of formula II are of special interest includes the following compounds and their pharmaceutically acceptable salts:

4-[5-(4-chlorophenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-phenyl - 3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide the Teal)- 1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3- (deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4 - were)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[3-(deformity)-5-(4-were)-1H-pyrazole-1 - yl]benzosulfimide,

4-[3-(deformity)-5-phenyl-1H - pyrazole-1-yl]benzosulfimide,

4-[3-(deformity)-5-(4 - methoxyphenyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[3-cyano - 5-(4-forfinal)-1H-pyrazole-1-yl]benzosulfimide,

4-[3- (deformity)-5-(3-fluoro-4-methoxyphenyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-fluoro-4-methoxyphenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-chloro-5 - phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3- (hydroxymethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-(N,N-dimethylamino) phenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide.

The term "hydrido group" denotes a single hydrogen atom (H). This radical hydrogen can be attached, for example, the oxygen atom with the formation of hydroxyl radical, or two hydrogen radicals can join the carbon atom with the formation of the methylene radical (-CH2-). Where used, the term "s or branched radicals, containing from one to about twenty carbon atoms or, preferably, from one to twelve carbon atoms. More preferred alkyl radicals are "lower alkyl" radicals containing from one to about ten carbon atoms. Most preferred are alkyl radicals containing from one to about six carbon atoms. Examples of such radicals include methyl, ethyl, n-propyl, ISO - propyl, n-butyl, ISO-butyl, sec-butyl, tert-butyl, pentyl, ISO-amyl, hexyl, etc.

The term "alkenyl" embraces linear or branched radicals containing at least one double carbon-carbon bond and from about two to twenty carbon atoms or, preferably, two to about twelve carbon atoms. The most preferred alkenylamine are "lower alkeneamine" radicals containing from two to about six carbon atoms. Examples of such radicals include ethynyl, n-propenyl, butenyl, etc., the Term "halogen atom" includes a halogen, such as fluorine atoms, chlorine, bromine or iodine. The term "halogenated" embraces radicals where one or more carbon atoms alkylene is s, dihalogenoalkane and POLYHALOGENATED radicals. Monoalkyl radicals, for example, can contain or iodine atom or bromine atom or a chlorine atom or a fluorine atom. Dihalogen and polyhalogen radicals can contain two or more identical atoms of halogen or a combination of different halogen atoms. "Lower halogenated" embraces radicals containing 1-6 carbon atoms. Examples halogenating radicals are vermeil, deformity, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, diperchlorate, dichloromethyl, defloratin, direcror, dichlorethyl and dichloropropyl.

The term "hydroxyalkyl" embraces linear or branched alkyl radicals containing from one to about ten carbon atoms, each of which can contain as a substituent one or more hydroxyl radicals. More preferred hydroxyalkyl radicals are "lower hydroxyalkyl" radicals containing from one to six carbon atoms and one or more hydroxyl radicals. Examples of such radicals include hydroxymethyl, hydroxyethyl, hydroxypropyl, guy is oxygenated radicals, each of which has an alkyl portion of one to about ten carbon atoms, such as methoxy group. More preferred alkoxy groups are lower alkoxy groups containing from one to six carbon atoms. Examples of such radicals include methoxy group, ethoxy group, propoxy group, butoxy group and tert-butoxy group.

The term "alkoxyalkyl" also embraces alkyl radicals containing two or more alkoxy radicals attached to the alkyl radical with the formation, thus, monoatomically or dialogshell. More preferred alkoxyalkyl radicals are "lower alkoxyalkyl" radicals containing from one to six carbon atoms and from one to two alkoxy radicals. Examples of such radicals include methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl and methoxypropyl. "Alkoxy group" or "alkoxyalkyl" can be further substituted by one or more halogen atoms such as fluorine atom, chlorine or bromine with the formation of halogenoalkane" and "halogenocarboxylic" radicals. Examples of such radicals are formatosi group, chloromethoxy group, triptoreline-group, three is the third means carbocyclic aromatic system, containing one, two or three rings, where these rings can be connected to each other by the type of hinged groups or may be condensed with each other. The term "aryl" embraces aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indan and biphenyl. The term "heterocyclic group" embraces saturated, partially saturated and unsaturated heteroaromatics cyclic radicals, where the heteroatoms may be selected from a nitrogen atom, sulfur or oxygen. Examples of saturated heterocyclic radicals are saturated three - to six-membered heterogenities group containing 1 to 4 nitrogen atoms (in particular, pyrrolidinyl, imidazolidinyl, piperidino group, piperazinil and etc.); saturated 3-6 membered heterogenities group containing from 1 to 3 oxygen atoms and 1 to 3 nitrogen atoms (in particular, morpholinyl and etc.); saturated 3-6 membered heterogenities group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms (in particular, diazolidinyl etc.). Examples of partially saturated heterocyclic radicals include dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazolo. The term "heteroaryl" embraces unsaturated heterocyclic radika is, Vlada unsaturated five - and six-membered heterogenities group containing 1 to 4 nitrogen atoms, for example, pyrrolyl, pyrrolidyl, imidazolyl, pyrazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (in particular, 4H-1,2,4 - triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl and so on ), tetrazolyl (in particular 1H-tetrazolyl 2N-tetrazolyl and so on), etc.; unsaturated condensed heterocyclic group, containing 1 to 5 nitrogen atoms, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, chinoline, ethenolysis, indazoles, benzotriazolyl, tetrachloropyridine (in particular, tetrazolo[1,5 - b]pyridazinyl and so on), etc.; unsaturated 3-6 membered heterogenities group containing an oxygen atom, for example, pyranyl, 2-furyl, 3-furyl, etc; unsaturated five - and six-membered group containing a sulfur atom, for example, 2-thienyl, 3-thienyl etc.; unsaturated five - and six-membered heterogenities group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl (in particular, 1,2,4-oxadiazolyl, 1,3,4 - oxadiazolyl, 1,2,5-oxadiazolyl and so on), etc.; unsaturated condensed heterocyclic group containing from 1 to 2 atoms is stechlinsee heterogenities group, containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example, thiazolyl, thiadiazolyl (in particular, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl and so on), etc.; unsaturated condensed heterocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms (in particular, benzothiazolyl, benzothiadiazole and so on), etc., This term also embraces radicals where heterocyclic radicals are fused with aryl radicals. Examples of such a condensed bicyclic radicals are benzofuran, benzothiophene, etc. Mentioned "heterocyclic group" may contain from 1 to 3 substituents such as lower alkyl, a hydroxyl group, an eye group, amino group and a lower alkylamino group. Preferred heterocyclic radicals are 5-to 10-membered condensed or unfused radicals. Preferred examples of heterocyclic radicals are benzofuran, 2,3-dihydrobenzofuran, benzothiazyl, indolyl, dihydroindole, bromanil, benzopyran, thiochroman, benzothiophen, benzodioxolyl, benzodioxolyl, pyridyl, thienyl, thiazolyl, oxazolyl, furyl and pyrazinyl.

The term "sulfonylurea group, both independently and in St. the hiccuping-SO2-. "Alkylsulfonyl group" embraces alkyl radicals attached to sulfonylurea the radical, where the alkyl described above. More preferred alkylsulfonyl radicals are "lower alkylsulfonyl" radicals containing from one to six carbon atoms. Examples of such lower alkylsulfonyl radicals are methylsulfonyl group, ethylsulfonyl group and propylsulfonyl group. The term "arylsulfonyl group" embraces aryl radicals, discussed earlier, which is attached to sulfonylurea the radical. An example of such a radical is phenylsulfonyl group. The terms "sulfonylurea group", "aminosulfonyl group" and "sultamicillin group, both independently and with such terms as "N-alkylaminocarbonyl group, N-killinaskully group", / "N, N-dialkylaminoalkyl group" and "N-alkyl-N-killinaskully group" refers to sulfanilyl radical, a substituted amino group with the formation of sulfonamidnuyu group (-SO2NH2). The terms "N-alkylaminocarbonyl group" and "N,N-dialkylaminoalkyl group" refers to selfamily radicals substituted, respectively, od radicals are "lower alkylaminocarbonyl group", containing from one to six carbon atoms. Examples of such lower alkylaminocarbonyl groups are N-methylaminomethyl group, N-ethylaminomethyl group and N-methyl-N - ethylaminomethyl group. The terms "N-killinaskully group and "N-alkyl-N-aryl-aminosulfonyl group" refers to sulfonylurea radicals substituted, respectively, with one aryl radical, or one alkyl and one aryl radical. The preferred N-alkyl-N - arylaminomethylene radicals are "lower N-alkyl-N - arylaminomethylene the radicals having alkyl radicals containing from one to six carbon atoms. Examples of such lower N-alkyl-N-killinaskully radicals are N-methyl-phenylenesulfonyl group and N-ethyl-phenylamino - sulfonylurea group.

The term "carboxy group" or "carboxyl group" by itself or with other terms, such as "carboxylic" denotes the group-COOH. The terms "alcoolica group" or "carboxylic" include radicals containing carboxyl radical, above, which is attached to the alkyl radical. Alcoholnye radicals may or may not have substituents, for example, the group ISO-butanole (ISO-Butyrina) group, valeryl (pantaneira group), isovaleryl, pivellina group, hexanoyl group, etc., the Term "carbonyl group" by itself or with other terms, such as "alkylcarboxylic group" means a radical -(C=O)-.

The term "alkylcarboxylic group" embraces radicals containing a carbonyl radicals, substituted alkyl radicals. More preferred alkylcarboxylic radicals are "lower alkylcarboxylic" radicals containing from one to six carbon atoms. Examples of such radicals are methylcarbamyl group and acylcarnitine group. The term "alkylcarboxylic" denotes an alkyl radical, substituted "alkylcarboxylic" radical. The term "alkoxycarbonyl group" means a radical containing an alkoxy radical, discussed earlier, which, through the oxygen atom attached to a carbonyl radical. Mostly "lower alkoxycarbonyl group includes alkoxy radicals containing from one to six carbon atoms. Examples of such "lower alkoxycarbonyl" ester radicals are substituted or unsubstituted methoxycarbonyl group, ethoxycarbonyl "alkoxycarbonyl" embraces radicals, including the previously discussed "alkoxycarbonyl group, a substituted alkyl radical. More preferred alkoxycarbonylmethyl radicals are "lower alkoxycarbonyl" that contains the lowest alkoxycarbonyl radicals, discussed earlier, is connected to the group, containing from one to six carbon atoms. Examples of such lower alkoxycarbonylmethyl radicals include methoxycarbonylmethyl, tert-butoxycarbonylmethyl and methoxycarbonylethyl. The term "aminocarbonyl group" by itself or with other terms, such as "aminocarbonyl", "N-alkylaminocarbonyl group, N-arylaminomethylene group, N,N-dialkylaminoalkyl group, N-alkyl-N - arylaminomethylene group, N-alkyl-N-gidroksilaminopurina group" and "N-alkyl-N-hydroxyarylalkyl" denotes an amide group of the formula-C(= O)NH2. The term "N-alkylaminocarbonyl group and N,N-dialkylaminoalkyl group" means aminocarbonyl radicals, which contain as substituents one alkyl radical, or two alkyl radicals, respectively. More preferred are "lower alkylaminocarbonyl group containing considered Raney "N-alkyl - N-arylaminomethylene group" means aminocarbonyl radicals, substituted, respectively, with one aryl radical or by one alkyl radical and one aryl radical. The term "aminocarbonyl" includes alkyl radicals, substituted aminocarbonyl radicals. The term "N - cycloalkylcarbonyl group" means aminocarbonyl radical, which is substituted by at least one cycloalkyl radical. More preferred are "lower cycloalkylcarbonyl group", having the lowest cycloalkyl radicals containing from three to seven carbon atoms, which is attached to aminocarbonyl the radical. The term "aminoalkyl" embraces alkyl radicals, substituted by amino radicals. The term "acylaminoalkyl covers aminoalkyl radicals, in which the nitrogen atom contains as a substituent alkyl radical. The term "amidino group" refers to a radical-C(=NH)-NH2. The term "cyanoaniline group" refers to a radical-C(=N-CN)-NH2. The term "heteroseksualci" embraces alkyl radicals substituted heterocyclic groups. More preferred heteroseksualnymi radicals are "lower heterocytolysine" radicals containing from one to six carbon atoms and heterocyclic radiative aryl-substituted alkyl radicals. Preferred Uralkalij radicals are "lower kalkilya" radicals, aryl radicals attached to alkyl radicals containing from one to six carbon atoms. Examples of such radicals are benzyl, diphenylmethyl, triphenylmethyl, phenylethyl and diphenylether. Aryl in the above aralkyl may be optionally substituted by halogen atom, alkyl, alkoxy group, halogenation or halogenoalkane group. The term "benzyl" and "phenylmethyl" are equivalent. The term "cycloalkyl" embraces radicals containing from three to ten carbon atoms. More preferred cycloalkyl radicals are "lower cycloalkyl" radicals containing from three to seven carbon atoms. Examples of these include such radicals as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. The term "cycloalkenyl" embraces unsaturated cyclic radicals containing from three to ten carbon atoms, such as cyclobutenyl, cyclopentenyl, cyclohexenyl and cycloheptenyl. The term "alkylthio group" includes radicals having a linear or branched alkyl radical containing from one to ten carbon atoms, attached to the TLD is safe group" embraces radicals, containing a linear or branched alkyl radical containing from one to ten carbon atoms, attached to a divalent group,- S(= O). The term "aminoalkyl" includes alkyl radicals, substituted by amino radicals. More preferred aminoalkyl radicals are "lower aminoalkyl", containing from one to six carbon atoms. Examples are aminomethyl, aminoethyl and aminobutyl. The term "acylaminoalkyl covers aminoalkyl radicals, the nitrogen atom contains as a substituent at least one alkyl radical. More preferred acylaminoalkyl radicals are lower acylaminoalkyl containing from one to six carbon atoms, which is attached to the lower aminoalkylindole the radical described above. The terms "N-alkylamino-group" and "N,N - dialkylamino group" denote amino groups which are substituted with one alkyl group and two alkyl groups, respectively. More preferred alkylamino-radicals are "lower alkylamino radicals containing from one to six carbon atoms, which is attached to the nitrogen atom. Suitable "alkylamino-groups may be mono -, dialkylamino-German "arylamino group" means amino group, which is substituted by one or two aryl radicals, such as N-phenylamino group. "Arylamino-radicals can be further substituted on the aryl ring radical.

The term "aralkylamines group" denotes amino groups which are substituted by one or two Uralkalij radicals, such as N - benzylamino group. "Aralkylamines-radicals can be further substituted on the aryl ring radical. The term "N-aralkyl-N-alkylamino group" "N-alkyl-N-arylamino group" denotes amino groups which are substituted on the amino group of one aranceles group and at least one alkyl radical, or one aryl radical and one alkyl radical, respectively. The terms "N-alluminati" and "N-aralkylamines" denote amino groups which are substituted with one aryl radical or one Uralkali radical, respectively, and the amino group attached to the alkyl radical. More preferred arylaminomethylene radicals are "lower alluminare" containing arylamino radical attached to the group comprising from one to six carbon atoms. Examples of these radicals are N-phenyliminomethyl and N-phenyl-N-methylaminomethyl. The terms "N-alkyl-N - alluminati" and "N-o, in which the amino group attached to the alkyl radicals. The term "acyl group" by itself or as part of other terms, such as "acylamino-group" denotes a radical, which is a residue formed after removal of hydroxyl groups from organic acids. The term "acylamino group" encompasses amino radicals, substituted acyl groups. Examples of "acylamino-radicals" are acetylamino - or acetamido group (CH3C(=O)-NH-), in which the amine may be further substituted by alkyl, aryl or aralkyl. The term "aaltio group" embraces aryl radicals containing from six to ten carbon atoms, attached to the divalent sulfur atoms. Example "aaltio group" is phenylthio group.

The term "Uralkali group" encompasses discussed earlier kalkilya radicals that are attached to the divalent sulfur atom. Example "Uralkali group" is benzylthio group. The term "aryloxy group" encompasses discussed earlier aryl radicals attached to the oxygen atom. An example of such radicals is phenoxy group. The term "Alcoxy group" includes oxygen-containing kalkilya radicals, attached posredstvo - radicals", in which the phenyl radicals attached to lower alkoxy radicals, discussed earlier. The term "halogenerator covers discussed earlier aryl radicals attached to halogenosilanes radicals. The term "carboxyglutamic" includes the previous carboxialkilnuyu radicals, the alkyl part of which is attached halogen atom. The term "alkoxycarbonylmethyl covers discussed earlier alkoxycarbonyl radicals, substituted halogenosilanes radical. The term "aminocarbonylmethyl covers discussed earlier aminocarbonyl radicals, zameshannye halogenosilanes radical. The term "alkylaminocarbonyl covers discussed earlier alkylaminocarbonyl radicals, substituted halogenosilanes radical. The term "alkoxycarbonylmethyl covers discussed earlier alkoxycarbonyl radicals and cyano group which is attached to Alchemilla the radical. The term "carboxymethylaminomethyl group covers discussed earlier aminocarbonyl radicals, substituted discussed earlier carboxialkilnuyu radicals. The term "alcoxycarboxylates covers examined the wound is Lamy. The term "cycloalkenyl covers discussed earlier cycloalkyl radicals containing from three to ten carbon atoms that are attached to the previously reviewed alkyl radicals. More preferred cycloalkenyl radicals are "lower cycloalkenyl" radicals, which cycloalkenyl radical attached to the previously discussed lower alkyl radicals. Examples include such radicals as cyclopropylmethyl, cyclobutylmethyl and cyclohexylethyl. The term "aralkyl" embraces aryl radicals attached to alkenyl radicals containing from two to ten carbon atoms, such as phenylbutyl or phenylethenyl or still.

The present invention includes pharmaceutical compositions for the treatment of inflammation associated with inflammatory diseases such as arthritis, which contain a therapeutically effective amount of the compounds of formula I together with at least one pharmaceutically acceptable carrier, auxiliary substance or diluent.

The present invention also includes a therapeutic method for the treatment of patients from inflammation or associated with inflammatory diseases, with the specified sposobstvala amount of the compounds of formula I.

The invention also includes the family of compounds of formula I, which represent its pharmaceutically acceptable salt. The term "pharmaceutically acceptable salts" embraces salts commonly used in the formation of alkali metal salts or addition salts of free acids and bases. The nature of salt is not crucial, provided that it is pharmaceutically acceptable. Suitable pharmaceutically acceptable acid additive salts of compounds of formula I can be obtained from inorganic acids or organic acids. Examples of such inorganic acids are hydrochloric acid, Hydrobromic acid, uudistoodetena acid, nitric acid, carbonic acid, sulfuric acid and phosphoric acid. Suitable organic acids can be selected from aliphatic, cycloaliphatic, aromatic, arylaliphatic, heterocyclic, hydroxy carboxylic and sulfonic acids, examples of which are formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, gluconic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, glucuronic acid is a, benzoic acid, Anthranilic acid, methylsulfonate, salicylidene acid, 4-hydroxybenzoic acid, phenylacetic acid, mandelic acid, albanova (Mamonova) acid, methanesulfonate, econsultation, benzosulfimide, Pantothenic acid, 2-hydroxyethanesulfonic-acid, toluensulfonate, sulfanilic acid, cyclohexanesulfonic, stearic acid, Allenova acid, beta-hydroxipropionic acid, salicylic acid, galactosemia acid and galacturonic acid. Suitable pharmaceutically acceptable additive salts of the bases of the compounds of formula I are salts with metals formed by aluminum, calcium, lithium, magnesium, potassium, sodium and zinc or organic salts formed N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, Ethylenediamine, meglumine (N-methylglucamine) and procaine. All of these salts may be obtained by conventional means from the corresponding compounds of formula I by the reaction of, for example, the appropriate base or acid with a compound of formula I.

General synthetic methods

Compounds of the present invention can be synthesized in accordance with the following uvarivaetsja, already defined earlier in the description of formula I.

Scheme I

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Synthetic Scheme I shows the derivation of the Tetra-substituted pyrazoles of the starting compound I. In the first stage synthetic Scheme I phenylmercaptan (1) is treated with a base and an alkylating agent (R3X, where X denotes a leaving group, such as tosyl) and receive the substituted ketone (2). In the second stage, the substituted ketone (2) is treated with base, such as sodium methoxide, and allermuir agent such as ester (R2COOCH3or the equivalent of ester (R2CO-imidazole) and receive the intermediate ketone (3) similarly to the method described in the publication Reid and Colvin, J. Amer. Chem. Soc., 72, 2948-2952 (1950). At the third stage of the diketone (3) is reacted with a substituted hydrazine in acetic acid or alcohol solvent to form a mixture of pyrazoles (4) and (5). Identification of target pyrazole (4) can be done chromatography or recrystallization.

Scheme II

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Synthetic Scheme II shows the formation of compounds of formula I, where R3 denotes the hydrogen atom. In the first stage, the ketone (1) is treated with a base, preferably NaOMe or NaH, and complex ester or the equivalent of ester and get promezhutochnye, such as absolute ethanol or acetic acid, is treated by boiling under reflux for 10 to 24 hours hydrochlorite salt or free base of the substituted hydrazine and get a mixture of pyrazoles (7) and (8). By recrystallization from a mixture of diethyl ether - hexane or chromatography receive connection (7), usually in the form of solid light yellow or brown color.

Scheme III

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Ha synthetic Scheme III shows the method of obtaining derivatives of 4,5-dihydrobenzo[g] indazole, which fall under the formula I. In the first stage, ethyl ester triperoxonane acid interacts with a base, such as a 25% solution of sodium methoxide in proton solvent such as methanol, and derived from 1-tetralone (9) with the formation of the intermediate diketone (10). In the second stage of the diketone (10) in anhydrous proton solvent such as absolute alcohol and acetic acid, is treated by boiling under reflux for 24 h free base or a hydrochloric acid salt of the substituted hydrazine and get a mixture of pyrazoles (11) and (12). By recrystallization receive 4,5 - dihydrobenzo[g]industriventilation (11).

Scheme IV

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On proizvodnjo of pyrazole (7), where R3 denotes a hydrogen atom. The chlorination is conducted by passing a current of chlorine gas at room temperature through a solution containing the compound (7).

Scheme V

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Synthetic Scheme V shows the derivation of the substituted ketones 18, which are used in Scheme I, but are not available on the market. Ketones can be obtained by standard acylation according to the method of Friedel-of substituted benzenes 14 using acid chlorides of the acids or anhydrides 15. Otherwise ketones can be obtained from phenylcarbonylamino 16 using conventional methods of ORGANOMETALLIC chemistry, where M denotes a metal, such as lithium, magnesium, etc. In an alternative method using ORGANOMETALLIC compounds originate from aldehydes 17, where M denotes a metal, such as lithium, magnesium, etc., followed by oxidation with a suitable reagent, such as chromic anhydride, and get ketones.

Scheme VI

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Synthetic Scheme VI shows an alternative regioselective method of producing pyrazole 21. Available on the market enone 19 can be epoxidizing and get epoxyketone 20 that handle hydrochloride 4-sulfonamidophenylhydrazine and get pichet 3-amino-4-substituted phenyl) from the source connection 22. Then the corresponding 5-(4-substituted aryl) pyrazoles can be netravati group R under standard conditions and to restore amino group, mainly hydrazine and palladium on coal. Further it is possible to carry out the alkylation at the amino-group.

Scheme VIII

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Synthetic Scheme VIII shows the derivation of the pyrazoles 26 of ester 24. Recovery of ester 24 to alcohol, preferably using lithium aluminum hydride (L-AH), followed by oxidation, preferably with manganese dioxide receive aldehyde 25. Various nucleophiles (such as hydroxamate and 1,3-dicarbonyl compounds) can condense with the aldehyde and get targeted oximes or olefins 26.

The following examples are detailed descriptions of methods of preparing compounds of formula I and formula II. These detailed descriptions correspond to the above General synthetic methods that are part of the present invention and serve to their explanation. These detailed descriptions are given only for illustration and do not limit the scope of the claims of the present invention. Everywhere are given the weight part, and temperature, unless specified, are given in degrees Celsius. Reducing the HRMS oboznachaet the ol-1-yl]benzosulfimide

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Stage 1: Getting 4,4,4-Cryptor-1-[4-(chloro)phenyl]- butane-1,3-dione

Ethyl ester triperoxonane acid (23,52 g, 166 mmol) is placed in a three-neck round bottom flask with a capacity of 500 ml and dissolved in methyl tert-butyl ether (75 ml). To mix the solution through an addition funnel for two minutes, add 25% solution of sodium methoxide (40 ml, 177 mmol). Then tert - butyl methyl ether (20 ml) was dissolved 4'-chloroacetophenone (23,21 g, 150 mmol) and the resulting solution for 5 minutes are added to the previously obtained reaction mixture. Leave the mix on the night of 15.75 hours) and added 3 N hydrochloric acid (70 ml). The organic layer is separated, washed with saturated salt solution, dried over magnesium sulfate, filtered and evaporated in vacuum, obtaining 35,09 g solid yellow-orange color. The solid is recrystallized from ISO-octane and get 31,96 g (85%) of Dion with so pl. 66-67oC.

Stage 2: Obtain 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide

To a stirred solution of 4,4,4-Cryptor-1-[4-(chloro) phenyl]-butane-1,3-dione (1,00 g, 4.0 mmol), obtained in stage 1, in ethanol (50 ml) was added the hydrochloride of 4-sulfonamidophenylhydrazine (982 mg, 4.4 mmol, 1,1 acecontrol chromatography high resolution the reaction product is a mixture 96:3 4-[5- (4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide and its regioisomer 4-[3-(4-chlorophenyl)-5- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide. After cooling to room temperature the reaction mixture is evaporated in vacuum. The residue is dissolved in ethyl acetate, washed with water and saturated salt solution, dried over magnesium sulfate, filtered and evaporated in vacuum, obtaining a solid light brown color, which is recrystallized from ethyl acetate and ISO-octane and get pyrazole (1.28 g, 80%, so pl. 143-145oC). Data liquid chromatography high-resolution show that the purified product is a mixture 99,5:0,5 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1 - yl] benzosulfimide and its regioisomer. Data1H NMR spectroscopy (CDCl3/CD3OD, 10/1): Delta 5,2 (singlet, 2H), 6,8 (singlet, 1H), 7,16 (doublet, J = 8.5 Hz, 2H), 7,35 (doublet, J = 8.5 Hz, 2H), 7,44 (doublet, J = 8,66 Hz, 2H), to $ 7.91 (doublet, J = 8,66 Hz, 2H);13C NMR (CDCl3/CD3OD, 10/1): Delta 106,42 (doublet, J = 0.03 Hz), to 121.0 (Quartet, J = 276 Hz), 125,5, 126,9, 127,3, 129,2, 130,1, 135,7, 141,5, 143,9 (Quartet, J = 37 Hz), 144, 0mm;19F NMR (CDCl3/CD3OD, 10/1): Delta -62,9. Gas chromatography-mass spectrum with electron ionisation: M+ = 401.

Example 2. 4-[5-(4-Were)-3-(trifluoromethyl)-1H-pyrazole - 1-yl]benzosulfimide

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Stage 1: Obtain 1-(4-were)-4,4,4-triptorelin-1,3 - dione

4'-Methylacetophenone (5,2 in methanol (25%). The mixture is stirred for 5 minutes and add 5.5 ml (46.2 mmol) of ethyl ether triperoxonane acid. Refluxed for 24 hours, cooling the mixture to room temperature and evaporated. Add 100 ml of 10% hydrochloric acid and the mixture extracted with ethyl acetate (4 x 75 ml). The organic extracts are combined, dried over magnesium sulfate, filtered and evaporated, receiving of 8.47 g (94%) of a brown oil, which was used in the next stage without further purification.

Stage 2: Obtain 4-[5-(4-were)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide

To dione obtained in stage 1 (4,14 g, 18.0 mmol) in 75 ml of absolute ethanol is added hydrochloride 4-sulfonamidophenylhydrazine. The reaction mixture in an argon atmosphere refluxed for 24 hours. After cooling to room temperature and filtering the reaction mixture is evaporated, getting 6,13 g solid orange color. It precrystallization from a mixture of methylene chloride/hexane and obtain 3.11 g (8.2 mmol, 46%) of product as a solid pale yellow color with so pl. 157-159oC. Elemental analysis: calculated for C17H14N3O2SF3: C, 53.54; H, 3.70, N, 11,02. Found: C, 53,17

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Stage 1: Obtain 3,5-dichloro-4-methoxyacetophenone

To a cooled solution (0oC) 7,44 g (55,8 mmol) trichloride aluminum in 25 ml of methylene chloride in the atmosphere of argon is added dropwise 2.5 ml of acetic anhydride. Stirred for 0.5 hour and added dropwise 4,18 g (23.6 mmol) of 2,6-dichloro - anisole. The reaction mixture was stirred at 0oC for 1 hour, allowed to warm to room temperature and stirred for 12 hours. Poured into a mixture of 6 ml of concentrated hydrochloric acid and 80 ml of ice water. The aqueous phase is extracted with ethyl acetate (3 x 75 ml). The organic extracts are combined, dried over magnesium sulfate, filtered and the solvent is distilled off, give crude product as yellow oil. According to NMR spectroscopy the acylation takes place exclusively in the para-position relative to the methoxy group. Crude oil is used without further purification.

Stage 2 and 3: Obtain 4-[5- (3,5-dichloro-4-methoxyphenyl)- 3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

The target connection receive similar stages 1 and 2 of Example 2 and purified on preparative plates chromatography elwira a mixture of hexane/ethyl acetate 10: 1; receive a solid yellow color. Elemental analysis: vicinay

Trichloride aluminum (4.9 g, to 36.8 mmol) are added to a solution of 2-Atalanta (2.5 g, 18.4 mmol) in methylene chloride (50 ml). Added dropwise acetylchloride (1.3 ml, 18.4 mmol) and refluxed with stirring for 0.5 hour. Cooled to room temperature, the reaction mixture is poured on crushed ice and extracted with methylene chloride. The organic layer is dried over magnesium sulfate, filtered and evaporated. The crude product chromatografic on the plates chromatotron thickness of 4000 microns, elwira a solution of 10% ethyl acetate - 90% hexane, and obtain 2.3 g of the target product.

Stage 2 and 3: Obtain 4-[5-(3-ethyl-4-methoxyphenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

The target connection receive similar stages 1 and 2 of Example 2. Elemental analysis: calculated for C19H18N3O3SF3: C, 53,64, H, AND 2.26, N, 9,88. Found: C, 53,69, H, 4,36, N 9,88.

Example 5. 4-[5-(3-Methyl-4-methylthiophenyl)-3-(trifluoromethyl)- -1H-pyrazole-1-yl]benzosulfimide

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Stage 1: Getting 2-methylthiazole

To a solution of thiocresol (1.0 g, 8.1 mmol) in 10 ml of dimethylformamide added methyl iodide (0.5 ml, 8.1 mmol) and potassium carbonate (1.1 g, 8.1 mmol). The reaction mixture was stirred at 50oC in accordance with the, obtaining 1.1 g of the target product.

Stage 2, 3 and 4: Obtain 4-[5-(3-methyl-4-methylthiophenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

The target connection receive similar stages 1, 2 and 3 of Example 4. Elemental analysis: calculated for C18H16N3O2S2F3: C, 50,58, H, OF 3.77, N 9,83. Found: C, 50,84, H, 3,62, N 9,62.

Example 6. 4-[5-(3-(3-Propenyl)-4-methoxyphenyl)-3- (trifter-methyl)-1H-pyrazole-1-yl]benzosulfimide

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Stage 1: Getting 3-allyl-4-methoxyacetophenone

To a solution of 3-allyl-4-hydroxyacetophenone (10 g, with 56.8 mmol) in 125 ml of tetrahydrofuran, add potassium hydroxide (3.2 g, with 56.8 mmol). Add excess dimethylsulfate and stirred the reaction mixture at a temperature of 50oC for 16 hours. The reaction mixture is cooled, evaporated and poured into a mixture of ethyl acetate and water. The organic layer is separated and washed with diluted sodium hydroxide solution to remove unreacted educt. An ethyl acetate solution is dried and evaporated, getting to 9.2 g C-allyl-4-methoxyacetophenone.

Stage 2 and 3: Getting 4-[5-(3-(3-propenyl)-4 - methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

The target connection receive according to the method similar>3S: C 54,92, N, 4,14, N, BEING 9.61. Found: C 54,70, H 4,12, N 9,43.

Example 7. 4-[5-(3-Propyl)-4-methoxyphenyl)-3-(trifluoromethyl) -1H-pyrazole-1-yl]benzosulfimide

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Stage 1: Obtain 3-n-propyl-4-methoxyacetophenone

To a solution of the product obtained in stage 1 of Example 6 (3 g, 17,0 mmol) in 50 ml of ethanol is added a catalytic amount of 4% palladium on coal. The reaction mixture was stirred in a Parr apparatus at room temperature under a pressure of 5 psig (34,47 kPa) for 0.5 hour. The reaction mixture is filtered and evaporated, receiving 4 grams of pure 3-propyl-4-methoxyacetophenone.

Stage 2 and 3: Obtain 4-[5-(3-n-propyl-4-methoxyphenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

The target connection receive on techniques similar to those shown in stages 1 and 2 of Example 2. Elemental analysis: calculated for C20H20N3F3O3S: C, 54,66, H, 4,59, N 9,56. Found: C, 54,84, H,4,65, N 9,52.

Example 8. 4-[5-(3-Cyclopropylmethyl)-4-methoxyphenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

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Stage 1: Getting 3-cyclopropylmethyl-4-methoxyacetophenone.

To a solution of the product obtained in stage 1 of Example 6 (3 g, 17,0 mmol), and catalytic amounts acetic all the amount of substance. The reaction mixture is filtered and chromatographic on the plates chromatotron thickness of 4000 microns, elwira a mixture of 20% ethyl acetate - 80% hexane, and obtain 2.5 g of the target ketone.

Stage 2 and 3: Obtain 4-[5-(3-cyclopropylmethyl-4-methoxy - phenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

The target connection receive on techniques similar to those shown in stages 1 and 2 of Example 2. Elemental analysis: calculated for C21H20N3F3SO3: C, 55,87, H, 4,47, N 9,31. Found: C, 55,85, H, 4,27, N 9: 30 A.m.

Example 9. 4-[4-Methyl-3-nitrophenyl)-3-(trifluoromethyl)-1H- -pyrazole-1-yl] benzosulfimide

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To a solution of the product obtained according to Example 2 (500 mg, 1,31 mmol) in 5 ml of sulfuric acid added nitric acid (0.6 ml, of 1.31 mmol) and the reaction mixture was stirred at room temperature for 0.5 hour. The mixture was poured on ice, the precipitated precipitate is filtered off and chromatographic on the plates 4000 microns, elwira a mixture of 20% ethyl acetate - 80% hexane, and obtain 410 mg of the target compound. Elemental analysis: calculated for C17H13N4O4SF3: C 47,89, H OF 3.07, N, 13,14. Found: C, 47,86, H, 2,81, N, 13,15.

Example 10. 4-[5-(3-Amino-4-were)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzolsulfonat ml, 0.7 mmol) in 10 ml of ethanol. The reaction mixture is refluxed for 15 minutes and then add the compound obtained in Example 9 (100 mg, 0.23 mmol) and the resulting reaction mixture is refluxed for 2 hours. The reaction mixture is cooled, filtered through celite and evaporated, receiving 100 mg of the target compound. Elemental analysis: calculated for C17H15N4O2SF3< / BR>
Stage 1: Obtain 4-[5-(4-bromomethylphenyl)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

The product obtained according to Example 2 (1.13 g, 3.0 mmol) and N-bromosuccinimide (0.64 g, 3.6 mmol) is dissolved in 40 ml of benzene and irradiated with a UV lamp for 3 hours. Allow the reaction mixture to cool to room temperature, poured into 50 ml water, the organic phase is separated, washed with saturated salt solution and dried over magnesium sulfate. The crude pyrazole receive in the form of oil of amber. It is cleaned by the method of radial-strip chromatography, elwira a mixture of 30% ethyl acetate - 70% hexane, and receive a 4-bromoethylene derived in the form of a yellow oil, which crystallizes upon standing.

Stage 2: Obtain 4-[5-(4-hydroxymethylene)-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

Broom within 120 hours. The reaction mixture is evaporated, the residue is dissolved in 50 ml of ethyl acetate and dried over magnesium sulfate. The crude product is obtained in the form of oil of amber. It is cleaned by the method of radial-strip chromatography, elwira a mixture of 30% ethyl acetate - 70% hexane, and obtain the target compound in a solid yellow color. Elemental analysis: calculated for C17H14N3O3SF3C, 51,38, H, 3,55, N, 10,57. Found: C, 51,28, H, 3,59, N 10,31.

Example 12. 4-[1-(4-(Aminosulfonyl)phenyl)-3-(trifluoromethyl)- 1H-pyrazole-5-yl]benzoic acid

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To the product obtained according to Example 11, in 2 ml of acetone add to 1.33 M solution of Jones reagent until then, until you see a steady orange color. The reaction mixture was poured into 20 ml of ethyl acetate and 20 ml of water and the organic layer was separated, washed with a saturated solution of sodium bisulfite and dried over magnesium sulfate. The crude product is filtered through a layer of silica gel/celite and get the target compound in a solid yellow color. The mass spectrum of the high-resolution: m/z 411,0507 (calculated for C17H12N3O4SF3: 411,0500).

The following compounds shown in Table 1, get on techniques similar to that shown in P is)- 1H-pyrazole-1-yl]benzosulfimide

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To a solution of the product obtained in Example 41 (240 mg, of 0.58 mmol) in dimethylformamide (3 ml) was added NaSMe (205 mg, 2.9 mmol) and boil the mixture under reflux for 2 hours. The mixture is cooled, poured into 0.1 N hydrochloric acid solution and extracted three times with ethyl acetate. The organic extracts are combined, dried over magnesium sulfate and evaporated. Clean evaporative chromatography, elwira a mixture of hexane/ethyl acetate (1:1), and obtain the target compound. Elemental analysis: calculated for C17H14N3O3SF3< / BR>
To a solution of the product obtained in Example 53 (431 mg, 1.0 mmol) in 10 methanol added 36 mg (0,17 mmol) hydrate chloride ruthenium (III), and then for 2 h in 1.5 ml of 30% hydrogen peroxide (14.7 mmol). Terminate the reaction by adding 25 ml of 1 M solution of sodium hydroxide in methanol, and evaporated, getting 1.24 g solid brown color. The solid is purified on a preparative plate chromatography, elwira a mixture of methanol - methylene chloride - ammonium chloride (2/97/1), and obtain 52 mg (0.14 mmol, 12%) of product as a solid yellow color.

Example 57. N-[4-[1-[4-(Aminosulfonyl)phenyl] -3- (trifluoromethyl)-1H-pyrazole-5-yl]phenyl-N-methylacetamide

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K 19 mg (0,051 mmol) protochloride methylene and stirred for 12 hours. The reaction mixture is evaporated and the residue is dissolved in 10 ml of ethyl acetate. After washing with saturated salt solution (2 x 10 ml) solution, dried over magnesium sulfate, filtered and evaporated, obtaining the target compound (18,4 mg, 74%) as a solid yellow color. The mass spectrum of the high-resolution: m/e 438,0976 (calculated for C19H17N4O3SF3: 438,0974.

Example 58. 4-[5-(4-Chlorophenyl)-3-(deformity)-1H-pyrazole - 1-yl]benzosulfimide

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Stage 1: Obtain 4,4-debtor-1-[4-(chloro)phenyl]butane - 1,3-dione

Ethyl ester DIPEROXY acid (24,82 g, 200 mmol) is placed in a three-neck round bottom flask with a capacity of 500 ml and dissolved in diethyl ether (200 ml). To mix the solution through an addition funnel over 2 minutes add 25% solution of sodium methoxide (48 ml, 210 mmol). Then in diethyl ether (50 ml) was dissolved 4'-chloroacetophenone (25,94 g, 200 mmol) and the resulting solution for 5 minutes added to the reaction mixture. Leave the mix overnight (18 h) and add 1 N hydrochloric acid (250 ml) and ether (250 ml). The organic layer is separated, washed with saturated salt solution (250 ml), dried over magnesium sulfate, filtered and evaporated in vacuum, obtaining and 46.3 g of solid W 31,96 g (69%) of Dion with so pl. 65-66,5oC.

Stage 2: Obtain 4-[5-(4-chlorophenyl)-3-deformity)-1H - pyrazole-1-yl] benzosulfimide

Dissolved in ethanol (10 ml) of the hydrochloride of 4-sulfonamidophenylhydrazine (1.45 g, 6.5 mmol, 1.3 equivalent) and 4,4-debtor - 1-[4-(chloro)phenyl]-butane-1,3-dione (of 1.16 g, 5 mmol), obtained in stage 1. The reaction mixture boiling under reflux is stirred for 20 hours. The reaction mixture cooled down to room temperature and evaporated in vacuum. The residue is dissolved in ethyl acetate, washed with water (100 ml) and saturated salt solution (100 ml), dried over magnesium sulfate, filtered and evaporated in vacuum, obtaining of 1.97 g of solid light brown color, which is recrystallized from ethanol and water and obtain 4-[5-(4-chlorophenyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide (1.6 g, 83%), so pl. 185-186oC.

Example 59. 4-[5-(3-Fluoro-4-methoxyphenyl)-3-(deformity)- 1H-pyrazole-1-yl]benzosulfimide

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Stage 1: Obtain 3'-fluoro-4'-methoxyacetophenone

Aluminium chloride (80,0 g, 0.6 mmol) and chloroform (750 ml) placed in a three-neck round bottom flask with a capacity of 2 liters, equipped with a mechanical stirrer and a bath with ice. To mix the solution is added dropwise acetylchloride (51,0 g to 0.65 mol) is ut, and then at a temperature of 5-10oC added dropwise 2-Floransa (and 62.6 g of 0.5 mol). The mixture is stirred at a temperature of 0 to 10oC for 1 hour and poured onto ice (1 l). The layers are separated and the aqueous phase is extracted with dichloromethane (2 x 250 ml). The organic extracts are combined, washed with water (2 x 150 ml), dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a volume of 300 ml. Add hexane, forming a white precipitate, which is marked by filtration and dried in air. The resulting material is recrystallized from a mixture of dichloromethane and hexane and get 77,2 g (92%) of a substance that can be used in the next stage, so pl. 92-94oC. PMR Spectrum (DMSO-d6): 7,8 (multiplet, 2H), 7,3 (triplet, 1H), 3.9 (singlet, 3H), 2,5 (singlet, 3H).

Stage 2: Obtain 4,4-debtor-1-(3-fluoro-4-methoxyphenyl) butane-1,3-dione

Ethyl ester DIPEROXY acid (4,06 g, to 32.7 mmol) was placed in an Erlenmeyer flask with a capacity of 250 ml and dissolved in methyl tert-butyl ether (50 ml). To the stirred solution was added a 25% solution of sodium methoxide (7,07 g, to 32.7 mmol), and then 3'- fluoro-4'-methoxyacetophenone (5.0 g, 29.7 mmol), obtained in stage 1. Stirred for 16 h and add 1 N hydrochloric acid (50 ml). Organi, in this fall solid brown (7.0 g, 96%) with T. pl. 70-72oC. PMR Spectrum (DMSO-d6): 8.0 (multiplet, 3H), 7,3 (triplet, 1H), 6,9 (singlet, 1H), 6.5 (triplet, 1H), 3.9 (singlet, 3H).

Stage 3: Obtain 4-[5-(3-fluoro-4-methoxyphenyl)-3- (deformity)-1H-pyrazole-1-yl]benzosulfimide

4,4-Debtor-1-(3-fluoro-4-methoxyphenyl)-butane-1,3-dione (7.0 g, 28.4 mmol), obtained in stage 2, was dissolved in ethanol (150 ml). To the stirred solution was added the hydrochloride of 4-sulfonamidophenylhydrazine (7,4 g, 33 mmol) and allowed to boil under reflux with stirring overnight (16 h). The mixture is cooled, water is added until, until you begin to fall for the crystals. The product distinguish by filtration and air-dried, obtaining the target compound in the form of solid light brown color (9,8 g, 87%) with T. pl. 159-161oC. PMR Spectrum (DMSO-d6): a 7.85 (doublet, 2H), 7,5 (multiplet, 6H), 7,3-6,9 (multiplet, 5H), 3.8 (singlet, 3H). Elemental analysis: calculated for C17H14N3SO3F3: C 51,38, H, 3,55, N 10,57. Found: C, 51,46, H, 3,52, N, 10,63.

Example 60. 4-[3-Deformity-5-(4-methoxyphenyl)-1H-pyrazole - 1-yl]benzosulfimide

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Stage 1: Getting 4,4,4-trifluoromethyl-1-(4-methoxyphenyl) butane-1,3-dione

To paramashiva is l) in diethyl ether (300 ml) in a round bottom flask with a capacity of 500 ml and add a solution of sodium methoxide in methanol (18.2 ml of a 25% aqueous solution, 79,91 mmol). The solution for half an hour becomes a dark purple color, and after 1.5 hours is formed suspension of gray. The reaction mixture is stirred for 60 hours. Add diethyl ether (300 ml) and the mixture is acidified (to pH 2) 1 N solution of hydrochloric acid. The mixture is transferred into a separating funnel and separated. The ether layer was separated, washed with water, dried over magnesium sulfate and filtered. Add hexane, which results in a precipitate 4,4,4-trifluoromethyl-1- (4-methoxyphenyl)butane-1,3-dione orange in the amount of 5.25, an Additional amount of product (3,43 g) was isolated after recrystallization from hexane one stripped off the mother liquor. Range PMR (CDCl3, 400 MHz): 15,58 (broadened singlet, 1H), 7,94 (doublet, J = 8,87 Hz, 2H), 6,98 (doublet, J = 8,87 Hz, 2H), of 6.49 (singlet, 1H), 6,00 (triplet, J = 54,55 Hz, 1H), 3,89 (singlet, 3H).

Stage 2: Obtain 4-[5-(4-methoxyphenyl)-3-deformity-1H-pyrazole-1-yl] benzosulfimide

A mixture of 4,4,4-trifluoromethyl-1-(4-methoxyphenyl)butane-1,3 - dione (2,006 g, 8,79 mmol) obtained in stage 1, and hydrochloride of 4-sulfonamidophenylhydrazine (2,065 g, 9,23 mmol) dissolved in ethanol (25 ml) and refluxed for 16 hours. Cool the mixture to room temperature, evaporated and recrystallized low brown (1,49 g, 45%) with T. pl. 133-135oC.1H NMR (CDCl3, 300 MHz): of 7.90 (doublet, J = 8,863 Hz, 2H), 7,45 (doublet, J = 8,863 Hz, 2H), 7,14 (doublet, J = 8,863 Hz, 2H), 6,88 (doublet, J = 8,863 Hz, 2H), 6,77 (triplet, J = 56,47 Hz, 1H), 6,68 (singlet, 1H), 4,96 (broadened singlet, 2H), 3,83 (singlet, 3H);19F NMR (CDCl3, 300 MHz): -112,70 (doublet, J = 57,9 Hz). Mass spectrum high resolution: (calculated for C17H15F2N3O3S: 379,0802. Found: 379,0839.

Elemental analysis: calculated for C17H15F2N3O3S: C, 53,82, H, 3,99, N, 11,08. Found: C, 53,75, H, 3,99, N, 11,04.

The following compounds shown in Table II, get on techniques similar to those shown in the Examples 58-60, using the appropriate acetophenone.

Example 82. 4-[5-(1,3-Benzodioxol-5-yl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide

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Stage 1: Obtain 1-(1,3-benzodioxol-5-yl)-4,4 - diformate-1,3-dione

Ethyl ester DIPEROXY acid (1,72 g, 11 mmol) dissolved in ether (25 ml). To the stirred solution was added a 25% solution of sodium methoxide (2.38 g, 11 mmol) and 3',4'-(methylenedioxy)acetophenone (1.64 g, 10 mmol). Stirred for 16 h and add 1 N hydrochloric acid (25 ml). The organic layer is separated and washed with water (2 x 25 ml), dried over sulfa next stage.

Stage 2: Obtain 4-[5-(1,3-benzodioxol-5-yl)-3- (deformity)-1H-pyrazole-1-yl]benzosulfimide

1-(1,3-Benzodioxol-5-yl)-4,4-diformate-1,3-dione (2.4 g, 10 mmol), obtained in stage 1, was dissolved in ethanol (100 ml). To a stirred mixture of the hydrochloride of 4-sulfonamidophenylhydrazine (2,46 g, 11 mmol) and refluxed for 16 hours. The mixture is cooled and water is added until the start of the slow allocation crystalline precipitate. Filtering emit solid light brown color (3,3 g, 84%) with T. pl. 214-218oC. PMR Spectrum (DMSO-d6): 7,86 (doublet, J = 8.7 Hz, 2H), 7,51 (doublet, J = 8.7 Hz, 2H), 7,49 (broadened singlet, 2H), 7,3-6,7 (multiplet, 5H), 6,06 (singlet, 2H). Elemental analysis: calculated for C17H13N3SO4F2: C, 51,91, H, 3,33, N, IS 10.68. Found: C, Better Than Anticipated At 51.90, H, 3,25, N, 10,65.

Example 83. 1-[4-(Aminosulfonyl)phenyl]-5-(4-chlorophenyl)- 1H-pyrazole-3-carboxylic acid

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Stage 1: obtain the methyl ester of 4-[4-(chloro)phenyl]- 2,4-dioxaborinane acid

In a three-neck round bottom flask with a capacity of 500 ml was placed dimethyl ester of oxalic acid (23,6 g, 200 mmol) and dissolved in diethyl ether (200 ml). To stir the solution using a dropping funnel for 2 minutes dobavlyaetsya ether (50 ml) and the resulting solution is added dropwise within 3 minutes, add to stir the reaction mixture. Leave the mix overnight (18 h) and then add 1 N hydrochloric acid (400 ml) and ethyl acetate (750 ml). The organic layer is separated, washed with saturated salt solution (350 ml), dried over magnesium sulfate, filtered and evaporated in vacuum, obtaining of 45.7 g of solid yellow. It is recrystallized from ethyl acetate and ISO-octane and get 23 g (48%) of Dion with so pl. 108,5-110,5oC.

Stage 2: Obtain 4-[4-(aminosulfonyl)phenyl]-5-(4 - chlorophenyl)-1H-pyrazole-3-carboxylic acid

Hydrochloride 4-sulfonamidophenylhydrazine (1.45 g, 6.5 mmol) and methyl ester of 4-[4-(chloro)phenyl] -2,4-dioxaborinane acid (1.2 g, 5 mmol) dissolved in ethanol (50 ml) and the reaction mixture is refluxed for 20 hours. Cool the mixture to room temperature, evaporated in vacuum and the residue is dissolved in ethyl acetate (200 ml), washed with water (100 ml) and saturated salt solution (100 ml), dried over magnesium sulfate, filtered and evaporated in vacuum, obtaining 1.7 g solid light brown color, which is recrystallized from a mixture of methanol and water, receiving 1.6 g (85%) solid white. It dissolved in a mixture of methanol (150 ml) and 3 N sodium hydroxide solution (75 ml) and with stirring Copacabana hydrochloric acid. The product is extracted with ethyl acetate (200 ml), the extract washed with saturated salt solution (100 ml), dried over magnesium sulfate, filtered and evaporated in vacuum, obtaining 1.4 g(74%) 4-[4-(aminosulfonyl) phenyl]-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid with so pl. 135oC (decomposition).

Example 84. Methyl ester 1-(4-aminosulphonylphenyl)-5-(3, 5-debtor-4-methoxyphenyl)-1H-pyrazole-3-carboxylic acid

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Stage 1: Obtain 3,5-debtor-4-methoxyacetophenone

To a stirred suspension of aluminium chloride (24,05 g, 180,40 mmol) in chloroform (300 ml) previously dried on a column of aluminum oxide, at a temperature of 4oC (in the bath with ice) in nitrogen atmosphere for 20 minutes add acetylchloride (11,0 ml, 152,65 mmol). The cooled mixture is stirred at a temperature of 0oC for 30 minutes and then added dropwise within 30 minutes add 2,6-differenital. Allow the mixture to warm to room temperature and left to mix overnight. Stop the reaction, slowly pouring the mixture into vigorously stirred mixture of ice water. The layers are separated and the aqueous phase is extracted with dichloromethane (2 x 50 ml). The organic extracts are combined and evaporated in vacuum, obtaining a flexible transparent liquid. It is placed in the pensii at a temperature of 45oC add methyl iodide (6 ml) and left under nitrogen to mix overnight. Add water (1 ml) and the mixture is heated for 14 hours. The reaction mixture is cooled to room temperature, diluted with water (250 ml) and extracted with diethyl ether (3 x 100 ml). The organic extract was washed with a saturated solution of sodium bicarbonate, sodium bisulfite (0,1 N solution), dried over magnesium sulfate, filtered and evaporated in a vacuum, getting a clear mobile liquid. It is subjected to distillation (30oC, 1 mm RT. Art.) and obtain 12.5 g of a transparent liquid that is a mixture of 3,5-debtor-4 - methoxyacetophenone and 3.5-debtor-4-acetoxystyrene in the ratio of 85: 15. Thus, the output is 41%. This ketone is then used without purification.

Stage 2: obtain the methyl ester 1-(4 - aminosulphonylphenyl)-5-(3,5-debtor-4-methoxyphenyl)-1H-pyrazole - 3-carboxylic acid

To a stirred solution of 3,5-debtor-4-methoxyacetophenone (6,46 g, 34,70 mmol) obtained in stage 1, and the dimethyl ester of oxalic acid (6,15 g, 52,05 mmol) in methanol (80 ml) in one step add a solution of sodium methoxide (13.4 ml of a 25% aqueous solution, 58,99 mmol) and leave the mixture was mixed overnight. The crude product is diluted chlorine is Agnes, filtered and evaporated in vacuum, obtaining the methyl ester of 4-(3,5-debtor-4-methoxyphenyl)-2,4 - dioxaborinane acid in the form of a solid crystalline substance whitish color, which is used without further purification. A mixture of ester 4-(3,5-debtor-4-methoxyphenyl)-2,4-dioxaborinane acid hydrochloride and 4-sulfonamidophenylhydrazine (7,76 g, 34,70 mmol) is dissolved in methanol and refluxed for 9 hours. Get a clear solution which is cooled to room temperature, and the formed precipitate was separated by vacuum filtration and gain of 5.45 g (37%, assuming a 3.5-debtor-4 - methoxyacetophenone) methyl ester 1-(4-aminosulphonylphenyl)-5- (3,5-debtor-4-methoxyphenyl)-1H-pyrazole-3-carboxylic acid in the form of a solid whitish with so pl. 185-190oC. 1H NMR (CDCl3/300 MHz) 7.95 is (doublet, J = 8,86 Hz, 2H), 7,49 (doublet, J = 8,86 Hz, 2H), 7,02 (singlet, 1H), 6,77 (multiplet, 2H), 4,99 (singlet, 2H), 4.04 the (singlet, 3H), 3,98 (singlet, 3H);19F NMR (CDCl3/300 MHz): -126,66. Elemental analysis: calculated for C17H13F2N3O3S: C, 51,06, H, 3,57, N, 9,92. Found: C, 51,06, H, 3,54, N 9,99.

Example 85. Methyl ester[1-(4-aminosulfonyl-phenyl)-5- (4-chlorophenyl)-1H-pyrazole-3-yl]carboxylic acid

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Stage 1: Poluchenie ml, equipped with a magnetic stirrer, is placed dimethyl ester of oxalic acid (15,27 g, 0,129 mol), 4'-chloroacetophenone (20,0 g, 0,129 mol) and dissolved in methanol (300 ml). At once add sodium methoxide (25% solution in methanol, 70 ml). The reaction mixture was stirred at room temperature for 16 hours. During this time, the reaction mixture is converted into an insoluble mass. The solid is crushed mechanically and add concentrated hydrochloric acid (70 ml), the resulting suspension is vigorously stirred at room temperature for one hour. Cool the suspension to 0oC and leave for 30 minutes. The solid is filtered off and the filter cake washed with cold water (100 ml). After drying receive the methyl ester of 4-[4-(chloro) phenyl]-2,4-dioxaborinane acid (16,94 g, 54,4%) in the form of an enol. Range PMR (CDCl3/300 MHz): 7,94 (doublet, J = 8,66 Hz, 2H), of 7.48 (doublet, J = 8,66 Hz, 2H),? 7.04 baby mortality (singlet, 1H), 3,95 (singlet, 3H), 3,48 (singlet, 1H).

Stage 2: Obtain methyl ester[1-(4-aminosulfonyl phenyl)-5-(4-chlorophenyl)-1H-pyrazole-yl]carboxylic acid

In a round bottom flask with a capacity of 100 ml, equipped with a magnetic stirrer and a tube for supplying nitrogen, was placed methyl ester 4- [4-(chloro)phenyl]-2,4-dioxaborinane acid 5.0 g, 20,78 ion mixture is refluxed for 16 hours. A precipitate. The suspension is cooled to 0oC, left for 0.5 hour, filtered off, washed with cold water and after drying in the air get to $ 7.91 g (91%) of crude product. 3.50 g of the obtained product is recrystallized from ethanol and receive 3,14 g (97%) of pure methyl ester[1-(4-aminosulfonyl phenyl)5-(4 - chlorophenyl)-1H-pyrazole-yl]carboxylic acids with so pl. 227oC. Range PMR (CDCl3/300 MHz): to $ 7.91 (doublet, J = 8,86 Hz, 2H), 7,44 (doublet, J = 8,86 Hz, 2H), 7,33 (doublet, J = 8,66 Hz, 2H), 7,14 (doublet, J = 8,66 Hz, 2H), 7,03 (singlet, 3H). Mass spectrum MH+ = 392. Elemental analysis: calculated for C17H14N3O4ClS: C, Br52.11, H, 3,60, N, Of 10.72, Cl, 9,05, S, 8,18. Found: C, 52,07, H, 3,57, N, 10,76, Cl, 9,11, S, 8,27.

Example 86. Ethyl ester[1-(4-aminosulfonyl phenyl)-5- (4-chlorophenyl)-1H-pyrazole-yl]carboxylic acid

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Methyl ester[1-(4-aminosulfonyl phenyl)-5-(4-chlorophenyl)- 1H-pyrazole-yl] carboxylic acid (Example 85) (0.10 g) was dissolved in absolute ethanol (10 ml) and add a catalytic amount of a 21% solution ethoxide sodium in ethanol. The reaction mixture, without controlling the temperature, stirred for 72 hours, and then add water (10 ml). The product is yet to crystallize, the mixture is cooled to 0oC and leave for 30 minutes. The product of the= 406. Elemental analysis: calculated for C18H16N3O4ClS: C, 53,27, H, 3,97, N, 10,35, Cl, A Total Of 8.74, S, Of 7.90. Found: C, 53,04, H, 4,00, N, 10,27, Cl, 8,69, S, 7,97.

The following compounds shown in Table III, get on techniques similar to those shown in the Examples 83-86, using the appropriate reagents.

Example 96. 4-[4-(Aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H - pyrazole-3-carboxamide

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1-[4-(Aminosulfonyl)phenyl] -5-(4-chlorophenyl)-1H-pyrazole - 3-carboxylic acid (Example 83) (1.08 g, of 2.86 mmol), hydroxybenzotriazole (0.66 g, 4.3 mmol) and the hydrochloride of 1-(3-dimethyl - aminopropyl)-3-ethylcarbodiimide (0.66 g, 3.4 mmol) dissolved in dimethylformamide (DMF) (20 ml) and stirred at room temperature for 5 minutes. To the resulting solution was added aqueous ammonia (30%, to 2.9 ml) and the reaction mixture is stirred for 18 hours. Then the resulting solution was poured into a mixture of ethyl acetate (200 ml) and 1 N hydrochloric acid (200 ml), shaken and the layers separated. The organic layer was washed with saturated sodium bicarbonate solution (150 ml) and saturated salt solution (150 ml), dried over magnesium sulfate, filtered and evaporated, obtaining 0.9 g of a solid substance of white color, which is recrystallized from ethyl acetate and ISO-on is CLASS="ptx2">

Example 97. [1-(4-Aminosulphonylphenyl)-5-(4-forfinal)- 1H-pyrazole-3-yl] carboxamide

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In a three-neck round bottom flask with a capacity of 250 ml, equipped with a thermometer, a tube for gas inlet, reflux condenser and magnetic stirrer, was placed methyl ester [1-(4-aminosulphonylphenyl)-5-(4-forfinal)-1H-pyrazole-yl] carboxylic acid (Example 88) (3.0 g, to 7.99 mmol), methanol (100 ml) and a catalytic amount of sodium cyanide. Within 16 hours, without controlling the temperature in the reaction vessel bubbled anhydrous ammonia. During this time the suspension becomes dark red color. Purge the flask with nitrogen at room temperature for 20 minutes, cooled to 0oC and leave for 30 minutes. The solid is filtered off and washed with cold water (50 ml) to give after drying of 1.87 g(65%) [1-(4-aminosulfonyl phenyl)-5-(4-forfinal)- 1H-pyrazole-yl]carboxamide in the form of a solid white color with so pl. 214-216oC.1H NMR (CDCl3/CD3OD/300 MHz): to 7.64 (doublet, J = 8,66 Hz, 2H), 7,14 (doublet, J = 8,66 Hz, 2H), 6,95 (multiplet, 2H), 6,82 is 6.67 (multiplet, 6H), 6,39 (singlet, 1H).19F NMR (CDCl3/CD3OD/282,2 MHz): -112,00 (multiplet). Mass spectrum MH+ = 361. Elemental analysis: calculated for C16H13N4O3FS: C, 53,33, H, 3,64, N, 15,55, S,pyrazole-3-yl]carboxamide

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Stage 1: obtain the methyl ester of 4-[4-forfinal]-2,4 - dioxaborinane acid

In a round bottom flask with a capacity of 1000 ml place the dimethyl ester of oxalic acid (18,80 g, strength of 0.159 mol), 4'-forceto-none (20,0 g, 0,145 mol) and dissolved in methanol (400 ml). The flask is placed in a tub with ultrasound (Bronsonic 1200) and for 25 minutes add the sodium methylate (25% solution in methanol, 70 ml). The reaction mixture was exposed to ultrasound at a temperature of 45oC for 16 hours. During this time, the reaction mixture is converted into an insoluble mass. The solid is crushed mechanically and add a solution of hydrochloric acid (1 N, 500 ml). The resulting white suspension is vigorously stirred on a magnetic stirrer at room temperature for one hour. Cool the suspension to 0oWith and leave for 30 minutes. The solid is filtered off and the filter cake washed with cold water (100 ml). After drying receive the methyl ester of 4-[4-forfinal]-2,4-diclobutrazol acid (22,91 g, 70.6 per cent) in the form of an enol.1H NMR (CDCl3/300 MHz): 8,03 (two doublet of doublets, J = 8,86 Hz, J= 8,66 Hz, J = 5,03 Hz, 2H), 7,19 (doublet of doublets, J = 8,66 Hz, J = 8,66 Hz, 2H),? 7.04 baby mortality (singlet, 1H), 3,95 (singlet, 3H);19F NMR (CDCl3/282,2 Hz): -103,9 (multiplet).

the items

In odnogolosy round bottom flask with a capacity of 500 ml, equipped with a magnetic stirrer, was placed methyl ester 4-[4-forfinal] - 2,4-diclobutrazol acid (1,00 g, 44,61 mmol) obtained in stage 1, the hydrochloride of 4-sulfonamidophenylhydrazine (10,98 g, 49,07 mmol) and methanol (200 ml). The suspension is heated and refluxed for 3 h and then cooled to room temperature. Cool the suspension to 0oC and leave for 30 minutes, filter, wash the precipitate on the filter with water (100 ml), dried and gain of 14.4 g (86%) of methyl ester 4-[1-(4 - aminosulphonylphenyl)-5-(4-forfinal)-1H-pyrazole-3-yl]carboxylic acid in the form of a solid white color.1H NMR (CDCl3/300 MHz) 7,84 (doublet, J = 8,66 Hz, 2H), was 7.36 (doublet, J = 8,66 Hz, 2H), 7,18 (two doublet of doublets, J = 8,66 Hz, J = 8,46 Hz, J = 4,85 Hz, 2H), 7,00 (doublet of doublets, J = 8,66 Hz, J = 8,46 Hz, 2H), 6,28 (singlet, 1H), 3,90 (singlet, 3H);19F NMR (CDCl3/282,2 MHz): -111,4 (multiplet). Mass spectrum MH+ = 376. Elemental analysis: calculated for C17H14N3O4FS: C, 54,40, H, 3,76, N, 11,19, S, 8,54. Found: C, 54,49, H, 3,70, N, 11,25, S, 8,50.

Stage 3: Obtain [1-(4-aminosulphonylphenyl)-5-(4 - forfinal)-1H-pyrazole-yl]carboxylic acid

In odnogolosy round bottom flask with a capacity of 500 ml, equipped with a magnetic m,0 g, 26,64 mmol), obtained in stage 2, and tetrahydrofuran (200 ml). Add aqueous sodium hydroxide solution (2,5 N, 27 ml) and water (25 ml) and the suspension is refluxed for 16 hours. During this time all solids dissolved. The reaction mixture cooled down to room temperature and add a solution of hydrochloric acid (1 N, 110 ml). The aqueous suspension is extracted with methylene chloride (2 x 200 ml), the organic extracts are combined, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuum, obtaining oil. His triturated with 300 ml of methylene chloride and obtained after filtration and drying 9.0 g(94%) [1-(4-aminosulphonylphenyl)-5- (4-forfinal)-1H-pyrazole-3-yl]carboxylic acid in the form of a solid white color with so pl. 136-142oC (decomposition).1H NMR (CDCl3/300 MHz): 7,93 (doublet, J = 8,66 Hz, 2H), 7,51 (doublet, J= 8,66 Hz, 2H), 7,31 (two doublet of doublets, J = 8,86 Hz, J= 8,66 Hz, J = a 4.83 Hz, 2H), 7,11 (doublet of doublets, J = 8,86 Hz, J = 8,66 Hz, 2H), 7,06 (singlet, 1H).19F NMR (CDCl3/282,2 MHz): -114,01 (multiplet).

Stage 4: Obtain N-(3-chlorophenyl)-[1-(4 - aminosulphonylphenyl)-5-(4-forfinal)-1H-pyrazole-3 - yl]carboxamide

In odnogolosy round bottom flask with a capacity of 100 ml, equipped with a magnetic stirrer, is placed [1-(4-aminosulfonyl is striazolo (0,206 g, 1,522 mmol), hydrochloride of 1-(3-dimethylaminopropyl)-3 - ethylcarbodiimide (0,318 g of 1.66 mmol) and N,N-dimethylformamide (30 ml). The solution was stirred at room temperature for 40 minutes and added 3-Chloroaniline (0,154 ml, 1,453 mmol). The reaction mixture was stirred at room temperature for 16 h and poured into an aqueous solution of citric acid (5%, 100 ml). The aqueous phase is extracted with ethyl acetate (2 x 60 ml), the organic extracts washed with aqueous citric acid solution (60 ml), saturated sodium bicarbonate solution (2 x 60 ml) and 50% saturated solution of sodium chloride (2 x 60 ml), dried over anhydrous magnesium sulfate, filtered and evaporated in vacuum, obtaining oil. His triturated with 20 ml of dichloromethane and get after filtration and drying of 0.43 (67%) of N-(3-chlorophenyl)-[1-(4-aminosulphonylphenyl)- 5-(4-forfinal)-1H-pyrazole-3-yl] carboxamide with so pl. 207-212oC.1H NMR (CDCl3/300 MHz): 8,90 (singlet, 1H), 7,86 (doublet, J = 8,66 Hz, 2H), 7,79 (triplet, J = 2,01 Hz, 2H), 7,46 (doublet of doublets, J = 7,05 Hz, J = a 2.01 Hz, 1H), 7,33 (doublet, J = 8,86 Hz, 2H), 7,21-7,11 (multiplet, 3H), 7,02-6,94 (multiplet, 4H).19F NMR (CDCl3/CD3OD)/282,2 MHz): -111,38 (multiplet). Mass spectrum MH+ = 470. Elemental analysis: calculated for C22H16N4O3ClFS: C, 56,11, H, 3,42, N, 11,90, Cl, For 6.81, S, 7,53. On the adikam, similar to the Examples 96-98, using the appropriate starting compound.

Example 117. 4-[3-Cyano-5-(4-forfinal)-1H-pyrazole-1 - yl]benzosulfimide

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In a dry three-neck flask with a capacity of 100 ml equipped with a reflux condenser, thermometer, dropping funnel with a knee to equalize the pressure, and magnetic stirrer, was placed anhydrous dimethylformamide (20 ml) and cooled to 0oC. for 20 seconds add chloride of oxalyl (0,530 ml, 6,105 mmol) in fact, due to exothermic reaction, the temperature increases by 5oC. the Resulting white precipitate soluble as the temperature of the mixture again reaches 0oC. Stir the mixture at 0oC for 10 minutes and with vigorous stirring for about 2 minutes, add a solution of [1-(4-aminosulfonyl phenyl)-5-(4-forfinal) -1H-pyrazole-3-yl] carboxamide (Example 97) in anhydrous dimethylformamide. Stirred for 15 minutes to terminate the reaction, add pyridine (1.0 ml, 12,21 mmol). The mixture is then poured into diluted hydrochloric acid (1 N, 100 ml) and extracted with ethyl acetate (2 x 75 ml). The organic extracts are combined and washed with 1 N hydrochloric acid (2 x 100 ml) and 50% saturated restaurology oil. It is placed in a column with silica gel, elute with a mixture of ethyl acetate and hexane (40% ethyl acetate) and after evaporation of the target fractions obtain 0.66 g (69%) of 4-[3-cyano-5-(4-forfinal)-1H-pyrazole - 1-yl] benzosulfimide in a solid white color with so pl. 184-185oC.1H NMR (CDCl3/300 MHz): 7,94 (doublet, J = 8,86 Hz, 2H), 7,44 (doublet, J = 8,68 Hz, 2H), 7.23 percent-7,07 (multiplet, 4H), 6.87 in (singlet, 1H), 4,88 (broadened singlet, 2H).19F NMR (CDCl3/282,2 MHz): -109,90 (multiplet). Mass spectrum MH+ = 343. Elemental analysis: calculated for C16H11N4O2FS: C, 56,14, H, 3,24, N, 16,37, S, 9,36. Found: C, 56,19, H, 3,16, N, 16,39, S, 9,41.

The following compounds shown in Table V, get on techniques similar to that shown in Example 117, using the appropriate starting compound.

Example 128. 4-[5-(4-Chlorophenyl)-3-(heptafluoropropyl)-1H - pyrazole-1-yl] benzosulfimide

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Stage 1: Getting 4,4,5,5,6,6,6-heptathlon-1-[4-(chloro) phenyl]hexane-1,3-dione

Ethyl ester heptacosanoic acid (5,23 g, 21.6 mmol) was placed in a round bottom flask with a capacity of 100 ml and dissolved in ether (20 ml). To the stirred solution was added a 25% solution of sodium methylate (4,85 g of 22.4 mmol) and then 4-chloracetophenone (3.04 from g to 19.7 mmol). Leave perepisivatsia, washed with saturated salt solution, dried over magnesium sulfate, filtered, evaporated in vacuo and recrystallized from ISO-octane, getting diketone in a solid white color (4,27 g, 62%) with T. pl. 27-30oC.1H NMR (CDCl3/300 MHz): 15,20 (broadened singlet, 1H), 7,89 (doublet, J = 8.7 Hz, 2H), 7,51 (doublet, J = 8.7 Hz, 2H), 6,58 (singlet, 1H).19F NMR (CDCl3/300 MHz): -80,94 (triplet), -121,01 (triplet), -127,17 (singlet). Mass spectrum, M + H = 351.

Stage 2: Obtain 4-[5-(4-chlorophenyl)-3-(heptafluoropropyl)-1H-pyrazole-1-yl]benzosulfimide

Hydrochloride 4-sulfonamidophenylhydrazine (290 mg, of 1.30 mmol) is added to a stirred solution of the diketone obtained in stage 1 (400 mg, to 1.14 mmol) in ethanol (5 ml). The reaction mixture is allowed to boil under reflux overnight (23,8 hours, the ethanol is evaporated in vacuo, the residue is dissolved in ethyl acetate, washed with water and saturated salt solution, dried over magnesium sulfate and evaporated in vacuum, obtaining a solid white color. It is passed through a column of silica gel, elwira 40% solution of ethyl acetate in hexane, and recrystallized from a mixture of ethyl acetate/isooctane, getting pyrazole in the form of a solid white color (0.24 g, 42%) with T. pl. 168-171oC.119F NMR (CDCl3/300 MHz): -80,48 (triplet), -111,54 (triplet), -127,07 (singlet).

Example 129. 4-[5-(4-Chlorophenyl)-3-(chlorodifluoromethyl)-1H - pyrazole-1-yl] benzosulfimide

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Stage 1: Obtain 4-chloro-4,4-debtor-1-[4-(chloro) phenyl]butane - 1,3-dione

Methyl ester 2-chloro-2,2-DIPEROXY acid (4,20 g, 29 mmol) was placed in a round bottom flask with a capacity of 100 ml and dissolved in ether (20 ml). To the stirred solution was added a 25% solution of sodium methylate (6,37 g, 29 mmol) and then 4'-chloroacetophenone (4,20 g of 26.5 mmol). Leave the mix on the night of 20.4 hours) at room temperature, transferred into a separating funnel, washed with 3 N hydrochloric acid (15 ml), saturated salt solution (20 ml), dried over magnesium sulfate, evaporated in vacuo and recrystallized from ISO-octane, getting diketone in a solid yellow color (of 3.78 g, 53%).1H NMR (CDCl3/300 MHz): 14,80 (broadened singlet, 1H), 7,87 (doublet, J = 8.7 Hz, 2H), 7,50 (doublet, J = 8.7 Hz, 2H), of 6.49 (singlet, 1H) so pl. 53-55oC.19F NMR (CDCl3/300 MHz): -66,03 (singlet). Mass spectrum, M+ = 267.

Stage 2: Obtain 4-[5-(4-chlorophenyl)-3-(chlorodifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide

Hydrochloride 4-sulfonamide is in ethanol (10 ml). The reaction mixture is allowed to boil under reflux overnight (of 15.75 hours, the ethanol is evaporated in vacuo, the residue is dissolved in ethyl acetate, washed with water and saturated salt solution, dried over magnesium sulfate and evaporated in vacuum, obtaining a solid white color. It is recrystallized from a mixture of ethyl acetate/ISO-octane, getting pyrazole in the form of a solid white color (0.32 g, 41%) with T. pl. 130-133oC.1H NMR (CDCl3/300 MHz): of 7.90 (doublet, J = 8,9 Hz, 2H), 7,47 (doublet, J = 8.7 Hz, 2H), 7,35 (doublet, J = 8.5 Hz, 2H), 7,19 (doublet, J = 8.7 Hz, 2H), 6,76 (singlet, 1H), 5,13 (broadened singlet, 2H).19F NMR (CDCl3/300 MHz): -48,44 (singlet). Mass spectrum, M+ = 417/419.

Example 130. 4-[3-(Dichloromethyl)-5-(3-fluoro-4-methoxyphenyl)- -1H-pyrazole-1-yl]benzosulfimide

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Stage 1: Obtain 3'-fluoro-4'-methoxyacetophenone

Aluminium chloride (80,0 g, 0.6 mol) and chloroform (750 ml) placed in a three-neck round bottom flask with a capacity of 2 liters, equipped with a mechanical stirrer and a bath with ice. To mix the solution is added dropwise acetylchloride (51,0 g to 0.65 mol), keeping the temperature in the range from 5 to 10oC. the Mixture is stirred at a temperature of 5oC for 10 minutes and then at a temperature of 5-10oC added dropwise 2-Floransa Ute and the aqueous phase extracted with dichloromethane (2 x 250 ml). The organic extracts are combined, washed with water (2 x 150 ml), dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a volume of 300 ml. Add hexane, forming a white precipitate, which is marked by filtration and dried in air. The resulting material is recrystallized from a mixture of dichloromethane and hexane and get 77,2 g (92%) of the substance crystallizes from a mixture, so pl. 92-94oC. PMR Spectrum (DMSO-d6): 7,8 (multiplet, 2H), 7,3 (triplet, J = 8.7 Hz, 1H), 3.9 (singlet, 3H), 2,5 (singlet, 3H).

Stage 2: Obtain 4,4-dichloro-1-(3-fluoro-4-methoxyphenyl) butane-1,3-dione

Methyl ether dichloracetic acid (1,57 g, 11 mmol) dissolved in ether (25 ml). To the stirred solution was added a 25% solution of sodium methylate (2.38 g, 11 mmol), and then 3'- fluoro-4'-methoxyacetophenone (1.68 g, 10 mmol), obtained in stage 1. Stirred for 16 h and add 1 N hydrochloric acid (25 ml). The organic layer was separated, washed with water (2 x 25 ml), dried over magnesium sulfate, filtered and evaporated. Received Dion used without further purification and further study.

Stage 3: Obtain 4-[3-(dichloromethyl)-5-(3-fluoro-4-methoxy - phenyl)-1H-pyrazole-1-yl]benzosulfimide

4,4-Dichloro-1-(3-FPO is th hydrochloride solution is added 4 - sulfonamidophenylhydrazine (2,46 g, 11 mmol) and refluxed with stirring for 16 hours. The mixture is cooled, water is added until, until you begin to fall for the crystals. The product distinguish filtering and get a solid light brown color (2.7 g, 63%) with T. pl. 190-193oC. PMR Spectrum (DMSO-d6): 7,84 (doublet, J = 8,4 Hz, 2H), 7,53 (singlet, 1H), of 7.48 (doublet, J = 8,4 Hz, 2H), 7,47 (broadened singlet, 2H), 7.3 to 7.0 (multiplet, 3H), 6,95 (singlet, 1H), 3,85 (singlet, 3H). Elemental analysis: calculated for C17H14N3SO3FCl2: C, 47,45; H, OR 3.28; N, 9,76. Found: C, 47,68; H, 3,42; N, 10,04.

Example 131. 4-[3-Vermeil-5-phenyl-1H-pyrazole-1-yl] benzosulfimide

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Stage 1: obtain the methyl ester of 4-phenyl-2,4-dioxaborinane acid

To a solution of dimethyl ester of oxalic acid (11,81 g, 100 mmol) in ether (200 ml) is added 24 ml of a 25% aqueous solution of sodium methylate in methanol and then a solution of acetophenone (12,02 g, 100 mmol) in ether (20 ml) and the mixture is left to mix overnight at room temperature. Poured into a mixture of 1 N hydrochloric acid and ethyl acetate, the organic layer is separated, washed with saturated salt solution, dried over magnesium sulfate, filtered and evaporated, getting to 18.4 g of crude butanoate.

Stage 2: the Floor is ucaut of butanoate, obtained in stage 1, using the methodology described in stage 2 of Example 2.

Stage 3: Obtain 4-[3-hydroxymethyl-5-phenyl-1H-pyrazole - 1-yl]benzosulfimide

To a solution of ester (4.0 g, 10.4 mmol), obtained in stage 2, in 50 ml of tetrahydrofuran, add portions of alumoweld lithium (0,592 g, 15.6 mmol) and leave the mixture overnight to boil under reflux. The reaction mixture is cooled and the reaction is interrupted by adding 1 N solution of sodium bisulfate, and extracted three times with ether. The organic extracts are combined, dried over magnesium sulfate and evaporated, obtaining 3.5 g of crude alcohol. Clean evaporative chromatography, elwira a mixture of hexane/ethyl acetate (1:1), and get the target connection.

Stage 4: Obtain 4-[3-vermeil-5-phenyl-1H-pyrazole-1 - yl] benzosulfimide

To a mixture of the alcohol obtained in stage 3 (212 mg, 0.64 mmol) in dichloromethane (4 ml) add diethylaminoacetate made (0.13 ml, 1.0 mmol). The reaction mixture was stirred at room temperature for 3 hours and poured into a mixture of water and dichloromethane. The aqueous layer was extracted with dichloromethane, the organic extracts are combined, washed with saturated salt solution and evaporated. The remainder chromatographic on silica gel (elwira is isleno for C16H14N3O2SF: C, 58,00, H, 4.26 DEATHS, N, 12,68. Found: C, 57,95, H, A 4.03, N 12,58.

The following compounds shown in Table VI, get on techniques similar to those shown in the Examples 128-131, using the appropriate substituted acetyl, acetate derivatives.

Example 137. 4-[5-(2-Pyrazinyl)-3-(deformity)-1H-pyrazole - 1-yl]benzosulfimide

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Stage 1: Obtain 4,4-debtor-1-(2-pyrazinyl)-butane-1,3 - dione

Ethyl ester DIPEROXY acid (2,23 g, 18 mmol) was placed in a round bottom flask with a capacity of 100 ml and dissolved in ether (10 ml). To the stirred solution was added a 25% solution of sodium methoxide (4.68 g, 22 mmol), and then acetylpyrazine (2.00 g, 16 mmol). After stirring for 2 hours, a precipitate in the reaction mixture was added tetrahydrofuran (10 ml). The reaction mixture is stirred for another 25,9 hour, and then added 3 N hydrochloric acid (10 ml). The organic layer is separated and washed with saturated salt solution (20 ml), dried over magnesium sulfate, evaporated in vacuum and recrystallized from a mixture of methylene chloride/ISO-octane, getting diketone in a solid brown color (2,23 g, 68%) with T. pl. 103 - 110oC.1H NMR (CDCl3/300 MHz): 14,00 (userend 6,03 (triplet, J = 54,0 Hz, 1H).19F NMR (CDCl3/300 MHz): -127,16 (doublet). Mass spectrum, M+ = 200.

Stage 2: Obtain 4-[5-(2-pyrazinyl)-3-(deformity)- 1H-pyrazole-1-yl] benzosulfimide

Hydrochloride 4-sulfonamidophenylhydrazine (0,37 g of 1.65 mmol) is added to a stirred suspension of diketone obtained in stage 1 (0,30 g, 1.50 mmol), in ethanol (10 ml). The reaction mixture is refluxed for 5.3 hours, the ethanol is evaporated in vacuo, the residue is dissolved in ethyl acetate, washed with water (20 ml) and saturated salt solution (20 ml), dried over magnesium sulfate and evaporated in vacuum, obtaining a solid brown color (0.36 g). It is recrystallized from a mixture of ethyl acetate/ISO-octane and get pyrazole in the form of a solid brown color (0.20 g, 38%) with T. pl. 191-194oC. 1H NMR (acetone-d6/300 MHz): 8,94 (doublet, J = 1.4 Hz, 1H), 8,62 (doublet, J = 2.4 Hz, 1H), charged 8.52 (doublet of doublets, J = 1.4 Hz, J = 2.4 Hz, 1H), 7,95 (doublet, J = 8.7 Hz, 2H), to 7.61 (doublet, J = 8.7 Hz, 2H), 7,30 (singlet, 1H), 7,02 (triplet, J = 54,6 Hz, 1H), 6.73 x (broadened singlet, 2H).19F NMR (acetone-d6/300 MHz): -113,67 (doublet). Mass spectrum, M+ = 351.

Example 138. 4-[5-(4-Methyl-1,3-benzodioxol-5-yl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide

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Stage 1: Obtain 4-methyl-1,3 water for 0.5 hour. Within 2 hours add 3-methylcatechol (8,89 g, 71,6 mmol) and the mixture refluxed for 1 hour. By distillation of the reaction mixture obtain the target compound in the form of a yellow oil. The mass spectrum of the high-resolution: m/e 136,0524 (calculated for C8H8O2: 136,0524).

Stage 2: Obtain 5-acetyl-4-methyl-1,3-benzodioxole (A) and 6-acetyl-4-methyl-1,3-benzodioxole (B)

13.8 g of phosphoric acid and 5 ml of acetic anhydride is heated to a temperature of 45oC up until the calcium sulfate in the drainage tube will not become liquid. Add the product obtained in stage 1, and stirred the reaction mixture at a temperature of 45oC for 4.5 hours. The reaction mixture cooled down to room temperature and add 150 ml of ice water, stopping the reaction. The aqueous phase is extracted with ethyl acetate (4 x 50 ml). The organic extracts are combined, dried over magnesium sulfate and filtered, obtaining the crude product in the form of oil red.

Oil chromatographic on silica gel, elwira a mixture of 10% ethyl acetate - 90% hexane, and get two products: A: Elemental analysis: calculated for C10H10O3: C 67,07, H, 5,66. Found: C, 67,41, H, 5,75, and B: mass spectrum, M+ = 178.

Stage 3 and 4: inania receive from A product according to the method shown in stages 1 and 2 of Example 2. Solid white color. Elemental analysis: calculated for C18H14N3O4SF3: C 50,82, H, 3,22, N, 9,88. Found: C, 50,71, H, 3,34, N, Of 9.55.

The following compounds shown in Table VII, get on techniques similar to those shown in the Examples 137-138, using the appropriate starting compound.

Example 170. 4-[5-(1-Cyclohexyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide

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4-[5-(1-Cyclohexenyl)-3-(deformity)-1H-pyrazole-1 - yl] benzosulfimide (Example 142) (0.31 g, 0.88 mmol) was dissolved in ethanol (15 ml), add 10% palladium on coal and the suspension is stirred at room temperature in hydrogen atmosphere under pressure of 36 psig (248,2 kPa) for 18,25 hour. The reaction mixture is filtered through celite and the ethanol is distilled off in vacuum, obtaining a solid white color, which is recrystallized from a mixture of methylene chloride/ISO-octane (0.31 g, 99%): so pl. 199-203oC. 1H NMR (acetone-d6/300 MHz): 8,05 (doublet, J = 8.7 Hz, 2H), 7,60 (doublet, J = 8.6 Hz, 2H), 6,69 (triplet, J = 55,0 Hz, 1H), 6,47 (singlet, 1H), 5,02 (broadened singlet, 2H), 2,67 (multiplet, 1H), 1,71-1,88 (multiplet, 5H).19F NMR (acetone-d6/300 MHz): -112,86 (doublet). 1,24 was 1.43 (m, 5H).

Example 172. 4-[5-phenyl-3-(3-hydroxypropyl)-1H-pyrazole-1 - yl] benzosulfimide

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60% dispersion of sodium hydride in mineral oil (4.0 g, 100 mmol) is washed twice with hexane (each 100 ml) and dried in a stream of nitrogen. Type e is for 1 hour add a solution of acetophenone (5.8 ml, 50 mmol) in ether (40 ml). Heat the mixture to 25oC and left to mix overnight. Cool the mixture to 0oC and terminate the reaction by adding ethanol (5 ml) and 10% aqueous solution of ammonium sulfate (100 ml).

The organic layer is separated, dried over magnesium sulfate and evaporated. The remainder chromatographic on silica gel, elwira a mixture of hexane/ethyl acetate (1: 1), and get the target ketone (3.4 g) as oil. Pyridine (of 0.34 ml, 4.2 mmol) and diketone (700 mg, 3.4 mmol) in methanol (3 ml) are added to a suspension of the hydrochloride of 4 - sulfonamidophenylhydrazine (750 mg, 3.4 mmol) in methanol (8 ml), the Mixture is left overnight to mix at a temperature of 25oC and evaporated in vacuum. The residue is dissolved in methylene chloride and washed with 1 N hydrochloric acid. The organic layer is separated, dried and evaporated. The remainder chromatographic on silica gel, elwira with ethyl acetate, and get the target pyrazole (435 mg) as a solid. Elemental analysis: calculated for C18H19N3O3S: C, 60,49, H, ARE 5.36, N, 11,75. Found: C, 60,22, H, 5,63, N, 11,54.

Example 173 4-[5-(4-Forfinal)-3-(3-hydroxypropyl)-1H - pyrazole-1-yl]benzosulfimide

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4-[5-(4-forfinal)-3-(3-hydroxypropyl)-1H-pyrazole-1 - yl] benzosulfimide get method for C18H18N3O3SF

To a solution of 4-[5-(4-forfinal)-3-(3-hydroxypropyl)-1H - pyrazole-1-yl] benzosulfimide (295 mg, 0.78 mmol) obtained in Example 173, in acetone (8 ml) was added Jones reagent. The mixture is stirred at a temperature of 25oC for 2 hours. The solution is filtered and the filtrate evaporated in vacuum. The residue is dissolved in ethyl acetate and washed with water (3 x). The organic solution is dried over magnesium sulfate and evaporated. The oil obtained is recrystallized from a mixture of ether - ethanol and get a target acid (149 mg), so pl. 180-182oC. Elemental analysis: calculated for C18H16N3O4SF: C, 55,52, H, 4,14, N, 10,79. Found: C, 55,47, H, 4,22, N, 11,50.

Example 175. 4-(3-ISO-butyl)-5-phenyl-1H-pyrazole-1-yl) benzosulfimide

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Stage 1: Obtain 2,3-epoxy-5-methyl-1-phenyl-3-hexanone

To a solution of 5-methyl-1-phenyl-1-HEXEN-3-one (2.0 g, 10.6 mmol) in 15 ml of ethanol and 5 ml of acetone is added dropwise a mixture of 30% hydrogen peroxide (2 ml) and 4 N sodium hydroxide solution (1.5 ml) and the resulting mixture was stirred at 25oC for 1-3 hours. Add water (50 ml), precipitated precipitate is filtered off and dried at 40oC in vacuum, obtaining 1.9 g of the epoxide in the form of a solid white color. Elemental analysis: calculated on the Il-5-phenyl-1H-pyrazole-1-yl) benzosulfimide

Epoxide obtained previously in stage 1 (1.26 g, 6,11 mmol), and hydrochloride of 4-sulfonamidophenylhydrazine (1,38 g of 6.17 mmol) is stirred with 20 ml of ethanol containing acetic acid (0.5 ml) and then refluxed for 3 hours, cooled and terminate the reaction by adding 50 ml of water. The aqueous layer was extracted with ethyl acetate (3 x 50 ml), the organic extracts are combined, dried over magnesium sulfate and evaporated. Clean evaporative chromatography, elwira a mixture of hexane/ethyl acetate (70:30), and obtain the target compound (0,41 g, 19%) as a solid white color. Elemental analysis: calculated for C19H21N3O2S: C, 64,20, H, 5,96, N 11,82. Found: C, 64,31, H, 6,29, N 11,73.

Example 176. Ethyl ester of 3-[1-[4-(aminosulfonyl)phenyl]-5-phenyl-1H-pyrazole-3-yl]-2-cyanopropionic acid

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Stage 1: Obtain 4-(3-formyl-5-phenyl-1H-pyrazole-1-yl) benzosulfimide

To a solution of the alcohol obtained in stage 3 of Example 131 (1.1 g, 3.3 mmol) in ethyl acetate (20 ml) is added manganese dioxide (5 g, 60 mmol) and the resulting mixture was allowed to mix overnight at room temperature. The mixture is filtered through celite and the solution evaporated, give crude aldehyde.

Stage 2: obtaining the ethyl ester of 3-is spent in stage 1 (1.2 g, 3.6 mmol) in benzene (18 ml) is added ethyl ether tsianuksusnogo acid (0,38 ml, 3.6 mmol), ammonium acetate (50 mg, 0.7 mmol) and glacial acetic acid (0.17 ml, 2.8 mmol). The solution is refluxed for 18 hours, cooled and poured into a mixture of water and ethyl acetate. The organic layer is separated, washed with saturated aqueous sodium bicarbonate, water and saturated salt solution. The organic solution is dried and evaporated. The remainder chromatographic on silica gel (elute with 40% hexane solution in ethyl acetate) and obtain the target compound (1.0 g, 66%). Elemental analysis: calculated for C21H18N4O4S: C, TO 59.82, H, 4,30, N, 13,22. Found: C, 59,70, H, 4,29, N, 13,26.

Example 177. 4-[5-(4-Chlorophenyl)-3-[[phenylmethoxy)imino] methyl]-1H-pyrazole-1-yl]benzosulfimide

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To a suspension of 220 mg (of 0.58 mmol) 4-[5-(4-chlorophenyl)-3 - formyl-1H-pyrazole-1-yl]benzosulfimide (get on stage 1 of Example 176) in dichloromethane (3 ml) is added pyridine (of 0.12 ml, 1.3 mmol) and the hydrochloride of O-benzylhydroxylamine (110 mg, of 0.68 mmol) and stirred the mixture at room temperature for 18 hours. Pour in a mixture of buffer solution with pH 7 and dichloromethane, the organic layer was separated, washed with water, dried and evaporated. Clean evaporative preliminary analysis: calculated for C23H19N4O3SCl

Stage 1: Getting 2-TRIFLUOROACETYL-1-tetralone

In odnogolosy round bottom flask with a capacity of 250 ml, equipped with a reflux condenser, a tube for nitrogen and a magnetic stirrer, was placed ethyl ester triperoxonane acid (28.4 g, 0.2 mol) and 75 ml of ether. To the resulting solution was added 48 ml of 25% solution of sodium methylate in methanol (0,21 mol). Within 5 minutes, add a solution of 1-tetralone (29,2 g, 0.2 mol) in 50 ml of ether. The reaction mixture was stirred at room temperature for 14 h and diluted with 100 ml of 3 N hydrochloric acid. The layers are separated and the organic phase is washed with 3 N hydrochloric acid, saturated salt solution, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuum. The residue is dissolved by boiling in 70 ml of an aqueous solution of ethanol, cooled to room temperature, fall at the same time the crystals of 2 - TRIFLUOROACETYL-1-tetralone, which is separated by filtration and dried, obtaining the pure product (32 g, 81%) with T. pl. 48-49oC.1H NMR (CDCl3): Delta of 2.8 (multiplet, 2H), 2,9 (multiplet, 2H), 7,2 (doublet, J = 3.0 Hz, 1H), was 7.36 (multiplet, 1H), 7,50 (multiplet, 1H), 7,98 (multiplet, 1H). 19F NMR (CDCl3): Delta -72,0. Data chromasomes[g]indazol-1-yl]benzosulfimide

In odnogolosy round bottom flask with a capacity of 100 ml equipped with a reflux condenser, a tube for nitrogen and a magnetic stirrer, was placed 2-TRIFLUOROACETYL-1-tetralone (1,21 g, 5.0 mmol) obtained in stage 1, the hydrochloride of 4-sulfonamidophenylhydrazine (1.12 g, 5.0 mmol) and 25 ml of absolute alcohol. The solution is refluxed for 15 hours and evaporated in vacuum. The residue is dissolved in ethyl acetate, washed with water, saturated salt solution, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuum. The residue is recrystallized from a mixture of ethyl acetate and ISO-octane and obtain 1.40 g 71% of pure product with so pl. 257-258oC.1H NMR (CDCl3/CD3OD), 4:1): Delta of 2.7 (multiplet, 2H), 2,9 (multiplet, 2H), 6,6 (multiplet, 1H), 6,9 (multiplet, 1H), 7,1 (multiplet, 1H), 7,16 (multiplet, 1H), 7,53 (multiplet, 2H), 7,92 (multiplet, 2H).19F NMR (CDCl3): Delta -62,5. The mass spectrum with ionization fast atom, M+H = 394.

Example 188. 4-[4,5-Dihydro-7-methyl-3-(trifluoromethyl)- 1H-benzo[g] indazol-1-yl]benzosulfimide

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Stage 1: Obtain 6-methyl-2-(TRIFLUOROACETYL)tetralone

Ethyl ester triperoxonane acid (5,33 g, 37.5 mmol) is dissolved in 50 ml of ether and treated with a solution of sodium methoxide (25% of districts and add 20 ml of 3 N hydrochloric acid. The layers are separated and the organic phase is washed with saturated salt solution, dried over magnesium sulfate and evaporated in vacuum, obtaining a brown oil (8,09 g), which is used without further purification.

Stage 2: Obtain 4-[4,5-dihydro-7-methyl-3- (trifluoromethyl)-1H-benzo[g] indazol-1-yl]benzosulfimide

Hydrochloride 4-sulfonamidophenylhydrazine (1.80 g, 8.0 mmol) is added to a stirred solution of the diketone obtained in stage 1 (1.86 g, 7,3 mmol) in ethanol (10 ml). The reaction mixture is boiled under stirring in the course of 14.8 hours. Cool the mixture and filtered. The filtrate is evaporated in vacuo, dissolved in ethyl acetate, washed with water and saturated salt solution, dried over magnesium sulfate and again evaporated in vacuum, obtaining the pyrazole in the form of a solid brown color (1.90 g, 64%) with T. pl. 215-218oC.1H NMR (acetone-d6, 300 MHz): 8,10 (doublet, 2H), 7,80 (doublet, 2H), 7,24 (singlet, 1H), 6,92 (doublet, 1H), 6,79 (broadened singlet, 2H), 6,88 (doublet, 1H), 3,02 (multiplet, 2H), 2,85 (multiplet, 2H), 2,30 (singlet, 3H).19F NMR (acetone-d6, 282 MHz): -62,46 (singlet). Mass spectrum high resolution: calculated for C19H17F3N3O2S: C, 408,0994. Found: 408,0989.

The following compounds are presented in the ethers.

Example 196. 4-[4,5-Dihydro-3-(trifter - methyl)-1H-thieno[3,2-g]indazol-1-yl]benzosulfimide

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Stage 1: Obtain 4-keto-4,5,6,7-tetrahydronaphthalene

In a round bottom flask containing acetic anhydride (30 ml) and phosphoric acid (0.6 ml), placed 4-(2-thienyl)butyric acid (28,42 g, 167 mmol) and refluxed for 3.2 hours. Pour the reaction mixture into 100 ml of water, extracted with ethyl acetate, washed with saturated salt solution, dried over magnesium sulfate and evaporated in vacuum, obtaining a brown oil (22,60 g), which is subjected to distillation in vacuo (1 mm RT.art., 107-115oC) and get a solid white color (13,08 g, 51%) with T. pl. 34-40oC. Range PMR (CDCl3, 300 MHz): 7,29 (doublet, J = 5,2 Hz, 1H), 6,99 (doublet, J = 5,2 Hz, 1H), 2,95 (triplet, J = 6.0 Hz, 2H), 2,47 (multiplet, 2H), 2.13 and (multiplet, 2H). Mass spectrum, M+H = 153.

Stage 2: Obtain 4-keto-4,5,6,7-tetrahydro-5-(TRIFLUOROACETYL) tianeptine

Ethyl ester triperoxonane acid (11,81 g, 83.1 mmol) dissolved in ether (50 ml) and treated with a solution of sodium methylate (25% solution, 18,35 g, 84,9 mmol), and then add a solution of 4-keto-4,5,6,7-tetrahydronaphthalene (12,57 g of 82.6 mmol) obtained in stage 1, in ether (25 ml). The reaction mixture was premesis is separated, washed with saturated salt solution, dried over magnesium sulfate and evaporated in vacuum, obtaining a solid brown color, which is recrystallized from a mixture of ether/hexane and get diketone (10,77 g, 52%) as needles brown, T. pl. 54-64oC.1H NMR (CDCl3, 300 MHz): 15,8 (singlet, 1H), 7,41 (doublet, J = 5,2 Hz, 1H), 7,17 (doublet, J = 5,2 Hz, 1H), 3.04 from (multiplet, 2H), 2.91 in (multiplet, 2H).19F NMR (CDCl3, 282 MHz): -70,37 (singlet). Mass spectrum, M+H = 249.

Stage 3: Obtain 4-[4,5-dihydro-3-(trifluoromethyl)-1H - thieno[3,2-g] indazol-1-yl]benzosulfimide

Hydrochloride 4-sulfonamidophenylhydrazine (2,36 g, 10.6 mmol) is added to a stirred solution of the diketone obtained in stage 2 (2.24 g, 9.0 mmol), in ethanol (20 ml). The reaction mixture is refluxed with stirring for 14.7 hours. The reaction mixture was filtered and washed with ethanol and water, getting pyrazole in the form of a solid white color (2,69 g, 75%) so pl. 288-290oC.1H NMR (acetone-d6, 300 MHz): 8,12 (doublet, J = 8.7 Hz, 2H), 7,83 (doublet, J = 8.7 Hz, 2H), 7,27 (doublet, J = 5,2 Hz, 1H), for 6.81 (broadened singlet, 2H), 6,59 (doublet, J = 5.4 Hz, 1H), 3,18 (multiplet, 2H), 3,01 (multiplet, 2H).19F NMR (acetone-d6, 282 MHz): -62,46 (singlet). The mass spectrum of high represen. 4-[5-(4-Chlorophenyl)-4-chloro-1H-pyrazole-1 - yl]benzosulfimide

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Stage 1: Obtain 3-[4-(chloro)phenyl]propane-1,3-dione

Ethyl formate (8,15 g of 0.11 mol) and 4'-chloroacetophenone (15,4 g of 0.1 mol) is stirred in 150 ml of ether at room temperature. Added dropwise a 25% solution of sodium methylate (23,77 g of 0.11 mol). The mixture is stirred at room temperature for 16 h and add 150 ml of 1 N hydrochloric acid. The layers are separated and the ether solution washed with saturated salt solution, dried over magnesium sulfate and evaporated in a vacuum, getting to 18.3 g of yellow oil. The resulting mixture was used in the next stage without further purification.

Stage 2: Obtain 4-[5-(4-chlorophenyl)-1H-pyrazole-1 - yl]benzosulfimide

3-[4-(Chloro)phenyl]propane-1,3-dione from step 1 (to 18.3 g of 0.1 mol) and the hydrochloride of 4-sulfonamidophenylhydrazine (22,4 g of 0.1 mol) dissolved in 150 ml of absolute ethanol and refluxed for 16 hours. The solution is cooled to room temperature, diluted with 100 ml of water and leave to stand, fell while the crystals of the pyrazole is separated by filtration and gain of 8.4 g (25%) solid white with so pl. 185-187oC. Range PMR (CDCl3, 300 MHz): 7,89 (doublet, J = 8.7 Hz, 2H), 7,76 (doublet, J = 1.8 Hz, 1H), 7,43 (duplicates the initial singlet, 2H). Elemental analysis: calculated for C15H12N3SO2Cl: C, 53,97, H, 3,62, N, 12,59. Found: C, 54,08, H, 3,57, N, 12,64.

Stage 3: Obtain 4-[5-(4-chlorophenyl)-4-chloro-1H-pyrazole - 1-yl]benzosulfimide

4-[5-(4-Chlorophenyl)-1H-pyrazole-1-yl]benzosulfimide from stage 2 (3.0 g, 9 mmol) is dissolved in 50 ml of acetic acid and added dropwise 9 ml of 1 M solution of chlorine in acetic acid. The mixture is stirred for 16 h and add saturated sodium bicarbonate solution until the reaction mixture on a flat piece of paper will not be neutral. The mixture is extracted with ethyl acetate (3 x 50 ml), the organic extracts are combined, washed with saturated sodium bicarbonate solution and saturated salt solution, dried over magnesium sulfate, filtered and evaporated. The resulting product is recrystallized from ISO-propanol, obtaining 2.6 g (78%) solid white with so pl. 168-171oC (decomposition). Range PMR (DMSO-d6, 300 MHz): 8,08 (singlet, 1H), 7,83 (doublet, J = 8.7 Hz, 2H), 7,55 (doublet, J = 8.7 Hz, 2H), 7,46 (broadened singlet, 2H), 7,44 (doublet, J = 8.7 Hz, 2H), 7,35 (doublet, J = 8.7 Hz, 2H). Elemental analysis: calculated for C15H11N3SO2Cl2: C, 48,93, H, 3,01, N, 11,41. Found: C, 49,01, H, 2,97, N, 11,41.

Example 198. 4-(4-Fortini is hydroxyacetophenone (2.5 g, 18.4 mmol) in 100 ml dichloromethane at a temperature of minus 78oC add triplify anhydride (10 g, of 35.4 mmol), and then 2,6-lutidine (4,1 ml of 35.4 mmol) and the mixture at a temperature of minus 78oC is stirred for 50 minutes. Pour in a mixture of methylene chloride and water, the organic layer is separated, washed with saturated salt solution, dried over sodium sulfate and evaporated, getting solid peach color. To a solution of the crude triflate in 100 ml of tetrahydrofuran, add 35 ml of 1 N solution of tetrabutylammonium in tetrahydrofuran. The mixture is refluxed for 15 minutes, cooled and poured into a mixture of ether and water. The ether layer is separated, washed with saturated salt solution, dried over sodium sulfate and evaporated. Clean evaporative chromatography on silica gel, elwira a mixture of hexane/ethyl acetate (20: 1), and get the alpha forcecon (0,852 g, 33.5 per cent).

Stage 2: Obtain 4-(4-forfinal-5-phenyl-1H-pyrazole-1-yl) benzosulfimide

A solution of 2-fortetienne (200 mg, 1,45 mmol) in 2 ml of dimethylformamide - dimethylacetal refluxed for 18 hours. The mixture is cooled and evaporated, receiving raw enaminoketone. Without further purification enaminoketone together with the hydrochloride of 4-Allardt, filtered and the filtrate is evaporated, receiving a yellow resin. Evaporative chromatography, gradient elwira a mixture of hexane/ethyl acetate 5:1 to 2:1, obtain 0.11 g of a solid substance is yellow. Recrystallized from a mixture of ether/hexane and get solid pale yellow color with so pl. 194-194,5oC. Elemental analysis: calculated for C15H12N3O2SF

In a three-neck round bottom flask with a capacity of 100 ml equipped with a reflux condenser, a tube for supplying gas and magnetic stirrer, was placed 4-[5-(4-chlorophenyl)-3-trifluoromethyl-1H - pyrazole-1-yl] benzosulfimide (Example 1) (500 mg, 1.2 mmol) and 50 ml of glacial acetic acid. The solution was stirred at room temperature and for 15 minutes pass current of chlorine gas. The solution was stirred at room temperature for 1.25 hours and diluted with 100 ml of water. Shaken out three times with ether, the ether extracts combined, washed with saturated salt solution, dried over magnesium sulfate, filtered and evaporated in vacuum, obtaining a solid which is recrystallized from a mixture of ether - petroleum ether and obtain 390 mg(75%) 4-[5-(4- chlorophenyl)-4-chloro-3-trifluoromethyl-1H-pyrazole-1 - yl]benzosulfimide with so pl. 180-182oC. PMR Spectrum (CDC singlet, 2H).

Example 200. 4-[4-Fluoro-5-phenyl-3-(trifluoromethyl)-1H - pyrazole-1-yl] benzosulfimide

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Stage 1: Getting 4,4,4-Cryptor-1-phenylbutane-1,3-dione

To a solution of 2-fortetienne (0,48 g, 3.4 mmol), obtained in stage 1 of Example 198, in 25 ml of tetrahydrofuran at a temperature of minus 78oC was added 1 N solution of bis(trimethylsilyl)amide lithium (4 ml) and the mixture is stirred at minus 78oC for 45 minutes. Add 1-(TRIFLUOROACETYL) imidazole (0,65 ml, 5.7 mmol) and the mixture is stirred at minus 78oC for 30 minutes and then 30 minutes at a temperature of 0oC. Terminate the reaction by adding 0.5 N solution of hydrochloric acid, poured into a mixture of ether and water, the ether layer is separated, washed with saturated salt solution, dried over magnesium sulfate and evaporated. After evaporation chromatography on silica gel, gradient elwira a mixture of hexane/ethyl acetate (from 10:1 to 4:1) receive a 1,3-diketone (0.34 g, 43%).

Stage 2: Obtain 4-[4-fluoro-5-phenyl-3-trifluoromethyl-1H - pyrazole-1-yl] benzosulfimide

Diketone obtained in stage 1 (0.34 g, 1,45 mmol), and hydrochloride of 4-sulfonamidophenylhydrazine (0.35 g, 1.56 mmol) in 15 ml of ethanol is refluxed for 15 hours. The mixture is cooled, filtered ethyl acetate (3:1), obtain 0.28 g of solid yellow. Recrystallized from a mixture of methylene chloride - hexane and get solid pale yellow color. Elemental analysis: calculated for C16H11N3O2SF4: C, 49,87, H, 2,88, N, 10,90. Found: C, Of 49.79, H, 2,88, N, 10,81.

Example 201. 4-[4-Methyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazole - 1-yl]benzosulfimide

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Stage 1: Obtain 2-methyl-1-phenyl-4,4,4-triptorelin-1,3 - dione

To a solution of propiophenone (965 mg, 7.2 mmol) in tetrahydrofuran (20 ml) at a temperature of minus 78oC add bis (trimethylsilyl)amide, sodium (7,9 ml of 1 M solution in tetrahydrofuran). The solution is stirred at minus 78oC for 0.5 hour and then heated for one hour to a temperature of minus 20oC. the Solution is again cooled to a temperature of minus 78oC and through the cannula add a solution of 1-(TRIFLUOROACETYL)imidazole (1.5 g, 9.1 mmol) in tetrahydrofuran (4 ml). The solution is heated to room temperature and left to mix overnight. Poured into a mixture of 1 N hydrochloric acid and ether. The organic solution is dried (over sodium sulfate) and evaporated, to give crude diketone (1.9 grams).

Stage 2: Obtain 4-[4-methyl-5-phenyl-3-(trifluoromethyl)-1H - pyrazole-1-yl]hydrochloride 4-sulfonamidophenylhydrazine (2.0 g, 9.0 mmol). The mixture is refluxed for 19 hours. Volatile matter is distilled off in vacuum and the residue is dissolved in ethyl acetate. The organic solution is washed with water and saturated salt solution, dried and evaporated. The remainder chromatographic on silica gel, elwira a mixture of hexane - ethyl acetate (2:1), and get the target pyrazole (1.52 g, 49%) with T. pl. 145-146oC. Elemental analysis: calculated for C17H14N3O2SF3: C, 53,54, H 3,70, N BR11.01. Found: C, 53,41, H 3,66, N 10,92.

Example 202. 4-[4-Ethyl-5-(3-methyl-4-methoxyphenyl)-3-(trifluoromethyl)- 1H-pyrazole-1-yl]benzosulfimide

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Stage 1: Obtain 4-methoxy-3-methylbutyrate

To a suspension of aluminium chloride (10.3 g, 77.2 mmol) in dichloromethane (40 ml) at a temperature of 0oC is added dropwise a solution of 2-methylanisole (5.0 ml, was 35.3 mmol) and butyric anhydride (5.8 ml, was 35.3 mmol). The reaction mixture was stirred at 0oC for 2 h, and then warmed to room temperature and left to mix overnight. The reaction mixture was poured into a mixture of concentrated hydrochloric acid (9 ml) and ice water (80 ml), extracted with dichloromethane and the organic layer washed with 2 N sodium hydroxide solution and saturated salt solution, dried and evaporated. Ostate).

Stage 2 and 3: Obtain 4-[4-ethyl-5-(3-methyl-4 - methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

The target compound synthesized from butyrophenones, obtained in stage 1, according to methodology described in stages 1 and 2 of Example 201, so pl. 135-136oC. Elemental analysis: calculated for C20H20N3O3SF3: C, 54,66, H, 4,59, N, 9,56. Found: C, 54,11, H Of 4.38, N 9,43.

Example 203. 4-[4-Cyclopropyl-5-phenyl-3-(trifluoromethyl)-1H - pyrazole-1-yl] benzosulfimide

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Stage 1: Getting 2-cyclopropylethanol

To a suspension of sodium cyanide (1.8 g, 37,0 mmol) in dimethyl sulfoxide (20 ml) at a temperature of 60oC is added dropwise (methyl bromide)cyclopropane (5.0 g, 37,0 mmol). Add the reagent with such speed that the reaction temperature was maintained at 60oC. after the addition was finished the reaction mixture is heated to 80oC for 15 minutes. Cooled and poured into a mixture of ether and water. The organic layer is separated and washed with 1 N hydrochloric acid and water, dried and evaporated. The residue is dissolved in ether (5 ml) and add a solution of phenylmagnesium (25 ml of 3 M solution in ether) in a mixture of ether (20 ml) and benzene (25 ml). The reaction mixture was stirred at room temperature for th phase is extracted with dichloromethane. The organic extracts are combined, dried and evaporated. The remainder chromatographic on silica gel, elwira a mixture of hexane/ethyl acetate (9: 1), and obtain the target compound (2.0 g, 34%).

Stage 2 and 3: Obtain 4-[4-cyclopropyl-5-phenyl-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

The target compound synthesized from acetophenone obtained in stage 1, according to methodology described in stages 1 and 2 of Example 201, so pl. 173-174oC. Elemental analysis: calculated for C19H16N3O2SF3: C 56,01, H 3.96 POINTS, N 10,31. Found: C, 55,85, H, 3,78, N, 10,19.

Example 204. 4-[4-Hydroxymethyl-5-phenyl-3-(trifluoromethyl) -1H-pyrazole-1-yl]benzosulfimide

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Stage 1: Obtain 4-[4-methyl bromide-5-phenyl-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

To a solution of 4-[4-methyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazole - 1-yl] benzosulfimide (500 mg, 1.3 mmol) obtained in Example 201, in a mixture of carbon tetrachloride (9 ml) and benzene (4 ml) is added N-bromosuccinimide (285 mg, 1.6 mmol). The mixture is irradiated quartz lamp for 3.5 hours, then poured into a mixture of dichloromethane and water, the organic layer is separated, dried and evaporated, obtaining the target product (412 mg, 69%).

Stage 2: Obtain 4-[4-formyl-5-phenyl-3-(trifluoromethyl)- 1H-pyrazole-1-yl]Bensalem kallidin (0,14 ml, 1.0 mmol). The solution is heated to a temperature of 120oC for 3 h and then left overnight at room temperature. Poured into a mixture of ethyl acetate and water, the organic layer is separated and washed with water, dried and evaporated. The remainder chromatographic on silica gel (hexane/ethyl acetate, 1:1) and obtain the target product (205 mg, 66%).

Stage 3: Obtain 4-[4-hydroxymethyl-5-phenyl-3- (trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide

To a solution of the aldehyde obtained in stage 2 (165 mg, 0.41 mmol), in methanol (3.5 ml) at a temperature of 0oC add sodium borohydride (16 mg, 0.41 mmol). The reaction mixture is stirred for 2.5 hours at a temperature of 0oC. Terminate the reaction by adding 1 M aqueous solution of potassium bisulfate (3 ml). The mixture is extracted with dichloromethane, the organic phase is separated, dried and evaporated. The remainder chromatographic on silica gel (hexane/ethyl acetate, 1:1) and obtain the target product (36 mg, 46%) with T. pl. 179-180oC. PMR Spectrum: Delta to $ 7.91 (multiplet, 2H), 7,53-7,40 (multiplet, 5H), 6.75 in (singlet, 2H), 4.53-in (doublet, J = 5.0 Hz, 2H), 4,30 (triplet, J = 5.0 Hz, 1H).

Example 205. 4-(4-Chloro-3-ISO-butyl-5-phenyl-1H-pyrazole-1-yl) benzosulfimide

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To a solution of pyrazole obtained in Example 175 (0.15 g, 0.42 mmol) in methylene chloride (10 mlney temperature for 2 hours, terminate the reaction by adding water, and the aqueous phase three times extracted with methylene chloride. The organic extracts are combined, dried over magnesium sulfate and evaporated, receiving the oil, which is purified chromatographically on silica gel, elwira a mixture of hexane/ethyl acetate (70:30), and get the target connection. The mass spectrum of the high-resolution m/z = 389,0970 (calculated for C19H20ClN3SO2, 389,0965).

The following compounds shown in Table X, get on techniques similar to those shown in the Examples 197-205, using the appropriate starting compound.

Example 259. 4-[4-Chloro-3-cyano-5-[4-(fluoro)phenyl] -1H - pyrazole-1-yl]-N-[(dimethylamino)methylene]benzosulfimide

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Increasing the polarity of the eluent used in the cleaning process according to Example 234, up to 60% ethyl acetate, obtained after evaporation of the corresponding fractions 4-[4-chloro-3-cyano-5-[4- (fluoro)phenyl]-1H-pyrazole-1-yl]-N-[(dimethylamino)methylene] benzosulfimide (0,485 g, 15%). The mass spectrum of high resolution (MLi +): calculated: 438.0779 found: 438,0714. Elemental analysis: calculated for C19H15N5O2FClS: C, Of 52.84, H, 3,50, N 16,22, Cl, 8,21, S, 7,42. Found: C, 52,76, H, 3,52, N, 16,12, Cl, 8,11, S, 7,35.

Example 260. 4-[4-Bromo-3-cyano-5-phenyl-1H-pyrazole-1-yl]- N-[(dimethyl is 4-bromo-3-cyano-5-phenyl-1H-pyrazole-1-yl] -N- [(dimethylamino)methylene] benzosulfimide (0,153 g, 28%). The mass spectrum of the high-resolution (M+): calculated: 457,0208 found: 457,0157. Elemental analysis: calculated for C19H16N5O2BrS: C, Of 49.79; H, 3.52, The N, 15,28, Br, 17,43, S, 6,99. Found: C, 49,85, H, 3,56, N, 15,10, Br, 17,52, S, 6,87.

Example 261. 4-[1-(4-forfinal)-3-(trifluoromethyl)-1H-pyrazole - 5-yl]benzosulfimide

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Stage 1: Obtaining N,N-bis(4-methoxybenzyl)-4-(aminosulfonyl) of acetophenone

To a solution of 4-(aminosulfonyl) acetophenone (2.0 g, 9.0 mmol) in dimethyl sulfoxide (25 ml) is added sodium hydride (450 mg, 19.0 mmol). The reaction mixture is stirred for 45 minutes, and then the cannula add a solution of 4-methoxybenzylamine (3.5 g, 19.0 mmol) in dimethyl sulfoxide (5 ml). The mixture is stirred at room temperature for 24 hours, poured into a mixture of ethyl acetate and buffer solution with pH 7. The aqueous phase is additionally extracted with ethyl acetate, the organic extracts combined, dried (over magnesium sulfate) and evaporated. The remainder chromatographic on silica gel (hexane/ethyl acetate, 2:1) and obtain the target product (815 mg, 21%).

Stage 2: Obtaining N, N-bis(4-methoxybenzyl)-4-[1-(4- forfinal)-3-trifluoromethyl-1H-pyrazole-5-yl]benzosulfimide

To 25% of the resultant solution of sodium methoxide in methanol (0.2 ml) is added ethyl ether triflorum billaut tetrahydrofuran (0.5 ml) and boil the mixture under reflux for 2 hours, and then left to mix overnight at room temperature. Poured into a mixture of ether and 1 N hydrochloric acid, the organic layer is separated, dried and evaporated, to give crude diketone (279 mg), which was diluted with absolute ethanol (2.5 ml). To the resulting suspension add pyridine (49 mg, of 0.62 mmol) and the hydrochloride of 4-forfamilies (80 mg, 0.50 mmol). The mixture is stirred at room temperature for 24 hours and evaporated in vacuum. The residue is dissolved in methylene chloride and washed with 1 N hydrochloric acid. The organic solution is dried and evaporated. The remainder chromatographic on silica gel (hexane/ethyl acetate, 3:1) and receive contains a protective group of the pyrazole (159 mg, 51%).

Stage 3: Obtain 4-[1-(4-forfinal)-3-trifluoromethyl-1H - pyrazole-5-yl] benzosulfimide

To a solution containing a protective group of the pyrazole (50 mg, 0.08 mmol) in a mixture of acetonitrile (1 ml) and water (0.3 ml) add suryamaninagar (360 mg, of 0.65 mmol). The reaction mixture was stirred at room temperature for 16 h, poured into water (15 ml) and extracted with ethyl acetate (2 x 25 ml). The organic extracts are combined, dried (over magnesium sulfate) and evaporated. The remainder chromatographic on silica gel (hexane/ethyl acetate, 2:1) and the floor is (triplet, 2H), 7,06 (singlet, 1H).

Example 262. 4-[1-(4-Methoxyphenyl)-3-(trifluoromethyl)-1H - pyrazole-5-yl]benzosulfimide

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The target connection receive similarly to the method shown in Example 261. The mass spectrum of the high-resolution m/z = 397,0702 (calculated for C17H14N3O3SF3, 397,0708).

Biological tests

The study of the swelling of the paws of rats, caused by the action of carrageenan

The study of the swelling of the paws of rats, caused by the action of carrageenan, carried out using the materials, the reagents and methods described in the publication Winter et al., Proc. Soc. Exp. Biol. Med., III, 544 (1962). Each group of rats Spraque-Dawley pick up so that the average weight of the animals was the same. For 16 h prior to the test rats cease to produce water. Rats orally administered 1 ml of the suspension of the compounds in the medium containing 0.5% methylcellulose and 0.025% surfactant, or blank media. After an hour in the soles of the feet administered as an injection of 0.1 ml of 1% solution of carrageenan in 0.9% sterile physiological saline and the volume of the paws after injection was measured using plethysmometer bias connected to the pressure sensor with digital indica is now, you have medication, compared with animals that were given a placebo, and determine the degree of suppression of edema, expressed in percent (Otterness and Bliven, Laboratory Models for Testing NSAIDS, in Non-Steroidal Anti-Inflammatory Drugs, (J. Lombardino, ed. 1985)).

The percentage of inhibition corresponds expressed in percent of the value of reduction of the volume of the paws, which is obtained in this study, compared to control animals, and the data for some compounds of the present invention are presented in Table XI.

Research analgesia in rats, caused by the action of carrageenan

The study of analgesia in rats, caused by the action of carrageenan, carried out using the same materials, the reagents and methods described in the publication Hargreaves. et al., Pain 32, 77 (1988). Rats Spraque-Dawley subjected to the same procedures as before the study of the swelling of the paws of rats, caused by the action of carrageenan. Three hours after injection of carrageenan in rats placed in a special container made of plexiglass with a transparent floor, which can accommodate a powerful lamp that is used as a source of thermal radiation. Twenty minutes start to heat stimulation of the paw, which was made by injection, or in prothiophos. Measure the time that elapses before the rat will hold out a paw. Determine the length of time between the individual movements of the paws for control animals and animals that made the injection, and determine the percentage of the amount of suppression increased pain sensitivity to test otdergivanija paws. The results obtained are presented in Table XI.

Evaluation of in vitro activity of Cox I and Cox II

Compounds of the present invention have the ability in vitro to inhibit cyclooxygenase II. Inhibitory activity of compounds of the present invention, shown in the Examples with respect to cyclooxygenase II is determined as follows.

A. Obtaining recombinant cyclooxygenase baculoviruses

Fragment 2000 base pairs, including the region encoding either cyclooxygenase I man or murinova cyclooxygenase I or cyclooxygenase II person or murinova cyclooxygenase II, clone site Bam H1 vector transfer baculovirus pVL 1393 ("Invitrogen") in order to generate vectors transfer baculovirus for Cox I and Cox II, similar to the methodology described in the publication of D. R. O'reilly et perenosa of baculovirus in insect cells SF9 (2108) along with 200 ng of linearized DNA plasmid of baculovirus method using calcium phosphate (Cm. M. D. Summers and G. E. Smith, A Manual of Methods for Baculovirus Vectors and Insect Cell Culture Procdures, Texas Agric. Exp. Station Bull. 1555 (1987).

Recombinant viruses cleaned, having three receiving treatment with plaques, and get solutions with great titer (107-108plaque-forming units) of baculovirus. To obtain on a large scale insect cells SF9 infect 10 l fermenters (0,5106per ml) with spare solutions of recombinant baculoviruses, so that the multiplier of infection of 0.1. After 72 hours the cells are centrifuged and the resulting tablet homogenized in a solution of Tris /sucrose (50 mm: 25% with pH 8.0) containing 1% 3-[(3-cholamidopropyl)dimethylammonio] -1 - propanesulfonate. Homogenized centrifuged for 30 minutes with an acceleration of 10000 x G and the resulting liquid above the sediment store before conducting research on the activity of cyclooxygenase at a temperature of minus 80oC.

b. Analysis on the activity of Cox I and Cox II

The activity of cyclooxygenase judged by the number of PE2 formed per unit time per mg protein, in this case, to determine the number of selected protoni]-1-propanesulfonate cell membrane of the insect, containing the appropriate enzyme cyclooxygenase, kept in the incubator in phosphate buffer solution based on potassium phosphate (50 mm, pH 8) containing epinephrine, phenol and hem, and additionally add arachidonic acid (10 mcm). Compounds before the addition of arachidonic acid pre-incubated in incubator together with the enzyme within 10-20 minutes. Reactions that can occur between the arachidonic acid and the enzyme is interrupted after 10 minutes of incubation at a temperature of from 37oC to room temperature by placing 40 μl of the reaction mixture in 160 μl of buffer solution used for enzyme-linked immunosorbent assay, which contains 25 μm indomethacin. The number of the resulting PE2 determined using standard methods enzyme-linked immunosorbent assay ("Cayman Chemical). The results are shown in Table XII.

The present invention also covers a class of pharmaceutical compositions containing one or more compounds of the present invention together with one or more non-toxic pharmaceutically acceptable carriers and/or diluents and/or auxiliary substances (called stessa the invention may be administered in any convenient way, preferably in the form of a pharmaceutical composition adapted for the method of appointment, in dosages that are effective for the intended treatment. The compounds and composition may, for example, be administered intravascular, intraperitoneal, subcutaneous, intramuscular injection or topically.

Pharmaceutical composition for oral destination may be, for example, in the form of a tablet, capsule, suspension or liquid. The pharmaceutical composition preferential prepared in the form of a unit dose containing a specific amount of the active ingredient. Examples of these unit doses are tablets or capsules. The active ingredients can also be administered by injection in the form of a composition in which as a suitable carrier can be used saline, dextrose or water.

The number assigned to therapeutically active compounds and dosage regimen for the treatment of painful conditions when using the compounds and/or compositions of the present invention depends on various factors, including age, weight, sex and medical condition of the patient, severity of the disease, the route and frequency of drug administration and concrete may contain the active ingredient in amounts of from about 0.1 to 2000 mg, preferably in quantities of from about 0.5 to 500 mg and most preferably in amounts of from about 1 to 100 mg Daily dosage may range from 0.01 to 100 mg/kg body weight, preferably from about 0.1 to about 50 mg/kg body weight and most preferably from about 1 to 20 mg/kg of body weight. Daily dosage may be administered in a single dose or one to four doses per day.

For therapeutic purposes, the compounds of the present invention are typically combined with one or more auxiliary compounds suitable for the specified target path. When administered compounds can be mixed with lactose, sucrose, starch powder, esters of cellulose with alkhanovym acids, alkyl esters of cellulose, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, gelatin, gum, sodium alginate, polyvinylpyrrolidone and/or polyvinyl alcohol, and then make of them a pill or capsule is an easy to use form. Such capsules or tablets may contain a composition for the controlled selection of medicines, for example they can be pmachine can be in the form of aqueous or non-aqueous isotonic sterile solutions or suspensions for injection. These solutions or suspensions can be obtained from sterile powders or granules having one or more carriers or diluents, which are already discussed above in connection with the compositions for oral purposes. The compounds can be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride and/or different buffer solutions. Other auxiliary compounds and methods of appointment of well-known and widely used in the pharmaceutical industry.

Although the present invention is described with specific ways of its implementation, the details of these embodiments of the invention should not limit the present invention.

1. Personalsafety benzosulfimide formula I

< / BR>
where R1is phenyl, which contains as a substituent in position, which may be substituted by one radical selected from a halogen atom, (C1- C10)alkyl, sulfamine group or group)

< / BR>
where R2selected from hydrogen, (C1- C10)alkyl, (C1- C6)halogenoalkane, ceanography, carboxyl group is of nalkyl, (C1- C6)alkoxycarbonyl(C2- C6)alkenyl, aminocarbonyl group, (C1- C6)aminocarbonylmethyl, (C1- C6)-N-alkylaminocarbonyl group, N-allamericanheroes group, (C3- C7)cycloalkylcarbonyl group, (C1- C6)carboxymethylaminomethyl group, (C1- C6)arelaxation(C1- C6)alkylaminocarbonyl group, (C1- C6)hydroxyalkyl;

R3selected from a hydrogen atom, (C1- C10)alkyl, halogen atom, ceanography, (C1- C6)hydroxyalkyl, (C1- C6)alkoxygroup, (C1- C6)alkylsulfonyl group and (C3- C7)cycloalkyl;

R4selected from phenyl (C2- C6)alkenyl, aryl, (C3- C7)cycloalkyl, (C3- C7)cycloalkenyl, teinila, furil, pyridyl, pyrazinyl, benzofuran, 2,3-dihydrobenzofuran, benzothiazyl, benzodioxolyl, benzodioxane, Romania or tigermania; where R4not necessarily contain as substituents in position, which may be substituted, one, two or three radicals selected from a halogen atom, (C1- C6)ancilliary, (C1boxilai group, (C1- C6)alkoxycarbonyl group, aminocarbonyl group, (C1- C6)halogenoalkane, a hydroxyl group, (C1- C6)alkoxygroup, (C1- C6)hydroxyalkyl group, (C1- C6)halogenoalkane group, sulfamine group, amino group, (C1- C6)-N-alkylamino group, (C1- C6)-N,N-dialkylamino, (C3- C7)cycloalkyl-(C1- C10)alkyl, nitro, group

< / BR>
or morpholinyl;

R5means (C1- C10)alkyl;

R7- (C1- C10)alkyl;

aryl where it occurs, represents phenyl, tetrahydronaphthyl, biphenyl or indan;

provided that R2is not a carboxyl group or stands, if R3denotes a hydrogen atom, and R4denotes phenyl; further provided that R4is not phenyl(C2- C6)alkenyl, when R2denotes a carboxyl group, aminocarbonyl group or ethoxycarbonyl group; further provided that R4is not 4-chlorophenyl, when R2denotes methyl, and R3denotes a bromine atom; further provided that R4is not unsubstituted tanila, when R2is when R1is phenyl not substituted allfamilies group; and further provided that R4is not phenyl when R2is stands and R3is bromine;

or its pharmaceutically acceptable salt.

2. Connection on p. 1, where R1denotes phenyl, which contains as a substituent in position, which may be substituted by one radical selected from fluorine atom, chlorine atom, methyl, sulfamine group

< / BR>
where R2selected from hydrogen, methyl, ethyl, isopropyl, tert-butyl, ISO-butyl, hexyl, formatie, diformate, trifloromethyl, chlormethyl, dichloromethyl, trichloromethyl, pentaborate, heptafluoropropyl, diperchlorate, dichloromethyl, deperately, deferrable, dichlorethyl, dichloropropyl, cyano group, carboxyl group, methoxycarbonyl group, ethoxycarbonyl group, isopropoxycarbonyl group, tert-butoxycarbonyl group, propoxycarbonyl group, butoxycarbonyl group, ISO-butoxycarbonyl group, phenoxycarbonyl group, acetyl, propionyl, butyryl, out-of butyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, cyanomethyl, ethoxycarbonylmethyl, aminocarbonyl enaminocarbonyl group, N-propylaminoethyl group, N-butylaminoethyl group, N-isobutyleneisoprene group, N-tert-butylaminoethyl group, N-intramyocardially group, N-phenylenecarbonyl group, cyclopentanecarbonyl group, cyclohexanecarbonyl group, carboxymethylaminomethyl group, benzyloxycarbonylamino group, hydroxypropyl, hydroxymethyl and hydroxyethyl;

R3selected from hydrogen, methyl, ethyl, ISO-propyl, tert-butyl, ISO-butyl, hexyl, fluorine atom, chlorine atom, bromine atom, ceanography, metoxygroup, methylsulfonyl group, cyclopropyl, cyclopentyl, hydroxypropyl, hydroxymethyl and hydroxyethyl;

R4choose from phenylethyl, phenyl, biphenyl, cyclohexyl, cyclopentyl, cycloheptyl, 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, 4-cyclohexenyl, 1-cyclopentenyl, 4-cyclopentenyl, benzofuran, 2,3-dihydrobenzofuran, 1,2,3,4-tetrahydronaphthyl, benzothiazyl, indanyl, Romania, tigermania, benzodioxolyl, benzodioxane, pyridyl, teinila, purile and pyrazinyl; where R4optional contains as a substituent in position, which may be substituted, one, two, or the filing, tert-butyl, ISO-butyl, hexyl, etilene, propenyl, methylsulfonyl, cyano group, carboxyl group, methoxycarbonyl group, ethoxycarbonyl group, ISO-propoxycarbonyl group, tert-butoxycarbonyl group, propoxycarbonyl group, butoxycarbonyl group, ISO-butoxycarbonyl group, phenoxycarbonyl group, aminocarbonyl group, formatie, diformate, trifloromethyl, chlormethyl, dichloromethyl, trichloromethyl, pentaborate, heptafluoropropyl, bromodifluoromethyl, diperchlorate, dichloromethyl, deperately, deferrable, dichlorethyl, dichloropropyl, hydroxyl group, metoxygroup, ethoxypropan, propoxylate, n-butoxypropyl, allfamilies group, hydroxypropyl, hydroxy-ISO-propyl, hydroxymethyl, hydroxyethyl, cryptometer, amino, N-methylaminopropyl, N-etilenovomu, N-ethyl-N-methylaminopropyl, N,N-dimethylaminopropyl, N,N-diethylaminopropyl, morpholinyl, cyclohexylmethyl, cyclopropylmethyl, cyclopentylmethyl, nitro group

< / BR>
where R7selected from methyl or ethyl;

or its pharmaceutically acceptable salt.

3. Connection on p. 2, selected from compounds and their pharmaceuticalorder)-1H-pyrazole-3-carboxylic acid,

ethyl ester 1-[4-(aminosulfonyl)phenyl]-5-(4-were)-1H-pyrazole-3-carboxylic acid,

ISO-propyl ester 1-[4-(aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid,

N-(4-were)-1-[4-(aminosulfonyl)phenyl] -5-(4-forfinal)-1H-pyrazole-3-carboxamide,

N-(3-chlorophenyl)-1-[4-(aminosulfonyl)phenyl] -5-(4-forfinal)-1H-pyrazole-3-carboxamide,

N-(3-forfinal)-1-[4-(aminosulfonyl)phenyl] -5-(4-forfinal)-1H-pyrazole-3-carboxamide,

N-(3-forfinal)-1-[4-(aminosulfonyl)phenyl] -5-(4-chlorophenyl)-1H-pyrazole-3-carboxamide,

fenilmetilovy ester of N-[[1-[4-(aminosulfonyl)phenyl] -5-(4-chlorophenyl)-1H-pyrazole-3-yl]carbonyl]glycine acid,

4-[5-(4-bromophenyl]-3-cyano-1H-pyrazole-1-yl]benzosulfimide,

4-[3-cyano-5-(4-forfinal)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl]-3-cyano-1H-pyrazole-1-yl]benzosulfimide,

4-[3-cyano-5-(4-methoxyphenyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[3-cyano-5-(4-were)-1H-pyrazole-1-yl]benzosulfimide,

4-[3-cyano-5-(4-methylthiophenyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(5-chloro-4-methoxyphenyl)-3-cyano-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(5-bromo-4-methoxyphenyl)-3-cyano-1H-pyrazole-1-yl]benzosulfimide,

4-[3-cyano-5-phenyl-1H-pyrazole-1-yl]peirsol-1-yl]benzosulfimide,

4-[4-bromo-5-(4-chlorophenyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(3,5-dichloro-4-methoxyphenyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-bromo-5-(4-were)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(4-were)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(3-chloro-4-methoxyphenyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(4-methoxyphenyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-bromo-5-(4-methoxyphenyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-cyano-5-(4-methoxyphenyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-ethyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-methyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-methoxyphenyl)-4-methyl-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-4-methyl-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-4-ethyl-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-ethyl-5-(4-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-ethyl-5-(4-methoxy-3-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-forfinal)-4-methyl-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-methyl-5-(4-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-fluoro-5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-bromo-5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(3,5-dichloro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-3-(deformity)-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[4-bromo-3-(deformity)-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-3-(deformity)-5-(4-methoxyphenyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-chloro-3-cyano-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(4-chlorophenyl)-3-cyano-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-3-cyano-5-(4-forfinal)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-bromo-3-cyano-5-(4-forfinal)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-bromo-3-cyano-5-phenyl-1H-pyrazole-1-yl] benzosulfimide, ethyl ester [1-(4-aminosulphonylphenyl)-4-bromo-5-(4-chlorophenyl)-1H-pyrazole-3-yl]carboxylic acid,

methyl ester [1-(4-aminosulphonylphenyl)-4-chloro-5-phenyl-1H-pyrazole-3-yl]carboxylic acid,

methyl ester [1-(4-aminosulphonylphenyl)-4-chloro-5-(4-chlorophenyl)-1H-erasmonova acid,

methyl ester [1-(4-aminosulphonylphenyl)-4-chloro-5-(4-forfinal)-1H-pyrazole-3-yl]carboxylic acid,

methyl ester [1-(4-aminosulphonylphenyl)-4-bromo-5-(4-forfinal)-1H-pyrazole-3-yl]carboxylic acid,

methyl ester [1-(4-aminosulphonylphenyl)-4-chloro-5-(3-chloro-4-methoxyphenyl)-1H-pyrazole-3-yl]carboxylic acid,

methyl ester [1-(4-aminosulphonylphenyl)-4-chloro-5-(3,5-dichloro-4-methoxyphenyl)-1H-pyrazole-3-yl]carboxylic acid,

methyl ester [1-(4-aminosulphonylphenyl)-5-(3-bromo-4-methoxyphenyl)-4-chloro-1H-pyrazole-3-yl]carboxylic acid,

4-[4-chloro-3-ISO-propyl-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-3-methyl-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-3-hydroxymethyl-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(4-chlorophenyl)-3-hydroxymethyl-1H-pyrazole-1-yl] benzosulfimide,

4[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-forfinal)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-cyanophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2,4-differenl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-methoxyphenyl)-3-(trifluoromethyl)-1 is>/BR>4-[5-(4-bromophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2,4-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-forfinal)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-AMINOPHENYL)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-fluoro-2-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-ethoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3,5-dimethyl-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-forfinal)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3-fluoro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chloro-3-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-ATI-yl]benzosulfimide,

4-[5-(2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methoxy-3-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-bromo-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-chloro-4-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3,4-acid)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3-chloro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-chloro-4-methoxy-5-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-ethyl-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-fluoro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methoxy-3-(3-propenyl)phenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3,5-dichloro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-chloro-4-forfinal)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3-fluoro-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-methyl-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-chloro-4-methylthiophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] be the-(4-methyl-3-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-(N-methylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-amino-4-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-methylthiophenyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-were)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-phenyl-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-methoxyphenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3-fluoro-4-methoxyphenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-fluoro-4-methoxyphenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3-chloro-4-were)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3-chloro-4-methoxyphenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chloro-3-were)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3,4-acid)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3,5-dichloro-4-methoxyphenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3,5-debtor-4-methoxyphenyl)-3-(deformity)-1H-pyrazole-1-yl]benzylphenol)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-methylsulfinylphenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3-(heptafluoropropyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(chlorodifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(pentafluoroethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-forfinal)-3-(3-hydroxypropyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3,5-dichloro-4-methoxyphenyl)-3-(3-hydroxypropyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(3-chloro-4-methoxyphenyl)-3-(chloromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3-(cyanomethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[3-(chlorodifluoromethyl)-5-(3-fluoro-4-methoxyphenyl)-1H-pyrazole-1-yl]benzosulfimide,

ethyl ester of 3-[1-(4-aminosulphonylphenyl)-5-(phenyl)-1H-pyrazole-3-yl]-2-cyano-2-methylpropanoate acid,

4-[5-(phenyl)-3-(permitil)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(5-bromo-2-thienyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(5-chloro-2-thienyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(1-cyclohexenyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(cyclohexyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(1,4-benzodioxan-6-yl)-3-(deformity)-1H-Pires 4-[5-(2-benzofuranyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(1,3-benzodioxol-5-yl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-benzofuran)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(5-bromo-2-thienyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(5-chloro-2-thienyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(5-indanyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(5-methyl-2-thienyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2,3-dihydrobenzofuran-2-yl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(1-cyclohexenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(1,2,3,4-tetrahydronaphtyl-5-yl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(2-benzothiazyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3,4-dihydro-2H-1-benzothiophen-7-yl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-methyl-1,3-benzodioxol-6-yl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-methyl-1,3-benzodioxol-5-yl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide.

4. Connection on p. 2, which is 4-[5-(4-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide or its pharmaceutically acceptable salt.

the d or its pharmaceutically acceptable salt.

6. Connection on p. 2, which is 4-[5-(3-fluoro-4-methoxyphenyl)-3-(deformity)-1H-pyrazole-1-yl] benzosulfimide or its pharmaceutically acceptable salt.

7. Personalsafety benzosulfimide formula I

< / BR>
where R1denotes phenyl, which contains the provision which may be substituted, sulfamylon group;

R2choose from a (C1- C6)halogenoalkane or (C1- C6)alkoxycarbonyl group;

R3and R4together form the fragment

< / BR>
where m = 2;

A is selected from phenyl and tanila;

R6refers to one, two or three radicals selected from (C1- C10)alkyl or (C1- C6)alkoxygroup, or its pharmaceutically acceptable salt.

8. Connection on p. 7, where R2choose from formatie, diformate, trifloromethyl, chlormethyl, dichloromethyl, trichloromethyl, pentaborate, heptafluoropropyl, diperchlorate, dichloromethyl, deperately, deferrable, dichlorethyl, dichloropropyl, methoxycarbonyl group, ethoxycarbonyl group, isopropoxycarbonyl group, tert-butoxycarbonyl group, propoxycarbonyl group, butoxycarbonyl group, ISO-Buin, two or three radicals selected from methyl, ethyl, ISO-propyl, tert-butyl, ISO-butyl, metoxygroup, ethoxypropan, propoxylate and n-butoxypropyl; or its pharmaceutically acceptable salt.

9. Connection on p. 8, selected from compounds and their pharmaceutically acceptable salts, members of the group, which includes:

4-[3-(deformity)-4,5-dihydro-7-methoxy-1H-benzo[g]indazol-1-yl]benzosulfimide,

4-[3-(deformity)-4,5-dihydro-7-methyl-1H-benzo[g] indazol-1-yl] benzosulfimide,

4-[4,5-dihydro-7-methoxy-3-(trifluoromethyl)-1H-benzo[g]indazol-1-yl]benzosulfimide,

4-[4,5-dihydro-3-(trifluoromethyl)-1H-benzo[g] indazol-1-yl] benzosulfimide,

4-[4,5-dihydro-7-methyl-3-(trifluoromethyl)-1H-benzo[g] indazol-1-yl] benzosulfimide,

methyl ester [1-(4-aminosulphonylphenyl)-4,5-dihydro-7-methoxy-1H-benzo[g]indazol-3-yl]carboxylic acid and

4-[4,5-dihydro-3-trifluoromethyl-1H-thieno[3,2, g] indazol-1-yl] benzosulfimide.

10. Pyrazolinones benzosulfimide formula I

< / BR>
where R1means phenyl containing as a substituent at the position, which may be substituted, one, two or three radicals selected from a halogen atom, or (C1- C6)alkoxygroup;

R2- (C
or its pharmaceutically acceptable salt.

11. Connection on p. 10, selected from compounds and their pharmaceutically acceptable salts, members of the group, which includes:

4-[1-(4-forfinal)-3-(trifluoromethyl)-1H-pyrazole-5-yl]benzosulfimide and

4-[1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl] benzosulfimide.

12. Personalsafety benzosulfimide formula II:

< / BR>
where R2choose from a (C1- C10)alkyl, (C1- C6)halogenoalkane, (C1- C6)alkoxycarbonyl group, ceanography, carboxyl groups, (C1- C6)zainoulline, aminocarbonyl group, (C1- C6)alkylaminocarbonyl group, (C3- C7)cycloalkylcarbonyl group, allamericanheroes group, (C1- C6)carboxymethylaminomethyl group, (C1- C6)arelaxation(C1- C10)alkylaminocarbonyl group, (C1- C6)aminocarbonylmethyl, (C1- C6)carboxyamide, (C1- C6)alkoxycarbonylmethyl and (C1- C6)hydroxyalkyl;

R3selected from a hydrogen atom, (C1- C10)and ylsulphonyl group and halogen atom;

R4selected from phenyl (C2- C10)alkenyl, aryl, (C3- C10)cycloalkyl, (C3- C10)cycloalkenyl, teinila, furil, pyrazinyl, benzofuran, 2,3-dihydrobenzofuran, benzothiazyl, benzodioxolyl, benzodioxane, Romania or tigermania; R4not necessarily contain as substituents in position, which may be substituted, one, two or three radicals selected from a halogen atom, (C1- C6)ancilliary, (C1- C6)alkylsulfonyl group, ceanography, nitro, (C1- C6)halogenoalkane, (C1- C10)alkyl, a hydroxyl group, (C2- C6)alkenyl, (C1- C6)hydroxyalkyl, carboxyl groups, (C1- C6)alkylamino, (C1- C10)dialkylamino, (C1- C6)alkoxycarbonyl group, aminocarbonyl group, (C1- C6)alkoxygroup, (C1- C6)halogenlampe, sulfamine group, amino group or morpholinyl, where aryl where it occurs, represents phenyl, tetrahydronaphthyl, indan or biphenyl;

provided that R2is not a carboxyl group or stands, if R3denotes a hydrogen atom, and R2denotes a carboxyl group, aminocarbonyl group or ethoxycarbonyl group; further provided that R4is not 4-chlorophenyl, when R2denotes methyl, and R3denotes a bromine atom; further provided that R4is not replaced by tanila, if R2denotes trifluoromethyl, and further provided that R4is not phenyl when R2is stands and R3is bromine;

or its pharmaceutically acceptable salt.

13. Connection on p. 12, selected from compounds and their pharmaceutically acceptable salts, members of the group, which includes:

4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-forfinal)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[5-(4-chlorophenyl)-3-(deformity)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-were)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[4-chloro-5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[3-(deformity)-5-(4-were)-1H-pyrazole-1-yl]benzosulfimide,

4-[3-(WPPT is sulfonamid,

4-[3-cyano-5-(4-forfinal)-1H-pyrazole-1-yl]benzosulfimide,

4-[3-(deformity)-5-(3-fluoro-4-methoxyphenyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(3-fluoro-4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide,

4-[4-chloro-5-phenyl-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-chlorophenyl)-3-(hydroxymethyl)-1H-pyrazole-1-yl]benzosulfimide,

4-[5-(4-(N, N-dimethylamino)phenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzosulfimide.

14. Pharmaceutical composition comprising a therapeutically effective amount of the compounds and a pharmaceutically acceptable carrier or diluent, with the specified connection selected from the group of compounds according to any one of paragraphs. 1 - 13.

15. The method of treatment of the patient from inflammation or associated with inflammation of the disease, wherein the patient in need of such treatment, administered the compound according to any one of paragraphs.1 - 13, per daily dose of 0.01 - 100 mg/kg body weight.

16. The method according to p. 15, wherein the daily dose is 1.0 - 20 mg/kg body weight.

17. The method according to p. 15, where the disease is associated with inflammation is arthritis.

18. The method according to p. 15, where the disease is associated with inflammation is pain.

19. Is:

30.11.93 - for all values of the radical R1except for group p. 1; for all values of the radical R2besides (C1- C10)alkyl, (C1- C10)zainoulline, (C1- C6)alkoxycarbonyl(C2- C6)alkenyl, (C3- C7)cycloalkylcarbonyl group, (C1- C6)carboxymethylaminomethyl group, (C1- C6)arelaxation(C1- C6)alkylaminocarbonyl group, p. 1 and p. 12; for all values of the radical R3besides (C1- C10)alkyl and (C3- C7)cycloalkyl, p. 1 and p. 12; for all values of the radical R4except phenyl(C2- C6)alkenyl, and for all values of the substituents of the radical R4besides (C2- C6)alkenyl, (C3- C7)cycloalkyl(C1- C10)alkyl and group p. 1; for all values of the radicals R1, R2, R3, R4, m, and R6when A is phenyl on p. 7; for all values of the radicals R1, R2, R3and R4p. 10; for all values of the radical R4except phenyl(C2- C10)alkenyl, and for all values of the substituents of the radical R4besides (C2- C6)alkenyl, p. 12; p. 14 p. 15 using the compounds according to paragraphs.1, 7, 10 and 12 with the values of Radik its pharmaceutically acceptable salts, pharmaceutical compositions and method of treatment of the patient from inflammation or associated with inflammation diseases from their use;

14.11.94 - values of the radical R1- group where R5- (C1- C10)alkyl, p. 1; the values of the radical R2- (C1- C10)alkyl, (C1- C10)cianelli, (C1- C6)alkoxycarbonyl(C2- C6)alkenyl, (C3- C7)cycloalkylcarbonyl group, (C1- C6)carboxymethylaminomethyl group, (C1- C6)arelaxation(C1- C6)alkylaminocarbonyl group, p. 1 and p. 12; the values of the radical R4- phenyl(C2- C6)alkenyl and values of the substituents of the radical R4- (C2- C6)alkenyl, (C3- C7)cycloalkyl(C1- C10)alkyl and the group-NR7-C(O)-CH3where R7- (C1- C10)alkyl, p. 1; value - thienyl p. 7; the values of the radical R4- phenyl(C2- C10)alkenyl and values of the substituents of the radical R4- (C2- C6)alkenyl p. 12; p. 14 p. 15 using the compounds according to paragraphs.1, 7 and 12 with the values of the radicals mentioned above in this section for this priority.

 

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< / BR>
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