Substituted 3-oxo-1,2,3,4-tetrahydroxinoxalines, pharmaceutical compositions (variants), methods for production and uses thereof

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to substituted 3-oxo-1,2,3,4-tetrahydroxinoxalines of general formula 1 , wherein R1 represents substituted sulfanyl or substituted sulfonyl group, containing as substituent optionally substituted C1-C4-alkyl, optionally substituted C3-C8-cycloalkyl, aryl-(C1-C4)alkyl optionally substituted in aril or alkyl group, heterocyclyl-(C1-C4)alkyl optionally substituted in heterocycle or alkyl group; R2 and R3 independently represent hydrogen, halogen, CN, NO2, optionally substituted hydroxyl, optionally substituted amino group, optionally substituted carboxylic group, optionally substituted carbamoyl group, optionally substituted arylcarbonyl group or optionally substituted heterocyclylcarbonyl group; R4 and R5 independently represent hydrogen or inert substituent. Claimed compounds are high effective kaspase-3 inhibitors and are useful in production of pharmaceutical compositions for treatment of diseases associated with excess apoptosis activation, as well as for experimental investigations of apoptosis in vivo and in vitro. Also disclosed are pharmaceutical composition in form of tablets, capsules or injections in pharmaceutically acceptable package, as well as method for production thereof and therapy method.

EFFECT: pharmaceutical composition for apoptosis treatment and investigation.

6 cl, 3 dwg, 8 ex, 1 tbl

 

This invention relates to novel 1,2,3,4-tetrahydroquinoxaline possessing physiological activity. More specifically, the present invention relates to new substituted 3-oxo-1,2,3,4-tetrahydroisoquinolinium acids, their esters and Amida possessing physiological activity.

The present invention relates also to a new chemotype substances, namely substituted 1,2,3,4-tetrahydroquinoxaline with specific physiological activity that can be used as a “molecular tools”, as well as active drug substances, selectively suppressing programmed cell death (apoptosis - Apoptosis: Pharmacological Implications and Therapeutic Opportunities. Kaufmann, S. H., Ed.; Academic Press: San Diego, 1997); and to pharmaceutical compositions containing these compounds as active substances; and to a method for treatment and prevention of the development of various diseases associated with increased activation of apoptosis. This exceptionally broad range of diseases includes, in particular, cardiovascular (e.g., acute ischemic lesion stroke, myocardial infarction); neurodegenerative, for example, Parkinson's disease and Alzheimer's disease (Ryan C., Salvesen G. Caspases and neuronal development. Biol Chem. 2003, 384(6):855-861), viral diseases (such as hepatitis C and AIDS), etc. (Cryns, V.L.; Yuan, J. The cutting edge: Caspases in apoptosis and diseae. In When Cells Die; Lockshin, R. A., Zakeri, Z., Tilly, J.L., Eds.; Wiley-Liss: New York, 1998; p.177-210).

The basis of the pharmacological effect of substituted 1,2,3,4-tetrahydroquinoxaline lies efficient suppression of apoptosis, exercisable by inhibiting cysteine protease - caspase-3, which plays a key role in the development of apoptosis.

Currently, it is quite clear that the life of multicellular organisms is based on the balance of continuous processes. Division and cell growth must be accompanied by an alternative process of removing old, damaged, mutated and other undesirable for the body cells. Managed form of programmed cell death with characteristic morphological and biochemical characteristics defined as apoptosis (Greek word corresponding to Russian "Listopad": Aro - branch, ptosis - falling) (Apoptosis: Pharmacological Implications and Therapeutic Opportunities. Kauftnann, S. H., Ed.; Academic Press: San Diego, 1997); (When Cells Die; Lockshin, R. A., Zakeri, Z., Tilly, J.L., Eds.; Wiley-Liss: New York, 1998). Today it is established that the violation of the control cell death leads to shifts of homeostasis and the development of various pathological conditions (Nicholson D.W. From bench to clinic with apoptosis-based therapeutic agents. Nature (London) 2000, 407:810-816). In the case of increased activation of apoptosis occur most serious pathology related to cardiovascular, neurodegenerative, infectious, metabolizes the m etc. diseases (V.L. Cryns; Yuan J. The cutting edge: Caspases in apoptosis and disease. In When Cells Die; Lockshin, R. A., Zakeri, Z., Tilly, J.L., Eds.; Wiley-Liss: New York, 1998; p.177-210). It has been shown that the course of AIDS and the number of severe diseases of the nervous system (Parkinson's disease, Alzheimer's disease) is characterized by increased activation of apoptosis (Hartmann A., Hunot, S., Michel P., Muriel M.-P., Vyas, S., Faucheux Century, Mouatt-Prigent, P., Turmel H., Srinivasan, A., Ruberg M., Evan G., Agid y, Hirsch E. Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in PA's disease. PNAS 2000, 97(6):2875-2880). During cerebral ischemia and stroke, a significant portion of the cells in the affected area dies it is by the mechanism of apoptosis. In relation to the cells of humans and animals apoptosis in most cases is associated with proteolytic activation cascade of caspases - family evolutionary conservative cysteine proteases that specifically break down proteins after aspartic acid residues. On the basis of structural homology caspase divided into subfamilies (a) caspase-1 (caspase 1, 4, 5), (b) caspase-2 (caspase-2), and C) caspase-3 (caspase 3, 6-10) (Nicholson, D.W.; Thornberry, N.A. Caspases: killer proteases. Trends Biochem. Sci. 1997, 22:299-306); (Nicholson D.W. Caspase structure, proteolytic substrates, and function during apoptotic cell death [Review]. Cell. Death. Diff. 1999, 6:1028-1042).

A particularly important role, in fact, defines the life prospects of cells, plays the caspase-3 (Porter, A.G.; Janicke, R.U. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999, 6:99-104).

Therefore, the search for high performance inhibi the Directors cassy-3, able to block apoptosis, is a very promising approach to the creation of fundamentally new cardioprotection (Chapman J., Magee W., Stukenbrok H., Beckius G., A. Milici, Tracey W.A novel nonpeptidic caspase-3/7 inhibitor, (S)-(+)-5-[1-(2-methoxymethylpyrrolidinyl)-sulfonyl]isatin reduces myocardial ischemic injury. Eur. J. Pharmacol. 2002, 456(1-3):59-68), neuroprotection (Scott C., Sobotka-Briner, S., Wilkins, D., Jacobs R., J. Folmer, W. Frazee, R. br, Ghanekar, S., D. Aharony Novel Small Molecule Inhibitors of Caspase-3 Block Cellular and Biochemical Features of Apoptosis. PharmacoI. Exp. Therap. 2003, 304(1):433-440), hepatic (Anselmo D., M. Katori, M. Kaldas, Hoglen N., Valentino K., Busuttil R., Kupiec-Weglinski W., Farmer, D. Apoptosis targeted therapy with the caspase inhibitor IDN-6556, ameliorates ex-vivo liver ischemia reperfusion injury. Am J Transplant 2002, 2(Suppl. 3):920) for the treatment and protection against a wide range of diseases, a key element of which is apoptosis.

Numerous studies conducted in recent years, led to the discovery of highly effective inhibitors of caspase-3 in a row peptide (Garcia-Calvo m, Peterson E., Leiting Century, Ruel R., Nicholson D., Thornberry N. Inhibition of human caspases by peptide-based and macromolecular inhibitors. J. Biol. Chem. 1998, 273:32608-32613) and coworkers peptide compounds (Karanewsky, D., Bai, X., Linton, S., Krebs J., Wu J., Pham C., Tomaselli K. Conformationally constrained inhibitors ofcaspase-1 and of the human CED-3 homologue caspase-3. Bioorg. Med. Chem. Lett. 1998, 8:2757-2762). An example of this type of compounds can be, for example, the following coworkers peptide derivatives developed by firms Idun Pharmaceuticals, Inc. (K.J. Tomaselli, Gladstone P.L., Temansky R.J. WO 0179162 October 25, 2001) and Vertex Pharmaceuticals Inc. (Golec, J., Lang, P., Diu-Hercend, A., Knegtel,R., Weber, P., Miller, K., Hercend, T., Mortimore, M., Miller, A. WO 0285899 October 31, 2002).

However, such compounds have very limited clinical use because of their poor pharmacokinetic and physicochemical properties (Scott C., Sobotka-Briner, S., Wilkins, D., Jacobs R., J. Folmer, W. Frazee, R. br, Ghanekar, S., D. Aharony Novel Small Molecule Inhibitors of Caspase-3 Block Cellular and Biochemical Features of Apoptosis. PharmacoI. Exp. Therap. 2003, 304(1):433-440). In this regard, continue to look for ones low-molecular kaspasky inhibitors. So, have been found quite effective inhibitors (IC50=5-40 PM) caspase-3 in a series of satinov, for example, (Chapman J., Magee W., Stukenbrok H., Beckius G., A. Milici, Tracey W. A novel nonpeptidic caspase-3/7 inhibitor, (S)-(+)-5-[l-(2-methoxymethylpyrrolidinyl) sulfonyl]isatin reduces myocardial ischemic injury. Eur J. Pharmacol. 2002, 456(1-3):59-68) and (Lee, D., Long, S.A., Murray, J.H. et al. Potent and selective nonpeptide inhibitors ofcaspases 3 and 7. J Med Chem 2001,44(12): 2015-2026)

However, the low selectivity of the compounds of this class stimulates further the search for inhibitors of caspase-3. So, recently discovered caspase inhibitors in a number of hintline, substances possess moderate activity and selectivity (Scott C., Sobotka-Briner, S., Wilkins, D., Jacobs R., J. Folmer, W. Frazee, R. br, Ghanekar, S., D. Aharony Novel Small Molecule Inhibitors ofCaspase-3 Block Cellular and Biochemical Features of Apoptosis. PharmacoL. Exp. Therap. 2003, 304(1:433-440).

There are various 3-oxo-1,2,3,4-tetrahydroquinoxaline, including with different types of biological activity (Riess, G.; Kleim, J.-P.; Rosner, M.; Paessens, A.; Blunck, M. Eur. Pat. EP 0655166 B1, 2003. Meichsner, C.; Riess, G.; Winkler, I. Eur. Pat. EP 0708093 B1, 2001. Billhardt, U.-M.; Rosner, M.; Riess, G.; Winkler, I.; Bender, R. Pat. EP 0509398 B1, 2001. Kleim, J.-P.; Bender, R.; Kirsch, R.; Meichsner, C.; Paessens, A. Antimicrob, Agents & Chemoter. 1995, 39(10), 2253-2257).

However, in the scientific and patent literature to date has no information about antiprotease activity of substituted 1,2,3,4-tetrahydroquinoxaline and biological activity of substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline acids, their esters and amides.

As a result of research aimed at finding new biologically active compounds, including selectively suppressing programmed cell death (apoptosis), the inventors have found that substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline are a new chemotypes ones inhibitors of caspase-3.

More specifically this invention relates to a “molecular tools” and active drug substances, selectively overwhelming programmed cell death (apoptosis); and to pharmaceutical compositions containing as active substances substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline, including new substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline is about acids and their esters and amides, and method of production thereof and method of its use for the treatment and prevention of the development of various diseases associated with increased activation of apoptosis, e.g., acute ischemic lesions (e.g., stroke, myocardial infarction), neurodegenerative (e.g., Parkinson's disease and Alzheimer's disease), viral diseases (such as hepatitis C and AIDS), etc. This invention relates to new substituted 3-oxo-1,2,3,4-tetrahydroisoquinolinium acids, their esters and Amida.

Below are definitions of terms used in the description of this invention:

“Combinatorial library” means a collection of compounds obtained by parallel synthesis, designed to search for a leader or optimize the biological activity of lead compounds, with each compound of the library meets the General scaffold and the library is a collection of related homologues or analogues.

“Focused library” means a combinatorial library, or a combination of several combinatorial library, or a set of libraries and substances that are organized in a special way, to increase the probability of finding hits and leaders, or to improve the efficiency of their optimization. The design of focused libraries, typically associated with directional search effectively the Directors (inhibitors, activators, agonists, antagonists, etc.) certain biological targets (enzymes, receptors, ion channels, and so on).

“Lead compound” means a compound with outstanding activity related to a particular disease.

“Scaffold” means the General structural formula or molecular skeleton or invariant connections area common to all compounds included in the combinatorial library.

“Gametip” means a series of compounds having a common structural formula, and with a certain common property, for example, some form of physiological activity. We can say, for example, "new gametip activators of potassium channels", or "known gametip kinase inhibitors", etc. As a rule, the presence of common structural fragment of compounds within one chemotype is a necessary and sufficient condition for the existence of common properties.

“Deputy” means a chemical moiety that is attached to scaffold or semi-synthesis in the process of their synthesis. As the Deputy may serve as a halogen atom, a hydroxyl group, carboxialkilnuyu group, carboxyl group, carnemolla group or inert Deputy.

“Inert Deputy” ("Non-interfering substituent"means low or directionspanel radical including, but not limited to the 1-C7alkyl, C2-C7alkenyl,2-C7quinil, C1-C7alkoxy, C7-C12aralkyl, substituted aralkyl,7-C12geterotsiklicheskikh, substituted geterotsiklicheskikh,7-C12alkaryl,3-C10cycloalkyl,3-C10cycloalkenyl, phenyl, substituted phenyl, toluyl, xylenyl, biphenyl,2-C12alkoxyalkyl,2-C10alkylsulfonyl,2-C10alkylsulfonyl, (CH2)m-O-(C1-C7alkyl), -(CH2)m-N(C1-C7alkyl)n, aryl, substituted aryl, substituted alkoxy, foralkyl, aryloxyalkyl, heterocyclyl, substituted heterocyclyl and nitroalkyl; where m and n have a value from 1 to 7. Preferred inert substituents are C1-C7alkyl, C2-C7alkenyl,2-C7quinil, C1-C7alkoxy, C7-C12aralkyl,7-C12alkaryl,3-C10cycloalkyl,3-C10cycloalkenyl, phenyl, substituted phenyl, (CH2)m-O-(C1-C7alkyl), -(CH2)m-N(C1-C7alkyl)n, aryl, substituted aryl, heterocyclyl and substituted heterocyclyl.

“Substituted group, substituted radical or scaffold” means a group, the radical or scaffold, which had the tsya Deputy, including, but not limited to inert Deputy, a halogen atom, a nitro-group, a cyano, alphagroup, hydroxyl group, amino group, carboxialkilnuyu group, carboxyl group, karbamoilnuyu group. For example, substituted alkyl means alkyl with one or more substituents, for example, hydroxyalkyl or methoxycarbonylethyl, aminoethoxyethanol, dimethylaminoethyl, 2-hydroxy-2-methoxycarbonyl-ethyl and others; substituted amino group means an amino group which has one or two substituent, for example, alluminare, N,N-dialkylamino, N-acyl-N-aryl-amino group, acetyl-methoxycarbonylmethylene group and others; substituted phenyl means phenyl, which has one or more substituents, such as 2-ethoxycarbonylphenyl, 4-amino-3-ethoxycarbonylphenyl, 3,4-diaminophenyl and other

“Optionally substituted group optionally substituted radical or scaffold” means a group, the radical or scaffold, including groups, radicals or scaffold with deputies and without deputies. For example, the concept of optional substituted amino group includes an unsubstituted amino group and amino group containing any, not inconsistent with chemistry substituents, including, but not limited to alluminare, N,N-dialkylamino, N-acyl-N-killingray, asilmetta is dicarbonitrile group and others

“Aryl” means one or more aromatic cycles, each of which includes 5 or 6 carbon atoms. “Aryl” may be condensed political, such as naphthalene or unfused, such as biphenyl. “Substituted aryl” has one or more “not interfering” deputies.

“Halogen” means fluorine atom, chlorine, bromine or iodine.

“Heterocycle” means one or more saturated or aromatic cycles with 5, 6 or 7 atoms, at least one of which is a heteroatom. Preferred heteroatoms are sulfur, oxygen and nitrogen. “Heterocycle” may be condensed political, such as benzimidazole, benzoxazole. benzthiazole, quinoline or unfused, for example, as bipyridyl.

“Azaheterocycle” means a Heterocycle comprising at least one nitrogen atom, such as benzimidazole, benzoxazole, benzthiazole, quinoline.

“Substituted heterocycle” means a heterocycle having one or more “not interfering” deputies.

“Parallel synthesis” means a method for chemical synthesis of combinatorial libraries of individual connections.

The aim of the present invention is to provide a new chemotype biologically active compounds selectively inhibit programmed cell death (apoptosis).

This goal is achieved physiologically active substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline General formula 1

in which:

R1is substituted sulfonyloxy group or substituted sulfonyloxy group containing as substituents optionally substituted C1-4alkyl, optionally substituted C3-8cycloalkyl, optionally substituted in the aryl and/or alkyl fragment arils1-4alkyl, optionally substituted in the heterocyclic and/or alkyl fragment heterocyclic1-4alkyl, optionally substituted aryl, optionally substituted heterocyclyl;

R2and R3independently from each other represent a hydrogen atom, halogen, CN, NO2, optionally substituted by a hydroxy-group or optionally substituted by an amino group, optionally substituted carboxyl group, optionally substituted carbamoyl, optionally substituted aryloxyalkyl group or optionally substituted geterotsiklicheskikh group;

R4and R5independently from each other represent: a hydrogen atom or an inert Deputy; having the properties of inhibitors of caspase-3 to obtain pharmaceutical compositions and experimental (in vitro, in vivo) studies processes apoptosis as pharmacological tools.

The aim of the present invention is also creating a new pharmaceutical compositions in the form of tablets, capsules or injections placed in pharmaceutically acceptable packing.

This goal is achieved by a pharmaceutical composition having properties of inhibitors of caspase-3 in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing, containing as active substance pharmaceutically effective amount of substituted 3-oxo-1,2,3,4-tetrahydroquinoxalin General formula 1.

The aim of the present invention is also creating a new pharmaceutical composition for treating and preventing various diseases of warm-blooded animals and humans associated with increased activation of apoptosis in the form of tablets, capsules or injections placed in pharmaceutically acceptable packing.

This goal is achieved by a pharmaceutical composition for treating and preventing various diseases of warm-blooded animals and humans associated with increased activation of apoptosis in the form of tablets, capsules or injections placed in pharmaceutically acceptable packing, containing as active substance pharmaceutically effective amount of 3-oxo-1,2,3,4-tetrahydroquinoxalin General formula 1.

The aim of the present invention I have provided is also a method of obtaining a new pharmaceutical compositions.

This goal is achieved by a method of obtaining a pharmaceutical composition having properties of inhibitors of caspase-3, by mixing the active substance with an inert filler, diluent and/or solvent, the distinctive feature of which is that as the active substance used pharmaceutically effective amount of 3-oxo-1,2,3,4-tetrahydroquinoxalin General formula 1.

The aim of the present invention is also a method of treating and preventing various diseases of warm-blooded animals and humans associated with increased activation of apoptosis.

This goal is achieved by introducing a warm-blooded animal or human pharmaceutical compositions containing as active substance pharmaceutically effective amount of 3-oxo-1,2,3,4-tetrahydroquinoxalin General formula 1.

The aim of the present invention is the creation of new biologically active 3-oxo,2,3,4-tetrahydroquinoxaline.

This goal is achieved substituted 3-oxo-1,2,3,4-tetrahydroisoquinolinium acids, their esters or inorganic salts of General formula 2

in which:

R1, R2, R4and R5have the above for compounds of General formula 1 value, and R6is not necessarily Thames is nnow the hydroxy-group, optionally substituted amino, optionally substituted, aryloxy or optional substituted heterocyclyl.

The scheme for synthesis of 3-oxo-1,2,3,4-tetrahydroquinoxaline General formula 1 and 2 are presented below and based on known reactions.

To obtain 3-oxo-1,2,3,4-tetrahydroquinoxalin General formula 1 and 2 can be used also published method (Riess, G.; Kleim, J.-P.; Rosner, M.; Paessens, A.; Blunck, M. Eur. Pat. EP 0655166 B1, 2003. Meichsner, C.; Riess, G.; Winkler, I. Eur. Pat. EP 0708093 Bl, 2001. Billhardt, U.-M.; Rosner, M.; Riess, G.; Winkler, I.; Bender, R. Pat. EP 0509398 Bl, 2001. Kleim, J.-P.; Bender, R.; Kirsch, R.; Meichsner, C.; Paessens, A. Antimicrob, Agents & Chemoter. 1995, 39(10), 2253-2257).

Used as source reagents are commercially available. Below the invention is described using specific examples of the preparation of specific compounds and combinatorial libraries. The structure of the obtained compounds was confirmed by the data of chemical, chromatographic and spectral analysis. Liquid-phase parallel synthesis of new compounds and combinatorial libraries was carried out using a special synths "CombiSyn-012-3000" [Mbaru, Aevidence, Patent of Russia 2180609, 2002; PCT WO 02/087740 A1, 2002.] and equipment [Technology Platform. In Custom Chemistry; Chemical Diversity Labs, Inc.; San Diego, CA, 2002; p.5.].

Biological (antiproteaznaya) activity of the compounds was determined on the serine protease (Ref the Aza 3), which are involved in the regulation of programmed cell death (apoptosis). The activity of Caspase 3 was determined by the rate of cleavage of the peptide substrate containing fluorescent molecule, (methylcoumarin) in accordance with the Protocol described in Technical Bulletin company Sigma-Aldrich [www.sigmaaldrich.com/sigma/bulletin/casp3fbul.pdf].

The invention is illustrated by, but is not limited to the following examples. All solvents and reagents were obtained from commercial sources, such as ACROS (Acros) (Belgium), Sigma-Aldrich (Sigma-Aldrich) (United States), Lancaster (Lancaster) (UK) and Chemdiv (ChemDiv) (USA). The melting point (TPL) were obtained on the instrument company Buchi (Buchi) (Switzerland) model-520.1H and13The NMR spectra were obtained on a spectrometer Gemini-300 (300 and 75 MHz, respectively) firm Varian (Varian) (USA) in CDCl3or dimethyl sulfoxide-d6. Chemical shifts are given in a scale of 6 (ppm). The internal standard tetramethylsilane was.

The content of the basic substance was controlled by HPLC on the device Shimadzu (Shimadzu) 10-AV (column Luna C18, Phenomenex, 25 cm 4.6 mm, UV detection at 215 and 254 nm) and LC-MS (VGH-MS) instrument Applied Biosystems (Shimadzu 10-AV LC, automatic sample Gilson-215, mass spectrometer API EH, UV (215 and 254 nm) and ELS detectors, column Luna C18, Phenomenex, 5 cm (2 mm).

Analytical TLC was performed on silica gel on aluminum plates Silufol UV254 (5 cm (15cm) (Kavalier, Czech Republic) or on glass slides with a 0.25-mm layer of silica gel 60 F254(Merck, Germany). Visualization was accomplished with UV light at a wavelength of 254 nm. For chromatographic purification of used silica gel 5-40 μm (Chemapol, Czech Republic) and 63 μm (EM Science, USA). In accordance with these LC/MS all the synthesized compounds had a basic substance content above 95% (unless otherwise specified).

Examples 1.

A common way to obtain 1,2,3,4-tetrahydroquinoxaline General formula 1 and 2.

A. General method of obtaining 2-amino-3-sulfonylamino acids 5. In a 2 l flask equipped with a magnetic stirrer and reflux condenser, load 1 mol of D,L-cysteine 3,1,1 mol of the appropriate alkylating reagent 4, 2.2 mol of NaOH and 500 ml of water. The reaction mixture is heated at 80-90°and With constant stirring 2-12 hours the Reaction mass is gradually cooled with stirring 10°and acidified with 2% hydrochloric acid to pH 5. The resulting product was separated, washed 5 times with 100 ml of water and dried. Get acid 5, which is used for further synthesis without additional purification. The yield of 85-95%.

B. General method of obtaining 2-(2-nitroaniline)-3-sulfanilamidnyh acids 7. In a 2 l flask equipped with a magnetic stirrer and reflux condenser, load 1 mol of the corresponding 2-halo-nitrobenzene 6, to 1.1 mol of the corresponding 2-amino-3-sulfonylamino the acid 5, 2 mol of NaOH and 500 ml of water. The reaction mixture is heated at 80-90°and With constant stirring 8-14 hours the Reaction mass is gradually cooled with stirring 10°and acidified with 10% hydrochloric acid to pH 3-4. The resulting product was separated, washed 5 times with 100 ml of water and dried. Get acid 7, which is used for further synthesis without additional purification. The yield of 70-90%.

Example 2. A common method of obtaining 2-sulfanilyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.1. Dissolve 1 mol of 2-(2-nitroaniline)-3-sulfonylamino acid 7 in 500 ml of aqueous ammonia in a 4 l flask. To the resulting solution was added portions 4 mol dithionite sodium at 50-60°C. the Reaction mass is heated with stirring to boiling and boiled for 1 h, the Reaction mass is then cooled to room temperature and carefully acidified with 6 N hydrochloric acid. The resulting mass, containing according to LC MS 2(-2-aminophenylamino)-3-sulfonylamino acid 8, incubated 4 h with stirring and 60-70°C. And then cooled to room temperature. The precipitate is filtered and washed on the filter until neutral wash water by Congo Red. The product is dried to constant weight. Get 1.1 with the release of 60-85%, including:

2-(2-Methyl-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1{1}:1H-NMR (DMSO-d6) 2.35 (s, 3H, CH3-Ar); 2.85 (s, 2H, --CH2-CH); 3.88 (t, 2H, S-CH2-Ar); 4.38 (ws, 1H, -CH-NH); 5.31 (ws, 1H, -NH-CH-); 6.99 (d, 1H, Ar); 7.27-7.64 (m, 6H, Ar); 11.36 (s, 1H, -NH-CO); 13.42 (ws, 1H, -COOH).

2-(2-Chloro-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {2}:1H-NMR (DMSO-d6) 2.94 (s, 2H, -S-CH2-CH); 3.88 (t, 2H, S-CH2-Ar);

4.42 (ws, 1H, -CH-NH); 5.35 (ws, 1H, -NH-CH-); 7.21 (d, 1H, Ar); 7.27-7.99 (m, 6H, Ar);

11.38 (s, 1H, -NH-CO); 12.66 (ws, 1H, -COOH).

2-(3-Fluoro-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1{3}:1H-NMR (DMSO-d6) 2.78 (s, 2H, -S-CH2-CH); 3.22 (t, 2H, S-CH2-Ar); 4.09 (ws, 1H, -CH-NH); 6.44 (s, 1H, -CH-NH); 6.71 (d, 1H, Ar); 6.85-7.88 (m, 6H, Ar); 11.40 (s, 1H, -NH-CO); 13.84 (ws, 1H, -COOH).

2-(2-Fluoro-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {4}:1H-NMR (DMSO-d6) 2.76 (s, 2H, -S-CH2-CH); 3.99 (t, 2H, S-CH2-Ar); 4.27 (ws, 1H, -CH-NH); 5.99 (s, 1H, -CH-NH); 6.71 (d, 1H, Ar); 6.66-7.08 (m, 3H, Ar); 7.29-8.08 (m, 3H, Ar); 10.94 (s, 1H, -NH-CO); 13.84 (ws, 1H, -COOH).

2-(3-Bromo-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1{5}: Mol. weight 497,29, LC MS m/z 408 (M+1).

2-(2,5-Dimethyl-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1{6}:1H-NMR (DMSO-d6) 2.12 (s, 3H, CH3-Ar); 2.65 (s, 3H, CH3-Ar); 2.85 (s, 2H, -S-CH2-CH); 3.67 (t, 2H, S-CH2-Ar); 4.21 (ws, 1H, -CH-NH); 5.12 (ws, 1H, -NH-CH-); 6.85 (d, 1H, Ar); 7.17-7.75 (m, 5H, Ar); 10.24 (s, 1H, -NH-CO); 12.42 (ws, 1H, -COOH).

2-(2-Chloro-4-fluoro-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {7}:1H-NMR (DMSO-d6) H-NMR 5 2.78 (s, 2H, -S-CH2-CH); 3.60 (t, 2H, S-CH2-Ar); 4.59 (ws, 1H, -CH-NH); 5.92 (ws, 1H, -NH-CH-); 6.64 (d, 1H, Ar); 7.45-802 (m, 5H, Ar); 11.39 (s, 1H, -NH-CO); 13.35 (ws, 1H, -COOH).

2-(4-Fluoro-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {8}

2-(2-Chloro-6-fluoro-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1{9}

2-(4-Methyl-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {10}

2-(4-Chloro-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {11}

2-(3-Chloro-benzylsulfamide)-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {12}

2-Methylsulfonylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1{13}

2-([1,3]Dioxolane-2-elmersolver)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {14}

3-Oxo-2-(pyridine-3-elmersolver)-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {15}

3-Oxo-2-(pyridine-2-elmersolver)-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {16}

2-(Octahydrophenanthrene-1-elmersolver)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {17}

2-(5-Methoxycarbonyl-thiophene-2-elmersolver)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1{18}

2-(dmntn-1-elmersolver)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.1 {19}.

6-Methyl-2-methylsulfonylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxalin 1.1 {20}: Mol. weight 222,31, LC MS m/z 223 (M+1).

8-Photo the-2-methylsulfonylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxalin 1.1{21}: Mol. weight 226,27, LC MS m/z 227 (M+1).

7-Acetylamino-2-methylsulfonylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxalin 1.1{22}: Mol. weight 265,34, LC MS m/z 266 (M+1).

2-Benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin 1.1{23}: Mol. weight 284,38, LC MS m/z 285 (M+1).

2-Benzylsulfamide-7-trifluoromethyl-3-oxo-1,2,3,4-tetrahydroquinoxalin 1.1{23}: Mol. weight 358,38, LC MS m/z 359 (M+1).

Example 3. A common method of obtaining 2-sulfanilyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.2.

In a three-neck 1 l flask, equipped with reflux condenser, thermometer and addition funnel, place of 0.1 mol of the appropriate 2-sulfanilyl-3-oxo-1,2,3,4-tetrahydroquinoxalin 1.1 and 300 ml of glacial acetic acid. To the resulting solution was added dropwise 2.5 mol 20% aqueous hydrogen peroxide for 1 h, maintaining the temperature of the reaction mass 70-80°With intensive cooling).

The reaction mass is boiled for 4 hours, then slowly cooled with stirring to 15°C. the Precipitate is filtered off, washed five times with 60 ml portions of cold water and then three times with 100 ml portions of cold ethanol. The precipitate is dried over pjatiokisi phosphorus to constant weight, get 1.2 out 70-80%, including:

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.2{7}3.38 (m, 1H, CH-CH2-SO2); 3.71 (d, 1H, CH-CH2-SO2, J=6.8 Hz); 4.43-4.62 (m, 3H, Alk); 6.29 (ws, 1H, -NH-CH-); 6.78-8.65 (m, 7H, Ar); 10.58 (ws, 1H, -NH-CO); 13.55 (ws, 1H,-COOH).

2-(2-Fluoro-benzylmaleimide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.2{2}

3-Oxo-2-n-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.2{3}2.26 (s, 3H, CH3-Ar); 3.21 (m, 1H, CH-CH2-SO2); 3.64 (d, 1H, CH-CH2-SO2, J=7.3 Hz); 4.26-4.44 (m, 3H, Alk); 6.00 (ws, 1H, -NH-CH-); 6.62 (d, 1H, Ar); 7.15-7.55 (m, 6N, AG); 10.12 (ws, 1H, -NH-CO); 12.44 (ws, 1H, -COOH).

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.2{4}

2-(3-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.2(5}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.2{6}

2-(3-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.2{7}

2-(2,5-Dimethyl-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.2{8}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.2{9}3.92 (m, 1H, CH-CH2-SO2);4.04 (d, 1H, CH-CH2-SO2, J=6.5 Hz); 4.55-4.71 (m, 3H, Alk); 6.02 (ws, 1H, -NH-CH-); 6.62-8.31 (t, 6N, AG); 10.29 (ws, 1H, -NH-CO); 13.65 (ws, 1H, -COOH).

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.2{10}2.28 (s, 3H, CH3-Ar); 3.25 (t, 1H, CH-CH2-SO2); 3.34 (d, 1H, CH-CH2-SO2, J=7.1 Hz); 4.00-4.13 (t, 3H, Alk); 6.32 (ws, 1H, -NH-CH-); 6.44 (d, 1H, Ar); 7.01-7.48 (t, 6N, AG); 11.07 (ws, 1H, -NH-CO); 13.14 (ws, 1H, -COOH).

2-(4-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.{11}3.36 (t, 1H, CH-CH2-SO2); 3.85 (d, 1H, CH-CH2-SO2, J=7.1 Hz); 4.48-4.65 (m, 3H, Alk); 6.12 (ws, 1H, -NH-CH-); 6.68 (d, 1H, Ar); 7.18-7.62 (m, 6H, Ar); 11.26 (ws, 1H, -NH-CO); 13.32 (ws, 1H, -COOH).

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 1.2{12}2.31 (s, 3H, CH3-Ar); 3.16 (m, 1H, CH-CH2-SO2); 3.28 (d, 1H, CH-CH2-SO2, J=7.3 Hz); 4.11-4.19 (m, 3H, Alk); 6.40 (ws. 1H, -NH-CH-); 6.58 (d, 1H, Ar); 7.12-7.51 (m, 6H, Ar); 10.96 (ws, 1H, -NH-CO); 14.00 (ws, 1H, -COOH).

2-Benzylmalonate-3-oxo-1,2,3,4-tetrahydroquinoxalin 1.2{13}: Mol. weight 316,38, LC MS m/z 317 (M+1).

2-Benzylmalonate-7-trifluoromethyl-3-oxo-1,2,3,4-tetrahydroquinoxalin 1.2{14}Saying. weight 384,38, LC MS m/z 385 (M+1).

Example 4. General method for the synthesis of substituted amides of 3-oxo-1,2,3,4-tetrahydroquinoxalin-7-carboxylic acid 2. Dissolve 300 mmol of the appropriate acid 1.1, 1.2 or 1.3 and 305 mmol carbonyl diimidazole, 100 ml of anhydrous dimethylformamide incubated 10 min at room temperature, and then 3 h the resulting solution was maintained at 80-90°C. the resulting solution was diluted with 500 ml of anhydrous dimethylformamide, and then distribute 120 reactors combinatorial synthesizer (5 ml reactor, approximately 3 mmol imidazoline acid). In each reactor was added 3.2 mmol of the corresponding primary or secondary amine in 3 ml of anhydrous dimethylformamide. Reaction to withstand the weight 8 h under stirring at 75-80°With, then add in each reactor of 50 ml of cold water. The precipitates are then filtered and Perekrest lizovyvatj from a mixture of ethanol-dimethylformamide. Get amides of 2 with a yield of 60-80%, including:

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid propylamide 2.1{1}:1H-NMR (DMSO-d6) 0.91 (t, 3H, CH3-CH2); 1.52 (q, 2H, CH3-CH2-); 2.29 (s, 3H, CH3-Ar); 2.78 (s, 2H, -S-CH2-CH); 3.17 (d, 2H, -CH2-NH); 3.75 (t, 2H, S-CH2-Ar); 4.13 (s, 1H, -CH-NH); 6.44 (s, 1H, -NH-CH-); 6.65 (d, 1H, Ar); 7.01-7.31 (m, 6H, Ar); 7.92 (t, 1H, CH2-NH-CO-); 10.42 (s, 1H, -NH-CO).

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.1{2}:1H-NMR (DMSO-d6) 2., 72-2 .93 (m, 4H, Alk); 3.45 (q, 2H, RP-CH2-CH2); 3.86 (t, 2H, S-CH2-Ar); 4.12 (s, 1H, -CH-NH); 6.28 (s, 1H, -CH-NH); 6.65 (d, 1H, Ar); 7.11-7.42 (m, 11H, Ar); 7.93 (t, 1H, CH2-NH-CO-); 10.42 (s, 1H, -NH-CO).

4-[2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carbonyl]-piperazine-1-carboxylic acid ethyl ester 2.1{3}: H-NMR (DMSO-d6) 1.29 (t, 3H, CH3-SNO); 2.84 (m, 1H, CH-CH2-S); 3.45, 3.53 (s, s, 8H, 4CH2-piperazine); 3.87 (t, 2H, S-CH2-Ar); 4.03-4.18 (m, 3H, Alk); 6.31 (s, 1H, -CH-NH); 6.70 (d, 1H, Ar); 6.85 (s, 2H, Ar); 7.22 (s, 2H, Ar); 7.36 (s, 2H, Ar); 10.42 (s, 1H, -NH-CO).

3-(2-Chloro-benzylsulfamide)-7-(4-phenylpiperazin-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{4}:1H-NMR (DMSO-d6) 2.85 (m, 2H, -S-CH2-CH); 3.2 (s, 4H, (CH2)2N-Ar); 3.70 (s, 4H, (CH2)2N-CO); 3.86 (t, 2H, S-CH2-Ar); 4.10 (s, 1H, -CH-NH); 6.31 (s, 1H, -CH-NH); 6.67-6.94 (m, 6H, Ar); 7.15-7.42 (m, 6H, Ar); 10.42 (s, 1H, -NH-CO).

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [2-(4-chlorophenyl)-ethyl]-amide 2.1{5}:1H-NMR (DMSO-d6) 2.74-2.91 (m, 4H, Alk); 3.43 (d, 2H, Ph-CH2-CH2); 3.86 (t, 2H, S-CH2-Ar); 4.11 (s, 1H, -CH-NH); 6.30 (s, 1H, -CH-NH); 6.68 (d, 1H, A); 7.12-7.45 (m, 11H, Ar); 7.96 (t, 1H, CH2-NH-CO-); 10.43 (s, 1H, -NH-CO).

3-(2-Chloro-benzylsulfamide)-7-[4-(2-fluoro-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1{6}:1H-NMR (DMSO-d6) 2.83 (m, 2H, -S-CH2-CH); 3.07 (s, 4H, (CH2)2N-Ar); 3.52 (s, 4H, (CH2)2N-CO); 3.86 (t, 2H, S-CH2-Ar); 4.10 (s, 1H, -CH-NH); 6.28 (s, 1H, -CH-NH); 6.70 (d, 1H, Ar); 6.84-7.14 (m, 6H, Ar); 7.17-7.43 (m, 4H, Ar); 10.43 (s, 1H, -NH-CO).

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide 2.1{7}:1H-NMR (DMSO-d6) 2.69-2.87 (m, 4H, Alk); 3.42 (m, 2H, Ph-CH2-CH2); 3.74 (t, 2H, S-CH2-Ar); 4.09 (s, 1H, -CH-NH); 6.33 (s, 1H, -CH-NH); 6.65 (d, 1H, Ar); 6.91 (t, 1H, Ar); 7.03-7.33 (m, 9H, Ar); 7.93 (t, 1H, CH2-NH-CO-); 10.40 (s, 1H, -NH-CO).

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methyl-benzylamine 2.1{8}:1H-NMR (DMSO-d6) 2.31 (s, 3H, CH3-Ar); 2.74 (m, 2H, CH-CH2-S); 3.72 (t, 2H, S-CH2-Ar); 4.08 (s, 1H, -CH-NH); 4.4 (d, 2H, -CH2-NH-CO); 6.33 (s, 1H, -CH-NH); 6.69 (d, 1H, Ar); 6.93 (t, 1H, Ar); 7.03-7.37 (m, 9H, Ar); 8.37 (t, 1H, CH2-NH-CO-); 10.41 (s, 1H, -NH-CO).

7-(3,4-Dihydro-1H-isoquinoline-2-carbonyl)-3-(3-perpenicularity)-3,4-dihydro-1H-cinoxacin-2-it 2.1{9}:1H-NMR (DMSO-d6) 2.75 (m, 2H, CH-CH2-S); 2.90 (t, 2H, Ar-CH2-CH2); 3.74 (m, 4H, Alk); 4.06 (s, 1H, -CH-NH); 4.65 (s, 2H, Ar-CH2-NH); 6.24 (s, 1H, -CH-NH); 6.69 (d, 1H, Ar); 6.88 (m, 3H, Ar); 7.02-7.15 (m, 6H, Ar); 7.22 (q, 1H, Ar); 10.40 (s, 1H, -NH-CO).

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 2-methoxy-benzylamine 2.1{10}:1H-NMR (DMSO-d6) 2.75 (m, 2H, CH-CH2-S); 3.64 (t, 2H, S-CH2-Ar); 3.88 (s, 3H, SNO); 4.11 (s, 1H, -CH-NH); 4.43 (d, 2H, -CH2-NH-CO); 6.37 (s, 1H, -CH-NH); 6.70 (d, 1H, Ar); 6.827.42 (m, 10H, Ar); 8.17 (t, 1H, CH2-NH-CO-); 10.45 (s, 1H,-NH-CO).

2-(2-Chloro-4-fluoro-benzosulfimide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (furan-2-ylmethyl)-amide 2.1{11} 2.81 (m, 2H, CH-CH2-S); 3.81 (t, 2H, S-CH2-Ar); 4.12 (s, 1H, -CH-NH); 4.42 (d, 2H, -CH2-NH-CO); 6.17 (s, 1H, -CH-NH); 6.30 (s, 1H, C-H Furyl); 6.37 (s, 1H, C-H Furyl); 6.65 (d, 1H, Ar); 7.00 (t, 1H, Ar); 7.17 (d, 1H, Ar); 7.25-7.43 (m, 4H, Ar); 8.35 (t, 1H, CH2-NH-CO-); 10.42 (s, 1H, -NH-CO).

3-(3-Fluoro-benzylsulfamide)-7-(3-methyl-4-m-tolyl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1 {12}

3-(2-Methyl-benzylsulfamide)-7-(4-phenylpiperazin-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{13}

3-(2-Methyl-benzylsulfamide)-7-(4-phenylpiperazin-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{14}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 2-chloro-benzylamine 2.1 {15}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide 2.1 {16}

7-[4-(2-Fluoro-phenyl)-piperazine-1-carbonyl]-3-(2-methyl-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1 {17}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.1{18}

2-(2-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 2-methoxy-benzylamine 2.1{19}

4-[2-(2-Fluoro-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carbonyl]-piperazine-1-carboxylic acid ethyl ester 2.1{20}

3-(2-FPO is-benzylsulfamide)-piperazin-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{21}

2-(2-Fluoro-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.1{22}

7-(1,4-Dioxa-8-Aza-Spiro[4.5]decane-8-carbonyl)-3-(2-fluoro-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{23}

3-(2-Fluoro-benzylsulfamide)-7-(4-phenyl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{24}

7-[4-(2-Chloro-phenyl)-piperazine-1-carbonyl]-3-(2-fluoro-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1 {25}

3-(2-Fluoro-benzylsulfamide)-7-(4-pyridin-2-yl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1 {26}

3-(2-Fluoro-benzylsulfamide)-7-[4-(4-methoxy-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1 {27}

3-(2-Fluoro-benzylsulfamide)-7-[4-(2-fluoro-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1 {28}

7-(4-Benzyl-piperazine-1-carbonyl)-3-(2-fluoro-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{29}

7-(2,3-Dihydro-indole-1-carbonyl)-3-(2-methyl-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1 {30}

7-(1,4-Dioxa-8-Aza-Spiro[4.5]decane-8-carbonyl)-3-(2-methyl-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{31}

4-{[2-(2-Methyl-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydro-cinoxacin-6-carbonyl]-amino}-piperidine-1-carboxylic acid ethyl ester 2.1 {32}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-dipropylamino-propyl)-amide 2.1{33}

7-[4-(2-METI is-phenyl)-piperazine-1-carbonyl]-3-(2-methyl-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1 {34}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide 2.1 {35}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid exiled 2.1 {36}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid reptiloid 2.1{37}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-morpholine-4-yl-ethyl)-amide 2.1 {38}

3-(2-Methyl-benzylsulfamide)-7-(3-methyl-n-tolyl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1 {39}

2-(3-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid acid (pyridine-3-ylmethyl)-amide 2.1{40}

2-(3-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-methoxy-ethyl)-amide 2.1{41}

2-(3-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid reptiloid 2.1{42}

2-(3-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid actilume 2.1 {43}

2-(3-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid exiled 2.1{44}

4-[2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carbonyl]-piperazine-1-carboxylic acid ethyl ester 2.1{45}

2-(2-Chloro-4-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-CT is about acid (2,2-diethoxy-ethyl)-amide 2.1{46}

2-(3-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid arylamide 2.1{47)

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (pyridine-3-ylmethyl)-amide 2.1{48}

3-(2,5-Dimethyl-benzylsulfamide)-7-(1,4-dioxa-8-Aza-Spiro[4.5]decane-8-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{49}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1{50}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3 .4-tetrahydroquinoxalin-6-carboxylic acid (3-dimethylamino-propyl)-amide 2.1{51}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-morpholine-4-yl-propyl)-amide 2.1 {52}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-dimethoxy-ethyl)-amide 2.1{53}

2-(2-Chloro-4-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 2-methoxy-benzylamine 2.1 {54}

2-(2-Chloro-4-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-b-carboxylic acid (3-morpholine-4-yl-propyl)-amide 2.1{55}

2-(2-Chloro-4-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 2-chloro-benzylamine 2.1{56}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methoxy-propyl)-amide 2.1{57}

2-(4-Fluoro-shall interculturality-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid exiled 2.1{58}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid propylamide 2.1{59}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid reptiloid 2.1 {60}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-morpholine-4-yl-ethyl)-amide 2.1{61}

4-[2-(2,5-Dimethyl-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carbonyl]-piperazine-1-carboxylic acid ethyl ester 2.1{62}

2-(2-Chloro-4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (pyridine-3-ylmethyl)-amide 2.1{63}

7-(1,4-Dioxa-8-Aza-Spiro[4.5]decane-8-carbonyl)-3-(3-fluoro-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1 {64}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methoxy-propyl)-amide 2.1{65}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-morpholine-4-yl-propyl)-amide 2.1{66}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid exiled 2.1{67}

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid arylamide 2.1{68}

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid propylamide 2.1{69}

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-arbonboy acid exiled 2.1{70}

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-methoxy-ethyl)-amide 2.1{71}

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid octylamide 2.1{72}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-ethoxy-propyl)-amide 2.1{73}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-methoxy-ethyl)-amide 2.1{74}

3-(2-Chloro-6-fluoro-benzylsulfamide)-7-(1,4-dioxa-8-Aza-Spiro[4.5]decane-8-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{75}

2-(2-Chloro-6-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid exiled 2.1{76}

2-(2-Chloro-6-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-methoxy-ethyl)-amide 2.1{77}

3-(2-Chloro-6-fluoro-benzylsulfamide)-7-(4-phenyl-piperidine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{78}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid actilume 2.1{79}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid arylamide 2.1{80}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid exiled 2.1{81}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (pyridine-3-ylmethyl)-amide 2.1{8}

2-(4-Methyl-benzoylformate-3-oxo-],2,3,4-tetrahydroquinoxalin-6-carboxylic acid arylamide 2.1{83}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid actilume 2.1{84}

2-(4-Methyl-benzylmaleimide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methoxy-propyl)-amide 2.1{85}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid propylamide 2.1{86}

7-(1,4-Dioxa-8-Aza-Spiro[4,5]decane-8-carbonyl)-3-(4-methyl-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{87}

2-(4-Methyl-benzylsulfamide-2-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-morpholine-4-yl-propyl)-amide 2.1{88}

7-(Azepin-1-carbonyl)-3-(2,5-dimethyl-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{89}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide 2.1{90}

2-(4-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-morpholine-4-yl-propyl)-amide 2.1{91}

2-(4-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid exiled 2.1{92}

2-(4-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid arylamide 2.1{93}

2-(4-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid actilume 2.1{94}

2-(4-Chlorobenzenesulfonamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methoxy-propyl)-amide 2.1{95}

3-(2-Chloro-benzylsulfamide)-7-(4-methyl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{96}

3-(2-Chloro-benzylsulfamide)-7-(4-pyridin-2-yl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{97}

3-(2-Chloro-benzylsulfamide)-7-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1{98}

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.1{99}

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methoxy-benzylamine 2.1{100}

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methyl-benzylamine 2.1{101}

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 3-methyl-benzylamine 2.1{102}

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-cyclohex-1-enyl-ethyl)-amide 2.1{103}

2-(2-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclohexylamine 2.1{104}

7-[4-(2,3-Dimethyl-phenyl)-piperazine-1-carbonyl]-3-(3-fluoro-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{105}

7-[4-(2,5-Dimethyl-phenyl)-piperazine-1-carbonyl]-3-(3-fluoro-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{106}

7-[4-(5-Chloro-2-methyl-phenyl)-piperazine-1-carbonyl]-3-(3-fluoro-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{107}

3-(3-Fluoro-benzylsulfamide)-7-(4-methyl-piperazin-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{108}

3-(3-Fluoro-benzylsulfamide)-7-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1{109}

3-(3-Fluoro-benzylsulfamide)-7-[4-(4-methoxy-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1{110}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid sec-butylamide 2.1{111}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-chloro-benzylamine 2.1{112}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.1{113}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid Isopropylamine 2.1{114}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.1{115}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (tetrahydro-furan-2-ylmethyl)-amide 2.1{116}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (furan-2-ylmethyl)-amide 2.1{117}

2-(3-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.1{118}

3-(2-Methyl-benzylsulfamide)-7-(piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{119}

7-[4-(2,3-Dimethyl-phenyl)-p is perazin-1-carbonyl]-3-(2-methyl-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{120}

3-(2-Methyl-benzylsulfamide)-7-(3-methyl-4-m-tolyl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{121}

3-(2-Methyl-benzylsulfamide)-7-[4-(3-trifluoromethyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1{122}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid sec-butylamide 2.1{123}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-chloro-benzylamine 2.1{124}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [2-(3,4-dimethoxy-phenyl)-ethyl]-amide 2.1{125}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methoxy-benzylamine 2.1{126}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methyl-benzylamine 2.1{127}

2-(2-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 3-methoxy-benzylamine 2.1{128}

2-(2-Methyl-benzylsulfamide-3-oxo-], 2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.1{129}

7-[4-(2,5-Dimethyl-phenyl)-piperazine-1-carbonyl]-3-(4-methyl-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{130}

3-(4-Methyl-benzylsulfamide)-7-(3-methyl-4-m-tolyl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{131}

3-(4-Methyl-benzylsulfamide)-7-(4-pyridin-2-yl-piperazine-1-carbonyl)-3,4-dihyd is about-1H-cinoxacin-2-it 2.1{132}

7-[4-(4-Fluoro-phenyl)-piperazine-1-carbonyl]-3-(4-methyl-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{133}

7-[4-(4-Methoxy-phenyl)-piperazine-1-carbonyl]-3-(4-methyl-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{134}

3-(4-Methyl-benzylsulfamide)-7-(morpholine-4-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 1.1{135}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentylamine 2.1{136}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methyl-benzylamine 2.1{137}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methyl-butyl)-amide 2.1{138}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.1{139}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-cyclohex-1-enyl-ethyl)-amide 2.1{140}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (furan-2-ylmethyl)-amide 2.1{141}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid benzylamine 2.1{142}

2-(4-Methyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.1{143}

7-[4-(2,5-Dimethyl-phenyl)-piperazine-1-carbonyl]-3-(4-fluoro-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{144}

7-[4-(5-X is the PR-2-methyl-phenyl)-piperazine-1-carbonyl]-3-(4-fluoro-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 2.1{145}

3-(4-Fluoro-benzylsulfamide)-7-(3-methyl-4-m-tolyl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-AOI 2.1{146}

3-(4-Fluoro-benzylalkyldimethyl)-7-(4-methyl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{147}

3-(4-Fluoro-benzylsulfamide)-7-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1{148}

7-(4-Benzo[1,3]dioxol-5-ylmethyl-piperazine-1-carbonyl)-3-(4-fluoro-benzylsulfamide)-3,4-dihydro-1H-cinoxacin-2-it 1.1{149}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-chloro-butylamide 2.1{150}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.1{151}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methoxy-benzylamine 2.1{152}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methyl-benzylamine 2.1{153}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 3-methoxy-benzylamine 2.1{154}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (1,2,3,4-tetrahydro-naphthalene-1-yl)-amide 1.1{155}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-ethyl-hexyl)-amide 2.1{156}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid furan-2-ylmethyl)-amide 2.1{157}

2-(4-Fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 1.1{158}

3-(4-Chloro-benzylsulfamide)-7-[4-(2,3-dimethyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1{159}

3-(4-Chloro-benzylsulfamide)-7-(3-methyl-4-m-tolyl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{160}

2-(4-Chloro-benzylsulfamide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid benzylamine 2.1{161}

2-(4-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.1{162}

2-(4-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopropylamino 2.1{163}

2-(4-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 3-methoxy-benzylamine 2.1{164}

2-(4-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (furan-2-ylmethyl)-amide 2.1{165}

2-(4-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.1{166}

2-(3-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methyl-butyl)-amide 2.1{167}

2-(3-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.1{168}

2-(3-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-cyclohex-1-enyl-ethyl)-amide 2.1{169

2-(3-Chloro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (furan-2-ylmethyl)-amide 2.1{170}

3-(2,5-Dimethyl-benzylsulfamide)-7-(pyrrolidin-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{171}

3-(2,5-Dimethyl-benzylsulfamide)-7-(4-pyridin-2-yl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{172}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [2-(3,4-dimethoxy-phenyl)-ethyl]-amide 2.1{173}

2-(2,5-Dimetapp-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.1{174}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid benzylamine 2.1{175}

3-(2-Chloro-6-fluoro-benzylsulfamide)-7-[4-(2,3-dimethyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1{176}

3-(2-Chloro-6-fluoro-benzylsulfamide)-7-[4-(2,5-dimethyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1{177}

3-(2-Chloro-6-fluoro-benzylsulfamide)-7-[4-(5-chloro-2-methyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1{178}

3-(2-Chloro-6-fluoro-benzylsulfamide)-7-(3,4-dihydro-1H-isoquinoline-2-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{179}

3-(2-Chloro-6-fluoro-benzylsulfamide)-7-[4-(3-trifluoromethyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-hetacillin-2-it 2.1{180}

3-(2-Chloro-6-fluoro-benzylsulfamide)-7-(4-pyridin-2-yl-piperazine-1-arbonyl)-3,4-dihydro-1H-cinoxacin-2-it 1.1{181}

3-(2-Chloro-6-fluoro-benzylsulfamide)-7-[4-(4-methoxy-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.1{182}

2-(2-Chloro-6-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid sec-butylamide 2.1{183}

2-(2-Chloro-6-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid tert-butylamide 2.1{184}

2-(2-Chloro-6-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-chloro-benzylamine 2.1{185}

2-(2-Chloro-6-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.1{186}

2-(2-Chloro-6-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid Isopropylamine 2.1{187}

2-(2-Chloro-6-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.1{188}

2-(2-Chloro-6-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 3-methoxy-benzylamine 2.1{189}

2-(2-Chloro-6-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-cyclohex-1-Anil-ethyl)-amide 2.1{190}

2-(2-Chloro-6-fluoro-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carbolic acid (furan-2-ylmethyl)-amide 2.1{191}

3-(2-Chloro-6-fluoro-benzylsulfamide)-7-(4-pyridin-2-yl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{192}

2-(2-Chloro-6-fluoro-benzisothiazol the Tyl-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methyl-benzylamine 2.1{193}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid tert-butyl ether 2.1{194}

3-(2,5-Dimethyl-benzylsulfamide)-7-(morpholine-4-carbolin)-3,4-dihydro-1H-cinoxacin-2-it 2.1{195}

3-(2,5-Dimethyl-benzylsulfamide)-7-(2-hydroxymethyl-pyrrolidin-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{196}

3-(2,5-Dimethyl-benzylsulfamide)-7-(7-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinoline-2-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{197}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-methyl-amide 2.1{198}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-hydroxyethyl)-methyl-amide 2.1{199}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid furan-2-ylmethyl-(tetrahydro-furan-2-ylmethyl)-amide 2.1{200}

2-(2,5-Dimethyl-benzylsulfamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid dimethylamide 2.1{201}

2-Methanesulfonamide-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1{202}

2-([1.3]Dioxolane-2-elmersolver)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1{203}

3-oxa-2-(pyridine-3-elmersolver)-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1{204}

3-oxa-2-(pyridine-3-elmersolver)-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1{205}

2-(Octahedrally-1-elmersolver)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1{206}

5-[6-(2,2-Diethoxycarbonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-2-elmersolver]-thiophene-2-carboxylic acid methyl ester 2.1{207}

2-(Adamantane-1-elmersolver)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1{208}

3-(3-Fluoro-benzylsulfamide)-7-(4-phenyl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.1{209}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 2-chloro-benzylamine 2.2{1}:1H-NMR (DMSO-d6) 2.42 (s, 3H, CH3-Ar); 3.36 (m, 1H, CH-CH2-SO2); 3.79 (d, 1H, CH-CH2-SO2, J=7.5 Hz); 4.45-4.65 (m, 5H, Alk); 6.17 (s, 1H, -NH-CH-); 6.78 (d, 1H, Ar); 7.11-7.49 (m, 10H, Ar); 8.50 (t, 1H, CH2-NH-CO-); 10.64 (s, 1H, -NH-CO).

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclooctylamine 2.2{2}1H-NMR (DMSO-d6) 1.47-1.83 (m, 12H, -(CH2)7-); 2.40 (s, 3H, CH3-Ar); 3.34 (m, 1H, CH-CH2-SO2); 3.79 (d, 1H, CH-CH2-SO2, J=7.1 Hz); 4.00 (m, 1H, -CH2-CH-CH2-); 4.44-4.68 (m, 3H, Alk); 6.04 (s, 1H, -NH-CH-); 6.72 (d, 1H, Ar); 7.14-7.40 (m, 6H, Ar); 7.58 (d, 1H, CH-NH-CO-); 10.58 (s, 1H, -NH-CO).

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (thiophene-2-ylmethyl)-amide 2.2{3}1H-NMR (DMSO-d6) 2.4 (s, 3H, CH3-Ar); 3.35 (m, 1H, CH-CH2-SO2); 3.77 (d, 1H, CH-CH2-SO2, J=7.5 Hz); 4.45-4.79 (m, 5H, Alk); 6.14 (s, 1H, -NH-CH-); 6.75 (d, 1H, Ar); 6.9 (t, 1H (Ar)); 6.96 (s, 1H, Ar); 7.14-7.25 (m, 4H, Ar); 7.35 (m, 3H, Ar); 8.56 (t, 1H, CH2-NH-CO-); 10.53 (s, 1H, -NH-C),

3-Oxo-2-methylmethanesulfonamide-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (thiophene-2-ylmethyl)-amide 2.2{4}1H-NMR (DMSO-d6) 2.36 (s, 3H, CH3-Ar); 3.22 (m, 1H, CH-CH2-SO2); 3.57 (d, 1H, CH-CH2-SO2, J=7.5 Hz); 4.42 (m, 1H, -CH-); 4.47 (dd, 2H, SO2-CH2-Ar, J=6.5 Hz); 4.58 (d, 2H, -CH2-NH-CO-, J=3.1 Hz); 6.14 (s, 1H, -NH-CH-); 6.75 (d, 1H, Ar); 6.9 (t, 1H (Ar)); 6.96 (d, 1H, Ar); 7.11-7.27 (m, 5H, Ar); 7.35 (m, 2H,Ar); 8.6 (t, 1H. CH2-NH-CO-); 10.53 (s, 1H, -NH-CO).

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclooctylamine 2.2{5}1H-NMR (DMSO-d6) 1.43-1.81 (m, 12H, -(CH2)7-); 2.36 (s, 3H, CH3-Ar); 3.18 (m, 1H, CH-CH2-SO2); 3.6 (d, 1H, CH-CH2-SO2, J=7.5 Hz); 3.95 (m, 1H, -CH2-CH-CH2-); 4.38-4.57 (m, 3H, Alk); 6.03 (s, 1H, -NH-CH-); 6.72 (d, 1H, Ar); 7.10-7.37 (m, 6H, Ar); 7.57 (d, 1H, CH-NH-CO-); 10.55 (s, 1H, -NH-CO).

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 2-chloro-benzylamine 2.2{6}1H-NMR (DMSO-d6) 2.37 (s, 3H, CH3-Ar); 3.22 (m, 1H, CH-CH2-SO2); 3.59 (d, 1H, CH-CH2-SO2, J=7.1 Hz); 4.35-4.62 (m, 5H, Alk); 6.16 (s, 1H, -NH-CH-); 6.78 (d, 1H, Ar); 7.06-7.52 (m, 10H, Ar); 8.49 (t, 1H, CH2-NH-CO-); 10.62 (s, 1H, -NH-CO).

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 2-chloro-benzylamine 2.2{7}1H-NMR (DMSO-d6) 3.37-3.85 (dd, dd, 2H, CH-CH2-SO2); 4.45 (m, 1H, -CH-); 4.5 (d, 2H, -CH2-NH-CO); 4.68 (s, 2H, -CH2-Ar), 6.23 (s, 1H, -NH-CH-); 6.77 (d, 1H, Ar); 7.09-7.45 (m, 8H, Ar); 7.62 (t, 1H,Ar); 8.51 (t, 1H, CH2-NH-CO-); 10.69 (s, 1H, -NH-CO),

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (thiophene-2-ylmethyl)-amide 2.2{8}1H-NMR (DMSO-d6) 3.35-3.42, 3.72-3.81 (dd, dd, 2H, CH-CH2-SO2); 4.47 (d, 1H,-CH-); 4.63 (d, 2H, -CH2-NH-CO-, J=2.9 Hz); 4.71 (s, 2H, -CH2-Ar), 6.15 (s, 1H, -NH-CH-); 6.74 (d, 1H, Ar); J=5.75 Hz); 6.9 (t, 1H, Ar); 6.96 (s, 1H, Ar); 7.09 (m, 5H, Ar); 7.61 (t, 1H, Ar); 8.57 (t, 1H, CH2-NH-CO-); 10.65 (s, 1H, -NH-CO).

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclooctylamine 2.2{9}1H-NMR (DMSO-d6) 1.43-1.85 (m, 12H, -(CH2)7-); 3.25 (m, 1H, CH-CH2-SO2); 3.67 (d, 1H, CH-CH2-SO2, J=7 Hz); 3.97 (m, 1H, -CH2-CH-CH2-); 6 4.43-4.62 (m, 3H, Alk); 6.08 (s, 1H, -NH-CH-); 6.74 (d, 1H, Ar); 7.25-7.65 (m, 7H, Ar); 10.58 (s, 1H, -NH-CO).

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3 .4-tetrahydroquinoxalin-6-carboxylic acid (thiophene-2-ylmethyl)-amide 2.2{10}1H-NMR (DMSO-d6) 3.24-3.7 (dd, 2H, CH-CH2-SO2); 4.42-4.72 (m, 5H, Alk), 6.21 (s, 1H, -NH-CH-); 6.77 (d, 1H, Ar); 6.84-7.06 (m, 3H, Ar); 7.15-7.91 (m, 7H, Ar); 8.59 (t, 1H, CH2-NH-CO-); 10.64 (s. 1H, -NH-CO).

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo, 1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methyl-butyl)-amide 2.2{11}1H-NMR (DMSO-d6) 0.94 (d, 6H, (CH3)2CH); 1.45 (q, 2H, CH-CH2-CH2); 1.64 (m, 1H, (CH3)2CH); 3.27 (m, 3H, Alk); 3.67 (d, 1H, -CH2-CH-CH2-, J=7.5 Hz); 4.45-4.62 (m, 3H, Alk); 6.1 (s, 1H, -NH-CH-); 6.75 (d, 1H, Ar); 7.31 (s, 4H, Ar); 7.43 (d, 1H, Ar); 7.51 (d, 1H, Ar); 7.62 (s, 1H, Ar); 7.78 (t, 1H, CH2-NH-CO-); 10.57 (s, 1H, -NH-CO).

2-(4-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (thiophene-2-ylmethyl)-amide 2.2{12}

2-(4-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 2-chloro-benzylamine 2.2{13}

2-(4-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclooctylamine 2.2{14}

2-(4-the ENT phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-piperidine-1-yl-propyl)-amide 2.2{15}

2-(4-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-dimethylamino-ethyl)-amide 2.2{16}

2-(4-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-piperidine-1-yl-propyl)-amide 2.2{17}

2-(4-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-diisobutylamine-propyl)-amide 2.2{18}

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-morpholine-4-yl-propyl)-amide 2.2{19}

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-morpholine-4-yl-propyl)-amide 2.2{20}

3-(3-Bromo-phenylmethanesulfonyl)-7-(1,4-dioxa-8-Aza-Spiro[4.5]decane-8-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{21}

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-diethylamino-propyl)-amide 2.2{22}

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-piperidine-1-yl-propyl)-amide 2.2{23}

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-ethoxy-propyl)-amide 2.2{24}

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [3-(2-methyl-piperidine-1-yl)-propyl]-amide 2.2{25}

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-carboxylic acid (2-azepin-1-yl-ethyl)-amide 2.2{26}

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [3-(3,5-dimethyl-piperidine-1-yl)-propyl]-amide 2.2{27}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid acid (3-pyrrolidin-1-yl-propyl)-amide 2.2{28}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-morpholine-4-yl-ethyl)-amide 2.2{29}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [3-(2-methyl-piperidine-1-yl)-propyl]-amide 2.2{30}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-methoxy-ethyl)-amide 2.2{31}

3-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-7-(1,4-dioxa-8-aza-spiro[4.5]ilecane-8-arbnl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{32}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [2-(4-methyl-piperidine-1-yl)-propyl]-amide 2.2{33}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-diethylamino-propyl)-amide 2.2{34}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-ethoxy-propyl)-amide 2.2{35}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [3-(3,5-dimethyl-piperidine-1-yl)-propyl]-amide 2.2{36}

2(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-diethylamino-ethyl)-amide 2.2{37}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-piperidine-1-yl-propyl)-amide 2.2{38}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methoxy-propyl)-amide 2.2{39}

7-(1,4-Dioxa-8-aza-spiro[4.5]dn-8-rbnl)-3-m-trimethylsilylmethyl-3,4-dihydro-1H-cinoxacin-2-it 2.2{40}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-diethylamino-ethyl)-amide 2.2{41}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-morpholine-4-yl-ethyl)-amide 2.2{42}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-ethoxy-propyl)-amide 2.2{43}

7-(1,4-Dioxa-8-az-siro[4.5]dane-8-arbnl)-3-o-trimethylsilylmethyl-3,4-dihydro-1H-cinoxacin-2-it 2.2{44}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-morpholine-4-yl-propyl)-amide 2.2{45}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-amide 2.2{46}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid benzyl-methyl-amide 2.2{47}

1-[2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carbonyl]-piperidine-4-carboxylic acid ethyl ester 2.2{48}

3-(2-chlorophenyl econsultancy)-7-(4-cyclohexyl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{49}

3-(2-Chloro-phenylmethanesulfonyl)-7-[4-(3-trifluoromethyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{50}

3-(2-Chloro-phenylmethanesulfonyl)-7-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{51}

7-(4-Benzo[1,3]dioxol-5-ylmethyl-piperazine-1-carbonyl)-3-(2-chloro-phenylmethane-sulfanilyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{52}

3-(2-Chloro-phenylmethanesulfonyl)-7-[4-(4-methoxy-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{53}

3-(2-Chloro-phenylmethanesulfonyl)-7-(morpholine-4-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{54}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid sec-butylamide 2.2{55}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-chloro-benzylamine 2.2{56}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.1{57}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methoxy-benzylamine 2.2{58}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopropylamino 2.2{59}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.2{60}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-ka is oil acid (tetrahydro-furan-2-ylmethyl)-amide 2.2{61}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 3-methoxy-benzylamine 2.2{62}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-cyclohex-1-enyl-ethyl)-amide 2.2{63}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (furan-2-ylmethyl)-amide 2.2{64}

2-(2-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.2{65}

7-(4-Cyclohexyl-piperazine-1-carbonyl)-3-(3-fluoro-phenylmethanesulfonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{66}

7-(3,4-Dihydro-1H-isoquinoline-2-carbonyl)-3-(3-fluoro-phenylmethanesulfonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{67}

3-(3-Fluoro-phenylmethanesulfonyl)-7-(4-pyridin-2-yl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{68}

3-(3-Fluoro-phenylmethanesulfonyl)-7-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{69}

2-(3-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methoxy-benzylamine 2.2{70}

2-(3-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methyl-benzylamine 2.2{71}

2-(3-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methyl-butyl)-amide 2.2{72}

2-(3-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydro cinoxacin-6-carboxylic acid phenethyl-amide 2.1{73}

2-(3-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (tetrahydro-furan-2-ylmethyl)-amide 2.2{74}

2-(3-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 3-methoxy-benzylamine 2.2{75}

2-(3-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (furan-2-ylmethyl)-amide 2.2{76}

2-(3-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid benzylamine 2.2{77}

2-(3-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.2{78}

7-(Pyrrolidin-1-carbonyl)-3-o-trimethylsilylmethyl-3,4-dihydro-1H-cinoxacin-2-it 2.2{79}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-chloro-benzylamine 2.2{80}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.2{81}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [2-(3,4-dimethyl-phenyl)-ethyl]-amide 2.2{82}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methyl-butyl)-amide 2.2{83}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-cyclohex-1-enyl-ethyl)-amide 2.2{84}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-to benovoy acid (furan-2-ylmethyl)-amide 2.2{85}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid benzylamine 2.2{86}

3-Oxo-2-o-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.2{87}

7-(3,4-Dihydro-1H-isoquinoline-2-carbonyl)-3-m-trimethylsilylmethyl-3,4-dihydro-1H-cinoxacin-2-it 2.2{88}

3-m-Trimethylsilylmethyl-7-[4-(3-trifluoromethyl-phenyl)-piperazin-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{89}

7-[4-(4-Fluoro-phenyl)-piperazine-1-carbonyl]-3-m-trimethylsilylmethyl-3,4-dihydro-1H-cinoxacin-2-it 2.2{90}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid sec-butylamide 2.2{91}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-chloro-benzylamine 2.2{92}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.2{93}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid [2-(3,4-dimethoxy-phenyl)-ethyl]-amide 2.2{94}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methoxy-benzylamine 2.2{95}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methyl-benzylamine 2.2{96}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (1-phenyl-ethyl)-amide 2.2{97}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopropylamino 2.2{98}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methyl-butyl)-amide 2.2 {99}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.2{100}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (tetrahydro-furan-2-ylmethyl)-amide 2.2{101}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 3-methoxy-benzylamine 2.2{102}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-cyclohex-1-enyl-ethyl)-amide 2.2{103}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (furan-2-ylmethyl)-amide 2.2{104}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid benzylamine 2.2{105}

3-Oxo-2-m-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.2{106}

3-p-Trimethylsilylmethyl-7-[4-(3-triptoreline)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-he 2.21{107}

7-(piperidine-1-carbonyl)-3-p-trimethylsilylmethyl-3,4-dihydro-1H-cinoxacin-2-it 2.2{108}

3-Oxo-2-p-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.2{109}

3-Oxo-2-p-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methyl-butyl)-amid{110}

3-Oxo-2-p-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.2{111}

3-Oxo-2-p-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (tetrahydrofuran-2-ylmethyl)-amide 2.2{112}

3-Oxo-2-p-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-ethyl-hexyl)-amide 2.2{113}

3-Oxo-2-p-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (furan-2-ylmethyl)-amide 2.2{114}

3-Oxo-2-p-trimethylsilylmethyl-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.2{115}

3-(4-Fluoro-phenylmethanesulfonyl)-7-(3-methyl-piperidine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{116}

3-(4-Fluoro-phenylmethanesulfonyl)-7-(pyrrolidin-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{117}

7-(4-Cyclohexyl-piperazine-1-carbonyl)-3-(4-fluoro-phenylmethanesulfonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{118}

7-[4-(2,5-Dimethyl-phenyl)-piperazine-1-carbonyl]-3-(4-fluoro-phenylmethanesulfonyl-methyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{119}

7-[4-(5-Chloro-2-methyl-phenyl)-piperazine-1-carbonyl]-3-(4-fluoro-phenylmethanesulfonyl-methyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2 {120}

3-(4-Fluoro-phenylmethanesulfonyl)-7-(4-pyridin-2-yl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{121}

3-(4-Fluoro-phenylmethanesulfonyl)-7-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{122}

7-(4-Benzo[1,3]dioxol-5-ylmethyl-piperazine-1-carbonyl)-3-(4-fluoro-phenylmethanesulfonyl-ylmethyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{123}

3-(4-Fluoro-phenylmethanesulfonyl)-7-[4-(4-methoxy-phenyl)-piperazine-1-carbonyl]-3.4-dihydro-1H-cinoxacin-2-it 2.2{124}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid sec-butylamide 2.2{125}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-chloro-benzylamine 2.2{126}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.2{127}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methoxy-benzylamine 2.2{128}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3 .4-tetrahydroquinoxalin-6-carboxylic acid 4-methyl-benzylamine 2.2{129}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (1-phenyl-ethyl)-amide 2.2{130}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopropylamino 2.2{131}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methyl-butyl)-amide 2.2{132}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid phenethyl-amide 2.2{133}

2-(4-Fluoro-phenylmethanesulfonyl)-3-ox is -1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (tetrahydrofuran-2-ylmethyl)-amide 2.2{134}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (1,2,3,4-tetrahydronaphthalen-1-yl)-amide 2.2{135}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-cyclohex-1-enyl-ethyl)-amide 2.2{136}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclohexylamine 2.2{137}

2-(4-Fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.2{138}

2-(4-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopropylamino 2.2{139}

2-(4-Chloro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methyl-butyl)-amide 2.2{140}

3-(3-Chloro-phenylmethanesulfonyl)-7-(3-methyl-piperidine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{141}

3-(3-Chloro-phenylmethanesulfonyl)-7-(3,4-dihydro-1H-isoquinoline-2-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{142}

3-(3-Chloro-phenylmethanesulfonyl)-7-[4-(3-triptoreline)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{143}

3-(3-Chloro-phenylmethanesulfonyl)-7-(4-pyridin-2-yl-piperazine-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{144}

3-(3-Chloro-phenylmethanesulfonyl)-7-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{145}

7-(4-Benzo[1,3]dioxol-5-ylmethyl-piperazine-1-carbonyl)--(3-chloro-phenylmethanesulfonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{146}

3-(3-Chloro-phenylmethanesulfonyl)-7-[4-(4-methoxy-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{147}

2-(2,5-Dimethyl-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid benzyl-methyl-amide 2.2{148}

7-(4-Cyclohexyl-piperazine-1-carbonyl)-3-(2,5-dimethyl-phenylmethanesulfonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{149}

7-(3,4-Dihydro-1H-isoquinoline-2-carbonyl)-3-(2,5-dimethyl-phenylmethanesulfonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{150}

3-(2,5-Dimethyl-phenylmethanesulfonyl)-7-[4-(3-trifluoromethyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-minoxidin-2-it 2.2{151}

3-(2,5-Dimethyl-phenylmethanesulfonyl)-7-[4-(4-fluoro-phenyl)-piperazin-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{152}

3-(2,5-Dimethyl-phenylmethanesulfonyl)-7-[4-(4-methoxyphenyl)-piperazin-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{153}

2-(2,5-Dimethyl-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-ethyl-hexyl)-amide 2.2{154}

2-(2,5-Dimethyl-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid benzylamine 2.2{155}

2-(2,5-Dimethyl-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.2{156}

1-[2-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carbonyl]-piperidine-4-carboxylic acid ethyl ester 2.2{157}

3-(2-Chloro-6-the tor-phenylmethanesulfonyl)-7-(pyrrolidin-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{158}

3-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-7-[4-(2,3-dimethyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{159}

3-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-7-[4-(5-chloro-2-methyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{160}

3-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-7-[4-(3-trifluoromethyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{161}

3-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-7-(morpholine-4-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{162}

2-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-chloro-benzylamine 2.2{163}

2-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.2{164}

2-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methoxybenzylamine 2.2{165}

2-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopropyl 2.2{166}

2-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (tetrahydrofuran-2-ylmethyl)-amide 2.2{167}

3-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-7-(pyrrolidin-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{168}

3-(2-Chloro-6-fluoro-phenylmethanesulfonyl)-7-[4-(2,5-dimethyl-phenyl)-piperazine-1-carbonyl]-3,4-dihydro-1H-cinoxacin-2-it 2.2{169}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-chloro-benzylamine 2.2{171}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid cyclopentolate 2.2{172}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-methoxybenzylamine 2.2{173}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (1-phenyl-ethyl)-amide 2.2{174}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (3-methyl-butyl)-amide 2.2{175}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2-cyclohex-1-enyl-ethyl)-amide 2.2{176}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydro-cinoxacin-6-carboxylic acid (furan-2-ylmethyl)-amide 2.2{177}

2-(2-Chloro-4-fluoro-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid butylamide 2.2{178}

3-(3-Bromo-phenylmethanesulfonyl)-7-(pyrrolidin-1-carbonyl)-3,4-dihydro-1H-cinoxacin-2-it 2.2{179}

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 4-chloro-benzylamine 2.2{180}

2-(3-Bromo-phenylmethanesulfonyl)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid 2-mercapto-benzylated 2.2{181

Example 5. Was focused library, including 880 compounds, including 408 substituted 3-oxo-1,2,3,4-tetrahydroquinoxalin 1 and 2, and tested it on antiprotease activity. Antiproteaznaya activity was determined by the serine protease (Caspase 3), which are involved in the regulation of programmed cell death (apoptosis). The activity of Caspase 3 was determined by the rate of cleavage of the peptide substrate containing fluorescent molecule (methylcoumarin). Removal methylcoumarin from the peptide molecules in the proteolytic reaction of the enzyme is accompanied by increased fluorescence intensity measurements which were performed with fluorescent parallel reader VICTOR2V (PerkinElmer, USA) at a wavelength of excitation of 355 nm and the wavelength of emission of 460 nm. For carrying out reactions used an optical 96-hole of the blade. In our experiments we used the caspase 3 and the fluorescent substrate of the company Sigma (USA). The reaction conditions and the composition of the medium used in accordance with the recommendation of the manufacturer. The starting solutions of test compounds were prepared by dissolution in DMSO (dimethyl sulfoxide) to a concentration of 10 mm. The original solutions of compounds were added to the enzyme solution in such an amount to obtain a final concentration of 10 mcmol 10 minute incubation of the enzyme with the test compound, to the solution was added an enzyme substrate and measurement of fluorescence was performed after 1 hour after addition of the substrate. For the correction on its own fluorescence of the tested compounds, fluorescent measurement (F

0
i
) was performed in a separate circuit boards that do not contain enzyme reagents (enzyme plus substrate). Full enzyme activity was measured by fluorescence in reaction wells containing all reaction components except the test compounds (F100), and zero activity was determined by the fluorescence of the wells containing the appropriate test connection and all the reaction reagents except the enzyme (F0).

Calculation of inhibition was produced by the following formula:

where Fi=F

e
i
-F
0
i
, subscript corresponds to the test compound, in the presence of which is measured fluorescence, and the superscripts (e) and (0) means the presence of elitaste enzyme reagent, respectively.

Some examples of the tested compounds showed when screening libraries of high activity, shown in the table below, and the concentration dependence of inhibition is shown in the figure.

Table

Proteasa activity of some substituted 1,2,3,4-tetrahydro-hinoksolinov
IDThe structure of connectionsIC50, nMActivity
1.2{10}3800Inhibition
1.2{14}780Inhibition
2.1{46}360Inhibition
2.1{50}240Inhibition

The concentration dependence of inhibition of caspase 3

2-(2-chloro-4-fluoro-benzylmaleimide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1 {46} (curve 1) and 2-(2,5-dimethyl-benzylmaleimide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1 {50} (curve 2) is shown in figure 1.

Example 6. Example ill Trichet preparation of tablets containing 50 mg of active ingredient. Mix 800 mg of starch, 800 mg of powdered lactose 200 mg of talc and 500 mg of 2-(2,5-dimethyl-benzylmaleimide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1 {50} and spracovavat in the bar. The resulting block is crushed into granules and sieved through a sieve, collecting the granules with a size 14-16 mesh. The obtained granules tabletirujut in a suitable form tablets weighing 280 mg each. According to the invention likewise receive pharmaceutical composition in the form of tablets containing as active ingredient other compounds of General formula 1 or 2.

Example 7. Capsules containing 200 mg of 2-(2,5-dimethyl-benzylmaleimide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1 {50}, according to the invention can be obtained by thorough mixing of compounds 2.1{50} with lactose powder in a 2:1 ratio. Received poroshkoobraznuju mix pack 300 mg in gelatin capsules of suitable size.

Example 8. Injectable compositions for intramuscular, intraperitoneal or subcutaneous injection can be prepared by mixing 500 mg of the active ingredient with suitable solubility, for example, 2-(2,5-dimethyl-benzylmaleimide)-3-oxo-1,2,3,4-tetrahydroquinoxalin-6-carboxylic acid (2,2-diethoxy-ethyl)-amide 2.1 {50}, 300 mg chlorine is butanol, 2 ml of propylene glycol and 100 ml of injectable water. The resulting solution is filtered and placed in 1 ml ampoules which are sealed and sterilized in an autoclave.

1. The application of physiologically active substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline General formula 1

in which R1is substituted sulfonyloxy group or substituted sulfonyloxy group containing as substituents optionally substituted C1-4alkyl, optionally substituted C3-8cycloalkyl, optionally substituted in the aryl and/or alkyl fragment arils1-4alkyl, optionally substituted in the heterocyclic and/or alkyl fragment heterocyclic1-4alkyl, optionally substituted aryl, optionally substituted heterocyclyl;

R2and R3independently from each other represent a hydrogen atom, halogen, CN, NO2, optionally substituted by a hydroxy-group or optionally substituted by an amino group, optionally substituted carboxyl group, optionally substituted carbamoyl, optionally substituted aryloxyalkyl group or optionally substituted geterotsiklicheskikh group;

R4and R5independently from each other represent a hydrogen atom or an inert Deputy, have settled their properties inhibitors of caspase-3,

to obtain pharmaceutical compositions and experimental (in vitro, in vivo) studies of apoptosis as pharmacological tools.

2. Pharmaceutical composition having the properties of inhibitors of caspase-3, in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing, containing as active substance pharmaceutically effective amount of substituted 3-oxo-1,2,3,4-tetrahydroquinoxalin General formula 1 according to claim 1.

3. Pharmaceutical composition for treating and preventing various diseases of warm-blooded animals and humans associated with increased activation of apoptosis, in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing, containing as active substance pharmaceutically effective amount of substituted 3-oxo-1,2,3,4-tetrahydroquinoxalin General formula 1 according to claim 1.

4. A method of obtaining a pharmaceutical composition according to claim 2 or 3 by mixing the active substance with an inert filler, diluent and/or solvent, characterized in that the active substance is used pharmaceutically effective amount of substituted 3-oxo-1,2,3,4-tetrahydroquinoxalin General formula 1 according to claim 1.

5. A method of treating and preventing various diseases heat is even animals and people associated with increased activation of apoptosis, by introducing a warm-blooded animal or human pharmaceutical composition according to claim 2 or 3.

6. Substituted 3-oxo-1,2,3,4-tetrahydroisoquinoline acids and their derivatives of General formula 2

in which R1, R3, R4and R5have the above for compounds of General formula 1 according to claim 1 value

R6is optionally substituted by a hydroxy-group, optionally substituted amino, optionally substituted, aryloxy or optional substituted heterocyclyl.



 

Same patents:

FIELD: pharmaceutical chemistry, in particular pharmaceutical compositions.

SUBSTANCE: new spyro(2H-1-benzopyrane-2,4'-piperidine) derivatives of general formula I

and pharmaceutically acceptable salts thereof are disclosed. In formula dotted line is optional bond; Y is 1-4 substituents independently selected from hydrogen, halogen, C1-C4-alkyl, optionally substituted with one or more halogen, C1-C6-alkyloxy, optionally substituted with halogen or C3-C6-cycloalkyl, C2-C6-alkenyloxy, C2-C6-alkinyloxy, C3-C6-cycloalkyloxy, C6-C12-aryloxy, arylalkyloxy, pyridilmethoxy, SR3, NR3R4, OSO2R5, and NR3SO2R4; or two Y together may form O-(CH2)n-O or O-(CF2)n-O, wherein n is 1 or 2: or Y is condensed C5-C6-aryl group; X is 1-3 substituents independently selected from hydrogen, halogen, hydroxyl, C1-C6-alkoxy, and C1-C4-alkyl; R1 is hydrogen, C1-C4-alkyl, or C6-C12-aryl; R2, R3, and R4 are independently hydrogen or C1-C4-alkyl; R5 is C6-C12-aryl. Also disclosed are pharmaceutical compositions including said derivatives and having activity in relation to CNS.

EFFECT: new compounds with valuable pharmacological action.

9 cl, 1 tbl, 83 ex

The invention relates to new derivatives of galantamine General formula I:

where R1-R5, G1-G3and W have the meanings indicated in the claims, and the invention relates to a method for producing these compounds, medicinal product and the method of its production

The invention relates to a derivative phthalazine General formula (I) or their pharmaceutically acceptable salts, or hydrates, where R1and R2are the same or different from each other and each represents a halogen atom, a C1-C4alkyl group which may be substituted by a halogen atom, a hydroxyl group or a C1-C4alkoxygroup, which may be substituted by a halogen atom, or cyano; X represents a cyano, a halogen atom, hydroxyimino, optional O-substituted C1-C4alkyl group, or a heteroaryl group selected from thiazoline, thienyl, pyrazolidine, triazolinones and tetrazolyl groups that may be substituted WITH1-C4alkyl group; Y represents a cyclic amino group (i) - (v) described in paragraph 1 of the claims; (vi) etinilnoy or ethyl group substituted WITH1-C4alkyl group, which, in turn, replaced by a number of deputies referred to in paragraph 1 of the claims; (vii) optionally substituted phenyl group; (viii) pyridyloxy or thiazolidine group

The invention relates to new spirochetes formula I

< / BR>
where Ar is phenyl, substituted phenyl where the substituents are: alkoxy, alkyl, alkoxyalkyl, phenoxy, halogen, pyridyloxy, alkoxyalkane, halogenfree; R1- H; R2- H1-C4alkyl; W represents O or one or more1-C4alkyl fragments; Y is independently one or more members of the group consisting of H2, SR3, alkoxy; R3- H, alkyl; Z is a carbocyclic or heterocyclic Spiro-fragment with a 3-7 member ring system, where the heterocyclic fragment includes 2 oxygen atom or sulfur, or one nitrogen atom and spirits may be unsubstituted or substituted by hydroxy, C1-C4the alkyl, benzyloxy; n=1-3; optical isomers, diastereomers or enantiomers or pharmaceutically acceptable salts

The invention relates to new derivatives of pyrrolidinone possessing biological activity, in particular derivatives of 1H-3-aryl-pyrrolidin-2,4-dione

FIELD: organic chemistry, pharmaceutical composition.

SUBSTANCE: new isoindoline-1-on-glucokinase activators of general formula I , as well as pharmaceutically acceptable salts or N-oxide thereof are disclosed. In formula A is phenyl optionally substituted with one or two halogen or one (law alkyl)sulfonyl group, or nitro group; R1 is C3-C9cycloalkyl; R2 is optionally monosubstituted five- or six-membered heterocyclic ring bonded via carbon atom in cycle to amino group, wherein five- or six-membered heteroaromatic ring contains one or two heteroatoms selected form sulfur, oxygen or nitrogen, one of which is nitrogen atom adjacent to carbon atom bonded to said amino group; said cycle is monocyclic or condensed with phenyl via two carbon atoms in cycle; said monosubstituted with halogen or law alkyl heteroaromatic ring has monosubstituted carbon atom in cycle which in not adjacent to carbon atom bonded to amino group; * is asymmetric carbon atom. Claimed compounds have glucokinase inhibitor activity and useful in pharmaceutical composition for treatment of type II diabetes.

EFFECT: new isoindoline-1-on-glucokinase activators useful in treatment of type II diabetes.

23 cl, 3 dwg, 43 ex

FIELD: organic chemistry, heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to nitrogen-containing heterocyclic derivatives of the formula (I): A-B-D-E (I) wherein A means 5- or 6-membered heteroaryl comprising one or two nitrogen atoms in ring; B means ethenylene; D mean phenylene; E means group -N(COR)-SO2-G wherein G means phenyl; R means 5- or 6-membered heteroaryl or heteroarylmethyl comprising one or two nitrogen atoms in ring, or group -(CH2)n-N(R5)R6 wherein n means a whole number from 1 to 5; R5 and R6 are similar or different and mean: hydrogen atom, (C1-C6)-alkyl, hydroxyalkyl, aminoalkyl; or R5 and R6 in common with nitrogen atom can form 5-7-membered cyclic amino-group -N(R5)R6 that can comprise, except for nitrogen atom, also oxygen, sulfur or nitrogen atom as a component forming the ring, or their N-oxides. Compounds of the formula (I) elicit anticancer activity and can be used in medicine.

EFFECT: valuable medicinal properties of compounds.

10 cl, 1 tbl, 24 ex

FIELD: organic chemistry or heterocyclic compounds, chemical technology.

SUBSTANCE: invention relates to technology for manufacturing heterocyclic compounds, in particular, to technology for manufacturing 3-methyl-1,2,4-triazolyl-5-thioacetate morpholinium that is known as a substance for pharmaceutical designation "thiotriazoline". Invention describes a method for preparing 3-methyl-1,2,4-triazolyl-5-thioacetate morpholinium that involves reaction of 3-methyl-1,2,4-triazolyl-5-thioacetic acid with morpholine in liquid medium wherein methylene chloride is used as a liquid medium. Method provides significant elevating the yield percent of the end product, enhances its quality and significant reducing industrial consumptions.

EFFECT: improved preparing method.

4 cl, 1 tbl, 4 ex

FIELD: organic chemistry, medicine, pharmacology.

SUBSTANCE: invention relates to new derivatives of carbamic acid esters of the general formula (I):

and their pharmaceutically acceptable salts eliciting activity with respect to metabotropic glutamate receptors mGlu of group I that can be used for treatment of acute and/or chronic neurological disorders. In the general formula (I) R1 means hydrogen atom or (C1-C7)-alkyl; R2 and R2' mean independently of one another hydrogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom or trifluoromethyl; X means oxygen (O), sulfur (S) atom or two hydrogen atoms not forming a bridge; A1/A2 mean independently of one another phenyl or 6-membered heterocycle comprising 1 or 2 nitrogen atom; B represents group of the formula:

wherein R3 means (C1-C7)-alkyl and others; Y means -O-, -S- or a bond; Z means -O- or -S-; or B means 5-membered heterocyclic group of formulae: (a) , (b) , (c) or (d) . Also, invention relates to methods for preparing compounds and to a medicinal agent based on thereof.

EFFECT: improved preparing methods, valuable medicinal properties of compounds.

22 cl, 1 tbl, 2 sch, 78 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of benzodiazepine. Invention describes a derivative of benzodiazepine of the formula (I): wherein dotted lines show the possible presence of a double bond; R1, R2, R3, R4 and R5 are given in the invention claim; n represents 0, 1, 2, 3 or 4; X represents sulfur atom (S) or -NT wherein T is give in the invention claim; A represents hydrogen atom, (C6-C18)-aryl group substituted optionally with one or more substitutes Su (as given in the invention claim) or (C1-C12)-alkyl; or in alternative variant R4 and R5 form in common the group -CR6=CR7 wherein CR6 is bound with X and wherein R6 and R7 are given in the invention claim, and their pharmaceutically acceptable salts with acids or bases. It is implied that compounds corresponding to one of points (a)-(e) enumerated in the invention claim are excluded from the invention text. Also, invention describes methods for preparing compounds of the formula (I) and a pharmaceutical composition eliciting the hypolipidemic activity. Invention provides preparing new compounds eliciting the useful biological properties.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

20 cl, 6 tbl, 192 ex

The invention relates to organic chemistry and can find application in medicine

The invention relates to new compounds of the formula (I)

in which Ar1means pyrazole which may be substituted by one or more groups R1, R2or R3; Ar2means naphthyl, tetrahydronaphthyl, each of which is optionally substituted by 0-1 groups R2; X means5-C8cycloalkenyl, phenyl, optionally substituted by a hydroxy-group or1-C4alkoxygroup, furan, pyridinoyl, pyrazolyl, pyridinyl, optionally substituted by a hydroxy-group or1-C4alkoxygroup, piperidinyl; Y represents a bond or a saturated branched or unbranched1-C4the carbon chain, with one methylene group is optionally replaced with NH, or and Y is optionally independently substituted by oxopropoxy; Z means morpholine, group, pyridinyl, furanyl, tetrahydrofuranyl, thiomorpholine, pentamethylbenzene, pentamethylbenzene, secondary or tertiary amine, the nitrogen atom of the amino group covalently linked to the following groups selected from a range that includes the C1-C3alkyl and C1-C5alkoxyalkyl; R1means31-C6alkyl which is optionally partially or fully galogenidov, halogen; R3means phenyl, pyrimidinyl, pyrazolyl, which is substituted by one branched or unbranched1-C6the alkyl, and pyridinyl, optionally substituted C1-C3alkoxygroup or amino group, W denotes O and its pharmaceutically acceptable salts

The invention relates to new derivatives of nitrogen-containing heterocyclic compounds of the formula

or their pharmaceutically acceptable salts, where R1represents H, COCOR2, COOR3or SO2R3, R2is1-6alkyl, C1-6alkenyl,5-7cycloalkyl, 2-thienyl, 3-thienyl, phenyl or substituted phenyl, R3is phenylalkyl,represents a saturated five-membered nitrogen-containing heterocyclic ring with one nitrogen atom or benzododecinium saturated six-membered nitrogen-containing heterocyclic ring;is oxazol, oxadiazole or thiazole, And is associated with carbon atom of the five-membered heteroaromatic rings and represents COO(CH2)mAr,where R1has the values listed above or is CONR4(CH2)mAr or (CH2)mO(CH2)nAr and R1cannot be COCOR2or SO2R3, R4represents H or<

The invention relates to organic chemistry and can find application in medicine

The invention relates to pharmaceutically acceptable salts of the compounds of formula (I) or solvate specified salts in which the compound of formula (I) is in the form of (R)-enantiomer, (S)-enantiomer or the racemate

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to new 2-aminopyridine derivatives of formula I , wherein R1 is cyano, carboxyl or carbamoyl; R2 is hydrogen, hydroxyl, C1-C6-alkoxy or phenyl; R3 and R4 are aromatic hydrocarbon such as phenyl or naphthyl, 5-14-membered 5-14-membered optionally substituted aromatic group, excepted cases, when (1) R1 is cyano, R2 is hydrogen, and R3 and R4 are simultaneously phenyl;(2) R1 is cyano, R2 is hydrogen, R3 is 4-pyridyl, and R4 is 1-pyridyl; (3) R1 is cyano, R2 is 4-methylphenyl, and R3 and R4 are simultaneously phenyl;(4) R1 is cyano, R2, R3 and R4 are simultaneously phenyl, or salts thereof. Derivatives of present invention have adenosine receptor antagonist activity and are useful in medicine for treatment of irritable bowel syndrome, constipation, and defecation stimulation.

EFFECT: 2-aminopyridine derivatives as adenosine receptor antagonists useful in medicine.

34 cl, 2 tbl, 179 ex

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