MXPA00002171A

MXPA00002171A - 6,7-asymmetrically disubstituted quinoxalinecarboxylic acid deri vatives, addition salts thereof, and processes for the preparation of both

Info

Publication number: MXPA00002171A
Application number: MXPA/A/2000/002171A
Authority: MX
Inventors: Yasuo Takano; Futoshi Shiga; Masanori Takadoi; Hideharu Uchiki; Jun Asano; Tsuyoshi Anraku; Kazunori Fukuchi; Junichiro Uda; Naoki Ando
Original assignee: Kyorin Pharmaceutical Co Ltd
Priority date: 1997-09-01
Filing date: 2000-03-01
Publication date: 2001-11-21

Abstract

Excitatory amino acid receptors comprising as the active ingredient 6,7-asymmetrically disubstituted quinoxalinecarboxylic acid derivatives or addition salts thereof, particularly compounds exhibiting antagonism against AMPA receptors;and processes for the preparation of both. The disubstituted quinoxalinecarboxylic acid derivatives are represented by formula (1), wherein Q is halogeno, optionally halogenated lower alkyl, Ar-P- (wherein Ar is phenyl optionally substituted with one or more substituting groups, or naphthyl;and P is lower alkylene, lower alkenylene, lower alkynylene, oxygen or sulfur) or L-A-;R is nitro, trifluoromethyl, optionally substituted amino or a group of general formula (7), R1 is aralkyl, phenyl, naphthyl, a 5- or 6-membered heterocycle or a fused ring thereof (which may have one or more substituting groups on the aromatic ring or the heterocycle), hydrogen, optionally halogenated lower alkyl or cycloalkyl;and R2 is hydroxyl, lower alkoxy or a group of general formula (6).

Description

DERIVATIVES OF THE QUINOXALINCARBOXILIC ACID ASISTRICTED ASYMMETRICALLY IN THE POSITIONS 6.7, SALTS OF ADDITION OF THEM, AND PROCESSES FOR THE PREPARATION OF BOTH Technical Field The present invention relates to asymmetrically disubstituted quinoxalinecarboxylic acid derivatives at positions 6,7 and their addition salts effective for the therapy of brain nerve cell disorder, as antagonists against the excitatory amino acid receptor, in particular, the AMPA receptor against selective antagonists in the non-NMDA receptor, the processes to prepare them, and the medicinal compositions containing those compounds.

Previous Technologies Glutamic acid, being an excitatory amino acid, is a major excitatory transmitting substance in the central nervous system of vertebrates, and is known as an amino acid that is contained in large quantities in the brain. It is known, however, that when it is released from the axon terminals of the nerves exceeding the physiological threshold, overstimulation to postsynaptic glutamic acid receptors causes the death of nerve cells. This is known as excitotoxicity. In recent years, it is being clarified that the excitotoxicity due to glutamic acid is deeply related to different diseases of the cerebral nerves, such as cerebral hemorrhage, cephalic damage, epileptic intussusception, Huntington's chorea, Parkinson's disease, amyotrophic lateral sclerosis and disease of Alzheimer's If such excitotoxicity can be effectively prevented, it is considered that a potential could be opened for the therapy of those intractable diseases, for which currently there are no therapeutic means at present. Generally classified, the glutamic acid receptor is divided into a receptor of the ion channel type and the receptor of the type that binds to protein G, and this receptor of the ion channel type is further divided into the NMDA receptor ( N-methyl-D-aspartic acid) and the non-NMDA receptor. In addition, the last non-NMDA receptor is classified into AMPA receptor (amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and KA receptor (cainic acid). Studies of these excitatory amino acid receptors are progressing and, above all, it is known that a drug with antagonism against the AMPA receptor in the non-NMDA receptor does not express the side effects (learning and memory disturbances, symptoms similar to those of schizophrenia). , etc.) that are inherent to a drug (MK-801 or similar) with antagonism against the NMDA receptor (Neurosci, Biobehav, Rev., 1992, 16, 13-24, J. Pharmacol, Exp. Ther., 1958, 245, 969-974), and that the protective effect on the cerebral nerves can still be expected after administration after ischemia (Science, 1990, 24J, 571-574). In addition, compounds with antagonism against the AMPA receptor, such as NBQX having a quinoxalindione structure have reported the disadvantage of causing kidney disturbances, etc., which are considered to be based on the physicochemical properties (J. Cereb. Metab., 1994, 14, 251-261), therefore, it is said that they are not satisfactory compounds. Now, as compounds with a structure similar to the quinoxalincarboxylic acid derivatives, are the compounds represented by a general formula (A) (TO) ? (wherein X independently denotes a chlorine or bromine atom, and R denotes a methyl or ethyl group), described in Japanese Unexamined Patent Publication No. Sho 56-5416 by Lilly Co. , as compounds with antiviral function, the compounds represented by a general formula (B) T T (where R and Ri independently denote halogen atoms, R 2 denotes a hydrogen, methyl or ethyl group, R 3 denotes a hydrogen, methyl, ethyl, hydroxyethyl, benzyl or ethoxycarbonylmethyl group, and R 4 denotes a cyclooctyl group, norbornyl or the like), in Japanese Unexamined Patent Publication No. Sho 56-81569 by Lilly Co. , also as compounds with antiviral function, and the like already known. However, positions 6 and 7 are symmetric in these compounds, and it is not known whether they have antagonism against the AMPA receptor in the excitatory amino acid receptor of the compounds of the invention, and have a structure different from that of the compounds of the invention. invention. In addition, the compounds represented by a general formula (C) (where R and R4 independently denote hydrogens, nitro or methoxy groups, Ri and R2 independently denote hydrogens, nitro or methoxy groups, or 5 halogen atoms (one of R, Ri, R2 and R4 is a group other than hydrogen, in the if Ri and R2 are not nitro groups or methoxy groups, Ri and R2 are independently halogen atoms together and R and R4 are hydrogens, and, in the case of one of R, Ri, R2 and R4 are a nitro group, any of Ri and R2 is a methoxy group), R3 denotes a hydrogen, a lower alkyl group, which may be substituted by halogen, a lower cycloalkyl group, a lower alkenyl group or a 2-chloroethyl group , and n denotes 0 or 2), described in Japanese Unexamined Patent Publication No. Sho 55-69514 by Lilly Co. , also as compounds with an antiviral function, are known, but the disclosed compounds have a structure different from that of the compounds of the invention and are not described as having antagonism against the AMPA receptor in the receptor • The excitatory amino acid of the compounds of the invention. In addition, W092-11245 described by Warner-Lambert Co. , the compounds represented by a general formula (D) (where Y denotes an oxygen, sulfur or nitrogen atom, Rx, R2, Rp and R? 2 denote hydrogens, lower alkyl groups, which can be substituted with halogen, halogen atoms, trifluoromethyl groups, cyano groups, nitro groups, methylthio groups, lower alkenyl groups, lower alkynyl groups, sulfonamide groups or the like, or arbitrarily two of Ri, R2, Rn and R12 can form a ring (a 6-membered ring or heterocycle, which may contain a heteroatom), and X denotes a sulfonylamide group, which may have a substituent, or the like), are known as compounds with antagonism against excitatory amino acid receptors. However, for those compounds, those which have asymmetric substituents at positions 6 and 7 of quinoxaline as the compounds of the invention are not described, and, with the disclosed compounds, no antagonism of AMPA and antagonism of glycine is shown. described can not be considered satisfactory either. The invention provides compounds with antagonism against the glutamic acid receptor which is considered to be an etiology that results in memory disturbances or dementia, due to diseases and selective cell death, in particular, with high affinity and selectivity against the AMPA receptor in the non-NMDA receptor, and with protective effect on brain nerve cells.

Description of the Invention 15 As a result of diligent studies to explore an antagonistic drug against the excitatory amino acid receptor, effective for the therapy of brain nerve cell disorders, in particular, a selective antagonist drug against the The AMPA receptor in the non-NMDA receptor, mainly in the development of a novel therapeutic drug for brain nerve cell disorder, the inventors have found that quinoxalincarboxylic acid derivatives disubstituted asymmetrically in The 6,7 positions of the invention and its addition salts have excellent antagonism against the AMPA receptor. Namely, according to the invention, it has been found that asymmetrically substituted quinoxalicarboxylic acid derivatives at positions 6, 7 represented by a general formula (1) [wherein, Q denotes a halogen atom, a lower alkyl group, which may be substituted with a halogen atom, of general formula (2) Ar-P (2) (where Ar denotes a phenyl group, which may have one or more substituents or naphthyl group, and P denotes a lower alkylene, lower alkenylene, lower alkynylene, oxygen or sulfur atom), general formula (3) LA- (3) (where L denotes a general formula (4) (where V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- or 6-membered heterocyclyl and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle) , hydrogen atoms, hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group, aldehyde group, the general formula (4-a) or the general formula (4-b) (where U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its ring the condensate (those may have one or more substituents on the aromatic or heterocyclyl ring), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes an aralkyl group, phenyl group, naphthyl group, heterocycle or 6 members and their fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group), or general formula ( 4-c) (where X denotes an oxygen atom or sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle) , lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, 5- or 6-membered heterocycles and their fused rings ( those may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups), the B ring denotes a saturated or unsaturated heterocycle and its ring condensed (those may have one or more substituents on the heterocycle or fused ring), which additionally may contain one or two oxygen, nitrogen or sugar atoms ufre, and m denotes 0 or 1, A denotes a single bond, lower alkylene, lower alkenylene or lower alkynylene, or the general formula (5) (where R6 and R7 denote identical or different hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom, cycloalkyl groups, phenyl groups, which may have one or more substituents or aralkyl groups, which may have one or more substituents); R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, R 2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote an atom of hydrogen, while the other denotes a phenyloxy group or aralkyloxy group (those may have one or more substituents on the aromatic ring), hydroxyl group or lower alkoxy group, and R denotes a nitro group, trifluoromethyl group, amino group, which may be substituted, or the general formula (7) 3 (wherein R10 and R11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, alkyl groups lower, which may be substituted with a halogen atom or cycloalkyl groups, or R10 and R11 may form a ring (which may additionally contain one or two heteroatoms) together with the hydrogen atom, and n denotes 1 to 2)] , and their addition salts have excellent antagonism against the AMPA receptor, and the invention is completed. Furthermore, according to the invention, it has been found that quinoxalincarboxylic acid derivatives disubstituted asymmetrically in the 6,7 positions represented by a general formula (1) d) [wherein, Q denotes a halogen atom, a lower alkyl group, which may be substituted with a halogen atom, the general formula (2) Ar-P (2) (where Ar denotes a phenyl group, which may have one or more substituents or naphthyl group, and P denotes a lower alkylene, lower alkenylene, lower alkynylene, oxygen or sulfur atom), or the general formula (5) (where R6 and R7 denote identical or different hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl group, phenyl groups, which may have one or more substituents or aralkyl groups, which may have one or more substituents); R denotes a nitro group, trifluoromethyl group, amino group, which may be substituted, or the general formula (7) (where R10 and Ru denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R10 and R11 may form a ring (which may additionally contain one or two heteroatoms) together with the nitrogen atom), and n denotes 1 to 2), R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), a hydrogen atom, a lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these can be used). having one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote a hydrogen atom, while the other denotes a phenyloxy group or aralkyloxy group (these may have one or more substituents on the aromatic ring), hydroxyl group or lower alkoxy group)], and their addition salts have excellent antagonism against the AMPA receptor. Furthermore, according to the invention, it has been found that quinoxalincarboxylic acid derivatives disubstituted asymmetrically at positions 6, 7 represented by a general formula d-a) (where L denotes a general formula (4) (where V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- or 6-membered heterocyclyl and its fused ring (these may have one or more substituents on an aromatic ring or heterocycle), hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group, aldehyde group, general formula (4-a) or the general formula (4-b) (where U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its ring condensate (those may have one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes an aralkyl group, phenyl group, naphthyl group, heterocycle or 6 members and their fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group), or general formula ( 4-c) (where X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle ), lower alkyl group, which may be substituted with a halogen atom or a cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, 5- or 6-membered heterocycles and their fused rings (those may have one or more substituents on the aromatic rings or J 19 heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups), ring B denotes a saturated or unsaturated heterocycle and its fused ring (these may have one or more substituents on the heterocycle) or condensed ring), which additionally may contain one or two oxygen, nitrogen or sulfur atoms, and m denotes 0 or 1, A denotes a single bond, lower alkylene or lower alkenylene, R1 denotes an aralkyl group, phenyl group, naphthyl group , 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may -ySt ~ v - * - F? T - - - having one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 can form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote a hydrogen atom, while the other denotes a phenyloxy group or aralkyloxy group ( those may have one or more substituents on the aromatic ring), a hydroxyl group or lower alkoxy group], and their addition salts have excellent antagonism against the AMPA receptor. Moreover, according to the invention, it has been found that qumoxalincarboxylic acid derivatives substituted asymmetrically at positions 6, 7 represented by a general formula (1-b) Where L denotes a general formula (4) (where V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- or 6-membered heterocyclyl and its fused ring (these may have one or more substituents on an aromatic ring or heterocycle) , hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group, aldehyde group, general formula (4-a) or the general formula (4-b) (where U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring ( may have one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its condensed ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group), or general formula (4-c) (where X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its ring Condensate (those may have one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or a cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, groups Phenyl, naphthyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups), ring B denotes a saturated or unsaturated heterocycle and its fused ring (those may have one or more substituents on the heterocycle or fused ring), which additionally may contain one or two oxygen, nitrogen or sulfur atoms, and m denotes 0 or 1, A denotes a single bond, lower alkylene or lower alkenylene, R denotes a nitro group, amino group, which may be substituted, or the general formula (7) (wherein R10 and R11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R10 and R11 may form a ring (which may additionally contain one or two heteroatoms) together with the nitrogen atom), and n denotes 1 to 2), R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote an atom of hydrogen, while the other denotes a phenyloxy group or an aralkyloxy group may have one or more substituents on the aromatic ring), a hydroxyl group or lower alkoxy group], and their addition salts have excellent antagonism against the receptor AMPA, leading to the conclusion of the invention. In the general formula (1-a) of the compounds of the invention, there can preferably be mentioned compounds wherein R 1 is a hydrogen atom, R 2 is a hydroxyl group or lower alkyl group, A is a single bond, and, in the general formula (4) for L, V is a lower alkylene and T is the general formula (4-a) or the general formula (4-c). As those preferable compounds, the following compounds, namely 3, 4-dihydro-7- (4- (hydroxymethyl) imidazol-1-yl) -3-oxo-6-trifluoromethyl-2-carboxylic acid ethyl trifluoromethyl-2-carboxylate, 3, 4-Dihydro-7- (4- (4-ethoxycarbonylphenyl) -carbamoyloxy) methyl) imidazol-1-yl) -3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid ethyl ester, 3,4-Dihydro- 7- (4- (((4-Ethoxycarbonyl-2-fluorophenyl) carbamoyloxy) methyl) imidazol-1-yl) -3-oxo-6-trifluoromethyl-2-carboxylic acid ethyl ester, Acid 7- (4- ((N - (4-carboxyphenyl) carbamoyloxy) -methyl) imidazol-1-yl) -3,4-dihydro-3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid, 3,4-Dihydro-7- (4- ( (N- (4-ethoxycarbonyl-2-fluorophenyl) carbamoyloxy) methyl) imidazol-1-yl) -3-oxo-6-trifluoromethyl-2-carboxylic acid ethyl ester, 7- (4- ((N- (4- carboxy-2-fluorophenyl) -carbamoyloxy) methyl) imidazol-1-yl) -3,4-dihydro-3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid, 3, -Dihydro-7- (4- (( N- (4-ethoxycarbonyl-methyl-phenyl) carbamoyloxy) methyl) imidazol-1-yl) -3-oxo-6-trifluoromethyl-2-ethyl-2-carboxylic acid carboxylate, 7- (4- ((N- (4-carboxymethylphenyl) ) -carbamoyloxy) -methyl) imidazol-1-yl) -3, 4-dihydro-3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid, 3,4-Dihydro-7- (4- (((4-ethoxycarbonylphenyl) -aminocarbonylamino) methyl) imidazol-1-yl) -3 ethyl -oxo-6-trifluoromethyl-2-carboxylic acid, 7- (4- (((4-carboxyphenyl) aminocarbonyl-amino) methyl) imidazol-1-yl) -3,4-dihydro-3-oxo-6 -trifluoromethyl-quinoxaline-2-carboxylic acid, 7- (3-formylpyrrol-1-yl) -3-oxo-l, 2,3,4-tetrahydro-6-trifluoromethylquinaxolin-2-carboxylic acid ethyl ester, Hydrochloride 7- ( 3- (aminomethyl) pyrrol-1-yl) -3-oxo-1,2,3-tetrahydro-6-trifluoromethylquinaxolin-2-ethyl carboxylate, 7- (3- (((4-ethoxycarbonylphenyl) aminocarbonyl-amino ) -methyl) pyrrol-1-yl) -3-oxo-l, 2,3, 4-tetrahydro-6-trifluoromethylquinaxolin-2-carboxylic acid ethyl ester, 7- (3- (((4-ethoxycarbonylphenyl-2-fluorophenyl) ) -aminocarbonylamino) methyl) pyrrol-1-yl) -3-oxo-l, 2,3,4-tetrahydro-6-trifluoromethylquinaxolin-2-carboxylic acid ethyl ester, 3,4-dihydro-7- (3- (( (4-ethoxycarbonylphenyl) -aminocarbonylamino) -methyl) pyrrol-1-yl) Ethyl-3-oxo-6-trifluoromethylquinaxolin-2-carboxylate, 7- (3- (((4-carboxyphenyl) aminocarbonyl-amino) -methyl) pyrrol-1-yl) -3,4-dihydro-3- acid oxo-6-trifluoromethylquinaxolin-2-carboxylic acid, 3,4-Dihydro-7- (3- (((4-ethoxycarbonyl-2-fluorophenyl) aminocarbonylamino) methyl) pyrrol-1-yl) -3-oxo-6-trifluoromethylquinaxolin -2-ethyl carboxylate, 7- (3- (((4-carboxy-2-fluorophenyl) aminocarbonylamino) methyl) pyrrol-1-yl) -3-dihydro-3-oxo-6-trifluoromethylquinaxolin-2- acid carboxyl, and the like may be mentioned. In the general formula (1-b) of the compounds of the invention, compounds where R is a nitro group, R is a hydrogen atom, R2 is an hydroxyl group, A is a single bond, and can be preferably mentioned, and , in the general formula (4) for L, V is a lower alkylene and T is the general formula (4-a) or the general formula (4-c). As those preferable compounds, the following compounds, namely, 3, 4-dihydro-6-nitro-7- (4- ((N-isopropyl-carbamoyloxy) methyl) imidazolyl) -3-oxo-quinoxaline-2-carboxylic acid , 7- (4- ((Nn-Buty-Icarbamoyloxy) methyl) -imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 7- (4- ((Nt-buty-carbamoyloxy) methyl) ) -imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 3,4-dihydro-6-nitro-3-oxo-7- (4- ((N-phenyl-carbamoyloxy) ) methyl) imidazolyl) quinoxaline-2-carboxylic acid, 7- (4- ((N- (4-isopropylphenyl) carbamoyloxy) -methyl) -imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxalin-2 acid carboxylic acid, 7- (4- ((N- (2-bromophenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid,% 9 7- (4- ((N- (3-bromophenyl) carbamoyloxy) methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 7- (4- (N-) acid (4-bromophenyl) carbamoyloxy) -methyl) imidazolyl) -3, -dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 7- (4- ((N- (2-chlorophenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 7- (- ((N- (3-chlorophenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6 acid -nitro-3-oxoquinoxalin-2-carboxylic acid, 7- (4- ((N- (4-chlorophenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxalin-2- acid carboxylic, 7- (4- ((N- (2,3-dichlorophenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 7- (4-carboxylic acid - ((N- (2,4-dichlorophenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 7- (4- ((N- (2 , 5-dichlorophenyl) carbamoyloxy) -methyl) imidazolyl) -3, -dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, Acid 7- (4- ((N- (2,6-dichlorophenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoqu-noxalin-2-carboxylic acid, 7- (4- (( N- (3,4-dichlorophenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxal? N-2-carboxylic acid, 7- (4- ((N- (3, 5-dichlorophenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 3,4-dihydro-7- (4- ((N- (4-methoxyphenyl ) -carbamoyloxy) methyl) imidazolyl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid, 3,4-dihydro-7- (4- ((N- (2-fluorophenyl) -carbamoyloxy) methyl) imidazolyl) - 6-Nitro-3-oxoquinoxalin-2-carboxylic acid, 3,4-dihydro-7- (4- ((N- (3-fluorophenyl) -carbamoyloxy) methyl) imidazolyl) -6-nitro-3-oxoquinoxalin-2 acid -carboxylic acid, 3-acid, -dihydro-7- (4- ((N- (4-fluorophenyl) -carbamoyloxy) methyl) imidazolyl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid, 3,4-dihydroxy acid 7- (4- ((N- (2-methylphenyl) -carbamoyloxy) methyl) imidazolyl) -6-nitro-3-oxoquihoxaline-2-carboxylic acid, 3i ^ Si \ y, 3, 4-Dihydro-7- (4- ((N- (3-methylphenyl) -carbamoyloxy) methyl) imidazolyl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid, 3,4-dihydro-3-acid (4- ((N- (4-methylphenyl) -carbamoyloxy) methyl) imidazolyl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid, Acid 3, -dihydro-6-nitro-3-oxo-7- (4 - ((N- (2-trifluoromethylphenyl) carbamoyloxy) methyl) imidazolyl) -quinoxaline-2-carboxylic acid, 3,4-dihydro-6-nitro-3-oxo-7- (4- ((NO-trifluoromethylphenyl) carbamoyloxy) acid ) ethyl) imidazolyl) -quinoxaline-2-carboxylic acid, 3,4-dihydro-6-nitro-3-oxo-7- (4- ((N- (4-trifluoromethylphenyl) carbamoyloxy) methyl) imidazolyl) -quinoxalin- 2-carboxylic acid, 3,4-dihydro-6-nitro-3-oxo-7- (4- ((N- (4-trifluoromethoxyphenyl) carbamoyloxy) methyl) imidazolyl) -quinoxaline-2-carboxylic acid, Acid 7, 4- ((N- (3-carboxyphenyl) carbamoyloxy) -methyl) imidazolyl) -3, -dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, Acid 7, - ((N- (4- carboxyphenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxalin-2-car boxyl, Acid 7, 4- (((2-fluorophenyl) aminocarnonylamino) -methyl) imidazolyl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid, 7, 4- (((4-carboxyphenyl) aminocarnonylamino) -methyl) imidazolyl) -3, -dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 7, 4- ((N-benzylcarbamoyloxy) methyl) imidazolyl ) - 3, 4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylate sodium, 3, 4-dihydro-6-nitro-3-oxo-7- (3- ((N-phenylacarbamoyloxy) methyl) -4-pyridon-l-yl) quinoxaline-2-carboxylic acid, 7- (3- ((N- (2-bromophenyl) carbamoyloxy) -methyl) -4-pyridon-l-yl) -3,4-dihydro acid -6-nitro-3-oxoquinoxaline-2-carboxylic acid, 7- (3- ((N- (3-bromophenyl) carbamoyloxy) -methyl) -4-pyridon-l-yl) -3,4-dihydro-6-acid -nitro-3-oxoquinoxalin-2-carboxylic acid, 7- (3- ((N- (4-bromophenyl) carbamoyloxy) -methyl) -4-pyridon-l-yl) -3,4-dihydro-6-nitro acid -3-oxoquinoxaline-2-carboxylic acid, 7- (3- ((N- (3-carboxyphenyl) carbamoyloxy) -methyl) -4-pyridon-1-yl) -3,4-dihydro-6-nitro-3 -oxoquinoxalin-2-carboxyl, Acid 3, -dihydro-6-nitro-3-oxo-7- (3-phenylaminocarbonylamino) -4-pyridon-l-yl) quinoxaline-2-carboxylic acid, 7- (3- ((2-Bromophenyl) aminocarbonylamino) -4-pyridon-1-yl) -3,4-dihydro-6-nitro-3-oxoquinoxal? -2-carboxylic acid, Acid 7- (3- ((3-bromophenyl) aminocarbonylamino) -4-pyridon-l-yl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 7- (3- ((4-bromophenyl) aminocarbonylamino) -4-pyridon-l-yl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 3,4-dihydro-7- (3- ((4-fluorophenyl) aminocarbonylamino) acid ) -4-pyridon-l-yl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid, 3,4-dihydro-7- (3- ((4-methylphenyl) aminocarbonylamino) -4-pyridone-1-acid il) -6-nitro-3-oxoquinoxaline-2-carboxyl, Acid 3, -dihydro-7- (3- ((4-methoxyphenyl) amino-carbonylamino) -4-pyridon-1-yl) -6-nitro- 3-oxoquinoxaline-2-carboxylic acid, 7- (3- (benzylaminocarbonylamino) -4-pyridon-1-yl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, benzyl) carbonylamino acid) -4- pyridon-1-yl) -3, 4-dihydro-6-ni.fro-3-oxoquinoxalin-2-carboxylic acid, 7 -3- ( 4-bromophenyl) carbonylamino) -4- pyridon-1-yl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid, 3-ethoxy-7- (4- (hydroxymethyl) imidazolyl) -6- nitroquinoxalin-2 ethyl-carboxylate, ethyl 7- (4- ((N- (4-bromophenyl) carbamoyloxy) methyl) -imidazolyl) -3-ethoxy-6-nitroquinoxaline-2-carboxylate, 3-Ethoxy-6-nitro-7 - (ethyl 4- (trifluoroacetamidomethyl) -imidazolyl) quinoxaline-2-carboxylate, 3-Ethoxy-6-nitro-7- (3- (hydroxymethyl) -4-pyridon-1-yl) -6-nitroquinoxalin-2- ethyl carboxylate, 7- (3-amino-4-pyridon-l-yl) -3-ethoxy-6-nitroquinoxaline-2-carboxylic acid ethyl ester, 7- (3- ((4-bromophenyl) aminocarbonylamino) -4- pyridon-1-yl) -3-ethoxy-6-nitroquinoxaline-2-carboxylic acid ethyl, and the like can be mentioned. In the description of the general formula (I) of the invention, for the substituents in the phases of "phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or 2S heterocycle), "" aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle) "," ring B denotes a saturated heterocycle or unsaturated and its condensed ring (these may have one or more substituents on the aromatic ring or heterocycle), which may additionally contain one or two oxygen, nitrogen or sulfur atoms "," aralkyl group, phenyl group, heterocycle of 5 or 6 members and their fused ring (those may have one or more substituents on the aromatic ring or heterocycle), "" phenyloxy group, aralkyloxy group (those may have one or more substituents on the aromatic ring or heterocycle), "" phenyl group, " which may have one or more substituents or aralkyl group which may have one or more substituents ", and" phenyl group, which may have one or more substituents or the naphthyl group ", is referred to the halogen atom no, hydroxyl group, lower alkyl group, which may be substituted with a halogen atom, lower alkoxy group, lower alkylthio group, lower alkoxycarbonyl group, nitro group, amino group, cyano group, carboxyl group, aldehyde group, lower alkyl group with a carboxyl group or the like. For the "lower alkyl groups", linear or branched with 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl or the like, are mentioned for the "cycloalkyl groups", those of 3 a are mentioned 7 carbon atoms, such as cyclopropyl, cyclopentyl, cyclohexyl or the like, for the "halogen atoms", are mentioned to fluorine, chlorine, bromine and iodine, for the "lower alkoxy groups", are mentioned to the straight chain or branched with 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy or the like, for the "lower alkylthio groups", those with straight or branched chain having 1 to 6 carbon atoms, such as methylthio, are mentioned, ethylthio, propylthio or the like, for "lower alkoxycarbonyl groups", straight or branched chain with 1 to 4 carbon atoms are mentioned, such as methoxycarbonyl, ethoxycarbonyl or the like, for the "aralkyloxy groups", benzyloxy is mentioned , phenylethyloxy, phenylpropyl oxy and the like, for the "aralkylthio groups", benzylthio, phenylthio, phenylpropylthio or the like are mentioned, and for the "amino groups which may be substituted", amino groups are mentioned which may be substituted with an acyl group or arylsulfonyl group , for example, acetyl, methanesulfonyl, phenylsulfonyl or the like, or which may be substituted with a lower alkyl group, which may be substituted with one or two halogen atoms, phenyl group, which may have one or two substituents and aralkyl group , which may have one or two substituents. The substituents referred to herein indicate the "substituents" defined above. Also, in the description, "heterocycles" in the phrases "phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle)", "aralkyl group , phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle) ", and" aralkyl group, phenyl group, 5- or 6-membered heterocycle and its Condensed ring (those may have one or more substituents on the aromatic ring or heterocycle), "are monocyclic or polycyclic saturated or unsaturated heterocyclic groups, which may have one or more substituents and which may contain one or two oxygen, nitrogen or nitrogen atoms. sulfur, and, for example, may be mentioned pyrrolidyl, piperidyl, piperacillus, morpholyl, thiomorpholyl, furanyl, thienyl, pyrazolyl, imidazolyl, oxacolyl, thiazolyl, pyridyl, pyrimidyl, pyridacyl, pyracil or the like, and their "fused rings" represent fused rings of the "heterocycles" with benzene and, for example, may be mentioned indolyl, tetrahydroquinolyl, benzoxazolidinyl, benzothiazolidinyl, benzofuranyl, benzothienyl, benzimidazolyl, quinolyl, isoquinolyl, quinazolyl, quinoxalyl, cinolyl and the like. In addition, for the "ring B denotes a saturated or unsaturated heterocycle and its fused ring, which additionally may contain one or two oxygen, nitrogen or sulfur atoms", the "heterocycles" and "their condensed rings" are mentioned, they also represent saturated or unsaturated heterocycles or their fused rings, which may be substituted with a carbonyl group, in which the carbonyl group may be substituted on the "heterocycles" and "their fused rings" and, for example, may be mentioned 2- pyrrolidone, 3-pyrrolidone, 2-imidazolidinone, 2-thiazolidinone, 4-thiazolidinone, 2-oxazolidinone, 4-oxazolidinone, 2-pyridone, 4-pyridone, 2-pyrimidinone, 4-pyrimidinone, 2-pyrimidinedione, 2-quinolone , 4-quinolone, etc. In addition, "rings (which may additionally contain one or two heteroatoms) may be formed together with a nitrogen atom" are saturated monocyclic or polycyclic heterocyclic groups, which may additionally contain one or two nitrogen, oxygen or sulfur atoms, and, for example, pyrrolidyl, piperidyl, piperazyl, morpholyl, thiomorpholyl, indolyl, tetrahydroquinolyl, etc. may be mentioned. The compounds of the invention can be prepared through, for example, the processes shown below. The compounds, where R 1 is a hydrogen atom, among the compounds represented by the general formula (1), can be synthesized by reacting the compounds represented by the general formula (10) (where Q, R and R are as described above, and R12 denotes a lower alkyl group, which may be substituted by a halogen atom or an aralkyl group, which may have one or more substituents), for 0.5 to 72 hours at 20 to 12 ° C without solvent or in a suitable solvent, for example, water, acetic acid, methanol or the like, using the appropriate acid, for example, hydrochloric acid, sulfuric acid, hydrobromic acid, trifluoroacetic acid or the like.

In addition, the compounds, where R 1 is a hydrogen atom, can also be synthesized between the compounds represented by the general formula (1), in the case of which R 2 is a lower alkoxy group among the compounds represented by the general formula (10) (where Q, R, R2 and R12 are as described above), reacting those compounds for 0.5 to 10 hours at 20 to 100 ° C in a suitable solvent of water, methanol, ethanol or the like, using a suitable alkali, for example, potassium hydroxide, lithium hydroxide or the like to convert to carboxylic acid, and then reacting for 0.5 to 72 hours at 20 to 120 ° C without solvent or in a suitable solvent, for example, water, acetic acid , methanol or the like using a suitable acid, for example, hydrochloric acid, sulfuric acid, hydrobromic acid, trifluoroacetic acid or the like. In addition, the compounds, where R 1 is a hydrogen atom, can also be synthesized between the compounds represented by the general formula (1), in the case where R 2 is a lower alkoxy group among the compounds represented by the general formula (10) (where Q, R, R2 and R12) are as described above), by reacting those compounds for 3 to 72 hours at 20 to 120 ° C without solvent or in a suitable solvent, for example, water, acetic acid, methanol or similar, using a suitable acid, for example, hydrochloric acid, sulfuric acid, hydrobromic acid, trifluoroacetic acid or the like to convert to an amide-ester form, and then reacting for 0.5 to 10 hours at 20 to 100 ° C in a solvent of water, methanol, ethanol or the like, using a suitable alkali, for example, potassium hydroxide, sodium hydroxide or the like. Further, when converted to compounds, with R2 being a lower alkoxy group, to the compounds, with R2 being a hydroxyl group, among the compounds represented by the general formula (1), the latter compounds can also be synthesized by reacting the first compounds during 0.5 to 10 hours from 20 to 100 ° C in a suitable solvent of water, methanol, ethanol or the like, using a suitable alkali, for example, potassium hydroxide or, lithium hydroxide or the like. In addition, the compounds, where R 1 is a hydrogen atom, among the compounds represented by the general formula (1), can also be converted to the compounds, where R 1 is substituted with a lower alkyl group, aralkyl group (which may have one or more substituents) or cyclic alkyl group, by reacting with alkyl halide, for example, methyl iodide or the like, aralkyl halide, for example, benzyl chloride, 4-methoxybenzyl chloride or the like or cyclic alkyl halide, for example , cyclopentyl bromide, cyclohexyl bromide or the like for 2 to 10 hours at 20 to 120 ° C in a suitable solvent, for example, tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N-dimethylacetamide or the like, using a base suitable, for example, sodium hydroxide, sodium carbonate, potassium carbonate or the like. In addition, the compounds represented by the general formula (1) can be synthesized by reacting the compounds represented by a general formula (11) (where Q, R, R1 and R2 are as described above), for 1 to 24 hours at 20 to 120 ° C in a suitable solvent, for example, tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, benzene, toluene or the like, using an oxidizing agent, for example, DDQ (dichlorodicyanoquinone). In addition, the compounds represented by the general formula (1) can also be synthesized by reacting the compounds represented by the general formula (11) for 1 to 72 hours L of 20 to 120 ° C in a suitable solvent, for example, tetrahydrofuran, dioxane , N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, ethanol, toluene or the like, using a suitable base, for example, triethylamine, diisopropylethylamine, sodium carbonate, potassium carbonate or the like. In addition, the compounds, L being the general formula (4) and, for T, W in the general formula (4-a) and the general formula (4-c) being an aralkyl group, phenyl group, naphthyl group, heterocycle of 5 or 6 members or with a fused ring (those may have one or more substituents on the aromatic ring or heterocycle) among the compounds, Q in the general formula (1) being represented by the general formula (3), can be synthesized by react the compounds represented by the general formula (12) (where La is the general formula (13) (where Ti denotes a hydroxyl group, thiol group or amino group, which may be substituted, and A, R, - -i, -2, ring B, V and m are as described above), with the compounds represented by a general formula (14) ZN = C = Xa (14) (where Z denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the ring aromatic or heterocycle),: € 5 lower alkyl group, which may be substituted by a halogen atom or a cyclic alkyl group, and Xa denotes an oxygen or sulfur atom), for 0.5 to 15 hours at 20 to 120 ° C in a suitable solvent, for example, methylene chloride, tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, benzene, toluene or the like, without a base or using a suitable organic base, for example, triethylamine or the like. Also, they can be synthesized by converting the compounds represented by the general formula (15) Z-Ai-D (15) (where Z denotes an alkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring ( may have one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or a cyclic alkyl group, Ai denotes a single bond, lower alkylene, lower alkenylene or lower alkynylene, and D denotes an amino group, a carboxyl group, an amide group or lower alkoxycarbonyl group), instead of the general formula (14), for the isocyanic (isothiocyanic) ester or carbamoyl chloride by a known process, and by reacting with 16 the general formula (12) similarly to the general formula (14). For example, in case D is an amino group, they can be converted to carbamoyl chloride or isocyanic (isothiocyanic) esters by reacting with phosgene (thiophosgene), phosgene dimer (2, 2, 2-trichloromethyl chloroformate) or its homologue (4-n-trophoxyl chloroformate or the like) for 1 to 5 hours at -10 to 50 ° C of a suitable solvent, for example, tetrahydrofuran, dioxane, benzene, toluene or the like, without base or using an organic base suitable, for example, triethylamine or the like. In addition, they can be converted to isocyanic ester by changing a carboxyl group to acid azide and then using the Crutius rearrangement or the Schmidt rearrangement in case D is a carboxyl group, and using the Hofmann rearrangement in case D is an amide group. In addition, in the case that D is a carboxyl group, they can also be converted to the isocyanic ester in a vessel, using DPPA (diphenylphosphoryl azide). In addition, the compounds, L being the general formula (4), among the compounds, Q being the general formula (1) represented by the general formula (3), can also be synthesized by reacting the compounds represented by the general formula (16). ) (where A, R, R1 and R2 are as described above), with the compounds represented by a general formula (17) (where T, V, and m are as described above, and R 13 denotes a lower alkyl group, which may be substituted by a halogen atom or an aralkyl group, which may have one or more substituents), for 0.5 to 5 hours at 20 to 120 ° C, without solvent or in a suitable solvent, for example, tetrahydrofuran, benzene, toluene, acetic acid or the like, using a suitable inorganic or organic acid, for example, hydrochloric acid, sulfuric acid, p-acid toluenesulfonic or similar.

In addition, the compounds, L being the general formula (4), between the compounds, Q being the general formula (1) represented by the general formula (3), can also be synthesized by reacting the compounds represented by a general formula (20). ) (where R and R are as described above, and Xb denotes a halogen atom), or the compounds represented by a general formula (20-a) (where R, R and Xb are as described above, and R1 denotes a lower alkyl group or an aralkyl group, which may have one or more substituents), which are obtained by reacting the general formula (20) with a halide of alkyl, for example, methyl iodide or the like, or aralkyl halide, for example, 4-methoxybenzyl chloride or the like for 2 to 10 hours at 20 to 120 ° C in a suitable solvent, for example, tetrahydrofuran, dioxane, N , N-dimethylformamide, N, N-dimethylacetamide or the like, using a suitable base, for example, sodium hydride, sodium carbonate, potassium carbonate or the like, with the compounds represented by a general formula (19) (where T, V, ring B and m are as described above) from 0.5 to 24 hours from 20 to 160 ° C without solvent or in a suitable solvent, for example, tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, benzene, toluene or the like, without base or using a suitable inorganic or organic base, for example, sodium hydride, sodium carbonate, potassium carbonate, triethylamine or the like. In addition, the compounds, with Q in the general formula (1) being the general formula (2) or the general formula (5), can also be synthesized by reacting the compounds represented by the general formula (20) (where R, R and Xb are as described above), or the compounds represented by the general formula (20-a) (where R, R1, R2 and Xb are as described above), which were obtained by reacting those of general formula (20) with alkyl halide, for example, methyl iodide or the like, or aralkyl halide, for example , 4-methoxybenzyl chloride or the like for 2 to 10 hours at 20 to 120 ° C in a suitable solvent, for example tetrahydrofuran, dioxane, N, -dimethylformamide, N, N-dimethylacetamide or the like, using a suitable base, for example , sodium hydride, sodium carbonate, potassium carbonate or the like, with the compounds represented by a general formula (13-a) Ar-PH (13-a) (where Ar and P are as described above), or a general formula (13-b) (13 *) (where R6 and R7 are as described above), for 0.5 to 24 hours at 20 to 160 ° C without solvent or a suitable solvent, for example, tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, N -methylpyrrolidone, acetonitrile, benzene, toluene or the like, without base or using a suitable inorganic or organic base, for example, sodium hydride, sodium carbonate, potassium carbonate, triethylamine or the like. In addition, the compounds, where L is the general formula (4) and where A is lower alkylene, among the compounds, where Q is in the general formula (1) represented by the general formula (3), they can also be synthesized by reacting the compounds represented by the general formula (18) (18)? 2 (where R, R1 and R2 are as described above, and E denotes a halogen atom), with the compounds represented by a general formula (19) (where T, V, ring B and m are as described above), for 0.5 to 48 hours at 20 to 160 ° C in a suitable solvent, for example, tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N- dimethylacetamide, N-methylpyrrolidone, acetonitrile, benzene, toluene or the like, without base or using a suitable inorganic or organic base, for example, sodium hydride, sodium carbonate, potassium carbonate, triethylamine or the like. In addition, the compounds, being lower alkylene, between the compounds, where Q in the general formula (1) being represented by the general formula (2) or the general formula (5), can also be synthesized by reacting the compounds represented by a general formula (18) (where R, R1, R2 and E are as described above), with the compounds represented by the formula general (13-a) Ar-PH (13-a) (where Ar and P are as described above), or the general formula (13-b) (where R6 and R7 are as described above), for 1 to 24 hours at 25 to 120 ° C in a suitable solvent, for example, tetrahydrofuran, N, N-dimethylformamide, benzene, toluene or the like, using an inorganic base or suitable organic, for example, sodium hydride, sodium carbonate, potassium carbonate, tetylamine or the like. In addition, the compounds represented by the general formula (1) or? to general formula (12) can also be synthesized by reacting the compounds represented by the general formula (21) (where Q and R are as described above), with diester cetomalónico acid faithful represented by a general formula (22) (where R > 14 denotes a lower alkyl group), for 2 to 12 hours at 25 to 100 ° C in a suitable solvent, for example, ethanol, methanol, tetrahydrofuran, or the like. In addition, the compounds, L being the general formula (4) and, for T, W in the general formula (4-a) and the general formula (4-c) being an aralkyl group, a phenyl group, a naphthyl group , 5 or 6 member heterocycle or its condensed ring (those may have one or more Substituents on the aromatic or heterocyclic ring), among the compounds, Q in the general formula (10) being represented by the general formula (3), can also be synthesized by reacting the compounds represented by a general formula (23). (where La, A, R, R2 and R12 are as described above), with the compounds represented by the general formula "(14) ZN = C = Xa (14) (where Z and Xa are as described above), for 1 to 15 hours at 20 to 120 ° C in a suitable solvent, for example, methylene chloride, tetrahydrofuran, dioxane, N, -dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, benzene, toluene or the like, without base or using a suitable organic base, for example, triethylamine, pyridine or the like, can also be synthesized by converting the compounds represented by the general formula (15) Z-Ai-D (15) (where Z, Ai and D are as described above), instead of the general formula (14), to isocyanic (isothiocyanic) ester or carbamoyl chloride through known processes, and reacting with the general formula (23) in a manner similar to the general formula (14) For example, in the case that D is an amino group, they can be converted to chloride - «- Sf • 671 carbamoyl or isocyanic ester (isothiocyanic) by reacting with phosgene (thiophosgene), phosgene dimer (2, 2, 2-trichloromethyl chloroformate) or its homologue (4-nitrophenyl chloroformate or the like) for 1 to 5 hours at -10 to 50 ° C in a suitable solvent, for example, tetrahydrofuran, dioxane, benzene, toluene or the like, without base or using a suitable organic base, for example , triethylamine or similar. In addition, they can be converted to isocyanic ester by changing a carboxyl group to acid azide and then using the Crutius array or the Schmidt array in case D is a carboxyl group, and using the Hofmann array in the case that D be an amide group. In addition, in the case that D is a carboxyl group, they can also be converted to isocyanic ester in a vessel, using DPPA (diphenylphosphoryl azide). In addition, the compounds, L being the general formula (4), among the compounds, Q being the general formula (10) represented by the general formula (3), can be synthesized by reacting the compounds represented by a general formula (24) -. - * - * (where R, R2, R12 and Xb are as described above), with the compounds represented by the general formula (19) (where T, V ring B and m are as described above), for 0.5 to 24 hours at 20 to 160 ° C without solvent or a suitable solvent, for example, tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N -dimethylacetamide, N-methylpyrrolidone, acetonitrile, benzene, toluene or the like, without base or using a suitable inorganic or organic base, for example, sodium hydride, sodium carbonate, potassium carbonate, triethylamine or the like. In addition, the compounds, Q being the general formula (10) being represented by the general formula (2) or the general formula (5), can also be synthesized by reacting the compounds represented by the general formula (24) $% ~ " * - * r- (where R, R2, R12 and Xb are as described above), with the compounds represented by the formula (13-a) Ar-PH (13-a) (where Ar and P are as described above), or the general formula (13-b) (where R6 and R7 are as described above), for 0.5 to 24 hours at 20 to 160 ° C without solvent or a suitable solvent, for example, tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, N -methylpyrrolidone, acetonitrile, benzene, toluene or the like, without base or using a suitable inorganic or organic base, for example, sodium hydride, sodium carbonate, potassium carbonate, triethylamine or the like. In addition, the compounds, L being the general formula (4) and A being lower alkylene, among the compounds, where Q in the general formula (10) represented by the general formula (3), can also be Z ~ A 9 be synthesized by reacting the compounds represented by a general formula (25) (where R, R, R> 12) and E are as described above), with the compounds represented by the general formula (19) (where T, V, ring B and m are as described above), for 0.5 to 48 hours at 20 to 160 ° C in a suitable solvent, for example, tetrahydrofuran, dioxane, N, Nd? methylformamide, N, N- dimethylacetamide, N-methylpyrrolidone, acetonitrile, benzene, toluene or the like, without base or using a suitable inorganic or organic base, for example, sodium hydride, sodium carbonate, potassium carbonate, tetylamine or the like. In addition, the compounds, being lower alkylene, among the compounds, Q being in the general formula (10) represented by the general formula (2) or the A. xf general formula (5), can also be synthesized by reacting the compounds represented by a general formula (25) (wherein R, R2, R12 and E are as described above), with the compounds represented by the general formula (13-a) Ar-PH (13-a) (where Ar and P are as described above), or the general formula (13-b) (where R6 and R7 are as described above), for 1 to 24 hours at 25 to 120 ° C in a suitable solvent, for example, tetrahydrofuran, N, N-dimethylformamide, benzene, toluene or the like, using an inorganic base or suitable organic, for example, sodium hydride, sodium carbonate, potassium carbonate, triethylamine or the like. In addition, the compounds, represented by the general formula (24) can be synthesized by reacting the compounds represented by the general formula (20) (where R, R and Xb are as described above), with alkyl halide, for example, methyl iodide or the like, aralkyl halide, for example, 4-methoxybenzyl chloride or the like for 2 to 24 hours from 20 to 120 ° C in a suitable solvent, for example, benzene, toluene, chloroform, methylene chloride, tetrahydrofuran or the like, using a suitable silver catalyst, for example, silver oxide, silver carbonate or the like. Also, they can be synthesized by reacting the compounds represented by the general formula (20) for 2 to 6 hours' from 0 to 120 ° C in a suitable solvent, for example, benzene, toluene, chloroform, methylene chloride, tetrahydrofuran or the like , using a borate, for example, tetramethyloxonium borate or the like. In addition, the compounds, where R is a nitro group, among the compounds represented by the general formula (20), can be synthesized by nitration. selective, that is, by reacting the compounds represented by a general formula (26) (where Xb and R are as described above), for 0.5 to 5 hours at -10 to 80 ° C in an acetic acid solvent, using a suitable nitrating agent, for example, concentrated nitric acid, fuming nitric acid, nitrate potassium or similar. In addition, the compounds represented by the general formula (20) can also be synthesized by reacting the compounds represented by a general formula (27) (wherein Xb and R are as described above), with cetomalonic acid diester represented by the general formula (22) O 14 R-O2C COrR 14 (22) r, "3 > - (where R14 is as described above), for 2 to 12 hours at 25 to 100 ° C in a suitable solvent, for example, ethanol, methanol, tetrahydrofuran or the like. Some of those compounds represented by the general formula (27) are known, and can be synthesized according to the usual procedures. In addition, the compounds represented by the general formula (20) can also be synthesized according to 092-11245, Japanese Unexamined Patent Publication No. Sho 56-81569 or similar, which show the following scheme.

Neral 28 29 30 (where Xb and R are as described above, and R15 denotes a lower alkyl group). In addition, the compounds, represented by the general formula (26) can also be synthesized by reacting the compounds represented by the general formula (31) (31) ^ (where Xb is as described above), with cetomalonic acid diester represented by the general formula (22) (where R> 14 is as described above), for 2 to 12 hours at 25 to 100 ° C in a suitable solvent, for example, ethanol, methanol, tetrahydrofuran or the like. Also, part of the compounds represented by the general formula (26) are known, and can also be synthesized according to W092-11245, Japanese Unexamined Patent Application No. Sho 56-81569 or similar, which show the following scheme . neural 32 33 34 (where Xb and R15 are as described above). In addition, the compounds, L being the general formula (4), between the compounds, Q in the general formula (11) represented by the general formula (3), can also be synthesized by reacting the compounds represented by a general formula (35). ) (where A, R1 and R2 are as described above), with the compounds represented by the general formula (17) (where T, V, R13 and m are as described above), for 5 to 48 hours at 20 to 80 ° C without a solvent or in a suitable solvent, for example, tetrahydrofuran, benzene, toluene, acetic acid or the like (to which a suitable inorganic or organic acid may be added, for example, hydrochloric acid, sulfuric acid, p-toluenesulfonic acid or the like). In addition, the compounds, L being the general formula (4) and, for T, W in the general formula (4-a) and the general formula (4-c) being an aralkyl group, a phenyl group, a naphthyl group, 5 or 6 membered heterocycle or its fused ring (they may have one or more substituents on the aromatic ring or herocycle), among the compounds, where Q in the general formula (11) represented by the general formula (3), may also be be synthesized by reacting the compounds represented by a general formula (36) (where La, A, R, R1 and R2 are as described above), with the compounds represented by the general formula (14) ZN = C = Xa (14) (where Z and Xa are as described above), during 1 to 5 hours at 20 to 120 ° C in a suitable solvent, for example, methylene chloride, tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, benzene, toluene or the like, without base or using a suitable organic base, for example, triethylamine or the like. Also, they can be synthesized by converting the compounds synthesized by the general formula (15) Z-Ax -D (15) (where Z, Ai and D are as described above), instead of the general formula (14), to ester isocyanic (isothiocyanic) or carbamyl chloride through known processes, and reacting with the general formula (36) similarly to the general formula (14). For example, in case D is an amino group, it can be converted to carbamoyl chloride or isocyanic ester (isothiocyanic) by reacting with phosgene (thiophosgene), phosgene dimer (2, 2, 2-trichloromethyl chloroformate) or its homologue (4-nitrophenyl chloroformate or similar) for 1 to 5 hours at -10 to 50 ° C in a suitable solvent, for example, tetrahydrofuran, dioxane, benzene, toluene or the like, without base or using a suitable organic base, for example, triethylamine or the like. In addition, they can be converted to isocyanic ester by changing the carboxyl group to acidic azide and then using the Crutius rearrangement or the Schmidt rearrangement in the case where D is a carboxyl group, and using the Hofmann rearrangement in case D be an amide group. In addition, in case D is a carboxyl group, they can also be converted to isocyanic ester in a vessel, using DPPA (diphenylphosphoryl azide).

In addition, the compounds, where R is a trifluoromethyl group, among the compounds represented by the general formula (11) can be synthesized by reducing the compounds represented by the general formula (1) through catalytic hydrogenation, that is, by hydrogenating from 20 to 80 ° C and environmental pressure of 5 atm in a suitable solvent, for example, ethanol, methanol, acetic acid or the like in the presence of a suitable catalyst, for example, a palladium on carbon, platinum oxide, rhodium-alumina or the like. In addition, the compounds, with R 1 being a hydrogen atom, among the compounds represented by the general formula (16) can be synthesized by reacting the compounds represented by a general formula (37) (where R, R2, R12 and A are as described above, and R, 16 and R> 17 denote, in an identical or different manner, a hydrogen atom, amino group protecting groups), for 3 to 72 hours from 20 a 120 ° C without a solvent or in a suitable solvent, for example, water, acetic acid, methanol or the like, using an acid 9 suitable, for example, hydrochloric acid, sulfuric acid, hydrobromic acid, trifluoroacetic acid or the like. In addition, the compounds, R2 being a hydroxyl group, among the compounds represented by the general formula (16), can also be synthesized by reacting the compounds represented by a general formula (38) (where R, R1, R2, A, R16 and R17 are as described above), for 0.5 to 10 hours at 20 to 100 ° C in a suitable solvent, for example, water, methanol, ethanol or the like, using an alkali suitable, for example, potassium hydroxide, sodium hydroxide or the like to convert to a carboxylic acid, and then reacting for 3 to 72 hours at 20 to 120 ° C without solvent or in a suitable solvent, for example, water, acid acetic acid, methanol or the like, using a suitable acid, for example, hydrochloric acid, sulfuric acid, hydrobromic acid, trifluoroacetic acid or the like. f > Here, the compounds, where A is a single bond or a lower alkylene between the compounds represented by the general formula (37) can be synthesized by reacting the compounds represented by the general formula (24) (wherein R, R2, R12 and Xb are as described above), or the compounds represented by the general formula (25) (where R, R2, R12 and E are as described above), with the compounds represented by a general formula (39) Ri6Ri7 _NH (3 9) (wherein R16 and R17 are as described above), for 0.5 to 48 hours at 20 to 160 ° C in a suitable solvent, for example, tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone , acetonitrile, benzene, toluene or the like, without base or using an inorganic or organic base, for example, sodium hydride, sodium carbonate, potassium carbonate, triethylamine or the like. In addition, the compounds represented by the general formula (25) can be synthesized by reacting the compounds represented by a general formula (40) (where R, R2 and R12 are as described above), for 1 to 12 hours at 20 to 100 ° C in a suitable solvent, for example, carbon tetrachloride, chloroform, acetic acid or the like, using a halogenating agent, example, N-bromosuccinamide (NBS), N-chlorosuccinamide (NCS), bromide or the like. In addition, the compounds, being lower alkylene, between the compounds represented by the general formula (38) can be synthesized by reacting the compounds represented by the general formula (18) -? (where R, R, R and E are as described above), with the compounds represented by the general formula (39) R16R17 -NH (39) (where R16 and R17 are as described above), for 5 to 48 hours from 20 to 160 ° C in a suitable solvent, for example tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, benzene, toluene or the like, without base or using an inorganic or organic base suitable, for example, sodium hydride, sodium carbonate, potassium carbonate, triethylamine or the like. In addition, the compounds represented by the general formula (18) can be synthesized by reacting the compounds represented by a general formula (41) (where R, R1 and R2 are as described above), for 1 to 12 hours at 20 to 100 ° C in a suitable solvent, for example, carbon tetrachloride, chloroform, acetic acid or the like, using a halogenating agent, example, N-bromosuccinamide (NBS), N-chlorosuccinamide (NCS), bromide or the like. In addition, the compound (42), where R is a trifluoromethyl group, where R1 is a hydrogen atom and A is a single bond, among the compounds represented by the general formula (35), can be synthesized by a process shown in the following scheme.

F C? N,, H V ?? H 42 44 45 This can be synthesized by reacting the synthesizable compound (43) through a known process with ketomalonic acid diester (22), for 1 to 6 hours at 20 to 120 ° C in a suitable solvent, for example, ethanol , methanol, tetrahydrofuran or the like to convert the compound (44), then nitrate this j compound, that is, reacting for 0.5 to 6 hours at -10 to 80 ° C without solvent or in a suitable solvent, for example, concentrated sulfuric acid, carbon disulfide or acetic acid, using a suitable nitrating agent, for example, concentrated nitric acid, fuming nitric acid, potassium nitrate or the like to convert the compound represented by the compound (45), and reducing it through catalytic hydrogenation, i.e., hydrogenating from 20 to 80 ° C under atmospheric pressure at 5 atm in a suitable solvent, for example, ethanol, methanol, acetic acid, dilute hydrochloric acid or mixed solvent thereof in the presence of a suitable catalyst, for example palladium on carbon, platinum oxide, rhodium-alumina or the like. -3C? 0 FJC? ? R «45a 45 42 (where R12 is as described above). Also, the compound (42) can be synthesized via the compound (45a) and the compound (45b), after nitration. Namely, it can also be synthesized by reacting the compound (45) with an alkyl halide, for example, methyl iodide or the like, or aralkyl halide, for example, 4-methoxybenzyl chloride for 2 to 24 hours from 20 a 120 ° C in a suitable solvent, for example, benzene, toluene, chloroform, methylene chloride, tetrahydrofuran or the like, using a suitable silver catalyst, for example, silver oxide, silver carbonate or the like to convert the compound (45a ), which is then reduced by catalytic hydrogenation, that is, by hydrogenation at 20 to 80 ° C under atmospheric pressure. atm in a suitable solvent, for example, ethanol, methanol, acetic acid, dilute hydrochloric acid or mixed solvent thereof in the presence of a suitable catalyst, for example, palladium on carbon, platinum oxide, rhodium-alumina or the like to convert the compound (45b), and further reacting this (45b) for 0.5 to 72 hours at 20 to 120 ° C without solvent or in a suitable solvent, for example, water, acetic acid, methanol or the like, using a suitable acid , for example hydrochloric acid, sulfuric acid, acid Bromhydric acid, trifluoroacetic acid or the like. Also, the compounds represented by the general formula (45a) can be synthesized by reacting the compounds represented by the formula chloroform, methylene chloride, tetrahydrofuran or the like, using a bor to *, for example, tatramethyloxonium borate or the like. In addition, the compounds represented by the general formula (21) can be synthesized by reacting, for example, the compounds represented by a general formula (46) (wherein Xb and R are as described above, and Pi and P2 denote hydrogen atoms or protective groups of the amino group), with the compounds represented by the general formula (19) (where T, V, ring B and m are as described above), to convert the compounds represented by a general formula (47), deprotecting those (general formula 48), and then reducing the nitro group, leading to phenylenediamine (formula general 21). 47 48 21 (where Q, R, Pi and P2 are as described above). The reaction of the general formula (46) and the general formula (19) can be achieved by reacting for 5 to 48 from 20 to 160 ° C in a suitable solvent, for example, tetrahydrofuran, dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, acetonitrile, benzene, toluene or the like, without base or using a suitable inorganic or organic base, for example, sodium hydride, sodium carbonate, potassium carbonate, triethylamine or the like. The deprotection of the general formula (47) can be conducted by reacting from 3 to 72 hours at 20 to 120 ° C without a solvent or in a suitable solvent, for example, water, methanol, ethanol, anisole or the like, using a suitable acid, for example, hydrochloric acid, sulfuric acid, hydrobromic acid, trifluoroacetic acid or the like, or for 0.5 to 10 hours at 20-100 ° C, using a suitable alkali, for example, potassium hydroxide, sodium hydroxide, or the like. The reduction of the nitro group of the formula generated (48) can be conducted by reacting from 20 to 60 ° C in water-alcohol, for example, water-ethanol, water-methanol or the like in the presence of sodium sulfide and sodium chloride. ammonium in the case that R is a nitro group. Furthermore, in the case that R is different from the nitro group, it can also be conducted by reacting through catalytic hydrogenation, that is, by hydrogenating from 25 to 80 ° C under atmospheric pressure to 5 atm in a suitable solvent, for example, ethanol, methanol, acetic acid or the like in the presence of a suitable catalyst, for example palladium on carbon, platinum oxide, rhodium-alumina or the like. In addition, it can also be conducted by reacting from 25 to 100 ° C in a suitable solvent, for example, ethanol, dilute hydrochloric acid, acetic acid or a mixed solvent thereof in the presence of tin chloride, zinc, iron, sodium hydrosulfite. or similar. In addition, the compounds, where R is the trifluoromethyl group, among the compounds represented by the general formula (46) can be synthesized by nitrating the general formula (50) synthesizable through a known process, i.e., 49 50 46 (where Xb, Pi and P2 are as described above), reacting for 0.5 to 2 hours at -10 to 80 ° C without a solvent or in a suitable solvent, for example, concentrated sulfuric acid, carbon disulfide or acetic acid, using a suitable nitrating agent, for example concentrated nitric acid, fuming nitric acid, potassium nitrate or the like. In addition, the compounds represented by the general formula (48) can also be converted to the general formula (1) according to W092-11245. Namely, the nitroaniline represented by the general formula (48) can be reacted with malonyl chloride to convert to the general formula (51), and then cyclized intramolecularly to become the general formula (52) which is deoxidized to convert to the general formula (1).

XX eneral 48 51 52 (where Q, R and R15 are as defined above).

BEST MODE FOR CARRYING OUT THE INVENTION Examples of the invention will be described to illustrate the invention in greater detail. io (Example 1) 7-Chloro-3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid methyl ester To a solution of methyl 7-chloro-3-dihydro-3-oxoquinoxaline-2-carboxylate (106 mg, 444 μmol) in acetic acid (1 ml) was added a solution of fuming nitric acid (39.5 μl, 888 μmol). ) in acetic acid (2 ml), and the mixture was stirred for 1 hour at 60 ° C. Water (10 ml) was added to the reaction mixture. The precipitate was collected by filtration, washed with water, and then air dried to obtain 66.6 mg of the title compounds as a yellow powder. Yield of 53%. ^ -RMN (DMS0-d6, d): 3.93 (3H, s), 7.91 (ÍH, s), 8. 29 (1H, s), 13.26 (ÍH, s broad).

(Example 2) Ethyl 3, 4-dihydro-7-fluoro-6-nitro-3-oxoquinoxaline-2-carboxylate Using ethyl 3,4-dihydro-7-fluoro-6-nitro-3-oxoquinoxaline-2-carboxylate (558 mg, 2.36 mmol) and following the same procedure as in Example 1, 297 mg of the title compound were obtained like a yellow powder. 45% yield. XH-NMR (CDC13, d): 1.49 (3H, t, J = 7.0Hz), 4.58 (2H, c, J = 7.0Hz), 7.89 (IH, d, J = 10.6Hz), 8.16 (IH, d , J = 6.2Hz).

(Example 3) ethyl 7-Bromo-3, 4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylate To a solution of ethyl 7-bromo-3, 4-dihydro-3-oxoquinoxaline-2-carboxylate (2.60 mg, 8.75 mmol) in acetic acid (35 ml) was added dropwise fuming nitric acid (1.40 ml, 31.5 mmol). ) at 60 ° C, and the mixture was stirred for 2 hours at the same temperature. The reaction mixture poured into water (300 ml). The precipitate was collected by filtration, washed with water, and then air dried to obtain 2.79 g of the title compound as a yellow powder. 93% yield. ^ -RMN (DMSO-de, d): 1.33 (3H, t, J = 7.3Hz), 4.40 (2H, c, J = 7.3Hz), 7.86 (H, s), 8.40. (ÍH, s), 13.24 (ÍH, s broad).

(Example 4) Ethyl 3,4-dihydro-7-methyl-6-nitro-3-oxoquinoxaline-2-carboxylate To a solution of ethyl 3, 4-dihydro-7-methyl-3-oxoquinoxaline-2-carboxylate (1.65 g, 7.10 mmol) in acetic acid (15 ml) was added dropwise fuming nitric acid (1.36 ml, 14.2 mmol). ), and the mixture was stirred for 1 hour at 60 ° C. The reaction mixture was poured into ice water and, after stirring for 25 minutes, the precipitate was collected by filtration. These were air dried and dissolved in ethyl acetate. In addition, the filtrate was extracted with ethyl acetate, which was combined with the next organic layer.

After drying over anhydrous sodium sulfate, the solvent was distilled. The residue obtained was purified by means of silica gel column chromatography [n-hexane-ethyl acetate = 1: 1] to obtain 887 mg of the title compound as a pale yellow powder. 45% yield. ^ -RMN (CDC13, d): 1.48 (3H, t, J = 7.3Hz), 2.65 (3H, s), 4.55 (2H, c, J = 7.3Hz), 7.91 (IH, s), 8.02 (IH) , s), 12.42 (H, broad).

(Example 5) 7-Chloro-3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 1 (64.6 mg, 228 μmol) in methanol (2 ml) was added a solution of IN aqueous potassium hydroxide (683 μl, 683 μmol), and the mixture was refluxed for 30 minutes. After cooling, water (5 ml) was added and the pH value was brought up to 4 using acetic acid, then the solvent was distilled. Water was added to the obtained residue and the crystals were collected by filtration. After washing with water, these were air dried to obtain 35.0 mg of the title compound as a yellow powder. 57% yield. mp 227-229 ° C (dec) HR-MS: 268.9824 (-1.5 MU).

(Example 6) 3,4-Dihydro-7-fluoro-6-nitro-3-oxoquin-xalin-2-carboxylic acid To a solution of the compound of Example 2 (100 mg, 356 μmol) in ethanol (3.5 ml) was added an aqueous solution of IN sodium hydroxide (711 μl, 711 μmol), and the mixture was refluxed for 2 hours. . After cooling, water (10 ml) was added and the pH value was brought to 4 using acetic acid, then the solvent was distilled off. After purifying the residue obtained with synthetic adsorbent agent HP-20P [water water: acetonitrile = 20: 1], it was lyophilized to obtain 69.0 mg of the title compound as a yellow powder. 77% yield. mp 213-215 ° C (decomposition).

HR-MS: 253. 0162 (+2 .7mmu] (Example 7) 7-Bromo-3,4-dihydro-6-nitro-3-oxoquin-xalin-2-carboxylic acid Using the compound of Example 3 (181 mg, 529 μmol) and following the same procedure as in Example 6, 107 mg of the title compound was obtained as a yellow powder. 64% yield. mp 218-220 ° C (decomposition). HR-MS: 312.9358 (+2. Mmu).

(Example 8) Acid 3, -di-idro-methyl-6-nitro-3-oxoquin-xalin-2-carboxylic acid To a suspension of the compound of Example 4 (231 mg, 833 μmol) in methanol (15 ml) was added an aqueous solution of potassium hydroxide (5 ml) (93.5 mg, 1.67 mol) at room temperature, and the mixture was stirred for 4 hours at room temperature and for an additional 30 minutes at 80 ° C. After cooling, the reaction mixture was distilled under reduced pressure. The obtained residue was dissolved in water and the pH value was brought to below 1 using concentrated hydrochloric acid under ice-cold cooling, which was stirred for 30 minutes. Subsequently, the precipitate was collected by filtration, washed with water and cold ethanol, and dried in the air to obtain 126 mg of the title compound as a pale yellow powder. 60% yield. mp 239-242 ° C. Analysis calculated for C? OH N305.1 / 10H20: C, 47.86; H, 2.89; N, 16.61. Found: C, 47.90; H, 2.92; N, 16.61.

(Example 9) Ethyl 7-fluoro-3-methoxy-6-nitroquinoxaline-2-carboxylate O2N '?' ^ '^ OMe A suspension of the compound of Example 2 (1.00 g, 3.56 mmol), methyl iodide (440 μL, 7.07 mmol) and silver oxide (990 mg, 4.31 mmol) in toluene (100 mL) was stirred for 2 hours at 100 ° C. After cooling, the reaction mixture was filtered using celite, and the solvent was distilled. The residue obtained was purified by means of column chromatography on silica gel [Dichloromethane: ethyl acetate = 4: 1] to obtain 580 mg of the title compound as a yellow powder. 55% yield. 1 H-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 4.18 (3H, s), 4.55 (2H, c, J = 7.3Hz), 7.95 (ΔH, d, J = 10.8Hz ), 8.57 (lH, d, J = 7.3Hz).

(Example 10) Ethyl 3-methoxy-7-methyl-6-nitroquinoxaline-2-carboxylate To a solution of the compound of Example 4 (1.42 g, 5.12 mmol) in anhydrous dichloromethane (80 ml) was added trimethyloxonium tetrafluoroborate (3.41 g, 23.1 mol) at room temperature under stirring, and the mixture it was stirred for 4.5 hours at room temperature and further refluxed for 1.5 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the organic layer was separated. The aqueous layer was further extracted with dichloromethane. The organic layers were combined and then dried over anhydrous sodium sulfate, the solvent was distilled off. The residue obtained was purified by means of column chromatography on silica gel [n-hexane: ethyl acetate = 10: 1] to obtain 762 mg of the title compound as a pale yellow powder. 51% yield. ^ -RMNÍCDCl:!, D): 1.47 (3H, t, J = 7.3Hz), 2.72 (3H, s), 4.17 (3H, s), 4.54 (2H, c, J = 7.3Hz), 8.03 (ÍH , s), 8.43 (ÍH, s).

(Example 11) 7- (Imidazol-1-yl) -3-methoxy-6-nitroquinoxaline-2-carboxylic acid ethyl ester A solution of the compound of Example 9 (1.41 g, 4.78 mmol) and imidazole (1.63 g, 23.9 mmol) in acetonitrile (10 mL) was stirred for 9 hours at 50 ° C. After diluting with dichloromethane, the reaction mixture was washed with brine. The aqueous layer was extracted with dichloromethane, which was combined with the above organic layer. After drying over anhydrous sodium sulfate, the solvent was distilled. The residue obtained was purified by means of silica gel column chromatography [n-hexane: ethyl acetate = 1: 1 ethyl acetate] to obtain 423 mg of the title compound as an orange liquid. Yield of 26%. 1 H-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 4.23 (3H, s), 4.56 (2H, c, J = 7.3Hz), 7.15 (ΔH, t, J = 1.5Hz ), 7.27 (ÍH, s), 7.72 (ÍH, s), 8.18 (ÍH, s), 8.46 (ÍH, s).

(Example 12) Ethyl 3-methoxy-6-nitro-7- (4-pyridon-1-yl) quinoxaline-2-carboxylate ? To a solution of the compound of Example 9 (180 mg, 610 μmol) in tetrahydrofuran (20 ml) was added 4-pyridone (290 mg, 3.05 mmol), followed by tube sealing, and the mixture was stirred for 4 hours at 100 ° C. ° C and for 18 hours at 90 ° C. After cooling, the reaction mixture was concentrated under reduced pressure and the residue obtained was purified by means of column chromatography on silica gel [chloroform: ethanol = 40: 1 - > 20: 1] to obtain 70.0 mg of the title compound as a pale yellow liquid. Performance of 31%. ^ -RN (CDC13, d): 1.47 (3H, t, J = 7.2Hz), 4.24 (3H, s), 4.56 (2H, c, J = 7.2Hz), 6.52 (2H, d, J = 7.8Hz ), 7.38 (2H, d, J = 7.8Hz), 8.22 (HH, s), 8.60 (HH, s).

(Examples 13 to 21) Through the same procedure as in Example 12, the compounds listed in Table 1 were obtained.

• J * 31 Table 1 Example R Example R Example R (Example 13) XH-NMR (CDC13, d): 1.46 (3H, t, J = 7.2Hz), 1.58-1.64 (2H, m), 1.71-1.77 (4H, m), 3.05 (4H, broad t, J = 4.8Hz), 4.13 (3H, s), 4.53 (2H, c, J = 7.2Hz), 7.69 (ÍH, s), 8.13 (ÍH, s).

(Example 14) XH-NMR (DMSO-de, d): 1.35 (3H, t, J = 7.3Hz), 2.86 (6H, s), 4.05 (3H, s), 4.43 (2H, c, J = 7.3 Hz), 7.66 (ÍH, s), 8.29 (ÍH, s).

(Example 15) ^ -RMN (CDCI3, d): 1.47 (3H, t, J = 7.3Hz), 3.27 (8H, s), 4.15 (3H, s), 4.55 (2H, c, J = 7.3Hz) , 6.94 (2H, dd, J = 8.8, 4.4Hz), 7.00 (2H, t, J = 8.8Hz), 7.80 (IH, s), 8.18 (IH, s).

(Example 16) XH-NMR (CDCl3, d): 1.47 (3H, t, J = 7.3Hz), 3.23-4.27 (4H, m), 3.28-3.33 (4H, m), 3.90 (3H, s), 4.15 (3H, s), 4.55 (2H, c, J = 7.3Hz), 6.90 (HH, d, J = 7.8Hz), 6.95- 7.05 (3H, m), 7.80 (HH, s), 8.17 (HH) , s).

(Example 17) * H-NMR (CDCI3, d): 1.47 (3H, t, J = 7.3Hz), 3.24-3.28 (4H, m), 3.34-3.38 (4H, m), 3.81 (3H, s) , 4.15 (3H, s), 4.55 (2H, c, J = 7.3Hz), 6.47 (ÍH, dd, J = 2.0, 7.8Hz), 6. 52 (ÍH, t, J = 2.0Hz), 6.60 (ÍH, dd, J = 7.8, 2.0Hz), 7.21 (ÍH, t, J = 7.8Hz), 7.79 (ÍH, s), 8.18 (ÍH, s).

(Example 18) XH-NMR (CDCl3, d): 1.47 (3H, t, J = 7.3Hz), 3.26-3.32 (4H, m), 3.58-3.62 (4H, m), 4.16 (3H, s), 4.55 (2H, c, J = 7.3HZ), 6.90 (2H, d, J = 7.3Hz), 7.81 (HH, s), 8.17 (2H, d, J = 7.3Hz), 8.22 (HH, s). 03 (Example 19) ^ -RMN (CDCI3, d): 1.47 (3H, t, J = 7.3Hz), 3.24- 3.28 (4H, m), 3.30-3.32 (4H, m), 4.15 (3H, s), 4.55 (2H, c, J = 7.3Hz), 6.90 (2H, d, J = 8.8Hz), 7.24 (2H, d, J = 8.8Hz), 7.80 (H, s), 8.19 (H, s) - .

(Example 20) XH-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 3.25-3.29 (4H, m), 3.35-3.39 (4H, m), 4.15 (3H, s), 4.55 (2H, c, J = 7.3HZ), 6.91 (IH, t, J = 7.3Hz), 6.99 (2H, d, J = 8.8Hz), 7.30 (2H, dd, J = 8.8, 7.3Hz), 7.80 (ÍH, s), 8. 18 (1H, s).

(Example 21) XH-NMR (CDCl3, d): 1.46 (3H, t, J = 7.3Hz), 2.62-2.65 (4H, m), 3.11-3.14 (4H, m), 3.53 (2H, s), 4.13 (3H, s), 4.53 (2H, c, J = 7.3Hz), 7.34-7.35 (5H, m), 7.71 (HH, s), 8.13 (HH, s).

(Example 22) Ethyl 3-methoxy-7- (4- (4-methoxyphenyl) p? Peracin-1-yl) -6-nitroquinoxaline-2-carboxylate *, To a solution of the compound of Example 9 (300 mg, 1.02 mmol) in triethylamine (15 ml) was added 4- (methoxyphenyl) -piperazine dihydrochloride (1.35 g, 5.10 mmol), followed by sealing the tube, and mixing it was stirred for 8 hours at 100 ° C. After cooling, the reaction mixture was concentrated under reduced pressure and the obtained residue was purified by means of column chromatography on silica gel [n-hexane: ethyl acetate = 5: 1 - > 4: 1] to obtain 145 mg of the title compound as a red powder. Yield of 30%. ^ -RM (CDC13, d): 1:47 (3H, t, J = 7.3Hz), 3.22-3.29 (8H, m), 3.79 (3H, s), 4.15 (3H, s), 4.55 (2H, c, J = 7.3Hz), 6.87 (2H, d, J = 9.3HZ), 6.96 (2H, d, J = 9.3Hz), 7.80 (HH, s), 8.18 (HH, s). * 95 (Examples 23 to 28) Through the same procedure as in Example 22, the compounds listed in Table 2 below were obtained. Table 2 Example R E j usu R E j e R 23 Cl 25 27 -N rr N- C02Et? Y_? -T -J (Example 23)? -NRM (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 3.22-3.26 (4H, m), 3.28-3.33 (4H, m), 4.15 (3H, s), 4.55 (2H, c, J = 7.3Hz), 7.02 (IH, dt, J = 1.5, 7.8Hz), 7.11 (IH, dd, J = 7.8, 1.5Hz), 7.26 (IH, dt, J = 1.5, 7.8Hz), 7.39 (HH, dd, J = 7.8, 1.5Hz), 7.81 (HH, s), 8.18 (HH, s).

(Example 24) XH-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 2.34 (3H, s), 3.24-3.29 (4H, m), 3.34-3.37 (4H, m), 4.15 (3H, s), 4.54 (2H, c, J = 7.3Hz), 6.74 (IH, d, J * 7.8Hz), 6.79 (IH, d, J = 7.8Hz), 6.81 (IH, s), 7.19 (IH, t, J = 7.8Hz), 7.79 (H, s), 8.18 (H, s).

(Example 25)? -NRM (CDC13, d): 1.46 (3H, t, J = 7.3Hz), 3.15-3.20 (4H, m), 3.39-4.04 (4H, m), 4.15 (3H, s), 4.54 (2H, c, J = 7.3Hz), 6.54 (HH, t, J = 5.4Hz), 7.77 (HH, s), 8.19 (1H, s), 8.35 (2H, d, J = 5.4Hz).

(Example 26)? -NRM (CDCI3, d): 1.47 (3H, t, J = 7.3Hz), 2.15 (3H, s), 3.063.13 (4H, m), 3.62-3.67 (2H, m), 3.77-3.83 (2H, m), 4.15 (3H, s), 4.54 (2H, c, J = 7.3Hz), 7.76 (IH, s), 8.20 (IH, s).

(Example 27) XH-NMR (CDCl3, d): 1.29 (3H, t, J = 6.8Hz), 1.47 (3H, t, J = 7.3Hz), 3.04-3.09 (4H, m), 3.63-3.68 ( 4H, m), 4.15 (3H, s), 4.18 (2H, c, J = 6.8Hz), 4.54 (2H, c, J = 7.3Hz), 7.75 (IH, s), 8.18 (IH, s).

(Example 28) XH-NMR (CDC13, d): 1.46 (3H, t, J = 7.3Hz), 1.72-1.82 (2H, s), 2.00-2.09 (2H, m), 2.91-2.99 (2H, m ), 3.28-3.38 (2H, m), 3.88-3.97 (IH, m), 4.14 (3H, s), 4.54 (2H, c, J = 7.3Hz), 7.73 (IH, s), 8.15 (IH, s).

(Example 29) 3-Methoxy-6-nitro-7-phenoxy-quinoline-2-carboxylic acid A suspension of the compound of Example 9 (590 mg, 2.00 mmol), phenol (941 mg, 10.0 mmol) and potassium carbonate (1.38 g, 10.0 mmol) in acetonitrile (20 ml) was stirred for 12 hours at 80 ° C in the sealed tube. After cooling, a small amount of water was added to the dissolved organic salt and then the solvent was distilled. The obtained residue was dissolved in saturated aqueous sodium hydrogen carbonate solution, which was then washed with ether. The aqueous layer was brought to pH 3 using concentrated hydrochloric acid, which was extracted with chloroform, dried over anhydrous sodium sulfate and then the solvent was distilled to obtain 407 mg of the title compound as a yellow amorphous material. 60% yield. XH-NMR (CDC13, d): 4.24 (3H, s), 7.18 (2H, d, J = 7.8Hz), 7.31 (ÍH, t, J = 7.3Hz), 7.-48 (2H, t, J = 7.8Hz), 7.51 (1H, s), 8.39 (ÍH, s).

(Example 30) 3-Methoxy-6-nitro-7- (3-nitrophenoxy) quinoxaline-2-carboxylic acid Through the same procedure as in Example 29, the title compound was obtained as a yellow solid. XH-NMR (CDC13, d): 4.26 (3H, s), 7.51 (HH, dd, J = 8.3, 2.44Hz), 7.64 (HH, t, J = 8.3HZ), 7.71 (HH, s), 7.95 (ÍH, t, J = 2.4Hz), 8.14 (ÍH, dd, J = 8.3, 2.0Hz), 8.50 (ÍH, s).

(Example 31) Ethyl 3-methoxy-6-nitro-7- (3-nitrobenzylamino) -quinoxaline-2-carboxylate A solution of the compound of Example 9 (200 mg, 677 μmol) and 3-nitrobenzylamine hydrochloride (383 mg, 2.03 mmol) in N, N-dimethylformamide (2 ml) was stirred for 6 hours at 100 ° C. After cooling, water was added, and the solution was extracted with chloroform. After drying over anhydrous sodium sulfate, the solvent was distilled. The residue obtained was purified by means of silica gel column chromatography [n-hexane: ethyl acetate = 4: 1] to obtain 38.8 mg of the title compound as a red powder. Yield of 13%. ? -NRM (CDC13.D): 1.43 (3H, t, J = 7.3Hz), 4.11 (3H, s), 4.50 (2H, c, J = 7.3Hz), 4.73 (2H, d, J = 5.4Hz), 7.21 (HH, s), 7.57 (HH, t, J = 7.8Hz), 7.73 (HH, d, J = 7.8Hz), 7.95 (HH, t, J = 5.4Hz), 8.18 (HH) , d, J = 8.3Hz), 8.25 (HH, s), 8.79 (HH, 5). j.00 (Example 32) Ethyl 3-methoxy-6-nitro-7-phthaloylquinoxaline-2-carboxylate A solution of the compound of Example 9 (600 mg, 2.03 mmol) and potassium phthalimide (1.88 g, 10.2 mmol) in acetonitrile (20 ml) was stirred for 24 hours at 110 ° C in the sealed tube. After cooling, ethyl acetate was added, washed with brine, and then dried over anhydrous sodium sulfate, the solvent was distilled off. The obtained residue was purified by means of column chromatography on silica gel [n-hexane: ethyl acetate = 5: 1 - > 3: 1] to obtain 70.0 mg of the title compound as a pale yellow powder. 8% yield. XH-NMR (DMSO-de, d): 1.37 (3H, t, J = 6.8Hz), 4.17 (3H, s), 4.48 (2H, c, J = 6.8Hz), 8.01 (2H, dd, J = 5.4, 2.9Hz), 8.10 (2H, dd, J = 5.9, 2.9Hz), 8.49 (IH, s), 8.71 (IH, s). 1G (Example 33) Ethyl 7- (imidazol-1-yl) methyl-3-methoxy-6-nitroquin-oxaline-2-carboxylate To a solution of the compound of Example 10 (121 mg, 415 μmol) in carbon tetrachloride (30 ml) was added N-bromosuccinimide (222 mg, 1.25 mmol) at room temperature, and the temperature was raised to 80 ° C. Then 2, 2'-azobisisobutyronitrile (20.5 mg, 125 μmol) was added, the reaction mixture was stirred for 5.5 hours. The insoluble fractions were filtered and the solvent was distilled, in this way, to obtain light brown powder. This was dissolved in acetonitrile (50 ml) and then imidazole (113 mg, 1.66 mmol) was added, the mixture was stirred for 5.5 hours at room temperature. The reaction mixture was concentrated under reduced pressure and the residue obtained was purified by means of silica gel column chromatography [n-hexane: ethyl acetate = 1:50] to obtain 102 mg of the title compound as light brown powder . 69% yield. : 02 * H-NMR (CDC13.}., D): 1.45 (3H, t, J = 7.3Hz), 4.19 (3H, s), 4.52 (2H, c, J = 7.3Hz), 5.67 (2H, s), 6.98 (IH, s), 7.19 (IH, s), 7.59 (IH, s), 7.63 (IH, s), 8.65 (ÍH, s).

(Example 34) Ethyl 7-dimethylaminomethyl-3-methoxy-6-nitroquinoxaline-2-carboxylate Through the same procedure as in the Example 33, the title compound was obtained as a brown oil. XH-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 2.23 (6H, s), 3.82 (2H, s), 4.17 (3H, s), 4.54 (2H, c, J = 7.3Hz), 8.19 (ÍH, s), 8.28 (ÍH, s).

(Example 35) 3,4-Dihydro-7-morpholino-6-nitro-3-oxaquinoline-2-carboxylic acid A solution of the compound of Example 9 (506 mg, 1.71 mmol) and morpholine (749 μl, 8.56 mol) in Acetonitrile (2 ml) was stirred for 6 hours at 80 ° C. After cooling, the reaction mixture was concentrated under reduced pressure. The residue obtained was purified by means of column chromatography on silica gel [n-hexane: ethyl acetate = 2: 1] to obtain red liquid. This was dissolved in methanol (2 ml) and then 5% aqueous potassium hydroxide solution was added. (5 ml), which was stirred for 24 hours at room temperature. The reaction mixture was adjusted to pH 3 using 3N hydrochloric acid, which was extracted with dichloromethane. It was then dried over anhydrous sodium sulfate, the solvent was distilled off. 3N hydrochloric acid (5 ml) was added thereto and the mixture was stirred for 65 hours. The deposited crystals were collected by filtration, washed with water and then air dried to obtain 275 mg of the title compound as a red powder. 48% yield. mp 213.5-214.5 ° C.

Analysis calculated for C? 3H? 2N406. 10H2O: C, 46.41; H, 4.13; N, 16.65. Found: C, 46.66; H, 4.00; N, 16.32.

(Example 36) 3,4-Dihydro-7- (imidazol-1-yl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid To the compound in Example 11 (423 mg, 1.23 mmol) was added 3N hydrochloric acid (20 ml), and the mixture was stirred for 6 hours at 80 ° C. Concentrated hydrochloric acid (2 ml) was added to the reaction mixture, which was stirred for an additional 10 hours. The precipitate was collected by filtration using water and methanol and dried in the air to obtain 166 mg of the title compound as a brown powder. 44% yield. pf > 300 ° C. Analysis calculated for C? 2H7N5? 5.1 / 2H20: C, 46.46; H, 2.60; N, 22.58. Found: C, 46.17; H, 2.44; N, 22.61.

, (Example 37) 3,4-Dihydro-6-nitro-3-oxo-7- (4-pyridon-1-yl) quinoxaline-2-carboxylic acid To a solution of the compound of Example 12 (1.34 g, 3.62 mmol) in ethanol (40 ml) was added water (10 ml) and aqueous sodium hydroxide solution IN (10.9 ml), and the mixture was refluxed for 4 hours. After cooling, Dowex XFS43279.00 cation exchange resin was added to neutralize. After filtering the resin, the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in 3N hydrochloric acid (70 ml) and the soluton was stirred for 4 hours at room temperature. After concentrating under reduced pressure, the residue obtained was washed with water and dried in air to obtain 1.00 g of the title compound as a yellow powder. 81% yield. mp 283-285 ° C. Analysis calculated for C? 4H9N406.4 / 5H20: C, 49.07; H, 2.82; N, 16.35. Found: C, 48.84; H, 2.62; N, 16.05. "| 06 (Example 38) 3,4-Dihydro-6-nitro-3-oxo-7- (piperidin-1-yl) quinoxaline-2-carboxylic acid Using the compound of Example 13 (70.0 mg, 194 μmol) and following the same procedure as in Example 37, 31.0 mg of the title compound was obtained as a purple powder. 50% discount pf > 300 ° C. HR-MS: 318.0977 (+ 1.3mmu).

(Example 39) 3,4-Dihydro-7-dimethylamino-6-nitro-3-ox-quinoxaline-2-carboxylic acid Using the compound of Example 14 (40.0 mg, 125 μmol) and following the same procedure as in Example 37, 5.00 mg of the title compound was obtained as a dark brown powder. Yield of 15% mp 194.5-196.5 ° C. HR-MS: 278.0641 (-l.Ommu).

(Example 40) 7- (4- (4-Fluorophenyl) piperazin-1-yl) -3-methoxy-6-nitro-quinoxaline-2-carboxylic acid To a solution of the compound of Example 15 (357 mg, 784 μmol) in ethanol (4 ml) was added water (1 ml) and aqueous solution of potassium hydroxide IN (1.57 ml, 1.57 mmol), and the mixture was subjected to reflux for 4 hours. After cooling, hydrochloric acid was added to adjust the pH value to 4 by adding brine. This was extracted with chloroform, dried over anhydrous magnesium sulfate and then the solvent was distilled to obtain 316 mg of the title compound as a red powder. 94% yield. Í? 8 * XH-NMR (DMSO-de, d): 3.2 (8H, s), 4.04 (3H, s), 7.02 (2H, dd, J = 9.3, 4.9Hz), 7.08 (2H, t, J = 9.3Hz) , 7.84 (ÍH, s) 31 (ÍH, s) (Examples 41 to 53) Through the same procedure as in Example 40, the compounds listed in the following Table 3 were obtained. Table 3 Example R Example R Example R 4 1 4 6 51 N rr Ac I \ and -N N- yy: "_ (Example 41) XH-NMR (DMS0-d6, d): 3.08-3.13 (4H, m), 3.17- 3.23 (4H, m), 3.80 (3H, s), 4.02 (3H, s), 6.90-6.99 (4H, m), 7.80 (H, s), 8.27 (H, s).

(Example 42) 2 H-NMR (DMSO-de, d): 3.15-3.20 (4H, m), 3.25- 3.30 (4H, m), 3.73 (3H, s), 3.98 (3H, s), 6.40 (OH) , dd, J = 8.3, 2.0Hz), 6.52 (ÍH, t, J = 2.0HZ), 6.59 (ÍH, dd, J = 8.3, 2.0Hz), 7.14 (HH, t, J = 8.3Hz), 7.72 (HH, s), 8.21 (HH, s).

(Example 43) XH-NMR (DMSO-de, d): 3.13-3.18 (4H, m), 3.19- 15 3.24 (4H, m), 3.70 (3H, s), 4.08 (3H, s), 6.85 ( 2H, d, J = 8.8Hz), 6.96 (2H, d, J = 8.8Hz), 7.89 (H, s), 8.36 (H, (Example 44) 20? -NRM (DMSO-de, d): 3.18-3.23 (4H, m), 3.58-3.65 (4H, m), 3.98 (3H, s), 7.10 (2H, d, J = 9.3 Hz), 7.71 (ÍH, s), 8.09 (2H, d, J = 9.3Hz), 8.23 (ÍH, s).

(Example 45)? -NRM (DMSO-d6, d): 3.10-3.16 (4H, m), 3.20-3.25 (4H, m), 4.04 (3H, s), 7.08 (H, d, J = 7.8, 1.5Hz), 7.25 (HH, dd, J = 7.8, 1.5Hz), 7.33 (HH, dt, J = 7.8, 1.5Hz), 7.44 (HH, dd, J = 7.8, 1.5Hz), 7.85 (HH, s), 8.30 (ÍH, s).

(Example 46)? -NRM (DMSO-de, d): 3.18-3.23 (4H, m), 3.25-3.29 (4H, m), 4.07 (3H, s), 7.02 (2H, d, J = 8.8Hz ), 7.27 (2H, d, J = 8.8Hz), 7.90 (IH, s), 8.36 (IH, s).

(Example 47) XH-NMR (DMSO-d6, d): 2.27 (3H, s), 3.20-3.21 (4H, m), 3.24-3.26 (4H, m), 4.05 (3H, s), 6.04 (H) , d, J = 7.8Hz), 6.79 (HH, d, J = 7.8Hz), 6.83 (HH, s), 7.12 (HH, t, J = 7.8Hz), 7.85 (HH, s), 8.33 (HH) , s).

(Example 48) XH-NMR (DMSO-de, d): 3.19-3.20 (4H, m), 3.27-3.29 (4H, m), 3.98 (3H, s), 6.82 (ΔH, t, J = 7.3Hz ), 7.00 (2H, d, J = 7.8Hz), 7.24 (2H, dd, J = 7.8-7.3Hz), 7.72 (IH, s), 8.21 (IH, s).

(Example 49)? -NRM (DMSO-de, d): 2.73-2.83 (4H, m), 3.12-3.18 (4H, m), 3.84 (2H, s), 4.05 (3H, s), 7.34-7.44 (5H, m), 7.81 (1H, s), 8.31 (ÍH, s).

(Example 50)? -NRM (DMSO-de, d): 3.07-3.14 (4H, m), 3.85-3.92 (4H, m), 3.98 (3H, s), 6.67 (H, t, J = 4.9Hz ), 7.73 ÍH, s), 8.23 (ÍH, s), 8.40 (2H, d, J = 4.9Hz).

(Example 51) XH-NMR (DMSO-de, d): 2.04 (3H, s), 3.00-3.04 (2H, m), 3.05-3.09 (2H, m), 3.54-3.59 (4H, m), 4.08 (3H, s), 7.87 (ÍH, s), 8.37 (ÍH, s.).

(Example 52) XH-NMR (DMSO-de, d): 1.21 (3H, t, J = 6.8Hz), 3. 01-3.07 (4H-m), 3.46-3.54 (4H, m), 4.07 (2H, c, J = 6.8Hz), 4.08 (3H, s), 7.90 (H, s), 8.36 (H, s).

(Example 53) XH-NMR (DMSO-d6, d): 1.47-1.58 (2H, m), 1.79- 1.89 (2H, m), 2.85-2.94 (2H, s), 3.15-3.24 (2H, m) , 3.61-3.70 (1H, m), 4.07 (3H, s), 7.76 (H, s), 8.30 (H, s). • &- ** 112 (Example 54) 3, 4-Dihydro-7- (4- (4-fluorophenyl) piperazin-1-yl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 40 (25.0 mg, 58.5 μmol) in acetic acid (5 ml) was added 47% hydrobromic acid (1 ml), and the mixture was stirred for 2 hours at room temperature. The reaction mixture was concentrated under reduced pressure and the residue The obtained was washed with water, then dried in air to obtain 14.0 mg of the title compound as a pale yellow powder. 56% yield. mp 235.5-237.5 ° C. Analysis calculated for C19H16FN5O5.7 / 10H20: c, 15.53.57; H, 4.12; N, 16.44. Found: C, 53.74; H, 3.77; N, 16.15. HR-BAR +: 414.1188 (-2.6mmu).

(Examples 55 to 58) Through the same procedure as in Example 54, the compounds listed in the following Table 4 were obtained. Table 4 Example R Example R (Example 55) mp 222-224 ° C. HR-BAR +: 441.1165 (+ 0.6mmu) (Example 56) mp 197-199 ° C. HR-BAR +: 398.1215 (+ 0.2mmu) (Example 57) mp 212-214 ° C.

HR-BAR +: 362.1153 (+ 5.2mmu) (Example 58) mp 213.5-215.5 ° C. HR-BAR +: 391.1126 (-0.2mmu) (Example 59) 3, 4-Dihydro-7- (4- (2-methoxyphenyl) piperazin-1-yl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid To the compound of Example 41 (314 mg, 715 μmol) 3N hydrochloric acid (10 ml) was added, and the mixture was refluxed for 4 hours. The reaction mixture was cooled with ice and the insoluble fractions were collected by filtration. These were washed with water and acetone in sequence and air-dried to obtain 247 mg of the title compound as a brown powder. 75% yield. mp 204-206 ° C.

Analysis calculated for c20H? 9N506.2.1H20: C, 51.86; H, 5.05; N, 15.12. Found: C, 51.96; H, 4.75; N, 14.86. HR-BAR +: 426.1411 (-2.0mmu).

(Example 60) 7- (4-Benzylpiperazin-1-yl) -3,4-dihydro-6-nitro-3-oxoquinaxolin-2-carboxylic acid To a solution of the compound of Example 49 (30.0 mg, 70.8 μmol) in methanol (5 ml) was added 47% hydrobromic acid (1 ml), and the mixture was stirred for 16 hours at 70 ° C. After cooling, the reaction mixture was concentrated under reduced pressure and the residue obtained was recrystallized from water to obtain 18.0 mg of the title compound as a pale yellow powder. 60% yield. mp 278-280 ° C Analysis calculated for c2oH? 9N505.4 / 5H20: C, 56.68; H, 4.90; N, 16.52. Found: C, 56.79; H, 4.65; N, 16.23.

HR-BAR +: 410. 1451 (- 1 .4mmu).

(Example 61) 3,4-Dihydro-7- (4-hydroxypiperidin-1-yl) 6-nitro-3-oxoqinoxalin-2-carboxylic acid To the compound of Example 53 (30.0 mg, 86.1 μmol) 3N hydrochloric acid (5 ml) was added, and the mixture was stirred for 2 hours at room temperature. The reaction mixture was concentrated and recrystallized from water to obtain 13.0 mg of the title compound as a brown powder. 44% yield. mp 253-255 ° C. Analysis calculated for C? 4H? 4N4H4? 6.3 / 10H2O: C 49.50; H, 4.33; N, 16.49. Found: C, 49.76; H, 4.19; N, 16.32. HR-BAR +: 334.0894 (-1.9mmu).

(Example 62) 3,4-Dihydro-6-nitro-3-oxo-7-phenoxy-quinoxaline-2-carboxylic acid '* \? 1 To a solution of the compound of Example 29 (400 mg, 1.17 mmol) in acetic acid (10 ml) was added concentrated hydrochloric acid (2 ml), and the mixture was allowed to stand overnight at room temperature. The reaction mixture was added to the water and the precipitate was collected by filtration. These were washed with water and chloroform in sequence and air-dried to obtain 79.5 mg of the title compound as a brown powder. 20% yield. mp 154-156 ° C (dec.). Analysis calculated for Ci5H9N306.3 / 4H20: C, 52.87; H, 3.11; N, 12.33. Found: C, 52.75; H, 3.12; N, 12.20. HR-MS: 327.0495 (+ 0.3mmu).

(Example 63) 3, 4-Dihydro-6-nitro-7- (3-nitrophenoxy) -3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 30 (277 mg, 717 μmol) in acetic acid (5 ml) was added concentrated hydrochloric acid (1 ml) at 60 ° C, and the mixture was stirred for 3 hours at the same temperature. Water was added to the reaction mixture and the precipitate was collected by filtration. These were washed with water and chloroform in sequence and dried in air to obtain 163 mg of the title compound as a yellowish brown powder. 58% yield. mp 198-200 ° C (decomposition). Analysis calculated for C? 5H8N408. H20: C, 46.16; H, 2.58; N, 14.36. Found: C, 46.46; H, 2.56; N, 14.26. HR-BAR +: 373.0424 (+ 0.4mmu).

(Example 64) 3,4-Dihydro-6-nitro-7- (3-nitrobenzyl-amino) -3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 31 (38.8 mg, 90.8 μmol) in methanol ( 1 ml) was added an aqueous solution of potassium hydroxide IN (182 μl, 182 μmol), and the mixture was refluxed for 1 hour. After cooling, acetic acid was added to bring the pH 4 and the solvent was distilled. Water was added to the residue, which was extracted with chloroform. After drying over anhydrous sodium sulfate, the solvent was distilled. The obtained residue was dissolved in acetic acid (1 ml) and then concentrated hydrochloric acid (0.2 ml) was added, which was allowed to stand overnight at room temperature. Water was added to the reaction mixture and the precipitate was collected by filtration. These were washed with water and chloroform in sequence and then air dried to obtain 27.2 mg of the title compound as a dark purple powder. Performance of 78%. mp 239-241 ° C. HR-BAR +: 386.0716 (-2.0mmu).

(Example 65) 3,4-Dihydro-6-nitro-3-oxo-7-phthaloyl-quinoxaline-2-carboxylic acid Using the compound of Example 32 (50.0 mg, 118 μmol) and following the same procedure as in Example 63, 5.70 mg of the title compound was obtained as a yellow powder. Yield of 13%. mp 297-299 ° C. HR-BAR-: 379.0289 (-2.5mmu).

(Example 66) 3, 4-Dihydro-7- (imidazol- -yl) methyl-6-nitro-3-oxoquinoxaline-2-carboxylic acid hydrochloride HCl ** € To the compound of Example 33 (102 mg, 285 μmol) was added 4N hydrochloric acid (15 ml), and the mixture was stirred for 2 hours at room temperature. Concentrated hydrochloric acid (1 ml) was added additionally to the reaction mixture to react for an additional 1.5 hours at 80 ° C and the solvent was redistilled under reduced pressure. The obtained residue was dissolved in water and, after treatment with activated charcoal, the solvent was distilled. A small amount of water and ethanol was added to the obtained residue and, after allowing to stand under cooling with ice while stirring, the precipitate was collected by filtration. These were washed with water with the mixed solution of water-ethanol and ethyl acetate in sequence and then air-dried to obtain 39.7 mg of the title compound as a pale yellow powder. Performance of 39%. pf > 300 ° C. Analysis calculated for C? 3H9N505. HCl .1 / 2H20: C, 43.29; H, 3.07; N, 19.41. Found: C, 43.38; H, 3.06; N, 19.48.

(Example 67) 3,4-Dihydro-7-dimethylaminomethyl-6-nitro-3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 34 (161 mg, 482 μmol) in 4N hydrochloric acid (15 ml) was added. He added concentrated hydrochloric acid (1 ml) at room temperature, and the mixture was stirred for 1 hour at room temperature and for 1 hour at 70 ° C. The solvent was distilled, acetonitrile was added to the obtained residue and the precipitate was collected by filtration. These were purified with synthetic SP850 adsorbent [water] to obtain 82.0 mg of the title compound as a yellow powder, Yield 57%. pf > 300 ° C. Analysis calculated for C? 2H? 2N405.3 / 10H2O: C, 48.42; H, 4.27; N, 18.82. Found: C, 48.35; H, 4.00; N, 18.77.

(Example 68) 7-Fluoro-3-methoxy-6-nitroquinoxalin-2-carboxamide To a suspension of the compound of Example 9 (542 mg, 1.84 mmol) in methanol (20 ml) was added 28% aqueous ammonia (1.5 ml), and the mixture was refluxed for 3 hours. Water was added to the residue obtained by distillation of the solvent under reduced pressure and the precipitate was collected by filtration. After air drying, these were dissolved in ethyl acetate, which was dried over anhydrous sodium sulfate. The solvent was distilled, the residue decanted with isopropyl ether and air dried to obtain 369 mg of the title compound as a reddish brown powder. Performance of 76%. ? -RMN (DMSO-de, d): 4.18 (3H, s), 7.97 (1H, d, J = 10.7Hz), 8.56 (ΔH, d, J = 7.3Hz).

(Example 69) 3, 4-Dihydro-7-fluoro-6-nitro-3-oxoquinoxalin-2-carboxamide To a solution of the compound of Example 68 (108 mg, 406 mmol) in acetic acid (3 ml) was added 48% hydrobromic acid (0.6 ml) at 0 ° C, and the mixture stirred for 1 hour at room temperature and for 1.5 hours at 60 ° C. The reaction mixture was poured into ice water, which was stirred for 20 minutes. The precipitate was collected by filtration and air dried to obtain 69.7 mg of the title compound as a yellowish brown powder. 68% yield. pf > 300 ° C. Analysis calculated for C9H5FN404: C, 42.87; H, 2.00; N, 22.22. Found: C, 42.89; H, 2.03; N, 21.96.

(Example 70) 3, 4-Dihydro-6-nitro-3-oxo-7- (4-pyridon-1-yl) quinoxaline-2-carboxamide To a solution of the compound of Example 68 (190 mg, 714 mmol) in tetrahydrofuran (10 ml) was added 4-pyridone (339 mg, 3.57 mmol), and the mixture was stirred for 24 hours at 110 ° C in a sealed tube. . After cooling, the solvent was distilled and ethanol was added. The precipitate was collected by filtration, washed with ethanol, water, ethanol and chloroform in sequence and then dried in the air to obtain a brown powder. 3N hydrochloric acid (5 ml) was added thereto and the mixture was stirred for 1 hour at room temperature. The reaction mixture was distilled under reduced pressure, the obtained residue was washed with water and dried in air to obtain 21.0 mg of the title compound as a yellowish brown powder. 8% yield. pf > 300 ° C. Analysis calculated for C, 46.75; H, 3.53; N, 19.47. Found: C, 47.15; H, 3.13; N, 19.14.

(Example 71) Ethyl 6-amino-7-fluoro-3-methoxyquinolaline-2-carboxylate The compound of Example 9 (300 mg, 1.02 mmol) was dissolved in ethanol (50 mL), and then 10% of palladium on carbon (60 mg) was added, the mixture was stirred for 2 hours under an atmosphere of hydrogen ( 1 atm).

The reaction mixture was filtered and the filtrate was t ^ concentrated under reduced pressure to obtain 260 mg of the title compound as yellow needles. 96% yield. ? -NRM (CDC13, d): 1.45 (3H, t, J = 7.3Hz), 4.10 (3H, s), 4.45 (2H, broad s). 4.50 (2H, c, J = 7.3Hz), 7.03 (HH, d, J = 8.8Hz), 7.65 (HH, d, J = 11.2Hz).

(Example 72) 6-amino-3,4-dihydro-7-fluoro-3-oxoquin-xalin-2-carboxylic To a solution of the compound of Example 71 (50.0 mg, 189 μmol) in methanol (1 ml) was added aqueous sodium hydroxide solution IN (500 μl), and the mixture was stirred for 1 hour at room temperature. After concentrating under reduced pressure, the reaction mixture was dissolved in acetic (3 ml) and 47% hydrobipic (1 ml) was added, which was allowed to stand overnight. The reaction mixture was concentrated under reduced pressure, the obtained residue was dissolved in aqueous sodium hydroxide solution, and then eluted through the synthetic adsorbent SP-850 [water].

. «Ja •, '• 127 After concentrating under reduced pressure, the eluate was made with IN hydrochloric . The precipitate was collected by filtration, washed with water, and then air dried to obtain 10.2 mg of the title compound as a reddish brown powder. Performance of 23%. pf > 300 ° C. Analysis calculated for C9H6FN303.3 / 5H20: C, 46.20; H, 3.10; N, 17.96. Found: C, 46.32; H, 3.02; N, 17.77.

(Example 73) 7- (3-Formylpyrrol-1-yl) -3-oxo-l, 2,3,4-tetrahydro-6-trifluoromethyl-2-carboxylic trifluoromethyl-2-carboxylate To a solution of ethyl 7-amino-3-oxo-l, 2,3, 4-tetrahydro-6-trifluoromethyl-2-carboxylic (3.60 g, 11.9 mmol) in acetic (60 ml) was added dropwise. , 5-dimethoxytetrahydrofuran-3-aldehyde (2.01 ml, 14.2 mmol) at 50 ° C, and the mixture was stirred for - * - * - * *% 28 1. 5 hours at the same temperature. The reaction mixture was poured into water (300 ml), which was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled. Methylene chloride was added to the obtained residue and the crystals were collected by filtration. These were washed with water with methylene chloride and then air-dried to obtain 2.57 g of the title compound as a yellow powder. The filtrate and washings were combined, concentrated under reduced pressure, and purified by column chromatography on silica gel [ethyl acetate-hexane = 2: 1] to obtain an additional 973 mg. Total yield in weight 3.54 g. Performance of 78%. XH-NMR (DMSO-d6, d): 1.18 (3H, t, J = 7.3Hz), 4.12-4.17 (2H, m), 4.84 (H, d, J = 2.0Hz), 6.60 (H, c, J = 1.5Hz), 6.82 (HH, s), 7.04 (HH, s), 7.16 (1H, s), 7.61 (HH, d, J = 1.5Hz), 7.79 (HH, s), 9.74 (HH, s), 11.02 (ÍH, s).

(Example 74) 7- (3- (aminomethyl) pyrrol-1-yl) -3-oxo-1, 2,3,4-tetrahydro-6-trifluoromethyl-2-carboxylic ethyl chloride To a solution of the compound of the Example 73 (1.98 g, 5.19 mmol) in ethanol (56 ml) was added hydroxylamine hydrochloride (778 mg, 11.2 mmol) and successively sodium acetate (919 mg, 11.2 mmol), and the mixture was refluxed for 2 hours . After cooling, water (300 ml) was added to the reaction mixture, which was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled. The residue obtained was dissolved in ethanol (80 ml) and, after adding palladium black (500 mg) and successively concentrated hydrochloric (4 ml), the mixture was stirred for 2 hours at room temperature in a flow of hydrogen (4). atm). A small amount of water was added to the reaction mixture and, after dissolving the hydrochloride, the catalyst was filtered and the solvent distilled. Acetone was added to the obtained residue and the crystals were collected by filtration. These were washed with water with acetone and then washed. dried in air to obtain 2.01 g of the title compound as a colorless powder, Yield 93%. XH-NMR (DMSO-d): 1.18 (3H, t, J = 7.3Hz), 3.90 (2H, c, J = 5.4Hz), 4.12-4.17 (2H, m), 4.83 (ΔH, d, J = 2.0Hz), 6.33 (HH, t, J = 2.4HZ), 6.69 (HH, s), 6.88 (HH, d, J = 2.4Hz), 6.98 (HH, s), 7.14 (HH, s), 7.64 (ÍH, s), 8.06 (3H, broad), 11.00 (ÍH, s).

(Example 75) 7- (3- (((4-ethoxycarbonylphenyl) aminocarbonylamino) -methyl) pyrrol-1-yl) -3-oxo-l, 2,3,4-tetrahydro-6-trifluoromethyl-2-oxo-carboxylate ethyl To a solution of the compound of Example 74 (1.03 g, 2.46 mmol) in N, N-dimethylformamide (25 ml) was added triethylamine (514 μl, 3.96 mmol) and successively ethyl 4-isocyanatobenzoate (564 mg, 2.95 mmol) at room temperature, and the mixture was stirred for 3 hours at the same temperature. The reaction mixture was poured into water (200 ml) and the precipitate was collected by filtration. These were washed with water and then with methylene chloride and dried in air to obtain 1.22 of the title compound as a yellowish white powder. 87% yield. XH-NMR (DMS0-d6, d): 1.17 (3H, t, J = 7.3Hz), 1.30 (3H, t, J = 7.3Hz), 4.11-4.17 (4H, m), 4.26 (2H, c, J = 7.3Hz), 4.81 (ÍH, d, J = 2.0Hz), 6.17 (ÍH, t, J = 2.0Hz), 6.46 (HH, t, J = 5.4Hz), 6.71 (HH, s), 6.80 (2H, s), 7.11 (HH, s), 7.52 (2H, d, J = 8.8Hz) , 7.83 (2H, d, J = 8.8Hz), 8.87 (HH, s), 10.94 (HH, s).

(Example 76) 7- (3- (((4-ethoxycarbonyl-2-fluorophenyl) -aminocarbonylamino) methyl) pyrrol-1-yl) -3-oxo-l, 2,3,4-tetrahydro-6- ethyl trifluoromethylquinoxaline-2-carboxylate Using the compound of Example 74 (900 mg, 2.15 mmol) and ethyl 3-fluoro-4-isocyanatobenzoate (901 mg, 3.23 mmol) and through the same procedure as in Example 75, 448 mg of the title compound were obtained as yellow powder. Performance of 35%. XH-NMR (DMSO-de, d): 1.17 (3H, t, J = 7.3Hz), 1.30 (3H, t, J = 7.3Hz), 4.11-4.19 (4H, m), 4.28 (2H, c, J = 7.3Hz), 4.81 (HH, d, J = 2.0Hz), 6.17 (HH, t, J = 2.0Hz), 6.71 (HH, s), 6.808 (HH, s), 6.814 (HH, s) , 7.00 (HH, t, J = 5.4Hz), 7.11 (HH, s), 7.52 (HH, s), 7.66 (HH, dd-J = 11.7, 2.0Hz), 7.72 (HH, dd, J = 8.8 , 2.0Hz), 8.39 (HH, t, J = 8.3Hz), 8.71 (HH, d, J = 2.9Hz), 10.94 (HH, s).

(Example 77) 3,4-Dihydro-7- (3- (((4-ethoxycarbonylphenyl) -aminocarbonylamino) methyl) pyrrol-1-yl) -3-oxo-6-trifluoro-methylquinoxaline-2-carboxylate ethyl 33 To a solution of the compound of Example 75 (100 mg, 174 μmol) in 1,4-dioxane (3 ml) was added 2,3-dichloro-5,6-dicyanoquinone (39.5 mg, 174 μmol), and the mixture was mixed. refluxed for 1 hour. After cooling, the solvent was distilled, methylene chloride was added to the obtained residue, and the crystals were collected by filtration. These were washed with water with methylene chloride and dried in air to obtain 94.2 mg of the title compound as a yellow powder. 95% yield. ? -RMN (DMSO-de, d): 1.30 (3H, t, J = 7.3Hz), 1.32 (3H, t, J = 7.3Hz), 4.19 (2H, d, J = 4.9Hz), 4.26 (2H) , c, J = 7.3Hz), 4.40 (2H, c, J = 7.3Hz), 6.25 (HH, t, J = 2.0Hz), 6.49 (HH, t, J = 5.4Hz), 6.92 (2H, s ), 7.52 (2H, d, J = 8.8Hz), 7.75 (H, s), 7.83 (2H, d, J = 8.8Hz), 7.91 (H, s), 8.90 (H, s), 13.21 (H) , s).

(Example 78) 3,4-dihydro-7- (3- (((4-ethoxycarbonyl-2-fluorophenyl) -aminocarbonylamino) methyl) pyrrol-1-yl) -3-oxo-6-trifluoromethylquinoxalin-3 ethyl carboxylate * "Í3A Using the compound of Example 76 (448 mg, 757 μmol) and following the same procedure as in Example 5, 252 mg of the title compound was obtained as a yellow powder. 57% yield. XH-NMP (DMSO-de, d): 1.31 (3H, t, J = 7.3Hz), 1.32 (3H, t, J = 7.3Hz), 4.21 (2H, d, J = 4.9Hz), 4.28 (2H , c, J = 7.3Hz), 4.40 (2H, c, J = 7.3Hz), 6.25 (HH, t, J = 2.0Hz), 6.93 (2H, d, J = 2.4Hz), 7.03 (HH, t , J = 5.4Hz), 7. 66 (HH, dd, J = 11.7, 2.0Hz), 7.72 (HH, dd, J = 8.8, 2.0Hz), 7.75 (HH, s), 7.92 (HH, s) , 8.39 (ÍH, t, J = 8.3Hz), 8.73 (ÍH, d, J = 2.5Hz), 13.21 (ÍH, s).

(Example 79) 7- (3- (((4-carboxyphenyl) aminocarbonylamino) methyl) pyrrol-1-yl) -3 acid, -dihydro-3-oxo-6-trifluoro-methylquinoxaline-2-carboxylic acid To a solution of the compound of Example 77 (85.2 mg, 174 μmol) in ethanol (2.4 ml) was added aqueous solution of potassium hydroxide IN (596 μl). , 596 μmol), and the mixture was refluxed for 1 hour. After cooling, the solvent was distilled, the residue dissolved in a small amount of water and brought to pH 4 with 4N hydrochloric acid. The solvent was distilled and a small amount of water was added again. The crystals were collected by filtration, washed with water, and then air dried to obtain 69.2 mg of the title compound as a yellowish brown powder. 87% yield. mp 234-236 ° C (decomposition). Analysis calculated for C23H? 6F3N5? 6.H20: C, 51. 79; H, 3.40; N, 13.13. Found: C, 51.91; H, 3.43; N, 12.82. HR-BAR-: 514.0968 (-0.6 mu). '' ád v (Example 80) 7- (3- (((Carboxy-2-fluorophenyl) aminocarbonylamino) -methyl) pyrrol-1-yl) -3,4-dihydro-3-oxo-6-trifluoromethyl-2-carboxylic acid To a solution of the compound of Example 78 (250 mg, 424 μmol) in ethanol (7.5 ml) was added IN aqueous sodium hydroxide solution (1.70 ml, 1.70 mmol), and the mixture was refluxed for 1 hour. After cooling, the solvent was distilled off, the residue was dissolved in water (5 ml) and pH 2 was brought with 4N hydrochloric acid. The precipitate was collected by filtration, washed with water, and then air dried to obtain 213 mg of the title compound as a yellow powder. 93% yield. mp 249-251 ° C (decomposition). Analysis calculated for C23H? 5F4N5? 5.1 / 2H20: C, 50.93; H, 2.97; N, 12.91. Found: C, 50.90; H, 2.99; N, 12.74. * * »< < - HR-BAR-: 532. 0882 (+0 .2mmu) (Example 81) Ethyl 3, 4-dihydro-7- (4- (hydroxymethyl) imidazol-1-yl) -3-oxo-6-trifluoromethyl-2-carboxylate ethyl To a solution of 4- (4- (hydroxymethyl) imidazol-1-yl) -5-trifluoromethyl-1,2-phenylenediamine (200 mg, 781 μmol) in ethanol (10 ml) was added diethyl ketomalonate. (142 μl, 937 μmol), and the mixture was refluxed for 4 hours. After cooling, the solvent was distilled and the obtained residue was purified by column chromatography on silica gel [methylene chloride-methanol (50: 1-10: 1)] to obtain 129 mg of the title compound as a pale yellow powder. Performance of 43%. XH-NMR (DMSO-de, d): 1.33 (3H, t, J = 6.8Hz), 4.40 (2H, c, J = 6.8Hz), 4.43 (2H, d, J = 5.4Hz), 5.01 (ÍH, t, - j J = 5.4Hz), 7.21 (1H, s), 7.75 (H, s), 7.78 (H, s), 8.03 (H, s), 13.26 (H, s).

(Example 82) 3, 4-dihydro-7- (4- (((4-ethoxycarbonylphenyl) -carbamoyloxy) methyl) imidazol-1-yl) -3-oxo-6-trifluoro-methyl-loxane-2-carboxylic acid ethyl ester To a solution of the compound of Example 81 (129 mg, 337 μmol) in N, N-dimethylformamide (2 ml) was added ethyl 4-isocyanatobenzoate (118 mg, 675 μmol), and the mixture was stirred for 1 hour at room temperature. environment, then left to rest statically during the night. The solvent was distilled and the residue obtained was purified by chromatography on silica gel [methylene chloride-ethanol (50: 1 20: 1)] to obtain 130 mg of the title compound as a pale yellow powder. 67% yield.

^ -RMN (DMSO-de, d): 1.30 (3H, t, J = 7.3Hz), 1.32 (3H, t, J = 6.8Hz), 4.28 (2H, c, J = 7.3Hz), 4.38 (2H , c, J = 6.8Hz), 5.11 (2H, s), 7.53 (HH, s), 7.61 (2H, d, J = 8.8Hz), 7.74 (HH, s), 7.86 (HH, s), 7.89 (2H, d, J = 8.8Hz), 8.02 (ÍH, broad), 10.20 (ÍH, s), 13.24 (ÍH, s broad).

(Example 83) 7- (4- (((4-carboxyphenyl) carbamoyloxy; methyl) imidazol-1-yl) -3,4-dihydro-3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid To a solution of the compound of Example 82 (130 mg, 227 μmol) in ethanol (5 ml) was added aqueous solution of potassium hydroxide IN (681 μl, 681 μmol) and successively water (1 ml), and the mixture was subjected to at reflux for 2 hours. After cooling, the solvent was distilled, water was added, and the pH value was brought to 2 using 3N hydrochloric acid. The precipitate is. * - uncle collected by filtration, washed with water and dried in air to obtain 32.0 mg of the title compound as a white powder. Yield of 26%. MP 278-280 ° C (decomposition). Analysis Calculated for C22H? 4F3N507.6 / 5H20: C, 49.02; H, 3.06; N, 12.99. Found: C, 49.37; H, 3.10; N, 12.66. HR-BAR-: 516.0760 (-0.7 mum).

(Example 84) 3-Ethoxy-7- (4- (hydroxymethyl) imidazolyl) -6-nitroquinoxaline-2-carboxylate ethyl To a solution of ethyl 3-ethoxy-7-fluoro-6-nitroquinoxaline-2-carboxylate (6.90 g, 22.3 mmol) in acetonitrile (70 ml) was added dropwise 4- (hydroxymethyl) imidazole hydrochloride (15.1 g, 112 mmol) and successively triethylamine (23.4 ml, 168 mmol) under the shade, and the mixture was refluxed for 16 hours. After cooling, the chloride was added. methylene to the reaction mixture, which was washed with water. The aqueous layer was extracted with methylene chloride, which was combined with the above organic layer. After drying over anhydrous sodium sulfate, the solvent was distilled. The obtained residue was purified by means of column chromatography on silica gel [ethyl acetate] to obtain 3.69 g of the title compound as a brown powder. Performance of 43%. However, 2.15 g of ethyl 3-ethoxy-7-fluoro-6-nitroquinoxaline-2-carboxylate was recovered. Performance of 31%. ^ -RMN (CDC13, d): 1.47 (3H, t, J = 7.1Hz), 1.53 (3H, t, J = 7.1Hz), 4.55 (2H, c, J = 7.2Hz), 4.66 (2H, c , J = 7.2Hz), 4.71 (2H, s), 7.09 (HH, s), 7.68 (HH, d, J = 1.5Hz), 8.15 (HH, s), 8.43 (HH, s).

(Example 85) 7- (4- ((N- (4-Bromophenyl) carbamoyloxy) methyl) -imidazolyl) -3-ethoxy-6-nitroquenoxalin-2-carboxylate ethyl '-' t m A solution of the compound of Example 84 (100 mg, 258 μmol) and 4-bromophenyl isocyanate (51.1 mg, 258 μmol) in methylene chloride (1 ml) was stirred for 3 hours at room temperature, and then the solvent was distilled to obtain 145 mg of the title compound as a yellow amorphous material. 96% yield. XH-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.1Hz), 4.55 (2H, c, J = 7.2Hz), 4.66 (2H, c , J = 7.0Hz), 5.23 (2H, s), 6.81 (HH, s), 7.24 (HH, s), 7.29 (2H, d, J = 8.8Hz), 7.41 (2H, dt, J = 8.8, 2.6Hz), 7.70 (HH, d, J = 1.5Hz), 8.15 (HH, s), 8.45 (HH, s).

(Example 86) 7- (4- ((N- (4-Bromophenyl) carbamoyloxy) methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxalen-2-carboxylic acid% (Example 86) To a solution of the compound of Example 85 (100 mg, 171 μmol) in acetic acid (3 ml) was added concentrated hydrochloric acid (0.5 ml), and the mixture was stirred for 16 hours at room temperature. The reaction mixture was concentrated under reduced pressure, water was added, and the precipitate was collected by filtration. These were washed with water, then with chloroform, and then air-dried to obtain 57.2 mg of the title compound as a yellow powder. 62% yield. mp 270-272 ° C (decomposition). Analysis Calculated for C2oH? 3BrN607.1 / 2H20: C, 44.62; H, 2.62; N, 15.61. Found: C, 44.97; H, 2.51; N, 15.26. HR-BAR +: 529.0123 (+ 1.5mum). Í4 - (Example 87) 7- (4- ((N-benzylcarbamoyloxy) methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylate sodium To a solution of the compound of Example 84 (100 mg, 258 μmol) in methylene chloride (3 ml) was added benzyl isocyanate (47.8 μl, 387 μmol), and the mixture was stirred for 6 hours at room temperature. The solvent was then distilled off, the residue was dissolved in acetic acid (3 ml), concentrated hydrochloric acid (0.6 ml) was added, and the mixture was stirred for 36 hours at room temperature. The reaction mixture was concentrated under reduced pressure and dissolved in 2N aqueous sodium hydroxide solution, which was washed with ethyl acetate. The aqueous layer was concentrated under reduced pressure and the precipitate was collected by filtration. These were washed with water, then with chloroform and then air-dried to obtain 49.0 mg of the title as a yellow powder. Yield of 36%. mp 222-224 ° C (decomposition). HR-BAR +: 487.0998 (+ 2.0mum).

(Example 88) 3,4-Dihydro-6-nitro-3-oxo-7- (4- ((N-phenylcarbaoyloxy) -methyl) imidazolyl) quinoxaline-2-carboxylic acid To a solution of the compound of Example 84 (100 mg, 258 μmol) in methylene chloride (3 ml) was added phenyl isocyanate (42.1 μl, 387 μmol), and the mixture was stirred for 6 hours at room temperature. After distilling off the solvent, the residue was dissolved in acetic acid (3 ml), concentrated hydrochloric acid (0.6 ml) was added, and the mixture was stirred for 36 hours at room temperature. The reaction mixture was concentrated under reduced pressure and dissolved in solution aqueous 2N sodium hydroxide, which was washed with ethyl acetate. This was neutralized with concentrated hydrochloric acid and the precipitate was collected by filtration. These were washed with water, then with chloroform and then air-dried to obtain 65.2 mg of the title compound as a whitish brown powder. Yield of 52%. mp 241-243 ° C (decomposition). HR-BAR +: 451.1008 (+ 0.5mmu).

(Examples 89 to 107) Through the same procedure as in Example 88, the compounds obtained in the following Table 5 are listed.

Table 5 Example Example R Example R Example 89"117 Example R Example R Example R Example (Example 89) mp 266-268 ° C (decomposition). Analysis calculated for C2oH? 3BrN607. HCl. H20: 1.15; H, 2.76; N, 14.40. Found: C, 41.07; H, 2.67; N, 14.35. HR-BAR +: 529.0140 (+ 3.3mmu). '? 48u (Example 90) mp 260-262 ° C (decomposition). Analysis calculated for C2oH? 3BrN607. H20: C, 43.89; H, 2.76; N, 15.36. Found: C, 44.24; H, 2.66; N, 15.03. HR-BAR +: 529.0084 (-2.3mmu) .. (Example 91) mp 250-252 ° C (decomposition). HR-BAR-: 483.0451 (-0.5mmu).

(Example 92) mp 215-217 ° C (decomposition). Analysis calculated for C20H? 3ClN6O7. HCl .1 / 2H20: C, 45.30; H, 2.85; N, 15.85. Found: C, 45.23; H, 2.95; N, 15.84. HR-BAR-: 483.0476 (+ 2.0mmu).

(Example 93) mp 205-207 ° C (decomposition) HR-BAR-: 483.0466 (+ 1.0mmu).

(Example 94) mp 217-219 ° C (decomposition). Analysis calculated for C2oH? 3FN607. HCl .1 / 2H20: C, 46.75; H, 2.94; N, 16.36.

Found: C, 47 * 16; H, 3.05; N, 16.21 HR-F-B +: 469.0915 (+ 0.7mmu).

(Example 95) mp 270-272 ° C (decomposition). HR-BAR +: 467.0748 (-0.4mmu) ..

(Example 96) mp 251-253 ° C (decomposition). Analysis calculated for C20H? 3FN607.1 / 2H20: C, 50. 32; H, 2.96; N, 17.60. Found: C, 50.01; H, 2.68; N, 17.65. HR-BAR-: 467.0787 (+ 3.6mmu).

(Example 97) mp 265-267 ° C (decomposition) HR-BAR +: 465.1156 (-0.3mmu).

(Example 98) mp 223-225 ° C (decomposition). Analysis calculated for C2? Hi6N60 .1 / 2H20: C, 3.28; H, 3.62; N, 17.75. Found: C, 53.27; H, 3.51; N, 17.61. HR-BAR-: 463.0996 (-O.ß mu). rso (Example 99) mp 252-254 ° C (dec.). Analysis calculated for C2? Hi6Ne07. HCl: C, 50.36; H, 3.42; N, 16.78. Found: C, 50.38; H, 3.64; N, 16.80. HR-BAR-: 463.1009 (+ 0.7mmu) ..

(Example 100) mp 256-258 ° C (decomposition). HR-BAR-: 517.0723 (+ 0.3mmu).

(Example 101) mp 230-232 ° C (decomposition). Analysis calculated for C21H13F3N6O-7. 1 / 4H20: C, 48. 2. 3; H, 2 60; N, 16 07 Found: C, 47.93; H, 2.52; N, 16.09. HR-BAR-: 517.0704 (-1.5mmu).

(Example 102) mp 203-205 ° C (decomposition). Analysis calculated for C2oH? 2C2Ne0. H20: C, 44.71; H, 2.63; N, 15.64. Found: C, 44.39; H, 2.40; N, 15.34. HR-BAR-: 517.0046 (-2.0mmu). 154 (Example 103) mp 218-220 ° C (decomposition). Analysis calculated for C2oH? 2C? 2N607. HCl .1 / 2H20: C, 42.54; H, 2.50; N, 14.88. Found: C, 42.79; H, 2.54; N, 14.95. HR-BAR-: 517.0062 (-0.5mmu) ..

(Example 104) mp 246-248 ° C (decomposition). Analysis calculated for C2oH? 2Ci2N607.1 / 2H20: C 45. 47; H, 2.48; N, 15.91. Found: C, 45.43; H, 2.28; N, 15.95. HR-BAR-: 517.0065 (-0.2mmu).

(Example 105) mp 199-201 ° C (decomposition). Analysis calculated for C? Hi6N607. H20: C, 47.01; H, 4.18; N, 19.35. Found: C, 47.19; H, 3.91; N, 19.40. HR-BAR-: 415.1001 (-0.2mmu).

(Example 106) mp 194-196 ° C (decomposition). Analysis calculated for C? 8H? 8N6? 7.1 / 2H20: C, 49.20; H, 4.36; N, 19.13. * l% 2 Found: C, 49.06; H, 4.23; N, 18.92 HR-BAR-: 429.1161 (+ 0.2mmu).

(Example 107) mp 185-187 ° C (dec.). HR-BAR-: 429.1140 (-1.9mmu). (Example 108) 3,4-dihydro-7-4- ((N- (4-methoxyphenyl) -carbamoyloxy) methyl) imidazolyl) -6-nitro-3-oxoquinoxaline-2-carboxylate sodium To a solution of the compound of Example 84 (100 mg, 258 μmol) in methylene chloride (1 ml) was added 4-methoxyphenyl isocyanate (50.1 μl, 387 μmol), and the mixture was stirred for 6 hours at room temperature. After distilling off the solvent, the residue was dissolved in acetic acid (3 ml) and concentrated hydrochloric acid (0.6 ml) was added, which was stirred for 24 hours at room temperature. The reaction mixture was concentrated under reduced pressure and dissolved in 2N aqueous sodium hydroxide solution, which was then washed with ethyl acetate. This was concentrated under reduced pressure and the precipitate was collected by filtration. These were washed with water, then with chloroform and then air-dried to obtain 70.2 mg of the title compound as a yellow powder. Yield of 53%. mp 265-267 ° C (decomposition). Analysis calculated for C2? Hi5N608 a.1 / 2H20: C, 49.32; H, 3.15; N, 16.43. Found: C, 49.51; H, 3.08; N, 16.58. HR-BAR +: 503.0913 (-1.4mmu).

(Example 109) 7- (4- ((N- (2,6-dichlorophenyl) carbamoyloxy) • methyl) -imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid A solution composed of Example 84 (100 mg, 258 μmol) and isocyanate 2-dichlorophenyl (72.8 mg, 387 μmol) in benzene (5 ml) was refluxed for 2 hours. After cooling, the reaction mixture was purified by column chromatography on silica gel [hexane-ethyl acetate = "1: 1] to obtain a yellow oil, which was dissolved in acetic acid (5 ml) and He added concentrated hydrochloric acid (1 ml), which was stirred for 24 hours at room temperature, the reaction mixture was concentrated under reduced pressure, dissolved in 2N aqueous sodium hydroxide solution, and then the insoluble fractions were filtered. to neutralize using concentrated hydrochloric acid, the precipitate was collected by filtration, which was washed with water, then ethyl acetate and then air-dried to obtain 9.8 mg of the title compound as a yellowish brown powder. mp 253-255 ° C (decomposition). HR-BAR-: 517.0087 (+ 2.1mmu).

(Examples 110 to 113) Through the same procedure as in Example 109, the compounds listed in the following Table 6 were obtained. '% & $ "• Table 6 Example 16 R 110 xx OCF, (Example 110) mp 252-254 ° C (decomposition) HR-BAR-: 533.0677 (+ 0.9mmu).

(Example 111) mp 263-265 ° C (decomposition) HR-BAR-: 491.1323 (+ 0.8mmu).

(Example 112) mp 234-236 ° C (decomposition). Analysis calculated for C20H? 2C? 2N6O7: C, 46.26; H, 2.33; N, 16.18. Found: C, 46.12; H, 2.38; N, 15.90. HR-BAR-: 517.0043 (-0.5mmu).

? Sp7 \ 7 (Example 113) mp 272-274 ° C (decomposition) HR-BAR-: 517.0090 (+ 2.4mmu).

(Example 114) 3,4-Dihydro-6-nitro-3-oxo-7- (4- ((N- (4-trifluoromethyl-phenyl) carbamoyloxy) methyl) imidazolyl) -quinoxaline-2-carboxylic acid A solution of the compound of Example 84 (100 mg, 258 μmol), 4-trifluoromethylbenzoic acid (73.6 mg, 387 μmol), diphenylphosphoric acid (83.4 μl, 387 μmol) and triethylamine (53.9 μl, 387 μmol) in benzene (5 ml ) was refluxed for 3 hours. After cooling, the reaction mixture was purified by column chromatography on silica gel [hexane-ethyl acetate = 1: 1] to obtain a yellow oil. This was dissolved in acetic acid (5 ml), and concentrated hydrochloric acid (1 ml) was added, which was stirred for 24 hours at room temperature. The reaction mixture was concentrated under reduced pressure, 2N aqueous sodium hydroxide solution was added, and the insoluble fractions were filtered. The filtrate was acidified with concentrated hydrochloric acid and the precipitate was collected by filtration. These were washed with water and ethyl acetate in sequence and then air dried to obtain 14.6 mg of the title compound as a yellow powder. Yield of 11%. mp 276-278 ° C (decomposition). HR-BAR-: 517.0703 (-l.ßmmu).

(Example 115) 7- (4- ((N- (4-carboxyphenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid A solution of the compound of Example-84 (100 mg, 258 μmol) and ethyl 4-isocyanatobenzoate (74.0 mg, 387 μmol) in benzene (5 ml) was refluxed for 2 hours. After cooling, the reaction mixture was purified by column chromatography on silica gel [hexane-ethyl acetate = 1: 1] to obtain a yellow oil. This was dissolved in acetic acid (5 ml) and concentrated hydrochloric acid (1 ml) was added, which was stirred for 24 hours at room temperature. The reaction mixture was concentrated under reduced pressure, water was added, and the precipitate was collected by filtration. These were washed with water, then with ethyl acetate and then air-dried to obtain a brown powder. This was dissolved in IN lithium hydroxide solution (15 ml) and the solution was stirred for 2.5 hours at room temperature. After filtering the insoluble fractions, the solution was acidified with concentrated hydrochloric acid and the precipitate was collected by filtration. These were washed with water and then air-dried to obtain 47.8 mg of the title compound as a brown powder. Yield of 37%. mp 268-270 ° C (decomposition). HR-BAR-: 493.0769 (+ 2.5mmu).

(Example 116) 7- (4- ((N- (3-carboxyphenyl) carbamoyloxy) -methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid Using the compound of Example 84 (500 mg, 1. 29 mmol) and ethyl 3-isocyanatobenzoate (321 μl, 1.94 mmol) and following the same procedure as in the Example 32, 297 mg of the title compound was obtained as a yellowish brown powder. 44% yield. mp 272-274 ° C (decomposition). Analysis calculated for C2? H? 4N609.3 / 2H20: C, 48.47; H, 3.29; N, 16.15. Found: C, 48.62; H, 3.13; N, 16.27. HR-BAR-: 493.0739 (-0.5mmu).

(Example 117) 3-Ethoxy-6-nitro-7- (4- (trifluoroacetamidomethyl) imidazolyl) quinoxaline-2-carboxylic acid ethyl ester To a solution of ethyl 3-ethoxy-7-fluoro-6-nitroquinoxaline-2-carboxylate (308 mg, 999 μmol) and 4- (trifluoroacetamidomethyl) imidazole (1.72 g, 8.91 mmol) in acetonitrile (10 ml) was added triethylamine (3.00 ml, 21.5 mmol), and the mixture was stirred for 15 hours at 130 ° C in a sealed tube. The reaction mixture was concentrated under reduced pressure and the residue obtained was purified by column chromatography on silica gel [methylene chloride] to obtain 179 mg of the title compound as a light brown powder. Yield of 37%. XH-NMR (CDC1, d): 1.47 (3H, t, J = 6.8Hz), 1.52 (3H, t, J = 7.3Hz), 4.545 (2H, s), 4.553 (2H, c, J = 7.3Hz) ), 4. 67 (2H, c, J = 6.8Hz), 7.12 (IH, d, J = 1.5HZ), 7.16 (IH, broad), 7.67 (IH, d, J = 1.5HZ), 8.16 (1H, s) , 8.46 (ÍH, s). 61 (Example 118) 3,4-Dihydro-7- (4- (((2-fluorophenyl) aminocarbonylamino) methyl) imidazolyl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 117 (177 mg, 367 μmol) in methanol (5 ml) was added an aqueous solution of potassium carbonate (5 ml) (700 mg, 5.06 mmol), and the mixture was allowed to stand statically during 5 hours at room temperature. This was neutralized with IN hydrochloric acid and then allowed to stand statically overnight, the mixture was concentrated under reduced pressure. The residue was made weakly basic with saturated aqueous sodium hydrogen carbonate solution. The precipitate was collected by filtration, washed with water and then dried in air. The obtained crystals were suspended in N, N-dimethylformamide (2 ml), then V62 was added 2-fluorophenyl isocyanate (31.0 μl, 282 μmol), and the mixture was stirred for 20 minutes at 60 ° C. The reaction mixture was concentrated under reduced pressure and the residue was collected by filtration, washed with water, dried in air and then washed with diisopropyl ether. The crystals obtained in this way were dissolved in concentrated acetic acid-hydrochloric acid (5: 1, 2 ml), which were allowed to stand statically overnight. Then the reaction mixture was concentrated under reduced pressure, ice water was added to the residue and the crystals were collected by filtration and washed with water. After air drying, these were washed with ethyl acetate and dried to obtain 59.9 mg of the title compound as a pale brown powder. Performance of 33%. mp 300 ° C. Analysis calculated for C2oH? 4FN706. 6 / 5H20: C, 49. 12; H, 3. 38; N, 20 05 Found: C, 49. 12; H, 3.23; N, 19.80.

(Example 119) 7- (4- (((4-carboxyphenyl) aminocarbonylamino) methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 117 (243 mg, 504 μmol) in methanol (7 ml) was added an aqueous solution of potassium carbonate (7 ml) (960 mg, 6.95 mmol), and then left to stand static during overnight, the mixture was concentrated under reduced pressure. Ice water was added to the residue and then made weakly acidic (pH 4) with IN hydrochloric acid, the solution made weakly basic (pH 8) with saturated aqueous sodium hydrogen carbonate solution, which was concentrated under reduced pressure. The obtained crystals were suspended in N, N-dimethylformamide (2 ml), then ethyl 4-isocyanatobenzoate (145 mg, 758 μmol) was added and the mixture was stirred for 4 hours at 60 ° C. Ethyl 4-isocyanatobenzoate (55.1 mg, 288 μmol) was added and the mixture was stirred for 5 hours at 80 ° C. The reaction mixture was concentrated under reduced pressure and the residue was collected by filtration, washed with water and then air dried. The crystals obtained in this way were dissolved in acetic acid-concentrated hydrochloric acid (5: 1, 6 ml) and the mixture was stirred for 8 hours at 30 ° C. Then, concentrated hydrochloric acid (1 ml) was added further and the mixture was stirred for 3 hours at 40 ° C. After the reaction mixture was concentrated under reduced pressure, a solution of lithium hydroxide monohydrate (105 mg, 2.50 mmol) in methanol-water (1: 1, 10 ml) was added to the residue, which was stirred for 2 hours. hours at 50 ° C. The reaction mixture was concentrated to about half the volume under reduced pressure and filtered. The filtrate was brought to pH 3 with 1 N hydrochloric acid and the precipitate was collected by filtration and washed with water. After air drying, these were washed with ethanol and methanol and dried to obtain 31.0 mg of the title compound as a light brown powder. Yield of 12%. mp 300 ° C (decomposition). Analysis calculated for C2? H? 5N708. HCl .4 / 5H20: C, 46.33; H, 3.07; N, 18.01. Found: C, 46.53; H, 3. 25; N, 17.84.

(Example 120) 3-Ethoxy-7- (3-hydroxymethyl) -4-pyridon-1-yl) -6-nitroquinoxaline-2-carboxylic acid ethyl ester To a solution of 4-chloro-3- (hydroxymethyl) pyridine (2.33 g, 16.2 mmol) in water (25 mL) was added sodium hydroxide (5.20 g, 130 mmol), and the mixture was refluxed for 24 hours . After cooling, the reaction mixture was neutralized with concentrated hydrochloric acid and concentrated under reduced pressure. The obtained residue was dissolved in N, N-dimethylformamide (20 ml), then 3-ethoxy-7-fluoro-6-nitroquinoxaline-2-carboxylic acid ethyl ester was added. (500 mg, 1.62 mmol), and the mixture was stirred for 4 hours at 110 ° C. The reaction mixture was poured into ice water, which was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled. The obtained residue was purified by means of column chromatography on silica gel [ethyl acetate] to obtain 410 mg of the title compound as a yellow powder. Performance of 61%. XH-NMR (CDC13, d): 1.47 (3H, t, J = 7.1Hz), 1.54 (3H, t, J = 7.1Hz), 4.56 (2H, c, J = 7.2Hz), 4.59 (2H, s ), Ét # "6 4. 68 (2H, c, J = 7.2Hz), 6.52 (1H, d, J = 8.0Hz), 7.41 (IH, dd, J = 7.3, 2.4Hz), 7.45 (1H, d, J = 2.4Hz), 8.20 (ÍH, s), 8.57 (ÍH, s).

(Example 121) 3,4-Dihydro-6-nitro-3-oxo-7- (3- ((N-phenylcarbamoyloxy) methyl) -4-pyridon-1-yl) oruinoxaline-2-carboxylic acid To a solution of the compound of Example 120 (100 mg, 241 μmol) in methylene chloride (1 ml) was added phenyl isocyanate (39.4 μl, 362 μmol), and the mixture was stirred for 8 hours at room temperature.

Hexane-methylene chloride (1: 1, 3 ml) was added to the reaction mixture and the precipitate was collected by filtration, followed by air drying. These were dissolved in acetic acid (3 ml), concentrated hydrochloric acid (0.6 ml) was added and the mixture was stirred for 24 hours at room temperature. Water was added to nzsi the reaction mixture and the precipitate was collected by filtration, then air dried to obtain 61.8 mg of the title compound as a yellow powder. 51% yield. mp 230-232 ° C (decomposition). Analysis calculated for C22H? 5N5? 8.3 / 2H20: C, 52.39; H, 3.60; N, 13.88. Found: C, 52.70; H, 3.41; N, 13.81. HR-BAR-: 476.0837 (-0.6mmu).

(Examples 122 to 124) Through the same procedure as in Example 121, the compounds listed in the following Table 7 were obtained. Table 7 Example position (Example 122) mp 195-197 ° C (decomposition). Analysis calculated for C22H? 4BrN508.3 / 2H20: C, 5.30; H, 2.94; N, 12.01. Found: C, 45.20; H, 2.63; N- > 12.17. * 68 HR-BAR-: 553.9958 (-fl.lmmu) (Example 123) mp 199-201 ° C (decomposition). Analysis calculated for C22H? 4BrN508. H20: C, 46.01; H, 2.81; N, 12.19. Found: C, 45.62; H, 2.59; N, 12.12. HR-BAR-: 553.9988 (+ 4.1mmu).

(Example 124) mp 230-232 ° C (decomposition) HR-BAR-: 553.9958 (tl.Ommu).

(Example 125) 7- (3- ((N- (3-carboxyphenyl) carbamoyloxy) methyl) -4-pyridon-1-yl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid 1 «9 To a solution of the compound of Example 120 (500 mg, 1.21 mmol) in methylene chloride (5 ml) was added ethyl 3-isocyanatobenzoate (302 μl)., 1.82 mmol), and the mixture was stirred for 8 hours at room temperature. Hexane-methylene chloride (1: 1, 5 ml) was added to the reaction mixture and the precipitate was collected by filtration, followed by air drying. These were dissolved in acetic acid (15 ml), concentrated hydrochloric acid (3 ml) was added and the mixture was stirred for 24 hours at room temperature. The reaction mixture was concentrated under reduced pressure, water was added and the precipitate was collected by filtration. Then, these were washed with ethyl acetate and air dried. These were dissolved in IN lithium hydroxide solution (15 ml) and the solution was stirred for 3 hours at room temperature. The insoluble fractions were filtered and then the solution was acidified with concentrated hydrochloric acid. The precipitate was collected by filtration, washed with water and then air dried to obtain 257 mg of the title compound as a yellow powder. Performance of 38%. mp 250-252 ° C (decomposition). Analysis calculated for C23H? 5N5O? O.5 / 2H20: C, 48.86; H, 3.56; N, 12.39. * f7" Found: C, 48.58; H, 3.29; N, 12.34 HR-BAR-: 520.0735 (-O.dmmu).

(Example 126) 7- (3-amino-4-pyridon-1-yl) -3-ethoxy-6-nitroquinoxaline-2-carboxylic acid ethyl ester A solution of ethyl 3-etox? -7-fluoro-6-n? Trochmoxal? N-2-carboxylate (3.99 g, 12.9 mmol) and 3-am? No-4-p? R? Dona (7.10 g, 64.5 mmol) in N, N-dimethylformamide (150 ml) was stirred for 8 hours at 100 ° C. The solvent was distilled and the residue obtained was dissolved in methylene chloride. Then, the solution was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled. The obtained residue was purified by means of column chromatography on silica gel [ethyl acetate] to obtain 2.50 g of the title compound as a brown powder. 49% yield.

XH-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.1Hz), 4.55 (2H, c, J = 7.2Hz), 4.67 (2H, c , J = 7.2Hz), 6.47 (HH, d, J = 7.3Hz), 7.03 (1H, d, J = 2.4Hz), 7.24 (HH, dd, J = 7.3Hz), 2.4Hz), 8.19 (HH) , s), 8.49 (ÍH, s).

(Example 127) 7- (3- ((4-bromophenyl) aminocarbonylamino) -4-pyridon-1-yl) -3-ethoxy-6-nitroquinoxaline-2-carboxylate ethyl A solution of the compound of Example 126 (69.9 mg, 175 μmol), and 4-bromophenyl isocyanate (34.7 mg, 175 μmol) in methylene chloride (5 ml) were stirred for 3 hours at room temperature. The precipitate was collected by filtration, washed with hexane-methylene chloride (1: 1) and then air dried to obtain 83.0 mg of the title compound as a yellow powder. 79% yield. 1 H-NMR (CDC13, d): 1.37 (3H, t, J = 8.8Hz), 1.44 (3H, t, J = 6.8Hz), 4.48 (2H, c, J = 6.8Hz), 4.63 (2H, c , J = 6.8Hz), 6.41 (HH, d, J = 7.8Hz), 7.38 (2H, d, J = 8.9Hz), 7.43 (2H, d, J = 9.3Hz), 7.95 (HH, dd ,. J = 7.8, 8.2Hz), 8.66 (2H, s), 8.67 (IH, d, J = 2.4Hz), 8.71 (IH, s), 9.76 (IH, (Example 128) 7- (3- ((4-Bromophenyl) aminocarbonylamino) 4-pyridon-1-yl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 126 (83.0 mg, 139 μmol) in acetic acid (3 ml) was added concentrated hydrochloric acid (0.6 ml), and the mixture was stirred for 24 hours at room temperature. Mix The reaction was poured into water (30 ml) and the precipitate was collected by filtration, washed with water and chloroform in sequence, and then air dried to obtain 72.9 mg of the title compound as a yellow powder. 91% yield. mp 252-254 ° C (dec.). Analysis calculated for C2iH? 3Br 607.2H20: C, 43.69; H, 2.977; N, 14.55. Found: C, 43.90; H, 2.59; N, 14.53. HR-BAR +: 541.0070 (-3.8mmu).

(Example 129) 3, 4-Dihydro-6-nitro-3-oxo-7- (3- (phenylamino-carbonylamino) -4-pyridon-1-yl) quinoxaline-2-carboxylic acid To a solution of the compound of Example 126 (100 mg, 250 μmol) in methylene chloride (5 ml) was added. added phenyl isocyanate (40.8 μl, 375 μmol), and the mixture was stirred for 8 hours at room temperature. Hexane-methylene chloride (1: 1, 3 ml) was added to the reaction mixture and the precipitate was collected by filtration. These were washed with hexane-methylene chloride (1: 1) and then placed in the air. These were dissolved in acetic acid (3 ml), then concentrated hydrochloric acid (0.6 ml) was added and the mixture was stirred for 24 hours at room temperature. The reaction mixture was poured into water (30 ml) and the precipitate was collected by filtration. These were washed with water and chloroform in sequence, and then air dried to obtain 63.5 mg of the title compound as a yellowish brown powder. Yield of 15 54%. mp 282-284 ° C (decomposition). Analysis calculated for C2? H? 4N607.1 / 2H20: C, 53.51; H, 3.21; N, 17.83. Found: C, 53.72; H, 3.59; N, 18.00 20 HR-BAR +: 463.1020 (+ 1.8mmu).

(Examples 130 to 135) Through the same procedure as in Example 129, the compounds listed in Table 8 below.

Table 8 Example R Example R (Example 130) mp 220-222 ° C (decomposition). Analysis calculated for C22H16 6O7. H20: C, 53.44; H, 3.67; N, 17.00 Found: C, 53.60; H, 3.59; N, 17.02. HR-BAR +: 477.1170 (+ l.lmmu).

(Example 131) ^ pf 298-300 ° C (decomposition). Analysis calculated for C2iH? 3BrN6? 7. H20: C, 45.10; H, 2.70; N, 15.03. Found: C, 45.31; H, 2.48; N, 14.77. HR-BAR +: 541.0086 (-2.1mmu).

(Example 132) mp 263-265 ° C (decomposition).

Analysis calculated for C2iH? 3BrN6? 7.1 / 2H20: C, 45.84; H, 2.56; N, 15.27. Found: C, 45.69; H, 2.65; N, 15.09. HR-BAR +: 541.0096 (-l.lmmu).

(Example 133) mp 300 ° C (decomposition). HR-BAR +: 481.0926 (+ 1.8mmu).

(Example 134) mp 280-282 ° C (decomposition) HR-BAR +: 477.1150 (-0.9mmu).

(Example 135) pf > 300 ° C (decomposition). Analysis calculated for C 2 H 6N608.3 / 2H20: C, 50.87; H, 3.69; N, 16.18. Found: C, 50.55; H, 3.49; N, 16.08. HR-BAR +: 493.1119 (+ l.lmmu).

(Example 136) 7- (3- ((4-Bromobenzyl) carbonylamino) -4-pyridon-1-yl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid A solution of the compound of Example 126 (100 mg, 250 μmol), 4-bromophenylacetic acid (53.8 mg, 250 μmol) and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (71.9 mg, 375 μmol) in Methylene chloride (3 ml) was stirred for 8 hours at room temperature. Methylene chloride (50 ml) was added to the reaction mixture, which was washed with water. After drying over anhydrous sodium sulfate, the solvent was distilled. The obtained residue was dissolved in acetic acid (3 ml), concentrated hydrochloric acid (0.6 ml) was added and the mixture was stirred for 24 hours at room temperature. The reaction mixture was poured into water (30 ml) and the precipitate was collected by filtration. These were washed with water and chloroform in sequence, and then air-dried to obtain 14.1 mg of the title compound as a yellow powder. 10% yield. mp 240-242 ° C (dec.). Analysis calculated for C22H? 4BrN5? 7 • H20: C, 47. 33; H, 2 89; N, 12 54 Found: C, 46.98; H, 3.19; N, 12.24. HR-BAR +: 540.0171 (+ 1.6mmu).

(Example 137) 7- (3- ((4-Bromophenyl) carbonylamino) -4-pyridon-1-yl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid A solution of 4-bromobenzoyl chloride (65.8 mg, 300 μmol) in methylene chloride (1 ml) at 0 ° C, and the mixture was stirred for 6 hours at room temperature. Hexane-methylene chloride (1: 1, 3 ml) was added to the 1: 9 mixture. reaction and the precipitate was collected by filtration. These were washed with hexane-methylene chloride (1: 1) and then air-dried. These were dissolved in acetic acid (3 ml), then concentrated hydrochloric acid (0.6 ml) was added and the mixture was stirred for 24 hours at room temperature. The reaction mixture was poured into water (30 ml) and the precipitate was collected by filtration. These were washed with water and chloroform in sequence, and then air-dried to obtain 79.2 mg of the title compound as a yellow powder. 56% yield. mp 230-232 ° C (decomposition). HR-BAR +: 526,0009 (tl.lmmu).

(Example 138) Morpholinamide 3, 4-dihydro-7-morpholino-6-nitro-3-oxoquinoxaline-2-carboxylic To the compound of Example 2 (195 mg, 694 μmol) was added morphol (2 ml), and the mixture was stirred for 5 hours at 150 ° C in a sealed tube. After cooling, f ' The reaction mixture was poured into water and the pH value was brought to 4 using acetic acid. The precipitate was collected by filtration, washed with water and then dried in the air to obtain 137 mg of the title compound as a dark red powder. 51% yield. mp 298-299 ° C. Analysis calculated for C? 7H? 9N5? 6: C 52. 44; H, 4 92; N, 17 99 Found: C, 52.41; H, 4.81; N, 17.72.

(Example 139) Ethyl 3-ethoxy-7-fluoro-6-nitroquinoxaline-2-carboxylate Using the compound of Example 2 (27.4 g, 97.4 mmol) and following the same procedure as in Example 9, 20.5 g of the title compound was obtained as a pale yellow powder. 68% yield. XH-NMR (DMSO-de, d): 1.36 (3H, t, J = 6.8Hz), 1.41 (3H, t, J = 7.3Hz), 4.47 (2H, c, J = 6.8Hz), 4.57 (2H , c, J = 7.3Hz), 8.33 (HH, d, J = 11.7Hz), 8.63 (HH, d, J = 7.8Hz).«ÍKÍ (Example 140) Ethyl 3-ethoxy-7- (3-fluoro-4-pyridon-1-yl) -6-nitroquinoxaline-2-carboxylate Using the compound of Example 139 (1.00 g, 3.23 mmol) and 3-fluoro-4-pyridone (1.83 g, 16.2 mmol), and following the same procedure as in Example 32, 930 mg of the title compound were obtained as a yellow amorphous material. Yield of 72%. XH-NMR (CDC13,): 1-46 (3H, t, J = 7.1Hz), 1.54 (3H, t, J = 7.1Hz), 4.56 (2H, c, J = 7.2Hz), 4.68 (2H, c, J = 7.0Hz), 6.68 (ÍH, t, J = 8.IHz), 7.36 (1H, dd, J = 7.6, 2.2Hz), 7.55 (ÍH, dd, J = 6.3, 2.4Hz), 8.22 (ÍH, s), 8.60 (ÍH, s).

(Example 141) 3,4-Dihydro-7- (3-fluoro-4-pyridon-1-yl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid Using the compound of Example 140 (120 mg, 323 μmol ) and following the same procedure as in Example 54, 100 mg of the title compound was obtained as a brown powder. 58% yield. mp 270-272 ° C (decomposition). HR-BAR +: 347.0412 (-1.6mmu).

(Example 142) 7- (3-Amino-4-pyridon-1-yl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid To the compound of Example 126 (100 mg, 250 μmol) was added 3N hydrochloric acid (5 ml), and the mixture was stirred for 1 hour at room temperature, which was then allowed to stand statically overnight. After the solvent was distilled, water was added and the precipitate was collected by filtration. These were washed with water and then air dried to obtain 74.0 mg of the title compound as a yellowish brown powder. 58% yield. pf > 300 ° C. Analysis calculated for C14H9N5O6.9H20: C, 44.55; H, 3.42; N, 18.55. Found: C, 44.17; H, 3.02; N, 18.28. HR-BAR-: 342.0484 (+ 0.9mmu).

(Example 143) 3-Ethoxy-7- (4-methylimidazolyl) -6-nitroquinoxalin-2-ethylcarboxylate Using the compound of Example 139 (500 mg, 1.62 mmol) and 4-methylimidazole (665 mg, 8.10 mmol), and following the same procedure as in Example 32, obtained 280 mg of the title compound as a yellowish brown amorphous material. 47% yield. ^ -RMN (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 1.52 (3H, t, J = 7.1Hz), 2.31 (3H, s), 4.55 (2H, c, J = 7.2Hz) ), 4.66 (2H, c, J = 7.0Hz), 6.83 (1H, s), 7.60 (IH, d, J = 1.5Hz), 8.12 (IH, s), 8.38 (IH, s) " (Example 144) Acid 3,4-dihydro-7- (4-met? L? M? Dazolyl) -6-nitro-3-oxoquxnoxalin-2-carboxyl? Co Using the compound of Example 143 (120 mg, 323 μmol) and following the same procedure as in Example 54, 70.0 mg of the title compound was obtained as a brown powder. 69% yield. mp 210-212 ° C (dec.). HR-BAR +: 316.0688 (-l.dmmu). r-JLdS- (Examples 145 to 149) Using the compound of Example 139 and following the same procedure as in Example 31, the compounds listed in the following Table 9 were obtained. Table 9 Example Ar R Example Ar (Example 145) XH-NMR (CDC13, d): 1.47 (3H, t, J = 7. 3Hz), 1.53 (3H, t, J = 7.3Hz), 2.28 (3H, s), 4.55 (2H, c , J = 7.3Hz), 4.67 (2H, c, J = 7.3Hz), 6.97 (IH, d, J = 1.5Hz), 7.01 (IH, d, J = 1.5Hz), 8.12 (IH, s), 8.42 (ÍH, s).

(Example 146) XH-NMR (CDC13, d): 1.25 (6H, d, J = 6.8Hz), 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.3Hz), 2.71 -2.79 (ÍH, m), 4.55 (2H, c, J = 7.3Hz), 4.67 (2H, c, J = 7.3Hz), 6.92 (ÍH, d, J = 1.0Hz), 7.14 (1H, d, J = 1.5Hz), 8.13 (1H, s), 8. 48 (ÍH, s). ** 8.6" (Example 147) XH-NMR (CDCl3, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.3Hz), 2.24 (6H, s), 4.23 (3H, s) , 4.56 (2H, c, J = 7.3Hz), 4.66 (2H, c, J = 7.3Hz), 6.66 (HH, s), 8.10 (HH, s), 8.44 (HH, s).

(Example 148) ^ -RMN (CDCI3, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.3Hz '), 4.55 (2H, c, J = 7.3Hz), 4.67 (2H, c, J = 7.3Hz), 7.30 (HH, m), 7.40-7.44 (3H, m), 7.76 (1H, t, J = 1.0Hz), 7.82 (HH, s), 7.84 (HH) , d, J = 1.5Hz), 8. 21 (ÍH, s), 8.45 (ÍH, s).

(Example 149) * H-NMR (CDCI3, d): 1.47 (3H, t, J = 7.3Hz), 1.55 (3H, t, J = 7.3Hz), 4.56 (2H, c, J = 7.3Hz), 4.70 (2H, c, J = 7.3Hz), 7.18 (H, t, J = 7.8Hz), 7.30-7.39 (2H, m), 7.91 (H, d, J = 7.8Hz), 8.08 (H, s) ), 8.28 (ÍH, s), 8.58 (ÍH, (Example 150) 7- (4-Ethoxycarbonylpiperidin-1-yl) methyl-3-methoxy-6-nitroquinoxaline-2-carboxylic acid ethyl ester «TS7 Using the compound of Example 10 (1.05 g, 3.61 mmol) and following the same procedure as in Example 33, 917 mg of the title compound was obtained as a yellowish-brown amorphous material. 57% yield. XH-NMR (CDC13, d): 1.25 (3H, t, J = 7.3Hz), 1.47 (3H, t, J = 7.3Hz), 1.70-1.76 (2H, m), 1.82-1.85 (2H, m) , 2.12-2.17 (2H, m), 2.24-2.30 (ÍH, m), 2.76-2.78 (2H, m), 3.87 (2H, s), 4.12 (2H, c, J = 7.3Hz), 4.17 (3H , s), 4.54 (2H, c, J = 7.3Hz), 8.20 (HH, s), 8.26 (HH, s).

(Example 151) 3,4-Dihydro-7- (2-methylimidazole?) -6-n? Tro-3-oxoquinoxal? N-2-carboXy? Co acid 'Í & B To a solution of the compound of Example 145 (218 mg, 587 μmol) in acetic acid (10 ml) was added concentrated hydrochloric acid (700 μl), and the mixture was stirred for 23 hours at room temperature. After distilling off the solvent, water was added and the precipitate was collected by filtration, followed by air drying, to obtain 97.4 mg of the title compound as a brown powder. Yield of 53%. mp 268-271 ° C (decomposition). HR-BAR-: 314.0514 (-1.2mmu).

(Examples 152 to 154) Through the same procedure as in Example 151, the compounds listed in the following Table 10 were obtained. Table 10 Example Ar (Example 152) mp 243-245 ° C (decomposition).

HR-BAR-: 342.0837 (-O.lmmu).

(Example 153) mp 229-231 ° C (decomposition). Analysis calculated for C 16 H 9 N 9 O 5 HCl: C, 49.56; H, 2.60; N, 18.06. Found: c, 49.68; H, 2.77; N, 18.16. HR-BAR-: 350.0545 (+ 1.9mmu).

(Example 154) mp 254-256 ° C (decomposition). Analysis calculated for C? EH? EN407. HCl. L / 10H2O: C, 46.35; H, 4.18; N, 13.51. Found: C, 46.36; H, 4.21; N, 13.72. HR-BAR-: 375.0954 (+ 1.4mmu).

(Example 155) 3-Ethoxy-7- (4-methoxybenzyl) amino-6-nitroquin-oxalin-2-ethylcarboxylate To a solution of the compound of Example 139 (2.00 g, 6.47 mmol) in tetrahydrofuran (15 ml) were added 4-methoxybenzylamine (1.06 g, 7.76 mmol) and successively triethylamine (785 mg, 7.76 mmol), and the mixture was subjected to reflux for 24 hours. After cooling, ethyl acetate was added and the solution was washed with brine. After the organic layer was dried over anhydrous magnesium sulfate, the residue obtained by distilling off the solvent was purified by means of silica gel column chromatography [methylene chloride methylene chloride-methanol (50: 1)] to obtain 2.09 g of the title compound as a purple powder. Performance of 76%. XH-NMR (DMSO-de, d): 1.32 (3H, t, J = 7.3Hz), 1.37 (3H, t, J = 7.3Hz), 3.72 (3H, s), 4.41 (2H, c, J = 7.3Hz), 4.47 (2H, c, J = 7.3Hz), 4.58 (2H, d, J = 6. 3Hz), 6.91 (2H, d, J = 8.8Hz), 7.22 (HI, s), 7.37 ( 2H, d, J = 8.8Hz), 8.08 (HH, t, J = 6.3Hz), 8.49 (HH, s).

(Example 156) ethyl l-Amino-3-ethoxy-6-nitroquinoxaline-2-carboxylate To a solution of the compound of Example 155 (2.09 g, 4.90 mmol) in anisole (5 ml) was added trifluoroacetic acid (5 ml), and the mixture was stirred for 6 hours at room temperature. The residue obtained by concentrating the reaction mixture was purified by means of column chromatography on silica gel [methylene chloride] to obtain 1.20 g of the title compound as purple powder. 80% yield. * H-NMR (DMSO-de, d): 1.35 (3H, t, J = 6.8Hz), 1.37 (3H, t, J = 7.3Hz), 4.43 (2H, c, J = 7.3Hz), 4.47 ( 2H, c, J = 6.8Hz), 7.12 (2H, s), 7.49 (H, s), 8.41 (1H, s).

(Example 157) 7-Amino-3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 156 '200 mg, 653 μmol) in ethanol (10 ml) were added 92 * ' aqueous sodium hydroxide solution IN (1.96 ml, 1.96 mmol) and water (2 ml), and the mixture was refluxed for 30 minutes. After cooling, the pH value was brought to 4 using 10% hydrochloric acid and brine was added, which was extracted with chloroform. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled to obtain 159 mg of a reddish brown powder. This was dissolved in ethanol (10 ml), then concentrated hydrochloric acid (2 ml) was added and the mixture was stirred for 24 hours at room temperature. The solvent was distilled off, the residue was washed with water and diisopropyl ether in sequence and then air dried to obtain 156 mg of the title compound as a brown powder. 95% yield. mp 300 ° C. HR-MS: 250.0311 (-2.7mmu).RRO (Example 158) 3, 4-Dihydro-6-nitro-3-oxo-7- (py-1-yl) quinoxaline-2-carboxylic acid S * - »» To a solution of the compound of Example 157 (50.0 mg, 200 μmol) in acetic acid (5 ml) was added 2,5-dimethoxytetrahydrofuran (31.7 mg, 240 μmol), and the mixture was stirred for 4 hours at 80 ° C. The reaction mixture was concentrated and then the residue was washed with water and diisopropyl ether in sequence to obtain 28.0 mg of the title compound as a brown powder. 47% yield. pf > 300 ° C. HR-MS: 300.0502 (+ 0.7mmu).

(Example 159) Ethyl 3-methoxy-7- (morpholin-1-yl) methyl-6-nitroquinoxaline-2-carboxylate Using the compound of Example 10 (792 mg, .72 mmol) and following the same procedure as in Example 33, 488 mg of the title compound was obtained as a brown oil. 48% yield. ^ -RMN (CDC13, d): 1.47 (3H, t, J = 6.9Hz), 2.44-2.47 (2H, m), 3.64-3.66 (2H, m), 3.90 (2H, s), 4.17 (3H, s), 4.54 (2H, c, J = 6.9Hz), 8.19 (HH, s), 8.27 (HH, s).

(Example 160) 3,4-Dihydro-7- (morpholin-1-yl) methyl-6-nitro-3-oxoquinoxaline-2-carboxylic acid hydrochloride Using the compound of Example 159 (487 mg, 1.29 mmol) and following the same procedure as in Example 151, 125 mg of the title compound was obtained as a brown powder. Yield of 26%. mp 209-211 ° C (decomposition). Analysis calculated for C? 4Hi4N406. HCl: C, 45.36; H, 4.08; N, 15.11. Found: C, 45.31; H, 4.35; N, 15.15. HR-BAR +: 335. 1004 (+ 1. 2mmu).

(Example 161) 3, 4-Dihydro-7-f luoro-4-methyl-6-nitro-3-oxoquinoxalin-2-ethylcarboxylate To a solution of the compound of Example 2 (345 mg, 1.23 mmol) in N, N-dimethylformamide (10 ml) was added a 50% dispersion of sodium hydride in oil (61.3 mg, 1.54 mmol), and the mixture was mixed. stirred for 30 minutes at room temperature. Then, after adding methyl iodide (95.5 ml, 1.54 mmol), the mixture was stirred for an additional 2 hours. The reaction mixture was poured into ice water, which was extracted with ethyl acetate. After drying the organic layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography on silica gel [hexane-ethyl acetate = 5: 2] to obtain 272 mg of the title compound as a pale yellow powder. 75% yield. ^ -R N (CDCI3, d): 1.45 (3H, t, J = 7.3Hz), 3.77 (3H, s), 4.53 (2H, c, J = 7.3Hz), 7.87 (IH, d, J = 10.3Hz), 8.04 (1H, d, J = 6.3Hz). lß ^ (Example 162) 3,4-Dihydro-5-fluoro-4-methyl-6-nitro-3-oxoquinoxaline-2-carboxylic acid Using the compound of Example 161 (207 mg, 701 μmol) and following the same procedure as in Example 62, 78.4 mg of the title compound was obtained as a greenish brown powder. 41% yield. mp 173-175 ° C. Analysis calculated for C? OH6FN305. 1 / 5H20: C, 44. 36; H, 2 38; N, 15 52 Found: C, 44.33; H, 2.25; N, 15.79. HR-BAR +: 268.0366 (-0.4mmu).

(Example 163) 3, 4-Dihydro-6-nitro-3-oxo-7-fluoromethyl-quinoxaline-2-carboxylic acid '191 To a solution of ethyl 3-hydroxy-6-nitro-3-oxo-7-trifluoromethyl-2-carboxylate (120 mg, 362 μmol) in ethanol (5 ml) was added aqueous sodium hydroxide solution. potassium IN (724 μl, 724 μmol), and the mixture was refluxed for 1 hour. After cooling, water was added and the pH value 3e led to 2 with concentrated hydrochloric acid. The precipitate was collected by filtration, washed with water and then air dried to obtain 102 mg of the title compound as a colorless powder. 88% yield. mp 213-215 ° C (decomposition). Analysis calculated for C? OH4F3N3Os. H20: C, 37.40; H, 1.88; N, 13.08. Found: C, 37.71; H, 1.94; N, 13.01. HR-MS: 303.0113 (+ 1.0mmu).

(Example 164) 7-Amino-3,4-dihydro-3-oxo-6-trifluoro-methylquinoxaline-2-carboxylic acid * lí To a solution of ethyl 7-amino-3, 4-d? Hydro-3-oxo-6-trifluoromethyl-2-carboxylate (55.9 mg, 186 μmol) in ethanol (2 ml) was added aqueous sodium hydroxide solution IN (446 μl, 446 μmol), and the mixture was refluxed for 1.5 hours. After cooling, the solvent was distilled, water was added and the pH value was brought to 2 with 4N hydrochloric acid. The solvent was distilled again and a small amount of water was added. The crystals were collected by filtration, washed with water and then air dried to obtain 24.2 mg of the title compound as a dark red powder. 45% yield. mp 218-220 ° C (decomposition). Analysis calculated for C? OH6F3N303. H0: C, 41.24; H, 2.77; N, 14.43. Found: C, 40.96; H, 2.70; N, 14.26. HR-EM: 273.0337 (-2.4mmu).

(Example 165) 3, 4-Dihydro-3-oxo-7- (pyrrol-1-yl) -6-trifluoromethyl-2-carboxylic acid To a solution of ethyl 3, 4-dihydro-3-oxo-7- (pyrrol-1-yl) -6-trifluoromethyl-2-carboxylate (67.0 mg, 191 μmol) in ethanol (2 ml) was added 1N aqueous sodium hydroxide solution (382 μl, 382 μmol), and the mixture was refluxed for 1 hour. After cooling, the residue obtained by distilling the solvent was dissolved in water and the pH value was brought to 2 with 4N hydrochloric acid. This was extracted with ethyl acetate and, after drying over anhydrous sodium sulfate, the solvent was distilled. A small amount of water was added to the residue obtained. The crystals were collected by filtration, washed with water and then air dried to obtain 52.9 mg of the title compound as a yellowish brown powder. 86% yield. mp 136-138 ° C (dec.). HR-BAR-: 322.0424 (-1.6mmu). e (Example 166) 3,4-Dihydro-7-imidazolyl-3-oxo-6-trifluoro-methylquinoxaline-2-carboxylate. of ethyl To a solution of 5-imidazolyl-4-trifluoromethyl-1,2-phenylenediamine (303 mg, 1.25 mmol) in ethanol (50 ml) was added diethyl ketomalonate (210 μl, 1.38 mmol) at room temperature, and the mixture was stirred at room temperature. refluxed for 6 hours. The reaction mixture was concentrated to half the volume under reduced pressure, then the precipitate was collected by filtration and washed with cold ethanol. The filtrate was distilled under reduced pressure, a small amount of the mixed solution of ethyl acetate-diisopropyl ether was added to the obtained residue and the precipitate was collected by filtration to obtain 148 mg of the title compound as a light yellowish brown powder. 34% yield. XH-NMR (DMSO-de, d): 1.34 (3H, t, J = 7.4Hz), 4.41 (2H, c, J = 7.4Hz), 7.14 (1H. S), 7.33 (H, s), 7.49 (ÍH, s), 7.93 (2H, s), 8.39 (ÍH, s), 13.30 (ÍH, s broad).

(Example 167) 3, 4-Dihydro-3-oxo-7- (4-pyridon-1-yl) -6-trifluoromethyl-2-carboxylic acid ethyl trifluoromethyl-2-carboxylate To a solution of 4- (4-pyridon-1-yl) -5-trifluoromethyl-2-nitroaniline (210 mg, 701 μmol) in ethanol (10 ml) was added 10% palladium on carbon (40.0 mg) at room temperature. environment, and the catalytic hydrogenation was conducted for 2 hours at room temperature under ambient pressure. The catalyst was filtered using celite and the filtrate was distilled under reduced pressure. After dissolving it in ethanol (3 ml), diethyl ketomalonate (214 μl, 1.40 mmol) was added and the mixture was refluxed for 5 hours. The residue obtained by concentrating the reaction mixture was purified by means of silica gel column chromatography. [methylene chloride-ethanol (50: 16: 1)] to obtain 158 mg of the title compound as a pale yellow powder. Performance of 59%. '~ 02 XH-NMR (DMSO-de, d): 1.33 (3H, t, J = 7.3Hz), 4.41 (2H, c, J = 7.3Hz), 6.19 (2H, d, J = 7.3Hz), 7.72 (2H , d, J = 7.3Hz), 8.33 (ÍH, s), 13.32 (ÍH, s broad).

(Example 168) 3,4-Dihydro-7-imidazolyl-3-oxo-6-trifluoromethyl-quinoxalin-2-carboxylic acid To a solution of the compound of Example 166 (141 mg, 400 μmol) in acetic acid (5 ml) was added 6N hydrochloric acid at room temperature, and the mixture was stirred for 3.5 hours at 80 ° C. Ethyl acetate was added to the residue obtained by distilling the solvent under reduced pressure. This was washed with brine, dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. A small amount of water was added to the obtained residue, which was stirred for 30 minutes under cooling with ice. The precipitate was collected by filtration and further recrystallized from water to obtain 48.7 mg of the title compound as a light reddish brown powder. Performance of 38%.

ZSw mp 232-234 ° C (dec.). Analysis calculated for C? 3H7F3N4? 3. 2H20: C, 43. 3. 4; H, 3. 08; N, 15 55 Found: C, 43.20; H, 2.70; N, 15.45. HR-BAR-: 323.0396 (+ 0.4mmu).

(Example 169) 3,4-Dihydro-3-oxo-7- (4-pyridon-1-yl) -6-trifluoromethyl-3-oxo-2-carboxylic acid To a solution of the compound of Example 167 (100 mg, 264 μmol) in ethanol (3 ml) was added lithium hydroxide solution IN (659 μl, 659 μmol), and the mixture was stirred for 1.5 hours at 50 ° C. After cooling, the insoluble fractions were filtered and the pH value was brought to 4 with 3N hydrochloric acid. The precipitate was collected by filtration, washed with water and then dried in air to obtain 83.0 mg of the title compound as a colorless powder. 90% yield. mp 300 ° C. 04 Analysis calculated for C? 4H8F3N304: C, 51.29; H, 2.30; N, 11.96. Found: C, 51.27; H, 2.46; N, 11.62.

(Example 170) 6- (Aminosulfonyl) -7-chloro-3,4-dihydro-3-oxoquinoxalin-2-ethylcarboxylate To a solution of 4-amino-2-chloro-5-nitrobenzenesulfonamide (2.00 g, 7.95 mol) in methanol (40 ml) were added 10% palladium on carbon (400 mg) and successively 10% hydrochloric acid ( 6 ml) at room temperature, and the catalytic hydrogenation was conducted for 2 hours at room temperature under ambient pressure. The catalyst was filtered using celite and the filtrate was distilled under reduced pressure.

After dissolving in ethanol (16 ml), diethyl ketomalonate (1.21 ml, 7.95 mmol) was added, which was stirred for 5 hours at room temperature. The precipitate was collected by filtration, washed with ethanol and then purified by column chromatography on silica gel [hexane-ethyl acetate = 1: 2] to obtain 288 mg of the title compound. Yield of 11%. XH-NMR (DMSO-d6, d): 1.32 (3H, t, J = 6.9Hz), 3.33 (3H, s), 4.39 (2H, c, J = 7.4Hz), 7.87 (HI, s), 8.01 (lHis), 8.12 (ÍH, s).

(Example 171) 6- (Aminosulfonyl) -7-chloro-3,4-dihydro-3-oxoquinoxalin-2-carboxylic acid To a suspension of the compound of Example 170 (200 mg, 603 μmol) in ethanol (6 ml) was added aqueous sodium hydroxide solution IN (1.21 ml, 1.21 mol), and the mixture was refluxed for 3 hours. Water was added to the reaction mixture, the pH value was brought to 4 with acetic acid and the solvent was distilled. The obtained residue was purified by Sepabeads ® SP850 synthetic adsorbent [water-acetonitrile water (20: 1 4: 1)] to obtain 58.5 mg of the title compound as a yellow powder. Performance of 32%. mp 213-214 ° C (decomposition).

Analysis calculated for C9H6CI O3S .4 / 5H20: C, 33.98; H, 2.41; N, 13.21. Found: C, 34.15; H, 2.72; N, 12.96. HR-BAR-: 303.9837 (+ 4.2mmu).

(Example 172) Ethyl 3-ethoxy-7-fluoro-6-methanesulfonylquinoxaline-2-carboxylate To a solution of ethyl 3-ethoxy-7-fluoro-6-methylthioquinoxaline-2-carboxylate (450 mg, 1.45 mmol) in chloroform (15 ml) was added 3-chloroperbenzoic acid (715 mg, 2.90 mmol) at room temperature , and the mixture was stirred for 3 hours at room temperature. Calcium hydroxide was added to the reaction liquor and the mixture was stirred for 10 minutes. Next, the insoluble fractions were filtered using celite and the filtrate was distilled under reduced pressure. The obtained residue was purified by means of column chromatography on silica gel [methylene chloride] to obtain 496 mg of compound | 07 of the title as colorless solids. Quantitative performance. ^ -RMN (CDCI3, d): 1.47 (3H, t, J = 6.9Hz), 1.50 (3H, t, J = 6.9Hz), 3.33 (3H, s), 4.54 (2H, c, J = 6.9Hz) ), 4.61 (2H, c, J = 6.9Hz), 7.89 (HH, d, J = 10.3Hz), 8.52 (HH, d, J = 6.9Hz).

(Example 173) 3-Ethoxy-7-fluoro-6-methanesulfonyl-quinoxaline-2-carboxylic acid To a solution of the compound of Example 172 (262 mg, 765 μmol) in ethanol (8 ml) was added IN aqueous sodium hydroxide solution (1.53 ml, 1.53 mmol), and the mixture was refluxed for 1.5 hours. Water was added to the reaction mixture and the pH value was brought to 3 with concentrated hydrochloric acid, which was extracted with ethyl acetate. After drying the organic layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain 199 mg of the title compound as a yellowish brown powder. 83% yield. '-Í * Í 8 aH-NMR (CDCI3, d): 1.56 (3H, t, J = 6.9Hz), 3.35 (3H, s), 4.70 (2H, c, J = 6.9Hz), 7.93 (ΔH, d, J = 9.3Hz ), 8.58 (ÍH, d, J = 6.8Hz).

(Example 174) 3,4-Dihydro-7-fluoro-6-methanesulfonyl-3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 173 (149 mg, 474 μmol) in acetic acid (3 ml) was added concentrated hydrochloric acid (1.5 ml) at room temperature, and the mixture was stirred for 24 hours at room temperature. The reaction mixture was distilled under reduced pressure. The obtained residue was purified with Sepabeads SP850 synthetic adsorbent [water water-acetonitrile (20: 14: 1)] to obtain 37.2 mg of the title compound as a yellow powder. Yield of 27%. mp 190-192 ° C. Analysis calculated for C? 0H7FN2O5S. H20: C, 39. 48; H, 2.98; N, 9.21. Found: C, 39.60; H, 2.62; N, 9.01. 3- * > HR-BAR-: 286.0089 (+2.9 mmu).

(Example 175) 7-Bromo-3,4-dihydro-3-oxo-6-trifluoro-methylquinoxaline-2-carboxylic acid To a solution of ethyl 7-bromo-3, 4-dihydro-3-oxo-6-trifluoromethyl-2-carboxylate (120 mg, 329 μmol) in ethanol (4 ml) was added aqueous sodium hydroxide solution. (1.32 ml, 1.32 mmol) and water (2 ml), and the mixture was refluxed for 30 minutes. After cooling with ice, the pH value was brought to 4 with 1.2N hydrochloric acid. The precipitate was collected by filtration, washed with water and then dried in air to obtain 91.0 mg of the title compound as a yellowish brown powder. Performance of 82%. mp 210-212 ° C (dec.). HR-MS: 335. 9358 (+0.1 mmu). 1 * 0 * (Example 176) Ethyl 3, 4-dihydro-7- (3-formylpyrrol-1-yl) -3-oxo-6-trifluoromethyl-2-carboxylate ethyl To a solution of the compound of Example 73 (2.00 g, 5.25 mmol) in 1,4-dioxane (100 ml) was added 2,3-d-chloro-5,6-dicanoquinone (1.25 g, 5.50 mol), and the mixture was stirred for 3 hours at room temperature. The precipitate was filtered and the residue obtained by distilling the solvent was purified by column chromatography on silica gel [ethyl acetate-hexane = 2: 1] to obtain 1.88 g of the title compound as a yellow amorphous material. 94% yield. XH-NMR (DMSO-de, d): 1.33 (3H, t, J = 7.3Hz), 4.41 (2H, c, J = 7.3Hz), 6.66 (ÍH, dd, J = 3.4, 1.5Hz), 7.13 (ÍH, s), 7.79 (ÍH, s), 7.88 (ÍH, s), 8.15 (ÍH, s), 9.79 (ÍH, s), 13.28 (ÍH, s).

(Example 177) 3,4-Dihydro-7- (3-formylpyrrol-1-yl) -3-oxo-6-trifluoromethyl-2-carboxylic acid To a solution of the compound of Example 176 (142 mg, 375 μmol) in ethanol (7.5 ml) was added aqueous solution of potassium hydroxide IN (825 μl, 825 μmol), and the mixture was refluxed for 1 hour. After cooling, the solvent was distilled off, the residue was dissolved in a small amount of water and then the pH value was brought to 2 using 4N hydrochloric acid.

The precipitate was collected by filtration, washed with water and then air dried to obtain 83.2 mg of the title compound as a yellowish brown powder. Performance of 61%. mp 158-160 ° C (decomposition). Analysis calculated for C23H16F3N5O6.2 / 3H20: C, 49.59; H, 2.59; N, 11.57. Found: C, 49.43; H, 2.73; N, 11.34. HR-BAR +: 352.0536 (-0'.9mmu).

(Example 178) 3, 4-Dihydro-7- (3- (((2-fluorophenyl) -aminocarbonylamino) methyl) pyrrol-1-yl) -3-oxo-6-trifluoromethyl-quinoxalin-2-cetboxylate ethyl To a solution of the compound of Example 74 (180 mg, 430 μmol) in N, N-dimethylformamide (4.3 ml) were added triethylamine (89.9 μl, 645 μmol) and 2-fluorophenyl isocyanate (57.9 μl, 516 μmol) at room temperature. The mixture was stirred for 4 hours at the same temperature. The reaction mixture was poured into water (50 ml), which was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled. Methylene chloride was added to the obtained residue. The precipitate was collected by filtration, washed with methylene chloride and then air dried to obtain 111 mg of a mixture of the title compound and the compound thereof tetrahydrate? (about 3: 2) as yellow powder. After dissolving these in 1,4-dioxane (4 ml), 2,3-dichloro-5,6-dicyanoquinone (23.6 mg, 104 μmol: the level used varied depending on the formation ratio) was added and the mixture was mixed. refluxed for 1 hour. After cooling, the precipitate was filtered and the solvent was distilled. Methylene chloride was added to the obtained residue. The precipitate was collected by filtration, washed with methylene chloride and then air dried to obtain 75.5 mg of the title compound as a yellowish brown powder. 34% yield. XH-NMR (DMSC-d6, d): 1.32 (3H, t, J = 6.9Hz), 4.19 (2H, d, J = 5.4Hz), 4.40 (2H, c, J = 6.9Hz), 6.24 (1H , t, J = 2.0Hz), 6.83 (ÍH, d, J = 5.4Hz), 6.89-6.94 (ÍH, m), 6.920 (ÍH, s), 6.924 (ÍH, s), 7.08 (ÍH, t, J = 7.8Hz), 7.14-7.19 (HH, m), 7.75 (HH, s), 7.92 (HH, s), 8.14-8.19 (HH, m), 8.33 (HH, d, J = 2.4Hz), 13.22 (ÍH, s).

(Example 179) 3,4-dihydro-7- (3- (((3-fluorophenyl) aminocarbonylamino) methyl) pyrrol-1-yl) -3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid ethyl ester Using the compound of Example 74 (180 mg, 430 μmol) and 3-fluorophenyl isocyanate (58.9 μl, 516 μmol), and following the same procedure as in Example 178, 95.9 mg of the title compound was obtained as a brown powder yellowish. Performance of 43%. ^ -RN (DMSO-de, d): 1.32 (3H, t, J = 6.8Hz), 4.18 (2H, d, J = 5.4Hz), 4.40 (2H, c, J = 6.8Hz), 6.24 (HI) , t, J = 2.0Hz), 6.41 (HH, d, J = 5.4Hz), 6.69 (HH, td, J = 8.3, 2.5Hz), 6.910 (HH, s), 6.914 (HH, s), 7.00 -7.02 (HH, m), 7.23 (HH, dd, J-15.2, 8.3Hz), 7.47 (HH, dt, J = 12.7, 2.5Hz), 7.75 (HH, s), 7.91 (HH, s), 8.72 (ÍH, s), 13.22 (ÍH, s).

(Example 180) 3-Dihydro-7- (3- (((4-fluorophenyl) aminocarbonyl amino) methyl) pyrrol-1-yl) -3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid ethyl ester ¬ Using the compound of Example 74 (180 mg, 430 μmol) and 4-fluorophenyl isocyanate (58.7 μl, 516 μmol) and following the same procedure as in Example 178, 132 mg of the title compound was obtained as a yellowish brown powder . Performance of 59%. 1 H-NMR (DMSO-de, d): 1.32 (3H, t, J = 6.8Hz), 4.17 (2H, d, J = 5.4Hz), 4.40 (2H, c, J = 6.8Hz), 6.24 (H) , t, J = 2.0Hz), 6.30 (HH, d, J = 5.4Hz), 6.90 (HH, s), 6.91 (HH, s), 7.03-7.08 (2H, m), 17.38-7.41 (2H, m), 7.75 (ÍH, s), 7.91 (ÍH, s), 8.49 (ÍH, s), 13.22 (ÍH, 5).

(Example 181) 3, 4-Dihydro-7- (3- (((2-fluorophenyl) aminocarbonylamino) methyl) pyrrol-1-yl) 3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid To a solution of the compound of Example 178 (74.0 mg, 143 μmol) in ethanol (3 ml) was added aqueous solution of potassium hydroxide IN (715 μl, 715 μmol), and the mixture was refluxed for 1 hour. After cooling, the solvent was distilled, and the residue was dissolved in a small amount of water, then the pH value was brought to 2 using 4N hydrochloric acid. The precipitate was collected by filtration, washed with water and then air dried to obtain 37.1 mg of the title compound as a yellowish brown powder, Yield 53%. mp 177-179 ° C. HR-BAR-: 488.0985 (-0.9 mmu).

(Example 182) 3, 4-Dihydro-7- (3- (((3-fluorophenyl) aminocarbonylamino) methyl) pyrrol-1-yl) 3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid Using the compound of Example 179 (131 mg, 253 μmol) and following the same procedure as in Example 181, 73.6 mg of the title compound was obtained as a yellowish brown powder. Yield of 83-d. mp 169-171 ° C. HR-BAR-: 488.0991 (+0.9 mmu).

(Example 183) 3,4-Dihydro-7- (3- (((4-fluorophenyl) aminocarbonylamino) methyl) pyrrol-1-yl) 3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid "" ii Using the compound of Example 180 (94.4 mg, 182 μmol) and following the same procedure as in Example 181, 90.3 mg of the title compound was obtained as a yellowish brown powder. Performance of 73%. mp 168-1"0 ° C HR-BAR-: 488.0985 (+ 0.3mmu).

(Example 184) 7- (3- (((4-Bromophenyl) aminocarbonylamino) -methyl) pyrrol-1-yl) -3,4-dihydro-3-oxo-6-tr? Fluoromethyl-quinoxalin-2- ethyl carboxylate 2 To a solution of the compound of Example 74 (200 mg, 478 μmol) in N, N-dimethylformamide (5 ml) were added 4-bromophenyl isocyanate (113 mg, 573 μmol) and triethylamine (99.9 μl, 717 μmol), and the mixture was stirred for 1 hour at 60 ° C. Triethylamine (666 μl, 4. 78 μmol) to the reaction mixture after stirring for an additional 4 hours, the solvent was distilled. Water was added to the obtained residue, which was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled. The residue obtained was purified by column chromatography on silica gel [methylene chloride-ethanol = 20: 1] to obtain 154 mg of the title compound as a yellow powder. 56% yield. XH-NMR (DMSO-de, d): 1.32 (3H, t, J = 7.3Hz), 4.17 (2H, d, J = 5.4Hz), 4.40 (2H, c, J = 7.3Hz), 6.24 (HI) , t, J = 2.0Hz), 6.37 (HH, d, J = 5.4Hz), 6.90 (HH, s), 6.91 (HH, s), 7.38 (4H, s), 7.75 (HH, s), 7.90 (ÍH, s), 8.62 (ÍH, s), 13.00-13.40 (ÍH, broad).

(Example 185) 7- (3- (((4-Bromophenyl) aminocarbonylamino) -methyl) pyrrol-1-yl) -3,4-dihydro-3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid To a solution of the compound of Example 184 (152 mg, 263 μmol) in ethanol (5 ml) was added 1N aqueous sodium hydroxide solution (789 μl, 789 μmol), and the mixture was refluxed for 1 hour. After distilling the solvent, water was added and the pH value was brought to 2 using 4N hydrochloric acid. The precipitate was collected by filtration, washed with water and chloroform in sequence and then air dried to obtain 133 mg of the title compound as a brownish-brown powder. 88% yield. mp 196-198 ° C (decomposition). Analysis calculated for C22H? 5BrF3N5? 4. / 3H20: C, 46.01; H, 3.10; N, 12.19. Found: C, 45.84; H, 2.82; N, 12.02. HR-BAR-: 548.0144 (-3.7mmu).

(Example 186) 3, 4-Dihydro-7- (3- (((3-ethoxycarbonylphenyl) aminocarbonylamino) methyl) pyrrol-1-yl) -3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid ethyl ester To a solution of the compound of Example 74 (200 mg, 478 μmol) in N, N-dimethylformamide (5 ml) were added ethyl 3-isocyanatobenzoate (94.9 μl, 573 μmol) and triethylamine (99.9 μl, 717 μmol), and the mixture was stirred for 3 hours at room temperature. Water was added to the reaction mixture, which was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was destined. Methylene chloride was added to the obtained residue, the crystals were collected by filtration and washed with methylene chloride, and then air-dried. These were dissolved in N, N-dimethylformamide (5 ml), triethylamine (666 μl, 4.78 μmol) was added and the mixture was stirred for 4 hours at 80 ° C. The residue obtained by distilling the solvent was purified by column chromatography on * 4 * silica gel [methylene chloride-ethanol = 20: 1] to obtain 63.0 mg of the title compound as a pale yellow powder. Performance of 23%. XH-NMR (DMSO-d6, d): 1.31 (3H, t, J = 6.9Hz), 1.32 (3H, t, J = 7.3Hz), 4.19 (2H, d, J = 5.4Hz), 4.30 (2H) , c, J = 6.9Hz), 4.40 (2h, c, J = 7.3Hz), 6.24 (HH, t, J = 2.0Hz), 6.36 (HH, d, J = 5.4Hz), 6.91 (2H, d , J = 2.0Hz), 7.36 (HH, t, J = 7.8Hz), 7.49 (HH, d (J = 7.8Hz), 7.61 (HH, dd, J = 8.31, 1.OHz), 7.75 (HH, s), 7.91 (ÍH, s) 18.09 (ÍH, t, J = 2.0Hz), 8.75 (ÍH, s), 3.22 (ÍH, s). HR-BAR-: 570.1626 (+2.6 mmu).

(Example 187) 7- (3- (((3-carboxyphenyl) aminocarbonylamino) methyl) pyrrol-1-yl) -3,4-dihydro-3-oxo-6-trifluoro-methyl-quinoxaline-2-carboxylic acid To a solution of the compound of Example 186 (60.0 mg, 105 μmol) in ethanol (2 ml) was added 1N aqueous sodium hydroxide solution (525 μl, 525 μmol), and the mixture was refluxed for 1 hour. After distilling the solvent, water was added and the pH value was brought to 3 using 4N hydrochloric acid. The precipitate was collected by filtration, washed with water and then air dried to obtain 50.7 mg of the title compound as a yellow powder. 88% yield. mp 300 ° C. Analysis calculated for C23H16F3N5O6. 2H20: C, 50. 10; H, 3. 66; N, 12 70 Found: C, 50.21; H, 3.67; N, 12.71. HR-BAR-: 514.1017 (+4.3, mmu).

(Example 188) 3,4-Dihydro-7- (3- ((3-phenylaminocarbonyl-amino) methyl) pyrrol-1-yl) -6-trifluoromethyl-2-carboxylic acid To a solution of the compound of Example 74 (200 mg, 478 μmol) in N, N-dimethylformamide (5 ml) were added phenyl isocyanate (62.3 μl, 573 μmol) and triethylamine (99.9 μl, 717 μmol), and the mixture was stirred for 1 hour at 60 °. C. Triethylamine (666 μl, 4. 78 μmol) was added to the reaction mixture and the mixture was stirred for an additional 4 hours, then the solvent was distilled off. Water was added to the obtained residue, which was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled. The residue obtained was purified by means of column chromatography on silica gel [methylene chloride-ethane] = 20: 1]. After dissolving it in ethanol (5 ml), aqueous sodium hydroxide solution (1.43 ml, 1.43 μmol) was added and the mixture was refluxed for 1 hour. After distilling the solvent, water was added and the pH value was brought to 2 using 4N hydrochloric acid. The precipitate was collected by filtration, washed with water and chloroform in sequence and then air dried to obtain 108 mg of the title compound as a yellow powder. 47% yield. pf > 300 ° C. i 35 Analysis calculated for c22Hi6F3N504.1 / 2H20: C, 55.00; H, 3.57; N, 14.58. Found: C, 54.95; H, 3.69; N, 14.32. HR-BAR-: 470.1058 (-1.8 mmu).

(Examples 189 to 205) Through the same procedure as in Example 188, the compounds listed in the following Table 11 were obtained.

Table 11 Ejeirplo X Ejenplo X Ejapplo % ^ Example X Example X Arpian Ej (Example 189) mp 165-167 ° C. HR-BAR-: 548.0154 (~ 2.7mmu: (Example 190) mp 207-209 ° C. HR-BAR-: 548.0226 (+ 4.5mmu).

(Example 191) mp 198-200 ° C. Analysis calculated for C22H? 5ClF3N504.4 / 3H20: C, 9.87; H, 3.36; N, 13.22.

Found: C, 49.94; H, 3.12; N, 13.01. HR-BAR-: 504.0683 (-0.3mmu).

(Example 192) pf > 300 ° C. Analysis calculated for C23Hi5F6N504.6 / 5H20: C, 49.24; H, 3.10; N, 12.48. Found: C, 49.18; H, 3.09; N, 12.38. HR-BAR-: 538.0934 [-1.6mmu).

(Example 193) mp 194-196 ° C. HR-BAR-: 538.0938 (-1.2mmu).

(Example 194) mp 183-185 ° C. Analysis calculated for C23H? 8F3 5? 4. H20: C, 54.87; H, 4.00; N, 13.91. ,. Found: C, 54.88; H, 3.92; N, 13.79. HR-BAR-: 484.1262 (+ 2.9mmu).

(Example 195) mp 198-200 ° C. Analysis calculated for c23H? 8F3N505.3 / 2H20: C, 52.28; H, 4.01; N, 13.25.

Found: C, 51.97; H, 3.66; N, 13.07 HR-BAR-: 500.1165 (-l.ßrnmu).

(Example 196) mp 235-237 ° C. Analysis calculated for C22H22F3Ns0.3 / 2H20: C, 55.55; H, 4.66; N, 12.96. Found: C, 55.64; H, 4.33; N, 12.69. HR-BAR-: 512.1569 (+ 2.4mmu).

(Example 197) pf > 300 ° C. Analysis calculated for C24H? 8F3N5? 6.5 / 3H20: C, 51.52; H, 3.84; N, 12.52. Found: C, 51.78; H, 3.74; N, 12.13. HR-BAR-: 528.1124 (-0.7mmu).

(Example 198) mp 277-279 ° C (decomposition). HR-BAR-: 528.1143 (+ 1.2mmu).

(Example 199) mp 189-191 ° C. HR-BAR-: 515.0917 (-l.Ommu) (Example 200) mp 195-197 ° C. HR-BAR-: 538.0300 (+ 0.4mmu) (Example 201) mp 223-225 ° C. Analysis calculated for C26Hi8F3N5? 4.5 / 4H20: C, 57.41; H, 3.80; N, 12.87. Found: C, 57.64; H, 3.69; N, 12.49. HR-BAR-: 520.1235 (+ 0.2mmu).

(Example 202) mp 162-164 ° C. HR-BAR-: 484.1227 (-0.6mmu) (Example 203) mp 218-220 ° C.

HR-BAR-: 476.1571 (+2.5 mmu) (Example 204) pf > 300 ° C. HR-BAR-: 450.1408 (+1.9 mmu) (Example 205) mp 198-200 ° C. HR-BAR-: 486.0858 (+1.1 mmu) (Example 206) 3, 4-Dihydro-7- (4- (((4-ethoxycarbonylphenyl) aminocarbonylamino) methyl) imidazol-1-yl) -3-oxo-6-trifluoromethyl-2-carboxylic acid ethyl trifluoromethyl-2-carboxylate To a solution of 3- (4- (((4-ethoxycarbonyl-phenyl) -aminocarbonylamino) methyl) imidazol-1-yl) -4-tri-fluoromethyl-1,2-phenylenediamine (500 mg, 1.08 mmol) in ethanol (30 ml) was added diethyl ketomonate (260 μl, 1.70 mmol), and the mixture was refluxed for 3 hours. Then, diethyl ketomalonate (130 μl, 852 μmol) was added further and the mixture was refluxed for an additional 2 hours. The residue obtained by concentrating the reaction mixture under reduced pressure was purified by means of column chromatography on silica gel [methylene chloride-methanol = 30: 1] to obtain 210 mg of the title compound as a yellow powder. 34% yield. LH-NMR (DMSO-de, d): 1.30 (3H, t, J = 7.3Hz), 1.32 (3H, t, J = 7.3Hz), 4.20-4.32 (4H, m), 4.40 (2H, c, J = 7.3Hz), 6.61 (HH, d, J = 5.4Hz), 7.30 (HH, s), 7.52 (2H, d, J = 8.8Hz), 7.78 (1H, s), 7.827 (HH, s) , 7.833 (2H, d, J = 8.8Hz), 8.09 (HH, s), 8.26 (HH, s), 13.26 (HH, s).

(Example 207) 7- (4- (((4-carboxyphenyl) aminocarbonylamino) methyl) -imidazol-1-yl-3,4-dihydro-3-oxo-6-trifluoro-methylquinoxaline-2-carboxylic acid To a suspension of the compound of Example 206 (207 mg, 362 μmol) in ethanol (5 ml), an aqueous solution (5 ml) of lithium hydroxide monohydrate (76.0 mg, 1.81 mmol) was added, and the mixture was stirred for 2 hours at 80 ° C. Then, an aqueous solution (5 ml) of lithium hydroxide monohydrate (76.0 mg, 1.81 mmol) was added and the mixture was stirred for 30 minutes additional at 90 ° C. After concentrating the reaction mixture to about half the volume, under reduced pressure, the pH value was brought to 2 with IN hydrochloric acid, under cooling with ice. The precipitate was collected by filtration, washed with water and then air-dried to obtain 155 mg of the title compound as a yellow-brown powder. Performance of 76%. mp 255 ° C (decomposition). Analysis Calculated for C22H? 5F3N6? 6? C 3 / 5H20: C, 46.88; H, 3.08; N, 14.91. Found: C, 47.02; H, 3.22; N.14.63. HR-BAR-: 515.0919 (-0.8 mmu) (Example 208) 3, 4-Dihydro-7- (4-formylimidazol-1-yl) -3-oxo-6-trifluoromethyl-2-carboxylic acid ethyl trifluoromethyl-2-carboxylate To a suspension of the compound of Example 81 (1.75 g, 4.58 mmol) in 1,4-dioxane (50 ml) was added manganese dioxide (1.99 g, 22.9 mmol), and the mixture was added to the mixture. refluxed for 24 hours. Next, manganese dioxide (1.99 g, 22.9 mmol) was added, and the mixture was refluxed for an additional 10 hours. After cooling, the manganese dioxide was filtered using celite and the solvent was distilled. Isopropyl ether was added to the obtained residue. The crystals were collected by filtration, washed with isopropyl ether and then air-dried to obtain 895 mg of the title compound as a yellow powder. 51% yield. ^ -RN (DMSO-d6, d): 1.32 (3H, t, J = 7.3Hz), 4.38 (2H, c, J = 7.3Hz), 7.76 (IH, s), 8.11 (IH, s), 8.18 (ÍH, s), 8.35 (ÍH, s), 9.84 (ÍH, s).

(Example 209) 7- (4- (Aminomethyl) imidazol-1-yl) 3-oxo-l, 2,3,4-tetrahydro-6-trifluoromethylquinoxaline-2-carboxylic acid ethyl chloride To a suspension of the compound of Example 208 (890 mg, 2.34 mmol) in ethanol (20 ml) was added hydroxylamine hydrochloride (325 mg, 4.68 mmol) and sodium acetate (384 mg, 4.68 mmol), and the mixture was refluxed for 4 hours. After cooling, the insoluble fractions were filtered using celite and the solvent was distilled. The obtained residue was purified by means of column chromatography on silica gel [methylene chloride-ethanol = 10: 1] to obtain a pale yellow powder. After dissolving it in ethanol (10 ml), 10% palladium-carbon (100 mg) and concentrated hydrochloric acid (0.5 ml) were added, and the mixture was stirred for 2 hours at room temperature, under an atmosphere of hydrogen ( 4 atm). The catalyst was filtered using celite and the solvent was distilled. Ethyl acetate was added to the obtained residue. The crystals were collected by filtration, washed with ethyl acetate and then dried with air to obtain 556 mg of the title compound as a pale yellow powder. 57% yield. ^ -RN (DMSO-de, d): 1.18 (3H, t, J = 7.3Hz), 4.15 (2H, c, J = 7.3Hz), 4.86 (IH, s), 7.21 (IH, s), 7.59 (ÍH, s), 7.83 (1H, s), 8.20-8.40 (4H, broad), 11.13 (ÍH, s). HR-BAR +: 384.1255 (-2.9 mmu).

# (Examples 210 to 214) Using the compound in Example 209 and following the same procedure as in Example 188, the compounds listed in the following Table 12 were obtained. Table 12 Example R Example R (Example 210) mp 224-226 ° C. HR-BAR-: 471.1030 (+0.1 mmu) (Example 211) mp 220-222 ° C. HR-BAR-: 549.0111 (-2.3 mmu) (Example 212) mp 219-221 ° C. HR-BAR-: 485.1172 (-1.4 mmu) (Example 213) mp 210-212 ° C. HR-BAR-: 501.1155 +2.1 mmu).

(Example 214) mp 212-214 ° C. HR-BAR-.521.1146 (-3.9 mmu).

(Example 215) 3, 4-Dihydro-3-oxo-7- ((4- (N-phenylcarbamoyloxy) methyl) imidazol-1-yl) -6-trifluoromethyl-2-carboxylic acid ethyl trifluoromethyl-2-carboxylate To a solution of the compound of Example 81 (200 mg, 523 μmol) in N, N-dimethylformamide (2 ml), phenyl isocyanate (114 μl, 1.05 mmol) was added, and the mixture was stirred for 2 hours at 60 ° C. Ethanol was added to the residue obtained by distilling the solvent and, after the insoluble fractions were filtered, the solvent was evaporated.

It was distilled. The residue obtained was purified by means of column chromatography on silica gel [ethyl acetate-hexane 1: 1 3: 1]] to obtain 120 mg of the title compound as a yellow powder. 46% yield.

XH-NMR (DMSO-de, d): 1.32 (3H, t, J = 6.8Hz), 4.40 (2H, c, J = 6.8Hz), 5.08 (2H, s), 6.98 (H, t, J) = 7.3Hz), 7.27 (HH, t, J = 7.3Hz), 7.53 (HH, s), 7.48 (2H, d, J = 7.3Hz), 7.78 (HH, s), 7.88 (HH, s), 8.12 (ÍH, s), 9.77 (ÍH, s), 13.30 (ÍH, s broad).

(Examples 216 to 231) Through the same process as in Example 215, the compounds listed in the following Table 13 were obtained. Table 13 Example R Example R Example R 138 Table 13 (continued) Example R Example R Example R (Example 216) XH-NMR (DMSO-de, d): 1.33 (3H, t, J = 6.8Hz), 4.40 (2H, c, J = 6.8Hz), 5.07 (2H, 5), 7.12 (1H, dt, J = 1.5, .8Hz), 7.37 (1H, dt, J = 1.5, 7.8HZ), 7.51 (IH, s), 7.52 (IH, dd, J = 1.5, 7.8Hz), 7.64 (1H, dd , J = 1.5, 7.8Hz), 7.78 (1H, S), 7.88 (H, S), 8.13 (H, s), 9.12 (H, s), 13.30 (H, broad).

(Example 217) XH-NMR (DMSO-de, d): 1.32 (3H, t, J = 6.8Hz), 4.40 (2H, c, J = 6.8Hz), 5.09 (2H, s), 7.18 (ÍH, d, J = 7.3Hz), 7. 25 (HH, t, J = 7.3Hz), 7.43 (HH, d, J = 7.3Hz), 7.54 (HH, s), 7.76 (HH, s), 7.78 (HH, s), 7.88 (HH, s ), 10.01 (ÍH, s), 13.29 (ÍH, s broad).

(Example 218) XH-NMR (DMSO-de, d): 1.32 (3H, t, J = 6.8Hz), 4.40 (2H, c, J = 6.8Hz), 5.08 (2H, s), 7.46 (4H, s), 7.53 (ÍH, s), 7.78 (1H, s), 7.88 (ÍH, s), 8.11 (1H, s), 9.95 (ÍH, s), 13.29 (ÍH, s broad).

(Example 219) 1H-MN (DMSO-de, d): 1.33 (3H, t, J = 6.8Hz), 4.40 (2H, c, J = 6.8Hz), 5.08 (2H, s), 7.11-7.26 (3H, m), 7.51 (HH, s), 7.60-7.67 (HH, m), 7.79 (HH, s), 7.88 (ÍH, s), 8.12 (ÍH, s), 9.45 (ÍH, s), 13.30 (1H, s broad).

(Example 220) XH-NMR (DMSO-d6, d): 1.32 (3H, t, J = 6.8Hz), 4.40 (2H, c, J = 6.8Hz), 5.08 (2H, s), 7.34 (1H, d, J = 8.8Hz), .50 (2H, d, J = 8.8Hz), 7.53 (IH, s), 7.78 (IH, s), i'24.0 7. 88 (1H, s), 8.11 (1H, s), 9.94 (1H, s), 13.28 (ÍH, s broad).

(Example 221) XH-NMR (DMSO-de, d): 1.32 (3H, t, 'J = 7.3Hz), 4.39 (2H, c, J = 6.8Hz), 5.11 (2H, s), 7.22 (H) , s), 7.53 (2H, s), 7.55 (H, s), 7.77 (H, s), 7.88 (H, s), 8.09 (H, s), 10.24 (H, s), 13.32 (1 H, s broad).

(Example 222) XH-NMR (DMSO-d6, d): 1.33 (3H, t, J = 7.3Hz), 4.40 (2H, c, J = 7.3Hz), 5.50 (2H, s), 7.45 (1H, t, J = 7.8Hz), 7.48 (HH, s), 7.50 (HH, d, J = 7.8Hz), 7.68 (HH, t, J = 7.8Hz), 7.72 (HH, d, J = 7.8Hz) , 7.78 (ÍH, s), 7.87 (1H, s), 8.11 (1H, s), 9.22 (ÍH, s), 13.30 (1H, s broad).

(Example 223) * H-NMR (DMSO-de, d): 1.32 (3H, t, J = 6.8Hz), 4.40 (2H, c, J = 6.8Hz), 5.12 (2H, s), 7.54 (HI) , s), 7.65 (2H, d, J = 8.8Hz), 7.69 (2H, d, J = 8.8Hz), 7.78 (HH, s), 7.88 (HH, s), 8.10 (HH, s), 10.23 (ÍH, s), 13.30 (ÍH, s broad). 2 * 1 (example 224) XH -RMN (DMSO-de, 6): 1.32 (3H, t, J = 7.3Hz), 2.23 (3H, s), 4.40 (2H, c, J = 7.3Hz), 5.06 (2H, s), 7.07 (2H, d, J = 8.3Hz), 7.35 (2H, d, J = 8.3Hz), 7.51 (1H, s), 7.78 (ÍH, s), 7.87 (1H, s), 8.11 (ÍH, s), 9.65 (ÍH, s), 13.28 (1H, broad s).

(Example 225) XH-NMR (DMSO-de, d): 1.32 (3H, t, J = 7.3Hz), 4.39 (2H, c, J = 7.3Hz), 5.05 (2H, s), 6.86 (2H, d, J = 8.8Hz), 7. 37 (2H, d, J-8.8HZ), 7.50 (IH, s), 7.76 (IH, s), 7.86 (ÍH, s), 8.07 (ÍH, s), 9.57 (ÍH, s), 13.27 (1H, s broad).

(Example 226) XH-NMR (DMSO-de, d): 1.17 (3H, t, J = 7.3Hz), 1.32 (3H, t, J = 7.3Hz), 3.57 (2H, s), 4.06 (2H , c, J = 7.3Hz), 4.40 (2H, c, J = 7f3Hz), 5.07 (2H, s), 7.16 (2H, d, J = 8.3Hz), 7.41 (2H, d, J = 8.3Hz) , 7.52 (ÍH, s), 7.78 20 (ÍH, s), 7.87 (ÍH, s), 8.11 (ÍH, s), 9.76 (ÍH, s), 13.30 (ÍH, s broad).

(Example 227) XH-NMR (DMSO-de, d): 1.32 (3H, t, J = 6.8Hz), 3.61 (3H, s), 3.62 (2H, s), 4.40 (2H, c, J = 6.8Hz), 5.08 (2H, s), 6.89 (ÍH, d, J = 7.3Hz), 7.22 (ÍH, t, J = 7.3Hz), 7.36 (IH, d, J = 7.3Hz), 7.41 (IH, s), 7.52 (IH, s), 7.78 (IH, s), 7.87 (IH, s), 8.12 (IH, s), 9.79. (ÍH, s), 13.29 (ÍH, s broad).

(Example 228) ^ -RMN (DMSO-de, d): 1.31 (3H, t, J = 6.8Hz), 1.32 (3H, t, J = 7.3Hz), 4.31 (2H, c, J = 6.8Hz), 4.40 (2H, c, J = 7.3Hz), 5.10 (2H, s), 7.43 (1H, t, J = 7.8Hz), 7.54 (HH, s), 7.59 (1H, d, J = 7.8Hz), 7.69 (HH, d, J = 7.8HZ), 7.78 (ÍH, s), 7.88 (ÍH, s), 8.12 (ÍH, s), 8.19 (ÍH, s), s 10.03 (ÍH, s), 13.30 (1H, s broad).

(Example 229) XH-NMR (DMSO-de, d): 1.33 (3H, t, J = 6.8Hz), 4.40 (2H, c, J = 6.8Hz), 5.12 (2H, s), 7.46-7.55 (4H, m), 7.59- 7.66 (HH, m), 7.74 (HH, d, J = 7.8Hz), 7.79 ( ÍH, s), 7.88- 7.98 (ÍH, m), 7.90 (ÍH, s), 8.05-8.10 (ÍH, m), 8.13 (ÍH, s), 9.68 (ÍH, s), 13.30 (1H, s broad ).

(Example 230) ^ -RM (DMSO-de, d): 1.32 (3H, t, J = 6.8Hz), 4.19 (ÍH, s), 4.21 (1H, s), 4.40 (2H, c, J = 6.8Hz), 4.96 (2H, s), 7.23 (2H, d, J = 7.3Hz), 7.26 (ÍH, s) , 7.31 (2H, t, J = 7.3Hz), 7.43 (IH, s), 7.77 (IH, s), 7.80 (IH, t, J = 7.3Hz), 7.84 (HH, s), 8.10 (HH, s), 13.26 (HH, s).

(Example 231) ^ -RN (DMSO-de, d): 1.03-1.26 (4H, m), 1.32 (3H, t, J = 7.3Hz), 1.49-1.79 (4H, m), 4.38 (2H, c , J = 7.3Hz), 4.90 (2H, s), 7.17 (H, d, J = 8.3Hz), 7.41 (H, s), 7.75 (H, s), 7.82 (H, s), 8.02 (H) , s), (Example 232) 3, 4-Dihydro-3-oxo-7- ((4- (N- (4-pyridyl) -carbamoyloxy) methyl) imidazol-1-yl) -6-trifluoromethyl-quinoxaline-2-carboxylate ethyl Í44 To a solution of isonicotinic acid (129 mg, 1.05 mmol) in benzene (5 ml) was added diphenylphosphoryl azide (226 μl, 1.05 mmol) and triethylamine (146 μl, 1.05 mmol), and the mixture was refluxed for 3 hours. hours. To this was added a solution of the compound of Example 81 (200 mg, 523 μmol) in N, N-dimethylformamide (1 ml), and the mixture was refluxed for an additional 2 hours. Ethyl acetate was added to the reaction mixture, which was washed with brine, then dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was purified by means of column chromatography on silica gel [methylene chloride-ethanol 30: 1 7: 1]] to obtain 87.0 mg of the title compound as a yellow powder. Performance of 33%. HR-BAR-: 510.1154 (+1.9 mmu).

(Example 233) 3, 4-Dihydro-3-oxo-7- ((4- (N- (3-thienyl) -carbamoyloxy) methyl.) Imidazol-1-yl) -6-trifluoromethyl-quinoxaline-2-carboxylate of ethyl Using the compound in Example 81 (200 mg, 523 μmol) and t-ofen-3-carboxylic acid (135 mg, 1.05 mmol) and following the same procedure as in Example 232, 204 mg of the compound of title like an orange powder. 77% yield. HR-BAR-: 506.0739 (-0.7 mmu).

(Example 234) 3,4-Dihxdro-3-oxo-7- ((4- (N- (benzofuran-2-yl) carbamoyloxy) methyl) imidazol-1-yl) -6-trifluoromethyl-1-quinoxaline-2-carboxylate of ethyl '236' To a solution of the compound of Example 81 (200 mg, 523 μmol and benzofuran-2-carboxylic acid (102 mg, 628 μmol) in N, N-dimethylformamide (5 ml) were added diphenylphosphoryl azide (226 μl, 1.05 mmol) and triethylamine (146 μl, 1.05 mmol). ), and the mixture was stirred for 6 hours at 60 ° C. Ethyl acetate was added to the reaction mixture, which was washed with brine, then dried over anhydrous magnesium sulfate, and the solvent was distilled. The obtained residue was purified by means of column chromatography on silica gel [ethyl acetate-hexane 1: 1) ethyl acetate] to obtain 114 mg of the title compound as a yellow powder. 40% yield. HR-BAR-: 540.1104 (-2.7 mmu).

(Example 235) 3,4-Dihydro-3-oxo-7- ((4- (N-phenyl-carbamoyloxy) methyl) -imidazol-1-yl) -6-trifluoromethyl-quinoxaline-2-carboxylic acid zn To a solution of the compound of Example 215 (100 mg, 199 μmol) in ethanol (4 ml) was added an aqueous solution of lithium hydroxide IN (697 μl)., 697 μmol) and water (4 ml), and the mixture was stirred for 1.5 hours at 50 ° C. After cooling, water was added, the insoluble fractions were filtered, and the filtrate was acidified using 3N hydrochloric acid. The precipitate was collected by filtration, washed with water and then air dried to obtain 63.0 mg of the title compound as a yellow powder. 64% yield. mp 193-195 ° C (decomposition). Analysis Calculated for C2? H? 4F3N505'6 / 5H20: C, 50.95; H, 3.34; N, 14.15. Found: C, 50.95; H, 3.06; N, 13.95. HR-BAR-: 472.0885 (+ i.6 mmu). süHHi (Examples 236 to 252) Through the same process as in Example 235, the compounds listed in the following Table 14 were obtained.

Example R Example R Example R 3 # 9 (Example 236) mp 152-154 ° C. HR-BAR-: 549.9987 (+1.3 mmu) (Example 237) mp 219-221 ° C. Analysis Calculated for C2? Hi3BrF3 505- / 2H2O: C44.95; H, 2.51; N, 12.47. Found: C, 44.80; H, 2.28; N, 12.21. HR-BAR-: 549.9981 (+0.7 mmu).

(Example 238) mp 218-220 ° C. Analysis Calculated for C2? H13BrF3N505-1 / 2H20: C, 44.94; H, 2.51; N, 12.47. Found: C, 45.00; H, 2.29; N, 12.23. HR-BAR-: 549.9969 (-0.4 mmu).

(Example 239) mp 184-186 ° C. Analysis Calculated for C2? H? 3F3N405'l / 2H20: C, 50.41; H, 2.82; N, 13.99. Found: C, 50.11; H, 2.72; N, 13.67. HR-BAR-: 490.0788 (+1.4 mmu).

(Example 240) mp 204-206 ° C. HR-BAR-: 506.0497 (+1.8 mmu) (Example 241) mp 204-206 ° C. Analysis Calculated for C21H12Cl2F3N5O5.6 / 5H20: C, 44.73; H, 2.57; N, 12.42. Found: C, 44.91; H, 2.31; N, 12.09. HR-BAR-: 540.0046 (-4.4 mmu).

(Example 242) mp 166-168 ° C. Analysis Calculated for C22H? 3F6N5? 5-H20: C, 47.24; H, 2.70; N, 12.52. Found: C, 47.36; H, 2.51; N, 12.21. HR-BAR-: 540.0732 (-1.1 mmu).

(Example 243) mp 194-196 ° C HR-BAR-: 540.0743 (+0.0 mmu) (Example 244) mp 179-181 ° C HR-BAR-: 486.1013 (-1.2 mmu) d i (Example 245) mp 210-212 ° C. Analysis Calculated for C22Hi6F3N5? 6"L / 2H20 C, 51.57; H, 3.34; N, 13.67, Found: C, 51.71; H, 3.13; N, 13.43, HR-BAR-: 502.0992 (+1.7 mmu).

(Example 246) mp 210-212 ° C. Calculated Analysis for C23Hi6F3N507-3 / 2H20: C, 49. 47; H, 3.34; N, 12.54. Found: C, 49.67; H, 3.10; N, 12.37. HR-BAR-: 530.0942 (+1.8 mmu).

(Example 247) mp 196-198 ° C. HR-BAR-: 530.0925 (+0.2 mmu) (Example 248) mp 208-210 ° C. Analysis Calculated for C25H? 6F3N505. 2.8H20 C, 52.32; H, 3.79; N, 12.20. Found: C, 52.09; H, 3.40; N, 12.01. HR-BAR-: 552.1044 (+1.9 mmu).

(Example 249) mp 165-167 ° C. HR-BAR-: 486.1043 (+1.8 mmu) (Example 250) mp 225-227 ° C. Analysis Calculated for C2iH2oF3N5? 5-7 / 10H20 C, 51.26; H, 4.38; N, 14.23. Found: C, 51.13; H, 4.16; N, 14.04. HR-BAR-: 78.1336 (-0.2 mmu).

(Example 251) mp 267-269 ° C (decomposition). Analysis Calculated for CigHi ^ NsOsS ^ .3H20: C, 43.82; H, 3.21; N, 13.44. Found: C, 43.96; H, 2.89; N, 13.07. HR-BAR-: 478.0433 (+0.0 mmu) (Example 252) mp 245-247 ° C (decomposition) HR-BAR-: 512.0789 (-2.9 mmu).

(Example 253) 7- ((4- (N- (3-carboxyphenyl) carbamoyloxy) -methyl) imidazol-1-yl) -3,4-dihydro-3-oxo-6-trifluoro-methyl-quinoxalin-2 acid -carboxylic To a solution of the compound of Example 228 (180 mg, 314 μmol) in acetic acid (5 ml) was added concentrated hydrochloric acid (1 ml), and the mixture was stirred for 2 hours at room temperature. Then, it was allowed to remain static overnight, water was added with ice, the precipitate was collected by filtration and washed with water. After dissolving it in an aqueous solution of lithium hydroxide IN, the more soluble fractions were filtered and the pH value was brought to 4 using 3N hydrochloric acid. The precipitate was collected by filtration, washed with water and then dried in air to obtain 25.0 mg of the title compound as a brown powder. 15% yield. mp 215-217 ° C (decomposition).

HR-BAR-: 516.0778 (+1.1 mmu).

(Example 254) 3, 4-Dihydro-3-oxo-7- ((4- (N- (4-pyridyl) carbamoyloxy) -methyl) imidazol-1-yl) -6-trifluoromethyl-quinoxaline-2-carboxylic acid To a solution of the compound of Example 232 (75.0 mg, 149 μmol in ethanol (2 ml) was added an aqueous solution of lithium hydroxide IN (522 μl, 522 μmol) and water (2 ml), and the mixture was stirred for 1.5 hours at 50 ° C. After cooling, ice water was added, the insoluble fractions were filtered, and the pH value was brought to 4 using 3N hydrochloric acid, which were concentrated under reduced pressure, purified with Sepabeads® SP850 synthetic adsorbent. [water- > water-acetonitrile (5: 1)] and recrystallized from water to obtain 5.0 mg of the title compound as a pale yellow powder. 7% yield. mp 254-256 ° C (dec.). HR-BAR-: 473.0844. +2.3 mmu).

(Example 255) 3, 4-Dihydro-3-oxo-7- ((4- (N- (4-quinolyl) carbamoyloxy) -methyl) imidazol-1-yl) -6-trifluoromethyl-quinoxaline-2-carboxylic acid To a solution of quinoline-4-carboxylic acid (182 mg, 1.05 mmol) in benzene (5 ml) was added diphenylphosphoryl azide (226 μl, 1.05 mmol) and triethylamine 146 μl, 1.05 mmol), and the mixture was subjected to reflux for 3 hours. To this was added a solution of the compound of Example 81 (200 mg, 523 μmol) in N, N-dimethylformamide (1 ml), and the mixture was refluxed for an additional 2 hours. Ethyl acetate was added to the reaction mixture, which was washed with brine, then dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was purified by means of '. 6 column chromatography on silica gel [methylene chloride-ethanol [30: 1 7: 1]] to obtain 188 mg 3,4-dihydro-3-oxo-7- ((4- (N- (4-quinolyl)] carbamoyloxy) methyl) -imidazol-1-yl) -6-trifluoromethyl-2-oxo-carboxylic acid ethyl ester, as a yellow powder. 65% yield. To a solution of ethyl ester (150 mg, 272 μmol) obtained in ethanol (3 ml) was added an aqueous solution of lithium hydroxide (950 μl, 950 μmol) and water (3 ml), and the mixture was stirred for 1.5 hours at 50 ° C. After cooling, ice water was added and the insoluble fractions were filtered. After dissolving them, adding 3N hydrochloric acid, the insoluble fractions were filtered. The filtrate was purified with Sepabeads® SP850 synthetic adsorbent [water-acetonitrile (20: l-> 5: 1)] and recrystallized from water to obtain 10.3 mg of the title coppant as a brown powder. 7% yield. mp 239-241 ° C (decomposition). HR-BAR-: 523.0975 (-0.2mmu).

(Example 256) 7- ((4- (N- (4-carboxy enyl) carbamoyloxy) -methyl) imidazol-1-yl) -3-dihydro-4-ethyl-3-oxo-6-trifluoromethylquinoxalin-2 acid -carboxylic To a solution of the compound of Example 82 (560 mg, 976 μmol) in N, N-dimethylformamide (10 ml) was added potassium carbonate (540 mg, 3.90 mmol) and iodoethane (625 μl, 7.81 mmol), and the mixture was stirred for 2 hours at 80 °. C. Next, iodoethane (625 μl, 7.81 ramol) was added and the mixture was stirred for an additional 16 hours. After distilling off the solvent, ethyl acetate was added and the solution was made acidic by adding additional 3N hydrochloric acid. The organic layer was separated, washed with brine, then dried over anhydrous magnesium sulfate and the solvent was distilled. The obtained residue was purified by means of column chromatography on silica gel [ethyl acetate-hexane (1: 3 »5: 1)] to obtain 102 mg of the 4-ethylquinoxalin ester as a yellow powder. After dissolving it in ethanol (2 ml), an aqueous solution of lithium hydroxide IN, (593 μl, 593 μmol) and water (2 ml) was added in sequence, and the mixture was stirred for 1.5 hours at 50 ° C. . After cooling, ice water was added and the more soluble fractions were filtered. After the pH value was brought to 4 by adding 3N hydrochloric acid, the crystals were collected by filtration, washed with water and with ethyl acetate in sequence, and then air dried to obtain 19.0 mg of the title compound like a light orange powder. 20% yield. mp 194-196 ° C. HR-BAR-: 544.1055 (-2.5mmu).

(Example 257) 3-Ethoxy-7- (4- ((N- (4-ethoxycarbonyl-phenyl) -carbamoyloxy) methyl) imidazolyl) -6-nitroquinoxaline-2-carboxylic acid ethyl ester To a solution of the compound of Example 84 (329 mg, 849 μmol) in benzene (30 ml), ethyl 4-isocyanatobenzoate (325 mg, 1.70 mmol) was added, and the mixture was refluxed for 2 hours. After cooling, the residue obtained by distilling the solvent was subjected to column chromatography on silica gel. [hexane-ethyl acetate = 1: 1] to obtain 488 mg of the title compound as an amorphous yellow material. 99% yield. 1 H-NMR (CDC13, d): 1.38 (3H, t, J = 6.9Hz), 1.46 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 6.9Hz), 4.35 (2H, c, J = 6.9Hz), 4.55 (2H, c, J = 7.3Hz), 4.66 (2H) , c, J = 6.9Hz), 5.25 (2H, s), 7.17 (HH, s), 7.25 (HH, d, J = 1.0Hz), 7.47 (2H, d, J = 8.8Hz), 7.71 (HH, d, J = 1.5Hz), 7.99 (2H, d, J = 8.8Hz), 8.15 (HH, s), 8.45 (HH, s).

(Examples 258 to 262) Through the same process as in the Example 257, the compounds listed in the following Table 15 were obtained.

Table 15 Example R Example R -% 60 (Example 258) X H-NMR (CDCl 3, d): 1.46 (3 H, t, J = 7.3 Hz), 1.53 (3H, t, J = 7.3Hz), 4.55 (2H, c, J = 7.3Hz), 4.67 (2H, c, J = 7.3Hz), 5.25 (2H, s), 7.11 (1H, s), 7.26 (ÍH, d, " J = 1.5Hz), 7.33-7.42 (2H, m), 7.57 (ÍH, dt, J = 8.3, 1.0Hz), 7. 71 (ÍH, d, J = 1.5Hz), 7.84 (ÍH, s) -, 8.16 (ÍH, s), 8.45 (ÍH, s).

(Example 259) 1 H-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 6.9Hz), 4.55 (2H, c, J = 7.3Hz), 4.67 (2H, c, J = 6.9Hz), 5.25 (2H, s), 6.82-6.89 (3H, m), 7.71 (ÍH, d, J = 1.5Hz), 8.04-8.07 (ÍH, broad), 8.16 ( ÍH, s), 8.45 (ÍH, (Example 260) XH-NMR (CDCI3, d): 1.46 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 6.9Hz), 4.55 (2H, c, J = 7.3Hz), 4.67 (2H, c, J = 6.9Hz), 5.27 (2H, s), 7.55 (HH, s), 7.71 (HH, d, J = 1.5Hz), 7.91 (2H, s), 8.16 (HH, s) , 8.46 (ÍH, s).

(Example 261) XH-NMR (CDCl3, d); 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.3Hz), 4.55 (2H, c, J = 7.3Hz), 4.66 (2H, c, 2 € 1 J = 7.3Hz), 5.30 (2H, d, J = 1.5Hz), 7.13 (IH, s), 7.45-7.52 (3H, m), 7.53 (IH, dd, J = 6.9, 1.5Hz), 7.66 ( ÍH, d, J = 8.3Hz), 7.72-7.90 (3H, m), 8.16 (1H, s), 8.45 (ÍH, s).

(Example 262) : 1.08-1.25- (2H, m), 1.30-1.44 (2H, m), 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 6.9Hz), 1.55-1.60 (2H, m), 1.67-1.72 (2H, m), 1.91-1.95 (2H, m), 3.48-3.52 (ÍH, m), 4.55 (2H, c, J = 7.3Hz), 4.66 (2H, c, J = 7.3Hz), 5.10 (2H, s), 7.18 (HH, d, J = 1.0Hz), 7.68 (HH, d, J = 1.5Hz), 8.14 (HH, s), 8.43 (HH, s).

(Example 263) 7- (4- ((N- ((4-Bromophenyl) methyl) carbamoyloxy) -methyl) imidazolyl) -3-ethoxy-6-nitroquinoxaline-2-carboxylic acid ethyl ester To a solution of the compound of Example 84 (150 mg, 387 μmol) and 4-bromophenylacetic acid (166 mg, 774 μm) μmol) in benzene (12 ml) was added diphenylphosphoryl azide (167 μl, 774 μmol) and triethylamine (108 μmol, 774 μmol), and the mixture was refluxed for 3 hours. After cooling, the residue obtained by distilling off the solvent was subjected to silica gel column chromatography [hexane-ethyl acetate = 2: 1] to obtain 121 mg of the title compound as an amorphous yellow material. Yield of 52%. XH-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.3Hz), 4.34 (2H, d, J = 6.4Hz), 4.55 (2H, c, J = 7.3Hz), 4.67 (2H, c, J = 7.3Hz), 5.16 (2H) , s), 7.17 (2H, d, J = 8.3Hz), 7.19 (ÍH, s), 7.45 (2H, d, J = 8.3Hz), 7.68 (ÍH, s), 8.14 (ÍH, s), 8.44 (ÍH, s).

(Examples 264 to 277) Through the same process as in Example 263, the compounds listed in the following were obtained Table 16 Example R Example R Example R (Example 264) ^ -RMNÍCDCls, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.3Hz), 4.37 (2H, d, J = 5.9Hz), 4.55 (2H) , c, J = 7.3Hz), 4.67 (2H, c, J = 7.3Hz), 5.17 (2H, s), 7.18-7.24 (3H, m), 7.38-7.44 (2H, m), 7.68 (ÍH, d, J = 1.0Hz), 8.15 (HH, s), 8.44 (HH, s).

(Example 265) 1 H-NMR (CDC 13, d): 1.47 (3 H, t, J = 7.3 Hz), 1.53 (3H, t, J = 6.9Hz), 4.46 (2H, d, J = 6.4Hz), 4.55 (2H, c, J = 7.3Hz), 4.67 (2H, c, J = 6.9Hz), 5.15 (2H, s), 5.30-5.40 (ÍH, broad), 7.12-7.33 (2H, m), 7.41 (ÍH, d, J = 6.9Hz), 7. 54 (ÍH, d, J = 7.8Hz), 7.68 (ÍH, s), - 8.14 (ÍH, s), 8.44 (ÍH, s).

(Example 266) ^ -R NCDCDls, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 6.9Hz), 2.82 (2H, t, J = 6.9Hz), 3.47 (2H, c, J = 6.9Hz), 4.55 (2H, c, J = 7.3Hz), 4.66 (2H) , c, J = 6.9Hz), 4. 55 (ÍH, broad), 5.12 (2H, s), 7.17-7.22 (3H, m), 7.27-7.31 (2H, m), 7.67 (ÍH, d, J = 1.5Hz), 8.14 (ÍH, s ), 8.43 (ÍH, s).

(Example 267) ^ -CDNÍCDCl;!, D): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 6.9Hz), 2.90 (6H, s), 4.55 (2H, c, J = 7.3Hz), 4.66 (2H, c, J = 6.9Hz), 5.21 (2H, s), 6.57 (ÍH, broad), 6.70 (2H, d, J = 8.8Hz), 7.69 (1H, d , J = 1.0Hz), 8.15 (HH, s), 8.44 (HH, s). 2 (35 (Example 268) 1 H-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 6.9Hz), 4.55 (2H, c, J = 7.3Hz), 4.67 (2H, c, J = 6.9Hz), 5.26 (2H, s), 6.63-6.69 (HH, m), 6.97-7.06 (2H, m), 7.26 (HH, d, J = 2.0Hz), 7.71 (HH, d, J = 1.0Hz), 7.90- 8.10 (ÍH, broad), 8.16 (ÍH, s), 8.45 (ÍH, s).

(Example 269) 1 H-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 6.9Hz), 4.55 (2H, c, J = 7.3Hz), 4.67 (2H, c, J = 6.9Hz), 5.28 (2H, s), 7.21 (2H, s), 7.27 (IH, d, J = 1.5Hz), 7.72 (IH, d, J = 1.5Hz), 7.80 (HH, d, J = 8.8Hz), 7.83 (HH, s), 8.17 (HH, s), 8.45 (HH, d, J = 9.3Hz), 8.46 (HH, s).

(Example 270) ^ -RMNÍCDCls, d): 1.46 (3H, t, J = 7.3Hz), 1.52 (3H, t, J = 6 .9Hz), 4.54 (2H, c, J = 7.3Hz), 4.66 (2H, c, J = 6.9Hz), 5.28 (2H, s), 7.01 (HH, s), 7.27 (HH, d, J = 1.0Hz), 7.35-7.46 (3H,), 7.71 (HH, d, J = 1.0Hz ), 7.75 (ÍH, d, J = 7.3Hz), 7.76 (ÍH, d, J = 8.8Hz), 7.99 (ÍH, s), 8. 15 (ÍH, s), 8.44 (ÍH, s).

, * Z66 (Example 271) ^ -RMNÍCDCls, d): 1.46 (3H, t, J = 7.3Hz), 1.52 (3H, t, J = 6.9Hz), 4.54 (2H, c, J = 7.3Hz), 4.66 (2H , c, J = 6.9Hz), 5.25 (2H, s), 7.25 (HH, s), 7.63 (HH, broad), 7.12-7.33 (2H, m), 7.74 (HH, d, J = 1.5Hz ), 8.03 (HH, d, J = 8.3Hz), 8.15 (HH, s), -8.29 (1H, dd, J = 4.9, 1.5Hz), 8.44 (HH, s), 8.55 (HH, d, J = 2.4Hz).

(Example 272) ^ -RMNfCDCla, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.3Hz), 4.55 (2H, c, J = 7.3Hz), 4.66 (2H , c, J = 7.3Hz), 5.30 (2H, s), 7.28 (IH, s), 7.73 (IH, s), 8.12 (IH, s), 8.17 (IH, s), 8.23 (1H, s), 8.30 ( ÍH, d, J = 2.4Hz), 8.46 (ÍH, s), 9.36 (ÍH, s).

(Example 273) 1 H-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.3Hz), 4.55 (2H, c, J = 7.3Hz), 4.66 (2H, c, J = 7.3Hz), 5.33 (2H, s), 7.30 (HH, s), 7.56 (HH, d, J = 8.3Hz), 7.70 (HH, s), 7.72 (HH, d, J = 5.4Hz), 7.74 (HH, s), 7.83 (HH, d, J-8.3Hz), 8.10 (HH, s), 8.17 (HH, s), 8.14 (1H, d, J = 4.9Hz) , 8.47 (ÍH, s), 8.83 (ÍH, d, J = 5.4Hz).

(Example 274) 1 H-NMR (CDC13, d): 1.45 (3H, t, J = 7.3Hz), 1.51 (3H, t, J = 7.3Hz), 4.53 (2H, c, J = 7.3Hz), 4.62 (2H, c, J = 7.3Hz), 5.25 (2H, s), 5.75 (IH, s), 6.74 (IH, td, J = 8.8, 2.5Hz), 7.00 (IH, dd, J = 9.8, 2.5 Hz), 7.11 (HH, dd, J = 8.8.4.4Hz), 7.25 (HH, d, J = 1.0Hz), - 7.73 (HH, s), 8.11 (1H, s), 8.40 (HH, s) , 8.75 (ÍH, s), 9.82 (ÍH, s).

(Example 275) 1 H-NMR (CDC13, d): 1.46 (3H, t, J = 6.9Hz), 1.53 (3H, t, J = 6.9Hz), 4.55 (2H, c, J = 6.9Hz), 4.66 (2H, c, J = 6.9Hz), 5.25 (2H, s), 6.60 (ÍH, dd, J = 3.9, 1.5Hz), 6. 80-6.86 (2H, m), 7.25 (HH, s), 7.52 (1H, s), 7.69 (HH, d, J = 1.5Hz), 8.15 (HH, s), 8.44 (HH, s).

(Example 276) 1 H-NMR (CDC13, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 6 .9Hz), 4.55 (2H, c, J = 7.3Hz), 4.66 (2H, c, J = 6.9Hz), 5.23 (2H, s), 6.94 (HH, dd, J = 4.9, l.OHz) 7.07 (HH, s), 7.20-7.24 (3H, m), 7.69 (HH, d, J = 1.0Hz), 8.15 (ÍH, s), 8.44 (ÍH, s).

(Example 277) ^ -RMNÍCDCla, d): 1.47 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.3Hz), 4.54 (2H, c, J = 7.3Hz), 4.66 (2H , c, J = 7.3Hz), 5.29 (2H, s), 6.52 (ÍH, s broad), 7.14-7.19 (2H, m), 7.32 (ÍH, d, J = 7.3Hz), 7.36 (ÍH, s ), 7.44 (IH, d, J = 7.3Hz), 7.71 (IH, s), 8.15 (lH, -s), 8.45 (IH, s).

(Example 278) 3,4-Dihydro-7- (4- ((N- (4-ethoxycarbonyl-phenyl) -carbamoyloxy) methyl) imidazolyl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 257 (488 mg, 844 μmol) in acetic acid (10 ml) was added hydrochloric acid (2.5 ml), and the mixture was stirred for 24 hours at room temperature. Water was added to the reaction mixture. The precipitate was collected by filtration, washed with water and then dried with air to obtain 372 mg of the title compound as a yellowish brown powder. 80% yield. mp 207-209 ° C (decomposition). Analysis Calculated for C23H? SN6? 9.3 / 2H20: C, 50.28; H, 3.85; N, 15.30. Found: C, 50.02; H, 3. 62; N, 14.94. HR-BAR-: 521.1057 (-0.8 mmu).

(Examples 279 to 288) Through the same process as in the Example 278, the compounds listed in the following Table 17 were obtained. Table 17 Example R Example R (Example 279) mp 242-244 ° C (decomposition) HR-BAR-: 474.0788 (-l.Ommu).

(Example 280) mp 209-211 ° C (decomposition). Analysis Calculated for C22H19N7O7. H20: C, 51.66; H, 4.14; N, 19.17. Found: C, 51.72; H, 4.15; N, 18.46. HR-BAR-: 492.1248 (-2.Ommu).

(Example 281) mp 241-243 ° C (decomposition). Analysis Calculated for C20H12F2 6O7.3 / 2H20: C, 46.79; H, 2.95; N, 16.37. Found: C, 46.90; H, 2.58; N, 16.11. HR-BAR-: 485.0650 (-0.7mmu).

(Example 282) mp 217-219 ° C (decomposition) HR-BAR-: 585.0613 (+ 1.9mmu).

(Example 283) mp 224-226 ° C (decomposition) Analysis Calculated for C2 Hi6N607. H20: C, 55.60; H, 3.50; N, 16.21. Found: C, 55.67; H, 3.39; N, 15.88. HR-BAR-: 499.1031 (+ 2.9mmu).

(Example 284) mp 275-277 ° C (decomposition). Analysis Calculated for C2 H? 6N607.3 / 4H20: C, 56.09; H, 3.43, N, 16.18. Found: C, 56.25; H, 3.36; N, 15.94. HR-BAR-: 499.1021 (+ 1.9mmu).

(Example 285) mp 212-214 ° C (decomposition). Analysis Calculated for C22H? 8N607 / 2H20: C, 4.21; H, 3.93; N, 17.24. Found: C, 54.22; H, 3.78; N, 17.21. HR-BAR-: 477.1151 (-0.8mmu).

(Example 286) mp 237-239 ° C (decomposition). Analysis Calculated for C2oH2oN6? 7. 3 / 4H20: C, 1.12; H, 4.61, N, 17.88. Found: C, 51.35; H, 4. 62; N, 17.44. HR-BAR-: 455.1324 (-2.0mmu).

(Example 287) pf > 300 ° C. Analysis Calculated for d8H? 2N807.HCl.3 / 5H20: C, 43.27; H, 2.86; N, 22.43. Found: C, 43.21; H, 2.83; N, 22.55. HR-BAR-: 451.0753 (+ 0.3mmu) ._ (Example 288) pf > 300 ° C. Analysis Calculated for C23H? 5N707.2HC1.3.3H20: C, 43.59; H, 3.75; N, 15.47. Found: C, 43.25; H, 3.36; N, 15.08. HR-BAR-: 500.0960 (+ 0.5mmu).

(Example 289) 7- (4- ((N- ((4-Bromophenyl) methyl) -carbamoyloxy) methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxa-lin-2-carboxylic acid To a solution of the compound of Example 263 (121 mg, 202 μmol) in acetic acid (2.5 ml) was added hydrochloric acid (0.5 ml), and the mixture was stirred for 20 hours at room temperature. Water was added to the reaction mixture and, after the precipitate was filtered, the reaction mixture was purified with Sepabeads® SP8S0 synthetic adsorbent [water? Water-acetonitrile (20: 1- > 2: 1)] to obtain 22.2 mg of the title compound as a yellow powder. 20% yield. mp 217-219 ° C (decomposition). Analysis Calculated for c2? H? 5BrN607.1 / 2H20: C, 45.67; H, 2.92; N, 15.22. Found: C, 45.71; H, 2.79; N, 15.20. HR-BAR-.541.0099 (-0.8mmu).

(Examples 290 to 293) Through the same process as in Example 289, the compounds listed in the following ± 74 were obtained Table 18. Example R (Example 290) mp 159-161 ° C (decomposition). Analysis Calculated for C2? Hi5BrN607: C, 46.43; H, 2.78; N, 15.47. Found: C, 46.55; H, 2.87; N, 14.92. HR-BAR-: 541.0085 (-2.2mmu).

(Example 291) mp 187-189 ° C (decomposition). Analysis Calculated for C2 H? 5BrN607: C, 46.43; H, 2.78; N, 15.47. Found: C, 46.13; H, 2.80; N, 15.34. HR-BAR-.541.0113 (+ 0.6mmu).

(Example 292) mp 218-220 ° C (dec.) Analysis Calculated for C20H? 2F2N6O7.2 / 3H20: C, 48.20; H, 2.68; N, 16.86. Found: C, 48.40; H, 2.85; N, 16.50. HR-BAR-: 485.0698 (+ 4.1mmu).

(Example 293) mp 228-230 ° C (decomposition). Analysis Calculated for C? 9H? 3N707-H2O: C, 48.61; H, 3.22; N, 20.89. Found: C, 48.38; H, 3.11; N, 20.99. HR-BAR-: 450.0784 (-1.5mmu). (Example 294) 3-Ethoxy-7- (4- ((N- (4-ethoxycarbonyl-2-fluorophenyl) carbamoyloxy) methyl) imidazolyl) -6-nitroquinoxaline-2-carboxylic acid ethyl ester To a solution of the compound of Example 84 (500 mg, 1.29 mmol) in methylene chloride (10 ml) was added ethyl 4-isocyanato-3-fluorobenzoate (541 mg, 2. 59 mmol), and the mixture was stirred for 2 hours at 11 room temperature. After allowing it to remain static overnight, the solvent was distilled and the obtained residue was purified by column chromatography on silica gel [hexane-ethyl acetate (2: 1 1: 2)] to obtain 670 mg of the compound of the title as a pale yellow powder. 87% yield. XH-NMR (DMSO-d6, d): 1.31 (3H, t, J = 6.8Hz), 1.36 (3H, t, J = 6.8Hz), 1.43 (3H, t, J = 6.8Hz), 4.30 (2H) , c, J = 6.8Hz), 4.48 (2H, c, J = 6.8Hz), 4.62 (2H, c, J = 6.8Hz), 5.14 (2H, s), 7.62 (1H, s), 7.70 ( HH, d, J = 11.2Hz), 7.77 (HH, d, J = 8.3Hz), 8.0C (1H, t, J = 8.3Hz), 8.46 (HH, s), 8.66 (HH, s), 9.93 (ÍH, s).

(Example 295) 3-Ethoxy-7- (4- ((N- (5-ethoxycarbonyl-2-fluorophenyl) carbamoyloxy) methyl) imidazolyl) -6-nitroquinoxaline-2-carboxylate of ethoxy Using the compound of Example 84 (200 mg, 516 μmol) and following the same procedure as in Example 294, 249 mg of the title compound was obtained as a pale yellow powder. 81% yield. ^ -RMN (DMSO-de, d): 1.31 (3H, t, J = 7.3Hz), 1.36 (3H, t, J = 7.3Hz), 1.43 (3H, t, J = 7.3Hz), 4.31 (2H , c, J = 7.3Hz), 4.48 (2H, c, J = 7.3Hz), 4.62 (2H, c, J = 7.3Hz), 5.12 (2H, s), 7.37 (ÍH, t, J = 9.3Hz ) ,. 7.62 (ÍH, s), 7.71- 7.75 (ÍH, m, 8.06 (ÍH, s), 8.38 (ÍH, d, J = 5.9Hz), 8.46 (ÍH, s), 8.66 (ÍH, s), 9.74 ( ÍH, s).

(Example 296) 3-Ethoxy-7- (4- ((N- (2-ethoxycarbonylphenyl) -carbamoyloxy) methyl) imidazolyl) ethyl 6-nitroquinoxaline-2-carboxylate Using the compound of Example 84 (200 mg, 516 μmol) and following the same procedure as in Example 294, 199 mg of the title compound was obtained as a pale yellow powder. 67% yield.

^ -RMN (DMSO-de, d): 1.32 (3H, t, J = 7.3Hz), 1.37 (3H, t, J = 7.3Hz), 1.43 (1H, t, J = 7.3Hz), 4.32 (2H , c, J = 7.3Hz), 4.48 (2H, c, J = 7.3Hz), 4.62 (2H, c, J = 7.3 Hz), 5.12 (2H, s), 7.16 (ÍH, t, J = 8.8Hz ), 7.625 (HH, s), 7.634 (HH, t, J = 8.8Hz), 7.95 (HH, d, J = 8.8Hz), 8.05 (HH, s), 8.18 (HH, d, J = 8.8Hz) ), 8.49 (ÍH, s),. 8.66 (ÍH, s), 10.33 (ÍH, s).

(Example 297) 7- (4- ((N- (4-carboxy-2-fluorophenyl) carbamoyloxy) methyl) -imidazolyl) -3,4, dihydro-6-nitro-3-oxo-quinoxaline-2-carboxylic acid To a suspension of the compound of Example 294 (670 mg, 1.12 mmol) in ethanol (50 ml) was added an aqueous IN solution of sodium hydroxide (3.37 ml, 3.37 mmol) and water (1 ml) successively, and The mixture was refluxed for 1 hour under Ar gas. After cooling, 47% hydrobromic acid (16 ml) was added "? • 27f9" and the mixture was stirred for 24 hours at room temperature. The reaction mixture was concentrated under reduced pressure and then washed with water, the residue was dried with air to obtain 254 mg of the title compound as a brown powder. 44% yield. mp 250-252 ° C (decomposition). HR-BAR-: 511.0683 (+ 3.3mmu).

(Example 298) 7- (4- ((N- ((4-Bromophenyl) methyl) -carbamoyloxy) methyl) -imidazolyl) 3,4-dihydro-6-nitro-3-oxoquinoxa-lin-2-carboxylic acid Using the compound of Example 295 (100 mg, 168 μmol), through the same procedure as in Example 297, 28.0 mg of the title compound was obtained as brown powder. Performance of 33%. pf > 300 ° C. HR-BAR-: 511.0633 (-1.7mmu).

(Example 299) 7- (4- ((N- (2-carboxyphenyl) carbamoyloxy) • methyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid Using the compound of Example 296 (97.0 mg, 197 μmol) and following the same procedure as in Example 297, 81.0 mg of the title compound was obtained as brown powder. Quantitative performance. mp 216-218 ° C (decomposition). HR-BAR-: 493.0752 (+ 0.8mmu).

(Example 300) 3,4-Dihydro-7- (4- ((N-2-ethoxycarbonyl-phenyl) carbamoyloxy) methyl) imidazolyl) -6-nitro-3-oxoquinoxaline-2-carboxylic acid jfe? To a solution of the compound of Example 296 (197 mg, 341 μmol) in acetic acid (5 ml) was added concentrated hydrochloric acid (1 ml), and the mixture was stirred for 4 hours at room temperature, then allowed to stand statically during the night. The reaction mixture was concentrated under reduced pressure and then washed with water, the residue was air-dried to obtain 17.0 mg of the title compound as a brown powder. 10% yield. mp 182-184 ° C (decomposition). HR-BAR-: 521.1070 (+ 1.3mmu).

(Example 301) Ethyl 3-Ethoxy-7- (4- (2-hydroxyethyl) imidazolyl) -6-nitroquinoxaline-2-carboxylate $ 82 To a solution of the compound of Example 139 (309 mg, 999 μmol) in N, N-dimethylacetamide (10 ml) was added 4- (2-hydroxyethyl) imidazole (270 mg, 2.41 mmol) and triethylamine (1 ml) in sequence , and the mixture was stirred for 15 hours at 120 ° C. The reaction mixture was concentrated under reduced pressure and purified by column chromatography on silica gel [methylene chloride - > methylene chloride-methanol (10: 1)] to obtain 114 mg of the title compound as a yellowish brown powder. 28% yield. XH-NMR (CDC13, d): 1.47 (3H, t, J = 6.8Hz), 1.53 (3H, t, J = 7.3Hz), 2.81 (1H, d, J = 4.4Hz), 2.87-2.92 (2H, m), 3.97 (2H, t, J = 5.9Hz), 4.55 (2H, c, J = 6.8Hz), 4.66 (2H, c, J = 7.3Hz), 6.94 (IH, d, J = 1.0Hz), 7.66 (1H, d, J = 1.0Hz), 8.15 (1H, s), 8.42 (ÍH, s).

(Example 302) 7- (4- (2- (N- (4-carboxyphenyl) carbamoyloxy) ethyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxalin-2-carboxylic acid To a solution of the compound of Example 301 (110 mg, 274 μmol) in acetonitrile (5 ml) was added ethyl 4-isocyanatobenzoate (57.0 mg, 298 μmol), and the mixture was allowed to stand statically overnight. The residue obtained by concentrating the reaction mixture under reduced pressure was purified by means of column chromatography on silica gel [methylene chloride - > methylene chloride-methanol (50: 1)]. This was dissolved in acetic acid-concentrated hydrochloric acid (5: 1, 6 ml) and stirred for 20 minutes at 80 ° C, then allowed to stand statically overnight at room temperature. The residue obtained by concentrating the reaction mixture under reduced pressure was suspended in aqueous solution of lithium hydroxide monohydrate (1 ml) (60.0 mg, 1.43 mol) and then dissolved by adding methanol (5 ml) and the solution was stirred for 2 hours at 50 ° C. IN hydrochloric acid was added to the obtained residue by concentrating the reaction mixture under reduced pressure to bring the pH value up to 2, which was again concentrated under reduced pressure. Water was added to the obtained residue, the crystals were collected by filtration, washed with water and with ethyl acetate in sequence, and then air dried to obtain 70.5 mg of the title compound as a yellowish brown powder. 51% yield. pf > 300 ° C. HR-BAR-: 507. 0902 (+ 0. Lp nu).

(Example 303) 7- (4- (Carboxymethyl) imidazolyl) -3,4-dihydro-6-nitro-3-oxoquinoxalin-2-carboxylic acid A solution of the compound of Example 139 (450 mg, 1.46 mol) and methyl imidazole-4-acetate (617 mg, 4.40 mmol) in acetonitrile (5 ml) was stirred for 15 hours at 110 ° C in a sealed tube. The reaction mixture was concentrated under reduced pressure and purified by column chromatography on silica gel. [methylene chloride]. This was dissolved in acetic acid-concentrated hydrochloric acid (5: 1, 3 ml) and allowed to settle statically overnight. The residue obtained by concentrating the reaction mixture under reduced pressure was dissolved in methanol, then aqueous solution of lithium hydroxide monohydrate (1 ml) (119 mg, 2.84 mmol) was added and the solution was allowed to stand statically overnight. 0.5N hydrochloric acid was added to the residue obtained by concentrating the reaction mixture under reduced pressure to acidify it, which was again concentrated under reduced pressure. Water was added to the obtained residue, the crystals were collected by filtration, washed with water and ethyl acetate in sequence, and then air dried to obtain 149 mg of the title compound as a reddish brown powder.

Yield of 27%. pf > 300 ° C.

Analysis calculated for C? 4H9N507. H20: C, 44.57; H, 2.94; N, 18.56. Found: C, 44.64; H, 3.11; N, 18.64. HR-BAR-: 358.0425 (+ 0.2mmu).

(Example 304) 3,4-Dihydro-7- (4- (hydroxymethyl) -imidazolyl) -6-nitro-3-oxoquinoxalin-2-carboxylic acid To the compound of Example 115 (200 mg, 405 μmol) was added aqueous solution of lithium hydroxide IN (5 ml), and the mixture was stirred for 2 hours at 80 ° C.

After cooling, the reaction mixture was acidified using concentrated hydrochloric acid and, after filtering the insoluble fractions, this was purified with Sepabeads SP850 'synthetic adsorbent [water-acetonitrile = 20: 1] to obtain 57.8 mg of the title compound as an orange powder. Performance of 43%. mp 240-242 ° C (dec.). HR-BAR-: 330.0458 (-1.7mmu).

S28J (Example 305) 3-Ethoxy-7- (3- ((N- (4-ethoxycarbonylphenyl) -carbamoyloxy) methyl) -4-pyridon-1-yl) -6-nitroquinoxaline-2-carboxylic acid ethyl ester To a solution of the compound of Example 120 (500 mg, 1.21 mol) in benzene (30 ml) was added ethyl 4-isocyanatobenzoate (463 mg, 2.42 mmol), and the mixture was refluxed 2 hours. After cooling, the precipitate was collected by filtration, washed with benzene and then air dried to obtain 692 mg of the title compound as a yellow powder. 94% yield. XH-NMR (CDC13, d): 1.37 (3H, t, J = 7.3Hz), 1.47 (3H, t, J = 7.3Hz), 1.54 (ΔH, t, J = 6.9Hz), 4.34 (2H, c , J = 7.3Hz), 4.55 (2H, c, J = 7.3Hz), 4.68 (2H, c, J = 6.9Hz), 5.15 (2H, s), 6.56 (ÍH, d, J = 7.8Hz), 7.39 (ÍH, dd, J = 7.8, 2.5Hz), 7.43 (2H, d, J = 8.8Hz), 7.71 (ÍH, d, J = 2.5Hz), 7.97 (2H, d, J = 8.8Hz), 8.22 (ÍH, s), 8.57 (ÍH, s).

% $% • (Example 306) 7- (3- ((N- (4-Ethoxycarbonylphenyl) -carbamoyloxy) methyl) -4-pyridon-1-yl) -3,4-dihydro-6-nitro-3-oxoquinoxalin-2-acid carboxylic To a solution of the compound of Example 305 (692 mg, 1.14 mmol) in acetic acid (12 ml) was added concentrated hydrochloric acid (3 ml), and the mixture was stirred for 18 hours at room temperature. Added Water was added to the reaction mixture and the precipitate was collected by filtration, washed with water and then air dried to obtain 548 mg of the title compound as a yellow powder. 86% yield. 15 * mp 201-203 ° C (decomposition). Analysis calculated for C25H? 9N5O? 0. 1 / 2H20: C, 53. 78; H, 3. 61; N, 12, 54. Found: C, 53.82; H, 3.69; N, 12.60. HR-BAR-: 548.1053 (-O.lmmu).

(Example 307) 7- (3- ((N- (4-carboxyphenyl) carbamoyloxy) methyl) -4-pyridon-1-yl) -3,4-dihydro-6-nitro-3-oxoquin-xalin-2 acid -carboxylic To a suspension of the compound of Example 306 (383 mg, 697 μmol) in water (4 ml) was added aqueous lithium hydroxide solution IN (6.97 ml, 6.97 mmol), and the mixture was stirred for 3 hours at room temperature. After the reaction mixture was purified with Sépabeads SP850 ® synthetic adsorbent [water: acetonitrile = 20: 1], water was added and the pH value was brought to 2 with concentrated hydrochloric acid. The precipitate was collected by filtration, washed with water and then dried with a re to obtain 253 mg of the title compound as a yellow powder. 65% yield. mp 231-233 ° C (decomposition). 2 * 9O Analysis calculated for C23H? 5N5O? O. 2H20: C, 4 9. 56; H, 3. 44; N, 12 56 Found: C, 49.32; H, 3.41; N, 12.47. HR-BAR-: 520.0740 (+ 0.0mmu).

(Example 308) 3-Ethoxy-7- ((4-hydroxymethyl) imidazol-1-yl) methyl-6-nitroquinoxaline-2-carboxylic acid ethyl ester 0 To a solution of ethyl 3-ethoxy-7-methyl-6-nitroquinoxaline-2-carboxylate (2.00 g, 6.55 mmol) in carbon tetrachloride (200 ml) was added N-bromosuccinimide (3.51 g, 19.7 mmol), then the reaction mixture was heated to 80 ° C. 2,2'-5-azobisisobutyronitrile (215 mg, 1.31 mmol) was added to the reaction mixture and the mixture was refluxed for 6 hours. After cooling, the insoluble fractions were filtered and the solvent was distilled. After dissolving the obtained residue in acetonitrile (50 ml), 4- (hydroxymethyl) imidazole hydrochloride (2.21 g, 16.4 g) was added. "- • &• mmol) and triethylamine (2.28 ml, 16.4 mmol) and the mixture was refluxed for 6 hours. The reaction mixture was distilled under reduced pressure and the residue obtained was purified by column chromatography on silica gel [ethyl acetate] to obtain 293 mg of the title compound as a yellowish white powder. Yield of 11%. ^ -RMN (CDC13, d): 1.44 (3H, t, J = 7.3Hz), 1.50 (3H, t, J = 7.3Hz), 4.51 (2H, c, J = 7.3Hz), 4.55 (2H, s ), 4.63 (2H, c, J = 7.3Hz), 5.77 (2H, s), 7.11 (IH, s), 7.41 (IH, s), 7.58 (IH, s), 8.63 (IH, s).

(Example 309) 3-Ethoxy-7- (4- ((N- (4-ethoxycarbonylphenyl) -carbamoyloxy) methyl) imidazolyl) methyl-6-nitroquinoxaline-2-carboxylic acid ethyl ester Using the compound of Example 308 (40.1 mg, 100 μmol) and following the same procedure as in Example 257, 49.2 mg of the title compound was obtained as a light brown powder. 83% yield. ^ -RN (CDC13, d): 1.39 (3H, t, J = 7.3Hz), 1435 (3H, t, J = 6.9Hz), 1.439 (3H, t, J = 7.3Hz), 4.35 (2H, c , J = 7.3Hz), 4.44 (2H, c, J = 6.9Hz), 4.49 (2H, c, J = 7.3Hz), 5.17 (2H, s), 5.76 (2H, s), 6.70-6.90 (ÍH , broad), 7.05 (2H, d, J = 8.3Hz), 7.31 (HH, s), 7.34 (HH, s), 7.70 (HH, s), 7.85 (2H, d, J = 8.8Hz), 8.47 (ÍH, s).

(Example 310) 3-Ethoxy-7- (4- ((N- (3-ethoxycarbonylphenyl) -carbamoyloxy) methyl) imidazolyl) methyl-6-nitroquinoxaline-2-carboxylic acid ethyl ester Using the compound of Example 308 (253 mg, 630 μmol) and following the same procedure as in Example 257, 314 mg of the title compound was obtained as a light brown powder. 84% yield. XH-NMR (DMSO-de, d): 1.32 (3H, t, J = 6.8Hz), 1.33 (3H, t, J = 7.3Hz), 1.35 (3H, t, J = 6.9Hz), 4.30 (2H , c, J = 6.8Hz), 4.37 (2H, c, J = 7.3Hz), 4.38 (2H, c, J = 6.9Hz), 5.20 (2H, s), 5.85 (2H, s), 6.88 (H) , s), 7.16-7.22 (2H, m), 7.25 (IH, s), 7.47 (IH, d, J = 6.9HZ), 7.57 (IH, s), 7.93 (IH, s), 8.29 (IH, s), 9.24 (ÍH, s).

(Example 311) 7- (4- ((N- (3-carboxyphenyl) carbamoyloxy) methyl) imidazolyl) methyl-3,4-dihydro-6-nitro-3-oxoquinoxaline-2-carboxylic acid To a solution of the compound of Example 310 (314 mg, 530 μmol) in acetic acid (4 ml) was added concentrated hydrochloric acid (1 ml), and the mixture was allowed to stand statically for 3 days at room temperature. Water was added to the reaction mixture, and the precipitate was collected by filtration, washed with water and then air dried. Aqueous sodium hydroxide solution IN (5.30 ml, 5.30 mmol) was added thereto and the mixture was stirred for 6 hours at room temperature. After filtering the insoluble fractions, the pH value was brought up to 2 with concentrated hydrochloric acid. The precipitate was collected by filtration, washed with water and then air dried to obtain 30.5 mg of the title compound as a yellowish brown powder. Yield of 11%. mp 229-231 ° C (decomposition). HR-BAR-: 507.0923 (+ 2.2mmu).

(Example 312) 3-Ethoxy-6-nitro-7- (3- ((phenylaminocarbonyl-amino) methyl) pyrrolidin-1-yl) quinoxaline-2-carboxylic acid ethyl ester 29"5 To a solution of the compound of Example 139 (1.00 g, 3.23 mmol) in acetonitrile (16 ml) was added 3- (aminomethyl) pyrrolidine (647 mg, 6.46 mmol), and the mixture was refluxed for 2 hours. The residue obtained by concentrating the reaction mixture under reduced pressure was purified by means of column chromatography on silica gel [methylene chloride-methanol = 20: 1] to obtain a dark red amorphous material. This was dissolved in methylene chloride (10 ml) and, after phenyl isocyanate (219 μl, 2.01 mmol) was added, the mixture was stirred for 2 hours at room temperature. The residue obtained by concentrating the reaction mixture was purified by means of column chromatography on silica gel [hexane-ethyl acetate = 1: 1] to obtain 401 mg of the title compound as a red powder. Performance of 24% XH-NMR (CDC13, d): 1.46 (3H, t, J = 6.9Hz), 1.47 (3H, t, J = 6.8Hz), 1.70-1.90 (HH, m), 2.00-2.20 (HH, m) , 2.50-2.70 (HH, m), 3.05-3.15 (HH, m), 3.20-3.50 (5H, m), 4.53 (2H, c, J = 6.9Hz), 4.54 (2H, c, J = 6.8Hz ), 5.10-5.30 (ÍH, broad), 6.60-6.70 (ÍH, broad), 7.00-7.10 (ÍH, m), 7.31 (4H, d, J = 4.4Hz), 7.38 (ÍH, s), 8.09 ( 1H, s).

(Example 313) 3, 4-Dihydro-6-nitro-3-oxo-7- (3- ((phenyl-aminocarbonylamino) methyl) pyrrolidin-1-yl) quinoxaline-2-carboxylic acid To a solution of the compound of Example 312 (401 mg, 789 μmol) in acetic acid (4 ml) was added concentrated hydrochloric acid (1 ml), and the mixture was stirred for 22 hours at room temperature. After the The reaction mixture was concentrated under reduced pressure, water (20 ml) was added and the pH value was brought to 9 using aqueous sodium hydroxide solution IN. This was washed with ethyl acetate and then the pH value was brought up to 2 with hydrochloric acid concentrate. The precipitate was collected by filtration, washed with water and then dried in air to obtain 42.0 mg of the title compound as a dark brown powder. Yield of 12%. pf > 300 ° C.

HR-BAR-: 451.1378 (+ 1.2mmu).

(Reference Example 1) Ethyl 3-Ethoxy-7-nitro-6-trifluoromethyl-2-carboxylate To a solution of 3, Ethyl 4-dihydro-3-oxo-6-trifluoromethyl-2-carboxylate (500 mg, 1.75 μmol) in concentrated sulfuric acid (5 ml) was added potassium nitrate (354 mg, 3.50 mmol) at 40 ° C, and the mixture was stirred for 3 hours at the same temperature. The reaction mixture was poured into ice water (100 ml), which was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled. Silver (I) oxide (811 mg, 3.50 mmol) was added to the obtained residue which was suspended in toluene (10 ml). Then, iodoethane (280 μL, 3.50 mmol) was added dropwise at 100 ° C and the mixture was refluxed for 2 hours. After cooling, the insoluble fractions were filtered using celite and the solvent was distilled. The obtained residue was subjected to silica gel column chromatography [hexane-ethyl acetate = 8:] to obtain 255 mg of the title compound as a yellowish-brown oily product. 41% yield. ^ -RMN (CDC13, d): 1.48 (3H, t, J = 7.3Hz), 1.53 (3H, t, J = 7.3Hz), 4.56 (2H, c, J = 7.3Hz), 4.68 (2H, d , J = 7.3Hz), 8.32 (ÍH, s), 8.67 (ÍH, s).

(Reference Example 2) 7-Amino-l, 2-dihydro-3-ethoxy-6-trifluoromethyl-quinoxaline-2-carboxylate ethyl To a solution of the compound of Reference Example 1 (4.98 g, 13.9 mmol) in ethanol (100 ml) was added 10% palladium on charcoal (500 mg), and the mixture was stirred for 3 hours at room temperature under an hydrogen. The catalyst was filtered using celite and then the solvent was distilled to obtain 4.01 g of the title compound as a yellow powder. 87% yield. XH-NMR (CDCl3, d): 1.25 (3H, t, J = 7.3Hz), 1.36 (3H, t, J = 7.3Hz), 3.98 (2H, broad), 4.18 (2H, c,? £ 9 J = 7.3Hz), 4.31-4.44 (2H, m), 4".49 (HH, d, J = 1.5Hz), 4.65 (HH, broad), 6.01 (HH, s), 7.18 (HH, s) .

(Reference Example 3) Ethyl 7-amino-3-oxo-l, 2,3,4-tetrahydro-6-trxfluoro-methylquinoxaline-2-carboxylate To a solution of the compound of Reference Example 2 (3.51 g, 10.6 mmol) in ethanol (35 ml) was added concentrated hydrochloric acid (7 ml), and the mixture was stirred for 20 hours at room temperature. After the solvent was distilled, water was added and the solution was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled to obtain 2.69 g of the title compound as a light brown powder. 84% yield. ^ -RMN (DMSO-d6, -): 1.16 (3H, t, J = 7.3Hz), 4.07-4.13 (2H, m), 4.53 (ÍH, d, J = 2.0Hz), 5.10 (2H, broad) , 6.18 (ÍH, s), 6.70 (ÍH, s), 7.04 (ÍH, d, J = 1.5Hz), 10.36 (ÍH, s). 300 (Reference Example 4) 5-Acetamido-2- ((4-hydroxymethyl) imidazol-1-yl) 4-nitrobenzotrifluoride To a solution of 5-acetamido-2-fluoro-4-nitrobenzotrifluoride (2.00 g, 7.51 mmol) in acetonitrile (40 ml) were added (4-hydroxymethyl) imidazole hydrochloride (5.07 g, 37.6 mmol) and triethylamine (10 ml. ), and the mixture was stirred for 24 hours at 120 ° C in a sealed tube. After cooling, ethyl acetate was added to the reaction mixture and washed with brine. It was then dried over anhydrous sodium sulfate and the solvent was distilled. The residue obtained was subjected to column chromatography on silica gel [methylene chloride-methanol (50: 1 20: 1)] to obtain 198 mg of the title compound as a pale yellow powder. 8% yield. XH-NMR (DMSO-de, d): 2.12 (3H, s), 4.41 (2H, d, J = 5.9Hz), 5.02 (H, t, J = 5.9Hz), 7.26 (H, s), 7.79 (ÍH, s), 8.13 (ÍH, S), 8.14 (ÍH, s), 10.69 (ÍH, s).

SOI (Reference Example 5) 5-Amino-2- ((4-hydroxymethyl) imidazol-1-yl) -4-nitrobenzotrifluoride To the compound of Reference Example 4 (17.0 mg, 59.2 μmol) was added 4N hydrochloric acid (1 ml), and the mixture was refluxed for 3 hours. The reaction mixture was concentrated under reduced pressure and the obtained residue was washed with water, then air dried to obtain 12.0 mg of the title compound as a yellow powder. 83% yield. XH-NMR (DMSO-de, d): 4.39 (2H, d, J = 5.4Hz), 4.96 (IH, t, J = 5.4Hz), 7.12 (IH, s), 7.60 (IH, s), 7.66 (2H, s), 7.95 (ÍH, s), 8.00 (ÍH, s).

(Reference Example 6) 4, 5-Diamino-2- ((4-hydroxymethyl) imidazol-1-yl) benzotri luoride To a solution of the compound of Reference Example 5 (220 mg, 728 μmol) in ethanol (5 ml ) palladium on charcoal 10% (20.0 mg) was added, and the mixture was stirred for 3 hours at room temperature under a hydrogen atmosphere. The catalyst was filtered and the solvent was distilled to obtain 200 mg of the title compound as a light orange powder. Quantitative performance. XH-NMR (DMS0-d6, d): 4.37 (2H, d, J = 5.9Hz), 4.89 (ΔH, t, J = 5.9Hz), 5.13 (2H, s), 5.42 (2H, s), 6.45. (ÍH, s), 6.87 (ÍH, s), 6.99 (ÍH, s), 7.52 (ÍH, s).

(Reference Example 7) Ethyl 3-Ethoxy-7-fluoro-6-methylthioquinoxaline-2-carboxylate To a solution of the compound of Example 139 (1.00 g, 3.23 mmol) in N, N-dimethylformamide (10 ml) was added sodium thiomethoxide (249 mg, 3.55 mmol) at room temperature, and the mixture was stirred for 8 hours at room temperature. 50 ° C. Water was added to the reaction mixture which was extracted with ethyl acetate. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue obtained was purified by means of column chromatography on silica gel [hexane-ethyl acetate = 4: 1] to obtain 450 mg of the title compound as a yellow powder. 45% yield. ^ -RMN (CDC13, d), 1.46 (3H, t, J = 6.9Hz), 1.49 (3H, t, J = 6.9Hz), 2.62 (3H, s), 4.51 (2H, c, J = 6.9Hz), 4. 57 (2H, c, J = 6.9Hz), 7.51 (HH, d, J = 7.3Hz), 7.68 (HH, d, J = 10.3Hz).

(Biological activity). * AMPA receptor binding experiment Crude synaptosome membrane preparations prepared from cerebral cortex of rats were added [3H] -AMPA (final concentration-5nM) which were selectively bound to the AMPA receptor, potassium thiocyanate (final concentration: 100mM) and the test compound, and the mixtures were incubated for 30 minutes at 0 ° C.

After the reactions were stopped by suction filtration, the radioactivity on the filter was measured with a flashing counter in the liquid state. The specific binding of [3 H] -AMPA was determined by subtracting the level of non-specific binding in the presence of glutamic acid (0.1 mM) from the range of the binding level. The [3 H] -AMPA linkage was placed in the absence of test compound 100, the concentration of the compound decreased by 50% (IC50 value) was determined and converted to Ki values to calculate the binding capacity of each compound to the AMPA receptor. (Eur. J. Pharmacol., 1993, 246, 195-204).

Table 19 Activity table -A Compound of rH] -AMPA Ki: nM) test Example 5 Cl 1260 Example 6 2010 3 ^ 5 Table 19 Activity table -A (continued) Example 7 Br 630 Example 8 CH. 330 Example 35 2040 \ Example 36 450 ^ - Example 37 330 Example 38 Me2N- 910 Example 62 860 Example 66 rv 360 Activity table -B Test compound Y U W rH] -AMPA Ki: nM) Example 79 CH NH 4 - C02H - Ph 37.3 Example 80 CH NH 2 - F - 4 - C02H - Ph 11.8 Example 83 N 0 4 - C02H - Ph 15.8 Activity table -C Test compound Y U w [JH] -AMPA Ki nM) Example 88 N 0 Ph 86.2 Example 96 N 0 2 - F- Ph 28.2 Example 101 N 0 2 - CF3 - Ph 32.2 Example 115 N 0 4 - C02H - Ph 21.6 Example 116 N 0 3 - C02H - Ph 27.3 Example 119 N NH 4 - C02H - Ph 28.2 Activity Table - D Test compound Y U W (JH) -AMPA Ki: nM) Example 121 N 0 pH 172 Example 123 N 0 2 - Br- Ph 48.1 Utility in the industry From the previous results, the acid derivatives asymmetrically disubstituted quinoxalincarboxyls at positions 6, 7 of the invention are novel compounds with excellent antagonism against the AMPA receptor of the excitable amino acid receptors, in particular, the non-NMDA receptor. Since those compounds of the invention inhibit the excitable amino acid bridge, which causes the death of nerve cells, to the AMPA receptor, they are effective for the therapy of brain nerve cell disorder, etc., because such an excitable amino acid, and compounds which express the same effects as the drugs with antagonism against the NMSA receptor may also be useful. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims

RE IVINDffCACXONE S Having described the invention as above, the content of the following claims is claimed as property:

1. Quinoxalincarboxylic acid derivatives substituted asymmetrically at positions 6,7, represented by a general formula (1) [characterized in that, Q denotes a halogen atom, a lower alkyl group, which may be substituted with a halogen atom, of general formula (2) Ar-P (2) (where Ar denotes a phenyl group, which may having one or more substituents or naphthyl group, and P denotes a lower alkylene, lower alkenylene, lower alkynylene, oxygen or sulfur atom), general formula (3) LA- (3) | 09 (where L denotes a general formula (4) (where V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle) , hydrogen atoms, hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group, aldehyde group, the general formula (4-a) or the general formula (4-b) (where U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring ( may have one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its condensed ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group), or general formula (4-c) ) (where X denotes an oxygen atom or sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle) , lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, 5- or 6-membered heterocycles and their fused rings ( may have one or more substituents on aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups), ring B denotes a saturated or unsaturated heterocycle and its fused ring (these may have one or more substituents on the heterocycle or its fused ring), which additionally may contain one or two oxygen, nitrogen atoms or sulfur, and m denotes 0 or 1, A denotes a single bond, lower alkylene, lower alkenylene or lower alkynylene, or the general formula (5) (where R6 and R7 denote identical or different hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom, cycloalkyl groups, phenyl groups, which may have one or more substituents or aralkyl groups, which may have one or more substituents); R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, R 2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycle), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote a hydrogen atom, while the other denotes a phenyloxy group or aralkyloxy group (those may have one or more substituents on the aromatic ring), hydroxyl group or lower alkoxy group), and R denotes a nitro group , trifluoromethyl group, amino group, which may be substituted, or the general formula (7) (wherein R10 and R11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, alkyl groups lower, which may be substituted with a halogen atom or cycloalkyl groups, or R10 and R11 may form a ring (which may additionally contain one or two heteroatoms) together with the hydrogen atom, and n denotes 1 to 2)] , and its addition salts.

2. Derivatives of asymmetrically disubstituted quinoxalinecarboxylic acid at positions 6, 7, represented by a general formula (1) [characterized in that, Q denotes a halogen atom, a lower alkyl group, which may be "-substituted with a halogen atom, the general formula (2) Ar-P (2) (where Ar denotes a phenyl group or naphthyl group, which may have one or more substituents, and P denotes a lower alkylene, lower alkenylene, lower alkynylene, oxygen or sulfur atom), the general formula (5) (where R6 and R7 denote identical or different hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom, cycloalkyl groups, phenyl groups, which may have one or more substituents or aralkyl groups, which may have one or more substituents); R denotes a nitro group, trifluoromethyl group, amino group, which may be substituted, or the general formula (7) (wherein R10 and R11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R10 and R11 may form a ring (which may additionally contain one or two heteroatoms) together with the hydrogen atom, and n denotes 1 to 2), R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), a hydrogen atom, a lower alkyl group, which may to be substituted with a halogen atom or cycloalkyl group, and R2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R8 and R9 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote an atom of hydrogen, while the other denotes a phenyloxy group or aralkyloxy group (those may have one or more substituents on the aromatic ring), hydroxyl group or lower alkoxy group], and their addition salts.

3. Quinoxalincarboxylic acid derivatives distributed asymmetrically at positions 6,7, represented by a general formula (1-a) (characterized by, L denotes a general formula (4; (where V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on an aromatic ring or heterocycle) , hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group, aldehyde group, general formula (4-a) or the general formula (4-b) (where U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring ( may have one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes a group 3? 8 aralkyl, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with one atom of halogen or cycloalkyl group), or general formula (4-c) (where X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle ), lower alkyl group, which may be substituted with a halogen atom or a cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, 5- or 6-membered heterocycles and their fused rings (those may have one or more substituents on aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups), ring B denotes a saturated or unsaturated heterocycle and its Condensed ring (those may have one or more substituents on the heterocycle or its fused ring), which additionally may contain one or two oxygen atoms, geno or sulfur, and m denotes 0 or 1), A denotes a single bond, lower alkylene or lower alkenylene, R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents 10 on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the rings Aromatics or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote a hydrogen atom, while the other denotes a phenyloxy group or aralkyloxy group (those may have one or more substituents on the aromatic ring), a hydroxyl group or lower alkoxy group)] , and its addition salts.

4. Asymmetrically substituted quinoxalinecarboxylic acid derivatives at positions 6, 7, represented by a general formula (1-b) [characterized because, L denotes a general formula (4) (where V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on an aromatic ring or heterocycle) , hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group or aldehyde group, the general formula (4-a) or the general formula (4-b) (where U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring ( may have one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its condensed ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group), or general formula (4-c) ) (where X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle ), lower alkyl group, which may be substituted with a halogen atom or a cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, 5- or 6-membered heterocycles and their fused rings (those may have one or more substituents on aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups), ring B denotes a saturated or unsaturated heterocycle and its condensed ring (those may have one or more substituents on the heterocycle or fused ring), which additionally may contain one or two oxygen atoms, nitróg eno or sulfur, and m denotes 0 or 1), A denotes a single bond, lower alkylene or lower alkenylene, R denotes a nitro group, a trifluoromethyl group, amino group, which may be substituted, or the general formula (7) (wherein R1G and R11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R10 and R11 may form a ring (which may additionally contain one or two heteroatoms) together with the hydrogen atom, and n denotes 1 to 2), R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, ipferior alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring ("which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote a hydrogen atom, while the other denotes a phenyloxy group or an aralkyloxy group (those may have one or more substituents on the aromatic ring), a hydroxyl group or lower alkoxy group], and their addition salts.

5. Quinoxalincarboxylic acid derivatives substituted asymmetrically in positions 6,7, represented by a general formula (8) [characterized in that V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- to 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle ), hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group or aldehyde group, the general formula (4-a) or the general formula (4-b) (wherein U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, heterocycle of 5 or 6 members and their condensed ring (those may have one or more substituents on the aromatic ring or heterocycle) lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes an aralkyl group, phenyl group, group naphthyl, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group) , or general formula (4-c) (where X denotes an oxygen atom or sulfur atom, denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, 5- or 6-membered heterocycles and their fused rings (these may be having one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups); A denotes a single bond, lower alkylene or lower alkenylene, R denotes a nitro group, trifluoromethyl group, amino group, which may be substituted, or the general formula (7) (wherein R10 and R11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which can be substituted with $ ^ 8 a halogen atom or cycloalkyl groups, or R10 and R11 can form a ring (which may additionally contain one or two heteroatoms) together with the hydrogen atom, and n denotes 1 to 2), and denotes a nitrogen atom or = CH-, R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, R 2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote a hydrogen atom, while the other denotes a phenyloxy group or aralkyloxy group (those may have one or more substituents on the aromatic ring), hydroxyl group or lower alkoxy group], and their addition salts.

6. The quinoxalincarboxylic acid derivatives substituted asymmetrically at positions 6,7, according to claim 5, represented by a general formula (8) [characterized in that V denotes a single bond or lower alkylene, A denotes a single bond or lower alkylene, Y denotes a nitrogen atom or = CH-, R denotes a nitro group, trifluoromethyl group or amino group, which may be substituted, R1 denotes a hydrogen atom, and R2 denotes a hydroxyl group, lower alkoxy group], and their addition salts.

7. The quinoxalincarboxylic acid derivatives substituted asymmetrically at positions 6,7, according to claim 1, represented by a general formula (8) [characterized in that V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- to 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle ), hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbopyl group, carboxyl group or aldehyde group, the general formula (4-a), or the general formula (4-b) (wherein U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group), or general formula (4-c) (where X denotes an oxygen atom or sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 5-membered heterocycle and its fused ring (these may have one or more substituents 832). on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, heterocycles of 5 or 6 members and their condensed rings (those may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups); A denotes a single bond, lower alkylene or lower alkenylene, R denotes a nitro group, trifluoromethyl group, amino group, which may be substituted, or the general formula (7) (where R, 10 and R, 11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms , lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups, or R 10 and R 11 can form a ring (which may additionally contain one or two heteroatoms) together with the hydrogen atom, and n denotes 1 to 2), R 1 denotes an aralkyl group, phenyl group , naphthyl group, 5 or 6 membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or group cycloalkyl, R2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with an "$ 3" atom nitrogen, or any of R8 and R9 denote a hydrogen atom, while the other denotes a phenyloxy group or aralkyloxy group (those may have one or more substituents on the aromatic ring), hydroxyl group or lower alkoxy group), and their addition salts.

8. The quinoxalincarboxylic acid derivatives substituted asymmetrically at positions 6, 7, according to claim 7, represented by a general formula (9) [characterized in that V denotes a single bond or lower alkylene, A denotes a single bond or lower alkenyl, R denotes a nitro group, trifluoromethyl group or amino group, which may be substituted, R1 denotes a hydrogen atom, and R2 denotes a hydroxyl group, lower alkoxy group], and their addition salts.

9. The quinoxalincarboxylic acid derivatives substituted asymmetrically at positions 6,7, according to claim 1, characterized in that the compound is 7- (3- (((4-carboxyphenyl) aminocarbonylamino) -methyl) pyrrole-1- il) -3,4-dihydro-3-oxo-6-trifluoro-methyl-quinaxolin-2-carboxylic acid, and its addition salt.

10. The quinoxalincarboxylic acid derivatives substituted asymmetrically at positions 6, 7, according to claim 1, characterized in that the compound is 7- (4 - (((4-carboxyphenyl) aminocarbonylamino) methyl) imidazol- -il) 3, 4-dihydro-3-oxo-6-trifluoromethyl-quinoline-2-carboxylic acid, and its addition salt.

11. The quinoxalincarboxylic acid derivatives substituted asymmetrically at positions 6, 7, according to claim 1, characterized in that the compound is 7- (4 - ((N- (4-carboxyphenyl) carbamoyloxy) methyl) imidazole-1 acid -yl) -3,4-dihydro-3-oxo-6-trifluoromethyl-quinoxaline-2-carboxylic acid, and its addition salt.

12. The quinoxalincarboxylic acid derivatives substituted asymmetrically at positions 6, 7, according to claim 1, characterized in that the compound is 7- (4 - ((N- (4-carboxyphenyl) carbamoyloxy) methyl) imidazolyl) - 3, -dihydro- 136 6-Nitro-3-oxoquinoxaline-2-carboxylic acid, and its addition salt.

13. Synthetic intermediates for the preparation of asymmetrically substituted quinoxalincarboxylic acid derivatives at positions 6, 7, in accordance with claim 1, represented by the general formula (10) [characterized in that, Q denotes a halogen atom, a lower alkyl group, which may be substituted with a halogen atom, of general formula (2) Ar-P (2) (where Ar denotes a phenyl group, which may be having one or more substituents or naphthyl group, and P denotes a lower alkylene, lower alkenylene, lower alkynylene, oxygen or sulfur atom), general formula (3) LA- (3) (where L denotes a general formula (4) ( where V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- to 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle), hydrogen atoms, hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group, aldehyde group, the general formula (4-a) or the general formula (4-b) (where U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its ring 3 $ 8 condensate (those may have one or more substituents on the aromatic ring or heterocycle) lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes an aralkyl group, phenyl group, naphthyl group, heterocycle of 5 or 6 members and their condensed ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group), or general formula (4) -c) (where X denotes an oxygen atom or sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 5-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle) , lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, 5- or 6-membered heterocycles and their fused rings ( may have one or more substituents on aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups), ring B denotes a saturated or unsaturated heterocycle and its fused ring (those may have one or more substituents on the heterocycle or fused ring), which additionally may contain one or two oxygen, nitrogen or sulfur, and m denotes 0 or 1, A denotes a single bond, lower alkylene or lower alkenylene), or the general formula (5) (where R6 and R7 denote identical or different hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom, cycloalkyl groups, phenyl groups, which may have one or more substituents or aralkyl groups, which may have one or more substituents); R denotes a nitro group, trifluoromethyl group, amino group, which may be substituted, or general formula (7) (wherein R 10 and R 11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and its condensed rings (those may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups, or R10 and R11 may form a ring ( which may additionally contain one or two heteroatoms) together with the hydrogen atom, and n denotes 1 to 2), R2 denotes a hydroxyl group, lower alkoxy group, the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote an atom of hydrogen, while the other denotes a phenyloxy group or aralkyloxy group (those may have one or more substituents on the aromatic ring), hydroxyl group or lower alkoxy group), and R12 denotes a lower alkyl group, which may be substituted with a halogen atom or aralkyl group, which may have one or more substituents].

14. Synthetic intermediates for the preparation of asymmetrically substituted quinoxalincarboxylic acid derivatives at positions 6,7, and their acid addition salts, according to claim 1, represented by the general formula (11) [characterized in that, Q denotes a halogen atom, a lower alkyl group, which may be 3 * 2 substituted with a halogen atom, of general formula (2) Ar-P (2) (where Ar denotes a phenyl group, which may have one or more substituents or naphthyl group, and P denotes a lower alkylene, lower alkenylene, alkynylene lower, oxygen or sulfur atom), general formula (3) LA- (3) (where L denotes a general formula (4) (where V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- to 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle) , hydrogen atoms, hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group, aldehyde group, the general formula (4-a) or the general formula (4-b) (where U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring ( may have one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its condensed ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group), or general formula (4-c) ) 4% (where X denotes an oxygen atom or sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 5-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle) , lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, 5- or 6-membered heterocycles and their fused rings ( may have one or more substituents on aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups), ring B denotes a saturated or unsaturated heterocycle and its fused ring (those may have one or more substituents on the heterocycle or fused ring), which additionally may contain one or two oxygen, nitrogen or sugar atoms ufre, and m denotes 0 or 1, A denotes a single bond, lower alkylene, lower alkenylene or lower alkynylene), ty &-0f or the general formula (5) (where R6 and R7 denote identical or different hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl group, phenyl groups, which may have one or more substituents or aralkyl groups, which may have one or more substituents); R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, R2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may * t ^ 46 having one or more substituents on the aromatic rings or heterocycle), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote a hydrogen atom, while the other denotes a phenyloxy group or aralkyloxy group (these may have one or more substituents on the aromatic ring), hydroxyl group or lower alkoxy group), and R denotes a nitro group, trifluoromethyl group, amino group, which may be substituted, or the general formula (7) (wherein R10 and R11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R10 and R11 they can form a ring (which can additionally contain one or two heteroatoms) together with the hydrogen atom, and n denotes 1 to 2)].

15. An antagonist against excitatory amino acid receptors with antagonism against the AMPA receptor, characterized in that it contains one or more classes of asymmetrically substituted quinoxalincarboxylic acid derivatives at positions 6, 7, represented by a general formula (1) [characterized park, Q denotes a halogen atom, a lower alkyl group, which may be substituted with a halogen atom, of general formula (2) Ar-P (2) (where Ar denotes a phenyl group or a group naphthyl, which may have one or more substituents and P denotes a lower alkylene, lower alkenylene, lower alkynylene, oxygen or sulfur atom), general formula (3) LA- (3) (where L denotes a general formula (4 ) (where V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- to 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle) , hydrogen atoms, hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group, aldehyde group, the general formula (4-a) or the general formula (4-b) (where U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may having one or more substituents on the aromatic ring or heterocycle) lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its condensed ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group), or general formula (4-c) (where X denotes an oxygen atom or sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 5-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle) , lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, 5- or 6-membered heterocycles and their fused rings ( may have one or more substituents on aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups), ring B denotes a saturated or unsaturated heterocycle and its fused ring (those may have one or more substituents on the heterocycle or fused ring), which additionally may contain one or two oxygen, nitrogen or nitrogen atoms. sulfur, and m denotes 0 or 1, A denotes a single bond, lower alkylene, lower alkenylene or lower alkynylene, or the general formula (5) (where R6 and R7 denote identical or different hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom, cycloalkyl groups,) phenyl groups, which may have one or more substituents or aralkyl groups, which may have one or more substituents; R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, R 2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) (where R and R denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycle), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote an atom of hydrogen, while the other denotes a phenyloxy group or aralkyloxy group (those may have one or more substituents on the aromatic ring), hydroxyl group or lower alkoxy group), and R denotes a nitro group, trifluoromethyl group, amino group, which may be substituted, or the general formula (7) (where R10 and R11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their ani the condensed (those may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups, or R10 and R11 may form a ring (the which may additionally contain one or two heteroatoms) together with the hydrogen atom, and n denotes 1 to 2), and their addition salts as effective ingredients.

16. An antagonist against the excitatory amino acid receptors with antagonism against the AMPA receptor, characterized in that it contains one or more classes of asymmetrically substituted quinoxalincarboxylic acid derivatives at positions 6, 7, represented by a general formula (1) [characterized in that Q - denotes a halogen atom, a lower alkyl group, which may be substituted with a halogen atom, the general formula (2) Ar-P (2) (where Ar denotes a phenyl group, which may have one or more substituents or naphthyl group, and P denotes a lower alkylene, lower alkenylene, lower alkynylene, oxygen or sulfur atom), or the general formula (5) (where R6 and R7 denote identical or different hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl group, phenyl groups, which may have one or more substituents or aralkyl groups, which may have one or more substituents); Yes 3 * 54 R denotes a nitro group, trifluoromethyl group, amino group, which may be substituted, or the general formula (7) (wherein R10 and R11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R10 and R11 may form a ring (which may additionally contain one or two heteroatoms) together with the nitrogen atom, and n denotes 1 to 2), R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), a hydrogen atom, a lower alkyl group, which may to be substituted with a halogen atom or cycloalkyl group, and R2 denotes a hydroxy group, lower alkoxy group, or the general formula (6) 35 * (where R8 and R9 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote an atom of hydrogen, while the other denotes a phenyloxy group or aralkyloxy group (those may have one or more substituents on the aromatic ring), hydroxyl group or lower alkoxy group], and their addition salts as effective ingredients.

17. An antagonist against excitatory amino acid receptors with antagonism against the AMPA receptor, characterized in that it contains one or more classes of asymmetrically substituted quinoxalincarboxylic acid derivatives at positions 6, 7, represented by a general formula (1-a) xz. x- (characterized because, L- denotes a general formula (4 (where V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on an aromatic ring or Heterocycle), hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group, aldehyde group, the general formula (4-a) 15 or the general formula (4-b) - Á - z. fc3S7 (where U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may having one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its condensed ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group), or general formula (4-c) (where X denotes an oxygen atom or a sulfur atom, denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents -en¬ on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or a cycloalkyl group, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, heterocycles of 5 or 6 members and their condensed rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups), ring B denotes a saturated or unsaturated heterocycle and its fused ring (these may have one or more substituents on the heterocycle or ring condensed), which additionally may contain one or two oxygen, nitrogen or sulfur atoms, and m denotes 0 or 1), A denotes a single bond, lower alkylene or lower alkenylene, R1 denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R2 denotes a hydroxyl group, lower alkoxy group, or the general formula (6) ^% 59 (wherein R8 and R9 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, alkyl groups lower, which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or any of R8 and R9 denote a hydrogen atom, while the other denotes a phenyloxy group or aralkyloxy group (those may have one or more substituents on the aromatic ring), a hydroxyl group or lower alkoxy group], and their addition salts as effective ingredients.

18. An antagonist against the excitatory amino acid receptors with antagonism against the AMPA receptor, characterized in that it contains one or more classes of quinoxalincarboxylic acid derivatives substituted asymmetrically in the 6,7 positions, represented by a general formula (1-b) (characterized because, L- denotes a general formula (4) (where V denotes a single bond, lower alkylene or lower alkenylene, T denotes a phenyl group, a naphthyl group, a 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on an aromatic ring or Heterocycle), hydroxyl group, thiol group, amino group, which may be substituted, lower alkoxycarbonyl group, carboxyl group or aldehyde group, the general formula (4-a) 15 or the general formula (4-b) - -z x • s s¿f ^? * ^ S ^^^^^^^^ (where U denotes an oxygen atom or a sulfur atom, X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring ( may have one or more substituents on the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group and R3 denotes a group Aralkyl, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its fused ring (these may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or 15 cycloalkyl group), or general formula (4-c) (where X denotes an oxygen atom or a sulfur atom, W denotes an aralkyl group, phenyl group, naphthyl group, 5- or 6-membered heterocycle and its ring 20 condensate (those may have one or more substituents. * < R-85 gfc., -,., On the aromatic ring or heterocycle), lower alkyl group, which may be substituted with a halogen atom or a group cycloalkyl, and R4 and R5 denote identical or different aralkyl groups, phenyl groups, naphthyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms , lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups), ring B denotes a saturated or unsaturated heterocycle and its fused ring (those may have one or more substituents on the heterocycle or fused ring), which additionally may contain one or two oxygen, nitrogen or sulfur atoms, and m denotes 0 or 1, A denotes a single bond, lower alkylene or lower alkenylene, R denotes a nitro group ro, trifluoromethyl group, amino group, which may be substituted, or the general formula (7) *** ¡f * '• * ^ «*" ?. " (wherein R10 and R11 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may have one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups , which may be substituted with a halogen atom or cycloalkyl groups, or R 10 and R 11 can form a ring (which may additionally contain one or two heteroatoms) together with the hydrogen atom, and n denotes 1 to 2), R 1 denotes an aralkyl group, phenyl group, naphthyl group, heterocycle or 6 members and their condensed ring (those may have one or more substituents on the aromatic ring or heterocycle), hydrogen atom, lower alkyl group, which may be substituted with a halogen atom or cycloalkyl group, and R2 denotes a group hydroxyl, lower alkoxy group, or the general formula (6) (where R and R9 denote identical or different aralkyl groups, phenyl groups, 5- or 6-membered heterocycles and their fused rings (these may 3 ? having one or more substituents on the aromatic rings or heterocycles), hydrogen atoms, lower alkyl groups, which may be substituted with a halogen atom or cycloalkyl groups, or R8 and R9 may form a ring (which may additionally contain one or two heteroatoms) together with a nitrogen atom, or either of R8 and R9 denote a hydrogen atom, while the other denotes a phenyloxy group or an aralkyloxy group (those may have one or more substituents on the aromatic ring), a hydroxyl group or lower alkoxy group)], and their addition salts as effective ingredients. SUMMARY OF THE INVENTION Excitatory amino acid receptors comprising as the active ingredient asymmetrically substituted quinoxalincarboxylic acids at positions 6, 7 or addition salts thereof, particularly compounds that exhibit antagonism against AMPA receptors; and processes for the preparation of both. The disubstituted quinoxalinecarboxylic acid derivatives are represented by the formula (1) wherein Q is halogen, optionally halogenated lower alkyl, Ar-P (where Ar is phenyl optionally substituted with one or more substituent groups, or naphthyl, and P is lower alkylene, lower alkenylene, lower alkynylene, oxygen or sulfur) or LA-; R is nitro, trifluoromethyl, optionally substituted amino or a group of the general formula (7), R1 is aralkyl, phenyl, naphthyl, a 5- or 6-membered heterocycle or a fused ring thereof (which may have one or more substituent groups on the aromatic ring or the heterocycle), hydrogen, alkyl or optionally halogenated lower cycloalkyl; and R2 is hydroxy, lower alkoxy or a group of the general formula (6).