NZ270088A

NZ270088A - Antiviral medicaments containing a quinoxaline and a nucleoside derivative

Info

Publication number: NZ270088A
Application number: NZ270088A
Authority: NZ
Inventors: Christoph Meichsner; Gunther Riess; Jorg-Peter Kleim; Manfred Rosner; Arno Paessens; Martin Blunck
Original assignee: Hoechst Ag
Priority date: 1993-12-09
Filing date: 1994-12-07
Publication date: 1998-04-27
Also published as: CN1108935A; EP0657166A1; ZA949785B; DE59410271D1; HUT70037A; IL111909A0; KR950016754A; AU697486B2; ATE236642T1; AU8042194A; CA2137605A1; HU221498B; HU9403518D0; EP0657166B1; DE4342024A1; JPH07196511A

Abstract

A combination product containing at least one nucleoside and a compound of the formulae I and/or Ia, <IMAGE> or the physiologically tolerated salts thereof, where the symbols X and n, and the substituents R<1>-R<5>, have the stated meanings, display antiviral activity.

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £70088 New Zealand No. International No. 270088 PCT/ TO BE ENTERED AFTER ACCEPTANCE AND PUBLICATION Priority dates: 09.12.1993; Complete Specification Filed: 07.12.1994 Classification:^) A61K31/495.70 Publication date: 27 April 1998 Journal No.: 1427 Title of Invention: Combination preparations comprising a quinoxaline and a nucleoside Name, address and nationality of applicant(s) as in international application form: HOECHST AKTIENGESELLSCHAFT, a German joint stock company of D-65926 Frankfurt am Main, Federal Republic of Germany NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION Patents Form 5 N.Z. No. NEW ZEALAND Patents Act 1953 COMPLETE SPECIFICATION COMBINATIONS PREPARATION COMPRISING A OUINOXALINE AND A NUCLEOSIDE We, HOECHST AKTIENGESELLSCHAFT, a Joint Stock Company existing under the laws of the Federal Republic of Germany, of D-65926 Frankfurt am Main, Federal Republic of Germany, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- N.Z. PATENT OFFiCE -7 DEC 1994 1 RECEIVED - 1 - (Followed by 1A) -IA- hoechst aktiengesellschaft ofjjb. yj/'t1 4U1 Bmt WIT Am Description Combination preparations comprising a quinoxaline and a 5 nucleoside The present invention relates to combination preparations comprising at least one quinozaline and at least one nucleoside. Quinoxalines are a well-known class of compound 10 (O. Hinsberg, J. Liebigs Ann. Chem. 237, 327 (1986)). Quinoxaline derivatives have been described in the petent literature for use in various applications in medicine. Austrian Patent 284,848 (19.12.67) mentions 1-N-dialkyl-aminoalkyl-3,4-dihydroquinoxalin-2(lH)-ones as spasmo-15 lytic agents. A series of patent applications by the Japanese company Sumitomo Chem. Co. Ltd. describe 4-N-aroyl-, arylacyl- and arylsulfonyl-3,4-dihydro-quinoxalin-2(lH)-ones which have an antiinflammatory action (JA 17,137/69 (11.4.66), JA 17,136/69 (8.4.66), 20 JA 7,008/422 (9.8.66), BE 706,623 (16.11.66)). 3,4-Dihydroquinoxalin-2(1H)-one-3-carboxamides are contained in US Patent US 3,654,275 (4.4.72). They, too, have an antiinflammatory action. In US Applications US 4,203,987 (21.5.79) and 4,032,639 (22.3.76), pyridinyl-25 alkyltetrahydropyrazino[l,2-a]quinoxalinone derivatives are described by American Home Prod. Corp. as antihypertensive and antisecretory reagents. A European Patent Application by Pfizer Inc. (EP 266,102 A (30.10.86)) includes 4-N-benzenesulfonyl-3,4-dihydroguinoxalin-30 2(1H)-one-l-alkylcarboxylic acids as aldose reductase inhibitors. However, an antiviral activity has not been demonstrated to date. A further document relating to quinoxalines is EP 0 509 398, to which reference is expressly made at 35 this point. Surprisingly, it has now been found that quinoxalines of the formulae I and la R2 and physiologically acceptcible salts or prodrugs thereof in combinaton with at least one nucleoside have an antiviral action, in particular against retroviruses, for example against the human immunodeficiency virus (HIV). In the compounds of the formula I or la according to the invention, 1) n is zero, one, two, three or four, the individual substituents R1 independently of one another are fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, hydroxyl, C1-Cfl-alkyl, C5-C8-cycloalkyl, Ci-Cg-alkoxy, (C1-C6-alkoxy)-(C1-C4-alkoxy), C1-C6-alkylthio, Cj-Cg-alkylsulfinyl, Ci-Cg-alkylsulfonyl, nitro, amino, azido, Cj-Cg-alkyl- amino, difCj-Ce-alkyl) amino, piperidino, morpholino, 1-pyrrolidinyl, 4-methylpiperazinyl, thiomorpholino, imidazolyl, triazolyl, tetrazolyl, C^-Ce-acyl, Ci-Ce-acyloxy, C^-Ce-acylamino, cyano, carbamoyl, carboxyl, (C1-C6-alkyl) oxycarbonyl, hydroxysulf onyl, sulfamoyl or a phenyl, phenoxy, phenoxycarbonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy, anilinosulfonyl, phenylsulfonyl-amino, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical which is substituted by up to five radicals R6 which are independent of one another, ' where R6 can be fluorine, chlorine, bromine, iodine, cyano, tri-fluoromethyl, trifluoromethoxy, nitro, amino, azido, Ci-Ce-alkyl, C3-C8-cycloalkyl, Cx-Ce-alkoxy, C1-C6-alkylthio, C^-Ce-alkylsulf inyl, Cj-Ce-alkyl-sulfonyl, Cj-Ce-alkyleunino, di(C1-C6-alkyl) amino, (Ci-Cg-alkyl)oxycarbonyl, phenyl, phenoxy, 2-, 3- or 4-pyridyl, R2 and R5 are identical or different and, independently of one another, are hydrogen, hydroxy1, Cj-Cg-alkoxy, aryloxy, Ci-Ce-acyloxy, cyano, amino, Cj-Ce-alkylamino, difCi-Ce-alkyl) amino, arylamino, Ci-Ce-acylamino, Ci-Ce-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino mercapto, hydroxyl, Ci-Ce-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-Ce-alkoxy, Ci-Ce-alkylamino, di^-Ce-alkyl) amino, C^-Ce-alkylthio, Ci-CB-alkyl-sulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; ' A ^ vQfjQ - 4 - C2-C8-alkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy1, Cj-Cg-acyloxy, benzoyloxy, 5 benzyloxy, phenoxy, Ci-Cg-alkoxy, Ci-CB-alkylaminfo, diCCi-Cg-alkyl) amino, Ci-CV-alkylthio, Cj-Co-alkyl-sulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl and carbamoy1; C3-Ca-allenyl, optionally substituted by fluorine, 10 chlorine or hydroxyl, C1-CA-alkoxy, oxo, phenyl; C3-CB-alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, 15 mercapto, hydroxyl, Cj-Cg-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-Cg-alkoxy, Cx-Cg-alkylamino, diJCj-Cg-alkyl) amino, Ci-Cg-alkylthio, Cx-Ce-alkyl-sulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl. or carbamoyl; 20 C3-C8-cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Ci-Cg-acyloxy, benzoyloxy, benzyloxy, phenoxy, Ci-Ce-alkoxy, C^-Cg-alkylamino, 25 di^-Cg-alkyl) amino, (^-Cg-alkylthio, Ci-Cs-alkyl- sulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C3-C8-cycloalkenyl, optionally substituted by 30 fluorine, chlorine, bromine, iodine, cyano> amino, mercapto, hydroxyl, C^-Cg-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-Cg-alkoxy, C^-C6-alkylamino, di (Ci-Cg-alkyl) amino, Ci-Cg-alkylthio, Ci-^a-alkyl-sulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or 35 carbamoyl; (C3-C8-cycloalkyl) - (Ci-C^-alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amiho, mercapto, hydroxyl, C1-C8-acyloxy, benzoyloxy, benzyloxy, phenoxy, Ci-Ce-alkoxy, C^-CB-alkylaminlfri ditCi-Cg-alkyl) amino, Ci-Cg-alkylthio, Ci-CB-alkyl-sulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; (C3-C8-cycloalkenyl) - (Cj-C^-alkyl), . optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amin&>, mercapto, hydroxyl, Ci-Ce-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-Cg-alkoxy, C^Ce-alkylamiriS, di(Cj-C6-alkyl) amino, Ci-Cg-alkylthio, Ci-CB-alkyE-sulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C^-Cg-alkylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, aminti, mercapto, hydroxyl, Ci-Cg-acyloxy, benzoyloxy-* benzyloxy, phenoxy, C^Cg-alkoxy, Ci-Cg-alkylamino ,• di (Cj-Cg-alkyl) amino, C^Cg-alkylthio, Ci-Ce-alkyiJ/-sulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C2-C8-alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Ci-C^-alkoxy, oxo, phenyl; (C3-C8-cycloalkyl)carbonyl, optionally substituted -B? fluorine, chlorine or hydroxyl, C^-C^-alkoxy, oxo-, phenyl; (C5-C8-cycloalkenyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, C^-C^-alkoxy, oxa, phenyl; (C3-C8-cycloalkyl) - (C^-Ca-alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, C^-C^-alkoxy, oxo, phenyl; (C5-C6-cycloalkenyl) - (Cx-C3-alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, C^-C^-alkoxy, oxo, phenyl; Cj-Ce-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, Cj-C^-alkoxy, Ci-C^-alkylamino, ditCi-C^-alkyl) amino, Ci-C^-alkylthio; C2-C8-alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cx-CA-alkoxy, oxo, phenyl; C2-C8-alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, C^-C^-alkoxy, oxo, phenyl; Ci-Ce-alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, C^-C^-alkoxy, oxo, phenyl; C2-C8-alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cj-CA-alkoxy, oxo, phenyl; C1-C8-alkylamino- and di (Cx-Ca-alkyl) aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, C1-CA-alkoxy, oxo, phenyl; pyrrolidin-l-yl, morpholino-, piperidino-, pipera-zinyl-, or 4-methylpiperazin-l-ylcarbonyl, in each case optionally substituted by Cx-CA-alkyl, C2-C6-alkenyl, Cx-CA-acyl, oxo, thioxo, carboxyl, or phenyl; C2-C8-alkenylamino- and ditCi-Cg-alkenyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Cx-CA-alkoxy, oxo, phenyl; Cx-C6-alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cx-CA-alkoxy, oxo, phenyl; Cj-C6-alkenylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cx-CA-alkoxy, oxo, phenyl; or aryl, arylcarbonyl, aryl(thiocarbonyl), (aryl-thio)carbonyl, (arylthio)thiocarbonyl, aryloxy-carbonyl, arylaminocarbonyl, (arylamino)thiocarbonyl, arylalkylaminocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl or aryl(alkylthio)carbonyl, each of which is substituted by up to five radicals R6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 5 carbon atoms, and R6 being as defined above, or heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or heteroaxrylalkenylcarbonyl, heteroaryloxycarbonyl, (heteroarylthio)carbonyl, heteroarylaminocarbonyl, heteroarylalkyloxycarbonyl, heteroaryl(alkylthio)carbonyl or heteroarylalkylaminocarbonyl, each of which is substituted by up to three radicals R6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms, and R* are identical or different and, independently of one another, are hydrogen, C^-Ce-alkyl which is optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, Cx-CA-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cx-CA-alkoxy, Cx-CA-alkylamino, di(C1-C4-alkyl) amino, Cx-CA-alkylthio, Cx-CA-alkyl- sulfonyl, C1-C4-alkylsulfinyl, carboxyl or carbamoyl; C2-C8-alkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, Ci-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-C^-alkoxy, C1-C4-alkylamino, di(C1-CA-alkyl) amino, Cx-C^-alkylthio, Ci-C^-alkylsulfonyl, Cj.-CA-alkylsulfinyl, carboxyl or carbamoyl; C3-C8-cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, Cj-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-C^-alkoxy, Cj-C*-alky lamino, di (C1-CA-alkyl) amino, Ci-C^-alky lthio, Cj-C^-alkylsulfonyl, Ci-C^-alkylsulfinyl, carboxyl or carbamoyl; C3-C8-cycloalkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, Cx-CA-acyloxy, benzoyloxy, benzyloxy, phenoxy, Ci-C^-alkoxy, Ci-C^-alkylamino, di(Cx-CA-alkyl) amino, Cj-C^-alkylthio, Cj-C*-alkylsulfonyl, Cj-C^-alkylsulfinyl, carboxyl or carbamoyl; aryl, arylalkyl, heteroaryl or heteroarylalkyl, each of which is substituted by up to five radicals R6 which are independent of one another, it being possible for the alkyl radical to contain 1 to 3 carbon atoms in each case, and Re being as defined above, R3 and R* or R3 and R5 can furthermore also be part of a saturated or unsaturated carbo- or heterocyclic ring which has 3 to 8 carbon atoms and which can optionally be substituted by fluorine, chlorine, hydroxyl, amino, Cx-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-Ce-acyloxy, benzoyloxy, C^-Ce-alkoxy, oxo, thioxo, carboxyl, carbamoyl or phenyl, is oxygen, sulfur, selenium or substituted nitrogen N-R2, it being possible for R2 have the above-mentioned meanings. In a preferred group of compounds of the formula I or la, 2) n is zero, one, two or three, the individual substituents R1 independently of one another are 10 fluorine, chlorine, bromine, trifluoromethyl, tri- fluoromethoxy, hydroxyl, Ci-C^-alkyl, C5-C6-cycloalkyl, C1-C4-alkoxy, (Cx-CA-alkoxy) - (Cx-CA-alkoxy), Cj-C^-alkylthio, Ci-C^-alkylsulfinyl, Ci-C^-alkylsulfonyl, nitro, amino, C^-C^-alkylamino, diJC^C^-alkyl) amino, 15 piperidino, morpholino, 1-pyrrolidinyl, 4-methylpiperazinyl, thiomorpholino, imidazolyl, C1-C4-acyl, Ci-C^-acyloxy, Cj-C^-acylamino, cyano, carbamoyl, carboxyl, (Cj-C^-alkyl) oxycarbonyl, hydroxysulfonyl or sulfamoyl 20 or a phenyl, phenoxy, phenoxycarbonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy, anilinosulfonyl, phenylsulfonyl-amino, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical which is substituted by up to two radicals R6 which are independent of one another, where R6 can be fluorine, chlorine, bromine, cyano, trifluoromethyl, nitro, amino, C^-C^-alkyl, C3-C7-cycloalkyl, Ci-C^-30 alkoxy, Ci-C^-alkylthio, C1-C4-alkylsulfinyl, Cj-C^- alkylsulfonyl, Ci-C^-alkylamino, dUCi-C^-alkyl) amino, - 10 - (Cj-C^-alkyl)oxycarbonyl, phenyl or phenoxy, is hydrogen and Rs is hydrogen, hydroxyl, cyano, amino, Cj-C6-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cj-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, Ci-C^-alkoxy, Cx-C^-alkylamino, difCj-C^-alkyl) amino, Ci-C^-alkylthio, oxo, thioxo, carboxyl or carbamoyl; C2-CB-alkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cj-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-C^-alkoxy, Ci-C^-alkylamino, diJCi-C^-alkyl) amino, C]-C4-alkylthio, oxo, thioxo, carboxyl or carbamoyl; C3-C8~allenyl, C3-Ca-alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C1-CA-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-C^-alkoxy, C1-CA-alkylamino, ditCj-C^alkyl) amino, Ci-C^-alkylthio, oxo, thioxo, carboxyl or carbamoyl; C3-C8-cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C1-CA-acyloxy, benzoyloxy, benzyloxy, phenoxy, C1-C4-alkoxy, Ci-C^-alkylamino, difCi-C^-alkyl) amino, Cj-CA-alkylthio, oxo, thioxo, carboxyl or carbamoyl; C3-C8-cycloalkenyl, 27 - li - h\ n Q n y y □ optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C^-C^acyloxy, benzoyloxy, benzyloxy, phenoxy, Cj-C^-alkoxy, Ci-C^-alkylamino, 5 difCx-C^-alkyl) amino, Ci-C^-alkylthio, oxo, thioxo, carboxyl or carbamoyl; (C3-Ce-cycloalkyl) - (Cx-Ca-alkyl) optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, 10 mercapto, hydroxyl, Ci-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, Ci-C^-alkoxy, Cj-C^-alkylamino, di^j-C^-alkyl) amino, Ci-C^alkylthio, oxo, thioxo, carboxyl or carbamoyl; (C3-C8-cycloalkenyl) - (Cj-Ca-alkyl), 15 optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cj-C^-acyloxy , benzoyloxy, benzyloxy, phenoxy, Ci-C^-alkoxy, Ci-C^-alkylamino, difCi-C^-alkyl) amino, Ci-C^-alkylthio, oxo, thioxo, 20 carboxyl or carbamoyl; Cj-Ce-alkylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C^-C^-acyloxy, benzoyloxy, 25 benzyloxy, phenoxy, Cj-C^-alkoxy, Cj-C^-alkylamino, difCi-C^-alkyl) amino, Cj-C4-alkylthio, oxo, thioxo, carboxyl or carbamoyl; C2-C6-alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Ci-C^-alkoxy, oxo, 30 phenyl; (C3-C6-cycloalkyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Ci-C^-alkoxy, oxo, phenyl; - 12 - 2700 (C5-C8-cycloalkenyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Cj-C^-alkoxy, oxo, phenyl; (C3-C6-cycloalkyl) - ((^-C^-alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Ci-C*-alkoxy, oxo, phenyl; (C5-C6-cycloalkenyl) - (C^-Cjj-alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Cj.-CA-alkoxy, oxo, phenyl; Ci-Cg-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, Cx-C4-alkoxy, Cj-C^-alkylamino, diCCj-C^-alkyl) amino, Cj-C^-alkylthio/ C2-C6-alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Ci-C^-alkoxy, oxo, phenyl; C2-C6-alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Ci-C^-alkoxy, oxo, phenyl; Ci-Ce-alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Ci-C^-alkoxy, oxo, phenyl; C2-C6-alkenylthiocarbonyl, opticnally substituted by fluorine, chlorine, hydroxyl, Ci-C^-alkoxy, oxo, phenyl; Ci-Cg-alkylamino- and difCj-Ce-alkylJaminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Cj-C^-alkoxy, oxo, phenyl; pyrrolidin-l-yl, morpholino-, piperidino-, pipera-zinyl-, or 4-methylpiperazin-l-ylcarbonyl; - 13 - C2-C6-alkenylamino- and di (Cj-Ce-alkenyl) tuflinocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Ci-C^-alkoxy, oxo, phenyl; Ci-C^-alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, Ci-C^-alkoxy, oxo, phenyl; C^-C^-alkenylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, Ci-C^-alkoxy, oxo, phenyl; or aryl, arylcarbonyl, aryl(thiocarbonyl), (aryl-thio)carbonyl, (arylthio)thiocarbonyl, aryloxy-carbonyl, arylaminocarbonyl, (arylamino)thiocarbonyl, arylalkylaminocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, aryl(alkylthio)carbonyl or arylalkoxycarbonyl, each of which is substituted by up to three radicals R6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 5 carbon atoms and R6 being as defined above, or 1- or 2-naphthylmethyl, 2-, 3- or 4-picolyl, 2- or 3-furylmethyl, 2- or 3-thienylmethyl, 2- or 3-pyrrolylmethyl, 2-, 3- or 4-pyridylcarbonyl, 2- or 3-furylcarbonyl, 2- or 3-thienylcarbonyl, 2- or 3-thienylacetyl, 2-, 3- or 4-picolyloxycarbonyl, 2-or 3-furylmethyloxycarbonyl, 2- or 3-thienylmethyl-oxycarbonyl, each of which is substituted by up to two radicals R6 which are independent of one another, nd 3 and Ra are identical or different and independently of one another are hydrogen, Ci-C6-alkyl, - 14 - optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, Cx-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, Ci-C^-alkoxy, C^-C^-alkylamino, di (C^-C^-alkyl) amino, Ci-C^-alkylthio, Cx-C^-alkyl-sulfonyl, Ci-C^-alkylsulfinyl, carboxyl or carbamoyl; C2-C8-alkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, Cj-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cj-C^-alkoxy, C^C*-alkylamino, di(C1-C4-alkyl) amino, Cj-C^-alkylthio, Ci-C^-alkylsulfonyl, Ci-C^-alkylsulfinyl, carboxyl or carbamoyl; C3-C8-cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, C^-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-C^-alkoxy, CX-CA-alkylaitu.no, di(C1-C4-alkyl) amino, Ci-C^-alkylthio, Ci-C^-alkylsulfonyl, C^-C^-alkylsulfinyl, carboxyl or carbamoyl; C3-Ce-cycloalkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, C^-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-C^-alkoxy, C^C^-alkylamino, difC^-CV-alkyl)amino, Ci-C^-alkylthio, Cx-C4-alkylsulfonyl, Cx-C^-alkylsulfinyl, carboxyl or carbamoyl aryl, arylalkyl, heteroaryl or heteroarylalkyl, each of which is substituted by up to three radicals R8 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms and R6 being as defined above, and R* can furthermore also be part of a saturated or unsaturated carbo- or heterocyclic ring which has 3 to 7 carbon atoms and which can optionally be substituted by fluorine, chlorine, hydroxyl, amino, Cj-C^-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, Cj-C^-acyloxy, benzoyloxy, Ci-C^-alkoxy, oxo, thioxo, carboxyl, carbamoyl or phenyl, and - 15 - X is oxygen, sulfur or selenium. In a yet more preferred group of compounds of the formula I or la, 3) n is zero, one or two, the individual substituents R1 independently of one another are fluorine, chlorine, bromine, trifluoromethyl, hydroxyl, Ci-C^-alkyl, Ci-C^-alkoxy, (Ci-C^-alkoxy) -(Ci-C^-alkoxy), Ci-C^-alkylthio, nitro, amino, (V-CV alkylamino, ditCj-C^-alkyl) amino, piperidino, morpho-lino, 1-pyrrolidinyl, 4-methylpiperazinyl, Cj-C^-acyl, Ci-C^-acyloxy, Ci-C^-acylamino, cyano, carbamoyl, carboxyl, (C1-CA-alkyl)oxycarbonyl, hydroxysulfonyl or sulfamoyl, or a phenyl, phenoxy, phenylthio, phenylsulfonyl, phenoxysulfonyl, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical which is substituted by up to two radicals R6 which are independent of one another, where R6 can be fluorine, chlorine, bromine, cyano, trifluoromethyl, nitro, amino, Ci-C^-alkyl, Ci-C^-alkoxy, (Cx-C4-alkyl)oxycarbonyl, phenyl or phenoxy, R2 is hydrogen and R3 is Ci-Ce-alkyl, optionally substituted by fluorine, chlorine, hydroxyl, Cj-C^-acyloxy, benzoyl- - 16 - oxy, benzyloxy, phenoxy, Cj-C^-alkoxy, Cj-C^-alkylamino, difC^-C^-alkyl) amino, Cj-C^-alkylthio, oxo, thioxo, carboxyl or carbamoyl; C2-C6-alkenyl, optionally substituted by fluorine, chlorine, hydroxyl, Cx-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, Ci-C^-alkoxy, C^-C^-alkylamino, ditCi-C^-alkyl) amino, Cj-C^-alkylthio, oxo, thioxo, carboxyl or carbamoyl; C3-C8-allenyl, C3-C8-alkynyl, optionally substituted by fluorine, chlorine, hydroxyl, C^-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, Ci-C^-alkoxy, Cj-C^-alkylamino, di (Ci-C^-alkyl) amino, C^-C^-alkylthio, oxo, thioxo, carboxyl or carbamoyl; C3-C8-cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, Cj-C^-alkyl, acyloxy, benzoyloxy, benzyloxy, phenoxy, Ci-C^-alkoxy, Ci-C^-alkylamino, di(C1-CA-alkyl) amino, C^-C^-alkylthio, oxo, thioxo, carboxyl or carbamoyl; C3-C8-cycloalkenyl, optionally substituted by fluorine, chlorine, hydroxyl, Cj-C^-alkyl, Cj-C^ acyloxy, benzoyloxy, benzyloxy, phenoxy, Cj-C^-alkoxy Ci-C^-alkylamino, difCj-^-alkyl) amino, Cj-C^-alkylthio oxo, thioxo, carboxyl or carbamoyl; (Cg-Cg-cycloalkyl) - (Ci-C^-alkyl), optionally substituted by fluorine, chlorine, hydroxyl, C^-C^-alkyl, Cj-C^ acyloxy, benzoyloxy, benzyloxy, phenoxy, C1-C4-alkoxy Ci-C^-alkyleunino, di(C1-C4-alkyl) amino, Cj-C^-alkylthio - 17 - oxo, thioxo, carboxyl or carbamoyl; (C3-C6-cycloalkenyl) - (Ci-Cj-alkyl), optionally substituted by fluorine, chlorine, hydroxyl, Ci-C^-alkyl, (a-C*-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-C^-alkoxy, C1-C4-alkylaminor difCj-C^-alkyl) amino, C^-C^-alkylthio, oxo, thioxo, carboxyl or carbamoyl; Cx-C6-alkylcarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, C^-C^-alkyl, Ci-C*-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-C^-alkoxy, Ci-C^-alkylamino, Ci-C^-alkenylamino, di(Cx-C4-alkyl)amino, 1-pyrrolidinyl, piperidino, morpholino, 4-methyIpiperazin-1-y1, C^-C^-alkylthio, oxo, thioxo, carboxyl or carbamoyl; C2-C6-alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxyl; (C3-C6-cycloalkyl) carbonyl, (Cs-C6-cycloalkeny 1) carbonyl, (C3-C6-cycloalkyl) - (C^-Ca-alkyl) carbonyl, (C5-C6-cycloalkenyl) - (Cj-Ca-alkyl) carbonyl, Ci-Cg-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, Ci-C^-alkoxy, Ci-C^-alkylamino, difCj-C^-alkyl) amino or Ci-C^-alkyl-thio; C2-C6-alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cx-C^-alkoxy; C2-C6-alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cj-C^-alkoxy; C^-Cg-alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Ci-C^-alkoxy; C2-C6-alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, C^-C^-alkoxy; C^-Cg-alkylamino- and difC^-Cg-alkyllaminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Ci-C^-alkoxy; pyrrolidin-l-yl, xnorpholino-, piperidino-, pipera-zinyl-, or 4-methylpiperazin-l-ylcarbonyl; C2-C6-alkenylamino- and difCi-Ce-alkenylJaminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, C^-C^-alkoxy; Ci-C^-alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, Ci-C^-alkoxy; C1-C4-alkenylsulf onyl; or aryl, arylcarbonyl, (arylthio)carbonyl, aryloxy-carbony1, arylaminocarbonyl, (arylamino)thiocarbonyl, arylsulfonyl, arylalkylaminocarbonyl, arylalkyl, arylalkenyl, arylalkylcarbonyl, arylalkoxycarbonyl or aryl(alkylthio)carbonyl, each of which is substituted by up to two radicals R6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms, and R6 being as defined above, or 1- or 2-naphthylmethyl, 2-, 3- or 4-picolyl, 2- or 3-furylmethyl, 2- or 3-thienylmethyl, 2- or 3-pyrrolylmethyl, 2-, 3- or 4-pyridylcarbonyl, 2- or 3-furylcarbonyl, 2- or 3-thienylcarbonyl, 2- or 3-thienylacetyl, 2-, 3- or 4-picolyloxycarbonyl, 2- or 3-furylmethyloxy- - 19 - wye carbonyl or 2- or 3-thienylmethyloxycarbonyl, each of which is substituted by up to two radicals R6 which are independent of one another, and R3 and R* are identical or different and independently of one another are hydrogen, Cx-C^-alkyl, optionally substituted by fluorine, chlorino, hydroxyl, amino, mercapto, C1-CA-acyloxy, benzoyloxy, phenoxy, Cj-C*-alkoxy, Ci-C^-alkylamino, difCj-C^-alkyl) amino, Cj-C*-alkylthio, Cx-C^-alkylsulfonyl, Ci-C^-alkylsulfin/l, carboxyl or carbamoyl; C2-C6-alkenyl, optionally substituted by fluorine or chlorine; C3-C6-cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, Cj-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cj-C^-alkoxy, Cj-C*-alkylamino, di(C1-CA-alkyl)eunino, C^-C^-alkylthio, Ci-C^-alkylsulfonyl, Cj-C^-alkylsulfinyl, carboxyl or carbamoyl; C3-CB-cycloalkenyl, optionally substituted by fluorine or chlorine; aryl, benzyl, heteroaryl or heteroarylmethy1, each of which is substituted by up to two radicals R6 which are independent of one another, R3 and R* can furthermore also be part of a saturated or unsaturated carbo- or heterocyclic ring which has 3 to 6 carbon atoms and which can optionally be substituted by fluorine, chlorine, hydroxyl, amino, Cj-C^-acyloxy, benzoyloxy, CX-CA-alkoxy, oxo, thioxo, carboxyl or carbamoyl, and X is oxygen or sulfur. * "* lii < -'O.^ 0 tiyy &>$ - 20 - In a yet again preferred group of compounds of the formula I or la, 4) n is zero, one or two, the individual substituents R1 independently of one another are fluorine, chlorine, bromine, trifluoromethyl, hydroxyl, C^-C^-alkyl, C^-C^-alkoxy, (Ci-C^-alkoxy)-10 (Cx-C2-alkoxy), C^-C^-alkylthio, nitro, amino, Cx-C4- alkylamino, di(C1-C4-alkyl) amino, piperidino, morpho-lino, 1-pyrrolidinyl, 4-methyIpiperazinyl, Cj-C^-acyl, Ci-C^-acyloxy, Cj-C^-acylamino, cyano, carbamoyl, carboxyl, (Cj-C^-alkyl) oxycarbonyl, hydroxy sulfonyl or 15 sulfamoyl or a phenyl, phenoxy, phenylthio, phenylsulfonyl, phenoxysulfonyl, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical, each of which is substituted by up 20 to two radicals R6 which are independent of one another, where R6 can be fluorine, chlorine, bromine, cyano, trifluoromethyl, nitro, amino, Ci-C^-alkyl, C^-C^-alkoxy, 25 alkyl)oxycarbonyl, phenyl or phenoxy, R2 is hydrogen and R5 is Cj-Ce-alkyl, optionally substituted by Ci-C^-alkoxy or Ci-C^-alkylthio; 21 - C2-C6-alkenyl, optionally substituted by oxo; C3-Ca-allenyl; C3-C8-alkynyl, in particular 2-butynyl; C3-C6-cycloalkyl; C5-C6-cycloalkenyl; (C3-C6-cycloalkyl) - (Ci-Cj-alkyl), in particular cyclopropylmethyl, optionally substituted by Cj-C*-alkyl; (C3-C6-cycloal.kenyl)-(C1-C2-alkyl), in particular cyclohexenylmethyl; Ci-Cg-alkylcarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, benzyloxy, phenoxy, Cj-C^-alkoxy, Cj-C^-alkylamino, Cx-C^-alkenylaxaino, di(C1-CA-alkyl)amino, 1-pyrrolidinyl, piperidino, morpholino, 4-methyIpiperazin-1-yl or Cx-C^-alkylthio; C2-C6-alkenylcarbonyl; Ci-Cg-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, Cx-CA-alkoxy, Ci-C^-alkylamino, diJCj-C^-alkyl) amino or Cj-C^-alkyl-thio; C2-C6-alkenyloxycarbonyl, in particular vinyloxy-carbonyl, allyloxycarbonyl, isopropenyloxycarbonyl, butenyloxycarbonyl or pentenyloxycarbonyl; C2-C6-alkynyloxycarbonyl, in particular propynyloxy-carbonyl or butynyloxycarbonyl; - 22 - CA-C6-alkylthiocarbonyl; C2-C6-alkenylthiocarbonyl, in particular allylthio-carbonyl; Cj-Ce-alkylamino- and di (Ci-Ce-alkyl) aminocarbonyl; pyrrolidin-l-yl, morpholino-, piperidino-, pipera-zinyl-, or 4-methylpiperazin-l-ylcarbonyl; C2-C6-alkenylamino- and di(C1-CB-alkenyl)euninocarbonyl; C^-C^-alkylsulf onyl; Ci-C^-alkenylsulf onyl; or aryl which is substituted by up to two radicals R6 which are independent of one another, in particular phenyl, arylcarbony1, in particular benzoyl, (arylthio)carbonyl, aryloxycarbonyl, arylamino-carbonyl, (arylamino)thiocarbonyl, arylalkylamino-carbonyl, arylsulfonyl, arylalkyl, in particular benzyl, phenylethyl, arylalkenyl, ary.lalkylcarbonyl, arylalkoxycarbonyl or aryl(alkylthio)carbonyl, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms and R6 being as defined above, or 1- or 2-naphthylmethyl, 2-, 3- or 4-picolyl, 2- or 3-furylmethyl, 2- or 3-thieny lmethyl, 2- or 3-pyrrolylmethyl, 2-, 3- or 4-pyridylcarbonyl, 2- or 3-furylcarbonyl, 2- or 3-thienylcarbonyl, 2- or 3-thienylacetyl, 2-, 3- or 4-picolyloxycarbonyl, 2-o:: 3-furylmethyloxycarbonyl, or 2- or 3-thienyl-me thy loxycarbonyl, each c t i?hich is substituted by up to two radicals R6 which are independent of one another, and , 27 ooe g - 23 - R3 and R* are identical or different and independently of one another are hydrogen, Ci-C^-alkyl, 5 optionally substituted by hydroxyl, mercapto, Cj-C*- alkoxy, Ci-C^-alkylthio, Ci-C^-alkylsulfonyl, CX-CA-alkylsulfinyl, carboxyl or carbamoyl; C2-C6-alkenyl, aryl, benzyl, thienyl or thienylmethyl, each of which 10 is substituted by up to two radicals R6 which are independent of one another, R6 being as defined above, R3 and R4 can also be part of a saturated or unsaturated carbo- or heterocyclic ring which has 3 to 6 carbon atoms and can 15 optionally be substituted by oxo or thioxo, and X is oxygen or sulfur. Compounds of the formula I or la as defined above wherein the substituents mentioned have the following meanings are very particularly important: 20 n is zero or one, the individual substituents R1 independently of one another are fluorine, chlorine, bromine, Cj-Ca-alkyl, C^Ca-alkoxy, 25 C2-C4-acyl or cyano, R2 is hydrogen and R5 is C2-C6-alkenyl, 20 ,, >>• ' K?) - 24 - C3-Ce-alkynyl, in particular 2-butynyl; (C3-C6-cycloalkyl)-(C1-C2-alkyl), in particular cyclopropylmethyl, optionally substituted by C^-C^-alkyl; (C^-Ce-cycloalkenylJ-tCi-Ca-alkyl), in particular cyclohexenylmethyl; C2-C6-alkylcarbonyl, C2-C6-alkenylcarbonyl; Cj-Ce-alkyloxycarbonyl; C2-C6-alkenyloxycarbonyl, in particular vinyloxy-ca.cbonyl, allyloxycarbonyl, isopropeny loxycarbonyl, butenyloxycarbonyl or pentenyloxycarbonyl; C2-C6-*lJcyny loxycarbonyl, in particular propynyloxycarbonyl or butynyloxycarbonyl; C2-C6-alkenylthiocarbonyl, in particular allylthio-carbonyl; Ci-C^-alkylsulf onyl; Ci-C^-alkenylsulf onyl; or arylalkyl, in particular benzyl or arylalkenyl, which is substituted by up to two radicals R8 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms and for the alkenyl radical to contain 2-3 carbon atoms, or 1-naphthylmethyl, 2- or 3-picolyl, 2-furylmethyl or 2- or 3-thienylmethyl, each of which is substituted by up to two radicals R6 which are independent of one 27 - 25 - another, where R6 is fluorine, chlorine, bromine, cyano, Cx-Ca-alkyI or Ci-C^-alkoxy, 5 and R3 and R* are identical or different and independently of one another are hydrogen, Ci-C^-alkyl, 10 optionally substituted by hydroxyl, mercapto, Cj-C*- alkoxy, C1-C2-alkylthio, and X is oxygen or sulfur. The alkyl groups in the above definitions can be straight-chain or branched. Unless otherwise defined, 15 they preferably contain 1-8, particularly preferably 1-6, in particular 1-4, carbon atoms. Examples are the methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl and 1,1-dimethylethyl group, and similar groups. 20 The alkenyl groups mentioned in the above definitions can be straight-chain or branched and contain 1 to 3 double bonds. Unless otherwise defined, these groups preferably contain 2-8, in particular 2-6, carbon atoms. Examples are the 2-propenyl, 1-methylethenyl, 2-butenyl, 25 3-butenyl, 2-methyl-2~propenyl, 3-methyl-2-butenyl, 2,3-dimethyl-2-butenyl, 3,3-dichloro-2-propenyl and pentadienyl groups and similar groups. 30 The alkynyl groups mentioned in the above definitions can b£ straight-chain or branched and contain 1 to 3 triple bonds. Unless otherwise defined, they contain preferably - 26 - 2-8, particularly preferably 3-6, carbon atoms. Examples are the 2-propynyl and 3-butynyl group and similar groups. Unless otherwise defined, the cycloalkyl and cycloalkenyl 5 groups mentioned in the above definitions contain preferably 3-8, particularly preferably 4-6, carbon atoms. Examples are the cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl or cyclohexenyl group. The acyl groups mentioned in the above definitions can be 10 aliphatic, cycloaliphatic or aromatic. Unless otherwise defined, they preferably contain 1-8, particularly preferably 2-7, carbon atoms. Examples of acyl groups are the formyl, acetyl, chloroacetyl, trifluoroacetyl, hydroxyacetyl, propionyl, butyryl, isobutyryl, pivaloyl, 15 cyclohexanoyl or benzoyl group. The aryl groups mentioned in the above definitions are preferably aromatic groups having 6-14 carbon atoms, in particular 6-10 carbon atoms, for example phenyl or naphthyl. 20 Suitable hetero atoms in the aboveroentioned heterocyclic rings or heteroaryl groups are, in particular, oxygen, sulfur and nitrogen, where, in the case of a nitrogen-containing ring which is saturated in this position, a structure N-Z is present in which Z is H or R5 with the 25 individual above-described definitions. Unless otherwise defined, the heterocyclic rings preferably have 1-13 carbon atoms and 1-6 hetero atoms, in particular 3-9 carbon atoms and 1-4 hetero atoms. Suitable radicals for the heteroaryl groups mentioned in 30 the above definitions are, for example, heteroaromatic radicals such as 2- or 3-thienyl, 2- or 3-furyl, 2-, 3-or 4-pyridyl, pyrimidyl, indolyl, quinolyl or iso-quinolyl. 270 27 - Examples of the aralkyl groups mentioned in the above definitions are benzyl, phenylethyl, naphthylmethyl or styryl. The abovementioned substituents R1 to Rs are preferably 5 trisubstituted, particularly preferably disubstituted, in particular monosubstituted, by the particular substituents mentioned. In the case of the particular definitions of composite substituents (such as, for example, arylalkoxycarbonyl), 10 the ranges which have been described above as being preferred for the individual substituents are also preferred. Depending on the various substituents, compounds of the formulae I and la can have several asymmetric carbon 15 atoms. The invention therefore relates both to the pure stereoisomers and to mixtures thereof such as, for example, the corresponding racemate. The pure stereoisomers of the compounds of the formulae I and la can be prepared directly by known methods or 20 analogously to known methods, or they can be resolved later. A variety of nucleosides can be employed according to the invention, with zidovudine (AZT), didanosine (DDI), dideoxycytidine (DDC) and lamivudine (3-TC®), stavudine 25 (D4T), BW 935U83 and BW 159U89 being particularly important, especially zidovudine. The nucleosides mentioned can be prepared by generally known processes (cf. Merck Index, 11th Edition Rahway, N.J. 1989, Drugs 45 (4), 488 et seq., 45 (5), 637 et seq., 1993, Gruds 44 30 (4), 656 et seq., 1992, Clin. Pharmacol. Ther. 55, No. 2, 198, 1994, Antiviral-Chem. Chemother, 2, No. 3, 125-32, 1991, Antiviral-Rest. 23, Suppl. 1, 67, 1994, Abstracts of the 34th JCAAC, Orlando 4.-7. 10.94). - 28 - The compounds o£ the formulae I and la can be prepared by known methods or modifications thereof (see, for example, Rodd's Chemistry of Carbon Compounds, S. Coffey, M. F. Ansell (Editor); Elsevier, Amsterdam, 1989; Vol. IV Part IJ, p. 301-311. Heterocyclic Compounds. R. C. Elderfield (Editor); Wiley, Mew York, 1957; Vol. 6, p. 491-495). The preparation of compounds of the formulae I and la as explained in 1) - 4) above is effected, for example, A) for preparing compounds of the formula I where X is oxygen and the radicals R1, R2, R3, R4 and Rs are as defined under 1) - 4), by reacting a compound of the formula II H | R 4 H with the definitions mentioned under 1) - 4) applying R1, R3 and RA, with a compound of the formula III R-Z (III) where R has the meanings for Rs and R2 which have been mentioned above under 1) - 4) with the exception of hydrogen, hydroxyl, C]-C6-alkoxy, aryloxy, C1-C6-acyloxy, amino, Cj-Cg-alkylamino, difCi-Cg-alkyI) amino, arylamino and Cj-Cg-acylaroino, and Z is a leaving group, or by B) preparing compounds of the formula I where X is sulfur and R1, R2, R3, R4 and R5 are as defined under 1) - 4) by reacting a compound of the formula I where X is oxygen and the definitions mentioned under 1) - 4) apply to R1, R2, R3, R4 and R5, with a sulfurizing reagent, or by C) preparing compounds of the formula la where X and the radicals R1 to R5 are as defined under 1) - 4), by reacting a compound of the formula IV where the definitions mentioned under 1) - 4) apply to R1, R3, R* and R5, with a compound of the formula III R2-Z (III) where the definitions described under 1) - 4) for formula I and la apply to R2, with the exception of hydrogen, hydroxyl, C^-Ce-alkoxy, aryloxy, Cj-C6-acyloxy, amino, 10 Ci-CB-alkylamino, di (C^-Ce-alkyl) amino, aryl amino or C1-C6-acylamino, and Z is a leaving group, or by D) preparing compounds of the formula I where X is oxygen and the radicals R1 to R5 are as defined under 1) - 4) by 15 cyclizing a compound of the formula V where R to R are as defined under 1) - hydroxyl, Ci-C^-alkoxy i optionally 4) and Y is halogenated C1-C4-acyloxy, chlorine, bromine or iodine, 10 or by E) preparing compounds of the formula I where X is oxygen, R* and Rs are hydrogen and the definitions mentioned under 1) - 4) apply to R1 to R3, from the quinoxa-linones of the formula XI XI where R1 to R3 are as defined under 1) - 4), by addition of hydrogen on the ON bond, or by F) preparing compounds of the formula I where X is oxygen and R1 to R3 are as defined under 1) - 4), from compounds of the formula VI VI where R1, R2 and R3 are as defined under 1) - 4), by 15 reacting them with chloroform or bromoform and a carbonyl compound of the formula XIII R3-C0-R* (XIII) where R3 and R4 are as defined under 1) - 4), or with o-(trihalomethyl)alkanols of the formula XIV 20 3r>4 Hal3C-C (OH) -R R' (XIV) where Hal is CI, Br or I, - 31 - in which R3 and R4 are as defined under 1) - 4), or by G) preparing compounds of the formula I where X is oxygen and R1, R2, R3, R4 and R5 are as defined under 1) - 4), by reacting a compound of the formula I where X is oxygen and the definitions mentioned under 1) - 4) apply to R1, R2, R5 and to R3 and R4, with the exception that at least one of the radicals R3 or R4 is hydrogen, with an alkylating reagent of the formula XV R'-Z (XV) where R' has the meanings mentioned above for R3 and R4 with the exception of hydrogen and Z is a leaving group, or by H) preparing compounds of the formula I where X is oxygen, R1, R2, R3 and R4 are as defined under 1) - 4) and R5 is C1-C8-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C^-Ce-acyloxy, benzoyloxy, phenoxy, C^-Cg-alkoxy, Cx-Ce-alkylamino, di(C1-C6-alkyl) amino, C^-Ce-alkylthio, cyano, carboxyl, carbamoyl, C3-C8-alkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, Cj-C6-acyloxy, benzoyloxy, phenoxy, Cj-Cg-alkoxy, Cj-Cg-alkylamino, di(C1-C6-alkyl) amino, Cx-Cg-alkylthio, cyano, carboxyl or carbamoyl, C3-C8-alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C1-C6-acyloxy, benzoyloxy, phenoxy, Cx-C6-sIkoxy, Ci-Cg-alkylamino, difCi-Ce-alkyl) amino, C^-C^-alkylthio, cyano, carboxyl or carbamoyl, C4-Ca-cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C^-Ce-acyloxy, benzoyloxy, phenoxy, Ci-Cg-alkoxy, C^-Ce-alkylamino, ditCfCg-alkyl) amino, Cj-C6-alkylthio, cyano, carboxyl or carbamoyl, C5-C8-cyclo-alkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C^-Ce-acyloxy, benzoyloxy, phenoxy, Cj-Cg-alkoxy, Ci-C6-alkylamino, Ci-Cg-dialkylamino, Cj-Cg-alkylthio, cyano, carboxyl or - 32 - carbamoyl, (Cj-Cj-alkoxyJ-JCi-Ce-alkyl) , difC^Ce-alkylaminoJ-tCi-Ce-alkyl) or (C3-C6-cycloalkyl)-alkyl, (C6-C8-cycloalkenyl)alkyl, or arylalkyl, naphthyl-alkyl or heteroarylalkyl, each of which is substituted by up to five radicals R8 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms, by reductive alkylation of a compound of the formula I where Rs is hydrogen and X is oxygen and the definitions mentioned under 1) - 4) apply to R1, R2, R3 and R*, with a carbonyl compound of the formula XVI, R"-C(»0)-R"' (XVI) where R" and R"' are identical or different and independently of one another are hydrogen, Ci-Cj-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C^-Cg-acyloxy, benzoyloxy, phenoxy, Ci-Cg-alkoxy, Cj-Cg-alkylamino, ditC^-Cg-alkyl) amino, (^-Cg-alkylthio, cyano, carboxyl or carbamoyl, C3-C7-alkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, Cj-Cg-acyloxy, benzoyloxy, phenoxy, C1-C6-alkoxy, Ci-Cg-alkylamino, di(Cj-C6-alkyl) amino, Ci-Cg-alkylthio, cyano, carboxyl or carbamoyl, C3-C7-alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C^-Cg-acyloxy, benzoyloxy, phenoxy, C^-Cg-alkoxy, Ci-Cg-alkylamino, dUCj-Cg-alkyl) amino, Ci-Cg-alkylthio, cyano, carboxyl or carbamoyl, C4-C8-cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C^-Cg-acyloxy, benzoyloxy, phenoxy, Ci-Cg-alkoxy, Ci-Cg-alkylamino, ditCi-Cg-alkyl) amino, Ci-Cg-alkylthio, cyano, carboxy?. or carbamoyl, C6-cycloalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, Cj-Cg-acyloxy, benzoyloxy, phenoxy, C^-Cg-alkoxy, C^-Cg-alkylamino, di(C1-C6-alkyl) amino, C^-Cg-alkylthio, cyano, carboxyl or carbamoyl, (C1-C6-alkoxy)-(C1-Cs-alkyl) , [ditCVCg-alkyl) amino]-(Cj-Cs-alkyl) or (C4-C6-cycloalkyl) -alkyl, (Cg-cycloalkenyl)alkyl, or arylalkyl, naphthylalkyl 33 - or heteroarylalkyl, each of which is substituted by up to five radicals R6 which are independent of one another, it being possible for the alkyl radical to contain in each case 0 to 2 carbon atoms, and where R" and R"' can be linked to each other to form a 4- to 8-membered ring, or I) preparing compounds of the formula I where X is oxygen and R1, R2, R3 and R4 are as defined under 1) - 4) and R3 is Ci-Ce-alky loxycarbonyl, Ci-Cg-alkylthiocarbonyl, C2-C8-alker/loxycarbonyl, C2-C8-alkenylthiocarbonyl, C2-C8-alkynyloxycarbonyl, Cx-Ca-alkylaminocarbonyl, C3-C6-alkenylaminocarbonyl, di (Ci-Ce-alkyl) aminocarbonyl, pyrrolidin-l-yl, morpholino-, piperidino-, piperazinyl-, 4-methylpiperazin-l-ylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Ci-CB-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-Cs-alkoxy, Cj-Ce-alkylamino, di (Cj-Cg-alkyl)-amino, Ci-Cg-alkylthio, Cx-Ce-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; or aryloxycarbonyl, arylthio(carbonyl), arylaminocar-bony1, heteroaryloxycarbonyl, heteroarylthiocarbonyl, heteroarylaminocarbonyl, arylalkyloxycarbonyl, (aryl-alkylthio)carbonyl, arylalkylaminocarbonyl, heteroalkyl-oxycarbonyl, (heteroalkylthio)carbonyl or heteroalkyl-aminocarbony 1, each of which is substituted by up to five radicals R8 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms, by reacting a compound of the formula XVII - 34 - ^700 XVII where the definitions mentioned under 1) - 4) apply to R1, R2, R3 and R4, n is 0, 1, 2 or 3, X is oxygen and U is a leaving group, with a compound of the formula XVIII 5 Nu-H (XVIH) where Nu is Cx-Ce-alkoxy, C2-C8-alkenyloxy, C2-C8-alkynyl-oxy, Ci-Ce-alkylthio, C2-C8-alkenylthio, Ci-Cs-alkylamino-and difCi-Ca-alkyl) amino, C2-Ce-alkenylamino- and ditCi-Ce-alkyl)amino, optionally substituted by fluorine, 10 chlorine, bromine, hydroxyl, Cj-C^-alkoxy, C^-C^-alkyl-amino, di(C1~C4-alkyl)amino, Cx-C4-alkylthio, pyrrolidin-l-yl, morpholino-, piperidino-, piperazinyl-or 4-methylpiperazin-l-ylcarbonyl, optionally substituted by Cj-C^-alkyl, C2-C6-alkenyl, Cx-C^-acyl, oxo, thioxo, 15 carboxyl or phenyl, or aryloxy, arylthio, arylamino, arylalkyloxy, arylalkylthio, arylalkylamino, heteroaryl-oxy, heteroarylthio.- heteroarylamino, heteroarylalkyloxy, heteroarylalkylthio or heteroarylalkylamino, each of which is substituted by up to five radicals Re (R6 is as 20 defined at the outset) which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms. The abovementioned method A preferably proceeds under the following conditions: 25 The substituent Z in formula III iB a suitable leaving - 35 - 1 C)-<y ^'U Q. group such as, for example, chlorine, bromine or iodine, a suitable radical of sulfuric acid, an aliphatic or aromatic sulfonate, or optionally halogenated acyloxy. The reaction is expediently carried out in an inert 5 solvent. Suitable solvents are, for example, aromatic hydrocarbons such as toluene or xylene, lower alcohols such as methanol, ethanol or 1-butanol, ethers such as tetrahydrofuran or glycol dimethyl ether, dipolar aprotic solvents such as N,N-dimethylformamide, N-methyl-2-pyrro-10 lidone, acetonitrile, nitrobenzene, dimethyl sulfoxide, or mixtures of these solvents. Two-phase systems with aqueous solutions of bases in the presence of a phase transfer catalyst such as, for example, benzyltriethylam-monium chloride, are also possible. 15 The presence of a suitable base, for example of an alkali metal carbonate, alkali metal hydrogen carbonate, alkaline earth metal carbonate or alkaline earth metal hydrogen carbonate such as sodium carbonate, calcium carbonate or sodium bicarbonate, of an alkali metal 20 hydroxide or alkaline earth mstal hydroxide such as potassium hydroxide or barium hydroxide, an alcoholate such as sodium ethanolate or potassium tert.-butylate, an organolithium compound such as butyllithium or lithium-diisopropylamine, an alkali metal hydride or alkaline 25 earth metal hydride such as sodium hydride or calcium hydride, an alkali metal fluoride such as potassium fluoride, or an organic base such as triethylamine or pyridine for scavenging the acid which is liberated during the reaction, may be expedient. 30 In some cases, the addition of an iodide, for example potassium iodide, is expedient. The reaction is generally carried out at temperatures between -10 and 160°C, preferably at room temperature. 35 To carry out this reaction, any nucleophilic substituents such as, for example, hydroxyl, mercapto or amino groups, 0 Hi P w U L (j - 36 - with the exception of the 1- and/or 4-position in compounds of the formula II or III, must, before the reaction is carried out, be derivatized in a suitable manner or provided with conventional protective groups 5 such as, for example, acetyl or benzyl, which can then be eliminated. The sulfurizing reagent which is preferably used for the reaction as described above under B) is 2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane 10 2,4-disulfide (Lawesson's reagent), bis(tricyclohexyltin) sulfide, bis(tri-n-butyltin) sulfide, bis(triphenyltin) sulfide, bis(trimethylsilyl) sulfide or phosphorus pentasulfide. The reaction is carried out expediently in an organic 15 solvent or in a solvent mixture, at room temperature or above, preferably at the boiling point of the reaction mixture, and, if possible, under anhydrous conditions. Suitable substances are, for example, carbon disulfide, toluene, xylene, pyridine and 1,2-dichloroethane. If the 20 tin sulfides or silyl sulfides which have been mentioned are used, it is advisable to carry out the sulfurization reaction in the presence of a Lewis acid, such as boron trichloride. In the presence of other carbonyl groups in a compound of 25 the formula I, for example in a compound where X is oxygen and one or more radicals R1 to Re are acyl, the carbonyl is to be protected by known methods prior to the sulfurization reaction by a suitable protective group, for example by acetalization; subsequent elimination of 30 the protective groups results in the desired compound. For the reaction described above under C, the substituent Z is a suitable leaving group, preferably chlorine, bromine or iodine, a suitable radical of sulfuric acid, an aliphatic or aromatic sulfonate, or optionally halo-35 genated acyloxy. The reaction conditions for this reaction correspond to - 37 - those of method A. The cyclization described under D) is effected in a suitable solvent such as methanol, ethanol, N,N-dimethyl-formamide or N-methylpyrrolidone, in the presence of a 5 base; suitable bases are alkali metal carbonates, alkali metal hydrogen carbonates, alkaline earth metal carbonates or alkaline earth metal hydrogen carbonates such as sodium carbonate, calcium carbonate or sodium bicarbonate, alkali metal hydroxides or alkaline earth metal 10 hydroxides such as potassium hydroxide or barium hydroxide, alcoholates such as sodium ethanolate or potassium tert.-butylate, organolithium compounds such as butyllithium or lithium diisopropylamine, alkali metal hydrides or alkaline earth metal hydrides such as sodium 15 hydride or calcium hydride, or an organic base such as triethylamine or pyridine - the latter substances can also be used as solvents, or organic or mineral acids such as glacial acetic acid, trifluoroacetic acid, hydroch .oric acid or phosphoric acid. The reaction is 20 preferably carried out at temperatures between 20 and 120°C, particularly preferably at room temperature. The compounds of the formula V, where R1 to R5 and Y are as defined under 1) - 5), can be obtained from compounds of the formula VI where R1, R2 and R5 are as defined under 1) - 4), by alkylation with a compound of the formula VII - 38 CO-Y VII where R3, R4 and Y are as defined under 1) - 5) and Z is as defined under A). The reaction conditions for this alkylation correspond to those given in method A. Simultaneous cyclization to give the dihydroquinoxaline of the formula I takes place under suitable conditions. Compounds of the formula V in which R1, R3 to R3 and Y are as defined under 1) - 5) and R2 is hydrogen can also be prepared from compounds of the formula VIII 10 "1 L R3 (VIII) where R1, R3 to R5 and Y are as defined under 1) - 5) by reducing the nitro group by known processes to the amino group. Simultaneous cyclization to give the dihydroquinoxaline 15 of the formula I takes place under suitable conditions, for example by carrying out the reduction in the presence of an acid. The reduction is carried out by standard methods (see, for example, Methoden der Organischen Chemie [Methods in 20 Organic Chemistry] (Houben-Weyl), E. Miiller (Editor); G. Thieme Verlag, Stuttgart, 1957; Vol. XI/1, p. 360-490), for example using tin(II) chloride in glacial acetic acid, TiCl3 in hydrochloric acid, or by catalytic hydrogenation, the choice of reagent being 25 determined by the chemical stability of the various substituents R1 and R3 to R3; if, for example, one of the radicals is alkenyl, the first method will be selected to obtain the double bond. n B - 39 - The phenylenediamines of the formula VI which are required as starting materials for the syntheses described are known from the literature or commercially available or can be synthesized by methods known from the litera-5 ture. N-ortho-nitrophenylamino acid derivatives of the formula VIII, where R1,, and R3 to R5 are as defined under 1) - 4) and Y is OR7, where R7 is hydrogen, Cj-Cg-alkyl, optionally in each case for example halogen-substituted phenyl, 10 benzyl or 9-fluorenylmethyl, can be obtained for example by eunination of ortho-halonitro aromatic substances of the formula IX IX where R1 is as defined under 1) - 4) and W is fluorine, 15 chlorine, bromine or iodine., with amino acids or their esters of the formula X C00R7 D ^ HN p 4 >. r5 where R3, R\ R5 and R7 are as defined under 1) - 5). The reaction can be carried out in the presence of an 20 inorganic or organic auxiliary base such as, for example, sodium carbonate, potassium carbonate, sodium hydroxide or triethylamine. It is advantageous to use an inert solvent at temperatures between 0 and 150°C, preferably at reflux temperature. Suitable solvents are open-chain 25 or cyclic ethers, for example tetrahydrofuran or glycol dimethyl ether, aromatic hydrocarbons, for example toluene or chlorobenzene, alcohols, for example ethanol, isopropanol or glycol monomethyl ether, dipolar aprotic solvents, for example N,N-dimethylformamide, 30 N-methyl-2-pyrrolidone or 1,3-dimethyl-tetrahydro- .0 n> U (J - 40 - 2(1H)-pyrimidinone. The N-ortho-nitrophenylamino acids of the formula VIII where Y is hydroxyl can, if desired or necessary, be converted by well-known standard methods into the acid 5 derivatives of the formula VIII where Y is hydroxyl, Ci-C^-alkoxy, optionally halogenated C^-C^-acyloxy, chlorine, bromine or iodine. Ortho-halonitroaromatic compounds of the formula IX and amino acids of the formula X are known from the litera-10 ture and commercially available or can be prepared by methods known from the literature. The reaction described above under E) is preferably effected by means of catalytic hydrogenation (using hydrogen) or hydrosilylation (using alkylsilanes, for 15 example diphenylsilane) in the presence of a hydrogenation catalyst, for example Raney nickel or palladium-on-charcoal, at a hydrogen pressure of 1 to 5 bar, or by means of a reducing agent from the class of the complex metal hydrides such as sodium borohydride or sodium 20 cyanoborohydride, or using metals, or metal salts, and acid such as, for example, zinc/glacial acetic acid or SnCl2/HCl. It is advantageous to carry out the reaction in an inert solvent such as lower alcohols, for example methanol or isopropanol, ethers such as tetrahydrofuran 25 or glycol dimethyl ether, dipolar aprotic solvents such as N,N-dimethylformamide, aromatic hydrocarbons such as toluene or xylene, or mixtures of these solvents, at temperatures between -20 and 100°C, preferably at room temperature. 30 If a chiral hydrogenation catalyst, for example di-/i-chloro-bis[ (cycloocta-lc,5c-diene)-rhodium(I) ]/ ( + ) or (-)-4,5-bis-(diphenylphosphinomethyl)-2,2-dimethyl-1,3-dioxolane, or a chiral complex metal hydride, for example sodium tris- (N-benzyloxycarbonyl-L-prolinoyloxy) -35 borohydride, are used in the above-described reaction, - 41 - the individual enantiomers can be prepared selectively. If, in compounds of the formula XI, substituents are present which can be hydrogenated or reduced under the above-described conditions, for example oxo, it is neces-5 sary to use an intermediate of the f ormula XI with substituents which are not attacked, but which can be derivatized to give the group required, for example hydroxyl. The substituents can also be provided with a customary protective group, for example an acetal protec-10 tive group, which can then be removed after the above-described reaction. Quinoxalinones of the formula XI where R1 to R3 are as defined under 1) - 4) can be obtained by known processes by. condensing a phenylenediamine of the formula VI, where 15 R1 and R2 are as defined under 1) - 4) and R9 is hydrogen, with an alpha-ketocarboxylic acid of the formula XII R3-CO-COOH (XII) where R3 is as defined under 1) - 4). The reaction is expediently carried out in an inert 20 solvent in a temperature range of between 0 and 1504C; examples of suitable solvents are alcohols, for example ethanol or isopropanol, open-chain or cyclic ethers, for example glycol dimethyl ether or tetrahydrofuran, or dipolar aprotic solvents, for example N,N-dimethyl-25 formamide or acetonitrile. The reaction described above under F) is expediently carried out in a two-phase system composed of an organic solvent or solvent mixture which is not miscible with water, composed of, for example, halogenated hydrocar-30 bons, for example dichloromethane or 1,2-dichloroethane, or aromatic hydrocarbons, for example toluene or xylene, and a concentrated aqueous solution of an alkali metal hydroxide cr alkaline earth metal hydroxide, for example sodium hydroxide or barium hydroxide. The presence of a 42 phase transfer catalyst such as, for example, benzyl-triethylammonium chloride or tetrabutylammonium bromide, is advantageous. The reaction is usually carried out at temperatures 5 between 0 and 50°C, preferably at room temperature. Substituents in compounds of the formulae VI and XIII, or XIV, which are not stable under the reaction conditions must be replaced by those which can be derivatized to the required group. The substituents can also be provided 10 with a customary protective group which can then be removed after the above-described reaction. In the reaction described above under 6), Z in formula XV is a suitable leaving group such as, for example, chlorine, bromine or iodine, a suitable sulfuric acid 15 radical, an aliphatic or aromatic sulfonate, or optionally halogenated acyloxy. The reaction conditions for this reaction correspond to those in method A. The reaction described under H) iB preferably effected by 20 catalytic hydrogenation (using hydrogen) in the presence of a hydrogenation catalyst, for example palladium-on-charcoal, at a hydrogen pressure of 1 to 5 bar, or by means of a reducing agent from the class of the complex metal hydrides, such as sodium borohydride, sodium 25 triacetoxyborohydride or sodium cyanoborohydride. The reaction is expediently carried out in an inert solvent, such as lower alcohols, for example methanol or isopropanol, ethers, for example tetrahydrofuran or glycol dimethyl ether, halogenated hydrocarbons, for 30 example dichloromethane or dichloroethane, at temperatures between -20 and 100°C, preferably at room temperature. The presence of an acid such as, for example, acetic acid or trifluoroacetic acid, or of a Lewis acid such as, for example, titanium tetrachloride, is - 43 - advantageous. If, in compounds of the formulae I and XVI, substituents are present which can be hydrogenated or reduced under the above-described conditions, for example oxo, the use of an intermediate of the formulae I and XVI with substituents which are not attacked but which can be derivatized to the required group, for example hydroxyl, is necessary. Acid-labile groups such as, for example, acetals, or groups which react under the reaction conditions, such as, for example, primary amines, are also to be avoided or to be provided with a customary protective group. The reaction described under I) is expediently carried out in an inert solvent. Examples of suitable solvents are aromatic hydrocarbons such as toluene or xylene, lower alcohols such as methanol, ethanol or 1-butanol, ethers such as tetrahydrofuran or glycol dimethyl ether, dipolar aprotic solvents such as N,N-dimethylformamide, N-methyl-2-pyrrolidone, acetonitrile, nitrobenzene, dimethyl sulfoxide, or mixtures of these solvents. Two-phase systems with aqueous solutions of bases in the presence of a phase transfer catalyst such as, for example, benzyltriethylammonium chloride, are also possible. The presence of a suitable base, for example an alkali metal hydroxide or alkaline earth metal hydroxide such as potassium hydroxide or barium hydroxide, of an alcoholate such as sodium ethanolate or potassium tert. -butylate, an organolithium compound such as butyllithium or lithium diisopropylamide, an alkali metal hydride or alkaline earth metal hydride such as sodium hydride or calcium hydride, an alkali metal fluoride such as potassium fluoride, or an organic base such as triethylamine or pyridine, may be useful. The reaction is usually carried out at temperatures between -10 and 160°C, preferably at room temperature. To carry out this reaction, any nucleophilic substituents in compounds XVII and XVIII which do not participate in - 44 - the reaction, such as, for example, hydroxyl, mercapto or amino groups, are to be derivatized in a suitable manner or to be provided with customary protective groups such as, for example, acetyl or benzyl, which can then be 5 eliminated. The compounds XVII which are required for the abovementioned reaction and in which the definitions described under 1) - 4) apply to Rx, R2, R3 and R4, n is 0, 1, 2 or 3, X is oxygen and U is a suitable leaving group, halogen 10 such as, for example, chlorine, bromine, iodine, a halogenated aliphatic or aromatic alcoholate such as, for example, 2,2,2-trichloroethoxy, chlorophenoxy, or a heterocycle which is linked via nitrogen such as, for example, imidazolyl, tri&zolyl or benzotriazolyl, are 15 prepared by reacting a compound of the formula I where Rs is hydrogen and X is oxygen, and the definitions described under 1) - 4) apply to R1, R2, R3 and R4, with a suitable carbonic acid derivative, for example phosgene, diphosgene, triphosgene, trichloroethyl chloroformate or 20 carbonyldiimidazole, or with a suitable halo carbonyl halide, for example bromoacetyl chloride. The reaction is expediently carried out in an inert solvent. Examples of suitable solvents are aromatic hydrocarbons such as toluene or xylene, ethers such as 25 tetrahydrofuran or glycol dimethyl ether, or halogenated hydrocarbons such as dichloromethane or dichloroethane. The presence of a suitable base, for example of an alkali metal hydroxide or alkaline earth metal hydroxide, such as potassium hydroxide or barium hydroxide, or an organic 30 base such as triethylamine or pyridine, may be useful. The reaction is usually carried out at temperatures between -30 and 160°C, preferably at room temperature. The present invention furthermore relates to the compounds as described under 1) to 4) in combination with a nucleoside as pharmaceuticals, preferably for treating viral diseases. Examples of fields of indication in human medicine which may be mentioned are: 1) The treatment and prophylaxis of human retroviral infections 2) For the treatment or the prophylaxis of diseases (AIDS) caused by HIV I (human immunodeficiency virus; previously termed HTLV III/LAV) and HIV II, and the stages associated therewith, such as ARC (AIDS-related complex) and LAS (lymph adenopathy syndrome), as well as the immunodeficiency and encephalopathy caused by this virus. 3) For the treatment or the prophylaxis of an infection with HTLV-I or HTLV-II 4) For the treatment or the prophylaxis of the AIDS carrier condition. Examples of indications in veterinary medicine which may be mentioned are: infections with a) maedivisna (in sheep and goats) b) progressive pneumonia virus (FPV) (in sheep and goats) c) caprine arthritis encephalitis virus (in sheep and goats) d) zwoegerziekte virus (in sheep) e) (equine) infectious anemia virus f) infections caused by feline leukemia virus g) infections caused by feline immunodeficiency virus. The combinations according to the invention are particularly important for controlling HIV and disease caused by HIV. The invention furthermore relates to pharmaceuticals comprising at least one combination of compounds according to the invention, and to the use of the above-mentioned compounds for the preparation of -46 — pharmaceuticals, preferably for the treatment of viral diseases, in particular for the treatment of diseases caused by HIV. The present invention furthermore relates to the use of 5 combinations of the abovementioned compounds for the preparation of pharmaceuticals for the treatment of viral diseases. The pharmaceuticals according to the invention can be administered enterally (orally), parenterally (intra-10 venously), rectally, subcutaneously, intramuscularly or locally (topically). They can be administered in the form of solutions, powders, (tablets, capsules including microcapsules), ointments (creams or gels) or suppositories. Suitable 15 adjuvants for such formulations are the liquid or solid fillers and extenders, solvents, emulsifiers, glidants, flavorings, colorings and/or buffer substances which are customary in pharmacology. 0.1 - 10, preferably 0.2-8 mg/kg of body weight are 20 administered once or several times daily as an expedient dosage. The dosage units used depend expediently on the specific pharmacokinetics of the substance used, or on the pharmaceutical formulation used. For example, the dosage unit of the compounds according 25 to the invention is 1 - 1500 mg, preferably 50 - 500 mg. The composition of the combination preparations according to the invention can vary within wide limits and be optimized by means of methods of the prior art. A suitable ratio in the compositon is, for example, between 30 1:1000 and 1000:1, preferably between 1:100 and 100:1. Experimental set-up HIV infection in cell culture - 47 The HIV test was carried out by the modified method of Pauwels et al. (cf. Journal of Virological Methods 20 (1988), 309-321). Normal human blood lymphocytes (PBLs) were enriched using Ficoll-Hypaque and stimulated in RPMI 5 1640, 20% fetal calf serum using phythemagglutinin (90 pg/ml) and interleukin-2 (40 U/ml). For the infection with the infectious HIV, PBLs were pelleted, and the cell pellet was subsequently suspended in 1 ml of HIV solution for the purpose of adsorption and incubated for 1 hour at 10 37°C. The virus adsorption solution was centrifuged, and the infected cell pellet was taken up in growth medium in such a way that 1 x 10s cells were present per ml. The cells which had been infected in this manner were 15 pipetted into the wells of 96-microtiter plates at a density of 1 x 10* cells/well. As an alternative, H9 cells were employed for the antiviral tests in place of the PBLs. The activity of the test compounds in combination was 20 tested by means of chequerboard titration. The first vertical row of the microtiter plate contained only growth medium and cells which had not been infected but were otherwise treated exactly as described above (cell control). The second vertical row of the microtiter 25 plate contained only HIV-infected cells (virus control) in growth medium. The remaining wells contained the compounds according to the invention - alone or in suitable combinations - in a range of concentrations starting from the wells of the 3rd vertical row of the 30 microtiter plate, from which the test substances were diluted further in steps of 2 (volume per well: 100 jil). For the combination, dilutions of substance 2 were prepared in a separate 96-microtiter plate and subsequently pipetted onto the prepared first plate. 100 pi 35 aliquots of the prepared HIV-infected cells (Bee above) were added to this. This gave test concentrations in a range of approximately 10-50 times above and below the IC-50 concentration. The batches were incubated at 37°C until the formation of syncytia on the host cell, which is typical for HIV, was detected under the microscope in the untreated virus control (between day 3 and day 6 post-infection). In the 5 untreated virus control, approximately 20-50 syncytia were found under these test conditions, while no syncytia were found in the untreated cell control. The supernatants of the 96-plate were then harvested and examined for HIV-specific antigen using an HIV-specific 10 ELISA test (Vironostika HIV Antigen, Organon Teknika). On the basis of the cut-off values of suitable cell or virus controls or internal test controls, the inhibitory values were converted into percent (%) inhibitory values, and the IC-50 values were determined as the concentration 15 of the treated and infected cells at which 50% of the virus-specific antigen was suppressed by the treatment with the compounds. To analyze the synergistic activity of the compounds, the differential values were determined of calculated and measured inhibitory values of each 20 combination (Prichard, M.N. et al., Antimicrob. Agents Chemoth. (1993), 37, 540-545). Differential values > zero mean that a synergistic activity can be described. For example, the compound of the formula A gave the following results: 25 (Table la and Table lb) Formula A H o^o HjC CHj Chemical name: S-4-Isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)- 3,4-dihydroquinoxaline-2(lH)-thione, melting point 101°C. Table la Tabulated difference between the calculated and the expected activity of AZT using formula (A) as an example Compound of formula (A) nM the 50 25 12 6 3 1 AZT nM 50 0 0 0 0 0 0 25 0 0 0 0 -17 -4 12 0 0 4 18 23 23 6 0 0 7 29 23 -17 3 0 0 10 33 10 -13 in • H 0 0 -2 40 17 3 0.7 i—i i -20 -5 7 17 3 Table lb Tabulated differences between the calculated and experimentally determined inhibitory values of 3'-TC and the exemplary compound of the formula (A) Compound of formula (A) nM the 50 25 12 6 3 1.5 3TC nM 50 0 0 0 2 -7 -60 25 0 0 0 40 70 30 12 0 0 0 47 60 20 6 0 0 0 30 40 22 3 0 0 0 34 17 0 A synergistic activity of the combinations can be found in the concentration range 0.7-12 nM AZT together with 1-6 nM of the quinoxaline. Equally synergistically active - 50 - are the quinoxaline and 3TC in the concentration range of 1.5-6 nM and 3-25 nM, respectively. To measure a synergistic toxicity of the compounds, substance concentrations were tested around the Tox-50 value of the 5 individual compounds and evaluated in the same manner. None of the tested combinations showed synergistic toxicity. The examples which follow and the content of the patent claims illustrate the present invention in greater 10 detail. Example I (3S)-6-Chloro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one A) (S)-N-(3-Chloro-6-nitrophenyl)alanine 2,4-Dichloronitrobenzene (21.0 g, 0.109 mol) and 23.0 g 15 (0.258 mol) of L-alanine were refluxed for 48 hours in 400 ml of 2-methoxyethanol with an addition of 120 ml of 2N sodium hydroxide solution. The mixture was subsequently concentrated in vacuo, and the residue was taken up in aqueous sodium hydrogen carbonate solution. 20 the mixture was extracted three times using ethyl acetate, the extract was then acidified with 6N hydrochloric acid, and the yellow product was extracted using ethyl acetate. The organic phase was washed once with saturated aqueous sodium chloride solution and dried 25 (magnesium sulfate), and the solvent was removed under reduced pressure. 14.7 g (55%) of a yellow solid of melting point 167-169°C remained (after crystallization from ethyl acetate). lH NMR (270 MHz, d6-DMSO) : 6 = 1.47 (d, J « 7 Hz, 3 H), 30 4.57 (quintet, J » 7 Hz, 1 H), 6.77 (dd, J » 9, 2 Hz, 1 H), 7.11 (d, J » 2 Hz, 1 H), 8.12 (d, J - 9 Hz, 2 H), 8.41 (br. d, J » 7 Hz, 1 H), 13.2 ppm (br., 1 H). MS: (M + H)+ = 245 B) (3S)-6-Chloro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one The product of Example IA (14.0 g, 0.057 mol) was dissolved in 400 ml of methanol and hydrogenated with Raney nickel catalysis at room temperature, using 1 atm hydro-5 gen. After the calculated amount of hydrogen had been taken up, the catalyst was removed by filtration with suction, and the reaction solution was concentrated in vacuot The residue was purified by silica gel chromatography using ethyl acetate/heptane « 1:2 and 1:1 10 as the eluent. The yield was 6.0 g (53%) of a brownish solid of melting point 122-123°C (after recrystallization from isopropanol/heptane). *H NMR (60 MHz, d6-DMS0) : 6 - 1.23 (d, J « 11 Hz, 3 H), 3.81 (dq, J » 11, 4 Hz, 1 H), 6.27 (br., 1 H), 6.3 - 6.9 15 (m, 3 H), 10.3 ppm (br., 1 H). MS: (M + H)+ « 197 [a]D23 - +77.3° (c - 1, MeOH) C) (3R)-6-Chloro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one The compound was prepared from D-alanine by the methods 20 described under Example IA and IB. Melting point 123-124°C (after recrystallization from isopropanol/heptane) The NMR data agree with those of the compound described in Example IB. 25 [a]D23 = -81.0° (c - 1, MeOH) D) (3RS)-6-Chloro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one The compound was prepared starting from D,L-alanine by the methods described in Examples IA and IB. Melting 30 point 110°C (after recrystallization from isopropanol/heptane) The NMR data agree with those of the compound described in Example IB. The following compounds of the formula I were synthesized analogously using the corresponding haloaromatic compounds and amino acid derivatives: Example II 5 (3S)-3-Benzyl-7-chloro-3,4-dihydroquinoxalin-2(1H)-one A) (S)-N-(4-chloro-2-nitrophenyl)-phenylalanine L-Phenylalanine (8.3 g, 0.05 mol) and 4.8 g (0.025 mol) of 2,5-dichloronitrobenzene were dissolved in 40 ml of anhydrous dimethyl sulfoxide (DMSO), and the stirred 10 solution was heated to 80°C under an argon atmosphere. Potassium tert.-butylate (4.2 g, 0.025 mol), dissolved in 30 ml of DMSO, was added dropwise in the course of 40 minutes. Stirring was continued for 3 hours at 80 to 90°C, the mixture was allowed to cool, and unreacted 15 phenylalanine was removed by filtration with suction and washed with water. The collected alkaline filtrates were extracted twice using diethyl ether to remove unreacted dichloronitrobenzene. The mixture was then acidified using glacial acetic acid and extracted several times 20 using ethyl acetate, and the extracts were dried over magnesium sulfate and evaporated. The product was obtained in the form of a red oil (6.7 g, 84%), which was further reacted without purification. B) (3S)-3-Benzyl-7-chloro-3,4-dihydroquinoxalin-2(1H)-one 25 The product of Example IIA (12 g) was dissolved in 300 ml of anhydrous methanol and hydrogenated at room temperature with palladium/charcoal catalysis, using 1 atm hydrogen. When the reaction had ended, solids were filtered off with suction, the liquid was concentrated, 30 and the concentrate was chromatographed on silica gel using diisopropyl ether as the eluent. This gave 1.32 g of the desired product which crystallized from iso-propanol, melting point 185°. *H NMR (270 MHz, d6-DMSO): 6 ■ 2.9 (m, 2 H), 4.08 (m 1 H), 6.09 (d, 1 H), 6.7 (m, 2 H), 6.78 (m, 1 H), 7.2 (m 5 H), 10.34 ppm (br. 8, 1 H). MS: (M + H)+ - 273, (M - 92)+ » 181. The compounds in Table 2 were prepared as described the above examples. Table 2 h No. r'n r3 r5 M.p.°C 1 i 5-c1 ch3 h Wax 2 6-Cl c2h5 h 120 3 6-Cl c2h4cooh h 4 6-Cl -ch2ch2co- 5 6-Cl (ch3)2ch h 6 6-Cl (ch3)2chch2 h Oil 7 6-Cl c2h5(ch3)ch h Oil 8 6-Cl c6h3ch2 h 156-157 9 6-Cl ch3sch2ch2 h 97 10 6-Cl ch3sch2 h 149 - 54 - 270oen No. R3 R5 M.p.°C 11 6-Cl ch2(oh) h 12 6-Cl ch3ch2ch2 h 75-77 13 7-Cl ch3 E 142 14 7-Cl (ch3)2ch h Oil 15 7-Cl ch3sc2h4 h 98 16 8-C1 ch3 h 17 6/7-Cl2 ch3 h 18 7-F ch3 h 230 19 6-F ch3 h Wax 20 6-F ch3 c3h3 182 21 6-F c6h5ch2 c3h5 22 7-CF3 ch3 h 147 23 6-CH30C2H40 C2H3 h 107 24 6-Cl c2h4oh h 211 25 6-Cl CH2-S-Bn h 170 26 6-Cl CH2-S-i.-Pr H 190 27 6-Cl CH20-t. -Bu h 128 28 6-CL c,h9 h 115 Bn =» benzyl i-Pr = isopropyl t-Bu = tert.-butyl - 55 - 2700gr. Example III (3S)-4-N-(Benzyloxycarbonyl)-6-chloro-3-methyl-3,4-di-hydroquinoxalin-2(1H)-one The compound of Example IB (1.0 g, 5.1 mmol) was dis-5 solved in 20 ml of dichloromethane. 10 ml of 211 aqueous sodium hydrogen carbonate solution were add&d, and 0.9 ml (90%; 5.7 mmol) of benzyl chloroformate was added with ice-cooling and vigorous stirring. The two-phase system was subsequently stirred for 60 hours at room tempera-10 ture. After 30 hours, another 0.2 ml (1.3 mmol) of benzyl chloroformate was added. When the reaction was complete, the phases were separated, the organic phase was washed once with water and dried (magnesium sulfate), and the solvent was removed in vacuo. The product was purified by 15 silica gel chromatography with methyl tert.-butyl ether/ heptane = 1:1 as the eluent. This gave 1.65 g (98%) of a white, foam-like product. *H NMR (270 MHz, d6-DMSO): 6-1.15 (d, J - 7 Hz, 3 H), 4.85 (q, J - 7 Hz, 1 H), 5.20 (d, J - 12 Hz, 1 H), 5.27 20 (d, J = 12 Hz, 1 H), 6.97 (d, J - 7 Hz, 1 H), 7.19 (dd, J = 8.2 Hz, 1 H), 7.3 - 7.45 (m, 5 H), 7.67 (d, J » 2 Hz, 1 H), 10.81 ppm (br. s, 1 H). MS: (M + H)+ « 381 Example IV 25 (3S) -4-N- (Benzy loxycarbonyl) -6-chloro-3-methyl-8-nitro- 3,4-dihydroquinoxalin-2(1H)-one The compound of Example III (1.5 g, 4.5 mmol) was nitrated in glacial acetic acid (15 ml). A total of 5 ml (124.3 mmol) of fuming nitric acid were added dropwise in 30 the course of 4 hours at 0°C to room temperature. The mixture was subsequently poured into 100 ml of ice-water, and the product, which was obtained in the form of a yellow solid, was filtered off, washed thoroughly with water, and dried. Melting point 85°C (subl.). » 270000 - 56 - *H NMR (270 MHz, d6-DMSO) s S - 1.22 (d, J « 8 Hz, 3 H), 4.89 (q, J = 8 Hz, 1 H), 5.24 (d, J « 12 Hz, 1 H), 5.31 (d, J = 12 Hz, 1 H), 7.35 - 7.5 (m, 5 H), 7.69 (s, 1 H), 8.00 (s, 1 H), 11.11 ppm (br. s, 1 H). 5 MS: (M + H)+ » 376 Example V (3S) -8-Amino-4-N- (benzyloxycarbonyl) -6-chloro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one The compound of Example IV (1.5 g, 4.0 mmol) was dis-10 solved in 150 ml of methanol and hydrogenated at room temperature with Raney nickel catalysis, using 1 atm hydrogen. When the calculated amount of hydrogen had been taken up, the catalyst was removed by filtration with suction, and the filtrate was concentrated in vacuo. The 15 product was purified by silica gel chromatography using ethyl acetate/heptane - 2:1 as eluent. The yield was 0.68 g (49%) of brownish solid of melting point 152-154°C. XH NMR (270 MHz, d6-DMSO) : £ - 1.11 (d, J - 8 Hz, 3 H), 20 4.79 (q, J « 8 Hz, 1 H), 5.15 (d, J » 12 Hz, 1 H), 5.24 (d, J - 12 Hz, 1 H), 5.38 (br. s, 2 H), 6.42 (s, 1 H), 7.3-7.4 (m, 6 H), 10.59 ppm (br. s, 1 H). MS: (M + H)+ = 346 Example VI 25 A) (3S)-6-Chloro-3-methyl-4-N-(3-methyl-2-buten-l-yl)- 3.4-dihydroquinoxalin-2(1H)-one The compound of Example IB (1.0 g, 5.0 mmol) was dissolved in 20 ml of acetonitrile and alkylated with 3-methyl-2-buten-l-yl bromide (90%; 0.92 ml, 7.0 mmol) at 30 room temperature in the presence of 1.0 g (7.0 mmol) of pulverulent potassium carbonate. After 7 hours, the reaction had ended. The mixture was filtered off with suction, the filtrate was concentrated in vacuo, and the 57 - 270 product was purified by silica gel chromatography using ethyl acetate/heptane ® 1:2 as eluent. The yield was 0.97 g (72%) of brownish solid of melting point 117-118°C (after crystallization from methyl tert.-butyl ether/ heptane). *H NMR (270 MHz, dB-DMS0): S - 1.02 (d, J ■ 8 Hz, 3 H), 1.74 (s, 6 H), 3.69 (dd, J - 14, 8 Hz, 1 H), 3.85 - 3.9 (m, 2 H), 5.19 (m, 1 H), 6.65 - 6.8 (m, 3 H), 10.47 ppm (br. s, 1 H). MS: (M + H)+ = 265 [q]D23 » +168.0° (c « 1, MeOH) B) (3R)-6-Chloro-3-methyl-4-N-(3-methyl-2-buten-l-yl)-3,4-dihydroquinoxalin-2(1H)-one The compound was prepared by the method described in Example VIA, starting from the compound of Example IC. Melting point 115-117°C (after recrystallization from isopropanol/diethyl ether) The NMR data agreed with those of the compound described in Example VIA. [a]D23 = -172° (c « 1, MeOH) C) (3RS)-6-Chloro-3-methyl-4-N-(3-methyl-2-buten-l-yl)-3,4-dihydroquinoxalin-2(1H)-one The compound was prepared by the method described in Example VIA starting with the compound of Example ID. Melting point 148-149°C (after recrystallization from isopropanol/diethyl ether) The NMR data agreed with those of the compound described in Example VIA. - 58 - Example VII (3S)-6-Chloro-3-methyl-4-N-(2-buten-l-yl)-3,4-dihydro-quinoxalin-2(1H)-one The substance was prepared analogously to the compound described in Example VIA, but with 2-buten-l-yl bromide as the alkylating agent. Melting point 87-88°C (after crystallization from diethyl ether/heptane) *H NMR (270 MHz, d6-DMSO): S » 1.01 (d, J - 8 Hz, 3 H), 1.70 (dd, J » 8, 1 Hz, 3 H), 3.C3 (dd, J - 16, 6 Hz, 1 H), 3.85 - 4.0 (m, 2 H), 5.47 (m, 1 H), 5.75 (m, 1 H), 6.65 - 6.8 (m, 3 H), 10.48 ppm (br. b, 1 H). MS: (M + H)+ » 251 Example VIII 4 -N-(Isopropenyloxycarbonyl)-3,3,7-trimethyl-3,4-di-hydroquinoxalin-2(1H)-one 3,3,7-Trimethyl-3,4-dihydroquinoxalin-2(lH)-one (0.4 g, 2.1 mmol) were dissolved in 10 ml of anhydrous pyridine, and the stirred solution was treated at room temperature with 0.24 ml (2.2 mmol) of isopropenyl chloroformate. The mixture was stirred for 6 hours at room temperature and treated with water, the precipitate which formed was filtered off with suction, washed with water and dried. This gave 0.4 g (69%) of colorless crystals of melting point 185#C. XH NMR (270 MHz, dB-DMS0): 6 « 1.5 (s, 6 H), 1.9 (s, 3 H), 2.25 (s, 3 H), 4.7 (m, 2 H), 6.7 - 6.9 (m, 2 H), 7.15 (d, J = 8 Hz, 1 H), 10.6 ppm (br. s, 1 H). MS: + - 274 Example IX (3S)-6-Chloro-4-N-(4-methoxyphenoxycarbonyl)-3-methyl-3,4-dihydroquinoxalin-2(1H)-one The compound of Example IB (0.5 g, 2.55 mmol) was dissolved in 10 ml of anhydrous N,N-dimethylformamide, and 0.41 ml (2.8 mmol) of triethylamine were added. To the - 59 - stirred mixture there was first added dropwise 0.42 ml (2.8 mmol) of 4-methoxyphenyl chloroformate and, after 2 hours, another 0.21 ml (1.9 mmol). When the reaction w?^> complete (18 hours), the solvent was stripped off 5 under reduced pressure, the residue was taken up in ethyl acetate, and the mixture was washed with water and dried (sodium sulfate). 0.48 g (54%) of a white solid remained after concentration. Melting point 187-190°C (after xecrystallization from isopropanol) 10 *H NMR (270 MHz, d6-DMSO): S - 1.24 (d, J » 8 Hz, 3 H), 3.77 (s, 3 H), 4.94 (q, J » 8 Hz, 1 H), 6.97 (dd, J = 8, 2 Hz, 1 H)f 7.03 (d, J - 8 Hz, 1 H), 7.2 - 7.3 (m, 3 H), 7.78 (s, 1 H), 10.89 ppm (br. s, 1 H). MS: (M + H)+ - 347 15 Example X (3S) -6-Chloro-4-N~ (4-f luorophenoxycarbonyl) -3-methyl-3,4-dihydroquinoxalin-2(1H)-one The compound was prepared analogously to the compound described in Example VIA, but 4-fluorophenyl chloro-20 formate was used as acylating agent. Melting point 168-170°C (after crystallization from isopropanol) *H NMR (270 MHz, dB-DMS0): S » 1.24 (d, J - 8 Hz, 3 H), 4.94 (q, J » 8 Hz, 1 H), 7.03 (d, 8 Hz, 1 H), 7.2 - 7.5 (m, 5 H), 7.83 (d, J « 2 Hz, 1 H), 10.90 ppm (br. s, 25 1 H). MS: (M + H)+ « 335 Example XI (3S) -6-Chloro-4-N- (4-chlorophenoxycarbonyl) -3-methyl-3,4-dihydroquinoxalin-2(1H)-one 30 The compound was prepared analogously to the compound described in Example VIA, but 4-chlorophenyl chloroformate was used as acylating agent. Melting point 185-188°C (after crystallization from isopropanol/diethyl ether) - 60 - *H NMR (270 MHz, d6-DMSO) S S ■ 1.25 (d, J » 8 Hz, 3 H), 4.94 (q, J » 8 Hz, 1 H), 7.04 (d, 8 Hz, 1 H), 7.25 (dd, J « 8, 2 Hz, 1 H), 7.35 - 7.6 (m, 4 H), 7.80 (s, 1 H), 10.91 ppm (br. 8, 1 H). 5 MSs (M + H)+ - 351 Example XII (3S) -4-N- (2-Bromoethyloxycarbonyl) -6-chloro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one The compound was prepared analogously to the compound 10 described in Example VIA, but 2-bromoethyl chloroformate was used for the acylation. Melting point 133-136°C (after crystallization from isopropanol) XH NMR (270 MHz, d6-DMSO) : S « 1,16 (d, J » 8 Hz, 3 H), 3.7 - 3.8 (m, 2 H), 4.4 - 4.6 (m, 2 H), 4.86 (q, 15 J = 8 Hz), 6.99 (d, 8 Hz, 1 H), 7.21 (dd, 8, 2 Hz, 1 H), 7.74 (d, J = 2 Hz, 1 H), 10.84 ppm (br. s, 1 H). MS: (M + H)+ « 348 Example XIII ( 3S) -6-Chloro-N- (isopropenyloxycarbonyl) -3-methyl-20 3,4-dihydroquinoxalin-2(1H)-one The substance was prepared analogously to the compound described in Example VIA, but isopropenyl chloroformate was used for the acylation. Melting point 158-159°C *H NMR (270 MHz, CDC13) s S = 1.33 (d, J » 8 Hz, 3 H), 2.02 25 (s, 3 H), 4.79 (s, 1 H), 4.83 (s, 1 H), 5.17 (q, J = 8 Hz, 1 H), 6.86 (d, J ■ 8 Hz, 1 H), 7.12 (dd, J « 8, 2 Hz, 1 H), 7.74 (br. s, 1 H), 9.28 ppm (br. s, 1 H). MS: (M + H)+ - 281 Example XIV 30 (3S) -6-Chloro-3-methyl-4-N- (vinyloxycarbonyl) -3,4-di-hydroquinoxalin-2(1H)-one The substance was prepared analogously to the compound described in Example VIA, but vinyl chloroformate was 270 - 61 - used for the acylation. Melting point 177-179®C *H NMR (270 MHz, CDC13) s 6 « 1.33 (d, J » 8 Hz, 3 H), 4.96 (dd, J = 14, 2 Hz, 1 H), 5.20 (q, J » 8 Hz, 1 H), 6.83 (d, J = 8 Hz, 1 H), 7.12 (dd, J ■ 8, 2 Hz, 1 H), 7.2 - 7.3 (m, 2 H), 7.71 (br. s, 1 H), 9.42 ppm (br. s, 1 H) . MS: (M + H)+ = 267 Example XV and Example XVI 6-Chloro-3,4-dihydroquinoxalin-2 (1H) -one was reacted with 3-methyl-2-buten-l-yl bromide analogously to the process described in Example VIA.. It was possible to isolate two products by silica gel chromatography. 6-Chloro-4-N-(3-methyl-2-buten-l-yl)-3,4-dihydro-quinoxalin-2(1H)-one Melting point 150-151°C (after recrystallization from ethyl acetate) *H NMR (270 MHz, d6-DMSO): 6 « 1.72 (s, 6 H), 3.67 (s, 2 H), 3.80 (d, J = 7 Hz, 2 H), 5.20 (m, 1 H), 6.7 - 6.8 (m, 3 H), 10.49 ppm (br. s, 1 H). MS: (M + H)+ »= 251 6-Chloro-4-N- (3-methyl-2-buten-l-yl) -3- (1,1-dimethyl-2-propen-l-yl)-3,4-dihydroquinoxalin-2(1H)-one Melting point 110-112°C (after crystallization from heptane) XH NMR (270 MHz, d6-DMS0) S 6 - 0.94 (s, 3 H) , 0.97 (s, 3 H), 1.65 (s, 3 H), 1.66 (s, 3 H), 3.77 (dd, J « 16, 7 Hz, 1 H), 4.23 (dd, J - 16, 7 Hz, 1 H), 4.8 - 4.9 (m, 2 H), 5.02 (m, 1 H), 5.75 (dd, J » 17, 11 Hz, 1 H), 6.6 - 6.7 (m, 3 H), 10.49 ppm (br. s, 1 H). MS: (M + H)+ - 319 The following compounds of the formula I were synthesized from the corresponding unsubstituted quinoxalinones in analogous manner and, if appropriate, derivatized further: Tcible 3 R No. rV R2 R3 R5 M.p. °C 1 1 b ch3 c2haOCH3 59 I 2 h cb3 c4h7 no I 3 h ch3 sC6Hu 100 1 4 5-Cl b ch3 C6Hh Oil 1 5 5-Cl b ch3 sCbhiX 135 1 Ot to SJ No. r» R2 R3 R5 M.p. °C 6 6-Cl h ch3 ALAC 180 - 182 7 6-Cl h ch3 aloc 124 - 127 8 6-Cl h ch3 so2ch3 184 I 9 6-Cl B ch3 so2c6h5 253 | 10 6-Cl h ch3 s02c6h*-4-ch3 259 - 262 i 11 6-Cl h ch3 S02c6ha-4-c1 > 270 I 12 6-Cl h ch3 s02c6h,-4-n02 > 270 1 13 6-Cl h ch3 so2ch=ch2 180 - 182 1 14 6-Cl h ch3 coch2och3 202 I 15 6-Cl h ch3 CSNH-c6ha-4-cn 216 1 16 6-Cl h ch3 coch2ch(ch3)2 Foam 8 Go • • • • No. r'n R2 R3 R5 M.p.°C 17 6-Cl h ch3 coc6h5 108 - 109 i 18 6-Cl h ch3 cocl 138 I 19 6-Cl h ch3 coch2ch2ch=ch2 Foam | 20 6-Cl h ch3 c2h„och3 78-79 1 21 6-Cl h ch3 ch2c6h5 155 - 156 1 22 6-Cl h ce3 2-c0-c4h30 105 - 107 1 23 6-Cl h ch3 cooch2ch3 149 - 153 1 24 6-Cl h ch3 c00(ch2)2ch3 113 - 116 jj 25 6-Cl h ch3 c00(ch2)3ch3 80-82 1 26 6-Cl h ch3 c00ch2ch(cfl3)2 131 - 132 1 " 6-Cl h ch3 coch2ch=ch2 130 1 Ot No. R'n R2 R3 R5 M.p.°C 28 6-Cl h ch3 coch2ch=chch3 155 29 6-Cl h c2h5 C5hb 128 30 6-Cl h c2h5 ipoc 175 1 31 6-Cl h c2h5 ceo 204 1 32 6-Cl h c2h5 aloc 148 - 150 | 33 6-ch30c2h40 H c2h5 ipoc 173 I 34 6-Cl h c3h7 ipoc 149 - 150 1 35 6-Cl h c3h7 ALOC 135 36 6-Cl h ch(ch3)2 c5h9 126 - 128 1 1 37 6-Cl h ch(ch3)2 ipoc 144 - 145 38 6-Cl h ch(ch3)2 ALOC Ot Ul r <T\ • • • • 1 No. R'n R2 R3 R5 m.p.°c 39 6-Cl h c2h4cooh c5hg 40 6-Cl h c,b9 c5h8 41 6-Cl h ch2c6h5 c5h9 134 1 42 6-Cl h ch2c6h5 ipoc 165 I 43 6-Cl b c2b4scb3 c5h9 011 1 44 6-Cl b c2b4scb3 ipoc 135 | 45 6-Cl h c2b4soch3 ipoc Oil I 46 6-Cl h cb2(oh) c5h9 47 6-Cl h ch2ch (ch3) 2 c5h9 011 1 I 48 6-Cl b ch2ch (ch3) 2 aloc 140 1 I 49 6-Cl b cbzcb (cb3) 2 ipoc 148 1 91 Ol No. r'n r2 r3 r5 m.p.°c 50 6,7-Cl2 h ch3 c5h9 51 8-C1 h ch3 c5h9 52 5-Cl h ch3 c5hg 150 decomp. 1 53 7-Cl h cb3 c5h9 011 I 54 7-Cl h ch3 ALOC 129 1 55 7-Cl h ch3 IPOC 166 1 56 7-Cl h ch(ch3)2 c5h0 221 1 57 7-Cl h ch(cb3)2 IPOC 151 58 7-Cl b cb(ch3)2 ALOC 142 59 7-Cl h ch2c6h3 CsHs Oil - 7-Cl h ch2c6h5 IPOC 178 1 I o\ 1*8 No. R1* R2 R3 R5 M.p.°C 61 i n h H C2BaSCB3 c5h9 98 62 7-Cl h C2HaSCH3 IPOC 148 I 63 7-Cl H c2b,sch3 ALOC 116 1 64 7-F H ch3 c5h9 75 1 65 7-F B cb3 ALOC 155 I 66 7-F H ch3 IPOC 168 1 67 6-F B ch3 C5H8 153 1 68 6-F B cb3 ALOC 120 I 69 6-F B ch3 IPOC 175 | 70 7-CF3 B ch3 c5hb 145 I 71 7-CF3 B ch3 IPOC 186 I o\ CO IN3 ::j> $ No. R'n r2 r3 r5 M.p.°C 72 7-c6h50 h ch3 c5h9 107 73 7-c6hso h ch3 ipoc 172 74 6-Cl h c2h4so2ch3 ipoc 160 decomp. 75 6-Cl h ch2sch3 c5h9 118 76 6-Cl h ch2sch3 ipoc 182 | 77 6-Cl h ch2soch3 ipoc 202 decomp. fl 78 6-Cl h ch2so2ch3 ipoc 212 decomp. g 79 6-Cl h ch(ch3)ch2ch3 c5h9 87 I 80 6-Cl h ch(ch3)ch2ch3 aloc 74 I 81 6-Cl h ch ( ch3) ch2ch3 ipoc 142 I 82 6-f h ch3 coch3 186 I Ot vo CD Co | oct - 821 h eho h*hsozho-2 to-9 £6 VSl - 2si h cho ho-ozho to-9 26 oh - 6€i shzoood shzdoooo*hzo h to-9 t6 1 2£2 ehdod ehd h to-9 06 8 8*t ehdzhdod eho h to-9 68 1 89 ehdz(zh0)0 0 ehd h to-9 88 I IT0 ehde (zEZ) ) od eho h to-9 LQ 891 tdzhdod ehd h to-9 98 08 sh9dzhooo eho h to-9 58 21t seh*doo-2 eho h to-9 fr8 s8t hozhooo eho h to-9 £8 do'tf'w s* E* > 'OR No. r'n R2 R3 R5 M.p.°C 94 6-Cl CH2Ph ch3 H 126 - 127 95 6-Cl c2h5ch(ch3)2 ch3 H 70 - 72 96 6-Cl ch3 ch3 c5h9 Oil 97 6-Cl ch3 ch3 h 115 I 98 6-Cl cooc(ch3)3 ch3 h 82 - 83 99 7-Cl c5ha ch3 c5h9 Resin 100 7-Cl C5H9 ch3 H 108 I 101 7-Ph0S02 C3H8 ch3 c5h9 Oil 102 7-Ph0S02 c5hb ch3 H Oil 103 c2h,och3 ch3 c2h4och3 Oil 104 6-Cl H ch3 so2c4h3s 264 m No. R'n R2 R3 R5 m.p.°c 105 6-Cl h -ch2ch2och2- 210 1 106 6-Cl h ch3 coch2n (c2h5) 2 108 1 107 6-Cl h ch3 c0ch2n (ch3) 2 166 108 6-Cl h ch3 c0ch2n(c2hj20 190 109 6-Cl h ch3 c0ch2n(ch2)4 185 110 6-Cl H ch3 coch2n (ch2) 5 164 111 6-Cl H ch3 C0CHZ- (4-methyl-piperazin-l-yl) 176 112 6-Cl h ch3 co-4-c5h«n 214 I 113 6-Cl H ch3 c0ch2nhch2ch=ch2 152 I 114 6-Cl H ch3 coch2c4h3s — .. ... 155 - 156 1 to No. RXn r2 R3 r5 M.p.°C 115 6-Cl H CH20-t. -Bu c5h9 Oil 116 6-Cl H CH20-t.-Bu ALOC Oil 117 6-Cl B CH20-t. -Bu IPOC 154 118 6-Cl H CH2S-I. -Pr c5h9 Oil 119 6-Cl H CH2S-i.-Pr IPOC 158 120 6-Cl H CH2S-Bn C5H9 Oil 121 6-Cl h CH2-S-Bn IPOC Oil 122 6,7-Cl2 h CH3 c5h8 160 123 6,7-Cl2 H ch3 IPOC I 124 6-Cl H IPOC 158 I 125 6-Cl h c.ba ALOC 100 I 126 6-Cl H ch3 ( CaH3S ) -2-CH2CO 156 1 127 6-Cl H ch2sch3 COOCH(CH3)2 157 8 128 6-CH30 b ch2sch3 IPOC 152 I 129 6-CH3O b cb2scb3 COOCH(CH3)2 165 1 w I VJ CD GO 74 C5H9 ■ 3-methyl-2-buten-l-yl CaH7 - 2-butenyl C5H11 - 3-methyl-l-butyl C6Hu - 2,2-diinethylcyclopropyl-l-methyl sC8Hn» 4-methyl-3-penten-2-yl C3H3 ■ 2-propen-l-yl (CH3)2CCHCO - 3,3-dimethylacryl IPOC « isopropenyloxycarbonyl ALAC ■» allylaminocarbonyl ALOC ■ allyloxycarbonyl CAH30 ■ furanyl CaH3S ■ thienyl C5HaN « pyridyl Ph ■ phenyl - 75 - Example XVII 6,7-Dimethoxy-3-methyl-3,4-dihydroquinoxalin-2(1H)-one 4,5-Dimethoxy-l,2-dinitrobenzene (34.2 g, 0.15 mol) was hydrogenated in 500 ml of methanol with Raney nickel 5 catalysis using 1 atm hydrogen. After the calculated amount of hydrogen had been taken up, the process was stopped, the catalyst was removed by filtration with suction, and the solvent was stripped off in vacuo. To remove the water completely, the mixture was taken up 10 twice in methanol and reconcentrated. 4,5-Dimethoxy-1,2-phenylenediamine (24.0 g), which remained as a brown oil, was refluxed for 48 hours in 200 ml of ethanol (96%) together with 17.1 ml (0.15 mol) of methyl 2-chloro-propionate, with an addition of 21.0 ml (0.15 mol) of 15 triethylassine. The solution, which was very dark, was concentrated, the concentrate was taken up in ethyl acetate, the mixture was washed twice with water and dried (sodium sulfate), and the solvent was stripped off in vacuo. 20 The crude product was crystallized by stirring with diethyl ether (6.2 g, 19%). A analytically pure sample of melting point 151°C was obtained by silica gel chromatography using ethyl acetate as the eluent. 1H NMR (60 MHz, d6-DMSO): 6 - 1.22 (d, J = 7 Hz, 3 H), 25 3.63 (s, 3 H), 3.67 (s, 1 H), 3.6 - 3.7 (m, 1 H), 5.62 (br. s, 1 H), 6.40 (s, 1 H), 6.45 (s, 1H), 9.90 ppm (br. s, 1 H). MS: M+ » 222 The following compounds of the formula I were synthesized 30 in analogous manner and, if appropriate, derivatized further: H - 76 - Table 4 No. R3 R3 x M.p.°C 1 6,7- (ch30)2 ch3 IPOC 0 133 2 6,7-(ch30)2 ch3 IPOC s 3 6-c6h5s ch3 csh9 0 115 4 7-c6h5s ch3 c5h9 0 107 5 6-C6HjS ch3 h 0 6 7-C6HsS ch3 h 0 7 6,7 (ch30) 2 ch3 h 0 151 Keys C5H9 = 3-methyl-2-buten-l-yl IPOC » isopropenyloxycarbonyl Example XVIII 5 (3RS)-6-Chloro-4-N-(cyclopropyl)-3-methyl-3,4-dihydro- quinoxalin-2(1H)-one A) (2RS)-N-(4-Chloro-2-cyclopropylaminophenyl)-(2-bromo-propionamide) 4-Chloro-2-cyclopropylaminonitrobenzene (2.10 g, 10 0.01 mol) was hydrogenated in 100 ml of methanol with Raney nickel catalysis, using 1 atm hydrogen. After the calculated amount of hydrogen had been taken up, the process was stopped, the catalyst was removed by filtration with suction, and the solvent was stripped off 15 in vacuo. To remove water completely, the mixture was taken up twice in methanol and reconcentrated. 4-Chloro-2-cyclopropylaminoaniline (1.80 g), which remained in the form of a brown oil, was dissolved in 50 ml of anhydrous 1,2-dimethoxyethane and cooled to -60°C, with stirring. # 2/00 ,Qa A solution of 1.1 ml (0.01 mol) of 2-bromopropionyl chloride in 5 ml of anhydrous 1,2-dimethoxyethane was slowly added dropwise, and stirring of the reaction mixture was continued for 2 hours at -60 - -70°C. The 5 mixture was then allowed to warm to approx. -20°C and poured into 150 ml of ice-cold, saturated aqueous sodium hydrogen carbonate solution. The mixture was extracted twice using ethyl acetate, and the organic phase was washed once with water, dried (sodium sulfate) and 10 concentrated in vacuo. After crystallization with diethyl ether/pentane, 2.51 g (79%) of the desired product of melting point 130°C remained. *H NMR (270 MHz, d6-DMSO) s 5 - 0.4 - 0.5 (m, 2 H), 0.7 - 0.8 (m, 2 H), 1.75 (d, J - 7 Hz, 3 H), 2.39 (m, 15 1 H), 4.72 (q, J - 7 Hz, 1 H), 5.6 (br. s, 1 H), 6.66 (dd, J - 8, 2 Hz, 1 H), 6.96 (d, J - 2 Hz, 1 H), 7.21 (d, J =» 8 Hz, 1 H), 9.36 ppm (br. s, 1 H). MS: (M + H)+ - 319, 317 B) (3RS)-6-Chloro-4-N-(cyclopropyl)-3-methyl-3,4-dihydro-20 quinoxalin-2(1H)-one The compound of Example XVIIIA (318 mg, 1.0 mmol) was dissolved in 20 ml of ethanol (96%), 0.28 ml (2.0 mmol) of triethylamine were added, and the mixture was refluxed for 18 hours. The solvent was removed under reduced 25 pressure, and the reaction product was purified by silica gel chromatography using ethyl acetate/heptane = 1:2 as eluent. The yield was 200 mg (85%) of white crystals of melting point 167°C (after crystallization from pentane). XH NMR (270 MHz, d6-DMS0): S = 0.40 (m, 1 H), 0.63 (m, 30 1 H), 0.76 (m, 1 H), 0.98 (m, 1 H), 1.12 (d, J » 7 Hz, 3 H), 2.47 (m, 1 H), 3.87 (q, J « 7 Hz, 1 H), 6.78 (s, 2 H), 7.0 (s, 1 H), 10.46 ppm (br. s, 1 H). MS: (M + H)+ - 237 The following compounds of the formula I were synthesized 35 analogously to the procedure described in Example XVIII using the correspondingly substituted ortho-nitroanilines 78 and 2-halo carboxylic acid derivatives and, if appropriate, derivatized further: Table 5 H No. r3 r* r5 X M.p.°C 1 6-Cl ch3 h c8h5 0 191 2 6-Cl ch3 ch3 c3hs 0 3 6-Cl ch3 ch3 c3h3 s 4 6-Cl ch3 ch3 c3h5 0 5 6-Cl ch3 ch3 c3h3 s Key: C3H5 «= cyclopropyl C6H5 » phenyl Example XIX 7-Chloro-l-N-(cyclopropyl)-3,3-dimethyl-3,4-dihydro-quinoxalin-2(1H)-one 4-Chloro-2-cyclopropylaminonitrobenzene (2.0 g, 9.4 mmol) was hydrogenated as described in Example XVIIIA. The resulting 4-chloro-2-cyclopropylaminoaniline (1.70 g) was taken up in 20 ml of dichloromethane. 1.6 ml (2.01 mmol) of chloroform, 1.8 ml (2.45 mmol) of acetone and 0.10 g (0.4 mmol) of benzyltriethylammonium chloride were added, and the reaction solution was cooled to 10°C. 4 ml of 50% strength sodium hydroxide solution were slowly added dropwise with vigorous stirring, during which process the reaction temperature should not exceed 10°C. After stirring for 5 hours at 10°C, the phases were diluted and separated. The organic phase was washed once with water, dried (magnesium sulfate) and evaporated in vacuo. The crude product was purified by silica gel chromatography using ethyl acetate/heptane -1:2 as the eluent. the yield was 1.0 g (42%) of white crystals of melting point 132-133°C (after recrystallization from toluene/heptane). *H NMR (270 MHz, d6-DMS0) : S - 0.45 - 0.55 (m, 2 H), 1.05 - 1.1 (m, 2 H), 1.19 (s, 6 H), 2.71 (m, 1 H), 6.09 (br. s, 1 H), 6.71 (d, J « 8 Hz, 1 H), 6.88 (dd, J - 8, 2 Hz, 1 H), 7.19 ppm (d, J - 2 Hz, 1 H). MS: (M + H)+ « 251 The following compounds of the formula I were synthesized in analogous manner and, if appropriate, derivatized further: - 80 - 2700 Table 6: H No. r'n R3 R* R5 M.p.°C 1 6-Cl CH3 ch3 c5h8 179 2 7-Cl ch3 ch3 CsH9 171 3 6,7-(CH30)2 ch3 ch3 h 4 6,7-(CH30)2 ch3 ch3 C5H9 5 ch3 ch3 sCfiHn 113 6 c6h5 ch3 h 7 c6h5 ch3 c5h9 8 6-Cl ch3 ch3 IPOC 128 9 7-Cl ch3 ch3 IPOC 169 10 7-CH3 ch3 ch3 C5H9 168 11 6-CH3O ch3 ch3 H 200 12 6-CH3O ch3 ch3 c3h9 138 13 6/7-COOH ch3 ch3 H > 240 14 6/7-COOH ch3 ch3 c3h9 180 No. R\, R3 R* R5 M.p.°C 15 8-ch3 ch3 ch3 H 140 16 8-ch3 ch3 ch3 c3hb 160 17 8-CH3 ch3 ch3 ipoc 127 18 6/7-CH3 c2h3 C2hs h 160 19 6-CH3 c2h5 c2h3 c3h9 100 20 7-ch3 c2h5 c2hs C3hb 110 21 7-F ch3 ch3 h 120 22 7-F ch3 ch3 c3h9 155 23 7 -c2h50 ch3 ch3 h 155 24 7-c2h50 ch3 ch3 c5h8 123 25 6-cooh ch3 ch3 C5hb 245 26 7 r 8- (ch3)2 ch3 ch3 h 196 27 7/8-(ch3)2 ch3 ch3 C5hb 155 28 6» 7-(ch3)2 ch3 ch3 h 248 29 6,7-(ch3)2 ch3 ch3 C3hb 200 30 6-Cl,7-(2,3-Cl2C6H30) ch3 ch3 h 211 31 6-Cl,7-(2,3-Cl2C6H30) ch3 ch3 C3hb 205 32 7-F ch3 ch3 ipoc 175 33 7-c2h50 ch3 ch3 ipoc 150 34 6/7-CH3 ch3 ch3 ipoc 152 82 - No. R1 R3 R4 R5 M.p.°C 35 7,8-(CH3)2 CHa CH3 IPOC 147 36 6,7-(CH3)2CH3 CHa CH3 IPOC 161 37 7-C6H5 CH3 CH3 H 167 38 7-C6H30 CH3 CH3 CSHQ 138 39 7-C6HsO CH3 ch3 IPOC 181 40 5-CH3 CH3 ch3 H 182 41 6-CHaO, 7-(4-pyridyl) CH3 CH3 H > 240 42 6-Cl, 7-piperidino CH3 ch3 H 219 43 6/7-Cl,7/6- morpholino (mixture) ch3 CH3 H 236 44 6/7-(N-methyl-piperazin-1-yl) ch3 CH3 H > 240 45 6/7-Cl,7/6- (N-methyl-piperazin-l-yl) CH3 CH3 H 147 46 6-Cl ch3 CH3 H 152-154 47 7-Cl CHa CH3 s H 48 6-Cl CH3 CH3 ALOC 128-129 49 7-Cl CH3 CH3 ALOC 144 50 6-Cl CH3 CH3 COOCH(CH3)2 118 51 7-Cl CH3 CHa COOCH(CH3)2 171 No. Rl» r3 R* R5 m.p.°c 52 7-(4-F-Ph-S020) ch3 ch3 h 53 7-(4-F-Ph-S020) ch3 ch3 IPOC 204 54 6-Cl,7-piperidino ch3 ch3 IPOC 152 55 6-Cl,7-morpholino ch3 ch3 IPOC 113 56 6-Cl,7-(N-methyl-piperazin-l-yl) ch3 ch3 IPOC 168 57 6-Cl,7-NEt2 ch3 ch3 h 141 58 6-Cl,7-NEt2 ch3 ch3 IPOC Oil 59 6,7-Cl2 ch3 ch3 h 232 60 6,7-Cl2 ch3 ch3 IPOC 171 61 7-(N-methyl-piperazinyl-l-yl) ch3 ch3 h 198 62 7-(N-methyl-piperazinyl-l-yl) ch3 ch3 IPOC 123 63 6-CH30 ch3 ch3 IPOC 128 64 7-Cl -(ch2)3- IPOC 172 65 7-Cl -(ch2)«- IPOC 181 66 6-Cl -(ch2)3- IPOC 157-158 67 6-Cl -(CH2),- IPOC 179-180 68 6-Clq ch3 ch3 COOC2H5 137 69 6-Cl ch3 ch3 cooc3h7 125 - 84 - Keys C3H8 - 3-methyl-2-buten-l-yl sCjjHu ■ 4-methyl-3-penten-2-yl IPOC «■ isopropenyloxycarbonyl Example XX 3.3-Dimethyl-4-N- (3-methyl-2-buten-l-yl) -3,4-dihydro-quinoxalin-2(1H)-one The compound waa prepared analogously to the compound described in Example VIA, starting from 3,3-dimethyl- 3.4-dihydroquinoxalin-2(lH)-one (J. T. Lai, Synthesis 1982, 71). Melting point 146-147°C (after crystallization from methyl tert.-butyl ether/heptane) XH NMR (270 MHz, d6-DMSO) : 6 - 1.27 (s, 3 H) , 1.68 (s, 3 H), 1.72 (s, 3 H), 3.88 (d, J - 7 Hz, 1 H), 5.15 (m, 1 H), 6.60 (d, J - 7 Hz, 1 H), 6.67 (t, J - 7 Hz, 1 2), 6.78 (d, J - 7 Hz, 1 H), 6.87 (t, J « 7 Hz, 1 H), 10.33 ppm (br. s, 1 H). MS: (M + H)+ » 245 Example XXI 4-N- ( 3-Methyl-2-buten-l-yl) -3, 4-dihydroquinoxalin-2(1H)-one-3-spiro-l'-cyclohexane The compound was prepared analogously to the compound described in Example VIA, starting from spiro[cyclo-hexane-l,3'-(3',4'-dihydroquinoxalin-(l'H)-one)] (J. T. Lai, Synthesis 1982, 71). Melting point 82-83°C (after crystallization from heptane) XH NMR (270 MHz, d6-DMSO) s S « 1.25 - 1.75 (m, 10 H), 3.75 (d, J = 6 Hz, 2 H), 5.07 (m, 1 H), 6.7 - 7.0 (m, 4 H), 10.15 ppm (br. s, 1 H). MSs (M + H)+ » 285 - 85 - Example XXII 4-N-(3-Methyl-2-buten-l-yl)-3,4-dihydroquinoxaline-2(1H)-thione-3-spiro-1'-cyclohexane The compound of Example XXI (500 mgr 1.8 mmol) was 5 refluxed for 1.5 hours under argon together with 370 mg (0.9 mmol) of 2,4-bis-(4-methoxyphenyl)-l,3'-dithia-2,4-diphosphetane 2,4-disulfide (Lawesson's reagent) in 10 ml of anhydrous toluene. The mixture was subsequently concentrated in vacuo, and the products were isolated by 10 silica gel chromatography using methyl tert.-butyl ether/heptane = 10:1 as eluent. The yield was 50 mg (9%) of yellow crystals of melting point 125°C. *H NMR (270 MHz, d6-DMS0): £ - 1.1 - 1.9 (m, 16 H), 3.64 (d, J = 7 Hz, 2 H), 4.99 (m, 1 H), 6.95 - 7.1 (m, 3 H), 15 7.18 (d, J - 7 Hz, 1 H), 12.2 ppm (br. s, 1 H). MS: (M + H)+ - 301 3,4-Dihydroquinoxaline-2 (1H) -thione-3-spiro-l '-cyclo-hexane was isolated as a further product in a yield of 110 mg (26%); yellow crystals of melting point 178°C. 20 NMR (270 MHz, CDC13 6 - 1.25 - 2.2 (m, 10 H), 4.18 (br. s, 1 H), 6.7 - 6.8 (m, 3 H), 6.97 (m, 1 H), 9.42 ppm (br. s, 1 H). MS: (M + H)+ « 233. Example XXIII 25 ( 3S)-6-Chloro-4-N-(isopropenyloxycarbonyl)-3-methyl- 3,4-dihydroquinoxaline-2(1H)-thione The compound of Example XIII (0.5 g, 1.78 mmol), dissolved in 10 ml of anhydrous pyridine, was refluxed for 4 hours together with 0.47 g (2.12 mmol) of phosphorus 30 pentasulfide. The mixture was concentrated in vacuo, and the residue was chromatographed on silica gel using ethyl acetate/heptane = 1:1 as eluent. This gave 0.25 g (47%) of a yellow crystalline solid of melting point 148-150°C (after recrystallization from ethyl acetate/heptane). m - 86 - *H NMR (270 MHz, de-DMSO): S - 1.24 (d, J » 7 Hz, 3 H), 1.96 (s, 3 H), 4.8 - 4.9 (m, 2 H), 5.28 (g, J ■ 7 Hz, 1 H), 7.22 (d, J - 8 Hz, 1 H), 7.30 (dd, J - 8, 2 Hz, 1 H), 7.72 (br. s, 1 H), 12.84 ppm (br. s, 1 H). MS: (M + H)+ - 297. The following compounds of the formula I were synthesized in analogous manner from the corresponding 3,4-dihydro-quinoxalin-2(1H)-ones: No 1 2 3 4 5 6 7 8 9 10 11 12 13 14 - 87 - M.p* °C CHq H C.H 5"9 119 6-Cl CH, H c5h9 109-110 6-Cl CHa H C6H5CH2 92 6-Cl H -CH2CH2CS- 6-C1 H -CH2CH2CH2CS- CRH 6"5 CHq C.H S"9 6-Cl CH, cha CrH 5«g 157 7-Cl CH, CHa C<H 5"9 160 7-Cl CH, CHa H 170 6-Cl CHa H ALOC 143-145 6-Cl cha CHa IPOC 153 7-Cl CH, CHa IPOC 174 6-Cl CH, CHa H 175 6-Cl c2h5 H IPOC 176-177 - 88 - 0 No. R'a R3 R* R5 M.p.°C 15 6-Cl c2h3 h aloc 159-161 16 6,7-(ch3)2 chs ch3 c5h9 173 17 6-Cl C3H7 h ipoc 154-155 18 6-Cl c3h7 h aloc 98-100 19 6-Cl ch3 h (2-c5h*n)-ch2 175-178 20 6-Cl ch3 h (3-c5h4n)-ch2 77 21 6-Cl ch3 ch3 ' aloc 153-154 22 6-Cl ch3 ch3 cooch(ch3)2 151 23 6-Cl ch2sch3 h ipoc 128 24 6-Cl ch3 ch3 cooc2h5 163 25 6-Cl ch3 ch3 cooc3h7 164 26 6-Cl c2h5 h (2-c5han)-ch2 162-164 27 6-Cl c*h9 h ipoc 132 28 6-Cl ch2sch3 h cooch(ch3)2 124 29 6-Cl ch2sch3 i (2-c5han)-CH2 159 30 6-ch30 CH2SCH3 h ipoc 154 31 6-ch3o ch2sch3 h cooch(ch3)2 163 32 6-Cl ch2sch3 h CH2c6ha-2-c1 Oil - 89 - Keys C5H8 « 3-methyl-2-buten-l-yl IPOC « isopropenyloxycarbonyl ALOC » allyloxycarbonyl C5HAN *= pyridyl 5 Example XXIV (3RS)-3-Methyl-4-N-(3-methyl-2-buten-l-yl)-2-methylthio-3,4-dihydroquinoxaline (3 RS)-3-Methyl-4-N-(3-methyl-2-buten-l-yl)-3,4-dihydroquinoxaline-2(1H)-thione (Table 7, No. 1) 10 (0.49 g, 2.0 mmol) was dissolved in 20 ml of ethanol (96%), and the solution was treated with 5.1 ml (2.2 mmol) of a 1% strength sodium ethanolate solution. After the mixture had been stirred for 15 minutes at room temperature, 0.14 ml (2.2 mmol) of methyl iodide was 15 added dropwise, and the mixture was stirred for a further 2 hours at room temperature. The reaction solution was concentrated, and the residue was chromatographed on silica gel. 500 mg (96%) of a yellow oil were isolated using ethyl acetate/heptane = Is6. 20 *H NMR d6—DMSO) i S = 0.96 (d, J «= 7 Hz, 3 H) , 1.72 (s, 6 H), 2.44 (a, 3 H), 3.71 (dd, J - 15, 6 Hz, 1 H), 3.89 (dd, J » 15, 6 Hz, 1 H), 4.00 (q, J - 7 Hz, 1 H), 5.20 (m, 1 H), 6.65 - 6.75 (m, 2 H), 7.02 (t, J » 8 Hz, 1 H), 7.11 ppm (d, J » 8 Hz, 1 H). 25 MS: (M + H)+ ■ 261 The following compound of the formula I was synthesized in the same manner: O r\ o g 30 4-Isopropenyloxycarbonyl-2- (isopropenyloxycarbonyl) -thio-3,3,7,8-tetramethyl-3,4-dihydroquinoxaline. Melting point: 115°C - 90 - Example XXV (3RS) -3-Methyl-4-N- (3-methyl-2-buten-l-yl) -3^-dihydroquinoxaline (1H)-one (3RS)-3-Methyl-3,4-dihydroquinoxalin-2(lH)-one (4.86 g, 5 0.03 mol) dissolved in 50 ml of N,N-dimethylformamide, was alkylated with 4.2 ml (0.033 mol) of 3-methyl-2-buten-l-yl bromide (90%) in the presence of 4.60 g (0.033 mol) of pulverulent potassium carbonate. The reaction mixture was stirred at room temperature until 10 reaction of the educt was complete. The solvent was then stripped off in vacuo, the residue was taken up in ethyl acetate and water, the phases were separated, the aqueous phase was extracted twice with ethyl acetate, and the combined organic extracts were washed twice with water. 15 Drying over sodium sulfate, concentration in vacuo and crystallization from pentane gave 5.80 g (34%) of white crystalline product of melting point 92-93°C. XH NMR (270 MHz, d6-DMSO): S » 0.99 (d, J = 7 Hz, 3 H), 1.72 (s, 6 H), 3.67 (dd, J - 15, 7 Hz, 1 H), 3.86 (q, 20 J - 7 Hz, 1 E), 3.88 (dd, J » 15, 7 Hz, 1 H), 5.21 (m, 1 H), 6.65 - 6.9 (m, 4 H), 10.31 ppm (br. s, 1 H). MS: (M + H)+ « 231 Example XXVI 3,3a-Dihydropyrrolo[1,2-a]quinoxaline-1,4(2H, 5H)-dione 25 2-Fluoronitrobenzene (14.1 g, 0.1 mol) and L-glutamic acid (45.0 g, 0.3 mol) were heated in 100 ml of 2-methoxyethanol at 95°C, with stirring, and 300 ml of 2N sodium hydroxide solution were added dropwise. Stirring was then continued for another 3 hours at this tempera-30 ture. After cooling, the solution was treated with 400 ml of methanol and hydrogenated under atmospheric pressure with Raney nickel as catalyst. When the uptake of hydrogen had ended, the catalyst was removed by filtration with suction, and the solution was 35 concentrated under reduced pressure. The residue was acidified with 250 ml of 2N hydrochloric • 270083 - 91 - acid and heated in a steam bath for approx. 30 minutes. The precipitate which resulted in this process was filtered off with suction, washed with water and alcohol and subsequently dried, melting point 255°C, decomposi-5 tion. *H NMR (60 MHz, d6-DMS0): 6 - 1.9 - 2.7 (m, 4 H), 4.5 (t, J - 8 Hz, 1 H), 6.8 - 7.3 (m, 3 H), 7.8 - 8.2 (m, 1 H), 10.7 ppm (br. s, 1 H). MS: (M + H)+ - 202 10 Example XXVII 7-Phenoxysulfonyl-3,3a-dihydropyrrolo[1,2-a]quinoxaline-1,4(2 H,5H)-dione The compound was obtained in analogous manner by reacting phenyl 4-chloro-3-nitrobenzenesulfonate with L-glutamic 15 acid, melting point 140°C (decomp.). NMR (60 MHz, de-DMSO): 8 - 1.6 - 2.5 (m, 4 H), 4.07 (t, J = 6 Hz, 1 H), 6.7 - 7.6 (m, 8 H), 10.57 ppm (br. s, 1 H) . MS: (M + H)+ - 358 20 Example XXVIII 3-Carboxymethyl-3,4-dihydroquinoxalin-2(1H)-one 2-Fluoronitrobenzene (14.1 g, 0.1 mol) and L-aspartic acid (40.0 g, 0.3 mol) were heated to 95°C in 100 ml of 2-methoxyethanol, with stirring, and 300 ml of 2N sodium 25 hydroxide solution were added dropwise. Stirring was then continued for 1 hour at this temperature. After the solution had cooled, it was treated with 500 ml of methanol and hydrogenated under atmospheric pressure with Raney nickel as catalyst. 30 When the uptake of hydrogen liad ended, the catalyst was removed by filtration with suction, and the solution was concentrated under reduced pressure. The residue was acidified with 500 ml of 2N hydrochloric acid, the mixture was subsequently concentrated, 35 neutralized with sodium acetate and extracted with ethyl acetate. The mixture was dried with sodium sulfate, the solvent was stripped off, and the residue was then obtained which was first oily and crystallized upon stirring with water, melting point 152-154°C. 5 *H NMR (60 MHz, d6-DMS0) : S » 2.5 - 2.7 (dd partly concealed, 2 H), 4.1 (td, J ■ 6, 2 Hz, 1 H), 5.98 (br. s, 1 H), 6.5 - 6.9 (m, 4 H), 10.30 (br. s, 1 H), 12.37 ppm (br. s, 1 H). MS: M+ = 206 10 CHN analysis: calculated C 58.2; H 4.8; N 13.6% found C 58.4; H 4.7; N 13.7% Example XXIX 7-Phenoxysulfonyl-3,4-dihydroquinoxalin-2(1H)-one A) Methyl N-[(2-nitro-4-phenoxysulfonyl)phenyl]glycinate 15 Phenyl 4-chloro-3-nitrobenzenesulfonate (62.7 g, 0.2 mol) and methyl glycinate hydrochloride (100.4 g, 0.8 mol), dissolved in 250 ml of methanol, were treated with 200 ml of triethylamine, and the mixture was refluxed for 15 minutes. After cooling, the mixture was treated with 1 1 20 of 2N acetic acid, subjected to filtration with suction and washed with water. The residue was recrystallized from ethyl acetate and washed with methanol and diiso-propyl ether, melting point 120-123°C. B) 7-Phenoxysulf onyl-3,4-dihydroquinoxalin-*2 (1H)-one 25 Methyl N-[(2-nitro-4-phenoxysulfonyl)phenyl]glycinate (36.6 g, 0.1 mol) was hydrogenated under atmospheric pressure in a mixture of 250 ml of N,N-dimethylformamide and 250 ml of methanol, with Raney nickel as catalyst. When the uptake of hydrogen had ended, the catalyst was 30 removed by filtration with suction, and the solution was freed from solvent in vacuo. The residue was dissolved in 40 ml of 2-methoxyethanol, and the mixture was heated for one hour in a steam bath. The resulting precipitate was filtered off with suction and washed with methanol, melting point 253-254°C. *H NMR (60 MHz, de-DMSO) s 6-4.0 (d, J « 4 Hz, 2 H), 6.6 - 7.6 (m, 9 H), 10.43 ppm (br. a, 1 H). MS: (M + H)+ » 305 5 Example XXX 4- (3-Methyl-2-buten-l-yl)-7-phenoxysulfonyl-3,4-dihydro-quinoxalin-2(1H)-one 7-Phenoxysulfonyl-3,4-dihydroquinoxalin-2(1H)-one (1.52 g, 5.0 mmol) in 20 ml of N,N-dimethylacetamide was 10 stirred for 8 hours at 100°C with 2 ml of 3-methyl-2-buten-l-yl bromide. After cooling, the mixture was treated with water and extracted with ethyl acetate. The solution was dried using magnesium sulfate and then concentrated, and the residue was chromatographed over a 15 silica gel column using ethyl acetate/heptane « 1:1. The fractions which contained the substance were evaporated on a rotary evaporator, and the product was subsequently stirred with pentane and filtered off with suction, melting point 132°C. 20 XH NMR (270 MHz, d6-DMSO) : 6 - 1.73 (s, 6 H) , 3.90 (s, 2 H), 3.93 (partly concealed d, J « 6 Hz, 2 H), 5.20 (br. t, J ■ 6 Hz, 1 H), 6.75 - 7.45 (m, 8 H), 10.66 ppm (s, 1 H). MS: (M + H)+ - 373 25 The following compounds of the formula 1 were synthesized in analogous manner using the corresponding haloaromatic substances and amino acid derivatives and, if appropriate, derivatized further on nitrogen atom 4: - 94 - Table 8 H No. R'n r! r* r5 M.p.®C 1 7-c6h5-0-s02 b ch20h H 199 2 7-c6h5-0-s02 H ch2oh c5h9 120 3 7-c6h5-0-s02 H ch2cooh e 230 decomp. 4 7-c6h5-0-s02 H ch2cooh c5h8 5 7-c6h5-0-s02 H ch2conh2 H 272 decomp. 6 7-c6h5-0-s02 H ch2conh2 c5h9 7 7-c6h5-0-s02 H CH2-4-Imi H 216 decomp. 8 7-c6h5-0-s02 H CH2-4-Imi c5h9 9 7-c6h5-co H h H 280 decomp. 10 7-c6h5-co H h c6h5-c0 277 decomp. 11 7-c6h5-0-s02 H ch3 H 148 12 7-c6h5-0-s02 H ch3 c5h9 Oil 13 7-c6h5-s02 H ch3 H 198 14 7-c6hs-s02 H ch3 C5H9 Oil - 95 - No. R'n R3 R* Rs M.p.°C 15 7-c6h5-s02 h ch3 ipoc 108 16 7-c6h5-0-s02 h h h 17 7-c6h5-0-s02 h h coch3 270 18 7-c6h5-0-s02 h ch3 ipoc Resin Key: CsHa « 3-methyl-2-buten-l-yl 4-Imi ■» 4-imidazolyl IPOC « isopropenyloxycarbonyl Example XXXI 5 6-Chioro-7-phenoxysulfonyl-1,2,3,3a-tetrahydro- pyrrolo[2,1-c]-quinoxalin-4(5H)-one A) Phenyl 2,4-dichloro-3-nitrobenzenesulfonate 2,6-Dichloronitrobenzene was stirred for 7 hours at 130°C with an excess of chlorosulfonic acid. After cooling, the 10 mixture was poured onto ice, the sulfochloride was filtered off with suction, washed to neutrality and dried over sodium hydroxide, melting point 91°C. The resulting sulfochloride (29.05 g, 0.1 mol) and phenol (11.5 g, 0.12 mol) were dissolved in 150 ml of acetone and treated 15 with 14 ml of triethylamine at 10 °C. The mixture was stirred for 1 hour with cooling, stirring was then continued for a further 4 hours at room temperature, the mixture was then treated with 200 ml of water, the resulting precipitate was filtered off with suction at 20 10°C, washed with water and dried in vacuo at 80°C, melting point 102°C. B) N-[(3-Chloro-2-nitro-4-phenoxysulfonyl)phenyljproline Phenyl 2,4-dichloro-3-nitrobenzenesulfonate (34.8 g, 0.1 mol), 69.0 g (0.6 mol) of L-proline, 200 ml of 2N sodium hydroxide solution and 200 ml of 2-methoxyethanol 5 were stirred for 10 minutes at 80°C. The clear solution was acidified at 50°C using concentrated hydrochloric acid and poured onto ice. The precipitate was filtered off with suction, washed with water to neutrality and dried at 80°C. Melting point 148°C (after recrystalliza-10 tion from methanol) C) 6-Chloro-7-phenoxysulfonyl-1,2,3,3a-tetrahydropyrrolo-[2,1-c]-quinoxalin-4(5H)-one N- [ (3-Chloro-2-nitro-4-phenoxysulf onyl) phenyl ]proline (38.0 g, 0.075 mol) in 500 ml of methanol and 25 ml of 15 concentrated ammonia solution was hydrogenated under atmospheric pressure with Raney nickel as catalyst. When the uptake of hydrogen had ended, the catalyst was removed by filtration with suction, the solution was concentrated, the residue together with 211 hydrochloric 20 acid was heated for approximately 30 minutes in a steam bath, cooled, subjected to filtration with suction and washed with water to neutrality. Melting point 197°C (after recrystallization from glacial acetic acid) Example XXXII 25 8- (4-Methyl-1-piperazinyl) - 3- (2-methylpropyl) -5-phenoxy-sulfonyl-3,4-dihydroquinoxalin-2(1H)-one A) Phenyl 2-chloro-4-(4-methyl-l-piperazinyl)-3-nitro-benzenesulfonate Phenyl 2,4-dichloro-3-nitrobenzenesulfonate (17.4 g, 30 0.05 mol) and 25 ml of methylpiperazine in 100 ml of isopropanol were refluxed for 10 minutes and subsequently concentrated. The residue was stirred with 50 ml of 50% methanol, filtered off with suction, anc! washed with 50% methanol and finally with water. Melting point 94-95°C (after recrystallization from cyclohexane) B) N-[(3-(4-Methyl-l-piperazinyl)-2-nitro-6-phenoxy-sulfonyl)-phenyl]leucine hydrochloride 5 Phenyl 2-chloro-4-(4-methyl-l-piperazinyl)-3-nitro-benzenesulfonate (41.1 g, 0.1 mol) and L-leucine (39.3 g, 0.3 mol) were stirred for 8 hours at 95°C in a mixture of 100 ml of N,N-dimethylformamide, 50 ml of 2-methoxy-ethanol and 100 ml of 2N sodium hydroxide solution. When 10 cold, the reaction mixture was acidified with concentrated hydrochloric acid. The precipitate was taken up in ethyl acetate, and the mixture was dried using sodium sulfate and freed from solvent in vacuo. This gave an orange oil. 15 C) 8-(4-Methyl-l-piperazinyl)-3-(2-methylpropyl)-5-phenoxysulfonyl-3,4-dihydroguinoxalin-2(1H)-one hydrochloride N-[(3-(4-Methyl-1-piperazinyl)-2-nitro-6-phenoxy-sulfonyl)-phenyl]leucine hydrochloride (25.3 g, 0.05 mol) 20 in 250 ml of methanol and 25 ml of glacial acetic acid was hydrogenated under atmospheric pressure using Raney nickel as catalyst. When the uptake of hydrogen had ended, the catalyst was removed by filtration with suction, the solution was 25 concentrated, and the residue together with 2N of hydrochloric acid was heated for approximately 10 minutes in a steam bath and then concentrated in vacuo. The residue was dissolved in water, the mixture was rendered alkaline using ammonia, and this was taken up in ethyl acetate. 30 The oil which remained after concentration was dissolved in 400 ml of diisopropyl ether, and the mixture was rendered neutral using ethanolic hydrochloric acid. The precipitate was filtered off with suction, washed with diisopropyl ether and dried, melting point 90°C and above 35 (decomp.). - 98 MS: M+ ■ 458 The following compounds of the formula I were synthesized in analogous manner using the corresponding haloaromatic substances and amino acid derivatives and, if appropriate, derivatized further on nitrogen atom 4: C H * Table 9 1 5 No. R3 R* R5 M.p.°C 1 h (ch3)2chch2 c3h9 2 h ch3 h 100 decomp. (hc1) 3 h ch3 c5h9 4 h h h 126 - 127 (base) 5 i H h csh9 Key: C3H9 «« 3-methyl-2-buten-l-yl Example XXXIII (3RS)-4-N-Cyclohexyl-3-methyl-3,4-dihydroquinoxalin-2(H)-one (3RS)-3-Methyl-3,4-dihydroquinoxalin-2(lH)-one (0.81 g, 0.005 mol) and 1 ml (0.1 mol) of cyclohexanone were introduced into 20 ml of 1,2-dichloroethane. - 99 - 10 15 Trifluoroacetic acid (1.9 ml, 0.025 mol) was added dropwise, during which process a clear solution formed with gentle heating. 2.1 g (0.01 mol) of sodium triacetoxyborohydride were added, the exothermic reaction was then allowed to proceed for 30 minutes with stirring, and quenching was then effected by adding saturated aqueous sodium hydrogen carbonate solution. The phases were separated, the organic phase was washed with saturated aqueous sodium chloride solution, dried (magnesium sulfate) and concentrated. The crude product was chromatographed on silica gel using ethyl acetate/heptane - 1:1. 1.15 g (94%) of the desired product were obtained, melting point 131-132*C (toluene/heptane). 2H NMR (270 MHz, d6-DMS0) : 1.0 - 2.0 (m, 10 H), 3.39 1 H), 6.68 - 6.94 (m, 4 H), 10.27 ppm (br MS: (M + H)+ - 245. S ■ (m, 0.97 1 H), (d, J - 7 Hz, 3.91 (q, J ■ s, 1 H) H), Hz, The following compounds of the formula I were synthesized 20 in analogous manner. Table 10 R f - 100 - No. R\, R3 R* R5 M.p.°C 1 ch3 h c2H3 106-107 2 ch3 H ch2c(ch3)3 162 3 CHj H c-C5Hq 120 4 6-Cl ch3 H c-C4H7 100 5 6-Cl ch3 H cshu 94-95 6 6-Cl ch3 H ch2c(ch3)3 158-160 7 6-Cl c2h5 h ch2c(ch3)3 158-159 8 6-Cl ch3 h ch=chcho 140-146 9 6-Cl ch3 H CH2C-CH3 166-168 10 6-Cl ch3 h 2-picolyl 198-199 11 6-Cl ch3 h 3-picolyl 136 12 6-Cl ch3 h 4-picolyl 191-193 13 6-Cl ch3 h furanyl-2-methyl 116-118 - 101 - 27U008 No, 14 6-Cl CH, H CH2C6H4-4-Br M.p.°C 149-150 15 6-Cl CH, H CH2C6H*-4-CN 95-96 16 6-Cl CH, H CH2C6HA-4-N02 117 17 6-Cl CH, H CH2C8H4-3-N02 125 18 6-Cl CH, H CH2C6H4-2-N02 153-154 19 6-Cl CH, H CH2C6HA-4-Cl 122-123 20 6-Cl CH, H CH2C6H4-3-Cl 156-157 21 6-Cl CH, H CH2C6H4-2-Cl 138 22 6-Cl CH, H CH2C6HA-4-F 147 23 6-Cl CH, H CH2C6H4-4-CBH5 164-165 24 6-Cl CH, H CH2C6H*-4-OC6H5 Oil 25 6-Cl CH, H CH2C6HA-4-CH3 60-62 26 27 6-Cl 6-Cl CH, H CH2C6HA- 4 -COOCH3 CH, H CH2C6H4-2,6-Cl2 139 190-191 28 6-Cl CH, H CH2C6H4-3,5-Cl2 139-140 29 6-Cl CH, H naphthyl-l-methyl 164-166 30 6-Cl CH, H naphthy1-2-methyl 161-164 31 6-Cl CH, H CH2CH2OCH3 78-79 32 6-Cl CHa H cyclohex-2-enyl Oil 33 6-Cl CH, H C2H,-C6H5 128 34 6-Cl CH, H thieny1-3-methyl 141-142 - 102 - Mo. R3 Ra R5 M.p.°C 35 rH a i vo CH3 ' 5-methylthienyl)-2-methyl 58-60 36 6-Cl ch3 b 3-methylthienyl)-2* methyl 124 37 6-Cl ch3 B thieny1-2-methyl 121-123 38 6-Cl ch3 b cb2cb«ck-c6b5 39 6-Cl CH2SCH; I CB2C6H4-2-Cl 128 40 6-Cl ch2sch3 * CB2C6B4-2-N02 134 41 6-Cl ch2sch3 b 2-picolylOil 42 6-Cl ch2sch3 B 08^3-2,4-012 143 43 6-Cl CH2S-i.PrI CB2C6B3-2,4-Cl2 Oil 44 6-Cl CH2S-Bn I CH2C6H3-2,4-Cl2 Oil 45 6-Cl ch2-s-e I I CB2C6H3-2,4-Cl2 46 6-Cl C2H5 b 2-picolyl 160-162 47 6-Cl ch3 b 6-CB3) 2-picolyl 158 Keys CsHn « 3-methyl-l-butyl c-C<,B7 » cyclobutyl c-C5Hg » cyclopentyl Example XXXIV (3RS) -3-Methy1-4-N- (3-oxo-l-butyl)-3,4-dihydroquinoxa.lin-2(1H)-one 3-Methyl-3,4-dihydroquinoxalin-2(1H)-one (0.5 g, 3.1 mmol) together with 0.35 ml (4.3 mmol) of methyl - 103 - ^ W \J |j vinyl ketone and a catalytic amount of triethylamine were stirred for 20 hours at room temperature in 20 ml of anhydrous ethanol. Silica gel chromatography with methyl tert.-butyl ether/heptane ■ 2:1 gave 620 mg (87%) of the 5 desired product, melting point 108-109°C (methyl tert.-butyl ether/heptane). *H NMR (270 MHz, d6-DMS0): S - 1.03 (d, J - 7 Hz, 3 H), 2.11 (s, 3H), 2.77 (t, J - 6 Hz, 2 H), 3.30 (m, 1 H), 3.50 (m, 1 H), 3.88 (g, J - 7 Hz, 1 H), 6.68 (m, 1 H), 10 6.78 (m, 1 H), 6.88 (m, 1 H), 10.31 ppm (br. s, 1 H). MS: (M + H)+ - 233, M+ - 232 Example XXXV (3S)-6-Chloro-4' N-chlorocarbonyl-3-methyl-3,4-dihydro-quinoxalin-2(1H)-one 15 The compound of Example IB (2.0 g, 0.01 mol) in 100 ml of anhydrous toluene was heated with bis-(trichloromethyl) carbonate (triphosgene) (1.5 g, 0.005 mol) for 1 hour at 80°C in the presence of 2 ml (0.014 mol) of triethylamine. After cooling, the mixture was washed with water 20 and saturated aqueous sodium chloride solution and dried (magnesium sulfate), and the solvent was removed under reduced pressure. The residue (2.5 g) crystallized after stirring with heptane, its purity being sufficient for preparative purposes. A sample of analytical purity was 25 obtained by silica gel chromatography using ethyl acetate/heptane = 1:1 as eluent. Melting point 142-144°C. *H NMR (270 MBz, d6-DMS0): 6 « 1.25 (d, J « 7 Hz, 3 H), 3.83 (q, J = 7 Hz, 1 B), 6.61 (dd, J « 6, 2 Bz, 1 H), 6.70 (s, 2H), 10.3 ppm (br. s, 1 H). 30 MS: (M + H)+ » 259 iU ^ u - 104 - Example XXXVI (3S) -6-Chloro-4-N- (2-methoxyethoxycarbonyl) -3-methyl-3,4-dihydroquinoxalin-2(lH)-one To a solution of 0.24 ml (3.0 mmol) of 2-methoxyethanol 5 in 10 ml of anhydrous 1,2-dimethoxyethane there was added 0.16 g of a 55% suspension of sodium hydride in mineral oil, and the reaction mixture was stirred for 30 minutes at room temperature. 0.50 g (1.9 mmol) of the compound of Example XXXV was subsequently added, with ice-cooling, 10 and the mixture was allowed to warm to room temperature and stirred for a further 30 minutes. The mixture was treated with saturated aqueous sodium chloride solution, extracted several times with ethyl acetate, the organic phase was washed once with saturated aqueous sodium 15 chloride solution and dried (magnesium sulfate), and the solvent was removed in vacuo. After silica gel chromatography (ethyl acetate/heptane » 1:1) and crystallization from ether/heptane, 0.29 g (51%) of the desired product was obtained, melting point 93-94°C. 20 XH NMR (200 MHz, d6-DMS0) : 6-1.13 (d, J « 7.5 Hz, 3 H) , 3.32 (s, 3 H), 3.6 (m, 2H), 4.24 (m, 1 H), 4.35 (m, 1 H), 4.81 (q, J - 7.5 Hz, 1 H), 6.98 (d, J - 9 Hz, 1 H), 7.2 (dd, J - 9, 3 Hz, 1 H), 7.66 (d, J - 3 Hz, 1 H, 10.81 ppm (br. 2, 1 H). 25 MS: (M + H)+ - 299 Example XXXVII (3S)-6-Chloro-3-methyl-4-N-[(phenylthio)carbonyl)]-3,4-dihydroquinoxalin-2(1H)-one To a solution of 0.31 ml (3.0 mmol) of thiophenol in 30 10 ml of 1,2-dimethoxyethane there was added 0.17 g of a 55% suspension of sodium hydride in mineral oil, with ice-cooling, and the mixture was stirred for 1 hour at room temperature. 0.5 g (1.9 mmol) of the compound of Example XXXV were introduced, again with ice-cooling, and - 105 - " ' W O U stirring was then continued for 2 hours at room temperature. For working-up, the mixture was treated with saturated aqueous sodium chloride solution, extracted twice with ethyl acetate and dried (sodium sulfate), and 5 the solvent was stripped off. The solid residue was recrystallized from heptane/isopropanol, 0.35 g (35%), melting point 194-195°C. *H NMR (200 MHz, d6-DMSO): 6-1.10 (d, J - 7 Hz, 3 H), 4.93 (q, J - 7 Hz, 1 H), 7.08 (d, J - 9 Hz, 1 H), 7.33 10 (dd, J « 9, 3 Hz, 1 H), 7.4 - 78,6 (m, 5 H), 7.78 (d, J - 3 Hz, 1 H), 10.16 ppm (br. e, 1 H). MS: (M + H)+ » 333, (M - C6H5SH + H)+ 223 The following compounds of the formula I were synthesized in analogous manner. Table 11 - 106 - H I R 4 R5 Mo. R3 R* R5 M.p.°C 1 6-Cl ch3 h cooch2ch=chch3 116-117 2 6-Cl ch3 h cooch2-c(ch3)2 87-89 3 6-Cl ch3 h cooch2c-ch 147 4 6-Cl ch3 h cooch2c-cch3 135 5 6-Cl ch3 h cosch2c6h5 158 6 6-Cl ch3 h coscb2ch»ch2 Oil 7 6-Cl ch3 h coocb2c(ch3)«cb2 125-127 8 6-Cl ch3 R COOC (CE3) 3 9 6-Cl ch3 h COO-cyclohex-2-en-1-y1 10 6-Cl ch3 h cooch (ch2och (ch3) 2) 2 Oil 11 6-Cl ch3 b cooch(ch3)2 141-142 12 6-Cl ch3 b COOC2ban(cb3)2 Oil 13 6-Cl ch3 h COOC2hasch3 108-110 </div>

Claims

<div class="application article clearfix printTableText" id="claims"> No. R'n r3 r4 r3 m.p.°c 14 6-Cl ch3 h COSC6Hj 194-195 15 6-Cl ch3 h c00ch2c6h4-2-n02 227-231 16 6-Cl ch3 h c00ch2c3h4-3-n02 183-185 17 6-Cl ch3 h COOCH2c6ha-4-c1 177-180 18 6-Cl ch3 h COOCH2C6H4-2-Cl 164 19 6-Cl ch3 h cooch2ch«chch2ch3 Oil 20 6-Cl ch3 H coo(3-picolyl) 160-161 21 6-Cl chg H coo(2-picolyl) 114-116 22 6-Cl ch3 H c00CH2c8ha-4-n02 230-233 23 6-Cl ch3 H cooch2ch2c ( ch3 ) «ch2 Oil 24 6-Cl ch3 H CO-(4-methyl piperazin-l-yl) Oil 25 6-Cl ch3 H co-n(ch2) 5 218-220 26 6-Cl ch3 h co-n(ch2h 200-203 27 6-Cl ch3 H CO-morpholin-1-yl 193-195 28 6-Cl ch3 H CO-HNCH2Ph 94-96 29 6-Cl ch3 H Cyclopropylmethyl-oxycarbonyl 119-122 Compound 31 of Table 7 is particularly important for the present invention. - 108 - WHAT WE CLAIM IS: J.. A synergistic conbination preparation comprising at least one nucleoside and at least one compound of the formula I and/or la, e7o "Sg (I) 10 (la) and physiologically acceptable salts and prodrugs thereof, where, in formulae I and la, n is zero, one, two, three or four, 15 20 the individual substituents R1 independently of one another are fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, hydroxyl, Ci-Ca-alkyI, C3-Ca-cycloalkyl, Ci-Cg-alkoxy, (C^Ca-alkoxy)-(Ci-C^-alkoxy), Cx-Cg-alkylthio, Cj-C6-alkyl-sulfinyl, Ci-Cg-alkylsulfonyl, nitro, amino, azido, Ci-Ce-alkylamino, difC^Ce-alkyl) amino, piperidino, morpholino, l-pyrrol^c^p^|.^ ^ ^ Intellectual Property Office 1 3 FEB 1998 of New Zealand - 109 - 4-methyIpiperazinyl, thiomorpholino, imidazolyl, triazolyl, tetrazolyl, Ci-Ce-acyl, C^-Co-acyloxy, Ci-Ca-acylamino, cyano, carbamoyl, carboxyl, (Ci-Cg-alkyl)oxycarbonyl, hydroxysulfonyl, sulfamoyl or a phenyl, phenoxy, phenoxycarbonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy, anilinosulfonyl, phenyl-sulfonylamino, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical which is substituted by up to five radicals R6 which are independent of one another, where R6 can be fluorine, chlorine, bromine, iodine, cyano, tri-fluoromethyl, trifluoromethoxy, nitro, amino, azido, Ci-Ce-alkyl, C3-C8-cycloalkyl, C^-Ce-alkoxy, Ci-Ce-alkylthio, Cx-Ce-alkylsulfinyl, Cx-C^-alkyl-sulfonyl, C^-Cg-alkylamino, di(C]-CB-alkyl) amino, (Cj-Cg-alkyl)oxycarbonyl, phenyl, phenoxy, 2-, 3-or 4-pyridyl, R2 and Rs are identical or different and, independently of one another, are hydrogen, hydroxyl, C1-C8-alkoxy, aryloxy, Ci-Ce-acyloxy, cyano, amino, C1-C6-alkylamino, ditCj-Ce-alkylJeuiiino, arylamino, C^-Ce-acylamino, Ci-CB-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Ci-Ca-acyloxy, benzoyloxy, benzyloxy, phenoxy, Ci-Cg-alkoxy, C j—C6—alkyl ami no, difCi-Ce-alkyl) amino, Cj-Ce-alkylthio, C^-Ce-alkyisulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; - 110 - 27008 C2-C8-alkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cx-C6-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cj-CB-alkoxy, Cj-Cg-alkylamino, di (C^-Cg-allcyl) amino, Cj-Cg-alkyl-thio, Ci-Cg-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl and carbamoyl; C3-Ce-allenyl, optionally substituted by fluorine, chlorine or hydroxyl, Ci-C^-alkoxy, oxo, phenyl; C3-C8-alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cj-Cg-acy loxy, benzoyloxy, benzyloxy, phenoxy, Ci-Cg-alkoxy, Cj-Cb-alkyl amino, di(Ci-Cg-alkyl) amino, Cj-Cg-alkylthio, Cj-Cg-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C3-C8-cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C1-C6-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cx-C6-alkoxy, C1-C8- alkyl ami no, di(C!-C6-alkyl) amino, Ci-Ca-alkylthio, Ci-Ca-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C3-C8-cycloalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C^-Cg-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cx-CB-alkoxy, Cx-C6-alkyl ami no , difC^-Ce-alkyl) amino, Cj-Cg-alkylthio, Cj-Ce-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; - Ill - (C3-C8-cycloalkyl) - (Ci-C^-alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C^-Cg-acyloxy, benzoyloxy, benzyloxy, phenoxy, Ci-Cg-alkoxy, Cj-Cg-alkylamino, di (C1-C6-alkyl) amino, Ci-Ce-alkylthio, Cj-Cs-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; (C3-C8-cycloalkenyl) - (Cx-C4-alky 1), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Ci-Cg-acyloxy, benzoyloxy, benzyloxy, phenoxy, C1-C6-alkoxy, Ci-Cj-alkyl amino, ditC^-Cg-alkyl) amino, Cj-Cfl-alkylthio, Ci-Cg-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; Cj-CQ-alkylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Ci-Cg-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cx-Cg-alkoxy, Ci-Ce-alkyl amino, di (C^-Cg-alkyl) amino, Cj-Cg-alkylthio, Ci-Cg-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C2-C8-alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Cx-C4-alkoxy, oxo, phenyl; (C3-C8-cycloalkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Ci-C^-alkoxy, oxo, phenyl; (C5-C8-eyeloalkenyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, - 112 - C1-CA-alkoxy, oxo, phenyl; (C3-C8-cycloalkyl)-(C1-C3-alkyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, C^-C^-alkoxy, oxo, phenyl; (C5-C6-cycloalkenyl) - (Cx-Ca-alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Cj-CA-alkoxy, oxo, phenyl; Ci-Ca-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, Cx-CA-alkoxy, Cx-CA-alkylamino, di(C1-CA-alkyl) amino, C^C^-alky 1 thio; C2-CB-alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cj-C^-alkoxy, oxo, phenyl; C2-C8-alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, C^-C^-alkoxy, oxo, phenyl; Ci-Ce-alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cj-C^-alkoxy, oxo, phenyl; C2-C8-alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cx-CA-alkoxy, oxo, phenjl; Ci-Ce-alkylamino- and di(Cx-C8-alkyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, C^C^-alkoxy, oxo, phenyl; pyrrolidin-l-yl, morpholino-, piperidino-, piperazinyl-, or 4-methylpiperazin-l-ylcarbonyl, in each case optionally substituted by Cx-CA-alkyl, C2-C6-alkenyl, Cx-CA-acyl, oxo, thioxo, carboxyl, or phenyl; C2-C8-alkenylamino- and di (Ci-Ce-alkenyl) amino-carbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Cj-CA-alkoxy, oxo, phenyl; Ci-Cg-alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cx-C^-alkoxy, oxo, phenyl; Cj-Cg-alkenylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cx-C^-alkoxy, oxo, phenyl; or aryl, arylcarbonyl, aryl(thiocarbonyl), (aryl-thio)carbonyl, (arylthio)thiocarbonyl, aryloxy-carbonyl, arylaminocarbonyl, (arylamino)thiocarbonyl, arylalkylaminocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkyl-carbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl or aryl(alkylthio)carbonyl, each of which is substituted by up to 5 radicals R6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 5 carbon atoms, and R6 being as defined above, or heteroaryl, heteroarylalkyl, heteroaryl-alkenyl, heteroarylalkylcarbonyl or heteroaryl-alkenylcarbonyl, heteroaryloxycarbonyl, (heteroary lthio )carbonyl, heteroarylaminocarbonyl, heteroarylalkyloxycarbonyl, heteroaryl-(alkylthio)carbonyl or heteroarylalkylaminocarbonyl, each of which is substituted by up to three radicals R6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms, and R* are identical or different and, independently of one another, are hydrogen, Cj-Cg-alkyl which is optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, - 114 - 27 C1-CA-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cx-C^-alkoxy, Cj-C^-alkylamino, difC^-C^-alkyl)-amino, C^-C^-alkylthio, Ci-C^-alkylsulfonyl, Cj-C*" alky1sulfinyl, carboxyl or carbamoyl; C2-C8-alkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, Cj-C*-acyloxy, benzoyloxy, benzyloxy, phenoxy, C^-C^-alkoxy, Cx-C^-alkylamino, difCx-C^-alkyl) amino, Cx-C^-alkylthio, Cx-C^-alkylsulfonyl, Cj-C^-alkyl-sulfinyl, carboxyl or carbamoyl; C3-C0-cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, Cx-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cx-C^-alkoxy, Cx-C^-alkylamino, difCx-C^-alkyl) -amino, Cx-C^-alkylthio, Cx-C^-alkylsulfonyl, Cx-C*-alkylsulfinyl, carboxyl or carbamoyl; C3-C8-cycloilkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, Cj-C^-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cx-CA-alkoxy, Cj-C^-alkylamino, di (Cx-C^-alkyl) -amino, Cj-C^-alkylthio, Cx-C^-alkylsulfonyl, Cj-C*-alkylsulfinyl, carboxyl or carbamoyl; aryl, arylalkyl, heteroaryl or heteroarylalkyl, each of which is substituted by up to five radicals R6 which are independent of one another, it being possible for the alkyl radical to contain 1 to 3 carbon atoms in each case, and R6 being as defined above, R3 and R4 or R3 and Rs can furthermore also be part of a saturated or unsaturated carbo- or heterocyclic ring which has 3 to 8 carbon atoms and which can optionally be substituted by fluorine, chlorine, hydroxyl, amino, C^-Ce-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Cj-Ce-acyloxy, - 115 - benzoyloxy, Cx-C6-alkoxy, oxo, thioxo, carboxyl, carbamoyl or phenyl, X is oxygen, sulfur, selenium or substituted nitrogen N-R2, it being possible for R2 to have the abovementioned meanings.
2. A combination preparation as claimed in claim 1, wherein the nucleoside is selected from the group consisting of zidovudine, didanosine, dideoxycytidine, lamivudine, stavudine, BW 935U83 and BW 1592U89.
3. A combination preparation as claimed in claim 1 or 2, which comprises zidovudine and S-4-isopropoxy-carbonyl-6-methoxy-3- (methy lthiomethyl) -3,4-dihydro-quinoxaline-2-(IB)-thione.
4. A pharmaceutical which comprises an effective amount of a combination preparation as claimed in one or more of claims 1-3, if appropriate in addition to customary auxiliaries and/or excipients.
5. A combination preparation as claimed in one or more of claims 1-3 for use as pharmaceutical.
6. A combination preparation as claimed in one or more of claims 1-3 for the preparation of pharmaceuticals for treating viral diseases.
7. A process for the preparation of a pharmaceutical, which comprises bringing a combination preparation as claimed in one or more of claims 1-3, if appropriate together with customary auxiliaries and/or excipients, into a suitable dosage form.
8. A combination preparation according to claim 1 substantially as herein described or exemplified. -116-
9. A pharmaceutical according to claim 4 substantially as herein described or exemplified.
10. A process according to claim 7 substantially as herein described or exemplified. END OF CLAIMS 270088 fi e c' t v ■. o Intellectual P'opeity Offic 1 3 FEB 1998 of Nr-; Zealand JECfiST AKTIENGESELLSCHAFT By Attorneys^ HEIflW HUbflES </div>