AU654178B2 - Quinoxalines, processes for their preparation, and their use - Google Patents

Abstract

Compounds of the formula I or Ia <IMAGE> in which n and the substituents R<1> - R<5> and also X have the same meaning, have antiviral activity.

Description

AUSTRALIA

Patents Act 1990 R~egulation 3.2(2)

ORIGINAL

COMPLETE SPECIFICATION STANDARD PATENT Application Number: Lodged: .0 0 0* 0 00. 0 0* *000 Invention Title: QUINOXALINES, PROCESSES FOR THEIR PREPARATION, AND THEIR USE 4.

00 000.

00 00 0 0100 0000 000000 The following statement is a full description of this invention, including the best method of performing it known to :-us HOECHST AKTIENGESELLSCHAFT HOE 91/F 111K Dr. WN/fe Description Quinoxalines, processes for their preparation, and their use The present invention relates to quinoxalines, to processes for their preparation, and to their use.

Quinoxalines are a well-known class of compound Hinsberg, J. Uebigs Ann.

Chem. 237, 327 (1986)).

Quinoxaline derivatives have been described in the patent literature for use in various applications in medicine.

Austrian Patent 284,848 (19.12.67) mentions 1-N-dialkylaminoalkyl- 3,4-dihydroquinoxalin-2(1 H)-ones as spasmolytic agents. A series of patent applications by the Japanese company Sumitomo Chem. Co. Ltd. describe 4-N-aroyl-, arylacyl- and arylsulfonyl-3,4-dihydroquinoxalin-2(1H)-ones which have an antiinflammatory action (JA 17,137/69 (11.4.66), JA 17,136/69 JA 7,008/422 BE 706,623 (16.11.66)). 3,4-Dihydroquinoxalin-2(1H)-one-3-carboxamides are S contained in US Patent US 3,654,275 They, too, have an antiinflammatory ?Q action. In US Applications US 4,203,987 (21.5.79) and 4,032,639 (22.3.76), pyridinylalkyltetrahydropyrazino[1,2-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-dihydroquinoxalin-2(1H)-one-1-alkylcarboxylic acids as aldose reductase inhibitors.

However, an antiviral activity has not been demonstrated to date.

Surprisingly, it has now been found that quinoxalines of the formulae I and la R N X C (I) 1 R4

R

and their tautomeric forms of the formula la -R3 N X R1 (la) R4 S and physiologically acceptable salts or prodrugs thereof 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, S the individual substituents R' independently of one another are fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, hydroxyl, C1-Cs-alkyl, C,-C-cycloalkyl, C,-C 6 -alkoxy, (Ci-C 6 -alkoxy)-(C,-C 4 -alkoxy), 0 ~C 1 -C.-alkylthio, Cl -C.-alkylsulfinyl, C 1

-C

6 -alkylsulfonyl, nitro, amino, azido, Cl-C.-alkylamino, di (C -C 6 -alkyl) amino, piperidino, morpholino, 1 -pyrrolidinyl, 4-methylpiperazinyl, thiomorpholino, imidazolyl, triazolyl, tetrazoyl, C 1

-C

6 -acyl, C,-C.-acyloxy, Cl-C,,-acylamino, cyano, carbamoyl, carboxyl, (0 1 -Cr,-alkyl)oxycarbonyl, hydroxysulforyl, sulfamoyl or a phenyl, phenoxy, phenoxycarbonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy, anilinosulfonyl, phenylsulfonylamino, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical which is substituted by up to five radicals R 6 which are independent of one another, where R 6 can be fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, azido, C 1

-C

6 -alkyl, C 3

-C

8 -CYCloalkyl, CI -Cr,-alkoxy, C 1 -C.-alkylthio, C,-C.-alkylsulfinyl, Cl-C.-alkylsulfonyl, Cl-C, 6 -alkylamir,,o, di (Cl -C.-alkyl) amino, (0 1 -C.-alkyl)oxycarbonyl, phenyl, phenoxy, 3- or 4-pyridyl, R 2 is hydrogen, C 1

-C

6 -alkoxy, hydroxyl, picolyl, cyclopropyl or isopropenyloxycarbonyl and R 5 is hydrogen, hydroxyl, Cl-C.-alkoxy, aryloxy, C,-C.-acyloxy, cyano, amino, C, -C 6 -alkyl amino, di(A -C6-alkyl) amino, arylamino, C-C-acylamino, C,-C.-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercaptd, hydroxyl, C,-C.-acyloxy, benzoyloxy, benzyloxy, phenoxy, C,-C, 5 -alkoxy, C,-C.-alkylamino, di AC -C 6 -alkyl) amino, C,-C.-alkylthio, C,-C6-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carba-moyl; 0 0 2

-C

8 ,-alkenyl, optionaly substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl,

C

1 -0 6 -acyloxy, benzoyloxy, benzyloxy, phenoxy. 01-cr,-alkoxy, C,-Cr 6 -alkylamino, d i (CI -0 6 -alkyl) amino, C,-Cd-alkylthio, Cl-C 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl and carbamoyl; 0 3 -C.-allenyl, optionally substituted by fluorine, chlorine or hydroxyl,

C

1

-C

4 -alile)-,y, oxo, phenyl; 0 3

-C

8 ,-alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, 0 1

-C

6 -acyloxy, benzoyloxy, berzyloxy, phenoxy, C 1 -C6-alkoxy, C 1 -C.-alkylamino, di(Cl-C 6 -alkyl)amino, 0 1

-C

6 -alkylthio, Cl-C 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl;

:C

3 -C8-cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, il q

C

1 -C.-acyloxy, benzoyloxy, benzyloxy, phenoxy, C,-C.-alkoxy, C 1

-C

6 -alkylamino, di (Cl-C 6 -alkyl)amino, Cl-C 6 -allcvlthio, Cl-C, 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C3-C,-cycloalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C -C4.

S:C..lx, ezyoy bnyoy heoy c- C,-C-acyoxy benoyloy, bnzyo)(y pheox 1 CC6 Ilkoxy, Cl-C 6 -alkylamino, di(Cl-C 6 -alkyl)amino, Cl-C 6 -alkylthio, C 1

-C

6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl;

(C,-C

8 ,-cycloalkyl)-(C 1

-C

4 -alkyl), optionally substituted by fluor-ine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C, Cc Ok 1.) C, -0 6 -acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C6-alkoxy, C 1

-C

6 -alkylamino, di(C 1

-C

6 -alkyl)amino, ClCaklho Cl-C, 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl;

(C

3

-C

8 -cycloalkeny)-(C,-C 4 -alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C C Ckk cAktl~

C,-C,

6 -acyloxy, benzoylkxy, benzyloxy, phenoxy, C,-C aloy lCaklmi, di (0 1

-C

6 -alkyl)amino, Cl-C 6 -alkylthio, 0 1 -0 6 -alkylsulfonyl, phenylsullonyl, oxo, thioxo, carboxyl or carbamoyl; 0 1

-C

6 -alkylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C I -C+ C*Z C 2 c~-Z-A.

Cl-C 6 cylcxy, benzoyloxy, benzyloxy, phenoxy, C,-C -alkoxy, C -C -aikylam ino, V- ejrroloAlilj pipe-ricM A6 mcrpko~r~o, rne+6 di 1 -C-alyl)aminjC 1

C

6 -lkythi,C 1 -C6-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl;

C

2 -C,-alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxyl Cl-C 4 -alkox\', oxo, phenyl; :ia(C,-C 6 -cycloalkyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, C 1

-C

4 -alkoxy, oxo, phenyl;

(C,-C

6 ,-cycloalkei-yl'.)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, C 1

-C

4 -alkoxy, oxo, phenyl; 6

(C

3

-C

8 -cycloalkyl)- (C 1

-C

3 -alkyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; (0 5

-C

6 -cycloalkenyl)-(C,-C 3 -alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, 0 1

-C

4 -alkoxy, oxo, phenyl; Cl-C.-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, C 1

-C

4 -alkoxy, C,-C 4 -alkylamino, di (C,-C 4 -alkyl)amino, C 1

-C

4 -alkylthio;

C

2 -C,-alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl;

C

2 -C,-alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; 0 1 -0 8 -alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyL, Cl-C 4 -alkoxy, oxo, phenyl; 0 2 -C,-alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl,

C

1 -0 4 -alkoxy, oxo, phenyl; C,-0 8 ,-alkylamino- and di(C,-C.-alkyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; pyrrolidin-1-yl, morpholino-, piperidino-, piperazinyl-, or 4-methylpiperazin- 1 -ylcarbonyl, in each case optionally substituted by 0 1 -0 4 -alkyl, C 2

-C

6 -alkenyl, 0 1

-C

4 -acyl, oxo, thioxo, carboxyl, or phenyl;

C

2 -C,-alkenylamino- and di(C-C 6 -alkenyI)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, C 1

-C

4 -alkoxy, oxo, phenyl; 7

C

1 -0 8 -alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, C 1

C

4 alkoxy, oxo, phenyl; C len~ufnl optionally substituted by fluorine, chlorine, hydroxyl, C1-C4alkoxy, oxo, phenyl; or aryl, arylcarbonyl, aryl (thiocarbonyl), (arylthio)carbonyt, (arylthio)thiocarbonyl, aryloxycarbonyl, arylaminocarbonyl, (arylamino)thiocarbonyl, arylalkylaminocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylaikoxycarbonyl or aryl (alkylthio)carbonyl, each of which is substituted by up to fVra radicals R 6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to carbon atoms, and R 6 being as defined above, or heteroaryl, heteroarylalkyl, heteroarylalkenyl, 1 heteroarylalkylcarbony or heteroarylalkenylcarbonyl, heteroaryloxycarbonyl, (heteroarylthio)carbonyl, heteroarylaminocarbonyl, heteroarylalkyloxycarbonyl, heteroaryl (alkylthio)carbonyl or heteroarylalkylaminocarbonyl, each of which is substituted by up to three radicals R 6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms,

R

3 and R' are identical or different and, independently of one another, are hydrogen, 0 1 -C.-alkyl which is optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, C 1

-C

4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, 0 1 -0 4 -alkoxy, C 1 -0 4 -alkylamino, di(0 1

-C

4 -alkyl)amino, C1-C4alkylthio, 0 1 -0 4 -al kylsulfonyl, 0 1 -0 4 -alkylsufinyl, carboxyl or carbamoyl; 0 2 -0 8 -alkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, Cl-0 4 -aCYloxy, benzoyloxy, benzyloxy, phenoxy, C, -0 4 -alkoxy, C1-C4- 8 alkylamino, di(C,-C 4 -alkyl)amino, C,-C 4 -alkylthio, C,-C 4 -alkylsulfonyl, C,-C4alkylsulfinyl, carboxyl or carbamoyl;

C

3

-C

8 -cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercaptc, C,-C4-acyloxy, benzoyloxy, benzyloxy, phenoxy, C,-C 4 -alkoxy, C,-C4 alkylamino, di(C,-C 4 -alkyl)amino, C,-C 4 -alkylthio, C,-C4-alkylsulfonyl, C,-C4alkylsulfinyl, carboxyl or carbamoyl;

C

3

-C

8 -cycloalkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, C,-C,-acyloxy, benzoyloxy, benzyloxy, phenoxy, C,-C 4 -alkoxy,

C,-C

4 -alkylamino, di(C,-C 4 -alkyl)amino, C,-C4-alkylthio, C,-C4-alkylsulfonyl, C,-C4 alkylsulfinyl, carboxyl or carbamoyl; aryl, arylalkyl, heteroaryl or heteroarylalkyl, each of which is substituted by up to five radicals R 6 which are independent of one another, it being possible for the alkyl radical to contain 1 to 3 carbon atoms in each case, and R 6 being as defined above,

R

3 and R 4 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,-C 6 -alkyl, C2-C 6 -alkenyl, C,-C 6 -alkynyl, C,-C-acyloxy, benzoyloxy, C,-C 6 -alkoxy, oxo, thioxo, carboxyl, carbamoyl or phenyl, X is oxygen, sulfur, selenium or substituted nitrogen N-R 2 it being possible for R2 :i to have the abovementioned meanings, with the exception of those compounds in which R 3 and R' are both hydrogen, and compounds in which R 2 and R 5 are hydrogen and R 3 and/or R 4 are/is arylalkyl, and compounds in which X is oxygen and R 2 and R 5 are hydrogen.

In a preferred group of compounds of the formula I or la, 2) n is zero, one, two or three, the individual substituents R' independently of one another a~re fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, hydroxyl, C 1

-C

4 alkyl, C.,-C 6 -cycloalkyl, C, -C 4 -alkoxy, (C 1

-C

4 -alkoxy)-(0 1

-C

4 -alkoxy), CI-C4alkylthio, C 1

-C

4 -alkylsulfinyl, Cl-C 4 -alkylsulfonyl, nitro, amino~, 0 1

-C

4 -alkylamino, di (0 1

-C

4 -alkyl) amino, piperidino, morpholino, 1 -pyrrolidinyl, 4-methylpiperazinyl, thiomorpholino, imidazolyl, Cl-0 4 -acyl, Cl-C 4 -acyloxy, 0 1

-C

4 -acylamino, cyano, carbamoyl, carboxyl, (Cl-C 4 -alkyl)oxycarbonyl, hydroxysulfonyl or sulfamoyl V or a phenyl, phenoxy, phenoxycarbonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulforiyloxy, anilinosulfonyl, phenylsulfonylamino, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical which is substituted by up to two radicals R 6 which rsre independent of one another, *where R 6 can be fluorine, chlorine, bromine, cyano, trifluoromethyl, nitro, amino, C 1

-C

4 -alkyl,

C

3

-C

7 -CYCloalkyl, Cl-C 4 -alkoxy, C 1

-C

4 -alkylthio, C 1

-C

4 -alkylsulfinyl, Cl-C'jalkylsulfonyl, Cl-C 4 -alkylamino, di(Cl-C 4 -alkyl)amino, (Cl-C 4 -alkyl)oxycarbonyl, phenyl or phenoxy, R 2 is hydrogen and R 5 is hy~gm hydroxyl, cyano, amino, Cl-0 6 -alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C 1

-C

4 acyloxy, benzoyloxy, berizyloxy, phenoxy, Cl-C 4 -alkoxy, C 1

-C

4 -alkylamino, di (Cl-0 4 -alkyl) amino, 0 1

-C

4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; 0 2 -C.-alkenyi, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cl-C47 acyloxy, benzoyiloxy, benzyloxy, phenoxy, C 1

-C

4 -alkoxy, Cl-0 4 -alkylamino, di (C0-C 4 -alkyl) amino, C, -04- alkylthio, oxo, thioxo, carboxyl or carbamoyl;

C

3 -0 5 -allenyl,

C

3 -0 8 -alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C,-C4- ~0 acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-0 4 -alkoxy, 0 1 -0 4 -alkylamino, di(0 1 -0 4 -alkyl)amino, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl;

C

3 -0 8 I-CYCloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C1-04acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C 4 -alkoxy, 0 1 -0 4 -alkylamino, d(0 1 -C-alkyl)amino, 0 1 C-alkylthio, oxo, thioxo, carboxyl or carbamoyl; fe* SiC -4 IC

C

3 -C,-CYCoalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapt?, hydroxyl, C,-C4acyloxy, benzoyloxy, benzyloxy, phenoxy, C,-0 4 -alkoxy, C 1 -0 4 -alkylamino, di(C 1

-C

4 -alkyl)amino, C,-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl;

(C

3

-C

8 -cycloalkyl)-(C,-C 2 -alkyl) optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl1, C 1

-C

4 acyloxy, benzoyloxy, benzyloxy, pnenoxy, C 1

-C

4 -alkoxy, C 1

-C

4 -alkylamino, di(C,-C 4 -alkyl)amino, Cl,-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl;

(C.-C

8 -cycloalkenyl)-(Cl-C 2 -alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, 01-04acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1

-C

4 -alkoxy, Cl-C 4 -alkylamino, di(A -0 4 -alkyl) amino, 01 -0 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; a. 0, *4,Cl-0 6 ,-alkylcarbonyl, .0 .optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cl-C,- 9:010acyloxy, benzoyloxy, benzyloxy, phenoxy, C,-C 4 -alkoxy, Cl-C 4 -alkylamino, di(C 1

-C

4 -alkyl)amino, C 1

-C

4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; 2 -0 6 -alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxyl, 0Cl-C 4 -alkoxy, oxo, phenyl; *eta (C 3 -C,-CYCloalkyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Cl-0 4 alkoxy, oxo, phenyl;

(C

5 -0 6 -CYCloalkenyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, C 1

-C

4 -alkoxy, oxo, phenyl; 12 (C3-C 6 -CYCloalkyl)-(Cj-C 2 -alkyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl;

(C

5

-C

6 -CYCloalkenyl)-(C 1

-C

2 -alkyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, C 1

-C

4 -alkoxy, oxo, phenyl; Cl-C, 6 -alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, Cl-C 4 -alkoxy, Cl-C 4 -alkylamino, di (C 1

-C

4 -alkyl)amino, C,-C 4 -alkylthio;

C

2 -C,-alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl,

C

1

-C

4 -alkoxy, oxo, phenyl;

C

2

-C

6 -alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Ci-C4-al koxy, oxo, phenyl;

C

1

-C

6 -alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl;

C

2

-C

6 -alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; Cl-Cr 6 -alkylamino- and di(C-C-alkyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, C 1

-C

4 -alkoxy, oxo, phenyl; 9:0.25pyrrolidin-1-yl, morpholino-, piperidino-, piperazinyl-, or 4-methylpiperazingoof 1 -ylcarbonyl; 5C 2

-C

6 -alkenylamino- and di(Ct C 6 -alkenyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; C,-C,-alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, C 1

-C

4 alkoxy, oxo, phenyl; C2 C 4 -alkenylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, C,-C4alkoxy, oxo, phenyl; or aryl, arylcarbonyl, aryl (thiocarbonyl), (arylthio)carbonyl, (arylthio)thiocarbonyl, aryloxcycarbonyl, 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 R 6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to carbon atoms and R 6 being as defined above, or 1- or 2-naphthylmethyl, 3- or 4-picolyl, 2- or 3-furylmethyl, 2- or ~.3-thienylmethyl, 2- or 3-pyrrolylmethyl, 3- or 4-pyridylcarbonyl, 2- or 3-furylcarbonyl, 2- or 3-thienylcarbonyl, 2- or 3-thienylacetyl, 3- or 555 4-picolyloxycarbonyl, 2- or 3-furylmethyloxycarbonyl, 2- or 3-thienylmethyl- S6 oxycarbonyl, each of which is substituted by up to two radicals R 6 which are 2 0 independent of one another, and R R 3 and R 4 are identical or different and independently of one another are hydrogen, 'SOS..Cl-C.-alkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, C 1

-C

4 acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C 4 -alkoxy, Cl-C 4 -alkylamino, W di(0 1

-C

4 -alkyl)amino, 0 1 -0 4 -alkylthio, Cl-0 4 -alkylsulfonyl, C 1

-C

4 -alkylsulfinyl, carboxyl or carbamoyl; 0 2 -0 8 -alkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, C4 acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -0 4 -alkoxy, C1-C4alkylamino, di(Cl-C 4 -alkyl)amino, 0 1

-C

4 -alkylthio, Cl-0 4 -alkylsulfonyl, C1-C4alkylsulfinyl, carboxyl or carbamoyl; 0 3 -0 8 -cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, 0 1

-C

4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, 0 1

-C

4 -alkoxy, C1-C4alkylamino, di(0 1 -0 4 -alkyl)amino, Cl-0 4 -alkylthio, Cl-C 4 Ilkylsulfonyl, 01-C4alkylsulfinyl, carboxyl or carbamoyl; 0 3 -C,-cycloalkenyi, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, 0 1

-C

4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C, -C 4 -alkoxy,

C

1

-C

4 -alkylamino, di(0 1

-C

4 -alkyl)amino, 0 1

-C

4 alkylthio, C 1

-C

4 -alkylsulfonyl, 01-04alkylsulfinyl, carboxyl or carbamoyl; 0 aryl, arylalky!. heteroaryl or heteroarylalkyl, each of which is substituted by up to three radicals R 6 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 6 being as defined above, R 3 and R 4 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, Cl-0 4 -alkyl, 0 2 -C,-alkenyl, C 2

-C

4 -alkynyl, Cl-C 4 -acyloxy, benzoyloxy, C 1

-C

4 -alkoxy, oxo, thioxo, carboxyl, carbamoyl or phenyl, and X is oxygen, sulfur or selenium.

WIn a yet more preferred group of compounds of the formula I or la, 3) n is zero, one or two, the individual substituents R' independently of one another are fluorine, chlorine, bromine, trifluoromethyl, hydroxyl, C 1

-C

4 -alkyl, C 1

-C

4 -alkoxy,

(C

1

-C

4 -alkoxy)-(C 1

-C

4 -alkoxy), Cl-C 4 -alkylthio, nitro, amino, C 1

-C

4 -alkylamino, di (Cl-C 4 -alkyl)amino, piperidino, morpholino, 1 -pyrrolidinyl, 4-methylpiperazinyl, Cl -C 4 -acyl, Cl-C 4 -acyloxy, Cl-C 4 -acylamino, cyano, carbamoyl, carboxyl, (C 1

-C

4 alkyl)oxycarbonyl, hydroxysulfonyl or sulfamoyl, :is: or a phenyl, phenoxy, phenyithic, phenylsulfonyl, phenoxysulfonyl, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical which is substituted by up to two radicals

R

6 which are independent of one another, where R 6 can be fluorine, chlorine, bromine, cyano, trifluoromethyl, nitro, amino, Cl-C 4 -alkyl, Cl-C 4 -alkoxy, (C 1

-C

4 -alkyl) oxycarbonyl, phenyl or phenoxy, R 2 iS hydrogen and R 5 is

C

1

-C

6 -aikyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -acyloxy, benzoyloxy, benzyloxcy, phenoxy, 0 C 1

-C

4 -alkoxy, Cl -C 4 -alkylamino, di (Cl-C 4 -alkyl)amino, CI-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl;

C

2

-C

6 -alkenyl, optionally substituted by fluorine, chlorine, hydroxyl, CI-C 4 -acyloxy, benzoyloxy, benzyloxCy, phenoxy, Cl-C 4 -alkoxy, C 1

-C

4 -alkylamino, di (0 1 -0 4 -alkyl)amino, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; C,,-C.-allenyl,

C

3

-C,

8 -alkynyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -aCYloxy, benzoylox(y, benzyloxy, phenoxy, :0.15Cl-C 4 -alkoxy, Cl-C 4 -alkylamino, di(A -0 4 -alkyl) amino, Cl-C 4 -alkylthio, oxo, thioxo, :carboxyl or carbamoyl;

C

3 -C,-cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, C,-Cg.alkyl, Cl-C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-0 4 -alkoxy, C 1

-C

4 -alkylamino, di(C 1

-C

4 -alky)amino, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl;

C

3

-CI

8 -CYCloalkenyl, optionally substituted by 0%10.fluorine, chlorine, hydroxyl, Cl-C 4 -alkyl, Cl-C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C 4 -alkoxy, Cl-C 4 -alkylamino, di(Cl-C 4 -alkyl)amino, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; W (C 3

-C

6 -cycloalkyl)-(Cl-0 2 -alkyl), optionally substituted by fluorine, chlorine, hydroxyl, CI-C 4 -alkyl, CI-C 4 -aCYloXY, benzoyloxy, benzyloxy, phenoxy, C,-C 4 -alkoxy, Cl-C 4 -alky'amino, di (C 1

-C

4 -alkyl)amino, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; (0 3

-C

6 -cycloalkenyl)- (C,-C 2 -aikyl), optionally substituted by fluorine, chlorine, hydroxyl, 0 1

-C

4 -alkyl, C 1

-C

4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C 4 -alkoxy, C 1

-C

4 -alkylamino, di(C 1

-C

4 -alkyl)amino, C 1

-C

4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; Cl-C 6 -alkylcarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkyl, Cl-C 4 -acyloxy, benzoyloxy, benzyloxy, :phenoxy, Cl-C 4 -alkoxy, Cl-C 4 -alkylamino, C,,C 4 -alkenylamino, di(Cl-C 4 alkyl)amino, 1-pyrrolidinyl, piperidino, morpholino, 4-methylpiperazin-1-yl, C 1

-C

4 alkylthio, oxo, thioxo, carboxyl or carbamoyl;

C

2

-C

6 -alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxyl;

(C

3 -C,-cycloalkyl~carbonyl,

(C

5

-C

6 -CYCloalkenyl)carbonyl,

(C

3

-C

6 -CYCloalkyl)-(Cl-C 2 -alkyl)carbonyl,

(C

5

-C

6 ,-cycloalkenyl)- (C 1

-C

2 -alkyl)carbonyl, Cl-Cr-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, 0 1

-C

4 -alkoxy, Cl-C 4 -alkylamino, di -C 4 -alkyl)amino or C 1

-C

4 -alkylthio; '4A;T 18

C

2 -C-alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl,

C

1

-C

4 -alkoxy;

C

2 -Cr 6 -alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl,

C

1

-C

4 -alkoxy;

C

1

-C

6 -alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy; 0 2

-C

6 -alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydrc-'xyl, 0 1

-C

4 -alkoxy;

G

1

-C

6 -alkylamino- and di(0 1

-C,

6 -alkyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, 0 1

-C

4 -alkoxy; pyrrolidin-1-yl, morpholino-, piperidino-, piperazinyl-, or 4-methylpiperazin- 1 -ylcarbonyl; 0 2

-C

6 -alkenylamino- and di(Q -C.-alkenyl)aminocarbonyl, in each case optionally substitul,'d by fluorine, chlorine, hydroxyl, Cl-0 4 -alkoxy;

C

1 -0 4 -alkylsulfonyl, optionally substiLuted by fluorine, chlorine, hydroxyl, C 1

-C

4 alkoxy; 1.-C 4 -alkenylsulfonyl; or aryl, arylcarbonyl, (arylthio)carbonyl, aryloxycarborvJ .wlnocarbonyl, (arylamino)thiocarbonyl, arylsulfonyl, arylalkylairinocarbonyl, arylalkyl, arylalkenyl, arylalkylcarbonyl, arylalkoxycarbonyl or aryl (alkylthio)carbonyl, each of which is substituted by up to two radicals R 8 which are independent of one 19 another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms, and R 6 being as defined above, or 1- or 2-naphthylmethyl, 3- or 4-picolyl, 2- or 3-furylmethyl, 2- or 3-thienylmethyl, 2- or 3-pyrrolylmethyl, 3- or 4-pyridylcarbonyl, 2- or 3-furylcarbonyl, 2- or 3-thienylcarbonyl, 2- or 3-thienylacetyl, 3- or 4-picolyloxycarbonyl, 2- or 3-furylrnethyloxycarbonyl or 2- or 3-thienylmethyloxycarbonyl, each of which is substituted by up to two radicals R 6 which are independent of one another, and R 3 and R 4 are identical or different and independently of one another are hydrogen, 0 1

-C

4 -alkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, C 1

-C

4 -acyloxy, benzoyloxy, phenoxy, Cl-0 4 -alkoxy, Cl-C 4 -alkylamino, dI(C 1

-C

4 -alkyl)amnino, C 1

-C

4 -alkylthio, C 1

-C

4 alkylsulfonyl, Cl-C 4 -alkylsulfinyl, carboxyl or carbamoyl; C.-0 6 alkenyl, optionally substituted by fluorine or chlorine;

C

3 -0 6 -cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, C 1

-C

4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1

-C

4 -alkoxy, C -04alkylam,'no, di(Cl-C 4 -alkyl)amino, Cl-C 4 -alkylthio, Cl-C 4 Ilkylsulfonyl, 01-04alkylsulfinyl, carboxyl or carbamoyl; 0 3 -CS-cycloalkenyl, optionally substituted by fluorine or chlorine; aryl, benzyl, heteroaryl or heteroarylmethyl, each of which is substituted by up to trio radicals R' which are independent of one another, 'W R 3 and R 4 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, Cl-C 4 -acyloxy, benzoyloxy, Cl-C 4 -alkoxy, oxo, thioxo, carboxyl or carbamoyl, and X is oxygen or sulfur.

In a yet again preferred group of compounds of the formula I or la, 4) n is zero, one or two, vq* the individual substituents R' independently of one another are fluorine, chlorine, bromine, trifluoromethyl, hydroxyl, 0 1

-C

4 -alkyl, Cl-0 4 -alkoxy,

(C

1

-C

4 -alkr-XY)-(Cj-C 2 -alkoxy), 0 1 -0 4 -alkylthio, nitro, amino, C 1

-C

4 -alkylamino, di (0 1

-C

4 -alkyl)amino, piperidino, morpholino, I -pyrrolidinyl, 4-methylpiperazinyl, C,-0 4 -acyl, C 1

-C

4 -acyloxy, C 1

-C

4 -acylamino, cyano, carbamoyl, carboxyl, (0-04alkyl)oxycarbonyl, hydroxysulfonyl or sulfamoyl or a phenyl, phenoxy, phenylthio, phenylsulfonyl, phenoxysulfonyl, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical, each of which is substituted by up to two radicals R 6 which are independent of one another, where R 6 can be fluorine, chlorine, bromine, cyano, trifluoromethyl, nitro, amino, C 1

-C

4 -alkyl,

C

1

-C

4 -alkoxy, (Cl-C 4 -alkyl)oxycarbonyl, phenyl or phenoxy, R 2 is hydrogen and R 5 is Cl-Cr 6 -alkyl, optionally substituted by Cl-C 4 -alkoxy or Cl-C 4 -alkylthio;

C

2 -C,-alkenyl, optionally substituted by oxo;

C.-C

6 -allenyl; C.-C.-alkynyl, in particular 2-butynyl;

:C

3

-CC

6 -cycloalkyl; C,,-0 6 -cycloalkenyl;

(C

3

-C

6 -cycloalkyl)-(C 1

-C

2 -alkyl), in particular cyclopropylmethyl, optionally substituted by Cl-C 4 -alkyl;

(C

3

-C

6 -cycloalkenyl)-(C'.'C 2 -alkyl), in particular cyclohexenyl methyl; Cl-C 6 -alkylcarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, benzyloxy, phenoxy, C 1

-C

4 -alkoxy, C 1

-C

4 -alkylamino, C :C 4 -alkenylamino, di(Cl-C 4 -alkyl)amino, 1-pyrrolidinyl, piperidino, morpholino, 4-methylpiperazin-1 -yI or Cl-C 4 -alkylthio; V C 2

-C

6 -alkenylcarbonyl; C,-0 6 -alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, C 1

-C

4 -alkoxy, C,-C 4 -alkylamino, dl(0 1

-C

4 -alkyl)amino or 0 1 -0 4 -alkylthio;

C

2

-C

6 -alkenyloxycarbonyl, in particular vinyloxycarbonyl, allyloxycarbonyl, isopropenyloxycarbonyl, butenyloxycarbonyl or pentenyloxycarbonyl; C27C 6 ,-alkynyloxycarbonyl, in particular propynyloxycarbonyl or butynyloxycarbonyl; Cl -C,,-alkylthiocarbonyl; 0 2

-C

6 -@lkenylthiocarbonyl, in particular allylthiocarbonyl; Cj,-C 6 -alkylamino- and di (C 1

-C

6 -alkyl)aminocarbonyl; pyrrolidin-1-yl, morpholino-, piperidino-, piperazinyl-, or 4-methylpiperazin- 1 -ylcarbonyl;

C

2 -C,-al ke nyl amino- and di(QgC- 6 -alkenyl)aminocarbonyl;

C

1

-C

4 -alkylsulfonyl; *4*25 Cl: C 4 -alkenyisulfonyl; or aryl which is substituted by up to two radicals R 6 which are independent of one another, in particular phenyl, arylcarbonyl, in particular benzoyl, (arylthio)carbonyl, aryloxycarbonyl, arylaminocarbonyl, (arylamino)thiocarbonyl, arylalkylaminocarbonyl, arylsulfonyl, arylalkyl, in particular benzyl, phe~ylethyl, arylalkenyl, arylalkylcarbonyl, arylalkoxycarbonyl or aryl(alkylthio)carbonyl, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms and R 6 being as defined above, or 1- or 2-naphthylmethyl, 3- or 4-picolyl, 2- or 3-furylmethyl, 2- or 3-thienylmethyl, 2- or 3-pyrrolylmethyl, 3- or 4-pyridylcarbonyl, 2- or 3-furylcarbonyl, 2- or 3-thienylcarbonyl, 2- or 3-thienylacetyl, 3- or 4-picolyloxycarbonyl, 2- or 3-furylmethyloxycarbonyl, or 2- or 3-thienylmethyloxycarbonyl, each of which is substituted by up to two radicals R 6 which are independent of one another, and

R

3 and R' are identical or different and independently of :1.15 one another are hydrogen,

C,-C

4 -alkyl, optionally substituted by hydroxyl, mercapto, C,-C 4 -alkoxy, C,-C 4 -alkylthio,

C,-C

4 -alkylsulfonyl, C,-C 4 -alkylsulfinyl, carboxyl or carbamoyl;

C

2

-C

6 -alkenyl, aryl, benzyl, thienyl or thienylmethyl, each of which is substituted by up to two radicals R 6 which are independent of one another, R 6 being as defined above,

R

3 and R 4 can also be part of a saturated or unsaturated carbo- or heterocyclic ring which has 3 to 6 carbon atoms and can 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: n is zero or one, the individual substituents R' independently of one another are fluorine, chlorine, bromine, C,-C 2 -alkyl, Cl-C 2 -alkoxy, C 2

-C

4 -acyl or cyano, R 2 is hydrogen and R' is :0.150 2 -C,-alkenyl, p. C 3 -C,-alkynyl, in particular 2-butynyl;

(C

3

-C

6 -CYCloalkyl)-(Cl-C 2 -alkyl), in particular cyclopropylmethyl, optionally substituted by C 1

-C

4 -alkyl;

(C

3

-C

6 -cycloalkenyl)-(Cl-C 2 -alkyl), in particular cyclohexenylmethyl; 0:6 C 2 -0 6 -alkylcarbonyl, 2 -C,,alkenylcarbonyl; Cl,-C 6 -alkyloxycarbonyl; qW C 2

-C

6 -alkenyloxycarbonyl, in particular vinyloxycarbonyl, allyloxycarbonyl, isopropenyloxycarbonyl, butenyloxycarbonyl or pentenyloxycarbonyl;

C

2 -0 6 -alkynyloxycarbonyf, in particular propynyloxycarbonyl or butynyloxycarbonyl;

C

2

-C

6 -alkenylthiocarbonyl, in particular allylthiocarbonyl; Cl-0 4 -alkylsulfonyl;

C

1

-C

4 -alkenylsulfonyl; or arylalkyl, in particular benzyl or arylalkenyl, which is substituted by up to two radicals R 6 which are independent of one another, it being possible for the alkyl 4CI 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 0:009:of which is substituted by up to two radicals R 6 which are independent of one another, .where R 6 is fluorine, chlorine, bromine, cyano, C 1

-C

2 -alkyl or Cl-0 2 -alkoxy, and R 3 and R 4 are identical or different and independently of one another are 1W hydrogen,

C,-C

4 -alkyl, optionally substituted by hydroxyl, mercapto, C,-C 4 -alkoxy, Cl-C 2 -alkylthio, and X is oxygen or sulfur.

The alkyl groups in the above definitions can be straight-chain or branched. Unless otherwise defined, 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.

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, 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.

The alkynyl groups mentioned in the above definitions can be straight-chain or branched and contain 1 to 3 triple bonds. Unless otherwise defined, they contain preferably 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 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 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, acety!, chloroacetyl, trifluoroacetyl, hydroxyacetyl, propionyl, butyryl, isobutyryl, pivaloyl, 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.

Suitable hetero atoms in the abovementioned heterocyclic rings or heteroaryl groups are, in particular, oxygen, sulfur and nitrogen, where, in the case of a nitrogencontaining ring which is saturated in this position, a structure N-Z is present in which Z is H or R 5 with the 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 the above definitions are, for example, heteroaromatic radicals such as 2- or 3-thienyl, 2- or 3-furyl, 3- or 4-pyridyl, pyrimidyl, indolyl, quinolyl or isoquinolyl.

Examples of the aralkyl groups mentioned in the above definitions are benzyl, phenylethyl, naphthylmethyl or styryl.

The abovementioned substituents R 1 to R 5 are preferably 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, arylalkoxyccrbonyl), 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 nave several asymmetric carbon 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 analogously to known methods, or they can be resolved later.

The compounds of 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, New York, 1957; Vol. 6, p.

491-495).

The present invention furthermore includes a process for the preparation of compounds of the formulae I and la as explained in 1) 4) above, which comprises A) for preparing compounds of the formula I where X is oxygen and the radicals R 1

R

2

R

3

R

4 and R 5 are as defined under 1) reacting a compound of the formula II

H

R

1 (I I) .20 N 0 S4R4 with the definitions mentioned under 1) 4) applying to R 1

R

3 and R 4 with a compound of the formula III R-Z (III) Swhere R has the meanings for R 5 and R 2 which have been mentioned above under 1) 4) with the exception of hydrogen, hydroxyl, C,-C 6 -alkoxy, aryloxy, Ci-C 8 -acyloxy, amino, C 1

-C

6 -alkylamino, di(C 1

-C

6 -alkyl)amino, arylamino and C,-C,-acylamino, and Z is a leaving group, or B) preparing compounds of the formula I where X is sulfur and R 1

R

2

R

3

R

4 and R 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 R 1

R

2

R

3

R

4 and R 5 with a sulfurizing reagent, or C) preparing compounds of the formula la where X and the radicals R' to R 5 are as defined under 1) by reacting a compound of the formula IV

H

N X

R

1 (Iv) n R3 R4

R

or *N X 1 R IVa) R3 R4

R

where the definitions mentioned under 1) 4) apply to R 3

R

4 and R 5 with a compound of the formula III

R

2 -Z (II) where the definitions described under 1) 4) for formula I and la apply to R 2 with the exception of hydrogen, hydroxyl, Ci-C 6 -alkoxy, aryloxy, Cl-C 6 -acyloxy, amino,

C,-C

6 -alkylamino, di(C,-C 6 -alkyl)amino, arylamino or C,-C-acylamino, and Z is a leaving group, or D) preparing compounds of the formula I where X is oxygen and the radicals R 1 to R are as defined under 1) 4) by cyclizing a compound of the formula V

R

2

NH

R-1 f CO-Y R3 R4

R

wi:ere R' to R 5 are as defined under 1) 4) and Y is hydroxyl, C,-C 4 -alkoxy, optionally ihalogenated C 1

-C

4 -acyloxy, chlorine, bromine or iodine, or 20 E) preparing compounds of the formula I where X is oxygen, R 4 and R 5 are hydrogen and the definitions mentioned under 1) 4) apply to R 1 to R 3 from the quinoxatinones of the formula XI 2 N X RR

XI

*i N where R' to R 3 are as defined under 1) by addition of hydrogen on the C=N bond, *or F) preparing compounds of the formula I where X is oxygen and R 1 to R 5 are as defined under 1) from compounds of the formula VI

R'

where R 2 and R 5 are as defined under 1) by reacting them with chloroform or bromoform and a carbonyl compound of the formula XIII

R

3

-CO-R

4 (XI1I) where R 3 and R 4 are as defined under 1) or with a-(trihalomethyl)alkanols of the formula XIV Hal3C-C(OH)-R 3

R

4

(XIV)

where Hal is Cl, Br or I, in which R 3 and R 4 are as defined under 1) 4), or G) preparing compounds of the formula I where X is oxygen and R 2

R

3

R

4 and R are as defined under 1) by reacting a compound of the formula I where X is oxygen and the definitions mentioned under 1) 4) apply to R 1

R

2

R

5 and to R 3 and

R

4 with the exception that at least one of the radicals R 3 or R 4 is hydrogen, with an :i30 alkylating reagent of the formula XV 0 R'-Z PXV where R' has the meanings mentioned above for R 3 and R 4 with the exception of hydrogen and Z is a leaving group, or H) preparing compounds of the formula I where X is oxygen, R 2 R 3 and R 4 are as defined under 1) 4) and R 5 is C,-0 8 -alkyl, optionally substituted by fluorine, Ohlorine, bromine, iodine, hydroxyl, C 1 -0 6 -acyloxy, benzoyloxy, phenoxy, C,-C.-alkoxy, 01-06- alkylamino, di(0 1

-C

6 -alkyl)amino, C 1 -0 6 -alkylthio, cyano, carboxyl, carbamoyl,

C

3 -C,-alkenyl, optionally substituted by fluorine, chlorine 'romine, iodine, hydroxyl, 0 1

-C

6 -acyloxy, benzoyloxy, pherioxy, C 1 -Cr,-alkoxy, 0 1 -Cr 6 -alkylamino, di -C.-alkyl) amino, Cl,-C 6 -alkylthio, cyano, carboxyl or carbamoyl, C 3

-C

8 -alkyrtyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, 0 1

-C

6 -acyloxy, benzoyloxy, phenoxy, 0 1

-C

6 -alkoxy, C 1

-C

6 -alkylamino, di(C 1

-C

6 -alkyl)amino, C 1

-C

6 -alkylthio, cyano, carboxyl or carbamoyl, C 4

-C

8 -cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, 0 1

-C

6 -acyloxy, benzoyloxy, phenoxy, 0 1 -C.-alkoxy,

C

1 -0 6 -alkylamino, di (C,-C.-alkyl) amino, 0 1

-C

6 -alkylthio, cyano, carboxyl or carbamoyl, C.-C.-cycloalkenyl, optionally substituted by fluorine, chlorine, brCr'nine, iodine, hydroxyl, C 1 -C.-acyloxy, benzoyloxy, phenoxy, Cl-0 6 ,-alkoxy, C 1

-C

6 -alkylamino, 0 1 -0 6 -dialkylamino, Cl-C.-alkylthio, cyano, carboxyl or carbamoyl, (C,-C.-alkoxy)-

(C

1

-C

6 -alkyl), di (Cl -0 6 '.alkylamino)- (Cl -C 6 alkyl) or (C 3

-C

6 -cycloalkyl) alkyl, (C 6

-C

8 .zrycloalkenyl)alkyl, or arylalkyl, naphthylalkyl or heteroarllky.', each of which is substituted by up to five radicals R 6 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 R 5 is hydrogen and X is oxygen and the definitions mentioned under 1) 4) apply to R 1 R 2 ,R 3 and with a carbonyl compound of the formula XVI, MW R"C(=O-R"'(XVI) where R" and are identical or different and independently of one another are hydrogen, C 1

-C

7 -alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, CI-Cr-acyloxy, benzoyloxy, phenoxy, 0 1 -C.-alkoxy, C,-C 6 -akylamino, di -Cr-alkyl) amino, Cl~-C 6 -alkylthio, cyano, carboxyl or carbamoyl, C 3

-C

7 -alkenyl, optionally substituted by fluvine, chlorine, bromine, iodine, hydroxyl, C 1

-C

6 -acyloxy, benzoyloxy, phenoxy, C> C 6 -alkylamino, di (0 1 -C.-alkyl)amino,

C

1 -0 6 -alkylthio, cyano, carboxyl or carbamoyl, 0 3 -0 7 -alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C 1

-C

6 -acyloxy, benzoyloxy, phenoxy, 0 1

-C

6 -alkoxy, C 1

-C

6 -alkylamino, di(C 1

-C

6 -alkyl)amino, Cl-C 6 -alkylthio, cyano, carboxyl or carbamoyl, C 4 -(;,-cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, Cl-C, 6 -acyloxy, benzoyloxy, phenoxy, C 1

-C

6 -alkoxy, C 1

-C

6 -alkylamino, di(Cl-0 6 -alkyl)amino, C 1 -C.-alkylthio, cyano, carboxyl or carbamoyl, C 8 -cycloalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, Cl-0 6 -acyloxy, benzoyloxy, phenoxy, C 1

-C

6 ,-alko~xy, C 1

-C

6 -alkylamino, di (C,-C 6 alkyl)amino,

C

1

-C

6 -alkylthio, cyano, carboxyl or carbamoyl, (C1 -C 6 -alkoxy)-(C 1

-C

5 -alkyl), [di (Cl -C.-al kyl) amino] -(Cl -C.-alkyl) or (C 4

-C

6 -cycloalkyl)alkyl. (C 6 -cycloalkenyl)alky,, or arylalkyl, naphthylalkyl or heteroarylalkyl, each of which is substituted by up to five radicals R 6 which are independent of one ancther, it being possible for the alkyl radical to contain in each case 0 to 2 carbon atoms, and where R" and 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 R 1

R

2

R

3 and R' are as deN,-,d under 1) 4) and R 5 is Cl-C.-alkyloxycarbonyl, 0 1 -C.-alkylthiocarbonyl,

C

2 -C,-alkenyloxycarbonyl, C 2 -%C,-alkenylthiocarbonyl, C 2 -C.-alkynyloxycarbonyl,

C

1

-C

6 -alkylaminocarbonyl, C,-C 6 -alkenylaminocarbonyl, di (C 1

-C

6 -alkyl)aminocarbonyl, pyrrolidin-1 -yl, morpholino., piperidino-, piperazinyl-, 4-methylpiperazin-1 -ylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, O.:bo hydroxyl, C 1

-C

6 -acyloXY, benzoyloxy, benzyloxy, phenoxy, C,-C,-alkoxy, 34 Cl-C 6 -alkylamino, di(Cl-C 6 -alkyl)amino, Ci -C 6 -alkylthio, Cl-C 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyi or carbamoyl; or aryloxycarbonyl, arylthio(carbonyl), arylaminocarbonyl, heteroaryloxycarbonyl, heteroarylthiocarbonyl, heteroarylaminocarbonyl, arylalkyloxycarbonyl, (arylalkylthio)carbonyl, arylalkylaminocarbonyl, heteroarylalkyloxycarbonyl, (heteroarylalkylthio)carbonyl or heteroarylalkylaminocarbonyl, 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 3 carbon atoms, by reacting a compound of the formula XVII R 3 XVI N 4

U

where the definitions mentioned under 1) 4) apply to RI, R2, R3 ancu -4 n isO0, 1, 2 or 3, X is oxygen and U is a leaving group, with a compound of the formula

XVIII

Nu-H (XVIII) 1 5 where Nu is CI-Cs-alkoxy, C 2 -Cs-alkenyloxy, C 2 -Ca-alkynyloxy, C 1

-C

8 -alkylthio,

C

2 -CB-alkenylthio, Oi-0 8 -alkylamino- and di(Cl-0 8 -alkyl)amino, and C 2 -0 8 alkenylamino- optionally substituted by fluorine, chlorine, bromine, hydroxyl, Ci-

C

4 -alkoxy, Ci -C 4 -alkylamino, di(C 1

-C

4 -alkyl)amino, Ci -C 4 -alkylthio, pyrrolidin-1 yI, morpholino-, piperidino-, piperazinyl- or 4-m ethyl pipe razi n- 1 -ylcarbo nyi, optionally substituted by Ci-C 4 -alkyl, C 2

-C

6 -alkenyl, Ci-C4-acyl, oxo, thioxo, carboxyl or phenyl, or aryloxy, arylthio, arylamino, arylalkyloxy, arylalkylthio, arylalkylamino, W heteroaryloxy, heteroarylthio, heteroarylamino, heteroarylalkyloxy, heteroarylalkylthio or heteroarylalkylamino, each of which is substituted by up to five radicals R 6

(R

6 is as 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: The substituent Z in formula III is a suitable leaving 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 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-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 of an alkali metal carbonate, alkali metal hydrogen carbonate, alkaline earth metal carbonate or alkaline earth metal hydrogen S carbonate such as soJium carbonate, calcium carbonate or sodium bicarbonate, of an alkali metal hydroxide or alkaline earth metal 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 lithiumdiisopropylamine, 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 for scavenging the acid which is liberated during the reaction, may be expedient.

36 SIn 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 0

C,

preferably at room temperature.

To carry out this reaction, any nucleophilic substituents such as, for example, hydroxyl, mercapto or amino groups, 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 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 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 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 tin sulfides or silyl sulfides which have been mentioned are used, it is advisable to carry out the 20 sulfurization reaction in the presence of a Lewis acid, such as boron trichloride.

6

S

In the presence of other carbonyl groups in a compound of the formula I, for example in a compound where X is oxygen and one or more radicals R 1 to R 6 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 the protective groups results in the desired compound.

S 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 :O aliphatic or aromatic sulfonate, or optionally halogenated acyloxy.

The reaction conditions for this reaction correspond to those of method A.

The cyclization described under D) is effected in a suitable solvent such as methanol, ethanol, N,N-dimethylformamide or N-methylpyrrolidone, in the presence of a 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 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 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, hydrochloric acid or phosphoric acid. The reaction is preferably carried out at temperatures between 20 and 1200C, particularly preferably at room temperature.

The compounds of the formula V, where R 1 to R 5 and Y are as defined under 1) can be obtained from compounds of the formula VI

I

NH

**R R 1N n VI

NH

I

525

R

9* where R 1

R

2 and R 5 are as defined under 1) by alkylation with a compound of the formula VII

CO-Y

R

3 VI I z

R

4 where R 3

R

4 and Y are as defined under 1) 5) and Z is as defined under 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 R 1

R

3 to R 5 and Y are as defined under 1) and R 2 is hydrogen can also be prepared from compounds of the formula VIII

NO

Rn 0R-Y (V II) N A-R3 R4

R

where R 3 to R 5 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 of the formula I takes place S 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 Organic Chemistryl (Houben-Weyl), E. Miller (Editor); G. Thieme Verlag, Stuttgart, 1957; Vol. XI/1, p. 360-490), for example using tin(ll) chloride in glacial acetic acid, TiCI, in hydrochloric acid, or by catalytic S. hydrogenation, the choice of reagent being determined by the chemical stability of the various substituents R 1 and R 3 to R 5 if, for example, one of the radicals is alkenyl, the first method will be selected to obtain the double bond.

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 literature.

N-ortho-nitrophenylamino acid derivatives of the formula VIII, where and R 3 to R are as defined under 1) 4) and Y is OR 7 where R 7 is hydrogen, C,-C 6 -alkyl, optionally in each case for example halogen-substituted phenyl, benzyl or 9-fluorenylmethyl, can be obtained for example by amination of ortho-halonitro aromatic substances of the formula IX

NO

2 R n -I

IX

W

where R' is as defined under 1) 4) and W is fluorine, chlorine, bromine or iodine, with amino acids or their esters of the formula X

COOR

7 A7o o R

X

HN R4 where R 3

R

4

R

5 and R 7 are as defined under 1) The reaction can be carried out in the presence of an inorganic or organic auxiliary base such as, for example, sodium carbonate, potassium carbonate, sodium hydroxide or triethylamine. It is S advantageous to use an inert solvent at temperatures between 0 and 1500C, preferably at reflux temperature. Suitable solvents are open-chain 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, N-methyl-2-pyrrolidone or 1,3-dimethyl-tetrahydro-2(1H)-pyrimidinone.

:Goo 0 SThe 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 derivatives of the formula VIII where Y is hydroxyl, C,-C 4 -alkoxy, optionally halogenated

C,-C

4 -acyloxy, chlorine, bromine or iodine.

Ortho-halonitroaromatic compounds of the formula IX and amino acids of the formula X are known from the literature 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 example diphenylsilane) in the presence of a hydrogeration 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 cyanoborohydride, or using metals, or metal salts, and acid such as, for example, zinc/glacial acetic acid or SnCI,/HCI. 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 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 1000C, preferably at room temperature.

If a chiral hydrogenation catalyst, for example rhodium(l)]/(+) 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)-borohydride, are used in the above-described reaction, the individual enantiomers can be prepared selectively.

If, in compounds of the formula XI, substituents are present which can be :b0 hydrogenated or reduced under the above-described conditions, for example oxo, it is necessary to use an intermediate of the formula 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 protective group, which can then be removed after the above-described reaction.

Quinoxalinones of the formula XI where R 1 to R 3 are as defined under 1) 4) can be obtained by known processes by condensing a phenylenediamine of the formula VI, where R' and R 2 are as defined under 1) 4) and R 5 is hydrogen, with an alphaketocarboxylic acid of the formula XII

R

3 -CO-COOH (XII) where R 3 is as defined under 1) 4).

The reaction is expediently carried out in an inert solvent in a temperature range of between 0 and 1500C; 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-dimethylformamide 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 hydrocarbons, 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 or alkaline earth metal hydroxide, for example sodium hydroxide or barium hydroxide. The presence of a phase transfer catalyst such as, for example, benzyltriethylammonium chloride or tetrabutylammonium bromide, is advantageous.

The reaction is usually carried out at temperatures between 0 and 50°C, preferably at .:so0 room temperature.

W 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 with a customary protective group which can then be removed after the above-described reaction.

In the reaction described above under Z in formula XV is a suitable leaving group such as, for example, chlorine, bromine or iodine, a suitable sulfuric acid 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) is preferably effected by catalytic hydrogenation (using hydrogen) in the presence of a hydrogenation catalyst, for example palladiumon-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 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 example dichloromethane or dichloroethane, at temperatures between -20 and 1000C, 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 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 S 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 :30 avoided or to be provided with a customary protective group.

0 The reaction described under 1) is expediently carried out in an inert solvent. Examples of suitable solvents are aromatic hydrocarbons such as toluene or xylene, lower alcohols such as methanoi, 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 and 1600C, preferably at room temperature.

To carry out this reaction, any nucleophilic substituents in compounds XVII and XVIII which do not participate in the reaction, such as, for example, hydroxyl, mercapto or 20 amino groups, are to be derivatized in a suitable manner or to be provided with 0* customary protective groups such as, for example, acetyl or benzyl, which can then be eliminated.

The compounds XVII which are required for the abovementioned reaction and in which the definitions described under 1) 4) apply to R 1

R

2

R

3 and R 4 n is 0, 1, 2 or 3, X is oxygen and U is a suitable leaving group, halogen such as, for example, chlorine, bromine, iodine, a halogenated aliphatic or aromatic alcoholate such as, for example, *o 2,2,2-trichloroethoxy, chlorophenoxy, or a heterocycle which is linked via nitrogen such as, for example, imidazolyl, triazolyl or benzotriazolyl, are prepared by reacting a :ba compound of the formula I where R 5 is hydrogen and X is oxygen, and the definitions I4 I I 44 Sdescribed under 1) 4) apply to R 1

R

2

R

3 and R 4 with a suitable carbonic acid derivative, for example phosgene, diphosgene, triphosgene, trichloroethyl chloroformate or carbonyldiimidazole, or with a suitable halo carbonyl hai°de, 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 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 base such as triethylamine or pyridine, may be useful.

The reaction is usually carried out at temperatures between -30 and 160 0 C, preferably at room temperature.

The present invention furthermore relates to the compounds as described under 1) to 4) as pharmaceuticals, preferably for treating viral diseases, in particular diseases caused by HIV.

The invention furthermore relates to pharmaceuticals comprising at least one compound according to the invention, and to the use of the abovementioned compounds for the preparation of 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 compounds of the S abovementioned formula I or IA in which

C

IW n is zero, one, twc" three or four, the individual substituents R' independently of one another are fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, hydroxyl, Cl-C.-alkyl, C.-C.-cycloalkyl, C 1

-C

6 -al koxy, (C 1

-C

6 -alkoxy)-(0 1

-C

4 -alkoxy), Cl,-C 6 -alky!thio, C 1

-C

6 -alkylsulfinyl, C 1

-C

6 -Rlkylsulfonyl, nitro, amino, azido, Cl-C, 6 -alkylamino, di (Cl -C,-alkyl) amino, piperidino, morpholino, 1 -pyrrolidinyl, 4-methylpiperazinyl, thiomorpholino, imidazolyl, triazolyl, tetrazolyl, C 1 -C,,-acyl, C, -C 6 -acyloxy, C 1

-C

6 -acylamino, cyano, carbamoyl, carboxyl, (C C,-akyl)oxycarbonyl, hydroxysulfonyi, sulfamoyl or a phenyl, phenoxy, phenoxycarbonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy, anilinosulfonyl, phenylsulfonylamino, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical which is substituted by up to five 6 radicals R 6 which are independent of one another, sees where R 6 can be fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, azido, C, -C 6 -alkyl, C 3 .CS-cycloalkyl, C,-C, 6 -alkcoxy, Cl-C6-alkylthio,

SW-C

6 -alkylsulfinyl, C,-C, 6 -alkylsulfonyl, Cl-C 6 -alkylamino, di(Cl-C 6 -alkyl)amino, (Cl-C 6 -alkyl)oxycarbonyl, phenyl, phenoxy, 3- or 4-pyridyl, 46

WR

2 and R 5 are identical or different and independently of one another are hydrogen, hydroxyl, Cl-C 6 -alkoxy, aryloxy, C 1

-C

6 -acyloxy, cyano, amino, 0, -C 6 -alkylamino, di (Cl -C.-alkyl) amino, arylamino, C,-C, 6 -acylamino, Cl-C.-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, 0 1

-C

6 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C,-C.-alkoxy, Cl-0 6 -alkylamino, di (0 1 -C6-alkyl) amino, Cl-C.-alkylthio, Cl-C.-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl;

C

2 -C,-alkenyl, optionally substituted by iluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cl-0 6 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C,-C.-alkoxy, 0 1 -0 6 -alkylamino, di (0l -0 6 ,-alky'i) amino, Cl-C 6 -alkylthio, Cl-C 6 -alkylsulfonyl, phenylsufonyl, oxo, thioxo, carboxyl and carbamoyl;

C

3 -C.-allenyl, optionally substituted by fluorine, chlorine or hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; 0 3 -0 8 -alkynyl, optionally substituted by *6 fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C~-~ayloxy, benzoyloxy, benzyloxy, phenoxy, C,-C.-alkoxy, ,-C-alkylamino, S di(Q 1

-C

6 -alkyI) amino, 0 1 -0 6 -alkylthio, Cl-C 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C-C8aCYCloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, 0 C,-C 6 -acyloxy, berizoyloxy, benzyloxy, phenoxy, Cl-C.-alkoxy, C 1

-C

6 -alkylamino, di (0 1

-C

6 -alkyl)amino, C,-C 6 -alkylthio, C,-C 6 -alkylsu'llonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; 0 3 -C,-cycloalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cl-C 6 -acyloxy, benzoyloxy, benzyloxKy, phenoxy, C,-C.-alkoxy, C 1 -0 8 -alkylamino, di (0 1

-C

6 -alkyl) amino, C,-C 6 -alkylthio, 0 1 ,-C.7alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl;

(C

3

-C

8 -cycloalkyl)-(C 1

-C

4 -alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cl -C 6 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1

-C

6 -alkoxy, C, -C 6 -alkylamino, di(Cl-C 6 -alkyl)amino, Cl-C6-alkylthio, C 1

-C

6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; 8 -cycloalkenyl)-(C 1

-C

4 -alky), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cl-C 6 -aCyloxy, benzoyloxy, benzyloxy, phenoxy, C 1

-C

6 -alkoxy, C 1

-C

6 -alkylamino, di(Cl-C 6 .alkyl)amino, C,-C.-alkylthio, Cl-C 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; Cl~-Cr 6 -alkylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C, -C 6 -acyloxy, benzoyloxy, benzyloxy, phenoxy, 0 1

-C,

6 -alkoxy, Cl-C.-alkyl amino, 48 di 6 -alkyl) amino, C 1

-C

6 alkylthio, C,-C, 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl;

C

2 -0 8 -alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl;

(C

3 -CS-cycloalkyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Cl-C 4 -al koxy, oxo, phenyl; (C.-C.-cycloalkenyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, 0 1

-C

4 -al kox(y, oxo, phenyl;

(C

3

-C

8 -cycloalkyl)- (0 1

-C

3 -alkyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, C 1 -0 4 -alkoxy, oxo, phenyl; (0 5 -0 6 -CYCloalkenyl)-(C 1

-C

3 -alkyl)carbonyl, optionally substituted by fluorine, ::*chlorine or hydroxyl, C 1

-C

4 -alkoxy, oxo, phenyl;

C

1 -C.-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, Cl,-C 4 -alkoxy, C 1

-C

4 -alkylamino, di (C 1

-C

4 -alkyl)amino, Cl-C 4 -alkylthio; C.-C.-alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl,

C

1 -0' 4 -alkoxy, oxo. phenyl; 2 5 C 2 -C.-alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl,

C

1

-C

4 -alkoxy, oxc', phenyl; C,-0 8 -alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl,

C

1

-C

4 -alkoxy, oxo, phenyl; 49

C

2 -0 8 -alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-0 4 -alkoxv, oxo, phenyl;

C

1

-C

8 ,-alkylamino- and di(C 1 -C.-alkyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; pyrrolidin-1 -yl, morpholino-, piperidino-, piperazinyl-, or 4-methylpiperazin- 1 -ylcarbonyl, in each case optionally substituted by C 1

-C

4 -alkyl, C 2

-C

6 -alkenyl, Cl-C 4 -acyl, oxo, thioxo, carboxyl, or phenyl;

C

2 -0 8 -alkenylamino- and di (CCC 6 -alkenyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl;

C

1

-C

6 -alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, 01-04alkoxy, oxo, phenyl;

QC

6 -alkenylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, C1-C4alkoxy, oxo, phenyl; or aryl, arylcarbonyl, aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio)thiocarbonyl, aryloxycarbonyl, arylaminocarbonyl, (arylamino)thiocarbonyl, .4 4 arylalkylaminocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl or aryl (alkylthio)carbonyl, each of which is substituted by up to five radicals R 6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to carbon atoms, and R 6 being as defined above, or heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or heteroarylalkenylcarbonyl, heteroaryloxycarbonyl, (heteroarylthio)carbonyl, heteroarylaminocarbonyl, heteroarylalkyloxycarbonyl, low heteroaryl(alkylthio)carbonyl or heteroarylalkylaminocarbonyl, each of which is substituted by up to three radicals R 6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms, R 3 and R 4 are identical or different and, independently of one another, are hydrogen, Cl-C 8 ,-alkyl which is optionally substituted by fluorine, chlorine, hydroxcyl, amino, mercapto, C 1 -C,-acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1

-C

4 -alkoxy, C,-C.,-alkylamino, di (Cl-0 4 -alkyl)amino, C 1

-C

4 alkylthio, Cl-C 4 -alkylsulfonyl, C 1

-C

4 -alkylsulfinyl, arboxyl or carbamoyl; 0 2 -C.-alkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, 0 1 -0 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1

-C

4 -alkoxy, C 1

-C

4 alkylamino, di (Cl-C 4 -alkyl)amino, 0 1

-C

4 -alkylthio, C 1 -0 4 -alkylsulfony[, C 1

-C

4 alkylsulfinyl, carboxyl or carbamoyl; C.-C.-cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, :*mercapto, 0 1

-C

4 aCYloxy, benzoyloxy, benzyloxy, phenoxy, C 1

-C

4 -alkoxy, C 1

-C

4 alkylamino, di (C,-C 4 -alkyl)amino, C 1

-C

4 -alkylthio, 0 1

-C

4 -alkylsulfonyl, C,-C47 alkylsulfinyl, carboxyl or carbamoyl;

C

3 -0 8 -cycloalkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, C 1

-C

4 -acylox(y, benzoyloxy, benzylox(y, phenoxy, Cl-C 4 -alkoxy, 0 1

-C

4 -alkylamino, di(C 1 -0 4 -alkyl)amino, C 1

-C

4 -alkylthio, C 1

-C

4 -alkylsulfonyl, C,-C 4 alkylsulfinyl, carboxyl or carbamoyl; aryl, arylalkyl, heteroaryl or heteroarylalkyl, each of which is substituted by up to five radicals R 6 which are independent of one another, it being possible for the alkyl radical to contain 1 to 3 carbon atoms in each case, and Rr' being as defined above,

R

3 and R 4 or R 3 and R 5 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,-C 6 -alkyl, C 2

-C

6 -alkenyl, C 2

-C

6 -alkynyl, C,-C 6 -acyloxy, benzoyloxy, Cl-C 6 -alkoxy, oxo, thioxo, carboxyl, carbamoyl or phenyl, X is oxygen, sulfur, selenium or substituted nitrogen N-R 2 it being possible for R 2 to have the abovementioned meanings, for the preparation of pharmaceuticals for the treatment of viral diseases.

The compounds mentioned and elucidated above under are preferred for this use.

The pharmaceuticals according to the invention can be administered enterally (orally), parenterally (intravenously), 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 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 administered once or several S 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 to the invention is 1 1500 mg, preferably 50 500 mg.

The compounds according to the invention can also be administered as a combination with other antiviral agents such as, for example, nucleoside analogs, protease inhibitors or adsorption inhibitors, immunostimulants, interferons, interleukins and colony-stimulating factors (for example GM-CSF, G-CSF, M-CSF).

Activity tests Test of preparations against HIV in cell culture Description of method Medium: RMPI pH 6.8 Complete medium additionally contains 20% fetal calf serum and 40 IU/ml recombinant interleukin 2.

Cells: Lymphocytes which have been isolated from fresh donor blood by means of Ficoll" gradient centrifugation are cultured for 36 hours in complete medium with an addition of 2 pg/ml phytohemagglutinin (Wellcome) at 37 0 C under 5% of CO After 10% of DMSO has been added, the cells are frozen at a density of 5 106 and stored in liquid S nitrogen. For the test, the cells are defrosted, washed in RPMI medium and cultured for 3 4 days in the complete medium.

Mixture: The test preparations were dissolved in DMSO at a concentration of 16.7 mg/ml and diluted in complete medium to 1 mg/ml.

0.4 ml of medium was introduced into 24-multiwell dishes. 0.1 ml of the dissolved 53 O preparation was added to the upper row of the dish, and, by transferring 0.1 ml portions, a geometric dilution series was established. Controls without preparation always contained 0.4 ml of complete medium containing 0.5% of DMSO. Lymphocyte cultures with a cell density of 5 a 105 cells/ml were infected by adding 1/50 volume supernatant from HIV-infected lymphocyte cultures. The titer of these culture supernatants was determined by end-point titration as 1 5 a 106 infectious units/ml.

After 30 minutes' incubation at 370°C, the infected lymphocytes were removed by centrifugation and taken up in an equal volume of medium. From this cell suspension, 0.6 ml aliquots were transferred into all wells of the test plate. The mixtures were incubated for 3 days at 370C.

Evaluation: The infected cell cultures were examined under the microscope for the presence of giant cells, which indicate active virus multiplication in the culture. The lowest concentration of preparation where no giant cells were observed was determined as inhibitory concentration against HIV. As a control, the supernatants from the culture plates were tested for the presence of HIV antigen with the aid of an HIV antigen test following the manufacturer's instructions (Organon).

Results: The results from this test are shown in Table 1.

Compound of T-cell culture assay Example No. MIC (pg/ml) III 0,8 IV 0,8 VI-A 0,16 V..0, Dompound of T-cell culture assay Example No. MIC (Ug/ml) VI-B Vt-C 0,8 VIl 0,16 X 0,8 X~i 0,8 AllI 0,16 XIV 0,16 3-7 0,08 3-21 0,16 3-23 0,08 3-24 0,08 3-25 0,4 3-26 0,4 3-29 0,4 3-30 0,01 3-32 0,4 3-33 0,4 3-36 3-44 0,8 4 .6 00 0:06.

Compound of T-cell culture assay Example No. MIC (pg/mi) 3-48 <0,8B 3-49 0,8 3-52 0,8 3-53 0,8 3-57 0,8 3-62 3-64 0,8 3-66 0,08 3-67 0,8 3-73 0,4 3-75 0,8 3-76 0,08 3-80 0,4 3-81 0,08 3-87 0,8 3-88 0,8 XX 6-1 0,4 6-16 0,8 0 .*0 0:0 0000 Compound of T-cell culture assay Example No. MIC (ug/mI) 6-17 0,8 6-19 0,8 6-20 0,8 6-22 0,8 6-27 0,4 6 32 <0,08 6-33 0,8 6-34 0,4 6-35 0,08 6-36 0,8 6-39 0,4 6-41 6-50 0,01 XXIII 0,01 7-1 <0,16 7-2 0,01 7-.3 0,01 7-7 0,04 7-10 0,04 .xo

S.

A S

A.

S

S

A. 4

S

A.

S. S Compound of T-celi culture assay Example No. MIC (yg/ml) 7-11 <0,01 7-12<CO8 7-13 0,08 7-14 <0,08 7-16 0,4 7-21 0,01 7-22 0,01 7-23 0,01 10-4 0,4 10-5 0,8 10-9 <0,8s 10-10 0,08 10-13 0,08 10-14 0,8 10-17 0,8 10-18 0,8 10-20 0,8 10-21 0,8 10-27 0,8

S

I I I Compound of T-cell culture assay Example No. MIC (pg/ml) 10-28 0,8 11-1 0,8 11-2 0,8 11-3 0,8 11-4 0,8 11-11 0,01 Assay of the substances for HIV reverse transcriptase inhibition The activity of reverse transcriptase (RT) was determined with the aid of a scintillation proximity assay (SPA).

The reagent kit for the RT-SPA was obtained from Amersham/Buchler (Braunschweig).

The enzyme RT (from HIV cloned in E. coli) originated from HT-Biotechnology Ltd, Cambridge, UK.

Mixture The assay was carried out using the manufacturer's (Amersham) protocol manual, .;PG with the following modifications: bovine serum albumin was added to the assay buffer to give an end concentration of 0.5 mg/ml I I

I

59 the assay was carried out in Eppendorf reaction vessels, using 100 pl volume per batch the manufacturer's RT concentrate (5000 U/ml) was diluted in Tris-HCI buffer 20 mM; pH 7.2; 30% of glycerol, to an activity of 15 U per ml the incubation time for the mixtures was 60 minutes (37 C) after stopping the reaction and "developing" with the bead suspension, 130 pl of mixture were transferred to 4.5 ml of Tris-HCI buffer, 10 mM; pH 7.4; 0.15 M NaCI, and the tritium activity was measured by means of a a-counter.

Assay For a pre-assay for inhibitory activity, the substances were dissolved in DMSO (stock S solution c 1 mg/ml), and tested as a 101, 10'2, 10"3, etc., dilution in DMSO.

To determine ICs0 values, the inhibitor stock solutions were diluted further in Tris-HCI buffer, 50 mM, pH 8, and tested in suitable concentrations.

The concentration corresponding to a 50% enzyme inhibition was determined from a plot of RT activity versus log Cinh.

The test results are shown in Table a.

S

The test results are shown in Table la.

Table la 6 S S S. Compound of Reverse Transcriptase Assay Example No. ICSO (pg/mi) V VI-A 0,08 VI-C 0,8 ViI 0,1 XiII 0,04 XIV 0,16 3-23 0,1 1 3-24 0,1 1 3-25 0,1 1 3-29 0,1 1 3-30 0,025 3-32 approx. 0,1 3-36 0,1 -1I 3-49 approx. 1 3-57 approx. 1 3-75 0,1 1 3-76 0,018 3-81 approx. 1 a a a a a.

a. a.

a. Compound of Reverse Transcriptase Assay Example No. IC_, (pg/ri ii) 6-1 approx. 1 6-8 0,1 -1 6-9 approx. 1 6-16 approx. I 6-17 0,1 -1 6-27 approx. 1 6-35 0,1 1 6-50 0,01-0,1 XXIII 0,025 7-1 0,08 7-2 0,07 7-3 0,07 7-7 0,1 7-10 0,11 7-11 0,01 7-12 approx. 1 7-13 0,1 1 7-16 approx. 1 10-9 app rox. 1 9* C P

DC

S

*5 0

C*

SC..

I

Compound of Reverse Transcriptase Assay Example No. 1C-4 (Pg/mi) 10-10 approx. 1 10-13 approx. 1 10-17 approx. 1 10-18 0,1 1 10-20 0,1 1 10-21 0,1 1 10-27 0,1 1 10-28 0,1 1 11-11 0,1 -1 10-34 0,1 1 11-6 01 1 11-5 0,1 -1 11-7 approx. I 11-13 approx. 1 7-20 0,1 1 7-14 0,01 0,1 7-15 0,01 -0,1 7-17 0,01 0,1 7-18 0,01 011 t i I 0:0.0 F Compound of Reverse Transcriptase Assay Example No. IC50 (pg/mi) 7-19 0,01 -0,1 7-21 0,01 -0,1 7-22 0,01 0,1 7-23 0,01 0,1 3-34 0,1 1 3-35 0,1 1 3-37 0,1 1 3-7 0,08 3-127 0,01 0,1 3-128 0,01 0,1 3-129 0,01 0,1 7-24 0,01 7-25 0,01 7-28 0,01 0,1 7-27 0,1 1 7-28 0,01 7-29 0,01 -0,1 7-30 0,01 L7-31 0,01 1C.50 =0.08 pg/ml I I I I 64 The examples which follow and the content of the patent claims illustrate the present invention in greater detail.

Example I (3S)-6-Chloro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one A) (S)-N-(3-Chloro-6-nitrophenyl)alanine 2,4-Dichioronitrobenzene (21.0 g, 0.109 mol) and 23.0 g (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, 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 (magnesium sulfate), and the solvent was removed under reduced pressure.

14.7 g of a yellow solid of melting point 167-169 0 C remained (after crystallization from ethyl acetate).

'H NMR (270 MHz, d 6 -DMSO): 6 1.47 J 7 Hz, 3 4.57 (quintet, J 7 Hz, 1 6.77 (dd, J 9, 2 Hz, 1 7.11 J 2 Hz, 1 8.12 J 9 Hz, 2 H), 8.41 (br. d, J 7 Hz, 1 13.2 ppm 1 H).

MS: (M 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 m9thanol and hydrogenated with Raney nickel catalysis at room temperature, using 1 atm hydrogen. 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 vacuo. The residue was purified by silica gel chromatography using ethyl acetate/heptane 1:2 and 1:1 as the eluent. The yield was 6.0 g of a brownish solid of melting point 122-123 0 C (after recrystallization from isopropanol/heptane).

1 H NMR (60 MHz, d6-DMSO): 6 1.23 J 11 Hz, 3 3.81 (dq, J 11, 4 Hz, 1 6.27 1 6.3 6.9 3 10.3 ppm 1 H).

MS: (M 197 2 3 +77.30 (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 described under Example IA and IB. Melting point 123-124oC (after recrystallization from isopropanol/heptane) The NMR data agree with those of the compound described in Example IB.

[a] 0 2 3 -81.00 (c 1, MeL;Oi) 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 point 110 0 C (after recrystallization from isopropanol/heptane) The NMR data agree with those of the compound described in Example IB.

o** The following compounds of the formula I were synthesized analogously using the .25 corresponding haloaromatic compounds and amino acid derivatives: I u 66 SExample II (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.j g (0.025 mol) of were dissolved in 40 ml of anhydrous dimethyl sulfoxide (DMSO), and the stirred solution was heated to 800C 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 900C, the mixture was allowed to cool, and unreacted 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 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, which was further reacted without pu'ification.

20 B) (3S)-3-Benzyl-7-chloro-3,4-dihydroquinoxalin-2(1H)-one 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, 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 isopropanol, melting point 185".

I'

67 'H NMR (270 MHz, d 6 7DMSO): 6 2.9 (in, 2 4.08 (in, 1 6.09 1 6.7 (n 2 6.78 (in, 1 7.2 (in, 5 10.34 ppm (br. s, 1 H).

MS: (M 273, (M 92)+ 181.

The compounds in Table 2 were prepared as described in the above examples.

Table 2 R? 1n Nr. RnR3ISMRO.C 1 5-Cl OH 3 H Wax 2 6-Cl CAH H 120 3 6-Cl C 2

H

4 000H H 4 6-Cl -CH 2

CH

2

CO-

6S-Cl (CHI)CH H 6 6-Cl (CH 3 2

CHCH

2 H Oil 7 6-Cl C 2

H

5

(CH

3 )CH H Oil 8 6-Cl CHCH 2 H -T 156-157 I Nr. 1nR3R 5

M.P.OC

9 6-Cl CH 3

SCH

2

CH

2 H 97 6-Cl CH.,SCH 2 H 149 11 6-Cl CH 2 (OH) H 12 6-Cl CHCHCH, H 75 -77 13 7-Cl CH 3 H 142 14 7-Cl (CHI)CH H Oil 7-Cl CH 3

SC

2

H

4 H 98 16 8-Cl CH 3

H

17 6,7-C 2

CH

3

H

18 7-F CH 3 H 230 19 6-F CH3 H Wax 6-F CH 3 CAH 182 21 6-F C 6

H

5

CH

2

C

3

H

22 7-CF 3

CH

3 H 147 23 6-0H 3 0C 2

H

4 0 C 2 1- 5 H 107 24 6-Cl C 2

H

4 OH H 211 6-Cl CH 2 -S-Bn H 170 26 6-Cl CH 2 -S-i.-Pr H 190 27 6-Cl CH 2 O-t.-Bu H 128 28 6-Cl CAH H 115 69 O Bn benzyl i-Pr isopropyl t-Bu tert.-butyl 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 dissolved in 20 ml of dichloromethane. 10 ml of 2N aqueous sodium hydrogen carbonate solution were added, and 0.9 ml 5.7 mmol) of benzyl chloroformate was added with icecooling and vigorous stirring. The two-phase system was subsequently stirred for hours at room temperature. 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 silica gel chromatography with methyl tert.-butyl ether/heptane 1:1 as the eluent. This gave 1.65 g of a white, foam-like product.

20 'H NMR (270 MHz, d.-DMSO): 6 1.15 J 7 Hz, 3 4.85 J 7 Hz, 1 5.20 J 12 Hz, 1 5.27 J 12 Hz, 1 6.97 J 7 Hz, 1 H), 7.19 (dd, J 8.2 Hz, 1 7.3 7.45 5 7.67 J 2 Hz, 1 10.81 ppm (br. s, 1 H).

MS: (M 381 .25 Example IV I (3S)-4-N-(Benzyloxycarbonyl)-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 ml). A total of 5 ml (124.3 mmol) of fuming nitric acid were added dropwise in w 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 850C (subl.).

'H NMR (270 MHz, d 6 -DMSO): 6 1.22 J 8 Hz, 3H), 4.89 J 8 Hz, 1 5.24 J 12 Hz, 1 5.31 J 12 Hz, 1 7.35 7.5 5 7.69 1 8.00 1 11.11 ppm (br. s, 1 H).

MS: (M H) 376 Example V (3S)-B-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 dissolved 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 S catalyst was removed by filtration with suction, and the filtrate was concentrated in vacuo. The product was purified by silica gel chromatography using ethyl acetate/heptane 2:1 as eluent. The yield was 0.68 g of brownish solid of melting point 152-1540C.

1 H NMR (270 MHz, d -DMSO): 6 1.11 J 8 Hz, 3 4.79 J 8 Hz, 1 5.15 J 12 Hz, 1 5.24 J 12 Hz, 1 5.38 (br. s, 2 6.42 (s, 1 7.3-7.4 6 10.59 ppm (br. s, 1 H).

MS: (M 346 71 SExample

VI

A) (3S)-6-Chloro-3-methyl-4-N-(3-methyl-2-buten-1-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-1-yl bromide 0.92 ml, mmol) at 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 product was purified by silica gel chromatography using ethyl acetate/heptane 1:2 as eluent.

The yield was 0.97 g of brownish solid of melting point 117-1180C (after crystallization from methyl tert.-butyl ether/heptane).

'H NMR (270 MHz, d 6 -DMSO): 6 1.02 J 8 Hz, 3 1.74 6 3.69 (dd, J 14, 8 Hz, 1 3.85 3.9 2 5.19 1 6.65 6.8 3 H), S 10.47 ppm (br. s, 1 H).

MS: (M 265 [a]D 2 3 +168.00 (c 1, MeOH) B) (3R)-6-Chloro-3-methyl-4-N-(3-methyl-2-buten-1-yl)-3,4-dihydroquinoxalin- 2(1H)-one The compound was prepared by the method described in Example VIA, starting S from the compound of Example IC. Melting point 115-117 0 C (after recrystallization from isopropanol/diethyl ether) The NMR data agreed with those of the compound described in Example VIA.

[a]D23 -1720 (c 1, MeOH) SC) (3RS)-6-Chloro-3-methyl-4-N-(3-methyl-2-buten-1-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.

Example VII (3S)-6-Chloro-3-methyl-4-N-(2-buten-1 -yl)-3,4-dihydroquinoxalin-2(1H)-one The substance was prepared analogously to the compound described in Example VIA, but with 2-buten-1-yl bromide as the alkylating agent. Melting point 87-88 0

C

(after crystallization from diethyl ether/heptane) 'H NMR (270 MHz, d 6 -DMSO): 6 1.01 J 8 Hz, 3 1.70 (dd, J 8, 1 Hz, 3 3.63 (dd, J 16, 6 Hz, 1 3.85 4.0 2 5.47 1 5.75 1 H), 6.65 6.8 3 10.48 ppm (br. s, 1 H).

MS: (M H) 4 251 Example VIII 4-N-(lsopropenyloxycarbonyl)-3,3,7-trimethyl-3,4-di-hydroquinoxalin-2(1H)-one 3,3,7-Trimethyl-3,4-dihydroquinoxalin-2(1H)-one (0.4 g, 2.1 mmol) were dissolved in 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 of colorless crystals of melting point 1850C.

'H NMR (270 MHz, d,-DMSO): 6 1.5 6 1.9 3 2.25 3 4.7 .n, 2 6.7 6.9 2 7.15 J 8 Hz, 1 10.6 ppm (br. s, 1 H).

MS: 274 I t I I 73 Example IX (3S)-6-Chloro-4-N-(4-methoxyphenoxycarbonyl)-3-methyl-3,4-dibydroquinoxalin- 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 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 was complete (18 hours), the solvent was stripped off 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 of a white solid remained after concentration. Melting point 187-190°C (after recrystallization from isopropanol) 'H NMR (270 MHz, de-DMSO): 6 1.24 J 8 Hz, 3 3.77 3 4.94 (q, J 8 Hz, 1 6.97 (dd, J 8, 2 Hz, 1 7.03 J 8 Hz, 1 7.2 7.3 (m, 3 7.78 1 10.89 ppm (br. s, 1 H).

MS: (M 347 *o Example

X

(3S)-6-Chloro-4-N-(4-fluoroph noxycarbonyl)-3-methyl-3,4-dihydroquinoxalin- 2(1H)-one The compound was prepared analogously to the compound described in Example VIA, but 4-fluorophenyl chloroformate was used as acylating agent. Melting point 168-170°C (after crystallization from isopropanol) 'H NMR (270 MHz, d 6 -DMSO): 6 1.24 J 8 Hz, 3 4.94 J 8 Hz, 1 7.03 8 Hz, 1 7.2 7.5 5 7.83 J 2 Hz, 1 10.90 ppm (br. s, 1 H).

MS: (M H) 335 OP Example XI (3S) -6-Chloro-4-N- (4-chlorophenoxycarbonyl)-3-methy-3,4-dihydroquinoxalin- 2(1 H)-one The compound was prepared analogously to the compound described in Example VIA) but 4-chiorophenyl chloroformate was used as acylating agent. i\elting point 185-1880 C (after crystallization from isopropanol/diethyl ether) 'H NMR (270 MHz, d.-DMSO): 6 1.25 J 8 Hz, 3 4.94 J 8 Hz, 1 7.04 8 Hz, 1 7.25 (dd, J 8, 2 Hz, 1 7.35 7.6 (in, 4 7.80 (s, 1 10.91 ppm (br. s, 1 H).

MS: (M 351 Example XII (2-Bromoethylowcycarbonyl)-6-chloro-3-methyl-3,4-dihydroquinoxalin- 2(1 H) -one The compound was prepared analogously to the compound described in Example VIA, but 2-bromoethyl chloroformate was used for the acylation. Melting point 133-1360C (after crystallization from isopropanol) 2O* 1 H NMR (270 MHz, d.-DMSO): 6 1.16 J 8 Hz, 3 3.7 3.8 (in, 2 4.4 4.6 (in, 2 4.86 J 8 Hz), 6.99 8 Hz, 1 7.21 (dd, 8, 2 Hz, 1 7.74 J 2 Hz, 1 10.84. ppm (br. s, 1 H).

:MS: (M 348 Example XIII (3S)-6-Chloro-N-(isopropenyloxycarbonyl)-3-methyl-3,4-dihydroquinoxalin-2(1 H)-one The substance was prepared analogously to the compound described in Example VIA, but isopropenyl chloroformate was used for the acylation. Melting point 158-1590C I 4 I 'H NMR (270 MHz, CDC 3 6 1.33 J 8 Hz, 3 2.02 3 4.79 (s, 1 4.83 1 5.17 J 8 Hz, 1 6.86 J 8 Hz, I 7.12 (dd, J 8, 2 Hz, 1 7.74 (br. s, 1 9.28 ppm (br. s, 1 H).

M S: (M H) 281 Example XIV (3S)-6-Chloro-3-methyl-4-N-(vinyloxycarbonyl)-3,4-di- hydroquinoxalin-2(1 H)-one The suWjstance was prepared analogously to the compound described in Example VIA, but vinyl chioroformate was used for the acylation. Melting point 177-179 0

C

1 H NMOR (270 MHz, CDCI 3 6 1.33 J 8 Hz, 3 4.96 (dd, J =14, 2 Hz, 1 5.20 J 8 Hz, 1 6.83 J 8 Hz, 1 7.12 (dd, J 8, 2 Hz, 1 H), 7.2 7.3 (in, 2 7.71 (br. s, 1 9.42 ppmn (br. s, 1 H).

MS: (M 267 Example XV and Example XVI 6-Chloro-3,4-dihydroquinoxalin-2 (1 H) -one was reacted with 3-methyl-2-buten-1 -yl bromide analogously to the process described in Example VIA. It was possible to *265 isolate two products by silica gel chromatography.

6 -Chilor o-4-N (3-m ethyl-2-buten-1I -yl) -3,4-dihy dro- quinoxalin-2(1 H)-one Melting point 150-1 51 00 (after recrystallization from ethyl acetate) 1 H NMR (270OMHz, d 6 -DMSO): 6 1.72 6 3.67 2 3.80 J 7 Hz, 2 5.20 (in, 1 6.7 6.8 (in, 3 10.49 ppm (br. s, 1 H).

MS: (M 251 0 6-ChlIo ro--N- (3-methyl-2-buten- 1 -yl) (1 ,1 -d imethyl-2-propen-i -yI) S: 3,4-dihydroquinoxalin-2(1 H)-one Melting point 110-1120C (after crystallization from heptane) 'H NMR (270 MHz, d 6 -DMSO): 6 0.94 3 0.97 3 1.65 3 1.66 3 3.77 (dd, J 16, 7 Hz, 1 4.23 (dd, J 16, 7 Hz, 1 4.8 4.9 (m, 2 5.02 1 5.75 (dd, J 17, 11 Hz, 1 6.6 6.7 3 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: Table 3

R

2 N 0 Rn H

N

9* 77 Nr. RF R 2 R 3 M.P.oC 1 H CH 3

C

2

H

4

OCH

3 59 2 H CH- 3

C

4 1- 7 110 3 H CH 3 sC 6 H, 100 4 5-Cl H CH 3

C

6 1- 11 Oil 5-Cl H CH 3 sC 6 1 135 6 6-Cl H OH 3 ALAC 180 -182 7 6-Cl H CH-1 ALOC 124 -127 8 6-Cl H CH 3

SO

2

CH

3 184 9 6-Cl H OH 3 S0 2

C

6

H

5 253 6-Cl H CF- 3 SO2CrH4-4-CH 3 259-262 11 6-Cl H OH 3 S0 2

C

6

H

4 -4-CI 270 12 6-Cl H OH 3 S0 2

C

6

H

4 -4-N0 2 270 13 6-Cl H OH 3 S0 2 CH H 2 180 -182 .0* 0

S

S .6 78 Nr. RnR2R 3 14 6-Cl H CH 3 C H 2 00H 3 202 6-Cl H CH 3

CSNH-C

6

,H

4 -4-CN 216 16 6-Cl H C-3 COCH 2

CH(CH

3 2 Foam 17 6-Cl H CH-3 COCf 6

H

5 108-109 18 6-Cl H CHI COCI 138 19 6-Cl H CH 3

COCH

2

CH

2

CH=CH

2 Foam 6-Cl H CH 3

C

2

H

4 0CH 3 78 -79 21 6-Cl H CH 3

CH

2

C

6

H

5 155 -156 22 6-Cl H CH3 2-CO-C 4

H

3 0 105 -107 23 6-Cl H CH 3

COOCH

2

CH

3 149 -153 24 6-Cl H CH 3 COO(CHI)CH, 113 -116 6-Cl H CH 3

COO(CH

2

CH

3 80 -82 26 6-Cl H CH 3

COOCH

2

CH(CH

3 2 131 -132 a..

a a. a a a@ a a 79 Nr. R' "R-)M.P.oc 27 6-Cl H CH 3 C H 2 CH =CH 2 130 28 6-Cl H CH 3

COCH

2 CH =CHCH 3 155 29 6-Cl H CAH C 5

H

9 128 6-Cl H CAH IPOC 175 31 6-Cl H C 2

H

5 CHO 204 32 6-Cl H CAH ALOC 148 -150 33 6-CHaOC 2

H

4 O H C 2

H

5 IPOC 173 34 6-Cl H CAH IPOC 149-1 6-Cl H CAH ALOC 135 36 6-Cl H CH(CH 3 2

C

5

H

9 126 -128 37 6-Cl H CH(CHI) IPOC 144 -145 38 6-Cl H CH(CH 3 2

ALOC

39 6-Cl H jC 2

H

4 COOH C 5

H

9 S S S S S S S S S S Nr. RnR2R3R 5

M.P.OC

6-Cl H C 4 9

C

5 1- 9 41 6-Cl H CHAC 6

H

5

C

5

)H

9 134 42 6-Ct H CHACH. IPOC 165 43 6-Cl H C 2

H

4

SCH

3

C

5 1- 9 Oil 44 6-Cl H CAHSCH, IPOC 135 6-Cl H C 2

H

4

SOCH

3 IPOC Oil 46 6-Cl H CH 2 (OH) CsH 9 47 6-Cl H CHCH(CH,) 2

C

5 9 Oil 48 6-Cl H CH 2

CH(CH

3 2 ALOC 140 49 6-Cl H CH 2

CH(CH

3 2 IPOC 148 6,7-C 2 H CH 3

C

5 1- 9 51 8-Cl H CH 3

C

5 9 52 5-Cl H CH 3

C

5 9 150 decomp.

a..

S S 555 *S V *5 S *S S 5*S S S S 5I S 5 SI 55 81 Nr. RnR2R3R5M.P.oc 53 7-Cl H CH 3

C

5 1- 9 Oil 54 7-Cl H CH3 ALOC 129 7-Cl H CH 3 IPOC 166 56 7-Cl H CH(CH 3

C

5 1- 9 221 511 7-Cl H CH(CH 3 2 IPOC 151 58 7-Cl H CH(CHI) ALOC 142 59 7-Cl H CH 2

C

6

H

5

C

5 1-1 9 Oil 7-Cl H CH 2

ZC

6 HS IPOC 178 61 7-Cl H C 2

H

4

SCH

3

C

5 1- 9 98 62 7-Cl H C 2

H

4

SCH

3 IPOC 148 63 7-Cl H C 2

H

4

SCH

3 ALOC 116 64 7-F H CH 3

C

5 1- 9 7-F H CF13 ALOC 155 0* S *5* S. 0* :0.S55 82 Nr. fnR2 66 7-F H OH 3 IPOC 168 67 6-F H CH 3 CAH 153 68 6-F H CH 3 AO 2 69 6-F H OH 3 IPOG 175 7-CF 3 H OH 3

CSH

9 145 71 7-CF 3 H OH 3 IPOC 186 72 7-C 6

H

5 0 H CH 3

C

5

H

9 107 73 7-C 6

H

5 0 H CH 3 IPOC 172 74 6-Cl H C 2

H

4

SO

2

CH

3 IPOC 160 decomp.

6-Cl H CH 2

SCH

3 CAH 118 76 6-Cl H CH 2 SCH, IPOC 182 77 6-Cf H CHSOCH 3 IPOC 202 decomp.

78 6-Cl H _CH 2

SO

2 CH, IPOC 212 decomp.

Nr. R'nR 2 R 79 6-Cl H CH(CH,)CH 2

CH

3

C

5 1- 9 87 6-Cl H CH(CH,)CH 2

CH

3 ALOC 74 81 6-Cl H CH(CH 3

)CH

2

CH

3 IPOC 142 82 6-F H CH 3 COCH3 186 83 6-Cl H CH 3

COCH

2 0H 185 84 6-Cl H CH 3 2-COC 4 1- 3 S 112 6-Cl H CH 3 COCHACH. 86 6-Cl H CH 3

COCH

2 CI 168 87 6-Cl H CH 3

CO(CH

2 3

CH

3 Oil 88 6-Cl H CH CO(CH 2 2 C;H, 68 89 6-Cl H CH 3

COCH

2

CH

3 148 6-Cl H CH 3

COCH

3 232 91 6-Cl H C 2

H

4

OCOOC

2

H

5

COOC

2

H-

5 139-140

S

S S S* Nr. R' 92 6-Cl CH 2 C -=CH CH 3 H 152-154 93 6-Cl 2-CH 2

CH

4 N ICH 3 H 128-130 94 6-Cl CH 2 Ph CH 3 H 126-127 6-Cl CH5CH(CH3) 2

CH

3 H 70-72, 96 6-Cl CH 3

CH

3

C

5

H

9 Oil 97 6-Cf CH 3

CH

3 H 115 98 6-Cl COOC(CH 3 3

CH

3 H 82-83 99 7-Cl C 5 1- 9

CH

3

C

5 1- 9 Resin 100 7-Cl CsH 9

ICH

3 H 108 101 7-PhOSO 2

C

5 1- 9

CH

3

C

5 1- 9 Oil 102 7-PhOSO 2

C

5 1- 9

CH

3 H oil 103 CZH 4

OCH

3

CH

3

C

2

H-

4 0CH 3 Oil 104 6-Cl H CH 3 S0 2

C

4

H

3 S 264 ft Nr. R'n R 2 1R3 R 5 M.P.oc 105 6-Cl H -CH 2

CH

2 00H 2 210 106 6-Cl H CH 3

COCH

2

N(C

2

H

5 2 108 107 6-Cl H CH 3

COCH

2 N(CHa,) 2 166 108 6-Cl H CH 3

COCH

2

N(C

2

H

4 190 109 6-Cl H CH 3

COCH

2

N(CH

2 4 185 110 6-Cl H CH 3

COCH

2

N(CH

2 164 111 6-Cl H CH 3 COCH (4-methyl- 176 piperazin-1 -yl) 112 6-Cl H cH 3 CO-4-CH 4 N 214 113 6-Cl H CH 3

COCH-

2

NHCH

2

CH=CH

2 152 114 6-Cl H CH 3

COCH

2

C

4

H

3 S 155-156 115 6-Cl H CH.O-t.-Bu .C 5 1- 9 oil 116 6-Cl H CH.O-t.-Bu ALOC Oil a. a a Nr. R' 2R3R 5

MROC

0 117 6-Cl H CH 2 O-t.-Bu IPOC 154 118 6-Cl H CH 2 S-i.-Pr C 5 1- 9 Oil 119 6-Cl H CH 2 S-i.-Pr IPOC 158 120 6-Cl H CH 2 S-Bn C 5 1- 9 121 6-Cl H CH 2 -S-Bn IPOC Oil 122 6,7-C12 H OH 3

C

5

H

9 160 123 6,7-CI2 H OH 3

IPOC

124 6-Cl H C 4 1- 9 IPOC 158 125 6-Cl H C 4 1- 9 ALOC 100 126 6-Cl H CH 3

(C

4

H

3 S)-2-CH 2 C0 156 127 6-Cl H CH 2 SCH, COOCH(CH 3 2 157 128 6-CH 3 O H CH 2

SCH

3 IPOC 152 129 6-CH 3 O H CH 2

SCH

3

COOCH(CH

3 2 165 I I I I 0l Key: C 5

H

9 3-methyl-2-buten-1-yl

C

4

H

7 2-butenyl 1 3-methyl-1-butyl

CA,

1 2,2-dimethylcyciopropyl-1 -methyl sCHl 1 4-methyl-3-penten-2-yi CAH 2-propen-1 -yl

(CH

3 2 00HCO 3,3-dimethylacryl IPOC isopropenyloxycarbonyl ALAC allylaminocarbonyl ALOC allyloxycarbonyl

C

4

H

3 0 furanyl CAHS thienyl

C

5

H

4 N pyridyl Ph phenyl 9 .9 88 Example XVII 6,7-Dimethoxy-3-methyl-3,4-dihydroquinoxalin-2(1H)-one 4,5-Dimethoxy-1,2-dinitrobenzene (34.2 g, 0.15 mol) was hydrogenated in 500 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 in vacuo.

To remove the water completely, the mixture was taken up twice in methanol and reconcentrated. 4,5-Dimethoxy-1,2-phenylenediamine (24.0 which remained as a brown oil, was refluxed for 48 hours in 200 ml of ethanol together with 17.1 ml (0.1.1 mol) of methyl 2-chloropropionate, with an addition of 21.0 ml (0.15 mol) of triethylamine. 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.

The crude product was crystallized by stirring with diethyl ether (6.2 g, A analytically pure sample of melting point 151 °C was obtained by silica gel chromatography using ethyl acetate as the eluent.

'H NMR (60 MHz, de-DMSO): e 1.22 J 7 Hz, 3 3.63 3 3.67 (s, 1 3.6 3.7 1 5.62 (br. s, 1 6.40 1 6.45 1H), 9.90 ppm (br. s, 1 H).

MS: M' 222 B The following compounds of the formula I were synthesized in analogous manner and, if appropriate, derivatized further: *e e I t I I Table 4 N

X

R

Nr. R1nR3R 5 X M.P.OC 1 6,7-(0H 3 0) 2

OH

3 IPOC 0 133 2 6,7-(CH 3

O)

2

OH

3 IPOC S 3 6-OHS OH 3

%C

5

H

9 0 115 4 7-0 6

H

5 S OH 3 0 5

H

9 0 107 6-C 6 HsS OH 3 H 0 6 7-CAHS OH 3 H 0 7 6,7(0H 3 0) 2

OH

3 H 0 151 Key: C 5 Hg

IPOC

3-methyl-2-buten-1 -yI isopropenyloxycarbonyl

S

*SS.

Example XVIII (3RS)-6-Ohloro-4-N-(cyclopropyl)-3-methyl-3,4-dihydroquinoxalin-2(1 H)-one A) (2RS)-N- (4-Ohloro-2-cyclopropylaminophenyl)-(2-bromopropionarnide) 4-Ohloro-2-cyclopropylaminonitrobenzene (2.10 g, 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 in

I

Svacuo. To remove water completely, the mixture was taken up twice in methanol and reconcentrated. 4-Chloro-2-cyclopropylaminoaniline (1.80 which remained in the form of a brown oil, was dissolved in 50 ml of anhydrous 1,2-dimethoxyethane and cooled to -600C, with stirring. 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 -700C. The mixture was then allowed to warm to approx. -200C 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 suifate) and concentrated in vacuo. After crystallization with diethyl ether/pentane, 2.51 g of the desired product of melting point 1300C remained.

'H NMR (270 MHz, d 6 -DMSO): 6 0.4 0.5 2 0.7 0.8 2 1.75 (d, J 7 Hz, 3 2.39 1 4.72 J 7 Hz, 1 5.6 (br. s, 1 6.66 (dd, J 8, 2 Hz, 1 6.96 J 2 Hz, 1 7.21 J 8 Hz, 1 9.36 ppm (br.

s, 1 H).

MS: (M 319, 317 B) (3RS)-6-Chloro-4-N-(cyclopropyl)-3-methyl-3,4-dihydroquinoxalin-2(1H)-one 020 The compound of Example XVIIIA (318 mg, 1.0 mmol) was dissolved in 20 ml of ethanol 0.28 ml (2.0 mmol) of triethylamine were added, and the mixture was refluxed for 18 hours. The solvent was removed under reduced pressure, and the reaction product was purified by silica gel chromatography using ethyl acetate/heptane 1:2 as eluent. The yield was 200 mg of white crystals of melting point 1670C (after crystallization from pentane).

'H NMR (270 MHz, d 6 -DMSO): 6 0.40 1 0.63 1 0.76 1 H), 0.98 1 1.12 J 7 Hz, 3 2.47 1 3.87 J 7 Hz, 1 6.78 2 7.0 1 10.46 ppm (br. s, 1 H).

MS: (M 237 91 The following compounds of the formula I were synthesized analog~ously to the procedure described in Example XVIII using the correspondingly substituted orthonitroanilines and 2-halo carboxylic acid derivatives and, if appropriate, derivatized further: Table R 1 n-

S.

S

S S S S S S

S

Nr. IRnR3R4R5 X M.P.OC 1 6-Cl OH 3 H CAH 0 191 2 6-Cl OH 3

OH

3 CAH 0 3 6-Cl OH 3

OH

3 CAH S 4 6-Cl OH 3

OH

3 CAH 0 5 6-Cl OH 3

OH

3 CAH S Key: CAH

C

6

H

5 cyclopropyl phenyl 4 I 92 SExample XIX 7-Chloro-1-N-(cyclopropyl)-3,3-dimethyl-3,4-dihydroquinoxalin-2(1 H)-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 100C. 4 ml of 50% strength sodium hydroxide solution were slowly added dropwise with vigorous stirring, during which process the reaction temperature should not exceed 100C. After stirring for 5 hours at 100C, 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 of white crystals of melting point 132-133°C (after recrystallization from toluene/heptane).

'H NMR (270 MHz, d 6 -DMSO): 6 0.45 0.55 2 1.05 1.1 2 1.19 S 6 2.71 1 6.09 (br. s, 1 6.71 J 8 Hz, 1 6.88 (dd, J 8, 2 Hz, 1 7.19 ppm J 2 Hz, 1 H).

i"'O MS: (M 251 The following compounds of the formula I were synthesized in analogous manner and, if appropriate, derivatized further: °e o a 0 Table 6:

R

1 n *4 4 4 4 4 .4 Nr. M.P.

0

O

1 6-Cl OH 3

OH

3

C

5

H

9 179 2 7-Cl OH 3

OH

3 0 5

H

9 171 3 6,7-(0H 3 0) 2

OH

3

OH

3

H

4 6,7-(CH 3

O)

2

OH

3

OH

3 0 5

H

9

OH

3

CH

3 sO 6

H

11 113 6 0 6

H

5

OH

3

H

7 C 6

H

5

OH

3 0 5

H

9 8 6-Cl OH 3

OH

3 IPOC 128 9 7-Cl OH 3

OH

3 IPOC 169 7-OH 3

OH

3

OH

3 0 5

H

9 168 11 6-CH 3 O OH 3

OH

3 H 200 12 6-CH 3 O OH 3

OH

3

C

5

H

9 138 13 6/7-OOOH OH 3

OH

3 H 240 Nr. R'nR 3 R R 5 0 14 6/7-COOH OH 3

OH

3

C

5

H

9 180 8-OH 3

OH

3

OH

3 H 140 16 8-OH 3

OH

3

OH

3 CAH 160 17 8-OH 3

OH

3

OH

3 IPOC 127 i8 6/7-OH 3 CAH CAH H 160 19 6-CH 3 CAH CAH 0 5

H

9 100 7-OH 3 CAH CAH 0 5

H

9 110 21 7-F OH 3

OH

3 H 120 22 7-F OH 3

OH

3 CAH 155 23 7-0 2

H

5 0 OH 3

OH

3 H 155 24 7-O 2

H

5 0 OH 3

OH

3

C

5

H

9 123 25 6-OOOH OH 3

OH

3

C

5

H

9 245 26 7,8-(CH 3 2

OH

3

OH

3 H 196 27 7,8-(0H 3 2

OH

3

OH

3 0 5

H

9 155 28 6,7-(0H 3 2

OH

3

OH

3 H 248 29 6,7-(0H 3 2

OH

3

OH

3 0 5

H

9 200 30 6-01,7- OH 3

OH

3 H 211 (2 ,3-01 2 0 6

H

3 0) 31 6-01,7- OH 3

OH

3

C

5

H

9 205 (2,3-01 2

OH

3 0) 32 7-F OH 3

OH

3 IPOO 175 33 7-0 2

H

5 0 OH 3

OH

3 IPOO 150 0 0 000 0 0 0 0 *000 00 0 0* 0* 0* 10 *4 *4 4 4 4* 4 *44* 4 444*44 4* 4 44 4*44 0* 44 4 Nr. R'nR 3 R 4

R

5 M.P.oc 34 6/7-OH 3

CH

3

CH

3 IPOC 152 7,8-(CH 3 2

OH

3

OH

3 IPOC 147 36 6,7-(CH 3 2

OH

3

OH

3 IPOC 161 37 7-C 6

H

5

OH

3

OH

3 H 1 67 38 7-0 6

H

5 0 OH 3

OH

3 0 5 Hq 138 39 7-C 6

H

5 0 OH 3 OHi IPOC 181 5-OH 3

OH

3

OH

3 H 182 41 6-CH 3 O, OH 3

OH

3 H 240 7-(4-Pyridyl) 42 6-Cl, OH 3

OH

3 H 219 7-Piperidino 43 6/7-01,7/6- OH 3

OH

3 H 236 Mbrpholino (mixture) 44 6/7-(N-Methyl- OH 3

OH

3 H 240 piperazin-1 -yI) 6/7-01,7/6- Of: 3

OH

3 H 147 (N-M ethylpiperazin-1 -yi) 46 6-Cl OH 3

OH

3 H 152-1 54 47 7-01 OH 3

OH

3

H

48 6-Cl OH 3

OH

3 ALOC 128-1 29 49 7-01 O OH 3 ALOC 144 4* a a. a S a a Nr. Rn 1 R 3 R R 5 M.P.oc 6-cl OH 3

OH

3

COOCH(CH

3 2 118 51 7-Cl OH 3

OH

3

OOOCH(CH

3 2 171 52 7-(4-F-Ph-S0 2 0) OH 3

OH

3

H

53 7-(4-F-Ph-S0 2 0) OH 3

CH

3 IPOC 204 ,94 6-01,7-Piperidino OH 3

CH

3 IPOC 152 6-01,7- OH 3

OH

3 IPOC 113 Morpholino 56 6-CI,7-(N- OH 3

CH

3 IPOC 168 Methylpipe razin-1 -yl) 57 6-01,7-NEt 2

OH

3

OH

3 H 141 58 6-Cl, 7-NEt 2

OH

3

OH

3 IPOC Oil 59 6,7-012 OH 3

OH

3 H 232 60 6,7-012 OH 3

OH

3 IPOC 171 61 7-(N-Methyl- OH 3

OH

3 H 198 piperazinyl-1 -yl) 62 7-(N-Methyl- OH 3

OH

3 IPOC 123 piperazinyl-1 -yl) 63 6-CH 3 O OH 3

OH

3 IPOC 128 64 7-Cl -(OH 2 3 IPOC 172 7-Cl -(OH 2 4 IPOC 181 66 6-Cl -(OH 2 3 IPOC 157-1 58 67 6-Cl -(OH 2 4 IPOC 179-180 Nr. RnR3 4R 5

M.P.

0

C

68 6-Clq OH 3

OH

3

COOC

2

H

5 137 69 6-Cl CH 3

OH

3

COOC

3 H L- 125 Key: CAH 3-methyl-2-buten-1-yl

SC

6

H

11 4-methyl-3-penten-2-yI IPOC =isopropenyloxycarbonyl Example XX 3,3-Dimethyl-4-N- (3-methyl-2-buten-1 -yl)-3,4-dihydroquinoxalin-2(1 H)-one The compound was prepared analogously to the compound described in Example VIA, starting from 3,3-dimethyl-3,4-dihydroquinoxalin-2(1H)-one T. Lai, Synthesis 1982, 71). Melting point 146-1470C (after crystallization from methyl tert.-butyl 0.15 ether/heptane) 1 H NMR (270OMHz, d,,-DMSO): J 1.27 3 1.68 3 1.72 3 3.88 .00.

J =7Hz, 1H), 5.15 1H), 6.60 J =7Hz, 1H), 6.67 (t,J 7Hz, 1H), 6.78 J 7 Hz, 1 6.87 J 7 Hz, 1 10.33 ppm (br. s, 1 H).

MS: (M 245 Example XXI O 4-N- (3-M ethyl-2-buten-1 -yl)-3,4-dihydroquinoxalin-2(1 H)-one-3-spiro-1 -cyclohexane The compound was prepared analogously to the compound described in Example VIA, starting from s pi ro [cycl ohexane-1, ,4'-dihydroquin oxal in- H)-one)] T.

Lai, Synthesis 1982, 71). Melting point 82-830C (after crystallization from heptare) 1 H NMR (270 MHz, d -DMSO): 6 1.25 1.75 (in, 10 3.75 J 6 Hz, 2 H), 5.07 (in, 1 6.7 7.0 (in, 4 10.15 ppm (br. s, 1 H).

MS: (M H)Y 285 Example XXII 4-N- (3-Methyl-2-buten-1 -yl)-3,4-dihydroquinoxaline-2(1 H)-thione-3-spiro- 1 '-cyciohexane The compound of Example XXI (500 mg, 1.8 mmol) was refluxed for 1.5 hours under argon together with 370 mg (0.9 mmol) of 2,4-bis-(4-methoxyphenyl)- 1,3-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 silica gel chromatography using methyl tert.-butyl ether/heptane 10:1 as eluent. The yield was 50 mg of yellow crystals of melting point 1250C.

1 H NMR (270 MHz, d 6 -DMSO): 6 1.1 -1.9 16 3.64 J 7 Hz, 2 H), 4.99 1 6.95 7.1 3 7.18 J 7 Hz, 1 12.2 ppm (br. s, 1 H).

MS: (M H) 4 301 3,4-Dihydroquinoxaline-2(1H)-thione-3-spiro-1'-cyclohexane was isolated as a further product in a yield of 110 mg yellow crystals of melting point 1780C.

'H NMR (270 MHz, cDCI, 6 1.25 2.2 10 4.18 (br. s, 1 6.7 6.8 (m, 3 6.97 I 9.42 ppm (br. s, 1 H).

MS: (M H) 233.

Example XXIII (3S)-6-Chloro-4-N-(isopropenyloxycarbonyl)-3-methyl-3,4-dihydroquinoxaline- 2(1 H)-thione The compound of Example XIII (0.5 g, 1.78 mmol), dissolved in 10 ml of anhydrous pyridir;., was refluxed for 4 hours together with 0.47 g (2.12 mmol) of phosphorus pentasulfide. The mixture was concentrated in vacuo, and the residue was chromatographed on silica gel using ethyl acetate/heptane 1:1 as eluent. This 30 gave 0.25 g of a yellow crystalline solid of melting point 148-150oC (after recrystallization from ethyl acetate/heptane).

99 H NMR (270 MHz, d 6 -DMSO): J 1.24 J 7 Hz, 3H), 1.96 3H), 4.8 -4.9 (in, 2 5.28 J 7 Hz, 1 7.22 J 8 Hz, 1 7.30 (dd, J 8, 2 Hz, 1 7.72 (br. s, 1 12.84 ppm (br. s, I H).

M S: (M H) 297.

The following compounds of the formula I were synthesized in analogous manner from the corresponding 3,4-dihydroquinoxalin-2(1 H)-ones: Table 7 R1n-

S

S.

S

S

Nr. R3R 4

R

5

M.P.C

1 OH 3 H 05H-9 119 2 6-Cl OH 3 H CsH 9 109-110 3 6-Cl OH 3 H CHCH 2 92 4 6-Cl H -CH 2

CH

2

CS-

6-Cl H -CH 2

CH

2

CH

2

CS-

6 CAH OH 3

CSH

9 7 6-C0 OH 3

OH

3

C

5 Hq 157 8 7-l H 3

OH

3

C

5

H

9 160 9 7-Cl OH 3 1 OH 3 H 170 100

S

r I 6-Cl COH 3 ALOC 143 145 11 6-Cl C H 3 O H 3 IPOC 153 12 7-Cl O H 3

COH

3 IPOC 174 13 6-Cl O H 3 C H 3 H 175 14 6-Cl CAH H IPOC 176-177 6-Cl CAH H ALOC 159-161 16 6,7-(CH 3 2

OH

3

OH

3

C

5

H

9 173 17 6-Cl CAH H IPOC 154-155 18 6-Cl CAH H ALOC 98-100 19 6-Cl OH 3 H (2-C 5

H

4

N)-CH

2 175-1 78 6-Cl OH 3 H (3-C 5

H

4

N)-CH

2 77 21 6-Cl OH 3

OH

3 ALOC 153-1 54 22 6-Cl OH 3

OH

3 COOCH(0H 3 2 151 23 6-Cl CH 2

SCH

3 H IPOC 128 24 6-Cl OH 3

OH

3 0000 2

H

5 163 25 6-Cl OH 3

OH

3 C000 3

H

7 164 26 6-Cl CAH H (2-C 5

H

4

N)-CH

2 162-164 27 6-Cl C 4

H,

9 H IPOC 132 28 6-Cl CH 2

SCH

3 H COOCH(CH 3 2 124 29 6-Cl CH 2 SCH, J (2-C 5

H

4

N)-CH

2 159 6-CH 3 0 CH 2

SCH

3 H IPOC 154 31 6-CH 3 0 OH 2 SCH, H COOCH(OH 3 2 163 32_ 6-Cl CH 2 SC O 3 H_ CH 2

CH

4 -2-CI Oil Key: C 5

H

9

IPOC

ALOC

C,

5

H

4

N

3-imethyl-2-buten-1 -yl isopropenyloxycarbonyl allyloqycarbonyl pyridyl Example XXIV (3 RS) Methyl N -(3-methyl-2-bute n- 1 -yl) -2-methylthilo-3,4-di hydroquinoxal ine (3 RS)-3-M ethyl-4-N- (3-methyl-2-buten-1 -yl)-3,4-dihydroquinoxaline-2(1 H)-thione (Table 7, No. 1) (0.49 g, 2.0 mmol) was dissolved in 20 ml of ethanol 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 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 of K at yellow oil were isolated using ethyl acetate/heptane 1:6.

PI H NMR d 6 -DMSO): J 0.96 J 7 Hz, 3 1.72 6 2.44 3 3.71 J =15, 6Hz, 1 3.89 (dd, J 15, 6 Hz, 1 4.00 J 7 Hz, 1 5.20 (in, 1 6.65 -6.75 (mn, 2 7.02 J 8 Hz, 1 7.11 ppm J 8 Hz, 1 MS: (M 261 The following compound of the formula I was synthesized in the same manner: 4-I sopropenyloxycarbonyl-2- (isoprope nyloxycarbony!) 4hio-3,3.' 3,4-dihydroquinoxaline.

Melting point: 1150C ,,:methyl- 102 Q Example XXV (3RS)-3-Methyl-4-N-(3-methyl-2-buten-1-yl)-3,4-dihydroquinoxalin-2(1 H)-one (3RS)-3-Methyl-3,4-dihydroquinoxalin-2(1H)-one (4 86 g, 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 in the presence of 4.60 g (0.033 mol) of pulverulent potassium carbonate. The reaction mixture was stirred at room temperature until 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. Drying over sodium sulfate, concentration in vacuo and crystallization from pentane gave 5.80 g of white crystalline product of melting point 92-930C.

'H NMR (270 MHz, d 6 -DMSO): 6 0.99 J 7 Hz, 3 1.72 6 3.67 (dd, J 15, 7 Hz, 1 3.86 J 7 Hz, 1 3.88 (dd, J 15, 7 Hz, 1 5.21 (m, 1 6.65 6.9 4 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 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 950C, with stirring, and 300 ml of 2N sodium hydroxide solution were added dropwise. Stirring was then continued for 25 another 3 hours at this temperature. 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 concentrated under reduced pressure.

The residue was acidified with 250 ml of 2N hydrochloric acid and heated in a steam bath for approx. 30 minutes. The precipitate which resulted in this process 103 was filtered off with suction, washed with water and alcohol and subsequently dried, melting point 2550C, decomposition.

'H NMR (60 MHz, d 6 -DMSO): 6 1.9 2.7 4 4.5 J 8 Hz, 1 H), 6.8 7.3 3 7.8 8.2 1 10.7 ppm (br. s, 1 H).

MS: (M H) 202 Example XXVII 7-Phenoxysulfonyl-3,3a-dihydropyrrolo[1,2-a]quinoxaline-1,4(2H,5H)-dione The compound was obtained in analogous manner by reacting phenyl 4-chloro- 3-nitrobenzenesulfonate with L-glutamic acid, melting point 1400C (decomp.).

'H NMR (60 MHz, d 6 -DMSO): 6 1.6 2.5 4 4.07 J 6 Hz, 1 H), 6.7 7.6 8 10.57 ppm (br. s, 1 H).

MS: (M 358 Example XXVIII 3-Carboxymethyl-3,4-dihydroquinoxalin-2(1 H)-one 2-Fluoronitrobenzene (14.1 g, 0.1 mol) and L-aspartic acid (40.0 g, 0.3 mol) were heated to 950C in 100 ml of 2-methoxyethanol, with stirring, and 300 ml of 2N sodium 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 Scatalyst.

When the uptake of hydrogen had 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, 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 152-1540C.

104 'H NMR (60 MHz, d 6 -DMSO): 6 2.5 2.7 (dd partly concealed, 2 4.1 (td, J 6, 2 Hz, 1 5.98 (br. s, 1 6.5 6.9 4 10.30 (br. s, 1 H), 12.37 ppm (br. s, 1 H).

MS: M 206 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(1 H)-one A) Methyl N-[(2-nitro-4-phenoxysulfonyl)phenyl]glycinate 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 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 diisopropyl ether, melting point 120-123 0

C.

oQ. B) 7-Phenoxysulfonyl-3,4-dihydroquinoxalin-2(1H)-one 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 S N,N-dimethylformamide and 250 ml of methanol, with Raney nickel as catalyst.

When the uptake of hydrogen had ended, the catalyst was 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, d 6 -DMSO): 6 4.0 J 4 Hz, 2 6.6 7.6 9 H), 10.43 ppm (br. s, 1 H).

MS: (M H) 4 305 105 O Example XXX 4-(3-Methyl-2-buten-1-yl)-7-phenoxysulfonyl-3,4-dihydroquinoxalin-2(1 H)-one 7-Phenoxysulfonyl-3,4-dihydroquinoxalin-2(1H)-one (1.52 g, 5.0 mmol) in 20 ml of N,N-dimethylacetamide was stirred for 8 hours at 100 0 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 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 0

C.

'H NMR (270 MHz, d 6 -DMSO): 6 1.73 6 3.90 2 3.93 (partly concealed d, J 6 Hz, 2 5.20 (br. t, J 6 Hz, 1 6.75 7.45 8 H), 10.66 ppm 1 H).

MS: (M H) 4 373 The following compounds of the formula I were synthesized in analogous manner using the corresponding haloaromatic substances and amino acid derivatives and, *a if appropriate, derivatized further on nitrogen atom 4:

S

106 Is Table 8 R 1 n -R 3 R 4 4%* Nr. r R M.P.oc 1 1 7-0 6

H

5 -O-S0 2 H CH 2 0H H 199 2 7-C 6

H

5 -O-S0 2 H CH 2 0H CAH 120 3 7-0 6

H

5 -O-S0 2 H C 2 000H H 230 decomp.

4 7-C 6

H

5 -O-S0 2 H CH 2 C00H C 5

H

9 7-C 6

H

5 -O-S0 2 H CH 2 C0NH 2 H 272 decomp.

6 7-C 6

H

5 -O-S0 2 H CH 2 C0NH 2 0 5 Hq 7 7-C 6

H

5 -O-S0 2 H CH 2 -4-Imi H 216 1 decomp.

8 7-C 6

H

5 -O-S0 2 H CH 2 -4-Imi CAH 9 7-C 6 H5-CO H H H 280 decomp.

7-0 6

H

5 -CO H H C 6

H.

5 -CO 277 dlecomp.

11 7-0 6

H

5 -O-S0 2 H OH 3 H 148 107 Nr. R' R 3

R

4

R

5

M.P.°C

12 7-C 6

H

5

-O-SO

2 H CH 3

C

5

H

9 Oil 13 7-C 6

H

5

-SO

2 H CH 3 H 198 14 7-CHs-SO H CH 3 C5sH Oil 7-C 6

H-SO

2 H CH 3 IPOC 108 16 7-C 6 HsO-SO 2 H H H 17 7-C 6

H

5

SO

2 H H COCH 3 270 18 7-C 6

H

s -OSO, H CH 3 IPOC Resin Key- C s H, 3-methyl-2-buten-l-yl 4-Imi 4-imidazolyl IPOC isopropenyloxycarbonyl r r Exasmple XXXI 6-Chloro-7-phenoxysulfonyl-1,2,3,3a-tetrahydropyrrolo[2,1-c]-quinoxalin-4(5H)-one A) Phenyl 2,4-dichloro-3-nitrobenzenesulfonate 2,6-Dichloronitrobenzene was stirred for 7 hours at 1300C with an excess of chlorosulfonic acid. After cooling, the mixture was poured onto ice, the sulfochloride was filtered off with suction, washed to neutrality and dried over S 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 with 14 ml of triethylamine at 100C. 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 100C, washed with water and dried in vacuo at 80°C, melting point 1020C.

108 B) N-[(3-Chloro-2-nitro-4-phenoxysulfonyl)phenyl]proline 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 were stirred for 10 minutes at 80 0 C. The clear solution was ecidified at 500C using concentrated hydrochloric acid and poured onto ice. The precipitate was filtered off with suction, washed with water to neutrality and dried at 800C. Melting point 1480C (after recrystallization from methanol) C) 6-Chloro-7-phenoxysulfonyl-1,2,3,3a-tetrahydropyrrolo[2,1-c]-quinoxalin- N-[(3-Chloro-2-nitro-4-phenoxysulfonyl)phenyl]proline (38.0 g, 0.075 mol) in 500 ml of methanol and 25 ml of 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 2N hydrochloric 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 1970C (after recrystallization from glacial acetic acid) Example XXXII 8-(4-Methyl-1-piperazinyl)-3-(2-methylpropyl)-5-phenoxysulfonyl- 3,4-dihydroquinoxalin-2(1H)-one .'23.

A) Phenyl 2-chloro-4-(4-methyl-1-piperazinyl)-3-nitrobenzenesulfonate Phenyl 2,4-dichloro-3-nitrobenzenesulfonate (17.4 g, 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, and washed with 50% methanol and finally with water.

Melting point 94-950C (after recrystallization from cyclohexane) W B) N-[(3-(4-Methyl-1-piperazinyl)-2-nitro-6-phenoxysulfonyl)-phenyl]leucine hydrochloride Phenyl 2-chloro-4-(4-methyl-1-piperazinyl)-3-nitrobenzenesulfonate (41.1 g, 0.1 mol) and L-leucine (39.3 g, 0.3 mol) were stirred for 8 hours at 950C in a mixture of 100 ml of N,N-dimethylformamide, 50 ml of 2-methoxyethanol and 100 ml of 2N sodium hydroxide solution. When 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.

C) 8-(4-Methyl- 1 -piperazinyl)-3-(2-methylpropyl)-5-phenoxysulfonyl- 3,4-dihydroquinoxalin-2(1 H)-one hydrochloride N-[(3-(4-Methyl-1-piperazinyl)-2-nitro-6-phenoxysulfonyl)-phenyl]leucine hydrochloride (25.3 g, 0.05 mol) 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 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. 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 suctinn, washed with diisopropyl ether and dried, melting point 900C and above (decomp.).

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: 110 Table 9 C H Nr. 3R4R 5

M.P.C

1 H (CHI)CHCH 2

C

5

H

9 2 H OH 3 H 100 decomp.

(HCI)

3 H OH 3

C

5

H

9 4 H H H 126 -127 (base) 5 H H

C

5

H

9 ge @6 0 6*Wt ego.

S

Key: 0 5

,H

9 3-methyl-2-buten-1-y 6. 0: sfe so0 Example XXXIII (3 RS) N-Cy cioh exyl-3-methyl-3,4-dihydroquinoxalin-2(H) -one (3RS)-3-Methyl-3,4-dihydroquinoxalin-2(1 H)-ine (0.81 g, 0.005 mol) and 1 ml (0.1 mol) of cyclohexanone were introduced into 20 ml of 1 ,2-dichloroethane.

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 111 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 of the desired product were obtained, melting point 131-1320C (toluene/heptane).

1 H NMR (270 MHz, d.-DMSO): 6 0.97 J 7 Hz, 3 1.0 2.0 10 H), 3.39 1 3.91 J 7 Hz, 1 6.68 6.94 4 10.27 ppm (br. s, 1 H).

MS: (M H) 245.

The following compounds of the formula I were synthesized in analogous manner.

Table o* r oeoooo r Nr. R'n R 3

R

4

R

5

M.P.OC

1 CH 3 H C 2

H

5 106-107 2 CH 3 H CH 2

C(CH

3 3 162 3 CH 3 H c-C 5

H

9 120 4 6-CI CH 3 H c-C4H 7 100 6-Cl CH 3 H C 5 H, 94-95 112 Nr. R'nR3 R 4

R

5 M.P.o0 69 6-Cl

CH

3 H CH 2 C(0H 3 3 158 -160 7 6-Cl CAH H CH 2

C(CH

3 3 158 -159 8 13-Cl CH 3 H CH=CHOHO 140 -146 9 6-Cl OH 3 H CH 2

O-=CH

3 166 -168 10 6-Cl OH 3 H 2-Picolyl 198 -199 11 6-Cl OH 3 H 3-Picolyl 136 12 6-Cl CH 3 H 4-Picolyl 191 -193 13 6-Cl CH 3 H Furanyl-2-methyl 116 -118 14 6-Cl OH 3 H 0H 2

C

6

H

4 -4-Br 149 -150 15 6-Cl OH 3 H 0H,0 6

H

4 -4-CN 95 -96 16 6-Cl OH 3 H 0H 2 0 6

H

4 -4-N0 2 117 17 6-Cl OH 3 H CH 2 0 6

H

4 -3-N0 2 125 18 6-Cl OH 3 H 0H 2

C

6

H

4 -2-N0 2 153 -154 19 6-Cl OH 3 H CH 2

CH

4 -4-Ol 122 123 20 6-Cl OH 3 H 0H 2

C

6

H

4 -3-CI 156 -157 21 6-Cl OH 3 H CH 2 0 6

H

4 -2-CI 138 22 6-Cl OH 3 H CH 2

C

6

H

4 -4-F 147 23 6-Cl OH 3 H 0H 2 0 6

H

4 -4-C 6

H

5 164-165 24 6-Cl OH 3 H CH 2

O,

6

H

4 -4-00DH 5 Oil 6-Cl CHII H 0H 2 0 5 H -4-CH 3 60-62 26 6-Cl OH 3 H CH 2 0 6

H

4 -4-COOOH 3 139 27 6-Cl OH 3 H, ClH 2 6

H

3 -26-C 2 190-191 Nr. RR3 R 4

R

5 M.P.oc 28 6-Cl CH 3 H CH 2

C,,H

3 -3,5-C 2 139-1 29 6-Cl OH 3 H NFAphthyl-1 -methyl 164-166 6-Cl OH 3 H Naphthyl-2-methyl 16 1-164 31 6-Cl OH 3 H CH 2

C."

2 00H 3 78-79 32 6-Cl CH 3 H Cyclotlex-2-enyl Oil 33 6-Cl CH 3 H C 2

H

4

-C

6

H

5 128 34 6-Cl OH 3 H Thien)yl-3-methyl 141-142 6-Cl OH 3 H (5-Methylthienyl)- 58-60 2-methyl 36 6-Cl OH 3 H (3-Methylthienyl)-2- 124 methyl 37 6-Cl OH 3 H Th ienyl-2-m ethyl 121-123 38 6-Cl CI-13 H CH 2 CH =CH-CH 5 59 39 6-Cl CH 2

SCH

3 H CH 2

C

6

H

4 -2-CI 128 6-Cl CH 2

SOH

3 H CHC 6

H

4 -2-N0 2 134 41 6-Cl CH 2

SOH

3 H 2-Picolyl Oil 42 6-Cl CH 2

SCH

3 H CH 2

CH

3 -2,4-CK- 143 43 6-Cl CH 2 S-i.Pr H CH 2

C

6

H

3 -2,4-C 2 Oil 44 6-Cl CH 2 S-Bn H CFHl'C 6

H

3 -2,4-Cl 2 Oil 6-0l CH 2 -S-H H CH 2 CcH 3 -2,4-C 2 46 6-Cl C 2 1- 5 H 2-Picolyl 160-162 47 6-Cl OH 3 H I(6-CH 3 )2-Picolyl 158 Key: CHj1 3-methyl-l-butyl c-C 4

H

7 cyclobutyl c-CsH cyclopentyl Example XXXIV (3RS)-3-Methyl-4-N-(3-oxo-1 -butyl)-3,4-dihydroquinoxalin-2(1 H)-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 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.-buty! ether/heptane 2:1 gave 620 mg of the desired product, melting point 108-1090C (methyl tert.-butyl ether/heptane).

'H NMR (270 MHz, de-DMSO): 6 1.03 J 7 Hz, 3 2.11 3H), 2.77 (t, J 6 Hz, 2 3.30 1 3.50 1 3.88 J 7 Hz, 1 6.68 (m, S 1 6.78 1 6.88 1 10.31 ppm (br. s, 1 H).

MS: (M 233, M' 232 Example XXXV (3S)-6-Chloro-4-N-chlorocarbonyl-3-methyl-3,4-dihydroquinoxalin-2(1H)-one The compound of Example IB (2.0 g, 0.01 mol) in 100 ml of anhydrous 'oluene was heated with bis-(trichloromethyl) carbonate (triphosgene) (1.5 g, 0.005 mol) for 1 hour at 800C in the presence of 2 ml (0.014 mol) of triethylamine. After cooling, the ::i mixture was washed with water 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 obtained by silica gel chromatography using ethyl acetate/heptane 1:1 as eluent. Melting point 142-144 C.

115 S'H NMR (270 MHz, d 6 -DMSO): 6 1.25 J 7 Hz, 3 3.83 J 7 Hz, 1 6.61 (dd, J 6, 2 Hz, 1 6.70 2H), 10.3 ppm (br. s, 1 H).

MS: (M H) 259 Example XXXVI (3S)-6-Chloro-4-N-(2-methoxyethoxycarbonyl)-3-methyl-3,4-dihydroquinoxalin- 2(1H)-one To a solution of 0.24 ml (3.0 mmol) of 2-methoxyethanol 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, 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 S: acetate, the organic phase was washed once with saturated aqueous sodium 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 of the desired product was obtained, melting point 93-94oC.

'H NMR (200 MHz, de-DMSO): 6 1.13 J 7.5 Hz, 3 3.32 3 3.6 (m, 2H), 4.24 1 4.35 1 4.81 J 7.5 Hz, 1 6.98 J 9 Hz, 1 7.2 (dd, J 9, 3 Hz, 1 7.66 J 3 Hz, 1 H, 10.81 ppm (br. 2, 1 H).

MS: (M H) 299 Example XXXVII (3S)-6-Chloro-3-methyl-4-N-[(phenylthio)carbonyl)]-3,4-dihydroquinoxalin-2(1 H)-one To a solution of 0.31 ml (3.0 mmol) of thiophenol in 10 ml of 1,2-dimethoxyethane there was added 0.17 g of a 55% suspension of sodium hydride in mineral oil, with 116 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 icecooling, and 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 the solvent was stripped off. The solid residue was recrystallized from heptane/isopropanol, 0.35 g melting point 194-195 0

C.

'H NMR (200 MHz, d.-DMSO): 5 1.10 J 7 Hz, 3 4.93 J 7 Hz, 1 7.08 J 9 Hz, 1 7.33 (dd, J 9, 3 Hz, 1 7.4 78.6 5 7.78 J 3 Hz, 1 10.16 ppm (br. s, 1 H).

MS: (M H) 333, (M C 6 HsSH 223 The following compounds of the formula I were synthesized in analogous manner.

Table 11

H

1 n R4

R

Nr. R'n R 3

R

4

R

5

M.P.°C

1 6-CI CH 3 H COOCH 2 CH =CHCH 3 116-117 2 6-CI CH 3 H COOCH 2

=C(CH

3 2 87-89 3 6-CI CH 3 H COOCH 2 C CH 147 4 6-CI CH3 H COOCH 2 C CCH 3 135 Nr. R'n R 3 R 4

R

5 M. P. 0

C

6-Cl OH 3 H COSCH 2

CH

5 158 6 6-Cl OH 3 H COSCH 2

CH=CH

2 Oil 7 6-Cl OH 3 H COOCH 2

C(CH

3

)=CH

2 125-127 8 6-Cl OH 3 H COOC(CHI) 9 6-Cl OH 3 H COO-Cyclohex-2-en-1-yl 6-Cl OH 3 H COOCH(CH,00H(CH 32 2 Oil 11 6-Cl OH 3 H COOCH(CH 3 2 141-142 12 6-Cl OH 3 H COOCAHN (CH 3 2 Oil 13 6-Cl OH 3 H COOC 2

H

4

SCH

3 108-110 14 6-Cl OH 3 H COSC 6

SH

5 194-195 6-Cl OH 3 H COOCH 2

CD

6

H

4 -2-NO 2 227-231 16 6-Cl OH 3 H COOCH 2

C

6

H

4 -3-N0 2 183-185 17 6-Cl OH 3 H COOCH 2 CAH-4-CI 177-181) 18 6-Cl OH 3 H COOCH 2

CH

4 -2-CI 164 19 6-Cl OH 3 H COOCH 2

CH=CHCH

2

CH

3 Oil 6-Cl OH 3 H C00(3-Picolyl) 160-161 21 6-Cl OH 3 H C00(2-Picolyl) 114-116 22 6-Cl OH 3 H CODOCH 2

C

6

H

4 -4-NO 2 230-233 23 6-Cl OH 3 H COOCH 2

CH

2 C(0H 3 )=0H 2 Oil 24 6-Cl OH 3 H CO-(4-Methylpiperazin-1 -yl) Oil 6-Cl OH 3 H CO-N(CH 2 5 218-220 26 6-Cl OH 3 H CO-N(CH 2 4 200-203 Nr. R'n R3 R 4

R

5 M.P.oc 27 6-Cl OH 3 H CO-Morpholin-1 -yl 193-195 28B 6-Cl OH 3 H CO-HNCH 2 Ph 94-96 29 6-Cl OH 3 H Cyclopropyl-methyloxy- 119-122 I I carbonyl 55*5 S S o

Claims (4)

1. A compound of the formula I or [a, 0. *0 S 0 00 5 0 S S S. 0 S S o 05 5050 OeSS S S S 500* 0**S S 0* 5* 0 5 S S 55 S S *055 0000** S *OSS 0 0 0**0 N 'R2 1R 3 and physiologically acceptable salts and prodrugs thereof, where, in formulae I and la, n is zero, one, two, or three, U) 4 r~e, HOE 91/F 111 K Vthe individual substituents R' independently of one another are fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, hydroxyl, C1-C4- alkyl, C 5 -C 6 -CYCloalky, Cl-C 4 -alkoxy, (C1,-C 4 -alkoxy)- (C 1 -C 4 -alkoxy), C.,-C4- alkylthio, C 4 -alkylsulfinyl, C.,-C 4 -alkylsulfonyl, nitro, amino, 0,-C 4 alkylamino, di(Cl-C 4 -alkyl)amino, piperidino, morpholinc, 1 -pyrrolidinyl,

4-methylpiperazinyl, thiomorpholino, imidazolyl, C.,-C 4 -acyl, C 1 -C 4 -acyloxy, C.,-C 4 -acylamino, cyano, carbamoyl, carboxyl, (C 1 -C 4 -alkyl)oxycarbonyl, hydroxysulfonyi or sulfamoyl o S S a phenyl, phenoxy, phenoxycarbonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy, anilinosulfonyl, phenylsulfonylamino, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyt radical which is substituted by up to two radicals R 6 which are independent of one another, where R' can be fluorine, chlorine, bromine, cyano, trifluoromethyl, nitro, amino, C.,-C 4 -alkyl, C 3 -C 7 -cycloalkyl, C.,-C 4 -alkoxy, C, -C 4 -alkylthio, C.,-C 4 -alkylsulfinyl, C1-C4- alkylsulfonyl, C.,-C 4 -alkylamino, di (C,-C 4 -alkyl)amino, (C 1 -C 4 -alkyl)oxycarbonyl, phenyl or phenoxy, R 2 is hydrogen and R 5 is ~2O S. S liydGege, hydroxyl, cyano, amino, C.,-C 6 -alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C1-C4- -acyloxy, benzoyloxy, benzyloxy, phenoxy, C.,-C 4 -alkoxy, Ci-C 4 -alkylamino, di(CA,-C 4 -alkyl) amino, Cl, 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; 0 2 -C 8 I-alkenyl, -2HO9/1K optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C 4 -alkoxy, Cl -C 4 -alkylamino, di(Cl-C 4 -alkyl)amino, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; C.-C.-allenyl, C 3 -C 8 ,-alkyny I, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C 1 -C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -0 4 -alkoxy, C 1 -0 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; C 3 -C,-cycloalkyl, optionally substituted by C: 1 Y fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, 1 -C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C 4 -alkoxy, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amIno, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; C 3 -C 8 -CYCloalkenyl, optionally substituted by ~~1 fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, 1 -C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; (C 3 -C 8 -CYCloalkyl)-(C 1 -C,-alkyl) optionally substituted by C C fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, 1 C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C 4 -alkoxy, Cl-C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, C 1 -C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; (C 3 -C-cycloalkenyl)-(C-C 2 -alkyl), g HE9/11K optionally substituted by 4 ZY fluorine, chlorine, bromine, iodine, cyano, Rmino, mercapto, hydroxyl, acylo, y, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 -alkoxy, Cl-C 4 -alkylamino, di(Cl-C 4 -alkyl)amino, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; Cl -0 6 -alkylcarbonyl, optionally substituted by C W-kY fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, 1 -C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl -C 4 -alkoxy, C, -C 4 -alkylamino, i 1 di (0 1 -C 4 -alkyl)amino C 1 -C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; 0. C 2 -C 6 -alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxyl, 0 1 -0 4 -alkoxy, oxo, phenyl; (0 3 -0 6 -cycloalkyl)carbonyl, optionally st.bstituted by fluorine, chlorine or hydroxyl, Cl-0 4 -alkoxy, oxo, phenyl; (C.-C.-cycloalkenyl)carbonyl, optionally substituted by fluorine, chlorine or *2a hydroxyl, 0 1 -C 4 -alkcoxy, oxo, phenyl; (C 3 -0 6 -cycloalkyl)-(0 1 -0 2 -alkyl~carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, C 1 -C 4 -alkoxy, oxo, phenyl; (0 5 -C 6 -CYcloalkenyl)-(C 1 -C 2 7alkyl)carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, C 1 -0 4 -alkoxy, oxo, phenyl; Cl-C 6 -alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, C 1 -C 4 -alkoxy, Cl -C 4 -alkyiamino, di (Cl-C 4 -alkyl)amino, Cl-C 4 -alkylthio; C 2 -C6-alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; 123 C 2 -C6-alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, C 1 -C 4 -alkoxy, oxo, phenyl; Cl-C 6 -alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; C 2 -C 6 -alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, CI-C 4 -alkoxy, oxo, phenyl; Cl-C 6 -alkylamino- and di(Cl-C 6 -alkyl)aminocarbonyl, in each casce optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; pyrrolidin-i-yl, morpholino-, piperidino-, piperazinyl-, or 4-methylpiperazin-1- optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, 0 1 -C 6 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 C 6 -alkoxy, Cl-C 6 -alkylamino, di(C 1 -0 6 )alkylamino, Ci -0 6 -alkylthio, Ci -06- alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl, C 2 -0 6 -alkenylamino- and di(C 2 -0 6 -alkenyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Cl-0 4 -alkoxy, oxo, phenyl; C-C 4 -alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, 0-C4- alkoxy, oxo, phenyl; C 2 -C 4 -alkenylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, Ci- C 4 -alkoxy, oxo, phenyl; or aryl, arylcarbonyl, aryl(thiocarbonyl), (arylthio)carbonyl, (arylthio)thiocarbonyl, aryloxycarbonyl, arylaminocarbonyl, (arylamino)thiocarbonyl, arylalkylamino- carbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbo nyl, or arylalkoxycarbonyl, or aryl (alkylthio)carbonyl, 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 carbon atoms and R6 being as defined above, HOE 91/F7 111 K ~or I1- or 2-naphthylmethyl, 3- or 4-picolyl, 2- or 3-furylmethyl, 2- or -3-thienylmethyl, 2- or 3-pyrrolylmethyl, 3- or 4-pyridylcarbonyl, 2- or 3-furylcarbonyl, 2- or 3-thienylcarbonyl, 2- or 3-thienylacetyl, 3- or 4-picolyloxycarbonyl, 2- or 3-furylmethyloxycarbonyl, 2- or 3-thienylmethyl- oxycarbonyl, each of which is substituted by up to two radicals R' which are independent of one another, and R 3 and R 4 are identical or different and independently of one another are hydrogen, .Cl-C 6 -alkyl, optionally substituled by fluorine, chlorine, hydroxyl, amino, mercapto, C -C4- acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 -alkoxy, Cl-C 4 -alkylamino, di(0 1 -C 4 -alkyl)amino, Cl-C 4 -alkylthio, Cl-C 4 -alkylsulfonyl, Cl-C 4 -alkylsulfinyl, carboxyl or carbamoyl; C 2 -C,-alkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, *mercapto, Cl 4 cyloxy, benzoyloxy, benzyloxy, phenoxy, 0 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, di (C 1 -C 4 -alkyl)amino, Cl-C 4 -alkylthio, C 1 -C 4 -alkylsulfonyl, Cl-C 4 -alkylsulfinyl, carboxyl or carbamoyl; Q -5 C 3 -C 8 -cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, C 1 -C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 -alkoxy, Cl-C 4 -alkylamino, di (Cl -C 4 -alkyl)amino, C, -C 4 -alkylthio, Cl -C 4 -alkylsulfonyl, Cl-C4-al kylsulfinyl, carboxyl or carbamoyl; C 3 -C,-cycloalkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, C 1 -C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 alkoxy, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, Cl-C 4 -alkylthio, C1-C4- 125 alkylsulfonyl, Ci-C 4 -alkylsulfinyl, carboxyl or carbamoyl; aryl, arylalkyl, heteroaryl or heteroarylalkyl, 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 R6 being as defined above, R3 and R4 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, C1-C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, C 1 C4-acyloxy, benzoyloxy, C1-C4-alkoxy, oxo, thioxo, carboxyl, carbamoyl or phenyl, and X is oxygen, sulfur or selenium with the exception of those compounds in add: .which R3 and R4 are both hydrogen. fe*@: S2. A compound of the formula I or la as claimed in claim 1 wherein the substituents in the abovementioned formulae have the following meanings: n is zero, 4 a a* doesone 0 a e or two, the individual substituents R1 independently of one another are fluorine, chlorine, bromine, trifluoromethyl, hydroxyl, C 1 -C 4 -alkyl, C 1 -C 4 alkoxy, (C1-C 4 -alkoxy)-(C1-C 4 -alkoxy), C 1 -C 4 -alkylthio, nitro, amino, Ci- C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, piperidino, morpholino, 1- pyrrolidinyl, 4-methylpiperazinyl, C 1 -C 4 -acyl, C 1 -C 4 -acyloxy, C1-C4- acylamino, cyano, carbamoyl, carboxyl, (C1-C 4 -alkyl)oxycarbonyl, hydroxysulfonyl or sulfamoyl,

126- Aai< HOE 91/17111 K a phenyl, phenoxy, phenylthio, phenylsulfonyl, phenoxysulfonyl, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical which is substituted by up to two radicals R 6 which are independent of one another, where R 6 can be fluorine, chlorine, bromine, cyano, trifluoromethyl, nitro, amino, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, (C 1 -C 4 -alkyl)oxycarbonyl, phenyl or phenoxy, R? is hydrogen and R 5 is Cl-C 6 -alkyl, optionally substituted by all fluorine, chlorine, hydroxyl, C 1 -C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, di(Cl-C 4 -alkyl)amino, C 1 -C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; C 2 -C 6 -alkenyl, optionally substituted by fluorine, chlorine, hydroxyl, CI -C 4 -aCYloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C 4 -alkoxy, C 1 -C 4 -alkylamino, di(Cl-C 4 -alkyl)amino, C 1 -C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; see* C 3 -C,-allenyl, C 3 -C,-alkynyl, optionally substituted by fluorine, chlorine, hydroxyl, C 1 -C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C4-al koxy, C 1 -C 4 -alkylamino, di(Cl-C 4 -alkyl)amino, C 1 -C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; iHOE 91/F 111 K C,,-C.-cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, C 1 -C 4 -alkyl, C 1 -C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, di(C 1 .C 4 -alkyl)amino, C 1 -C 4 alkylthio, oxo, thioxo, carboxyl or carbamoyl; C 3 -C 8 -CYCloalkeryi, optionally substituted by fluorine, chlorine, hydroxyl, C 1 -C 4 -alkyl, C 1 -C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, di (Cl -C 4 -alkyl)amino, C 1 -C 4 alkylthio, oxo, thioxo, carboxyl or carbamoyl; (C 3 -C 6 -cycloalkyl)- (0 1 -C 2 -alkyl), optionally subsiituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkyl, C 1 -C 4 -aCYloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, di(C,-C 4 -alkyl)amino, C 1 -C 4 alkylthio, oxo, thioxo, carboxyl or carbamoyl; *20optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -akl Cl-C 4 ayoybnylxenyo, phenoxy, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, di(Cl-C 4 -alkyl)amino, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; 2-3Cl-C 6 -alkylcarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, C 1 -C 4 -alkyl Cl-C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 -al koxy, Cl-C 4 -alkylamino, C--C 4 -alkenylamino, di(Cl-C 4 alkyl)amino, I .pyrrolidinyl, piperidino, morpholino, 4-methylpiperazin-1 -yl, Cl-C 4 -alkylthio, oxo, thioxo, carboxyl or carbamoyl; 4 HOE 91/F7 111 K C,-C,-alkenylcarbonyl, optionally substituted by fluorine, chlorine or "'ydroxyl; (C 3 -C.'-CYCloalkyl)carbonyl, (C,-Cr,-cycloalkenyl)carbonyl, (C 3 -C 6 -cycloalkyl)- (0 1 -C 2 -alkyl)carbonyl, (0 5 -C 6 -cycloalkenyl)- (Cl -C 2 -alkyl)carbonyl, Cl-C,-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, C, -C 4 -alkoxy, C 1 -C 4 -alkylamino, di (0 1 -C 4 -alkyl)amino or Cl-C 4 -alkyl- thio; C 2 -C6-alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, i hydroxyl, C,-C 4 -alkoxy; *Cl-0 6 -alkynlthocarbonyl, optionally substituted by fluorine, chlorine,hyrxl hydr-aoxy0- 4 loy C2-C 6 -alkeylthiocarbonyl, optionally substituted by fluorine, chlorine,hyrx, hydroxyl, Cl-C 4 -alkoxy; C 1 -0 6 -alkylamino- and di(C 1 -C 6 -alkyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, C 1 -C 4 -alkoxy; pyrrolidin-1-yI, morpholino-, piperidino-, piperazinyl-, or 4-methylpiperazin- 1 -ylcarbonyl; HOE 91/F 111 K C 2 -C,-alkenylamino- and di (CC-C 6 -alkenyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy; 0 1 -0 4 -alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, C 1 -C 4 -alkoxy; CIA7C 4 -alkenylsulfonyI; or aryl, arylcarbonyl, (arylthio)carbonyl, aryloxycarbonyl, arylaminocarbonyl, (arylamino)thiocarbonyl, arylsulfonyl, arylalkylaminocarbonyl, arylalkyl, arylalkenyl, arylalkylcarbonyl, aryl (alkylthio)carbonyl or arylalkoxycarbonyl, each of which is substituted by up to two radicals R 6 which are independent oi one another, it being possible for the alkyl radical to contain in each case *6 1 io 3 carbon atoms and R 6 being as defined above, *46 or 1- or 2-naphthyl methyl, 3- or 4-pircolyl, 2- or 3-furylmethyl, 2- or 3-thienylmethyl, 2- or 3-pyrrolylmeth/l, or 4-pyridylcarbonyl, 2- or 3-furylcarbonyl, 2- or 3-thienylcarbonyl, 2- or 3-thienylacetyl, 3- edterk4-picolyloxycarbonyl, 2- or 3- 2b furylmethyloxycarbonyl, 2- or 3-thienylmethyloxycarbonyl each of which is substituted by up to two radicals R 6 which are independent of one another, and R' and R' 'are identical or different and independently of one another are hydrogen, C 1 -C 4 -alkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, Cl-C 4 -acyloxy, benzoyloxy, phenoxy, C, -0 4 -alkoxy, C, -C 4 -alkylamino, di (Cl-C 4 -alkyl) amino, Cl-C 4 -alkylthio, C1-04- alkylsulfonyl, Cl-C 4 -alkylsulfinyl, carboxyl or carbamoyl; C 2 -C 6 -alkenyl, optionally substituted by fluorine o~r chlorine; 130: 3e HOE 91/F7 111 K C 3 -0 0 -CYCloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, CI-C 4 -acyloXY, benzoyloxy, benzyloxy, phenoxy, Cl-C 4 -alkoxy, C, -C 4 -alkylamino, di (Cl-C 4 -alkyl)amino, Cl-C 4 -alkylthio, Cl-C 4 -alkylsulfonyi, Cl-C 4 -alkylsulfinyl, carboxyl or carba-moyl; C 3 -C.-cycloalkenyl, optionally substituted by fluorine or chlorine; aryl, benzyl, heteroaryl or hetLeroarylmethyl, each of which is substituted by up to two radicalis R 6 which are 11independent of one another, R 3 and R 4 can furthermore also be 0 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, Cl-C 4 -acyloxy, benzoyloxy, C 1 -C 4 -alkoxy, oxo, thioxo, 0: 0. carboxyl or carbamoyl, and X is oxygen or sulfur. A~ A compound of the formula I or la as claimed in claims 1- 1 wherein the ,a0 abovementioned substituents have the following meanings: n is zero, one or two, the individual substituents R' independently of one another are fluorine, chlorine, bromine, trifluoromethyl, hydroxyl, Cl-C 4 -alkyl, C 1 -C 4 -alkoxy, (Cl-C 4 -alkoxy)-(Cl-0* 2 -alkoxy), C 1 -C 4 -alkylthio, nitro, amino, C 1 -C 4 -alkylamino, di(0 1 -C 4 -alkvl)amino, piperidino, morpholino, 1-pyrrolidinyl, 4-methylpiperazinyl, Cl-C 4 -acyl, C 1 -C 4 -acyloxy, Cl-C 4 -acylamino, cyano, carbamoyl, carboxyl, (0 1 -C 4 -alkyl)oxycarbonyl, hydroxysulfonyl or sulfamoyl or )2,fHOE 91/F 111 K a phenyl, phenmxy, phenylthio, phenylsulfonyl, phenoxysulfonyl, benzoyl, 2-pyridyl, 3-pyridyl or 4-pyridyl radical which is substituted by up to two radicals R 6 which are independent of one another, where R 6 can be fluorine, chlorine, bromine, cyano, trifluoromethyl, nitro, amino, C 1 -0 4 -alkyl, 0 1 -C 4 -alkoxy, (C 1 -C 4 -alkyl)oxycarbonyl, phenyl or phenoxy, R 2 is hydrogen and R 5 is substituted by C 1 -C 4 -alkoxy or C 1 -0 4 -alkylthio; 0 2 -C,-alkenyl, optionally substituted by oxo; 0 3 -C,-allenyl; 0 3 -C 8 -alkynyl, in particular 2-butynyl; C 3 -0 6 -cycloalkyi; C 5 -C.-cycloalkeny'l; (C3-C 6 -CYC'oalkyl)-(Cl-C 2 -aIky1), in particular cyclopropylmethyl, optionally substituted by C 1 -C 4 -alkyl; (C 3 -C 6 -cycloalkenyl)-(0 1 -C 2 .alkyl), in particular cyclohexenylmethyl; 4. 4. 4 4* 4 0 4 *ti* 0 4*0*4* /W8 HOE 91/F 111 K C 1 -C.-alkylcarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, benzyloxy, phenoxy, C 1 -C 4 -al koxy, C 1 -C 4 alkylamino, C2:C 4 -alkenylamino, di (C 1 -C 4 -alkyl)amino, 1 -pyrrolidinyl, piperidino, morpholino, 4-methylpiperazin-1-yl or C 1 -C 4 -alkylthio; C 2 -Cr,-alkenylcarbonyi; CI-Cr 6 -alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, C, -C 4 -alkoxy, C, -C 4 -alkylamino, di (Cl -C 4 -alkyl) amino or C, -C 4 -alkyl- thio; C 2 -C,-alkenyloxycarbonyl, in particular vinyloxycarbonyl, allyloxycarbonyl, isopropenyloxycarbonyl, butenyloxycarbonyl or pentenyloxycarbonyl; C 2 -C 6 -aikyny...,'oxycarbonyl, in particular propynyloxycarbonyl or butynyloxycarbonyl; Cl-C.-alkylthiocarbonyl; C 2 -C,-alkenylthiocarbonyl, in particular allylthiocarbonyl; C 1 -C 6 -alkylamino- and di(Cl-C 6 -alkyl)aminocarbonyl; pyrrolidin-1-yl, morpholino-, piperidino-, piperazinyl-, or 4-methylpiperazin- 1 -ylcarbonyl; C 2 -C 6 -alkenylamino- and di (C:C 6 -alkenyl)aminocarbony; Cl-C-al kylsulfonyl; Q -C 4 -alkenylsulfonyl; ~Iu~y I 6 A~r O~ HOE 91/F 111 K or aryl which is substituted by up to two radicals R 6 which are independent of one another, in particular phenyl, arylcarbonyl, in particular benzoyl, (arylthio)carbonyl, aryloxycarbonyl, arylaminocarbonyl, (arylamino)thiocarbonyl, arylalkylaminocarbonyl, arylsulfonyl, arylalkyl, in particular benzyl, phenylethyl, arylalkenyl, arylalkylcarbonyl, arylalkoxycarbonyl or aryl(alkylthio)carbonyl, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms and R 6 being as defined above, or 1- or 2-naphthylmethyl, 3- or 4-picolyl, 2- or 3-furylmethyl, 2- or 3-thienylmethyl, 2- or 3-pyrrolylmethyl, 3- or 4-pyridylcarbonyl, 2- or 3-furylcarbonyl, 2- or 3-thienylcarbonyl, 2- or 3-thienylacetyl, 3- or *.".4-picolyloxycarbonyl, 2- or 3-furyimethyloxycarbonyl, or 2- or 3-thienyl- methyloxycarbonyl, each of which is substituted by up to two radicals R" iwhich are independent of one another, and R 3 and R 4 are identical or different and independently of 2 one another are hydrogen, C,-C 4 -alkyl, optionally substituted by hydroxyl, mercapto, C,-C 4 -alkoxy, C,-C 4 -alkylthio, C,-C 4 -alkylsulfonyl, C,-C 4 -alkylsulfinyl, carboxyl or carbamoyl; C,-C,-alkenyl, aryl, benzyl, thienyl or thienylmethyl, each of which is substituted by up to two radicals R 6 which are independent of one another, R§ having the meaning as defined above O .Ad HOE 91/F 111 K R 3 and R 4 can also be part of a saturated or unsaturated carbo- or heterocyclic ring which has 3 to 6 carbon atoms and can optionally be substituted by oxo or thioxo, and X is oxygen or sulfur. 8. A process for the preparation of compounds of the formula I as claimed in claim 1, which comprises A) for preparing compounds of the formula I where X is oxygen and the radicals R 1 R 2 R 3 R 4 and R 5 are as defined in claim 1, reacting a compound of the formula 11 H S S5 R n- (II) with the definitions mentioned in claim compound of the formula III R-Z 1 applying to R 1 R 3 and R 4 with a (IlI) where R has the meanings for R 5 and R 2 which have been mentioned in claim 1 cr- o, -wih-the at hydrogen, hydroxyl, Cl-C 6 -alkoxy, aryloxy, C,-C.-acyloxy, amino, C,-C 6 -alkylamino, di(C,-C 6 -alkyl)amino, arylamino and C,-C 6 -acylamino, and Z is a leaving group, or B) preparing compounds of the formula I where X is sulfur and R 1 R 2 R 3 R 4 and R are as defined in claim 1 by reacting a compound of the formula I where X is A; (r~ j3( HOE 91/F 111 K W oxygen and the definitions mentioned in claim 1 apply to R 2 R 3 R 4 and R 5 with a sulfurizing reagent, or C) preparing compounds of the formula la where X and the radicals R' to R 5 are as defined in claim 1, by reacting a compound of the formula IV RIn- (IV) 4@ S S N X R3 N I R4 (IVoa) where the definitions mentioned in claim 1 apply to R 1 R 3 R 4 and R 5 with a compound of the formula III R 2 -Z °S where the definitions described in claim 1 for formula I and la apply to R 2 with-the- cM^ e<c~uAro *exeti~ ef hydrogen, hydroxy, C,-C-alkoxy, aryloxy, C,-C 6 -acyloxy, amino, C,- C,-alkylamino, Di(C,-C 6 -allyl)amino, arylamino, C,-C 6 -acylamino and Z is a leaving group, or D) preparing compounds of the formula I where X is oxygen and the radicals R 1 to R 5 are as defined in claim 1 by cyclizing a compound of the formula V 13G SHOE 91/F 111 K R2 NH 1 CO-Y R4 R 4 where R 1 to R 5 are as defined in claim 1 and Y is hydroxyl, C,-C 4 -alkoxy, optionally halogenated Cl-C 4 -acyloxy, chlorine, bromine or iodine, or E) preparing compounds of the formula I where X is oxygen, R 4 and R 5 are hydrogen and the definitions mentioned in claim 1 apply to R 1 to R 3 from the quinoxalinones of the formula XI R 2 N X I 1 I R3 XI R1 X I where R 1 to R 3 are as defined at the outset, by addition of hydrogen on the C= N bond, or S F) preparing compounds of the formula I where X is oxygen and R' to R 5 are as defined in claim 1, from compounds of the formula VI Ins HOE 91/F 111 K R 1 where R 1 R 2 and R 5 are as defined in claim 1, by reacting them with chloroform or bromoform and a carbonyl compound of the formula XIII R -CO-R 4 (XIII) where R 3 and R 4 are as defined in claim 1, or with a-(trihalomethyl)alkanols of the formula XIV Hal3C-C(OH)-R 3 R 4 (XIV) where Hal is Cl, Br or I, in which R 3 and R 4 are as defined at the outset, or G) preparing compounds of the formula I where X is oxygen and R 2 R 3 R' and R 5 are as defined in claim 1, by reacting a compound of the formula I where X is oxygen and the definitions mentioned in claim 1 apply to R 1 R 2 R 5 and to R 3 and R 4 with the exception that at least one of the radicals R' or R 4 is hydrogen, with an alkylating reagent of the formula XV R'-Z (XV) where R' has the meanings mentioned above for R 3 and R 4 with the exception of hydrogen and Z is a leaving group, ~A-44 HOE 91/17 -11 K *or H) preparing compounds of the formula I where X is oxygen, RI, R 2 R 3 and R 4 are as defined in claim 1 and R 5 is Cl-C.-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, Cl-C 6 -acyloxy, benzoyloxy, phenoxy, Cl-C.-alkoxy, C,-C.-alkylamino, di (0 1 -C.-alkyl) amino, C 1 -C 6 -alkylthio, cyano, carboxyl, carbamoyl, C 3 -C,-alkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C 1 -0 6 -acyloxy, benzoyloxy, phenoxy, 0 1 -C.-alkoxy, C 1 -C 6 -alkylamino, d i (A-C 6 -al kyl) amino, Cl-C 6 -alkylthio, cyano, carboxyl or carbamoyl, C 3 -0 8 ,-alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, Cl-C 6 -acyloxy, benzoyloxy, phenoxy, C 1 -C 6 -alkoxy, C 1 -C 6 alkylamino, di (Cl-C.-alkyl) amino, C 1 -C 6 -alkylthio, cyano, carboxyl or carbamoyl, C 4 -C 8 -cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C 1 -C 6 -acyloxy, benzoyloxy, phenoxy, C 1 -C 6 -alkoxy, C,-C, 6 -alkylamino, di (Cl -C,-alkyl) amino, Cl-C 6 -alkylthio, cyano, carboxyl or carbamoyl, C.-C.-cyclo- alkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C 1 -C 6 -acyloxy, benzoyloxy, phenoxy, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylamino, di (Cl -C-alkyl) amino, Cl-C 6 -alkylthio, cyano, carboxyl or carbamoyl, (Cl-C 6 -alkoxy)- (C-C 6 -alkyl), di (0 1 -C 6 -alkylamino)-(Cl-0 6 -alkyl) or (C 3 -C 6 -cycloalkyl)alkyl, (0 6 -0 8 -cycloalkenyl)alkyl, or arylalkyl, naphthylalkyl or heteroaryllkyl, each of which is substituted by up to five radicals R 6 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 R 5 is hydrogen and X is oxygen and the definitions mentioned in claim 1 apply to R 1 R R 3 and R with a carbonyl compound of the formula XVI, where R" and are identical or different and independently of one another are hydrogen, Cl-C 7 -alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C 1 -0 6 -aCYloxy, benzoyloxy, phenoxy, Cl-C.-alkoxy, C,-C.-alkylamino, di PC, -C 6 -alkyl) amino, C 1 -C 6 -alkylthio, cyano, carboxyl or carbamoyl, C 3 -C7-alkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, Cl-C-acyoxy, HOE 91/F 111 K Wbenzoyloxy, phenoxy, Cl-C 6 -alkoxy, Cl-C6-ai kylamino, di(C 1 -C 6 -alkyl)amino, C, -C 6 -alkylthio, cyano, carboxyl or carbamoyl, C 3 -C 7 -alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C,-C, 6 -acyloxy, benzoyloxy, phenoxy, C,-C.-alkoxy, C 1 -C, 6 -alkylamino, di (C0 1 -Cr 6 -alkyl) amino, C,-C 6 ,-alkylthio, cyano, carboxyl or carbamoyl, C 4 -C 8 -cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, Cl-0 6 -acyloxy, benzoyloxy, phenoxy, C, -Cr 6 -alkoxy, C, -C 6 -alkylamino, di (C 1 -C 6 -alkyl)amino, C 1 -C 6 -alkylthio, cyano, carboxyl or carbamoyl, C.-cycloalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, hydroxyl, C 1 -C 6 -acyloxy, benzoyloxy, phenoxy, Cl-C 6 -alkoxy, C 1 -C 6 -alkylamino, di (C,-C.-alkyl) amino, C,-C.-alkylthio, cyano, carboxyl or carbamoyl, -C.-alkcxy/)-(Cl-C 5 -alkyi), [di (Cl-C.alkyl) amino] -(Cl-C.-alkyl) or (C 4 -C 6 -Cccoalkyl) alkyl, (C 6 -cycloalkenyl)alkyl, or arylalkyl, naphthylalkyl or heteroarylalkyl, each of which is substituted by up to five radicals R' 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 can be linked to each other to form a 4- to 8-membered ring, or 1) preparing compounds of the formula I where X is oxygen and R 2 R 3 and R' are as defined in claim 1 and R 5 is C,-C.-alkyloxycarbonyl, C,-C 8 -alkylthiocarbonyl, C 2 -C,-alkenyloxycarbonyl, C 2 -C,-alkenylthiocarbonyl, C 2 -C,-alkynyloxycarbonyl, C 1 -C 6 -alkylaminocarbonyl, C,-C 6 -alkenylaminocarbonyl, di (C-0 6 -alkyl)aminocarbonyl, pyrrolidin-1 -yl, morpholino-, piperidino-, piperazinyl-, 4-methylpiperazin-1-ylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cl-C, 6 -acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C, 6 -alkoxy, C 1 -C 6 -alkylamino, di(C 1 -C 6 -alkyl)amino, Cl-C 6 -alkylthio, Cl-C 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; or aryloxycarbonyl arylthio (carbonyl), arylaminocarbonyl, heteroaryloxycarbonyl, heteroarylthiocarbonyl, heteroarylaminocarbonyl, arylalkyloxycarbonyl, (aryl- Fhe\ Aay-o-r-Y I o.Ak"1I- Oxcc,,A, o^v.A alkylthio) carbonv1, arylalkylaminocarbonyl, heteoaW4kxGabI--+ C tk4ro-' 0~o 11 e-~ccr-/ i allo44~ k-yIM (boto±e-oaIkytio-ilrbonyl or heteroalky'!aminocnar-bmn4 each of which is substituted by up to five radicals R 6 which are independent of one another, it being possible for 140 the alkyl radical to contain in each case 1 to 3 carbon atoms, by reacting a compound of the formula XVII R2 N X R1, n R XVII R4 N N: R 4 (CH 2 )n U where the definitions mentioned in claim 1 apply to Ri, 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 whr Nu-H (XVIII) *where Nu is C 1 -C 8 -alkoxy, C 2 -Ca-alkenyloxy, C2-O8-alkynyloxy, Cl-C-alkylthio, C 2 -C 8 -alkenylthio, C 1 -CB-alkylamino- and di(C 1 -C 8 -alkyl)amino, and C2-C8- alkenylamino- optionally substituted by fluorine, chlorine, bromine, hydroxyl, C,- C 4 -alkoxy, C1-C4-alkylamino, di(C 1 -C 4 -alkyl)amino, C1-C 4 -alkylthio, pyrrolidin-1- yl, morpholino-, piperidino-, piperazinyl- or 4-methylpiperazin-1-ylcarbonyl, optionally substituted by C 1 -C 4 -alkyl, C2-C 6 -alkenyl, C1-C4-acyl, oxo, thioxo, carboxyl or phenyl, or aryloxy, arylthio, arylamino, arylalkyloxy, arylalkylthio, *0*9 arylalkylamino, heteroaryloxy, heteroarylthio, heteroarylamino, heteroaryl- alkyloxy, heteroarylalkylthio or heteroarylalkylamino, each of which is substituted by up to five radicals R6 (R6 is as 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. A pharmaceutical comprising an effective amount of at least one compound of the formula la as claimed in one or more or claims 1-3 in adjunct with pharmaceutically acceptable carriers and excipients. 141 6. A process for the preparation of a pharmaceutical as claimed in claim which comprises formulating an effective amount of a compound of the formula I or la together with customary pharmaceutical auxiliaries to give a suitable dosage form. 7. A method of treatment of diseases caused by viruses, in particular diseases caused by HIV, comprising administering to a patient requiring such treatment, an effective amount of a compound of the formula I or la R 2 R4 X 9. R' R (Ia) R3 9. Rs R 4 R Na X 2 *R Sin which the individual substituents Ri independently of one another are fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, hydroxyl, 1 -Calkyl, Cs-Cs-cycloalkyl, Ci -COs-alkoxy, (C 1 -C 6 -alkoxy)-(C 1 in whi-alkoxy), n is zero, one, two, three or four, the individual substituents RI independently of one another are fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, hydroxyl, CI-Cs-alkyl, C5-C8-cycloalkyl, C1-Cs-alkoxy, (Ci-C6-alkoxy)-(Cl- y C4-alkoxy), HOE 91/F 111 K C 1 -C 6 -alkylthio, Cl-C6-alkylsulfinyl, Cl -Cd-alkylsulfonyl, nitro, amino, azido, C 1 -C 6 -alkylamino, di (C 1 -C 6 -alkyl)amino, piperidino, morpholino, I -pyrrolldinyl, 4-methylpiperazinyl, thiomorpholino, imidazolyi, triazolyl, tetrazolyl, C,-C, 6 -acyl, C,-C 6 -acyloxy, C 1 -C 6 -acylamino, cyano, carbamoyl, carboxyl, (C -C 6 -alkyl)oxycarbon 1, hydroxysulfonyl, sulfamnoyl or a phenyl, phenoxy, phenoxycarbonyl, phenylthio, phenylsufinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy, anilinosulfonyl, phenylsulfonylamirio, benzoyl, 2-pyridyl, 3-,pyridyl or 4-pyridyl radical which is substituted by up to five radicals R 6 which are independent of one another, where R 6 can be fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, :nitro, amino, azido, Cl-C 6 Ilkyl, C 3 -C 8 -CYCloalkyl, 0 1 -C 6 -alkoxy, Cl-C 6 -alkylthio, 0 00 0 Cl-C.-alkylsulfinyl, Cl-C 6 -alkylsulfonyl, Cl-C6-alkylamino, di(Cl-C 6 -alkyl)amino,

600.0: (C 1 -0 6 -'-alkyl)oxycarbonyl, phenyl, phenoxy, 3- or 4-pyridyl, R 2 and R 5 are identical or different and independently of one another are hydrogen, hydroxyl, Cl-C 6 -alkoxy, aryloxy, CI-C 6 -acyloxy, cyano, amino, C, -C 6 -alkylamino, di (C 1 -C 6 -alkyl)amino, arylamino, C 1 -C 6 -acylamino, C,-C.-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, .Q.**Cl-C 6 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C,-C 6 -alkoxy, Cl -C 6 -alkylamino, di (C 1 -C 6 -alkyl) amino, C, -C, 6 -alkylthio, C 1 -C 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C 2 -C,-alkenyl, optionally substituted by '11 HOE 91/F 111 K (Th fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, Cl-C.-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-Cr 6 -alkoxy, C 1 -C, 5 -alkylamino, di -C.-aikyi)amino, C 1 -C.-aikyithio, Cl-C.-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl and carbamoyl; C 3 -C,-allenyl, optionally substituted by fluorine, chlorine or hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; C, 3 ,C. 3 -alkynyI, optionally substituted by fluorine, ohiorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C,-C 6 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C.-alkoxy, C, -C6-alkylamino, di (CI -C.-alkyl) amino, C, C-ly~ho Cl-C 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C 3 -Cg-cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C 1 -C.-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-Cr,-alkoxy, Cl-C.-alkylamino, di(C 1 -C,,-alkyl)amino, C,-C.-alkylthio, C,-C.-alkylsi.'1onyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C 3 -C,-cycloalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, fImercapto, hydroxyl, C,-C.-acyioxcy, benzoyloxy, benzyloxy, phenoxy, Cl-C, 6 -alkoxy, C 1 -C6-al kyl amino, di (C,-C.-alkyl) amino, 0 1 -C.-alkylthio, C 1 -C 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; (C 3 -C 8 -cycloalkyl)-(C-C 4 -alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C 1 -Cr,-acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C 6 -alkoxy, HOE 91/F' 111 K C 1 -C 6 -alkylamino, di(C 1 -C 6 -alkyl)amino, C,-C.-al kylthio, C,-C.-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; (C 3 -C 8 -CYCloalkenyl)-(C 1 -C 4 -alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C,-C.-acyloxy, benzoyloxy, benzyloxy, phenoxy, C,-C.-alkoxy, Cl-C.-alkylamino, di (Cl-C.-alkyl)amnino, Cl-C.-alkylthio, Cl-C.-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; Cl-C.-alkylcarbojnyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxyl, C,-0 6 .acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C6-alkoxy, C,-0 6 -alkylamino, d i(CI -C,-alkyl) amino, C,-C.-alkylthio, Cl-C 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxyl or carbamoyl; C 2 -C,-alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; (C 3 -C,-cycloalkyl)carbonyi, optionally substituted by fluorine, chlorine or hydroxyl, C, -C 4 -alkoxy, oxo, phenyl; (0 5 ,-C.-cycloalkenyl)carbonyl, optionally substituted by fluorine, chlorine or .4t; hydroxyl, Cl-C 4 -alkoxy, 3xo, phenyl; (C 3 -C 8 -cycloalkeyl)-(C -C 3 -alkyl)carbonyl, optionally substituted by fluorine, chlorine or thydroxyl, CI-C 4 -alkoxy, oxo, phenyl; HOE 91/F 111 K C 1 -C.-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino, di(C 1 -C 4 alkyl)amino, C 1 -C 4 -alkylthio; C 2 -C,-alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; C 2 -C 8 ,-alkynyloxycarbonyl, optionally substituted by fiorine, chlorine, hydroxyl, C 1 -C 4 -al koxy, oxo, phenyl; Cl-C.-alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 alkoxy, oxo, phenyl; C 2 -C.-alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -al koxy, oxo, phenyl; C 1 -C.-alkylamino- and dI (C 1 -C.-alkyl) aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, C 1 -C 4 -alkoxy, oxo, phenyl; pyrrolidin-1 -yl, morpholino-, piperidino-, piperazinyl-, or 4-methylpiperazin- 1-ylcarbonyl, in each case optionally substituted by Cl-C 4 -alkyl, C.-C 6 -alkenyl, Cl-C 4 -acyl, oxo, thioxo, carboxyl, or phenyl; P. C 2 -0 8 -alkenylamino- and di (CCC 6 -alkenyl)aminocarbonyl, in each case optionally substituted by fluorine, chlorine, hydroxyl, Cl-C 4 -alkoxy, oxo, phenyl; .o 1 -C6-alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, C 1 -C 4 -alkoxy, oxo, phenyl; C,:C 6 -alkenylsulfonyl, optionally substituted by fluorine, chlorine, hydroxyl, C 1 -C 4 -alkoxy, oxo, phenyl; 'T or arlrylcarbonyl, aryl(thiocarbonyl), (arylthio)carbonyl, <A) 04,5 HOE 91/17111 K (arylthio)thiocarbonyl, aryloxycarbonyl, arylaminocarbonyl, (arylamino)thio- carbonyl, arylalkylaminocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl or aryl(alkylthio)carbonyl, each of which is substituted by up to five radicals R' which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 5 carbon atoms, and R 6 being as defined above, or heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarboiyl or heteroarylalkenylcarbonyl, heteroaryloxycarbonyl, (heteroarylthio)carbonyl, heteroaryl 1 aminocarbonyl, heteroarylalkyloxycarbonyl, 'hateroaryl (alkylthio)carbonyl or heteroarylalkylaminocarbonyl, each of which is substituted by up to three radicals R 6 which are independent of one another, it being possible for the alkyl radical to contain in each case 1 to 3 carbon atoms, R 3 and R 4 are identical or different and, independently of one another, are hydrogen, C 1 -C 8 -alkyl which is optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, Cl-0 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C 4 -alkoxy, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, C, -0 4 -alkylthio, Cl -C 4 -alkylsulfonyl, C 1 -C 4 -alkylsulfinyl, carboxyl or carbamoyl; C 2 -C,-alkenyl, optionally substituted by fluorine or chlorine, hydroxy, amino, mercapto, C 1 -C 4 -acyloXY, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 -alkoxy, Cl-C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, C 1 -C 4 -alkylthio, Cl-C 4 -alkylsulfonyl, Cl-C 4 -alkylsulfinyl, carboxyl or carbarnoyl; C.-C 8 -cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, Cl-C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, Cl-C 4 -alkoxy, 0 1 -C 4 -alkylamino, di(Cl-C 4 -alkyl)amino, C 1 -0 4 -alkylthio, Cl-C 4 -alkylsulfonyl, C 1 -C 4 -alkylsulfilnyl, carboxyl or carbamoyl; )fd HOE 91/FI111 K C 3 -C 8 -CYCloalkenyl, optionally substituted by fluorine or chlorine, hydroxyl, amino, mercapto, C 1 -C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, Cl-C' 4 -alkylamino, di (C,-C 4 -alkyl)amino, C 1 -C 4 -alkylthio,CC- alkylsulfonyl, Cl-C 4 -alkylsylfinyl, carboxyl or carbamoyl; aryl, arylalkyl, heteroaryl or heteroarylalkyl, each of which is substituted by up to five radicals R 6 which are independent of one another, it being possible for the alkyl radical to contain 1 to 3 carbon atoms in each case, and R' being as defined above, R 3 and R 4 or R 3 and R 5 can furthermore also be part of a saturated or unsaturated carbo- or heterocyclic ring which has 3 to B carbon atoms and which can optionally be substituted by fluorine, chlorine, 15 hydroxyl, amino, C 1 -0 6 -alkyl, C 2 -0 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 ,-C 6 ,-acyloxy, benzoyloxy, Cl-C.-alkoxy, oxo, thioxo, carboxyl, carbamoyl or phenyl, Soo X is oxygen, sulfur, selenium or substituted nitrogen N-R it being possible for R 2 to have the abovementioned meanings, tor teprpatoofhrm -Getalfr th ttm n f diseases cause -by viruses, inprticular DATED this 13th day of April 1992. HOECHST AKTIENGESELLSCHAFT WATERMARK PATENT TRADEMARK ATTORNEYS "THE ATRIUM" 290 BURWOOD ROAD HAWTHORN. VIC. 3122. r o-v i4