CA2309332C

CA2309332C - 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors

Info

Publication number: CA2309332C
Application number: CA002309332A
Authority: CA
Inventors: Ulrich Niewohner; Mazen Es-Sayed; Helmut Haning; Thomas Schenke; Karl-Heinz Schlemmer; Jorg Keldenich; Erwin Bischoff; Elisabeth Perzborn; Klaus Dembowsky; Peter Serno; Marc Nowakowski
Original assignee: Bayer AG
Current assignee: Bayer Intellectual Property GmbH
Priority date: 1997-11-12
Filing date: 1998-10-31
Publication date: 2002-12-03
Anticipated expiration: 2018-10-31
Also published as: JP2001522851A; BG104406A; PL340400A1; DK1174431T3; NO20021714D0; HRP20000292B1; US7704999B2; SE0001745L; EE200000291A; SE522809C2; US6362178B1; ES2172945T3; AR013759A1; US6890922B2; CA2309332A1; US7696206B2; SI1049695T1; KR100430355B1; HU227841B1; WO1999024433A1

Abstract

The 2-phenyl-substituted imidazotriazinones having short, unbranched alkyl radicals in the 9-position are prepared from the corresponding 2-phenyl-imidazotriazinones by chlorosulphonation and subsequent reaction with the amines. The compounds inhibit cGMP-metabolizing phosphodiesterases and are suitable for use as active compounds in pharmaceuticals, for the treatment of cardiovascular and cerebrovascular disorders and/or disorders of the urogenital system, in particular for the treatment of erectile dysfunction.

Description

23189-8549(S)

2-Phenyl-substituted imidazotriazinones as phosphodiesterase inhibitors The present invention relates to 2-phenyl-substituted imidazotriazinones, to processes for their preparation and to their use as pharmaceuticals, in particular as inhibitors of cGMP-metabolizing phosphodiesterases.
The published specification DE 28 11 780 describes imidazotriazines as bronchodilators having spasmolytic activity and inhibitory activity a5~ainst phosphodiesterases which metabolize cyclic adenosin monophosphate (cA.~I~IP-PDEs, nomenclature according to Beavo: PDE-III and PDE-N). An inhibitory action against phosphodiesterases which metabolize cyclic guanosin monophosphate (cGMP-PDEs.
nomenclature according to Beavo and Reifsnyder (Trends in Pharmacol. Sci. 11, 150-155, 1990) PDE-I, PDE-II and PDE-V) has not been described. Compounds having a sulphonamide group in the aryl radical in the 2-position are not claimed.
Furthermore, FR 22 13 058, CH ~9 46 71, DE 22 » 172, DE 23 64 076 and EP 000 9384 describe imidazotriazinones which do not have a substituted aryl radical in the 2-position and are likewise said to be bronchodilators having cAMP-PDE
inhibitory action.
WO 94/28902 dcscribes pyrazolopyrimidinones which are suitable for treating Impotence.
The compounds according to the invention are potent inhibitors either of one or of more of the phosphodiesterases which metabolize cyclic guanosin 3'.5'-monophosphate (cGMP-PDEs). According to the nomenclature of Beavo and Reifsnyder (Trends in Pharmacol. Sci. 11, 150-155, 1990) these are the phosphodiesterase isoenzymes PDE-I, PDE-11 and PDE-V.
An increase of the cGMP concentration can lead to beneficial antia~~regatory, antithrombotic, antiprolific, antivasospastic, vasodilative, natriuretic and diuretic effects. It can influence the short- or long-term modulation of vascular and cardiac ' Le A 32 733-Foreisn countries inotropy, of the pulse and of cardiac conduction (1.C. Stoclet, T. Keravis, N.
Komas and C. Kugnier, Exp. Opin. Invest. Drugs ( 1995), 4 ( 11 ), 1081-1100).
The present invention, accordingly, provides 2-phenyl-substituted imidazotriazinones of the general formula (1) Rs ~"'"°~ ~ 1' ,N. 1 - (1) R
in which R' represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, R'' represents straight-chain alkyl having up to 4 carbon atoms, R3 and R4 are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to 8 carbon atoms, or represents a straight-chain or branched alkyl chain having up to 10 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of trifluoromethyl, trifluoromethoxy, hydroxyl, halogen, carboxyl, benzyloxycarbonyl, straight-chain or branched alkoxycarbonyl having up to 6 carbon atoms and/or by radicals of the formulae -S03H, -(A)a NR'R8, -O-CO
NR~~RB~, -S(O)b-R9, -P(O)(OR'°)(OR' ~), Le A 32 733-Foreign countries

-3-F O
O
F O
F ' O and/or O O
O
in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or 502, R', R~~, R8 and R8~ are identical or different and each represents hydrogen, or represents cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms, a 5- to 6-membered unsaturated, partially unsaturated or saturated, optionally benzo-fused heterocycle having up to 3 heteroatoms from the group consisting of S, N
and O, where the abovementioned ring systems are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, vitro, trifluoromethyl, trifluoromethoxy, carboxyl, halogen, straight chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms or by a group of the formula -{S02)~
NR~2R~3, in which L,e A 32 ?33-Foreisn countries

-4-c represents a number 0 or 1, R~2 and R~3 are identical or different and each represents hydrogen or , straight-chain or branched alkyl having up to 5 carbon atoms, or R', R~~, R8 and R8~ each represent straight-chain or branched alkoxy having up to 6 carbon atoms, or represents straight-chain or branched alkyl having up to $ carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, halogen, aryl having 6 to 10 carbon atoms, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms or by a group of the formula -(CO)d-NR~4Ris, in which R~4 and R~5 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and d represents a number 0 or 1, or R' and R8 and/or R~~ and R8~ together with the nitrogen atom form a 5- to 7-membered saturated heterocycle which may optionally contain a Le A 32 733-Foreign countries

-5-further heteroatom from the group consisting of S and O or a radical of the formula -NR~6, in which R'6 represents hydrogen, aryl having 6 to 10 carbon atoms, benzyl, a 5- to 7-membered aromatic or saturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and O
which is optionally substituted by methyl, or ~"'" 10 represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl, R9 represents aryl having 6 to 10 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms, R1° and R" are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and/or the alkyl chain listed above under R3/R4 is optionally substituted by cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or by a S- to ?-membered partially unsaturated, saturated or unsaturated, optionally benzo-fused heterocycle which may contain up to 4 heteroatoms from the group consisting of S, N
and O or a radical of the formula -NR~~, in which R~~ represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight=chain or branched acyl or alkoxy having in each case up to 4 carbon atoms, ' I,e A 32 733-Forei n countries

-6-or represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl and straight-chain or branched alkoxy having up to 6 carbon atoms, and where aryl and the heterocycle are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of vitro, halogen, -S03H, straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy andlor by a radical of the formula -S02-NR~8Ri9, in which R~8 and R~9 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms, and/or R3 or R4 represents a group of the formula -NR2°R2', in which R2° and R'~ have the meanings of R~8 and R~9 given above and are identical to or different from them, and/or R3 or R4 represents adamantyl, or represents radicals of the formulae 23189-8549 (S) O ~ ~OH

IC\HO C6H5 . SOZ SOZ

O
Of OU
or represents cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or represents a 5- to 7-membered partially unsaturated, saturated or unsaturated, optionally benzo-fused heterocycle which may contain up to 4 heteroatorns from the group consisting of S, N and O, or a radical of the formula -NR", in which R'''' has the meaning of R~6 given above and is identical to or different from it, or represents carboxyl, formyl or straight-chain or branched acyl having up to 5 carbon atoms, and where cycloalkyl, ,uyl and/or the heterocycle are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, triazolyl, trifluoromethyl, trifluoromethoxy, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro and/or by groups of the formulae -SO~H, -OR'3, (SO~)~NR'°R''S, -P(O)(OR'6)(OR'~), in which ~
Le A 32 733-Foreign countries _g_ a represents a number 0 or 1, R23 represents a radical of the formula or O~O
represents cycloalkyl having 3 to 7 carbon atoms, or represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms which is optionally substituted by cycloalkyl having 3 to

7 carbon atoms, benzyloxy, tetrahydropyranyl, tetrahydrofuranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, carboxyl, benzyloxycarbonyl or phenyl which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkoxy having up to 4 carbon atoms, hydroxyl and halogen, and/or alkyl which is optionally substituted by radicals of the formulae "'! -CO-NR28R'9 or -CO-R3o, in which R2$ and R''9 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 8 carbon atoms, or R''8 and R'9 together with the nitrogen atom form a 5- to 7-membered saturated heterocycle which may optionally contain a further heteroatom from the group consisting of S and O, Le A 32 733-Foreign countries and R3° represents phenyl or adamantyl, S
R24 and R25 have the meanings of R'$ and R'9 given above and are identical to or different from them, R26 and R27 have the meanings of R'° and R'' given above and are identical to "'"~~, 10 or different from them and/or cycloalkyl, aryl and/or the heterocycle are optionally substituted by straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl, carboxyl, by a 5- to 7-membered 15 heterocycle having up to 3 heteroatoms from the group consisting of S, N
and O, or by groups of the formula -S02-R3', P(O)(OR3'')(OR33) or -NR34R3s, in which 20 R3' represents hydrogen or has the meaning of R9 given above and is identical to or different from it, R32 and R33 have the meanings of R~° and R' ~ given above and are identical to or different from them, R34 and R35 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl or by straight-chain or branched alkoxy having up to 4 carbon atoms, or Le A 32 733-Foreign countries R'~ and R35 together with the nitrogen atom form a 5- to 6-membered saturated heterocycle which may contain a further heteroatom from the group consisting of S and O, or a radical of the formula -NR36, . in which R36 represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 7 carbon atoms or straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl, or R3 and R4 together with the nitrogen atom form a 5- to 7-membered unsaturated or saturated or partially unsaturated, optionally benzo-fused heterocycle which may optionally contain up to 3 heteroatoms from the group consisting of S, N and O, or a radical of the formula -NR3~, in which R3' represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, trifluoromethyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, or by groups of the formula .. Le A 32 733-Foreign countries -(D) fNR38R39~ -CO-(CH2)g-O-CO-R'°, -CO-(CH2)n-OR4~ or -P(O)(OR42)(OR43), in which g and h are identical or different and each represents a number 1, 2, 3 or 4, and f represents a number 0 or 1, D represents a group of the formula -CO or -S02, R;$ and R39 are identical or different and each has the meaning of R' and R$ given above, R4° represents straight-chain or branched alkyl having up to 6 carbon atoms, R4~ represents straight-chain or branched alkyl having up to 6 carbon atoms, Ra2 and R43 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or R;' represents a radical of the formula -(CO);-E, .
in which L,e A 32 733-Forei ng~countries i represents a number 0 or 1, E represents cycloalkyl having 3 to 7 carbon atoms or benzyl, represents aryl having 6 to 10 carbon atoms or a 5- to 6-membered aromatic heterocycle having up to 4 heteroatoms from the group consisting of S, N and O, where the abovementioned ring systems are optionally mono- or polysubstituted by identical or different constituents selected from the group consisting of nitro, halogen, -S03H, straight-chain or branched alkoxy having up to 6 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy, or by a radical of the formula -S02-NR'4R4s, in which R~ and R45 have the meanings of Rl8 and R~9 given above and are identical to or different from them, or E represents radicals of the formulae '' .CH3 _ N~O~N~O. , ~./
or - ~ , Le A 32 733-Forei n countries and the heterocycle listed under R3 and R4, which is formed together with the nitrogen atom, is optionally mono- or polysubstituted, if appropriate also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 6 carbon atoms, vitro and groups of the formulae -P(O)(OR"~)(OR4'), O
=NR°e or -(GO).NR°9Rso O , in which R°6 and R4' have the meanings of R'° and R' ~ given above and are identical to or different from them, R4$ represents hydroxyl or straight-chain or branched alkoxy having up to 4 carbon atoms, j represents a number 0 or 1, and R49 and RS° are identical or different and have the meanings of R~4 and R~5 given above, and/or the heterocycle listed under R'~ and R4, which is formed together with the nitrogen atom, is optionally substituted by straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different L.e A 32 733-Foreisn countries substituents selected from the group consisting of hydroxyl, halogen, carboxyl, cycloalkyl or cycloalkyloxy having in each case 3 to 8 carbon atoms, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, or by a radical of the formula -S03H, -NRS~RS'- or P(O)OR530RSa, in which RS ~ and R52 are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, R5~ and R54 are identical or different and have the meanings of Rt°
and R~ ~ given above, and/or the alkyl is optionally substituted by aryl having 6 to 10 carbon atoms which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, hydroxyl, straight-chain or branched alkoxy having up to 6 carbon atoms, or by a group of the formula -NRS~~RS'~, in which RS~~ and RS''~ have the meanings of R5~ and R52 given above and are identical to or different from them, and/or the heterocycle listed under Ri and R°, which is formed together with the nitrogen atom, is optionally substituted by aryl having 6 to 10 carbon atoms or by a 5- to 7-membered saturated, partially unsaturated or unsaturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, optionally also ~
Le A 32 733-Foreign countries attached via a nitrogen function, where the ring systems for their part may be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, or R3 and R4 together with the nitrogen atom form radicals of the formulae - _ N,(CH2)3 CH3 NJ ~II
O N
CH3 ~ N+
C
O
o~
, N+
i~
CH~H3 RS and R6 are identical or different and each represents hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, hydroxyl or represents straight-chain or branched alkoxy having up to 6 carbon atoms, and their salts, hydrates, N-oxides and isomeric forms.
The compounds according to the invention may exist in stereoisomeric forms which are related either as image and mirror image (enantiomers), or which are not related as image and mirror image (diastereomers). The invention relates both to the enantiomers or diastereomers and to their respective mixtures. The racemic forms can, just like the ~
Le A 32 733-Foreign countries diastereomers, be separated in a known manner into the stereoisomerically pure constituents.
The substances according to the invention may also be present as salts. In the context of the invention, preference is given to physiologically acceptable salts.
Physiologically acceptable salts can be salts of the compounds according to the invention with inorganic or organic acids. Preference is given to salts with inorganic acids, such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid or sulphuric acid, or to salts with organic carboxylic or sulphonic acids, such as, for example, acetic acid, malefic acid, fumaric acid, malic acid, citric acid, tartaric acid, lactic acid, benzoic acid, or methanesulphonic acid, ethanesulphonic acid, phenylsulphonic acid, toluenesulphonic acid or naphthalenedisulphonic acid.
Physiologically acceptable salts can also be metal or ammonium salts of the compounds according to the invention. Particular preference is given to, for example, sodium, potassium, magnesium or calcium salts, and also to ammonium salts which are derived from ammonia or organic amines, such as, for example, ethylamine, di-or triethylamine, di- or triethanolamine, dicyclohexylamine, dimethylaminoethanol, arginine, lysine, ethylenediamine or 2-phenylethylamine.
In the context of the invention, an optionally ~benzo-fused heterocycle generally represents a saturated, partially unsaturated or unsaturated S- to 7-membered heterocycle which may contain up to 4 heteroatoms from the group consisting of S, N
and O. Examples which may be mentioned are: azepine, diazepine, indolyl, isoquinolyl, quinolyl, benzo[bJthiophene, benzo[b]furanyl, pyridyl, thienyl, tetrahydrofuranyl, tetrahydropyranyl, furyl, pyrrolyl, thiazolyl, triazolyl, tetrazolyl, isoxazolyl, imidazolyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, piperazinyl, N-methylpiperazinyl or piperidinyl. Preference is given to quinolyl, furyl, pyridyl, thienyl, piperidinyl, pyrrolidinyl, piperazinyl, azepine, diazepine, thiazolyl, triazo(yl, tetrazolyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl and thiomorpholinyl.
CA 02309332 2000-OS-09 ' Le A 32 733-Foreign countries In the context of the invention, a straight-chain or branched acyl radical having 1 to 6 carbon atoms represents, for example acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, butylcarbonyl, isobutylcarbonyl, pentylcarbonyl and hexylcarbonyl.
Preference is given to a straight-chain or branched acyl radical having 1 to 4 carbon atoms. Particular preference is given to acetyl and ethylcarbonyl.
In the context of the invention, a stnai~ht-chain or branched alkox~ having 1 to 6 or 1 to 4 carbon atoms represents methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, n-pentoxy and n-hexoxy. Preference is given to a straight-chain or branched alkoxy radical having 1 to 6, 1 to 4 or 1 to 3 carbon atoms. Particular preference is given to a straight-chain or branched alkoxy radical having 1 to 3 carbon atoms.
In the context of the invention, a straight-chain or branched alkoxycarbonyl radical having 1 to 6 carbon atoms represents, for example, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl and tert-butoxycarbonyl. Preference is given to a straight-chain or branched alkoxycarbonyl radical having 1 to 4 carbon atoms.
Particular preference is given to a straight-chain or branched alkoxycarbonyl radical having 1 to 3 carbon atoms.
In the context of the invention, a straisht-chain or branched alkyl radical having 1 to 4, 1 to 6, 1 to 8 and 1 - 10 carbon atoms represents, far example, methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl and n-decyl.
Preference is given to straight-chain or branched alkyl radicals having 1 to 3, 1 to 4 or 1 to 8 carbon atoms. Particular preference is given to straight-chain or branched alkyl radicals having 1 to 4 or 1 to 3 carbon atoms.
In the context of the invention, straight-chain alkyl having up to 4 carbon atoms represents, for example, methyl, ethyl, n-propyl and n-butyl. .

Le A 32 733-Foreign countries f C~-C,o~Ar~ generally represents an aromatic radical having 6 to 10 carbon atoms.
Preferred aryl radicals are phenyl and naphthyl.
In the context of the invention, cycloalkyl havin;~ 3 to 8 or 3 to 7 carbon atoms S represents, for example, cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl, cycloheptyl or cyclooctyl. Preference is given to: cyclopropyl, cyclopentyl and cyclohexyl.
In the context of the invention, cycloalkylox having 3 to 8 carbon atoms represents cyclopropyloxy, cyclopentyloxy, cyclobutyloxy, cyclohexyloxy, cycloheptyloxy or cyclooctyloxy. Preference is given to: cyclopropyloxy, cyclopentyloxy and cyclohexyloxy.
In the context of the invention, halogen generally represents fluorine, chlorine, bromine and iodine. Preference is given to fluorine, chlorine and bromine.
Particular preference is given to fluorine and chlorine.
In the context of the invention and depending on the abovementioned substituents, a 5-to 6-membered or 7-membered saturated heterocycle, which may contain a further heteroatom from the group consisting of S, N and O represents, for example, morpholinyl, piperidinyl, piperazinyl, tetrahydropyranyl or tetrahydrofuranyl.
Preference is given to moipholinyl, tetrahydropyranyl, piperidinyl and piperazinyl.
In the context of the invention, a S- to 6-membered aromatic heterocycle having up to 3 or 4 heteroatoms from the group consisting of S, O and N represents, for example, pyridyl, pyrimidyl, pyridazinyl, thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl or imidazolyl. Preference is given to pyridyl, pyrimidyl, pyridazinyl, furyl and thiazolyl.
In the context of the invention, a S- to 6-membered unsaturated,_partially unsaturated and saturated heterocycle which may contain up to 3 or 4 heteroatoms from the group consisting of S, O and N represents, for example, pyridyl, pyrimidyl, pyridazinyl, thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, piperidinyl, piperazinyl or Le A 32 733-Foreign countries morpholinyl. Preference is given to pyridyl, pyrimidyl, piperazinyl, pyridazinyl, morpholinyl, furyl and thiazolyl.
The compounds according to the invention, in particular the salts, may also be present as hydrates. In the context of the invention, hydrates are those compounds which contain water in the crystal. Such compounds may contain one or more, typically 1 to 5, equivalents of water. Hydrates can be prepared, for example, by crystallizing the compound in question from water or from a water-containing solvent.
,, 10 Preference is given to compounds of the general formula (I) according to the invention in which R~ represents straight-chain or branched alkyl having up to 3 carbon atoms, R' represents straight-chain alkyl having up to 3 carbon atoms, R3 and R4 are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to 6 carbon atoms, or .
represents a straight-chain or branched alkyl chain having up to 8 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- to trisubstituted by identical or different constituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, benzyloxycarbonyl, straight-chain or branched alkoxycarbonyl having up to 5 carbon atoms; and/or by radicals of the formulae -S03H, -(A)~ NR~RB, -O-CO-NR~~RB~, -S(O)b-R9, -P(O)(OR~°)(OR~ ~), Ix A 32 733-Foreisn countries ° ° 1 O
i i ° ' i ° and/or O O
O
in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or SO~, R', R'', R$ and R$' are identical or different and each represents hydrogen, or cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, piperidinyl ''"~ and pyridyl, where the abovementioned ring systems are optionally mono- to trisubstituted by identical, or different substituents selected from the group consisting of hydroxyl, vitro, trifluoromethyl, trifluoromethoxy, carboxyl, fluorine, chlorine, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a group of the formula -(SO~)~ NR~''R~3, in which c represents a number 0 or 1, Le A 32 733-Foreign countries R~2 and R~3 are identical or different and each represcnts hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or S
R', R'~, R$ and R8~ each represent straight-chain or branched alkoxy having up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 7 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, phenyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a group of the formula -(CO)d-NR~4R~5, in which R" and R~5 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and d represents a number 0 or 1, or R' and R8 andlor R'~ and R8~ together with the nitrogen atom form a pyrrolidinyl, morpholinyl, piperidinyl or triazolyl ring or radicals of the formulae Le A 32 733-Foreign countries ~3 N--N a - S

-N N_R~s ~ _ ,s or ~ ~ R
in which S R'6 represents hydrogen, phenyl, benzyl, morpholinyl, pyrrolidinyl, piperidinyl, piperazinyl or N-methylpiperazinyl, or represents straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl, R9 represents straight-chain or branched alkyl having up to 3 carbon atoms, R'° and R~ ~ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and/or the alkyl chain listed under R3/R4 is optionally substituted by cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, pyridyl, quinolyl, pyrrolidinyl, pyrimidyl, moipholinyl, furyl, piperidinyl, tetrahydrofuranyl or by radicals of the formulae O~O -N N-R"
or in which L,e A 32 733-Foreign countries R" represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl or alkoxy having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl and straight-chain or branched alkoxy having up to 4 carbon atoms, and where phenyl and the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, -S03H, straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms, hydroxyl, and/or by a radical of the formula -S02_NR18R~9, in which R'8 and R'9 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and/or R3 or R4 represents a group of the formula -NR''°R''~, in which R2° and R'-~ have the meanings of R~g and, R~9 given above and are identical to or different from them, and/or i ' 23189-8549 (S) R3 or R4 represents adamantyl, or represents radicals of the formulae O ~ OH

,C\HO CsHs ~ SOZ S02 O
Of O
or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl, morpholinyl, oxazolyl, thiazolyl, quinolyl, isoxazolyl, pyridyl. tetrahydrofuranyl, tetrahydropyranyl or represents radicals of the formulae -NON-R~ -N
N-R~
or N , I~
R
in which R'' has the meaning of R~6 given above and is identical to or different from it, or represents carboxyl, formyl or straight-chain or branched acyl having up to 3 carbon atoms, Le A 32 733-Foreign countries and where cycloalkyl, phenyl and/or the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, triazolyl, trifluoromethyl, trifluoromethoxy, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 5 carbon atoms, nitro and/or by groups of the formulae -S03H, -OR23, (SOz)~NR24R~5, -Pt0)~OR26OOR2~), in which a represents a number 0 or 1, R2; represents a radical of the formula or O ~O
represents cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl or cycloheptyl, represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms which may optionally be substituted by cyclopropyl, cyclopentyl, ~yclohexyl, benzyloxy, tetrahydropyranyl, tetrahydrofuranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, benzyloxycarbonyl or phenyl which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkoxy having up to 3 carbon atoms, hydroxyl, fluorine and chlorine, Le A 32 733-Foreign countries and/or where alkyl is optionally substituted by radicals of the formulae -CO-NR28R29 or -CO-R3o, in which R28 and R29 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms, or "' 10 R2$ and R29 together with the nitrogen atom form a morpholinyl, pyrrolidinyl or piperidinyl ring, and 1 S R3° represents phenyl or adamantyl, R2' and R''5 have the meanings of R'8 and R'9 given above and are identical to or different from them, 20 R26 and R''' have the meanings of R'° and R" given above and are identical to or different from them and/or cycloalkyl, phenyl and/or the heterocycles are optionally substituted by straight-chain or branched alkyl having up to 4 carbon 25 atoms which is optionally substituted by hydroxyl, carboxyl, pyridyl, pyrimidyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, triazolyl or by groups of the formula -SO~-R3', -P(O)(OR32)(OR33) or -NR34R3s, in which Le A 32 733-Foreign countries R3' has the meaning of R9 given above and is identical to or different from it, R32 and R33 have the meanings of R'° and R" given above and are identical to or different from them, R34 and R35 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl or straight-chain or branched alkoxy having up to 3 carbon atoms, or R34 and R35 together with the nitrogen atom form a morpholinyl, triazolyl or thiomorpholinyl ring or a radical of the formula -N N-R~
in which R36 represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 5 carbon atoms or straight-chain or branched alkyl having up to 4 carbon atoms which is optionally substituted by hydroxyl, or R; and R4 together with the nitrogen atom form a morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl ring, or a radical of the formula ~ L.e A.32 733-Foreign countries -N N-R~' U
in which R3' represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or represents straight-chain or branched alkyl having up to 5 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, trifluoromethyl, carboxyl, straight chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by groups of the formula -(D)f_NR38R39, -CO-(CH2)g-O-CO-R4°, -CO-(CHI),,-ORa~ or -P(O)(OR4'')(OR4s), in which g and h are identical or different and each represents a number l,2or3, ' and f represents a number 0 or 1, D represents a group of the formula -CO or -SO~, R3$ and R39 are identical or different and have the meanings of - 30 R' and R$ given above, Le A 32 733-Foreign countries R4° represents straight-chain or branched alkyl having up to 4 carbon atoms, R4' represents straight-chain or branched alkyl having up to 4 carbon atoms, R42 and R°3 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up '° 10 to 3 carbon atoms, or R3' represents a radical of the formula -(CO);-E , in which i represents a number 0 or 1, E represents cyclopentyl, cyclohexyl, cycloheptyl, benzyl, phenyl, pyridyl, pyrimidyl or furyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, -S03H, straight-chain or branched alkoxy having up to 4 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy or by a radical of the formula -S02-NR~R4s, in which R'~4 and R45 have the meanings of R'g and R'9 given above and are identical to or different from them, Le A 32 733-Forei~~n countries or E represents radicals of the formulae - ~N-CH3 or - ~ , and the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally mono- to trisubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 5 carbon atoms, nitro and groups of the formulae -P(~)(4R~)(~R4~), O
C
O =NR or ~ -(CO)~NR°9Rso in which R°6 and R°' have the meanings of R~° and R~ ~ given above and are identical to or different from them, Le A 32 733-Foreign countries R48 represcnts hydroxyl or straight-chain or branched alkoxy having up to 3 carbon atoms, j represents a number 0 or 1, and R°9 and RS° are identical or different and have the meanings of R" and R'S given above, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 5 carbon atoms which is optionally mono- or polysubstituted by identical or differetlt substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a radical of the formula -S03H, -NRS'R52 or -P(O)OR530RSa, in which RS' and R52 are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms;
R53 and R54 are identical or different and have the meanings of R'°
and R" given above, and/or the alkyl is optionally substituted by phenyl which for its part may be mono- to trisubstituted by identical or different substituents Le A 32 733-Foremen countries selected from the group consisting of fluorine, chlorine, hydroxyl, straight-chain or branched alkoxy having up to 4 carbon atoms, or by a group of the formula -NRS~~RS''~, in which RS ~ ~ and RS''~ have the meanings of RS ~ and R52 given above and are identical to or different from them, ~ and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by phenyl, pyridyl, piperidinyl, pyrrolidinyl or tetrazolyl, optionally also attached via a nitrogen function, where the ring systems for their part rnay be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 5 carbon atoms, or R3 and R4 together with the nitrogen atom form radicals of the formulae N,(CH2)3 CH3 .NJ ~II
CH3 ' O-N
N+
C~

or N+ , CH~H3 Le A 32 733-Foreign countries R3 and R6 are identical or different and each represents hydrogen, hydroxyl or represents straight-chain or branched alkoxy having up to 4 carbon atoms, and their salts, N-oxides, hydrates and isomeric forms.
Particular preference is given to compounds of the general formula (I) according to the invention ~"""~ 10 in which R~ represents straight-chain or branched alkyl having up to 3 carbon atoms, R'' represents straight-chain alkyl having up to 3 carbon atoms, R3 and R4 are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to 4 carbon atoms, or represents a straight-chain or branched alkyl chain having up to 6 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, straight-chain or branched alkoxycarbonyl having up to 4 carbon atoms, and/or by radicals of the formulae -SO~H, -(A)a NR~R8, -O-CO-NR~~R8~, -S(O)b-R9, -P(O)(OR'°)(OR"), ~ Le A 32 733-Foreign countries O ° 1 O
i i O and/or O O
O
in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or S02, R', R'', R8 and R8' are identical or different and each represents hydrogen, or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl, piperidinyl and pyridyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, vitro, carboxyl, fluorine, chlorine, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a group of the formula -(SO~)~ NR~2R~3, in which c represents a number 0 or 1, CA 02309332 2000-OS-09 .

~ L.e A 32 733-Foreign countries R'2 and R'3 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, or R?, R'~, R8 and R8~ each represent methoxy, or represent straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, "~ 10 chlorine, phenyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a group of the formula -(CO)d-NR'4Ris, in which R'4 and R'S are identical or different and each represents hydrogen, methyl or ethyl, and d represents a number 0 or 1, or R' and R$ and/or R~~ and R8~ together with the nitrogen atom form a morpholinyl, piperidinyl or triazolyl ring or radicals of the formulae - Le A 32 733-Forei~,~n countries N /I~---N \ a -- S
.

-N N-R's , ~ . ~s ~ or ~ R
in which R'6 represents hydrogen, phenyl, benzyl, motpholinyl, pyrrolidinyl, piperidinyl, piperazinyl or N-methylpiperazinyl, or represents straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl, R9 represents methyl, R'° and Ri ~ are identical or different and each represents hydrogen, methyl or ethyl, and/or the alkyl chain listed under R3/R' is optionally substituted by cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, morpholinyl, furyl, tetrahydrofuranyl, or by radicals of the formulae O~O _ N_Rn or in which ~
Le A 32 733-Foreign countries R" represents hydrogen, hydroxyl, formyl, acetyl or alkoxy having up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl and straight-chain or branched alkoxy having up to 3 carbon atoms, and where phenyl and the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, -S03H, straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, hydroxyl, and/or by a radical of the formula -SO~_NR'8R'9, in which R'$ and R'9 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and/or R3 or R4 represents a group of the formula -NR2°R2', in which R'° and RZ' have the meanings of R'$ and R'9 given above and are identical to or different from them, and/or i 23189-8549(S) R3 or R4 represents adamantyl, or represents radicals of the formulae O ~ OH
~H3~ I , 1 CHO C6H5 ~ S02 SOZ

O
Of O~ , or represents cyclopentyl, cyclohexyl, cycloheptyl, phcnyl, morpholinyl, oxazolyl, thiazolyl, quinolyl, isoxazolyl, pytidyl, tetrahydrofuranyl, tetrahydropyranyl, or represents radicals of the formulae -N~N-R~ -N
, N R~
or N , I~
. R
in which R''' has the meaning of R~6 given above and is identical to or different from it, or represents formyl or acetyl, and where cycloalkyl, phenyl and/or the heterocycles are optionally mono- or disubstituted by identical or different substituents selected ~
L,e A 32 733-Foreign countries from the group consisting of fluorine, chlorine, triazolyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 4 carbon atoms, nitro, and/or by groups of the formulae -SO~H, -ORS, (S02)~NR24R'-5, -P(O)(ORz6)(OR''~), S
in which a represents a number 0 or 1, R23 represents a radical of the formula or O~O
represents cyclopropyl, cyclopentyl, cyclobutyl or cyclohexyl, represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by cyclopropyl, cyclohexyl, benzyloxy, tetrahydropyranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, benzyloxycarbonyl or phenyl which for its part may be mono- or disubstituted by identical or different substituents selected from the group consisting of methoxy, hydroxyl, fluorine or chlorine, and/or where alkyl is optionally substituted by radicals of the formulae -CO-NR28R29 or -CO-R3°, in which Le A 32 733-Foreign countries _40_ R28 and R~ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or ~ R2$ and R29 together with the nitrogen atom form a moipholinyl, pyrrolidinyl or piperidinyl ring, and R3° represents phenyl or adamantyl, R24 and R25 have the meanings of R'$ and R'9 given above and are identical to or different from them, R'6 and R2' have the meanings of R'° and R" given above and are identical to or different from them and/or cycloalkyl, phenyl and/or the heterocycles are optionally substituted by straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl, carboxyl, pyridyl, pyrimidyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, triazolyl or by groups of the formula -S02-R3', P(O)(OR~'')(OR33) or -NR34R3s, in which R; ~ represents methyl, R3' and R3; have the meanings of R'° and. R" given above and are identical to or different from them, Le A 32 733-Foreign countries R~ and R35 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl or methoxy, or S R~ and R35 together with the nitrogen atom form a morpholinyi, triazolyl or thiomorpholinyl ring, or a radical of the formula -N N-R~
in which R36 represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 3 carbon atoms or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl, or R3 and R° together with the nitrogen atom form a morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl ring, or a radical of the formula -N N-R3' U , in which L.e A 32 733-Foreign countries R3' represents hydrogen, hydroxyl, formyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by groups of the formula -(D) f NR38R39, -CO-(CH2)g O-CO-R4o, -CO-(CH2),,-OR4~ or -P(O)(OR42)(OR43), in which g and h are identical or different and each represents a number 1 S 1 or 2, and f represents a number 0 or 1, D represents a group of the formula -CO or -S02, R3g and R~9 are identical or different and have the meanings of R' and R8 given above, R4° represents straight-chain or branched alkyl having up to 3 carbon atoms;
R4~ represents straight-chain or branched alkyl having up to 3 carbon atoms, Ix A 32 733-Foreign countries R42 and R43 are identical or different and each represents hydrogen, methyl or ethyl, or R3' represents a radical of the formula -(CO);-E, in which i represents a number 0 or 1, E represents cyclopentyl, benzyl, phenyl, pyridyl, pyrimidyl or furyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, -SO~H, straight-chain or branched alkoxy having up to 3 carbon atoms, hydroxyl, or by a radical of the formula -S02-NR"~R4s, in which R'4 and R4s have the meanings of R1$ and R~9 given above and are identical to or different from them, or E represents radicals of the formulae ~ Le A 32 733-Foreign countries or - ~ , and the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally mono- to trisubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or groups of the formulae -P(O)(OR46)(OR4'), O
O =NR or _(COfNRasRso in which R°6 and R°' have the meanings of R~° and R~ ~ given above and are identical to or different from them, R48 represents hydroxyl or methoxy, j represents a number 0 or 1, and R°~ and RS° are identical or different and have the meanings of R~4 and R'S given above, Le A 32 733-Foreign countries and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents S selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, cyclopropyl, cycloheptyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a radical of the formula -S03H, -NRS~Rs2 or P(O)OR530RSa, ("''' 10 in which R5~ and RS'' are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, R53 and RS° are identical or different and have the meanings of R~° and R ~ 1 given above, and/or the alkyl is optionally substituted by phenyl which for its part may be mono- to disubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, hydroxyl, methoxy, or by a group of the formula -NRS~~RS''~, in which RS ~ ~ and RS''~ have the meanings of RS' and R52 given above and are identical to or different from them, and/or the heterocycles listed under Rz and R', which are formed together with the nitrogen atom, are optionally substituted by phenyl, pyridyl, piperidinyl, pyrrolidinyl or tetrazolyl, if appropriate also ~ Le A 32 733-Foreign countries attached via a nitrogen function, where the ring systems for their part may be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, . or R3 and R4 together with the nitrogen atom form radicals of the formulae N ~ (CH2)3 CH3 NJ ~II
CH3 ' O-N
NM
C~

N' , i~
CH~H3 RS and R6 are identical or different and each represents hydrogen, hydroxyl or represents straight-chain or branched alkoxy having up to 3 carbon atoms, and their salts, N-oxides, hydrates and isomeric forms.
Very particular preference is given to compounds of the general formula (I), in which R~ represents methyl or ethyl, ' L.e A 32 733-Foreign countries t R2 represents ethyl or propyl, R3 and R' are identical or different and each represents a straight-chain or branched alkyl chain having up to 5 carbon atoms which is optionally substituted up to two times by identical or different substituents selected from the group consisting of hydroxyl and methoxy, or R3 and R4 together with the nitrogen atom form a piperidinyl, morpholinyl, thiomorpholinyl ring, or a radical of the formula -N N-R3' / , in which R3' represents hydrogen, formyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by groups of the formulae -(D)f.NR38R39 or -P(~)(~R4')(~R4~), in which f represents a number 0 or 1, ' Lx A 32 733-Forei;~n countries D represents a group of the formula -CO, R38 and R39 are identical or different and each represents hydrogen or methyl, R42 and R43 are identical or different and each represents hydrogen, methyl or ethyl, or R3' represents cyclopentyl, and the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally mono- or disubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or groups of the formulae -P(O)(OR46)(OR4') or -(CO);NR°9RSO, '"""1 in which R~ and R4' are identical or different and each represents hydrogen, methyl or ethyl, j represents a number 0 or 1, and ' Le A 32 733-Foreign countries R49 and Rs° are identical or different and each represents hydrogen or methyl and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, carboxyl, or by a radical of the formula P(O)OR530RSa, in which R53 and R54 are identical or different and each represents hydrogen, methyl or ethyl, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by pyrrolidinyl or piperidinyl attached via nitrogen, RS represents hydrogen, and ' R6 represents ethoxy or propoxy, and their salts, hydrates, N-oxides and isomeric forms.
Likewise, very particular preference is given to those compounds of the general formula (I) according to the invention in which RS represents hydrogen and the radicals R6 and -SO~NR;R4 are in a position para to one another at the phenyl ring.

' Le A 32 733-Foreisn countries Particularly preferred compounds are listed in Table A.
Table A:
Structure HsC~O H
x HCI
C_ .~

HsC~O HN i \N~N ~N

N
c~
N
I , Le A 32 733-Foreign countries Structure .. O CH3 HsC~O HN i \ \N~N /N

N x 2 HCI
c~
N
I
111~""'"~'~ C2Hs O CHa H3C~O HN
\ N.N / N
I/

N
C
N

HaC~O HN i N , \ ~N.N /
I /

N
C~
N
I
(CH2)2 OH

Le A 32 733-Fore~n countries Structure HsC~O HN
\ N.N /N

N
C~
N
I
C2Hs O
CzHs HsC~O HN i \N~N /N
CHs N
C~
N
I

O CHs HsC~'O HN ~ N
\ ~N'N /

N
C~

Le A 32 733-Forei,en countries Structure O CHs HsC~O HN
\ N.N / N

N
H

HsC~O HN i \ \N~N / N

~N1 O CHs HsC~O HN i \ ~N' N / N
I/

~N1 23189-8549 (S) HsC~O H
CI ~
x 3 H20 C~~
N~
H
H3~J
The invention furthermore provides a process for preparing the compounds of the general formula (I). The process comprises reacting a compound of the general formula (V) O R~
HN ~ \
Rs \ wN ~ N ~N M

in which Rl, R2, RS and R6 are as defined above, with an amine of general formula (VI) HNR3R4 (VI) in which R3 and R4 are as defined above, in inert solvent.
The compound of formula (I) can then be converted to a salt, especially a pharmaceutically acceptable salt, or a hydrate, if required.
The compound of formula (V) can be prepared by reacting a compound of the general formula (II) ' 23189-8549 (S) O R' O
R2~ O~ (II) O
in which R1 and R2 are each as defined above and L represents straight-chain or branched alkyl having up to 4 5 carbon atoms, with a compound of the general formula (III) Rs N H
'NH
x HCI (III) Rs in which 10 RS and R6 are each as defined above, in a two-step reaction in the systems ethanol and phosphorus oxytrichloride/
dichloroethane into a compound of the general formula (IV) O R' HN ~~\N
w ~N~
_N
RS R2 (IV) Rs in which 15 R1, R2 , RS and R6 are each as de f fined above .

' 23189-8549 (S) This is reacted in a further step with chlorosulphonic acid to give the compound of the general formula (V) O R' HN ~ \
R6 w N ~N
R5 \ ~ N ~ Rz in which R1, R2, RS and R6 are each as defined above.
The process according to the invention can be illustrated using the following scheme as an example:

' F.e A 32 733-Foreign countries N
C~ N

~N
CH3 N ~ ~ HCI
H O CH3 i 1. ethanol 2. phosphorus oxytrichloride / dichlorethane O CHs C
N ~ N
~N.N~
~ i CHs chlorosulphonic acid O CHs C
N ~ N
wN~N~

~N-CH3 O CHs C
_V N r N
~N~
-N

S02 ~N-CH3 Solvents which are suitable for the individual steps are the customary organic solvents which do not change under the reaction conditions. These preferably include ethers, such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether, or hydrocarbons, such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, or ~
. Le A 32 733-Foreign countries -5$-halogenated hydrocarbons, such as dichloromethane, trichloromethane, carbon tetrachloride, dichloroethane, trichloroethylene or chlorobenzene, or ethyl acetate, dimethylformamide, hexamethylphosphoric triamide, acetonitrile, acetone, dimethoxyethane or pyridine. It is also possible to use mixtures of the abovementioned solvents. Particular preference is given to ethanol for the first step and dichloroethane for the second step.
The reaction temperature can generally be varied within a relatively wide range. In general, the reaction is carried out in a range of from -20°C to 200°C, preferably of from 0°C to 70°C.
The process steps according to the invention are generally carried out under atmospheric pressure. However, it is also possible to operate under superatmospheric pressure or under reduced pressure (for example, in a range of from 0.5 to 5 bar).
The reaction to give the compounds of the general formula (V) is carried out in a temperature range of from 0°C to room temperature, and at atmospheric pressure.
The reaction with the amines of the general formula (Vn is carried out in one of the abovementioned chlorinated halogens, preferably in dichloromethane.
The reaction temperature can generally be varied 'within a relatively wide range. In general, the reaction is carried out at temperatures in a range of from -20°C to 200°C, preferably of from 0°C to room temperature.
The reaction is generally carried out at atmospheric pressure. However, it is also possible to operate under superatmospheric pressure or under reduced pressure (for example in a range of from 0.5 to 5 bar).
Some of the compounds of the general formula (IT) are known, or they are novel, and they can then be prepared by ~ Le A 32 733-Foreign countries t S
converting compounds of the general formula (VIn R2-CO-T (VIn in which R2 is as defined above "''" 10 and T represents halogen, preferably chlorine, initially by reaction with compounds of the general formula (V)I~
R' H02C_ _NH2 (VIII) in which R~ is as defined above in inert solvents, if appropriate in the presence of a base and trimethylsilyl chloride, into the compounds of the general formula (IX) R' R? CO-NH"C02H (IX) in which R' and R' are each as defined above, c Le A 32 733-Foreign countries _60_ and finally reacting with the compound of the formula (X) O
CI' _C02L (X) in which L is as defined above, in inert solvents, if appropriate in the presence of a base.
Suitable solvents for the individual steps of the process are the customary organic solvents which do not change under the reaction conditions. These preferably include ethers, such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether, or hydrocarbons, such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, or halogenated hydrocarbons, such as dichloromethane, trichloromethane, carbon tetrachloride, dichloroethylene, trichloroethylene or chlorobenzene, or ethyl acetate, dimethylformamide, hexamethylphosphoric triamide, acetonitrile, acetone, I S dimethoxyethane or pyridine. It is also possible to use mixtures of the abovementioned solvents. Particular preference is given to dichloromethane for the first step and to a mixture of tetrahydrofuran and pyridine for the second step.
Suitable bases are generally alkali metal hydrides or alkali metal alkoxides, such as, for example, sodium hydride or potassium tert-butoxide, or cyclic amines, such as, for example, piperidine, pyridine, dimethylaminopyridine or C,-C4 alkylamines, such as, for example, triethylamine. Preference is given to triethylamine, pyridine and/or dimethylaminopyridine.
The base is generally employed in an amount of from 1 mol to 4 mol, preferably from 1.2 mol to 3 mol, in each case based on 1 mol of the compound of the formula (X).
The reaction temperature can generally be varied within a relatively wide range. In general, the reaction is carried out in a range of from -20°C to 200°C, preferably of from 0°C to 100°C.

'' Le A 32 733-Foreign countries The compounds of the general formulae (VII), (VIII), (IX) and (X) are known per se, or they can be prepared by customary methods.
S The compounds of the general formula (III) can be prepared by reacting compounds of the general formula (XI) -CN
Rs (XI) in which RS and R6 are each as defined above with ammonium chloride in toluene and in the presence of trimethylaluminium in hexane in a temperature range of from -20°C to room temperature, preferably at 0°C
and atmospheric pressure, and reacting the resulting amidine, if appropriate in situ, with hydrazine hydrate.
The compounds of the general formula (XI) are known per se, or they can be prepared by customary methods. , Some of the compounds of the general formula (IV) are known, or they are novel, in which case they can be prepared by known methods (cf. David R. Marshall, Chemistry and Industry, 2 May 1983, 331-335].
Compounds of the general formula (V) are novel per se, however, they can be prepared from the compounds of the general formula (IV) in accordance with the publication Organikum, VEB Deutscher Verlag der Wissenschaften, Berlin 1974, pages 338 - 339.

Lx A 32 733-Foreign countries !~

The compounds of the general formula (n according to the invention have an unforeseeable useful pharmacological activity spectrum.
They inhibit either one or more of the cGMP-metabolizing phosphodiesterases (PDE I, PDE II and PDE V). This results in an increase of cGMP. The differentiated expression of the phosphodiesterases in different cells, tissues and organs, as well as the differentiated subcellular localization of these enzymes, in combination with the selective inhibitors according to the invention make it possible to selectively address the various cGMP-regulated processes.
Moreover, the compounds according to the invention enhance the activity of substances such as, for example EDRF (endothelium derived relaxing factor), ANP (atrial natriuretic peptide), of nitrovasodilators and all other substances which increase the cGMP concentration in a manner different from that of phosphodiesterase inhibitors.
They can therefore be employed in pharmaceuticals for treating cardiovascular disorders, such as, for example, for treating hypertension, neuronal hypertonia, stable and unstable angina, peripheral and cardial vascularpathies, arrhythmiae, for treating thromboembolic disorders and ischaemias such as myocardial infarction, stroke, transistory and ischaemic attacks, angina pectoris, obstruction of peripheral circulation, prevention of restenoses after thrombolysis therapy, percutaneous transluminal angioplasty (PTA), percutaneous transluminal coronary angioplasties (PTCA) and bypass. Furthermore, they may also be of significance for cerebrovascular disorders.
Owing to their relaxing action on smooth muscles, they are suitable for treating disorders of the urogenital system such as hypertrophy of the prostate, incontinence and in particular for treating erectile dysfunction and female sexual dysfunction.

Le A 32 ?33-Forei;~n countries t Activi ot~phosphodiesterases (PDEs) The cGMP-stimulated PDE II, the cGMP-inhibited PDE III and the cAMP-specific PDE N were isolated either from porcine or bovine heart myocardium. The Ca''+-calmodulin-stimulated PDE I was isolated from porcine aorta, porcine brain or, preferably, from bovine aorta. The cGMP-specific PDE V was obtained from porcine small intestine, porcine aorta, human platelets and, preferably, from bovine aorta.
Purification was carried out by anion exchange chromatography over MonoQO
Pharmacia, essentially following the method of M. Hoey and Miles D. Houslay, Biochemical Pharmacology, Vol. 40, 193-202 (1990) and C. Lugman et al., Biochemical Pharmacology, Vol. 35, 1743-1751 (1986).
The enzyme activity is determined using a test mixture of 100 ml in 20 mM
tris/HCl-buffer pH 7.5 containing 5 mM MgCh, 0.1 mg/ml of bovine serum albumin and either 800 Bq[ 3H]CAMP or [3H]cGMP. The final concentration of the nucleotides in question is 10'~ moUl. The reaction is initiated by addition of the enzyme and the amount of enzyme is such that during the incubation time of 30 min, approximately 50% of the substrate are converted. To test the cGMP-stimulated PDE II, (3H]CAMP is used as substrate and 10'~ mol/1 of non-labelled cGMP are added to the mixture. To test the Ca'+-calmodulin-dependent PDE I, 1 mM of CaCh and 0.1 mM of calmodulin are added to the reaction mixture. The reaction is quenched by addition of 100 ml of acetonitrile containing 1 mM cAMP and 1 mM ANIP. 100 ml of the reaction mixture are separated by HPLC, and the cleavage products are determined quantitatively on-line using a continuous scintillation counter. The substance concentration measured is the concentration at which the reaction rate is reduced by 50%. Additionally, the "phosphodiesterase (3H] cAMP-SPA enzyme assay" and the "phosphodiesterase [3H]
cGMP-SPA enzyme assay" from Amersham Life Science were used for testing. The test was carried out according to the test protocol of the manufacturer. To determine the activity of PDE Q, the [3H]CAMP SPA assay was used, and 10'~ M cGMP were added to the reaction mixture to activate the enzyme. To rrieasure PDE I, 10-' M
calmodulin I,e A 32 733-Foreign countries and 1 mM CaCl2 were added to the reaction mixture. PDE V was measured using the [3H]cGMP SPA assay.
Inhibition of the phosphodiesterases in vitro Ex. No. PDE I PDE II PDE V
ICS [nM] ICS [nM] ICS jnM]

16 300 >1000 2 19 200 >1000 2 20 200 >1000 2 26 100 >1000 1 27 200 >1000 3 32 100 >1000 4 260 300 >1000 10 275 50 >1000 3 338 200 >1000 5 In principle, inhibition of one or more phosphodiesterases of this type results in an increase of the cGMP concentration. Thus, the compounds are of interest for all therapies in which an increase of the cGMP concentration is considered to be beneficial.
The cardiovascular effects were investigated using SH-rats and dogs. The substances were administered intravenously or orally.
The erection-stimulating action was investigated using rabbits which were awake (Naganuma H, Egashira T, Fuji 1, Clinical and Experimental Pharmacology and Physiology 20, 177-183 (1993)]. The substances were administered intravenously, orally or parenterally.

Le A 32 733-Foreign countries The novel active compounds and their physiologically acceptable salts (for example hydrochlorides, maleates or lactates) can be converted in a known manner into the customary formulations, such as tablets, coated tablets, pills, granules, aerosols, syrups, emulsions, suspensions and solutions, using inert non-toxic, pharmaceutically suitable excipients or solvents. In this case the therapeutically active compound should in each case be present in a concentration from approximately 0.5 to 90% by weight of the total mixture, i.e. in amounts which are sufficient in order to achieve the dosage range indicated.
The formulations are prepared, for example, by extending the active compounds using solvents and/or excipients, if appropriate using emulsifiers and/or dispersants, it optionally being possible, for example, to use organic solvents as auxiliary solvents if the diluent used is water.
Administration is carried out in a customary manner, preferably orally, transdermally or parenterally, for example perlingually, buccally, intravenously, nasally, rectally or inhalatively.
For human use, in the case of oral administration, it is good practice to administer doses of from 0.001 to 50 mg/kg, preferably of 0.01 mglkg - 20 mg/kg. In the case of parenteral administration, such as, for example, via mucous membranes nasally, buccally or inhalatively, it is good practice to use dopes of 0.001 mg/kg -0.5 mg/kg.
In spite of this, if appropriate it may be necessary to depart from the amounts mentioned, namely depending on the body weight or the type of administration route, on the individual response towards the medicament, the manner of its formulation and the time or interval at which administration takes place. Thus, in some cases it may be adequate to manage with less than the abovementioned minimum amounts, while in other cases the upper limit mentioned has to be exceeded. In the case of the administration of relatively large amounts, it may be advisable to divide these into several individual doses over the course of the day.

Le A 32 733-Foreign countries The compounds according to the invention are also suitable for use in veterinary medicine. For use in veterinary medicine, the compounds or their non-toxic salts can be administered in a suitable formulation in accordance with general veterinary practice.
Depending on the kind of animal to be treated, the veterinary surgeon can determine the nature of use and the dosage.

' Le A 32 733-Forei;~n countries Starting materials Examute 1A
2-Butyrylaminopropionic acid ~' ~3 22.27 g (250 mmol) of D,L-alanine and 55.66 g (550 mmol) of triethylamine are dissolved in 250 ml of dichloromethane, and the solution is cooled to 0°C. 59.75 g (550 mmol) of trimethylsilyl chloride are added dropwise, and the solution is stirred for 1 hour at room temperature and for 1 hour at 40°C. After cooling to -10°C, 26.64 g (250 mmol) of butyryl chloride are added dropwise, and the resulting mixture is stirred for 2 hours at -10°C and for one hour at room temperature.
With ice-cooling, 125 ml of water are added dropwise and the reaction mixture is .
stirred at room temperature for 15 minutes. The aqueous phase is evaporated to dryness, the residue is titrated with acetone and the mother liquor is filtered off with "'' suction. The solvent is removed and the residue is chromatographed. The resulting product is dissolved in 3N aqueous sodium hydroxide solution and the resulting solution is evaporated to dryness. The residue is taken up in conc. HCl and once more evaporated to dryness. The residue is stirred with acetone, precipitated solid is filtered off with suction and the solvent is removed under reduced pressure.
This gives 28.2 g (71 %) of a viscous oil which crystallizes after some time.
200 MHz 'H-NMR (DMSO-d6): 0.84, t, 3H; 1.22, d, 3H; 1.50, hex, 2H; 2.07, t, 2H;
4.20, quin., 1 H; 8.09, d, 1 H.

Le A 32 733-Foreisn countries ' Example ZA
2-Butyrylamino butyric acid HO
NH
O
O' 25.78 g of 2-aminobutyric acid (250 mmol) and 55.66 g (550 mmol) of triethylamine are dissolved in 250 ml of dichloromethane, and the solution is cooled to 0°C.
59.75 g (550 mmol) of trimethylsilyl chloride are added dropwise, and the solution is stirred for 1 hour at room temperature and for 1 hour at 40°C. After cooling to -10°C, 26.64g (250 mmol) of butyryl chloride are added dropwise, and the resulting mixture is stirred for 2 hours at -10°C and for one hour at room temperature.
With ice-cooling, 125 ml of water are added dropwise, and the reaction mixture is stirred at room temperature for 15 minutes. The organic phase is admixed with aqueous sodium hydroxide solution and the organic solvent is removed under reduced pressure. After acidification, the precipitated solid is stirred once with water and twice with petroleum ether and dried at 45°C under reduced pressure. This gives 29.1 g (67%) of a colourless solid.
200 MHz ~H-NMR (DMSO-d6):0.88, 2t, 6H; 1.51, quart., 2H, 1.65, m, 2H, 2.09, t, 2H, 4.10, m, 1 H; 8.01, d, 1 H; i 2.25, s, m 1 H.

Le A 32 733-Foreign countries Example 3A
2-Ethoxybenzonitrile ~~N
25 g (210 mmol) of 2-hydroxybenzonitrile are refluxed with 87 g of potassium carbonate and 34.3 g (314.8 mmol) of ethyl bromide in 500 ml of acetone overnight.
The solid is filtered off, the solvent is removed under reduced pressure and the residue is distilled under reduced pressure. This gives 30.0 g (97%) of a colourless liquid.
200 MHz ~H-NMR (DMSO-d6): 1.48, t, 3H; 4.15, quart., 2H; 6.99, dt, 2H; 7.51, dt, 2H.
Example 4A
2-Ethoxybenzamidine hydrochloride O NH CIH
~NH2 21.4 g (400 mmol) of ammonium chloride are suspended in 375 ml of toluene, and the suspension is cooled to 0°C. 200 ml of a 2M solution of trirnethylaluminium in hexane are added dropwise, and the mixture is stirred at room temperature until the evolution of gas has ceased. After addition of 29.44 g (200 mmol) of 2-ethoxybenzonitrile, the reaction mixture is stirred at 80°C (bath) overnight.

a Lx A ~32 733-Forei n countries With ice-cooling, the cooled reaction mixture is added to a suspension of 100 g of silica gel and 950 ml of chloroform, and the mixture is stirred at room temperature for 30 minutes. The mixture is filtered off with suction, and the filter residue is washed with the same amount of methanol. The mother liquor is concentrated, the resulting residue is stirred with a mixture of dichloromethane and methanol (9:1 ), the solid is filtered off with suction and the mother liquor is concentrated. This gives 30.4 g (76%) of a colourless solid.
200 MHz 'H-NMR (DMSO-d6): 1.36, t, 3H; 4.12, quart., 2H; 7.10, t, 1H; 7.21, d, 1H; 7.52, m, 2H; 9.30, s, broad, 4H.
Example SA
2-Propoxybenzonitrile H3C~0 CN
75 g (630 ml) of 2-hydroxybenzonitrile are refluxed with 174 g ( 1.26 mol) of potassium carbonate and 232.2 g ( 1.89 mol) of ethyl bromide in 1 1 of acetone overnight. The solid is filtered off, the solvent is removed under reduced pressure and the residue is distilled under reduced pressure.
b.p.: 89°C (0.7 mbar) Yield: 95.1 g (93.7%) Le A 32 733-Foreisn countries Example 6A
2-Propoxybenzamidine hydrochloride H3C~0 NH
~NH2 x HCI
21.41 g (400 mmol) of ammonium chloride are suspended in 400 ml of toluene and cooled to 0-5°C. 200 ml of a 2M solution of triethylaluminium in hexane are added dropwise, and the mixture is stirred at room temperature until the evolution of gas has ceased. After addition of 32.2 g (200 mmol) of 2-propoxybenzonitrile, the reaction mixture is stirred at 80°C (bath) overnight. With ice-cooling, the cooled reaction mixture is added to a suspension of 300 g of silica gel and 2.851 of ice-cooled chloroform, and the mixture is stirred for 30 minutes. The mixture is filtered off with suction and the filter residue is washed with the same amount of methanol.
The solvent is distilled off under reduced pressure, the residue is stirred with 500 ml of a mixture of dichloromethane and methanol (9:1 ), the solid is filtered off and the mother liquor is concentrated. The residue is stirred with petroleum ether and filtered off with suction. This gives 22.3 g (52%) of product.
~H-NMR (200 MHz, CD30D): 1.05 (3H); 1.85 (sex, 2H); 4.1 (A, 2H); 7.0 - 7.2 (m, 2H); 7.5 - 7.65 (m, 2H).
Example 7A
2-Ethoxy-4-methoxybenzonitrile H3C~O
i~N
HsC.O /

Le A 32 733-Foreign countries 30.0 g (201 mmol) of 2-hydroxy-4-methoxybenzonitrile are refluxed with 83.4 g of potassium carbonate (603 mmol) and 32.88 g (301 mmol) of bromoethane in 550 ml of acetone for 18 hours. After filtration, the solvent is removed under reduced pressure and the residue is purified by silica gel chromatography (cyclohexane:ethyl S acetate = 10:1 ): 35.9 g of an oil Rf = 0.37 (cyclohexane:ethyl acetate = 3:1 ) 200 MHz 'H-NMR (CDC13): 1.48, t, 3H; 3.85, s, 3H; 4.12, quart., 2H; 6.46, m, 2H;
7.48, d, 1 H.
Example 8A
2-Ethoxy-4-methoxybenzamidine hydrochloride H3C~O NH
CIH
~NH2 H3C.0 /
6.98 g ( i 30 mmol) of ammonium chloride are suspended in 150 ml of toluene, and the suspension is cooled to 0°C. 70 ml of a 2M solution of trimethylaluminium in hexane are added dropwise, and the mixture is stirred at room temperature until the evolution of gas has ceased. After addition of 11.56 g (65 mmol) of 2-ethoxy-4-methoxybenzonitrile, the reaction mixture is stirred at 80°C (bath) overnight.
With ice-cooling, the cooled reaction mixture is added to a suspension of 100 g of silica gel and 950 ml of dichloromethane, and the mixture is stirred at room temperature for 30 minutes. The mixture is filtered off with suction and the filter residue is washed with the same amount of methanol. The mother liquor is concentrated, the resulting residue is stirred with a mixture of dichloromethane and methanol (9:1 ), the solid is filtered off with suction and the mother liquor is concentrated. The residue is stirred with petroleum ether and filtered off with suction.
This gives 7.95 g (50%) of a solid.

Le A 32 733-Foreign countries 200 MHz ~H-NMR (DMSO-d6): 1.36, t, 3H; 3.84, s, 3H; 4.15, quart., 2H; 6.71, m, 2H; 7.53, d, 1H, 8.91, s, broad, 3H.
Examule 9A
2-(2-Ethoxyphcnyl)-5,7-dimethyl-3H imidazo[5,1-f][ 1,2,4]triazin-4-one 24.4 g (0.186 mol) of N-acetyl-D,L-alanine are initially charged in 200 ml of absolute tetrahydrofuran, and 45 ml of absolute pyridine and 0.5 g of 4-dimethylaminopyridine are added. The mixture is heated to reflux, and 51.85 g (0.372 mol) of ethyl oxalyl chloride are added dropwise. The mixture is heated under reflux for a further 90 minutes, cooled, poured into ice-water and extracted three times with ethyl acetate. The organic phase is dried over sodium sulphate, concentrated and taken up in 62.5 ml of methanol. 9 g of sodium bicarbonate are added and the mixture is stirred under reflux for 2.5 hours and filtered.
With ice-cooling, 9.54 g ( 190.65 mmol) of hydrazine hydrate are added dropwise to a solution of 38.26 g (190.65 mmol) of 2-ethoxy-4-methoxybenzamidine hydrochloride in 250 ml of methanol, and the resulting suspension is stirred at room temperature for another 30 minutes. The methanolic solution described above is added to this reaction mixture, and the mixture is stirred at a bath temperature of 70°C for 4 hours.
After filtration, the mixture is concentrated, the residue is partitioned between dichloromethane and water, the organic phase is dried over sodium sulphate and the solvent is removed under reduced pressure.

Le A 32 733-Foreign countries The residue is taken up in 250 ml of 1,2-dichloroethane, 32.1 ml (348 mmol) of phosphorus oxychloride are added dropwise and the mixture is heated under reflux for two hours. The mixture is cooled, concentrated, taken up in a little methylene chloride and admixed with diethyl ether, and the solid is filtered off with suction.
After the silica gel chromatography (methylene chloride/methanol 95:5), the solution is concentrated and the crystalline residue is stirred with diethyl ether.
Yield: 8.1 g ( 14.9% of theory) 200 MHz'H-NMR (CDCl3): 1.58, t, 3H; 2.62, s, 3H; 2.68, s, 3H; 4.25, q, 2H;
7.04, d, 1 H; 7.12, t, 1 H; 7.5, dt, 1 H; 8.19, dd, 1 H; 10.02, s, 1 H.
Example 10A
2-(2-Ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f)[ 1,2,4)triazin-4-one 7.16 g (45 mmol) of 2-butyrylamino-propionic acid and 10.67 g of pyridine are dissolved in 45 ml of THF and, after addition of ,a spatula tip of DMAP, heated to reflux. 12.29 g (90 mmol) of ethyl oxalyl chloride are slowly added dropwise, and the reaction mixture is refluxed for 3 hours. The mixture is poured into ice-water and extracted three times with ethyl acetate and the organic phase is dried over sodium sulphate and concentrated using a rotary evaporator. The residue is taken up in 15 ml of ethanol and refluxed with 2.15 g of sodium bicarbonate for 2.5 hours. The cooled solution is filtered.
With ice-cooling, 2.25 g (45 mmol) of hydrazine hydrate are added dropwise to a solution of 9.03 g (45 mmol) of 2-ethoxybenzamidine hydrochloride in 45 ml of Le A 32 733-Foreisn countries ethanol, and the resulting suspension is stirred at room temperature for another 10 minutes. The ethanolic solution described above is added to this reaction mixture, and the mixture is stirred at a bath temperature of 70°C for 4 hours.
After filtration, the mixture is concentrated, the residue is partitioned between dichloromethane and water, the organic phase is dried over sodium sulphate and the solvent is removed under reduced pressure.
This residue is dissolved in 60 ml of 1,2-dichloroethane and, after addition of 7.5 ml of phosphorus oxychloride, refluxed for 2 hours. The mixture is diluted with dichloromethane and neutralized by addition. of sodium bicarbonate solution and solid sodium bicarbonate. The organic phase is dried and the solvent is removed under reduced pressure. Chromatography using ethyl acetate and crystallization afford 4.00 g (28%) of a colourless solid, Rf = 0.42 (dichloromethanelmethanol =
95:5) 200 MHz'H-NMR (CDC13): 1.02, t, 3H; 1.56, t, 3H; 1.89, hex, 2H; 2.67, s, 3H;
3.00, t, 2H; 4.26, quart., 2H; 7.05, m, 2H; 7.50, dt, 1 H; 8.17, dd, 1 H; 10.00, s, 1 H.
Example 11A
2-(2-Propoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4-one 7.16 g (45 mmol) of 2-butyrylaminopropionic acid and 10.67 g of pyridine are dissolved in 45 ml of tetrahydrofuran and, after addition of a spatula tip of dimethylaminopyridine, heated to reflux. 12.29 g (90 mmol) of ethyl oxalyl chloride are slowly added dropwise, and the reaction mixture is refluxed for 3 hours.
The Le A 32 733-Forei n countries mixture is poured into ice-water and extracted three times with ethyl acetate, and the organic phase is dried over sodium sulphate and concentrated using a rotary evaporator. The residue is taken up in 15 ml of ethanol and refluxed with 2.15 g of sodium bicarbonate for 2.5 hours. The cooled solution is filtered.
With ice-cooling, 2.25 g (45 mmol) of hydrazine hydrate are added dropwise to a solution of 9.66 g (45 mmol) of 2-propoxybenzamidine hydrochloride in 45 ml of ethanol, and the resulting suspension is stirred at room temperature for another 10 minutes. The ethanolic solution described above is added to this reaction mixture, and the mixture is stirred at a bath temperature of 70°C for 4 hours.
After filtration, the mixture is concentrated, the residue is partitioned between dichloromethane and water, the organic phase is dried over sodium sulphate and the solvent is reduced under reduced pressure.
This residue is dissolved in 60 ml of 1,2-dichloroethane and, after addition of 7.5 ml of phosphorus oxychloride, refluxed for 2 hours. The mixture is diluted with dichloromethane and neutralized by addition of sodium bicarbonate solution and solid sodium bicarbonate. The organic phase is dried and the solvent is removed under reduced pressure. Crystallization from ethyl acetate gives 2.85 g ( 19.1 %) of a yellow solid, chromatographic purification of the mother liquor gives a further 1.25 g (8.4%) of the product. Rf = 0.45 (dichloromethane/methanol = 95:5) 200 MHz ~H-NMR (CDC13): 1.03, t, 3H; 1.15, t, 3H; 1.92, m, 4H; 2.67, s, 3H;
3.01, t, 2H; 4.17, t., 2H; 7.09, m, 2H; 7.50, dt, 1H; 8.17, dd, 1H; 10.02, s, 1H.

Le A~ 32 733-Foreign countries _77_ Examule 12A
2-(2-Ethoxy-4-methoxyphenyl)-5-methyl-7-propyl-3H-imidazo[5,1-fJ( 1,2,4]triazin-4-one 5.50 g (34.8 mmol) of 2-butyrylaminopropionic acid and 8.19 g of pyridine are dissolved in 35 ml of tetrahydrofuran and, after addition of a spatula tip of dimethylaminopyridine, heated to reflux. 9.43 g (69 mmol) of ethyl oxalyl chloride are slowly added dropwise, and the reaction mixture is refluxed for 3 hours.
The mixture is poured into ice-water and extracted three times with ethyl acetate, and the organic phase is dried over sodium sulphate and concentrated using a rotary evaporator. The residue is taken up in 11 ml of methanol and refluxed with 1.65 g of sodium bicarbonate for 2.5 hours. The cooled solution is filtered.
With ice-cooling, 1.73 g (34.5 mmol) of hydrazine hydrate are added dropwise to a solution of 7.95 g (34.5 mmol) of 2-ethoxy-4-methoxybenzamidine hydrochloride in 35 ml of ethanol, and the resulting suspension is stirred at room temperature for another 30 minutes. The methanolic solution described above is added to this reaction mixture, and the mixture is stirred at a bath temperature of 70°C for 4 hours.
After filtration, the mixture is concentrated, the residue is partitioned between dichloromethane and water, the organic phase is dried over sodium sulphate and the solvent is removed under reduced pressure.
This residue is dissolved in 46 ml of 1,2-dichloroethane and, after addition of 5.74 ml of phosphorus oxychloride, refluxed for 2 hours. The- mixture is diluted with dichloromethane and neutralized by addition of sodium bicarbonate solution and solid sodium bicarbonate. The organic phase is dried and the solvent is removed " Le A 32 733-Foreign countries _78_ under reduced pressure. Chromatography (dichloromethane:methanol = 50:1) gives 0.31 g (2.5%) of a solid.
Rf = 0.46 (dichloromethane:methanol = 20:1 200 MHz ~H-NMR (CDCl3): 1.03, t, 3H; 1.58, t, 3H; 1.88, m, 2H; 2.62, s, 3H;
2.98, t, 2H; 3.89, s, 3H; 4.25, quart., 2H; 6.54, d, 1 H, 6.67, dd, 1 H; 8.14, d, 1 H; 9.54, s, 1 H.
Example 13A
!!~" 10 2-(2-Ethoxyphenyl)-5-ethyl-7-propyl-3H imidazo[5,1-f][1,2,4]triazin-4-one 29.06 g ( 167.8 mmol) of 2-butyrylaminobutyric acid and 39.76 g of pyridine are dissolved in 170 ml of tetrahydrofuran and, after addition of a spatula tip of dimethylaminopyridine, heated to reflux. 45.81 g (335.5 mmol) of ethyl oxalyl chloride are slowly added dropwise, and the reaction mixture is refluxed for 3 hours.
The mixture is poured into ice-water and extracted three times with ethyl acetate, and the organic phase is dried over sodium sulphate and concentrated using a rotary evaporator. The residue is taken up in 15 ml of methanol, and half of the solution is refluxed with 7.96 g of sodium bicarbonate for 2.5 hours. The cooled solution is filtered.
With ice-cooling, 4.20 g (83.9 mmol) of hydrazine hydrate are added dropwise to a solution of 16.83 g (83.9 mmol) of 2-ethoxybenzamidine hydrochloride in 85 ml of ethanol, and the resulting suspension is stirred at room temperature for another 10 minutes. The methanolic solution described above is added to this reaction mixture, L.e A 32 733-Foreign countries and the mixture is stirred at a bath temperature of 70°C for 4 hours.
After filtration, the mixture is concentrated, the residue is partitioned between dichloromethane and water, the organic phase is dried over sodium sulphate and the solvent is removed under reduced pressure.
This residue is dissolved in 112 ml of 1,2-dichloroethane and, after addition of 14 ml of phosphorus oxychloride, refluxed for 2 hours. The mixture is diluted with dichloromethane and neutralized by addition of sodium bicarbonate solution and solid sodium bicarbonate. The organic phase is dried and the solvent is removed under reduced pressure. Chromatography (dichloromethane:methanol = 50:1 ) gives 3.69 g ( i 2.4%) of a colourless solid, Rf = 0.46 (dichloromethane:methanol =
20:1 ) 200 MHz ~H-NMR (CDC13): 1.32, t, 3H; 1.57, t, 3H; 1.94, m, 8H; 3.03, quart., 2H;
3.64, quin., 1 H; 4.27, quart., 2H; 7.06, d, 1 H; 7.12, t, 1 H; 7.50, dt, 1 H,

8.16, dd, 1 H;

9.91, s, 1 H.
Example 14A
4-Ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride 7.25 g (25.5 mmol) of 2-(2-ethoxyphenyl)-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]-triazin-4-one are initially charged, and 26.74 g (0.23 mol) of chlorosulphonic acid are added with ice-cooling. The mixture is stirred at room temperature overnight and poured into ice-water, and the crystals are filtered off with suction and dried in a vacuum desiccator.

Le A 32 733-Foreign countries Yield: 9.5 g (97% of theory) 200 MHz ~H-NMR (d6-DMSO): 1.32, t, 3H; 2.63, s, 3H; 2.73, s, 3H; 4.13, q, 2H;
7.15, d, 1 H; 7.77, m, 2H; 12.5, s, 1 H;
Example 15A
4-Ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fJ[ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride At 0°C, 2.00 g (6.4 mmol) of 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-imidazo[5,1-fj[1,2,4]triazin-4-one are slowly added to 3.83 ml of chlorosulphonic acid. At room temperature, the reaction mixture is stirred overnight, and then poured into ice-water and extracted with dichloromethane. This gives 2.40 g (91%) of a colourless foam.
200 MHz ~H-NMR (CDC13): 1.03, t, 3H; 1.61, t, ZH; 1.92, hex, 2H; 2.67, s, 3H;
3.10, t, 2H; 4.42, quart., 2H; 7.27, t, 1 H; 8.20, dd, 1 H; 8.67, d, 1 H; 10.18, s, 1 H.

Le A 32 733-Foreign countries Example 16A
4-Propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fj[ 1,2,4Jtriazin-2-yl)-benzenesulphonyl chloride n At 0°C, 2.80 g (8.6 mmol) of 2-(2-propoxy-phenyl)-5-methyl-7-propyl-imidazo[5,1-fJ[1,2,4Jtriazin-4-one are added slowly to 5.13 ml of chlorosulphonic acid. The reaction mixture is stirred at room temperature overnight and then poured into ice-water and extracted with dichloromethane. This gives 3.50 g (96%) of a colourless foam.
Rf= 0.49 (dichloromethane/methanol = 95:5) 200 MHz'H-NMR (CDC13): 1.03, 2t, 6H; 1.95, m, 4H; 2.81, s, 3H; 3.22, t, 2H;
4.11, t., 2H; 7.09, m, 1 H; 8.06, dd, 1 H; 8.21 m, 1 H; 12.0, s, 1 H.
Example 17A
4-Ethoxy-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4Jtriazin-2-yl)-benzenesulphonyl chloride H3( V=J=V

Le A 32 733-Foreign countries At 0°C, 0.31 g (0.9 mmol) of 2-(2-ethoxy-4-methoxyphenyl)-5-methyl-7-propyl-3H-imidazo[5,1 f]-[1,2,4]triazin-4-one are added slowly to 0.54 ml of chlorosulphonic acid. The reaction mixture is stirred at room temperature overnight and then poured into ice-water and extracted with dichloromethane. This gives 0.355 g (89%) of a colourless foam.
Rf = 0.50 (dichloromethane/methanol = 20:1 ) 200 MHz'H-NMR (CDC13): 1.05, t, 3H; 1.66, t, 3H; 1.95, m, 2H; 2.61, s, 3H, 3.11, t, 2H; 4.15, s, 3H; 4.40, quart., 2H; 6.65, s, 1 H, 8.72, s, 1 H; 9.75, s, 1 H.
Example 18A
4-Ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-fJ [ 1,2,4]triazin-2-yl)-benzene-sulphonyl chloride ~"' At 0°C, 1.70 g (5.21 mmol) of 2-(2-ethoxy-phenyl)-5-ethyl-7-propyl-imidazo[5,1-f][ 1,2,4jtriazin-4-one are added slowly to 3.12 ml of chlorosulphonic acid. The reaction mixture is stirred at room temperature overnight and then poured into ice-water and extracted with dichloromethane. This gives 2.10 g {94%) of a colourless foam.
400 MHz 'H-NMR (CDCI3): 1.03, t, 3H; 1.35, t, 3H; 1.62, t, 3H; 1.92, sex., 2H;
3.07, quart., 2H; 3.12, t, 2H; 4.42, quart., 2H; 7.38, d, 1 H; 8.19, dd, I H;
8.70, d, 1 H;

10.08, s, broad, 1 H.

Le A 32 733-Foreitzn countries Example 19A
Diethyl (4-piperidinylmethyl)-phosphonate t'.OC2Hs ~OC2H5 N
I
H
2.11 g (528 mmol) of 60% strength sodium hydride are initially charged in 50 ml of absolute tetrahydrofuran, and 15.7 g (52.8 mmol) of diethyl methanediphosphonate are added dropwise. The mixture is stirred at room temperature for another 30 minutes, and 10.1 g (52.8 mmol) of 1-benzyl-4-piperidone are then added. The mixture is stirred for one hour at room temperature and for one hour under reflux, concentrated, admixed with water and extracted three times with dichloromethane, and the organic phases are dried over sodium sulphate and concentrated. The residue is hydrogenated in 50 ml of ethanol over 1.7 g of 10% palladium-carbon at room temperature and 3 bar. The catalyst is filtered off with suction and the filtrate is concentrated.
Yield: 12.5 g ( 100% of theory) 400 MHz, ~H-NMR (CDCI3): 1.13, m, 2H; 1.32, ~, 6H; 1.69, dd, 2H; 1.74 - 1.95, m, 4H; 2.62, dt, 2H; 3.05, m, 2H; 4.1, m, 4H.

Le A 32 733-Foreign countries Examute 20A
S-Methyl-4-furoxanecarbaldehyde O
HsC H
O _.N~ O ~N
40 g (571 mmol) of crotonaldehyde are dissolved in 80 ml of acetic acid and, at 0°C, admixed dropwise with a solution of 137 g ( 1.99 mol) of sodium nitrite in 300 ml of water. The mixture is stirred at room temperature for 2 hours, diluted with 800 ml of water and extracted 3 times with dichloromethane. The organic phase is dried, and chromatography (cyclohexane/ethyl acetate) gives 13.8 g (18.9%) of 5-methyl 4-furoxanecarbaldehyde.
200 MHz ~H-NMR (CDC13):2.39, s, 3H; 10.10, s, 1H.
Example Z1A
5-Methyl-4-furoxanecarbonyl chloride O
C CI
O_.N.O.N
13.5 g ( 105 mmol) of 5-methyl-4.-furoxanecarbaldehyde are dissolved in 200 ml of acetone and, at 0°C, admixed dropwise with a solution of 16.86 g ( 168 mmol)~ of chromium trioxide in 120 ml of a 2.2M sulphuric acid. The mixture is stirred at 10-15°C for 2 hours and then at room temperature overnight. With cooling, 100 ml of isopropanol are added dropwise and, after 30 minutes, the solvent is removed under reduced pressure. The aqueous . phase is extracted 3 times with ether, the organic phase is dried over magnesium sulphate and the solvent is removed under reduced pressure. The residue is dissolved in 1M sodium hydroxide solution and the solution Le A 32 733-Foreign countries is extracted 3 times with ether. The aqueous phase is acidified and extracted 3 times with ether. The organic phase is dried and the solvent is removed under reduced pressure. The residue is stirred with petroleum ether and filtered off with suction.
6.92 g of the residue are refluxed with 10 ml of thionyl chloride in 20 ml of dichloromethane for 6 hours. The mixture is diluted with toluene, filtered and concentrated using a rotary evaporator. The residue is once more taken up in dichloromethane, admixed with 10 mi of thionyl chloride and refluxed for 48 hours.
The solvent is removed under reduced pressure and the residue is distilled under reduced pressure. This gives 2.00 g (25%) of colourless crystals.
200 MHz ~H-NMR (CDC13): 2.41,.s.
Example 22A
1-(5-Methyl-4-furoxanecarbonyl)-4-tert-butyl-oxycarbonyl-piperazine p H~C~CH3 O
O _.NØ N
2.75 g ( 14.7 mmol) of Boc-piperazine and 1.49 g of triethylamine are dissolved in ml of dichloromethane and, at 0°C, admixed a little at a time with 2.00 g 20 ( 12.3 mmol) of 5-methyl-4-furoxanecarbonyl chloride. The mixture is stirred for 30 minutes at 0°C and for 2 hours at room temperature, diluted with dichloromethane and washed with water. The solvent is removed under reduced pressure and the residue is purified by chromatography (cyclohexane/ethyl acetate). This gives 3.33 g (87%) of 1-(5-methyl-4-furoxanecarbonyl)-4-tent-butyl-oxycarbonyl-piperazine.
200 MHz'H-NMR (CDC13): 1.50, s, 9H; 2.30, s, 3H; 3.55, m, 4H; 3.78, m, 2H;
3.87, m, 2H.

Le A 32 733-Foreign countries Examine 23A
1-(5-Methyl-4-furoxanecarbonyl)-piperazine trifluoroacetate H3C O N/'-~-~ .~ O
~N.H O- F
F
O-'N.O. N F
3.12 g (10 mmol) of 1-(S-methyl-4-furoxanecarbonyl)-4-tert-butyl-oxycarbonyl-piperazine are dissolved in 20 ml of dichloromethane and, at 0°C, admixed with 2 ml of trifluoroacetic acid. The mixture is allowed to warm to room temperature and stirred for 72 hours. After addition of 10 ml of ether, the precipitate is filtered off with suction and dried. This gives 2.47 g (83%) of 1-(5-methyl-4-furoxanecarbonyl)-piperazine trifluoroacetate.
200 MHz'H-NMR (DMSO-d6): 2.18, s, 3H; 3.18, m, 2H; 3.25, m, 2H; 3.83, m, 2H;
3.90, m, 2H; 8.89, s, broad, 2H.

' L.e A 32 733-Forei~tn countries _87_ Prerraration examQles Example 1 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H
imidazo[5,1-f]-[ 1,2,4]triazin-4-one H
O=S=O
N
N
I

0.1 g (0.26 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo-[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride are dissolved in lOml of dichloromethane and cooled to 0°C. After addition of a spatula tip of DMAP, 80 mg (0.784 mmol) of N-methylpiperazine are added and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane, the organic phase is washed with ammonium chloride solution and dried over sodium sulphate and the solvent is removed under reduced pressure. The residue is chromatographed over silica gel (dichloromethane/methanol 9:1 ).
Yield: 40 mg (34.5% of theory) Mass spectrum: 447 (M+H); 284; 256; 224.

Le A 32 733-Forei~Yn countries _88_ Example 2 2-[2-Ethoxy-5-(4-hydroxyethylpiperazine-1-sulphonyl)-phenyl)-5,7-dimethyl-3H
imidazo[5,1-f]-[ 1,2,4]triazin-4-one H3C~
O=S=O
N
c~
N
OH
By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-fj[ 1,2,4Jtriazin-2-yl)-benzenesulphonyl chloride and 100 mg (0.784 mmol) of 4-hydroxypiperazine, 45 mg (36.1% of theory) of 2-[2-ethoxy-5-(4-hydroxy-ethylpiperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-fJ-( 1,2,4)triazin-4-one are obtained.
Mass spectrum: 477 (M+H); 284; 256; 239.

Le A 32 733-Foreign countries Example 3 2-[2-Ethoxy-S-(4-hydroxypiperidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-fj-[ 1,2,4)triazin-4-one H3C~
O=S=O
i N
OH
By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4.-oxo-3,4-dihydroimidazo[5,1-f][ 1,2,4)triazin-2-yl)-benzenesulphonyl chloride and 80 mg (0.784 mmol) of 4-hydroxypiperidine, 35 mg (29.8% of theory) of 2-[2-ethoxy-S-(4-hydroxy-piperidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[S,1-fj-[1,2,4]triazin-4-one are obtained.
200 MHz ~H-NMR (CDC13): 1.61, t, 3H; 1.69, m, 2H; 1.94, m, 2H; 2.67, s, 3H;
2.70, s, 3H; 3.02, m, 2H; 3.30, m, 2H; 3.84, m, 1 H; 4.37, q, 2H; 7.18, d, 1 H;
7.90, dd, 1 H;
8.52, d, 1 H; 9.73, s, 1 H.

L.e A 32 733-Foreign countries Example 4 2-[2-Ethoxy-5-(4-hydroxymethylpiperidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f ] [ 1,2,4J triazin-4-one O=S=O
t N
OH
By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-fJ[ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 90 mg (0.784 mmol) of 4-hydroxymethylpiperidine, 22 mg (18% of theory) of 2-[2-ethoxy-5-(4-hydroxy-methylpiperidine-1-sulphonyl)-phenylJ-5,7-dimethyl-3H-imidazo[5,1-fJ( 1,2,4Jtriazin-4-one are obtained.
200 MHz ~H-NMR (CDCl3): 1.38, dt, 2H; 1.62, t, 3H; 1.82, dd, 2H; 2.35, dt, 2H;
2.78, s, 3H; 2.84, s, 3H; 3.5, d, 2H; 3.87, d, 2H; 4.39, q, 2H; 7.21, d, 1H;
7.95, dd, 1 H; 8.51, d, 1 H; 10.03, bs, 1 H.

Le A 32 733-Foreign countries Examule 5 2-[2-Ethoxy-5-(3-hydroxypyrrolidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H
imidazo[5,1-f]-[ 1,2,4]triazin-4-one H3C~
O=S=O
N
OH
By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-fJ[ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 70 mg (0.7$4 mmol) of 3-hydroxypyrrolidine, 13 mg (11.1% of theory) of 2-[2-ethoxy-S-(3-hydroxy-pyrrolidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo-[5,1-f][ 1,2,4]triazin-4-one are obtained.
Mass spectrum: 434 (M+H) Example 6 4-Ethoxy-N-ethyl-N-(2-hydroxyethyl)-3-(5,7-dimethyl-4-oxo-3,4-dihydro-imidazo[5,1-f]-[ 1,2,4]triazin-2-yl)benzenesulphonamide O=S=O
i H3C~N~OH

L.e A 32 733-Forei~~n countries By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)- .
benzenesulphonyl chloride and 70 mg (0.784 mmol) of 2-(ethylamino)-ethanol, 23 mg (20.1 % of theory) of 4-ethoxy-N-ethyl-N-(2-hydroxyethyl)-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo-[5,1-fj[ 1,2,4)triazin-2-yl)-benzene-sulphonamide are obtained.
200 MHz'H-NMR (CDC13): 1.2, t, 3H; 1.6, t, 3H; 2.17, bs, 1H; 2.69, s, 3H;
2.75, s, 3H; 3.33, m, 4H; 3.8, t, 2H; 4.36, q, 2H; 7.18, d, 1 H; 7.99, dd, 1 H; 8.6, d, 1 H; 9.84, bs, l H.
Example 7 N,N-Diethyl-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazoj5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide H

O=S=O
H3C~N~CH3 By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzene-sulphonyl chloride and 60 mg (0.784 mmol) of diethylamine, 21 mg ( 18.6% of theory) of N,N-diethyl-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydro-imidazo[5, l-f] [ 1,2,4]triazin-2-yl)-benzenesulphonamide are obtained.
200 MHz'H-NMR (CDC13): 1.18, t, 6H; 1.61, t, 3H; 2.68, s, 3H; 2.72, s, 3H;
3.29, q, 4H; 4.35, q, 2H; 7.15, d, 1 H; 7.95, dd, 1 H; 8.58, d, 1 H; 9.8, bs, 1 H.

' Le A 32 733-Foreign countries Example 8 2-[2-Ethoxy-5-(4-(2-pyrimidinyl)-piperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-imidazo-(5,1-f][ 1,2,4]triazin-4-one O CHs H3C~0 HN ~ N
\ ~N.N~

O=S=O
i N
C
N
N~N
S
By the same method, starting with 100 mg {0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-fJ[ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 130 mg (0.784 mmol) of 1-(2-pyrimidinyl)-piperazine, 38 mg (28.2% of theory) of 2-[2-ethoxy-5-(4-(2-pyrimidinyl)-piperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo-[5,1-f][1,2,4]triazin-4-one are obtained.
200 MHz'H-NMR (CDCI3)_ 1.6, t, 3H; 2.68, s, 3H; 2.72, s, 3H; 3.12, t, 4H;
3.96, t, 4H; 4.34, q, 2H; 6.5, t, 1 H; 7.18, d, 1 H; 7.9, dd, 1 H; 8.28, d, 2H; 8.51, d, 1 H; 9.7, bs, 1H.

' Le A 32 733-Foreisn countries Example 9 2-(2-Ethoxy-5-(morpholine-4-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4-one H3C~
O=S=O
i N
C~
s O
By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][ 1,2,4]triazin-2-yl)- ' benzenesulphonyl chloride and 70 mg (0.784 mmol) of morpholine, 28 mg (24.2%
of theory) of 2-[2-ethoxy-S-(morpholine-4-sulphonyl)-phenyl]-5,7-dimethyl-3H
imidazo[5,1-fJ[ 1,2,4]triazin-4-one are obtained.
200 MHz'H-NMR (CDC13): 1.53, t, 3H; 2.69, s, 3H; 2.72, s, 3H; 3.06, t, 4H;
3.77, t, 4H; 4.39, q, 2H; 7.2, d, 1 H; 7.91, dd, 1 H; 8.51, d, 1 H; 9.78, bs, 1 H.

' Le A 32 733-Foreign countries Example 10 2-[2-Ethoxy-5-( 1,4-dioxa-6-azaspiro[4.4]nonane-6-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4-one H3C~
O=S=O
l N
O
~J
By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 100 mg (0.784 mmol) of 1,4-dioxa-6-azaspiro[4.4]nonane, 45 mg (35.3% of theory) of 2-[2-ethoxy-5-(1,4-dioxa-6-azaspiro[4.4]nonane-6-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]-triazin-4-one.
200 MHz ~H-NMR (CDC13): 1.58, t, 3H; 2.02, t, 2H; 2.61, s, 3H; 2.65, s, 3H;
3.32, s, 2H; 3.41, t, 2H; 3.88, m, 4H; 4.34, q, 2H; 7.17, d, 1H; 7.92, dd, 1H; 8.51, d, 1H;
9.92, bs, 1 H.

~
L,e A 32 733-Forei,~n countries Examine 11 N,N-B is-(2-methoxyethyl)-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydro-imidazo[5,1-f]-[ 1,2,4]triazin-2-yl)-benzenesulphonamide O=S=O
i ~O~N~O~CH3 By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzene-sulphonyl chloride and 100 mg (0,784 mmol) of bis-(2-methoxyethyl)-amine, 37 mg (27.5% of theory) of N,N-bis-(2-methoxy-ethyl)-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide are obtained.
200 MHz 'H-NMR (CDC13):1.58, t, 3H; 2.61, s, 3H; 2.64, s, 3H; 3.3, s, 6H;
3.46, t, 4H; 3.56, t, 4H; 4.32, q, 2H; 7.12, d, i H; 7.95, dd, 1 H; 8.51, d, 1 H; 9.9, bs, 1 H

Le A 32 733-Foreign countries _97_ Example 12 N-(3-Isoxazolyl)-4.-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonamide O CHs H3C~O HN ~ N
N~N

O=S=O
H~N N~O
By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo [5,1-f] [ 1,2,4] triazin-2-yl )-benzenesulphonyl chloride and 70 mg (0.784 mmol) of 3-aminoisoxazol, 20 mg (17.2% of theory) N-(3-isoxazolyl)-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide are obtained.
200 MHz ~H-NMR (CDCl3): 1,6, t, 3H; 2.73, s, 3H; 2.81, s, 3H; 4.35, q, 2H;
6.6, d, 1 H; 7.14, d, 1 H; 8.05, dd, 1 H; 8.27, d, 1 H; 8.63, d, 1 H; 9.61, bs, 1 H.

Le A 32 733-Foreign countries Example 13 2-[2-Ethoxy-5-(2-t-butoxycarbonylaminomethyimorpholine-4-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4-one H3C~
O=S=O
N H

O ~,[

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 170 mg (0.784 mmol) of 2-t-butoxycarbonyl-aminomethylmorpholine, 64 mg (42.2 % of theory) of 2-[2-ethoxy-5-(2-t-butoxycarbonylaminomethylmorpholine-4-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.
Mass spectrum: 563 (M+H) L.e A 32 733-Foreign countries Examule 14 2-[2-Ethoxy-5-(4-phenylpiper~azine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f]-[ 1,2,4]triazin-4-one H3C~
O=S=O
i N
C~
N
By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 130 mg (0.784 mmol) of 1-phenylpiperazine, 38 mg (28,3 % of theory) of 2-[2-ethoxy-5-(4-phenylpiperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4-one are obtained.
200 MHz ~H-NMR (CDCI3):1.62, t, 3H; 2.72, s, 3H; 2.77, s, 3H; 3.25, m, 8H;
4.38, q, 2H; 6.92, m, 2H; 7.02, d, 1 H; 7.18-7.37, m, 3 H; 7.94, dd, 1 H; 8.55, m, 1 H; 9.79, bs, 1 H.

- Le A 32 733-Foreign countries Example 15 2-(2-Ethoxy-5-(3-hydroxy-3-methoxymethylpyrrolidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H imidazo[5,1-f][ 1,2,4]triazin-4-one O=S=O
N
OH b_CHs By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 100 mg (0.784 mmol) of 3-hydroxy-3-methoxymethylpyrrolidine, 30 mg (23.5% of theory) of 2-(2-ethoxy-5-(3-hydroxy-3-methoxymethylpyrrolidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.
Mass spectrum: 478 (M+H) Le A 32 733-Foreign countries Example 16 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f)[ 1,2,4]triazin-4-one N
C
N
I
CHs 1.23 g (3 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f)[1,2,4)triazin-2-yl)-benzenesulphonyl chloride are dissolved in 40 ml of dichloromethane and cooled to 0°C. After addition of a spatula tip of DMAP, 0.90 g (9.00 mmol) of N-methylpiperazine are added, and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane, the organic phase is washed twice with water and dried over sodium sulphate and the solvent is removed under reduced pressure. Crystallization from ether gives 1.25 g ''? (88%) of a colourless solid.
200 MHz'H-NMR (CDCl3): 1.01, t, 3H; 1.59, t, 3H; 1.88, hex, 2H; 2.29, s, 3H;
2.51, m, 4H; 2.63, s, 3H; 3.00, t, 2H; 3.08, m, 4H; 4.33, quart., 2H, 7.17, d, ,1 H;
7.88, dd, 1 H; 8.44, d, 1 H; 9.75, s, 1 H.

Le A 32 733-Foreign countries Example 17 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-S-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one lactate ''" N OH
C ~ H
N~H s 100 mg (0.211 mmol) of 2-[2-ethoxy-S-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f] [ 1,2,4]triazin-4-one are suspended in 5 ml of ether and admixed with 20 rng of an 85% strength solution of lactic acid in water.
The mixture is stirred at room temperature for 10 minutes and evaporated to dryness.
The residue is titrated with ether and filtered off with suction. This gives 110 mg (92%) of 2-[2-ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-S-methyl-7-propyl-3H-imidazo[5,1-fJ[1,2,4]triazin-4-one lactate.
200 MHz ~H-NMR (DMSO-db): 0.92, t, 3H; 1.22] d, 3H; 1.31, t, 3H; 1.74, m, 1H;
2.15, s, 3H; 2.38, m, 4H; 2.81, t, 2H; 2.91, m, 4H; 4.05, quart., 1H; 4.21, quart., 2H;
7.40, d, 1H; 7.85, m, 2H; 11.71, s, broad, 1H.

~
Le A 32 733-Forei,Pn countries Exam~Ie 1$
2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride N
C
N~H
CHs 100 mg (0.211 mmol) of 2-[2-ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are suspended in 5 ml of diethyl ether, admixed with 0.23 ml of a 1M solution of HCl in ether and stirred at room temperature for 15 minutes. The solvent is removed under reduced pressure.
This gives 107 mg (97%) of 2-[2-ethoxy-S-(4-methyl-piperazine-1-sulphonyl) phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride.
200 MHz 'H-NMR (DMSO-db): 0.93, t, 3H; 1.35, t, 3H; 1.75, sex., 2H; 2.72, s, 3H;
2.86, m, 4H; 3.15, m, 2H; 3.45, m, 2H; 3.81, m, 2H; 4.25, quart., 2H; 7.45, d, 1 H;
7.95, m, 2H; 11.39, s, 1 H; 11.90, s, 1 H.

Le A 32 733-Foreign countries Examale 19 2-[2-Ethoxy-5-(4.-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4-one H3C~
C
N
C
N
H3~J
470 mg ( 1.14 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride are dissolved in 20 ml of dichloromethane and cooled to 0°C. 390 mg (3.42 mmol) of N-ethylpiperazine are added, and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane, the organic phase is washed twice with water and dried over sodium sulphate and the solvent is removed under reduced pressure.
Crystallization from ether gives 370 mg (66%) of a colourless solid.
400 MHz ~H-NMR (CDCI~): 1.01, t, 3H; 1.59, t, 3H; 1.88, hex, 2H; 2.42, quart., 2H;
2.56, m, 4H; 2.63, s, 3H; 3.00, t, 2H; 3.10, m, 4H; 4.33, quart., 2H, 7.17, d, ,1 H; 7.88, dd, 1 H; 8.44, d, 1 H; 9.75, s, 1 H.

~
Le A 32 733-Foreign countries Example 20 2-[2-Ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride N

HsC
0.35 g (0.712 mmol) of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are suspended in 8 ml of ether and dichloromethane is added until a homogeneous solution is formed. 0.8 ml of a 1 M solution of HCl in ether is added, and the mixture is stirred at room temperature for 20 minutes and filtered off with suction. This gives 372 mg (99%) of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4-one hydrochloride.
200 MHz 'H-NMR (DMSO-d6): 0.96, t, 3H; 1.22; t, 3H; 1.36, t, 3H; 1.82, sex., 2H;
2.61, s, 3H; 2.88, m, 2H; 3.08, m, 6H; 3.50, m, 2H; 3.70, m, 2H; 4.25, quart., 2H;
7.48, d, 1 H; 7.95, m, 2H; 11.42, s, 1 H; 12.45, s, 1 H.

Le A 32 733-Foreign countries Examule 21 2-[2-Ethoxy-5-(4-methyl-1-amino-piperazine-I-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4.-one By the same method, starting with 0.04 g (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5, I-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 0.03 g (0.29 mmol) of I-amino-4-methylpiperazine, 40 mg (83%) of 2-[2-ethoxy-5-(4-methyl- I-amino-piperazine- I-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4.-one are obtained.
Rf = 0.09 (dichloromethane/methanol = 19:1 ) 200 MHz 'H-NMR (CDC13): 1.02, t, 3H; 1.59, t, 3H; 1.90, sex., 2H; 2.22, s, 3H;
2.40, m, 4H; 2.62, s, 3H; 2.71, m, 4H; 3.00, m, 2H; 4.32, quart., 2H; 7.14, d, IH;
1 S 8.05, dd, 1 H; 8.60, d, 1 H.

- Le A 32 733-Porei;en countries Example 22 2-[2-Ethoxy-5-(4-hydroxyethyl-1-amino-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazoj5,1-f][ 1,2,4]triazin-4-one ~N~NH
NJ
f HO
By the same method, starting with 0.04 g (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo [5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 0.04 g (0.29 mmol) of 1-amino-4-hydroxyethylpiperazine, 46 mg (91%) of 2-[2-ethoxy-5-(4-hydroxyethyl-1-amino-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f)[1,2,4]triazin-4-one are obtained.
Rf = 0.08 (dichloromethane/methanol = 19:1 ) 200 MHz ~H-NMR (CDC13): 1.02, t, 3H; 1.59, t, 3H; 1.90, sex., 2H; 2.49, m, 6H;
2.62, s, 3H; 2.71, m, 4H; 3.00, t, 2H; 3.55, t, 2H; 4.31, quart., 2H; 7.14, d, 1H; 8.05, dd, 1 H; 8.60, d, 1 H.

L,e A 32 733-Foreign countries Example 23 , N,N-bishydroxyethylamindethyl-4-ethoxy-3-(5-methyl(-4-bxo-7-propyl-3,4-dihydro-imidazo.~,~.-~~1,2,~7triazin-2-yl)benzene~ulphonamide H3C~
C
(~"'~, HN
OH
N~
H
By the same method, staortW g wdth 0:04 g (0.097 mnol.) of 4-ethoxy=3 (5-methyl- .
4-oxo-7-prapyl-3,4-d~rc~O-imidam/5,1 f//1,2,4/triazvi-2-yl)brl,pt~yl deride and 0.043 g (0.29 mml) of N,N~ishydmxyethylandr~o-ethylartrino, 46 mg (91~
of N,Nbishychnxyp~tt~rlardr~oethyl-4-ethoxy-3-(5-methyl-4-oxo-7-psnpyl-3,4-~~~"o , ~ ,1-~7~'1, 2; ~'aiaiitr2 y7,) 1~.~ are obtained.
200 MHz 'H-NMR (CDC13): 1.02, t, 3H; 1.53, t, 3H; 1.70, m, 2H; 1.86, sex., 2H;
2.9, m, 9H; 2.95, t, 2H; 3.09, t, 2H; 3.65, t, 4H; 4.28,.quart., 2H; 7.14, d, 1H; 7.95, dd, 1 H; 8.35, d, 1 H.

Le A 32 733-Foreign countries Example 24 2-(2-Ethoxy-5-(4-dimethoxyphosphorylmethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H imidazo[5,1-fJ[ 1,2,4Jtriazin-4-one 1~'' N
C
N
H3~-~. J
O~P
O.CHs By the same method, starting with 0.4 g (0.97 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride, 390 mg of triethylamine and 0.86 g (2.99 mmol) of 4-dimethoxyphosphorylmethyl-piperazine frifluoroacetate, 321 mg (53%) of 2-[2-ethoxy-5-(4-dimethoxyphosphoryl-methyl-piperazine-1-sulphonyl)-phenyl]-S-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4Jtriazin-4-one are obtained.
R f = 0.4 (dichloromethane/rnethanol = 20:1 ) 200 MHz ~H-NMR (CDC13): 1.02, t, 3H; 1.60, t, 3H; 1.88, sex., 2H; 2.62, s, 3H;
2.75, m, 4H; 3.02, t, 2H; 3.11, m, 4H; 3.70, s, 3H; 3.75, s, 3H; 4.35, quart., 2H; 5.30, s, 2H; 7.18, d, 1 H; 7.88, dd, 1 H; 8.45, d> 1 H; 9.71, s, 1 H.

L.e A 32 733-Foreien countries Example 25 2-[2-Ethoxy-5-(4-diethoxyphosphorylmethyl-piperidine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-fj[ 1,2,4jtriazin-4-one H3C~
C
N
O
H3C O.P
°1 By the same method, starting with 0.4 g (0.97 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 0.86 g (3.7 mmol) of 4-diethoxyphosphorylmethyl-piperidine, 366 mg (49%) of 2-[2-ethoxy-5-(4-diethoxyphosphorylmethyl-piperidine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H imidazo[5,1-fj[1,2,4]triazin-4-one are obtained.
R f = 0.4 (dichloromethane/methanol = 20:1 ) 200 MHz ~H-NMR (DMSO-db): 0.92, t, 3H; 1.20, t, 6H; 1.35, t, 3H; 1.75, m, 7H;
2.25, m, 2H; 2.82, t, 2H; 3.61, d, 2H; 3.95, quin., 4H; 4.21, quart., 2H;
7.38, d, 1 H;
1 S 7.87, m, 2H; 11.70, s, 1 H.

~
I,e A 32 733-Foreign countries Example 26 2-[2-Ethoxy-5-(4-hydroxy-piperidine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[S,1-f] [ 1,2,4] triazin-4-one N
H
By the same method, starting with 531 mg ( 1.29 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 393 mg (3.88 mmol) of 4-hydroxypiperidine, 400 mg (64%) of 2-[2-ethoxy-5-(4-hydroxy-piperidine-1-sulphonyl)-phenyl]-S-methyl-7-propyl-3H-imidazo[5,1-f] [ 1,2,4]triazin-4-one are obtained.
200 MHz ~H-NMR (DMSO-d6): 0.941, t, 3H; 1.32, t, 3H; 1.45, m, 2H; 1.71, m, 4H;
2.48, s, 3H; 2.82, m, 4H; 3.1 1,m, 2H; 3.55, m, 1H; 4.20, quart., 2H; 4.72, d, 1H, 7.39, d, l H; 7.87, m, 2H; 11.70, s, 1 H.

~
Le A 32 733-Foreign countries Example 27 2-{ 2-Ethoxy-5-j4-{2-hydroxy-ethyl)-piperazine-1-sulphonyl]-phenyl }-5-methyl-7-propyl-3H imidazo[5,1-f][1,2,4]triazin-4-one '' N
C~
N
H
By the same method, starting with 411 mg ( 1 mmol) of 4-ethoxy-3-(5-methyl-4.-oxo-7-propyl-3,4-dihydro-imidazo[S,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 391 mg (3 mmol) of 4-hydroxyethylpiperazine, 380 mg (75%) of 2-{2-ethoxy-5-(4-{2-hydroxy-ethyl)-piperazine-1-sulphonyl]-phenyl }-5-methyl-7-propyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4-one are obtained.
Rf = 0.198 (dichloromethane/methanol = 95:5) 200 MHz ~H-NMR (CDCI3):1.02, t, 3H; 1.61, t, 3H; 1.87, hex., 3H; 2.60, m, 7H;
3.00, t, 2H; 3.10, m, 4H; 3.60, t, 2H; 4.36, quart., 2H; 7.18, d, 1 H, 7.89, dd, 1 H, 8.47, d, 1 H, 9.71, s, 1 H.

~
Le A 32 733-Foreign countries Example 28 2-{ 2-Ethoxy-5-[4-(2-hydroxy-ethyl )-piperazine-1-sulphonyl)-phenyl } -5-methyl-7-propyl-3H imidazo[5,1-f)[1,2,4)triazin-4-one hydrochloride N
N:. H
H
200 mg (0.39 mmol) of 2-{2-ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulphonyl)-phenyl }-5-methyl-7-propyl-3H imidazo[5,1-f)[ 1,2,4]triazin-4-one are suspended in ether, admixed with 2 ml of a 1 M solution of HCl in ether and stirred at room temperature for 20 minutes. The solvent is removed, giving 209 mg ( 100%) of 2-{2-ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulphonylJ-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f)[1,2,4)triazin-4-one hydrochloride.
200 MHz ~H-NMR (DMSO-d6): 0.96, t, 3H; 1.35,x, 3H; 1.70, sex., 2H; 2.59, s, 3H;
2.85, t, 2H; 2.99, t, 2H; 3.18, m, 4H; 3.59, d, 2H; 3.75, m, 4H; 4.25, quart., 2H; 7.49, d, 1 H; 7.95, m, 2H; 10.62, s, 1 H; 12.31, s, 1 H.

Le A 32 733-Foreign countries i Example 29 2-{ 2-Ethoxy-5-[4-(3-hydroxy-propyl)-piperazine-1-sulphonyl]-phenyl }-5-methyl-7-propyl-3H-imidazo[5,1-f] [ 1,2,4]triazin-4-one N
N
OH
By the same method, starting with 150 mg (0.37 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 158 mg (1.09 mmol) of 4-(3-hydroxypropyl)-piperazine, 167 mg (83%) of 2-{2-ethoxy-5-[4-(3-hydroxy-propyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4-one are obtained.
Rf = 0.52 (dichloromethane/methanol = 10:1 ) 200 MHz'H-NMR (CDC13):1.02, t, 3H; 1.61, t, 3H; 1.70, m, 5; 2.62 m, 8H; 3.00, t, 2H; 3.10, m, 4H; 3.72, t, 2H; 4.36, quart., 2H; 7.18, d, 1 H, 7.89, dd, 1 H, 8.47, d, i H, 9.71, s, 1 H.

Le A 32 733-Foreign countries Example 30 N-Allyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f j [ 1,2,4]triazin-2-yl)benzenesulphonamide N
CH OH
By the same method, starting with 420 mg ( 1.02 mmol) ( 1 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 300 mg (3 mmol) of allylhydroxyethylamine, 400 mg (82%) of N-allyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-(S-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo(5,1-f)(1,2,4]triazin-2-yl)benzenesulphonamide are obtained.
R f = 0.345 (dichloromethane/methanol = 95:5) 200 MHz'H-NMR (CDCl3):1.02, t, 3H; 1.61, t, 3H; 1.90, m, 2H; 2.22, s, broad, 1H;
2.62, s, 3H; 2.99, t, 2H; 3.31, t, 2H; 3.78, t, 2H; 3.92, d, 2H; 4.37, quart., 2H; 5.23, 1 S m, 2H; 5.71, m, 1 H; 7.15, d, 1 H; 7.98, dd, 1 H; 8.56, d, 1 H; 9.66, s, 1 H.

~
Le A 32 733-Foreign countries Example 31 N-Ethyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[S,1-f] [ 1,2,4]triazin-2-yl)benzenesulphonamide '' N
OH
By the same method, starting with 411 mg ( 1.0 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 267 mg (3 mmol) of ethylhydroxyethylamine, 325 mg (70%) of N-ethyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)benzenesulphonamide are obtained.
Rf = 0.29 (dichloromethane/methanol = 95:5) 200 MHz ~H-NMR (CDC13):1.02, t, 3H; 1.20, t, 3H; 1.61, t, 3H; 1.88, sex., 2H;
2.30, s, broad, 1H; 2.62, s, 3H; 2.99, t, 2H; 3.32, m, 4H; 3.78, t, 2H; 3.80, m, 2H;
4.37, quart., 2H; 7.15, d, 1 H; 7.98, dd, 1 H; 8.56, d, 1 H; 9.70, s, 1 H.

Le A 32 733-Foreisn countries Example 32 N,N-Diethyl-4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)benzenesulphonamide N
~1 By the same method, starting with 400 mg (0.97 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 210 mg (2.92 mmol) of diethylamine, 398 mg (89%) of N,N-diethyl-4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo [5,1-f] [ 1,2,4]triazin-2-yl)benzenesulphonamide are obtained.
R f = 0.49 (dichloromethane/methanol = 20:1 ) 200 MHz ~H-NMR (CDC13):1.02, t, 3H; 1.20, t, 6H; 1.49, t, 1.61, t, 3H; 1.88, sex., 2H; 2.30, s, broad, 1H; 2.62; s, 3H; 2.99, t, 2H; 3.32, m, 4H; 3.78, t, 2H;
3.80, m, 2H;
1 S 4.37, quart., 2H; 7.15, d, 1 H; 7.98, dd, 1 H; 8.56, d, 1 H; 9.70, s, 1 H.

Le A 32 733-Foreien countries Example 33 N-(2-Methoxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fj[ 1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide H3C~O~NH
By the same method, starting with 1.23 g (3 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4Jtriazin-2-yl)-benzenesulphonyl chloride and 680 mg (9 mmol) of 2-methoxyethylamine, 900 mg (67%) of N-(2-methoxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f]( 1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide are obtained.
Rf = 0.25 (dichloromethane/methanol = 95:5) 400 MHz 'H-NMR (CDCl3): 1.01, t, 3H, 1.58, t, 3H; 1.88, sex., 2H; 2.62, s, 3H;
3.01, t, 2H; 3.18, quart., 2H; 3.30, s, 3H; 3.45, t, 2H; 4.32, quart., 2H;
5.12, t, 1H;
7.13, d, 1 H, 7.97, dd, 1 H, 8.53, d, 1 H; 9.82, s, 1 H.

Le A 32 733-Foreign countries Examule 34 N-(2-N,N-Dimethylethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro imidazo[5,1-f) [ 1,2,4]triazin-2-yl )-4-ethoxy-benzenesulphonamide H
H3C~N~NH
I
CHs By the same method, starting with 210 mg (0.49 mmol) of 4-ethoxy-3-{5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 130 mg (9 mmol) of 2-N,N-dimethylethylamine, 150 mg (59%) of N-(2-N,N-dimethylethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fj[1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide are obtained.
200 MHz ~H-NMR (CDCl3): 1.01, t, 3H, 1.62, m, 4H; 1.88, sex., 2H; 2.11, s, 6H;
2.39, t, 2H; 2.63, s, 3H; 3.01, m, 3H; 4.38, quart., 2H; 7.13, d, 1H, 7.97, dd, 1H, ~"~, 8.53, d, 1 H; 9.82, s, 1 H.

L.e A 32 733-Foreien countries Examule 35 N-[3-( 1-Morpholino)propyl]-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo [5,1-f] [ 1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonarnide S
By the same method, starting with 1.23 g (3 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 1.3 g (9 mmol) of 3-( 1-morpholino)-propylamine, 1.38 g (88%) of N-[3-( 1-morpholino)propyl]-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide are obtained.
Rf= 0.23 (dichloromethane/methanol = 95:5) 200 MHz ~H-NMR (CDCl3): 1.01, t, 3H, 1.58, t, 3H; 1.72, m, 2H; 1.88, sex., 2H;
2.46, m, 6H; 2.62, s, 3H; 3.01, t, 2H; 3.15, t, 2H; 3.71, t, 4H; 4.32, quart., 2H; 7.13, d, 1 H, 7.97, dd, 1 H, 8.53, d, 1 H; 9.79, s, 1 H.

Le A 32 733-Foreien countries Examule 36 N-{ 3-[ 1-(4-Methyl)piperazino]-propyl }-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide H3C~ ~O H
I ~ \N~
H3C~ I
N~ O=S=O
1" 5 ~N~NH
By the same method, starting with 0.04 g (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fj[ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 0.05 g (0.29 mmol) of 3-( 1-(4-methyl-)piperazino]-propylamine, 0.04 g (77%) of N-{3-[1-(4-methyl)piperazino]-propyl}-3-(5-methyl-4.-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fj(1,2,4]triazin-2-yl)-4.-ethoxy-benzenesulphonamide is obtained.
Rf = 0.11 (dichloromethane/methanol = 95:5) 200 MHz ~H-NMR (CDCl3): 1.01, t, 3H, 1.55, t, 3H;1.68, m, 2H; 1.88, sex., 2H;
2.27, s, 3H; 2.45, m, 8H; 2.62, s, 3H; 2.98, m, 3H; 3.10, t, 2H; 3.46, s, 1H;
4.30, quart., 2H; 7.13, d, 1 H, 7.97, dd, 1 H, 8.53, d, 1 H.

~
Le A 32 733-Foreign countries Example 37 2-{ 2-Ethoxy-5-[4-(2-methoxy-ethyl)-piperazine-1-sulphonylj-phenyl }-5-methyl-7-propyl-3H imidazo[5,1-f][1,2,4]triazin-4.-one N
C
N
H3C~0 By the same method, starting with 40 mg (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo(S,1-f ] [ 1,2,4)triazin-2-yl)-benzenesulphonyl chloride and 40 mg (0.29 mmol) of 4-methoxyethylpiperazine, 50 mg (99%) of 2-{2-ethoxy-5-[4-(2-methoxy-ethyl)-piperazine-1-sulphonyl]-phenyl }-5-methyl-7-propyl-3H-imidazo[5,1-f}[ 1,2,4]triazin-4-one are obtained.
R f = 0.27 (dichloromethane/methanol = 95:5) 200 MHz 'H-NMR (CDCl3):1.02, t, 3H; 1.61, t, 3H; 1.87, hex., 3H; 2.60, m, 9H;
2.97, t, 2H; 3.10, m, 4H; 3.60, s, 3H; 3.46, t, 2H; 4.36, quart., 2H; 7.18, d, 1H, 7.89, dd, 1 H, 8.47, d, 1 H, 9.71, s, 1 H.

Le A 32 733-Foreign countries Examule 38 2- { 2-Ethoxy-5-[4-(2-N,N-dimethyl-ethyl)-piperazine-1-sulphonyl]-phenyl } -5-methyl-7-propyl-3H imidazo[5,1-f][1,2,4]triazin-4-one H3C~
C
N
C~
N
HsC.N.CHs By the same method, starting with 40 mg (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[S,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 50 mg (0.29 mmol) of 4-(2-N,N-dimethyl)-ethylpiperazine, 50 mg (99%) of 2-{2-ethoxy-5-[4-(2-N,N-dimethyl-ethyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4-one are obtained.
R f = 0.11 (dichloromethane/methanol = 95:5) 200 MHz 1H-NMR (CDCI3):1.02, t, 3H; 1.61, t, 3H; 1.87, hex., 3H; 2.20, s, 6H;
2.42, m, 4H; 2.58, m, 4H; 2.63, s, 3H; 2.99, m, 3H; 3.10, m, 4H; 4.36, quart., 2H;
7.18, d, 1 H, 7.89, dd, 1 H, 8.47, d, 1 H, 9.71, s, 1 H.

Le A 32 733-Forei n countries Example 39 2- { 2-Ethoxy-5-[4-(3-N,N-dimethyl-propyl)-piperazin-1-sulphonyl]-phenyl } -5-methyl-7-propyl-3H-imidazo[5,1-f] [ 1,2,4]triazin-4-one N
C
N
H3C~N
I
CHs By the same method, starting with 100 mg (0.243 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 130 mg (0.73 mmol) of 4-(3-N,N-dimethyl)-propylpiperazine, 72 mg (54%) of 2-{2-ethoxy-5-[4-(3-N,N-dimethyl-propyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H imidazo[5,1-f][1,2,4]triazin-4-one are obtained.
R~ = 0.08 (dichloromethane/methanol = 95:5) 200 MHz ~H-NMR (CDC13):1.02, t, 3H; 1.61, t, 3H; 1.87, sex., 3H; 2.20, s, 6H;
2.25, m, 2H; 2.38, t, 2H; 2.52, m, 4H; 2.63, s, 3H; 2.99, m, 6H; 4.33, quart., 2H;
7.18, d, 1 H, 7.89, dd, 1 H, 8.47, d, 1 H, 9.71, s, 1 H.

I_x A 32 733-Foremen countries Example 40 2-[2-Ethoxy-5-(4-dioxolano-piperidine-1-sulphonyl)-phenyl]-S-methyl-7-propyl-imidazo[5,1-f] [ 1,2,4]triazin-4-one H3C~
C

'' N
O~O
By the same method, starting with 100 mg (0.243 mmol) of 4-ethoxy-3-(S-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4Jtriazin-2-yl)-benzenesulphonyl chloride and 100 mg (0.73 mmol) of 4-dioxolanopiperidine, 111 mg (88%) of 2-[2-ethoxy-5-(4-dioxolano-piperidine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-imidazo[5,1-fJ[1,2,4]triazin-4.-one are obtained.
200 MHz'H-NMR (CDC13):1.02, t, 3H; 1.61, t, 3H; 1.80, m, 6H; 2.63, s, 3H;
2.99, t, '' 2H; 3.20, m, 4H; 3.90, s, 4H; 4.33, quart., 2H; 7.18, d, 1 H, 7.89, dd, 1 H, 8.47, d, 1 H, 9.71, s, 1H. , Le A 32 733-Foreign countries Examine 41 2-[2-Ethoxy-5-(4-(5-methyl-4-furoxanecarbonyl)-piperazine-1-sulphonyl)-phenyl]-5-methyl-?-propyl-3H imidazo(5,1-f][1,2,4]triazin-4-one 410 mg (1.0 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo(5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride are dissolved in 10 ml of dichloromethane and cooled to 0°C. 590 mg (2.00 mmol) of 1-(5-methyl-4-furoxanecarbonyl)-piperazine trifluoroacetate and 400 mg of triethylamine are i0 added, and the reaction mixture is stirred at room temperature overnight.
The mixture is diluted with dichloromethane, the organic phase is washed with ammonium chloride solution, 1M hydrochloric acid and water and dried over sodium sulphate and the solvent is removed under reduced pressure. Crystallization from ether gives 448 mg (74%) of a colourless solid.
200 MHz ~H-NMR (CDC13): 1.01, t, 3H; 1.59, t, 3H; 1.88, hex, 2H; 2.25, s, 3H;
2.63, s, 3H; 3.00, t, 2H; 3.20, m, 4H; 3.90, m, 2H; 4.02, m, 2H; 4.33, quart., 2H, 7.19, d, 1 H; 7.89, dd, 1 H; 8.48, d, 1 H; 9.57, s, 1 H.

Le A 32 733-Foreign countries Example 42 2-{ 2-Ethoxy-5-[4-acetyl-piperazine-1-sulphonyl]-phenyl }-5-methyl-7-propyl-3H-imidazo[5,1-f] [ 1,2,4)triazin-4-one N
C~
N
H3CI ' O
By the same method, starting with 40 mg (0.097 mmol) of 4-ethoxy-3-(S-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 40 mg (0.29 mmol) of N-acetylpiperazine, 9 mg ( 18%) of 2-{ 2-ethoxy-5-[4-acetyl-piperazine-1-sulphonyl]-phenyl}-S-methyl-7-propyl-3H imidazo[5,1-f][1,2,4)triazin-4-one are obtained.
Rf = 0.34 (dichloromethane/methanol = 95:5) 200 MHz ' H-NMR (CDCl3):1.02, t, 3H; 1.6 i, t, 3H; 1.87, sex., 3H; 2.05, s, 3H; 2.63, s, 3H; 3.00, m, 6H; 3.59, m, 2H; 3.72, m, 2H; 4.33; quart., 2H; 7.18, d, 1H, 7.89, dd, 1 H, 8.47, d, 1 H, 9.71, s, 1 H.

Le A 32 733-Foreign countries Example 43 2- { 2-Ethoxy-5-[4-formyl-piperazine-1-sulphonyl]-phenyl } -5-methyl-7-propyl-imidazo[5,1-fJ[ 1,2,4]triazin-4-one H3C~
C

N
C~
N
HI 'O
By the same method, starting with 40 mg (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl )-benzenesulphonyl chloride and 30 mg (0.29 mmol) of N-formylpiperazine, 35 mg (73%) of 2-{2-ethoxy-5-[4-formyl-piperazine-1-sulphonyl]-phenyl }-5-methyl-7-propyl-3H
imidazo[5,1-f][ 1,2,4]triazin-4-one are obtained.
R~ = 0.29 (dichloromethane/methanol = 95:5) 200 MHz ~H-NMR (CDC13):1.02, t, 3H; 1.61, t, 3H; 1.87, sex., 3H; 2.05, s, 3H;
2.63, s, 3H; 3.00, m, 6H; 3.50, m, 2H; 3.69, m, 2H; 4.33, quart., 2H; 7.18, d, 1H, 7.89, dd, 1 H; 8.00, s, 1 H; 8.47, d, 1 H, 9.71, s, 1 H.

Le A 32 733-Fore~ountries Example 44 2-[2-Ethoxy-S-(3-butylsydnoneimine)-1-sulphonyl )-phenyl]-5-methyl-7-propyl-3H
imidazo[S,1-f] [ 1,2,4]triazin-4-one 110 mg (0.6 mmol) of 3-butylsydnoneimine hydrochoride are dissolved in 2.5 ml of pyridine and cooled to 0°C. 210 mg (0.5 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fJ [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride are added, and the reaction mixture is stirred for 2 hours at 0°C and overnight at room temperature. The mixture is diluted with dichloromethane, the organic phase is washed with water and dried over sodium sulphate and the solvent is removed under reduced pressure. Chromatography (dichloromethane/methanol) gives 16 mg (6%) of 2-[2-ethoxy-S-(3-butylsydnoneimine)-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f) [ 1,2,4]triazin-4-one.
Rf = 0.41 (dichloromethane/methanol = 95:5) 200 MHz tH-NMR (CDC13): 1.01, 2t, 6H; 1.47, sex., 2H; 1.55, t, 3H; 1.88, m, 2H;
2.04, quin., 2H; 2.62, s, 3H; 2.98, t, 2H; 4.29, quart., 2H; 4.41, t, 2H;
7.08, d, 1H;
7.56, s, 1 H; 7.98, dd, 1 H; 8.58, d, 1 H; 9.79, s, broad, 1 H.

Le A 32 733-Foreign countries Examine 45 5-Methyl-2-[5-(4-methyl-piperazine-1-sulphonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazo[5,1-f] [ 1,2,4]triazin-4-one N
~~N

0.85 g (2 mmol) of 4-propoxy-3-(5-methyl-4.-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]-triazin-2-yl)-benzenesulphonyl chloride are dissolved in 20 ml of dichloromethane and cooled to 0°C. After addition of a spatula tip of DMAP, 0.60 g (6.00 mmol) of N-methylpiperazine is added and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane, the organic phase is washed with ammonium chloride solution and dried over sodium sulphate and the solvent is removed under reduced pressure. Crystallization from ether gives 0.80 g (77%) of a colourless solid.
Rf = 0.233 (dichloromethane/methanol = 95:5) ' 200 MHz 'H-NMR (CDC13): 1.00, t, 3H; 1.15, t, 3H; 1.87, hex, 2H; 1.99, hex., 2H;
2.30, s, 3H; 2.52, m, 4H; 2.62, s, 3H; 2.99, t, 2H; 3.10, m, 4H; 4.21, t, 2H;
7.17, d, 1 H; 7.87, dd, 1 h, 8.48, d, 1 H, 9.70, s, 1 H.

Le A 32 733-Foreisn countries Example 46 S-Methyl-2-[S-{4-methyl-piperazine-1-sulphonyl)-2-propoxy-phenyl]-7-propyl-3H
imidazo[5,1-f)[1,2,4)triazin-4.-one hydrochloride N+-HCI
CHs 22 mg (0.045 mmol) of 5-methyl-2-[S-(4-methyl-piperazine-1-sulphonyl)-2-propoxy-phenyl)-7-propyl-3X-imidazo[5,1-f)[ 1,2,4)triazin-4.-one are dissolved in 2 ml of ether and 1 ml of dichloromethane and admixed with 0.1 ml of a 1 M solution of HCl in ether. After 20 minutes, the precipitate is filtered off with suction and dried.
200 MHz ~H-NMR (CDC13): 0.95, t, 3H; 1.75, m, 2H; 2.56, s, 3H; 2.75, m, 4H;
2.97, t, 2H; 3.15, m, 2H; 3.44, m, 2H; 3.81, m, 2H; 4.15, t, 2H; 7.47, d, 1H; 7.95, m, 2H;

11.12, s, 1 H; 12.22, s, 1 H.

a L.e A 32 733-Foreign countries Example 47 2-[5-(4-Hydroxypiperidine-1-sulphonyl)-2-propoxy-phenyl]-5-methyl-7-propyl-3H
imidazo[5,1-f][ 1,2,4]triazin-4-one IV
OH
By the same method, starting with 850 mg (2 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo [5,1-f] [ 1,2,4] triazin-2-yl )-benzenesulphonyl chloride and 610 mg (6 mmol) of 4-hydroxypiperidine, 736 mg (75%) of 2-[5-(4-hydroxypiperidine-1-sulphonyl)-2-propoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.
Rf = 0.07 (dichloromethane/methanol = 95:5) 200 MHz ~H-NMR (CDC13): 1.01, t, 3H; 1.16, t, 3H; 1.80, m, 9H; 2.65, s, 3H;
3.00, m, 4H; 3.32, m, 2H; 3.85,m, 1 H; 4.22, t., 2H; 7.17, d, l H; 7.89, dd, 1 H;
8.50, d, 1 H;
11.70, s, 1 H.

Le A 32 733-Foreign countries Example 48 2-[S-(4-Hydroxymethylpiperidine-1-sulphonyl)-2-propoxy-phenyl]-S-methyl-7-propyl-3H imidazo[S,1-f][ 1,2,4]triazin-4-one S HO
By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-{S-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[S,1-f] ( 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 3S mg (0.3 mmol) of 4-hydroxymethylpiperidine, 41 mg (82%) of 2-[S-(4-hydroxymethylpiperidine-1-sulphonyl)-2-propoxy-phenyl]-S-methyl-7-propyl-3H-imidazo[S,1-f][1,2,4]triazin-4-one are obtained.
Rf = O.S2 (dichloromethane/methanol = 9:1 ) 200 MHz 'H-NMR {CDC13): 1.001, t, 3H; 1.16, t, 3H; 1.60, m, 4H; 1.82, m, SH;
2.31, t, 2H, 2.62, s, 3H, 2.98, t, 2H, ; 3.48, d, 2H; 3.85, d, 2H; 4.21, t, 2H; 7.,17, d, 1S 1H; 7.88, dd, 1H, 8.45, d, 1H; 9. 71, s, 1H.

Le A 32 733-Foreisn countries Example 49 2-{ 5-[4-(2-hydroxyethyl)-piperazine-1-sulphonyl]-2-propoxy-phenyl }-S-methyl-7-propyl-3H imidazo[5,1-f][1,2,4]triazin-4-one N
N
OH
By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 39 mg (0.3 mmol) of 4-hydroxymethylpiperazine, 50 mg (96%) of 2- { 5-[4-(2-hydroxyethyl)-piperazine-1-su lphonyl]-2-propoxy-phenyl } -5-methyl-7-propyl-3H imidazo[5,1-f][1,2,4]triazin-4-one are obtained.
R f = 0.43 (dichloromethane/methanol = 9:1 ) 200 MHz ~H-NMR (CDC13): 1.01, t, 3H; 1.15, t, 3H, 1.88, m, 2H, 2.00, m, 2H, 2.62, m, 9H, 3.00, t, 2H, 3.07, m, 4H, 3.58, t, 2H, 4.23, t, 2H; 7.19, d, 1 H; 7.88, dd, 1 H, 8.43, d, 1 H, 9.85, s, 1 H.

Le A 32 733-Foreign countries Example 50 N-( 1,1-Dioxotetrahydro-1 ~.6-thiophene-3-yl)-3-(5-methyl-4.-oxo-7-propyl-3,4-dihydro-imidazo- [5,1-fJ[ 1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide NH
S
.. ,, O O
By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fJ [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 41 mg (0.3 mrnol) of 2-aminosulpholane, 8 mg ( 14%) of N-( 1,1-dioxotetrahydro-176-thiophene-3-yl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo-[5,1-fJ[1,2,4Jtriazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.
Rf = 0.49 (dichloromethane/methanol = 9:1 ) 200 MHz'H-NMR (CDC13): 1.01, t, 3H, 1.15, t, 3H, 1.85, m, 2H; 1.99, m, 2H;
2.30, m, 1 H; 2.50, m, 1 H; 2.62, s, 3H; 2.95, m, 4H; 3.21, m, 1 H; 4.20, m, 3H;
5.98, s, 1 H;
7.18, d, 1 H, 7.98, dd, 1 H; 8.S l ,d, 1 H, 9.71, s, 1 H. 1 Le A 32 733-Foreign countries Example 51 N-(2-Dimethylaminoethyl)-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide H3C~
C
HsC~N~'~/N~CHs By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 31 mg (0.3 mmol) of 1,1,4-trimethyldiaminoethane, 39 mg (79%) of N-(2-dimethylaminoethyl)-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.
Rf = 0.28 (dichloromethane/methanol = 9:1 ) 200 MHz ~H-NMR (CDCl3): 1.01, t, 3H, 1.15, t, 3H, 1.88, m, 2H; 2.01, m, 2H;
2.25, s, 6H; 2.50, t, 2H; 2.62, s, 3H; 2.82, s, 3H; 3.01, t, 2H; 3.18, t, 2H; 4.21, t, 2H; 7.16, d, 1 H, 7.91, dd, 1 H, 8.50, d, 1 H; 9.70, s, 1 H.

Le A 32 733-Foreign countries Example 52 3-(5-Methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fJ [ 1,2,4]triazin-2-yl)-N-(3-moipholin-4-yl-propyl)-4-propoxy-benzenesulphonamide By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fJ[ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 43 mg (0.3 mmol) of 1-(3-aminopropyl)-morpholine, 52 mg (97%) of (5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-N-(3-moipholin-4-yl-propyl)-4.-propoxy-benzenesulphonamide are obtained.
Rf = 0.33 (dichloromethane/methanol = 9:1 ) 200 MHz ~H-NMR (CDC13): 1.01, t, 3H, 1.15, t, 3H, 1.71, m, 2H; 1.93, m, 4H;
2.43, m, 6H; 2.62, s, 3H; 2.98, t, 2H; 3.12, t, 2H; 3.70, m, 4H; 4.21, t, 2H; 7.15, d, 1H;
7.96, dd, 1 H; 8.55, d, 1 H; 9.85, s, 1 H.

Le A 32 733-Foreign countries Examule 53 N,N-Bis-(2-hydroxyethyl)-3-(5-methyl-4.-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide N
HO OH
By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 32 mg (0.3 mmol) of bishydroxyethylamine, 34 mg (69%) of N,N-bis-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fj[1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.
Rf = 0.36 (dichloromethane/methanol = 9:1 ) 200 MHz ~H-NMR (CDCI3): 1.01, t, 3H; 1.15, t, 3H; 1.85, m, 2H; 1.97, m, 2H;
2.60, s, 3H; 2.98, t, 2H; 3.33, t, 4H; 3.87, t, 4H; 4.20, t, 2H; 7.15, d, 1H; 7.92, dd, 1H;
8.49, d, 1 H; 9.85, s, 1 H. , - Le A 32 733-Foreign countries Example 54 N-(3-Hydroxybenzyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fj [ 1,2,4Jtriazin-2-yl)-4-propoxy-benzcnesulphonamide i3 NH
OH
By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo(S,1-fJ[1,2,4Jtriazin-2-yl)-benzenesulphonyl chloride and 37 mg (0.3 mmol) of 3-hydroxybenzylamine, 4 mg (8%) of N-(3-hydroxybenzyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo(5,1-fJ[1,2,4Jtriazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.
R f = 0.43 (dichloromethane/methanol = 9:1 ) 200 MHz ~H-NMR (CDC13):1.01, t, 3H, 1.13, t, 3H; 1.83, m, 2H; 1.96, m, 2H;
2.59, s, 3H, 2.96, t, 2H, 4.16, m, 4H, S.OS, t, 1H; 6.52,'s, 1H; 6.70, m, 2H; 7.06, m, 2H;
7.93, dd, 1 H, 8.41, d, 1 H, 9.77, s, 1 H.

I,e A 32 733-Foreign countries -Example 55 N-Ethyl-N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide H
O=S=O CH3 N
OH
By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(S-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 27 mg (0.3 mmol) of ethylhydroxyethylamine, 18 mg (38%) of N-ethyl-N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f)[1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.
R f = 0.48 (dichloromethane/methanol = 9:1 ) 200 MHz'H-NMR (CDCl3):1.01, t, 3H; 1.15, 2t, 6H; 1.75, s, 2H; 1.85, m, 2H;
1.98, "'" m, 2H; 2.40, s, 1H; 2.62, s, 3H; 2.99, t, 2H; 3.32, m, 4H; 3.90, quart., 2H, 4.21, quart., 2H; 7.15, d, 1 H; 7.95, dd, 1 H; 8.55, d, 1 H, x.73, s, 1 H.

Le A 32 733-Foreien countries Examote 56 N-(3-Ethoxypropyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide NH
/U
S CHs By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[S,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 31 mg (0.3 mmol) of 3-ethoxypropylamine, 47 mg (96%) of N-(3-ethoxypropyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [
1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.
Rf = 0.60 (dichloromethane/methanol = 9:1 ) 200 MHz 1H-NMR (CDCl3): 1.01, t, 3H; 1.15, m, 6H; 1.89, m, 7H; 2.62, s, 3H;
3.00, t, 2H; 3.12, quart., 2H; 3.46, m, 4H; 4.20, t, 2H; 5.52, m, 1H; 7.15, d, 1H;
7.98, dd, 1 S 1 H; 8.55, d, 1 H, 9.85, s, 1 H.

~
Le A 32 733-Foreign countries Example 57 2-[5(4-Hydroxypiperidine-1-sulphonyl)2-propoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f J[ 1,2,4]triazin-4-one N
OH
By the same method, starting with 212 mg (0.5 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4] triazin-2-yl)-benzenesulphonyl chloride and 152 mg ( 1.5 mmol) of 4-hydroxypiperidine, 125 mg (50%) of 2-[5(4-hydroxypiperidine-1-sulphonyl)2-propoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.
R f = 0.07 (dichloromethane/methanol = 19:1 ) 200 MH2'H-NMR (CDCi3): 1.05, t, 3H; 1.18, t, 3H, 1.98, m, 8H, 2.71, s, 3H;
3.10, m, 2H; 3.28, m, 4H; 3.88, m, 1 H; 4.28, t, 2H; 7.21,, d, 1 H; 7.97, dd, 1 H, 8.45, d, 1 H.
10.45, s, 1 H.

' L.e A 32 733-Foreign countries Example 58 3-(5-Methyl-~4~-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-4-propoxy-N-pyridin-4-yl-benzenesulphonamide H
NH
NJ
By the same method, starting with 85 mg (0.2 mmol) of 4-propoxy-3-($-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f)[ 1,2,4Jtriazin-2-yl)-benzenesulphonyl chloride and 56 mg (0.6 mmol) of 4-aminopyridine, 24 mg (25%) of 3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-N-pyridin-4-yl-benzenesulphonamide are obtained after 18 hours at reflux in 1 ml of THF.
Rf = 0.13 (dichloromethane/methanol = 9:1 ) 200 MHz ~H-NMR (CDC13 + CD30D): 1.01, t, 3H; 1.09, t, 3H; 1.90, m, 4H; 2.50, s, ''! 3H; 2.99, t, 2H; 4.16, t, 2H; 7.05, d, 2H; 7.15, d, 1H; 7.88, d, 2H; 8.05, dd, 1H; 8.41, d, 1 H.

Le A 32 733-Forei~ n~ countries Examule 59 N,N-Diethyl-3-(5-methyl-4-oxo-7-propyl-3,4-di hydro-imidazo[5,1-f j [
1,2,4]triazin-2-y1~4-propoxy-benzenesulphonamide N
~1 By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 22 mg (0.6 mmol) of diethylamine, 42 mg (92%) of N,N-diethyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.
Rf = 0.64 (dichloromethane/methanol = 9:1 ) 200 MHz ~H-NMR (CDCl3): 1.01, t, 3H; 1.18, 2t, 9H; 1.92, 2 hex., 4H; 2.62, s, 3H;
3.00, t, 2H, 3.29, quart., 4H; 4.21, t, 2H; 7.13, d, 1H; 7.93, dd, 1H, 8.51, d, 1H, 9.85, s, 1 H.

' Le A 32 733-Foreign countries Example 60 1-[3-(5-Methyl-4.-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fJ[ 1,2,4)triazin-2-yl)-4-propoxy-benzenesulphonyl]-piperidine-4-carboxylic acid H3C~
C
N
HO O
By the same method, starting from 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f) [ 1,2,4] triazin-2-yl )-benzenesulphonyl chloride and 14 mg (0.6 mmol) of piperidinecarboxylic acid in 1 ml of a mixture of THF and water ( 1:1 ) with 26.5 mg of sodium carbonate, 21 mg (41 %) of 1-[3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fJ[ 1,2,4Jtriazin-2-yl)-4-propoxy-benzenesulphonyl)-piperidine-4-carboxylic acid are obtained.
R f = 0.28 (dichloromethane/methanol = 9:1 ) 200 MHz ~H-NMR (CDC13): 0.90, t, 3H; 1.04, t, 3H; 1.80, m, 4H; 2.21, m, 2H, 2.51, s, 3H, 2.85, m, 2H, 3.56, m, 6H; 4.10, t, 2H; 7.12, d, 1 H, 7.71, dd, 1 H, 8.10, d, 1 H, 10.72, s, broad, 1 H.

I,e A 32 733-Foreign countries Example 61 5-Methyl-2-[5-(morpholine-4-sulphonyl)-2-propoxy-phenyl J-7-propyl-3H
imidazo[5,1-tJ[ 1,2,4]triazin-4-one '' N
C~
By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[S,1-f] [ 1,2,4)triazin-2-yl)-benzenesulphonyl chloride and 26 mg (0.3 mmol) of morpholine, 34 mg (71%) of 5-methyl-2-[5-(morpholine-4-sulphonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazo[5,1-f J [ 1,2,4] triazin-4-one are obtained.
Rf = 0.64 (dichioromethane/methanol = 9:1 ) 200 MHz ~H-NMR (CDC13): 1.01, t, 3H; 1.16, t, 3H, 1.89, hex., 2H, 2.00, hex., ZH;
2.63, s, 3H; 3.02, m, 4H; 4.25, t, 2H, 7.19, d, 1 H, 7.89, dd, 1 H; 8.48, d, 1 H; 9.78, s, 1H. , ' L.e A 32 733-Foreip,~n countries Example 62 N-(2-Hydroxyethyl)-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide H3C~N
OH
By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 23 mg (0.63 mmol) of methylhydroxyethylamine, 25 mg (54%) of N-(2-hydroxyethyl)-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.
Rf = 0.53 (dichloromethane/methanol = 9:1 ) 200 MHz ~H-NMR (CDCI3): 1.01, t, 3H; 1.15, t, 3H; 1.82, m, 2H; 1.99, hex., 2H;
2.40, s, broad, 1H, 2.62, s, 3H, 2.89, s, 3H; 2.99, t, 2H; 3.21, t, 2H; 3.80, s, broad, 2H; 4.21, t, 2H, 7.16, d, 1H; 7.92, dd, 1H, 8.50, d, 1~H, 9.79, s, 1H.

' Le A 32 733-Foreign countries Example 63 N-(2-Hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-4-propoxy-N-propyl-benzenesulphonamide N

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(S-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 31 mg (0.6 mmol) of propylhydroxyethylamine, 20 mg (40%) of N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fj [
1,2,4]-triazin-2-yl)-4-propoxy-N-propyl-benzenesulphonamide are obtained.
Rf = 0.52 (dichloromethane/methanol = 9:1 ) 200 MHz'H-NMR (CDC13): 0.90, t, ,3H; 1.01, t, 3H; 1.15, t, 3H; 1.52, m, 2H, 1.88, m, 2H, 2.00, m, 2H; 2.40, s, 1H; 2.63, s, 3H, 3.01, t, 2H, 3.22, m, 4H; 3.80, quart., 2H; 4.21, t, 2H, 7.15, d, 2H, 7.95, dd, 1 H, 8.55, d, 1 H; 9.75, s, 1 H.
CA 02309332 2000-OS-09~

' L,e A 32 733-Foreign countries Examyle 64 N-[2-(3,4-Dimethoxy-phenyl)ethyl]-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide H3C~N
D~CH3 / ~.CH3 By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 59 mg (0.3 mmol) of N-methyl-3,4-dimethoxyphenylethylamine, 45 mg (78%) of N-[2-(3,4-dimethoxyphenyl)-ethyl]-N-methyl-3-(S-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.
R f = 0.35 (dichloromethane/methanol = 19:1 ) 200 MHz'H-NMR (CDC13): 0.90, t, 3H; 1.07, t, 3H; 1.78, m, 2H; 1.92, m, 2H;
2.55, s, 3H; 2.73, s, 3H; 2.78, m, 2H; 2.89, t, 2H; 3.23, t, 2H, 3.80, s, 6H, 4.15, t, 2H, 6.65, m, 3H, 7.05, d, 1 H, 7.75, dd, 1 H, 8.41, d, 1 H, 9.67, s, 1 H.

' 23189-8549 (S) Example 65 N-Allyl-N-{2-hydroxyethyl)-3-(S-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl}-4-propoxy-benzenesulphonamide H3C.~
C
N

S
By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 31 mg (0.3 mmol) of allylhydroxyethyiamine, 34 mg (70%) of N-allyl-N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.
R~ = 0.52 (dichloromethane/methanol = 9:1 ) 200 MHz ~H-NMR (CDCl3):1.01, t, 3H; 1.15, t, 3H; 1.85, m, 2H; 1.99, m, 2H;
2.38, s, broad, 1H, 2.63, s, 3H; 3.00, t, 2H, 3.32, t, 2H, 3.86, t, 2H, 3.90, d, 2H;
4.25, t, 2H, 5.21, m, 2H, 5.71, m, 1H; 7.15, d, 1h, 7.95, dd, 1H; 8.55, d, 1H, 9.77, s, 1H.

23189-8549 (S) Examyle 66 N-Allyl-N-cyclopentyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f) [ 1,2,4)triazin-2-yl)-4-propoxy-benzenesulphonamide N
CHz By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f) [ 1,2,4)triazin-2-yl)-benzenesulphonyl chloride and 38 mg (0.3 mmol) of allylcyclopentylamine, 33 mg (64%) of N-allyl-N-cyclopentyl-3-(5-methyl-4.-oxo-7-propyl-3,4-dihydro-inudazo[5,1-f)[
1,2,4)triazin-2-yl)~-propoxy-benzenesulphonamide are obtained.
Rf = 0.43 (dichloromethanelmethanol = 19:1 ) 200 MHz 'H-NMR (CDCl3):1.01, t, 3H;1.15, t, 3H; 1.53, m, 9H; 2.00, m, 4H, 2.63, s, 3H; 3.00, t, 2H; 3.80, m, 2H, 4.21, t, 2H, 5.20, m, 2H; 5.88, m, 1H, 7.12, d, 1H, 7.95, dd, 1 H, 8.55, d, 1 H, 9.75, s, 1 H.

i ' 23189-8549 (S) Example 67 N-Allyl-N-ethyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f] [ 1,2,4]-triazin-2-yl )-4.-propoxybenzenesulphonamide js i N' '~CH

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 26 mg (0.3 mmol) of allylethylamine, 30 mg (64%) of N-allyl-N-ethyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-fJ [ 1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.
R~ = 0.44 (dichloromethane/methanol = 19:1 ) 200 MHz 'H-NMR (CDC13):1.01, t, 3H;1.15, t, 6H;1.89, m, 2H, 2.01, m, 2H, 2.63, s, 3H, 3.00, t, 2H, 3.27, quart., 2H, 3.87, d, 2H, 4.23, t, 2H, 5.20, m, 2H, 5.72, m, 1H;
7.15, d, 1 H, 7.95, dd, 1 H, 8.55, d, 1 H; 9.80, s, 1 H. , Le A 32 733-Foreign countries Example 68 2-[2-Ethoxy-4-methoxy-5-(4-mcthylpiperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3 H-imidazo[5,1-f] [ 1,2,4]triazin-4.-one H3( V=J=V
N
C~
N
I
S CHs 20 mg (0.045mmo1) of 4-ethoxy-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo-[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride are dissolved in 0.5 ml of dichloromethane and admixed with a spatula tip of dimethylaminopyridine and 14 mg (0.136 mmol) of N-methylpiperazine, and the reaction mixture is stirred at room temperature overnight. Purification over silica gel gives 12.8 mg (55%) of 2-[2-ethoxy-4-methoxy-S-(4-methylpiperazine-1-sulphonyl)phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f] [ 1,2,4]triazin-4-one.
R f = 0.22 (dichloromethane/methanol = 20:1 ).
200 MHz 'H-NMR (CDC13): 0.94, t, 3H; 1.55, t, 3H; 1.80, m, 2H; 2.24, s, 3H;
2.42, t, 4H; 2.55, s, ,3H; 2.92, t, 2H; 3.19, t, 4H, 3.91, s, 3H; 4.25, quart., 2H;
6.48, s, 1H;
8.57, s, 1 H; 9.54, s, 1 H.

, L,e A 32 733-Foreign countries Example 69 2-{ 2-Ethoxy-5-[4-(2-hydroxyethyl)-piperazine-1-sulphonyl]-4-methoxy-phenyl }-5-methyl-7-propyl-3H-imidazo[5,1-f] [ 1,2,4]triazin-4-one V-J=V
~o""" N
C~
N
OH
By the same method, starting with 20 mg (0.045 mmol) of 4-ethoxy-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo [5,1-f] [ 1,2,4)triazin-2-yl)-benzenesulphonyl chloride and 18 mg (0.14 mmol) of 4-hydroxyethylpiperazine, 11 mg (46%) of 2-{2-ethoxy-5-[4-(2-hydroxyethyl)-piperazine-1-sulphonylJ-4-methoxyphenyl }-5-methyl-7-propyl-3H-imidazo[5,1-f][ 1,2,4]triazin-4-one are obtained.
Rf = 0.34 (dichloromethane/methanol = 15:1 ) 200 MHz 1H-NMR (CDC13): 0.94, t, 3H; 1.55, t, 3H; 1.80, m, 3H; 2.52, m, 9H;
2.92, t, 2H; 3.20, t, 4H; 3.44, t, 2H; 3.92, s, 3H; 4.25, quart., 2H; 6.49, s, 1H;
8.56, s, 1H;
9.55, s, 1 H.

Le A 32 733-Foreittn countries Example 70 4-Ethoxy-N-ethyl-N-(2-hydroxyethyl)-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonamide V-~-V
N
OH
By the same method, starting from 20 mg (0.045 mmol) of 4-ethoxy-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 12 mg (0.14 mmol) of ethylhydroxyethylamine, 8 mg (34%) of 4-ethoxy-N-ethyl-N-(2-hydroxyethyl)-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonamide are obtained.
Rr = 0.45 (dichloromethane/methanol = 15:1 ) 200 MHz'H-NMR (CDCl3): 1.02, t, 3H; 1.18, t, 3H; 1.61, t, 2H; 1.88, m, 2H;
2.39, s, broad, 1H; 2.65, s, 3H; 3.00, t, 2H; 3.38, quart., 2H; 3.45, t, 2H; 3.78, m, 2H; 4.01, s, 3H; 4.20, quart., 2H; 6.58, s, 1 H; 8.67, s, 1 H; 9.61, s, 1 H.

Le A 32 733-Foreisn countries Example 71 4-Ethoxy-N-(4-ethoxyphenyl)-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonamide H3C~0 I\
HaC.O /
O=S=G
''' N
(\
H3C~~ /
By the same method, starting with 20 mg (0.045 mmol) of 4-ethoxy-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzene-sulphonyl chloride and 19 mg (0.14 mmol) of 4-ethoxyaniline, 7 mg (34%) of 4-ethoxy-N-(4-ethoxyphenyl)-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide are obtained.
Rf = 0.36 (dichloromethane/methanol = 20:1 ) 200 MHz ~H-NMR (CDC13): 1.02, t, 3H; 1.33, t, 3H, 1.59, t, 3H, 1.86, hex., 2H, 2.62, s, 3H; 3.02, t, 2H; 3.92, quart., 2H; 4.11, s, 3H; 4.31, quart., 2H;
6.58, s, 1H, 6.72, d, 2H; 6.88, s, broad, 1 H; 6.99, d, 2H, 8.50, s; 1 H; 9.59, s, 1 H.

Le A 32 733-Foreign countries Example 72 4-Ethoxy-N-ethyl-N-(2-hydroxy-ethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f j [ 1,2,4)triazin-2-yl)benzenesulphonamide 'N
C(H
OH
0.64 g ( 1.5 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-fJ[1,2,4]triazin-2-yl)-benzenesulphonyl chloride are dissolved in 20 ml of dichloromethane and cooled to 0°C. After addition of a spatula tip of dimethylaminopyridine, 0.40 g (4.50 mmol) of 2-(ethylamino)-ethanol are added, and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane, the organic phase is washed with water and dried over sodium sulphate and the solvent is removed under reduced pressure. Chromatography (dichloromethane/methanol = 95:5) gives 0.454 g (63%) of a colourless solid.
200 MHz ~H-NMR (CDCl3):1.02, t, 3H; 1.20, t, 3H; 1.35, t, 3H; 1.61, t, 3H;
1.88, sex., 2H; 2.25, s, broad, 1 H; 3.01, m, 4H; 3.32, m, 4H; 3.70, m, 2H; 3.80, m, 2H;
4.37, quart., 2H; 7.15, d, 1 H; 7.98, dd, 1 H; 8.56, d, 1 H; 9.70, s, 1 H.

Le A 32 733-Foreisn countries Example 73 ' N-(2-Methoxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo [S,1-f] [ 1,2,4]triazin-2-yl)-4-ethoxybenzenesulphonamide H3C~.' O=S=O CH3 H3C~O~NH
By the same method, starting with 40 mg (0.094 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f j [ 1,2,4)triazin-2-yl)-benzenesulphonyl chloride and 21 mg (0.282 mmol) of 2-methoxyethylamine, 15 mg (34%) of N-(2-methoxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5, I-f] [
1,2,4]triazin-2-yl)-4.-ethoxybenzenesulphonamide are obtained.
Rf = 0.2 (ethyl acetate/cyclohexane = 2:1 ) 200 MHz 'H-NMR (CDCl3): 0.97, t, 3H;1.25, t, 3H; 1.53, t, 3H; 1.82, sex., 2H;
2.97, m, 4H; 3.11, m, 2H; 3.22, s, 3H; 3.39, t, 2H; 4.37, quart., 2H; 5.00, t, IH; 7.17, d, 1 H, 7.97, dd, 1 H, 8.53, d, 1 H; 9.82, s, 1 H.

Le A 32 733-Foreign countries Examule 74 N,N-B is-(2-methoxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f] [ 1,2,4]triazin-2-yl)-4-ethoxybenzenesulphonamide N
H C, J ~ ,CH

By the same method, starting with 40 mg (0.094 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 38 mg {0.28 mmol) of bismethoxyethylamine, 17 mg (34%) of N,N-bis-(2-methoxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][
1,2,4]triazin-2-yl)-4-ethoxybenzenesulphonamide are obtained.
R f = 0.34 (ethyl acetate%yclohexane = 2:1 ) 200 MHz ~H-NMR (CDCI;): 0.97, t, 3H;1.27, t, 3H; 1.53, t, 3H; 1.80, sex., 2H;
2.95, m, 4H; 3.22, s6H; 3.39, m, 4H; 3.49, m, 4H; 4.27, quart., 2H; 7.17, d, 1H, 7.97, dd, 1 H, 8.53, d, 1 H; 9.82, s, 1 H. , ~
Le A 32 733-Foreign countries Example 75 2-[S-(4-Hydroxypiperidine-1-sulphonyl)-2-ethoxyphenyl]-5-ethyl-7-propyl-3H-imidazo[5,1-f]-[ 1,2,4]triazin-4-one CHs (~"'' N
OH
By the same method, starting with 640 mg ( 1.5 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[S,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 460 mg (4.5 mmol) of 4-hydroxypiperidine, 485 mg (66%) of 2-[5-(4-hydroxy-piperidine-1-sulphonyl)-2-ethoxyphenyl]-5-ethyl-7-propyl-3H-imidazo[5,1 f ][ 1,2,4]triazin-4-one are obtained.
Rf = 0.37 (dichloromethane/methanol = 19:1 ) 200 MHz ~H-NMR (CDCl3): 1.02, t, 3H; 1.32, t, 3H; 1.60, t, 3H; 1.80, m, 7H;
2.97, m, 6H; 3.30, m, 2H; 3.82, m, 1H; 4.34, quart., 2H; 7.17, d, 1H; 7.90, dd, 1H, 8.45, d, 1 H. 9.75, s, 1 H.

Le A.32 733-Foreign countries Example 76 2-[5-(4-Hydroxymethylpiperidine-1-sulphonyl)-2-ethoxy-phenylJ-5-ethyl-7-propyl-3H imidazo[5,1-fJ[1,2,4Jtriazin-4-one H
N
HO
By the same method, starting with 40 mg (0.094 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-fJ [ 1,2,4Jtriazin-2-yl)-benzenesulphonyl chloride and 33 mg (0.28 mmol) of 4-hydroxymethylpiperidine, 23 mg (48%) of 2-[5-(4-hydroxymethylpiperidine-1-sulphonyl)-2-ethoxyphenylJ-5-ethyl-7-propyl-3H imidazo[5,1-f)[1,2,4)triazin-4-one are obtained.
R f = 0.38 (dichloromethane/methanol = 10:1 ) 200 MHz 1H-NMR (CDC13): 1.01, t, 3H; 1.33, t, 3H; 1.60, t, 3H; 1.80, m, 8H;
2.41, m, 2H, 3.00, m, 4H; 3.56, m, 4H; 4.35, quart, 2H; '7.,17, d, 1 H; 7.88, dd, 1 H, 8.45, d, 1H; 9.71, s, 1H.

Le A 32 733-Foreign countries Example 77 2- { 2-Ethoxy-5-[4-(2-hydroxyethyl )-piperazine-1-sulphonyl ]-phenyl } -5-ethyl-7-propyl-3H-imidazo[S,1-f][ 1,2,4]triazin-4-one N
N
OH
By the same method, starting with 40 mg (0.094 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f] [ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 37 mg (0.28 mmol) of 4-hydroxyethylpiperazine, 35 mg (71%) of 2-{2-ethoxy-S-[4-(2-hydroxyethyl)-piperazine-1-sulphonyl]-phenyl }-5-ethyl-7-propyl-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.
Rf = 0.65 (dichloromethane/methanol = 10:1 ) Le A 32 733-Foreign countries Examule 78 2-[2-Ethoxy-5-(4-methylpiperazine- I -sulphonyl)-phenyl]-5-ethyl-7-propyl-3H
imidazo(5,1-f)-( 1,2,4]triazin-4-one H3C~
C
N
c N
I
CHs By the same method, starting with 640 mg ( 1.50 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f]( 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 450 mg (4.5 mmol) of 4-hydroxyethylpiperazine, 495 mg (66%) of 2-(2-ethoxy-5-(4-methylpiperazine-1-sulphonyl)-phenyl)-5-ethyl-7-propyl-3H-imidazo[5,1-fJ[1,2,4)triazin-4-one are obtained.
R~ = 0.30 (dichloromethane/methanol = 19:1 ) 200 MHz ~H-NMR (CDCl3):1.01, t, 3H; 1.35, t, 3H; 1.61, t, 3H; 1.89, sex., 2H;
2.31, s, 3H; 2.53, m, 4H; 3.05, m, 8H; 4.35, quart., 2H; .7.17, d, 1 H; 7.89, dd, 1 H; 8.48, d, 1 H; 9.65 , s, 1 H.

Le A 32 733-Foreign coi untries Example 79 2-(2-Ethoxy-5-(4-methylpiperazine-1-sulphonyl)-phenyl]-5-ethyl-7-propyl-3H-imidazo[5,1-f][1,2,4Jtriazin-4.-one hydrochloride N
C~-N., H
CHs 300 mg (0.61 mmol) of 2-[2-ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-ethyl-7-propyl-3H-imidazo[S,l-fj(1,2,4]triazin-4-one are dissolved in a mixture of ether and dichloromethane and admixed with 2 ml of a 1M solution of HCl in ether.
After 20 minutes, the precipitated solid is filtered off with suction and dried.
200 MHz ~H-NMR (DMSO-db): 0.95, t, 3H; 1.32, 2t, 6H; 1.80, sex., 2H; 2.76, m, 4H; 3.01, m, 4H; 3.15, m, 2H; 3.44, m, 2H; 3.81, m, 2H; 4.25, quart., 2H;
7.49, d, ~'1 1 H; 7.95, m, 2H; 11.25, s, 1 H; 12.30, s, 1 H.

~
Le A 32 733-Foreign countries Example 80 3-(5-Ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][ 1,2,4]triazin-2-yl)-N-(3-mocpholin-4-yl-propyl)-4-ethoxybenzenesulphonamide By the same method, starting with 640 mg ( 1.5 mmol) of 4-ethoxy-3-(5-ethyl-4.-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][ 1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 650 mg (4.5 mmol) of 1-(3-aminopropyl)-morpholine, 476 mg (59%) of 3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f] ( 1,2,4]triazin-2-yl)-N-(3-morpholin-4-yl-propyl)-4-ethoxy-benzenesulphonamide are obtained.
R f = 0.18 (dichloromethane/methanol = 19:1 ) 200 MHz 'H-NMR (CDCl3): 1.01, t, 3H; 1.32, t, 3H; 1.60, t, 3H; 1.70, m, 3H;
1.89, sex., 2H; 2.43, m, 7H; 3.01, m, 4H; 3.15, t, 2H; 3.70, m, 4H; 4.35, quart., 2H; 7.15, d, i H; 7.95, dd, 1H; 8.55, d, 1 H; 9.82, s, 1 H.

Le A 32 733-Foreign countries Example 81 N-(2-Hydroxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][ 1,2,4]triazin-2-yl)-4-ethoxy-N-propyl-benzenesulphonamide N

By the same method, starting with 640 mg ( 1.5 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo 7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 464 mg (4.5 mmol) of propylhydroxyethylamine, 600 mg (81%) of N-(2 hydroxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo [5,1-fJ [
1,2,4]triazin-2 yl)-4-ethoxy-N-propylbenzenesulphonamide are obtained.
R f = 0.73 (dichloromethane/methanol = 10:1 ) 200 MHz 1H-NMR (C1JC13): 0.91, t, ,3H; 1.01, t, 3H; 1.32, t, 3H; 1.62, m, 5H;
1.88, m, 2H; 2.32, s, 1H; 3.01, m, 4H; 3.22, m, 4H; 3.80, m, 2H; 4.35, t, 2H; 7.15, d, 2H, 7.95, dd, 1 H, 8.55, d, 1 H; 9.75, s, 1 H.
The sulphonamides listed in Tables 1, 2, 3, 4 and 6 below were prepared by means of automated parallelsynthesis from 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and the appropriate amine using one of the three standard procedures below.
The sulphonamides listed in Table 5 were prepared by the same methods by means of automated parallelsynthesis from 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-Le A 32 733-Foreign countries imidazo[5,1-b][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and the appropriate amore.
The purity of the final products was determined by means of HPLC, and they were S characterized by LC-MS. The content of the desired compound according to HPLC-MS is given in per cent in the tables in the column "HPLC". Standard procedure A
was used with amines having acidic functionalities, standard procedure B was used with amines having neutral functionalities, standard procedure C was used with amines having additional basic functionalities.
In the structural formulae of Tables 1, 2, 3, 4, 5 and 6 below, hydrogen atoms are in some cases not shown. Nitrogen atoms having a free valency are therefore to be understood as -NH- radical.
Standard procedure A: Reaction of amines having acidic functionalities 0.05 mmol of amine, 0.042 mmol of sulphonyl chloride and 0.10 mmol of Na2C03 are initially charged, and 0.5 ml of a mixture of THF/H~O is pipetted in by hand.
After 24 h at RT, the mixture is admixed with 0.5 ml of 1M H~S04 solution and filtered through a two-phase cartridge (500 mg of Extrelut (upper phase) and 500 mg of Si02, mobile phase ethyl acetate). The product is obtained after concentrating the filtrate under reduced pressure.
Standard procedure B: Reaction of amines having neutral functionalities 0.125 mmol of amine are initially charged and 0.03 mmol of sulphonyl chloride as a solution in 1,2-dichloroethane is pipetted in by the synthesizer. After 24 h, the mixture is admixed with 0.5 ml of 1 M H2S04 and filtered through a two-phase cartridge (500 mg of Extrelut (upper phase) and 500 mg of Si02, mobile phase:
ethyl acetate). The filtrate is concentrated under reduced pressure.

' Le A 32 733-Foreign countries Standard procedure C: Reaction of amines having basic functionalities 0.05 mmol of amine are initially charged and 0.038 mmol of sulphonyl chloride as a solution in 1,2-dichloroethane and 0.05 mmol of triethylamine as a solution in 1,2-dichloroethane is pipetted in by the synthesizer. After 24 h, the solution is initially admixed with 3 ml of saturated NaHC03 solution and the reaction mixture is filtered through a two-phase cartridge. The product is obtained after concentrating the filtrate under reduced pressure.
All reactions are monitored by thin-layer chromatography. If the reaction is not ~"~"'a 10 complete after 24 h at RT, the mixture is heated to 60°C for a further 12 h and the experiment is subsequently terminated.

Le A 32 733-Foreign Countries Table 1: .-_, Ex. No. Structure ~ o ~ HPLC MZ + H
~3 0 CH3 \ NiN /N
82 / 525.6315 83 526 O=S=O
N
OH
0 CH Chiral ~0 N i \ NiN /N
83 ~ 525.6315 71 526 0 =S =O
N
OH
W

~0 N -~
\ \ iN / N
'N
84 CH 555.658 91 556 0=S=O
N
O~CH3 OH

Le A 32 733-Foreign Countries Ex. No. Struchrre 1~ oil HPLC MZ + H
\s 0 CHa 0 N ~\
\ \ ~N / N
_N
85 C H 3 477.5869 76 478 0=S=0 i N
HO
~CH3 H3 ~C
~3 O CH3 O N ~\
\ \ iN / N
I ~N
86 O=S=O CH3 525.63 i5 81 526 HsC N
HO /
O N ~\
\ ~ iN / N
~N
87 ~ 463.5598 65 464 O=S=O
N

OH

L.e A 32 733-Foreign Countries Ex. No. Structure ~~ o ~ HPLC MZ + H

l\0 N
\ ~ iN / N
'N
88 CH 531.6793 83 532 O=S=O
N
OH
H
\3 0 CH3 0 N ~\
\ NON /N
89 C H 463.5598 40 464 O=S=O
HaC N

OH

~0 N
~ ~N ~ N
~N
90 ( / 463.5598 44 464 O =S =0 HO N

Le A 32 733-Foreisn Countries Ex. No. Structure ~ o~~ HPLC MZ + H
\a 0 CH3 O N
\ NiN /N
91 O=S=0 CH' 581.6962 76 582 N
H3C' O
H aC 0 /
I 3 O C~"'13 l\ O N ~ \
\ NiN /N
92 ~ 475.5273 61 476 O O- ~ =O
N
O
' 3 O CH3 [\O N
\ ~ ~N / N
'N
93 ~ / 421.4785 80 422 O=S=O
H3CwO~N

Le A 32 733-Foreign Countries Ex. No. Stnecture i~ o ~ HPLC MZ + H
O CH

O N
\ NiN / N
(/
94 CH3 475.5709 81 476 O=S=O
N
OV
' 3 O CH3 [\O N
NON ~ N
/

O=S=O
95 491.614 97 492 HaC N
~1 \a 0 CH3 ~ \_ ,N ~ N
N
96 C H 3 567.7127 80 568 0=S=0 j \
i ~~CH3 Hl0 ' Le A 32 733-Foreign Countries Ex. No. Structure . ~ oil HPLC MZ + H
p CH3 O N
\ ~ iN /N
'N
97 CH 521.6405 94 522 0=S=0 H3C' N

H3C O~CH

\s 0 CHs \ ~ ~N / N
~N
98 CH3 477.5869 70 478 0=S=0 N

HO CHs ~0 N~ iC
I N
\ NON /
99 ~ / 535.6239 88 536 0~ O-~-0 O ~/~.N

L.e A~ 32 733-Foreign Countries Ex. No. Structure ~ o ~ HPLC MZ + H

O N
\ ~ ~N / N
~N

O=S=O
100 ~ 553.6857 88 554 O

NI Y
\ \ iN /N
-N
101 ~ / 529.6197 85 530 0 0=~=0 0 ~/N

~0 N
\ ~ iN / N
~N
102 ~ / 539.6586 91 540 \ CH3 0=~=0 \/~\/N

' Le A 32 733-Foreign Countries ' - 176 -Ex. No. Structure ~ old HPLC MZ + H
\s 0 CH3 0 N ~\
\ NiN /N

0=S=0 103 ( 520.6121 55 521 N
0~0 ,N
HsC ~CH3 ' 3 0 CH3 '\ 0 N
\ NiN /N
104 ~ 502.6404 82 503 O =S =O
wN ~N
CH3 O CH.3 \ ~ iN /N
-N
105 ~ 564.712 i 86 565 0=S=0 N
I N

' Le A 32 733-Foreign Countries Ex. No. Structure ~~ oil HPLC MZ + H
\3 O CH3 O N
\ NiN / N
_ ~3 106 O ~ O 524.6467 85 525 N
HsCw N

O N ~\
\ NiN / N
/
_ _ CH3 107 O- ~ -O 538.6738 85 539 N
N
/ I \CHa CH3 p CH3 ~0 N ~-~N
\ ~ ~N /
'N
108 C H 546.694 84 547 =p 3 ~N N

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ + H
[g/mol]

'O N
\ NiN /N
504.6127 90 505 O =S=0 ~N ~/N
OJ

Le A 32 733-Foreign Countries Table 2:
Ex. No. Structure ~~~ ~ HPLC MZ+H

[\0 N
\ NrN /N
110 ~ / 507.6134 74 508 0=S=0 I
HO~N~O~CH3 [\0 N
\ NrN /N
111 ~ 539.6586 75 540 0 =S =0 I
HO' ~ /N /
C1YH 3 ~' \
CH3 O CH3 , ~O N i _ \ NrN / N
112 HO _ CH3 599.711 S 83 600 ~NS O CH3 O
O

' Le A 32 733-Foreign Countries Ex. No. Structure . ~~~ ~ HPLC MZ+H

l\0 N
\ NiN / N
113 ( / 535.6675 60 536 HO 0=S=0 w N~CH3 OH

O N
~ NON ~N
114 ~ / 521.6405 95 522 O=S=O
I
H3C~0~/N~OH
. CH3 O CHs ~O N i \ /N /~N
-N
115 HO CH3 569.6851 84 570 S=O
N
O

Lx A 32 733-Foreign Countries Ex. No. Structure ~~ ~ HPLC MZ+H
\s 0 CHa \ NON /N
116 ~ 608.5486 85 608 CH
HO_ "_S-0 s \~-~\''~N C I
CI
\3 0 CHa \ NiN /N
117 I / 569.6851 88 570 CH
HO_ "-S-0 / H3 3 '~' N ~ 0 ~O N
\ W ~N /.N
~N
118 ( / 463.5598 94 464 O=S=O
I
N~~OH
H3C~

Le A 32 733-Foreien Countries Ex. No. Structure ~ ~~~ HPLC MZ+H

O N
\ \ iN / N
'N
119 ~ , 535.6675 93 536 O=S=O
I
H3C ~0 ~N ~O ~CH3 \0 N
\ NiN /N
120 ~ / 517.6522 71 518 0=S=0 0 N~CH3 ~O N
\ NiN' /N
121 H3~~
561.7058 92 562 ~S=0 N\
J,0 Le A 32 733-Foreign Countries Ex. No. Structure ~~~ ~ HPLC MZ+FI
~3 ~ CH3 O N
\ NiN /N
122 ~ 539.6586 85 540 0=S=0 .~ '~OH
NN
' 3 O CH3 [\0 N
\ NiN / N
123 ~ S 18.6834 87 519 CH3 O=S=0 ~N ~N ~CH3 ~CH3 ~0 N i ~ NON ~~N
124 ~ ~H 588.1307 30 588 CI ~ 0=
OH

Le A 32 733-Foreisn Countries r Ex. No. Structure ~~~ ~ HPLC MZ+H

[\0 N
\ N iN / N

125 ~=S-0 550.685 83 551 N
C
N
\
~3 0 CH3 \0 N
\ NiN /N

126 ~=S-0 542.7057 77 543 N
N

[\0 N ~\
\ \ iN / N
~N
127 ~ 502.6404 91 503 0=S=0 I
N
H'C /
N
~CH3 L.e A 32 733-Foreign Countries Ex. No. Structure ~ ~1~ HPLC MZ+H
\a O CH3 O N
'~. ~N / N
'N
128 / 490.6292 45 491 i H3 O=S=O
,N N ~
H3C ~ CH3 p CH3 O N
\ ~ iN / N
I _N
129 O=S=O ~H3 568.7003 66 569 HaC
N
CH3 O CH3 , ~O N ~-\ W iN /.N
I -N
130 ~H 534.6828 86 535 O=S=O

~CH3 N
~CH3 Le A 32 733-Foreign Countries Ex. No. Structure . ~~ o ~ HPLC MZ+H
\a 0 CH3 \ NON /N
131 I ~ 580.7551 95 581 CH
H3C~ 0=S=0 3 /N~N ._-~3 O CH3 \0 N
\ NiN /N
132 ~ 576.7205 87 577 0=S=O
H3C~N OH
~O
N_ /
\s O CH
O N
\ NiN /.N , CH
133 0=S=O 3 598.7296 60 599 N
N

Le A 32 733-Foreign Countries Ex. No. Structure ~~~ ~ HPLC MZ+H
' 3 ~ CH3 '\O N
\ ~ iN / N
-N
O=S=O
134 N S 16.6675 95 517 N

0 N ~\
\ N ~N / N

0=S=0 135 ~ 528.6786 80 529 N
N

Le A 32 733-Foreign Countries Ex. No. Structure ~~ a~~ HPLC MZ+H

~O N
\ NON /N
136 ~ , 538.6738 85 539 0=S=0 ~ N N-CHI

~0 N
\ NiN /N
137 I i 533.6981 68 534 iH3 0=i=O
H3C~N~N~N~CH3 NON /N
138 ~ ~ 516.6675 91 517 0=S=O

CA 02309332 2000-OS-09 ' Le A 32 733-Foreisn Countries Ex. No. Structure ~~~ ~ HPLC MZ+H
0 CHa \ NON /N
139 ~ / 489.598 85 490 0=S=0 N OH
~3 O CH3 \O N
\ ~ iN / N
~N
140 / ~ 475.5709 83 476 O=S=O
I
N
HO

~0 N ~- ' \ NON /~N

141 ~ 503.6251 85 504 0=S=0 I
N OH

Le A 32 733-Foreign Countries Ex. No. Structure ~~ o ~ HPLC MZ+H
\s O CH

O N
\ NiN / N
142 CH3 489.598 91 490 O=S=O
I
N
OH
~3 O CH3 \\O N
\ \ ~N / N
~N
143 ~ ~ 461.5438 78 462 O=S=O
I
N
HO
\a 0 CH3 \ ~ iN / N
~N
144 ~ 539.6586 88 540 O=S=0 I
\ N~OH

Le A 32 733-Foreign Countries Ex. No. Structure ~ ~ ~ HPLC MZ+H
13 ~ CH3 O N
\ NON /N
i 145 ~ ~ ~H3 539.6586 58 538 o=s=o ~J\OH
\a O CH

O N
\ ~ iN / N
'N
146 ~ 511.6044 80 S 12 ~3 O=S=O
\ N~OH
CH3 , O N
\ NiN /N
147 I ~ 505.6411 90 506 _ CH3 HsC~NS OOH

Le A 32 733-Foreign Countries Table 3:
Ex. No. Structure . ~ o ~ HPLC MZ + H

\ NiN /N
_ _ CH3 148 0 - ~ -0 565.70 38 566 N
OH

O N
\ NiN /N
149 H3C~0 CH3 643.77 85 644 Ha; 0=S-0 0 ~"' ~O~CH
N a O

L,e A 32 733-Foreign Countries Ex. No. Structure ~~ o ~ HPLC MZ + H

(\0 N ~\
\ NiN /N
l50 C H 3 525.63 80 526 0=S=0 \s 0 CHa \ ~ iN / N
-N
151 / 525.63 78 526 0=S=0 ~'0 H

' Le A 32 733-Foreign Countries Ex. No. Strucdrre ~~ old HPLC MZ + H

~0 N i N/N ~~N

0=S=0 I
152 N 560.63 51 561 N

0 \ /'0 'C'~H 3 \s 0 CH3 \ ~ iN / N
~N
153 0=S=0 CH3 503.65 78 504 N
N
H3C~ ~CH3 Le A 32 733-Foreign Countries Ex. No. Structure {~ o ~ HPLC MZ + H
~3 0 CH3 0 N ~\
\ \ iN / N
~N
154 C H 3 522.63 82 523 0 =S =0 I
N
N
O

O N
\ NiN / N

155 O=S=O 502.60 84 503 N
IN
O~
I

Ix A 32 733-Forei,~n Countries . -196 -Ex. No. Structure ~~ o ~ HPLC MZ + H

[\0 N
\ ~ ~N / N
~N
156 CH3 488.57 83 489 0=S=0 N
N
HO~

~0 N
~ N,N / N
/

157 0=S=0 536.65 82 537 N
N

Le A 32 733-Foreign Countries Ex No. Structure 1~ oil HPLC MZ + H
\s 0 CH3 \ NiN /N
158 I 490.63 90 491 -.S-H3C~N~N~CH3 ~0 N i _ \ NON ~N

159 0=S=0 537.65 83 538 N
N
N~

Le A 32 733-Foreien Countries Ex. No. Structure . i~ o~~ HPLC MZ + H
~3 O CH3 \O N
\ N ~N / N
160 ~ / 504.66 91 SOS

0=S=0 I
H3C~N~N~CH3 ~CH

~0 N i ~N
~ ,N /
_N
161 0=S=0 CH3 589.81 65 590 I
N

H3C ~ CH3 \ ~ ~N / N
'N
162 CH3 488.61 88 489 0 =S =0 N
N

Lx A 32 733-Foreign Countries Ex. No. Structure ~ o ~ HPLC MZ + H

~0 N
\ NiN /N
163 ~ CH 566.73 32 567 0=S =0 ' I
N

'3 p CH3 \ \ iN / N
'N
l64 ~ 501.61 75 502 0=~= 0 N / ~N
0 CH3 ., \ N iN ~ N
165 C H 3 491.6 I 91 492 0=S=0 N

Le A 32 733-Forei ng Countries Ex. No. Structure ~ a~i HPLC MZ + H

_O N i ~N
. ~ NON /
166 ~ / 477.59 ?3 478 O =S =0 HO
N
CH3 O CH Chiral O N
\ NiN / N
I
167 O=S=O CH3 525.63 81 526 HsC ,,. N
HO
CH3 ., l\ O N
\ N iN / N
I
168 CH3 488.57 70 489 0=S=0 ~~N
C' ~~JJ~'N
OJ
CA 02309332 2000-OS-09, Le A 32 733-Foreign Countries Ex. No. Structure ~~~ HPLC MZ + H

~0 N- Y\
\ N iNI / N
169 0=S=0 CH3 511.60 76 512 N
HO

~0 N
\ NiN /N
170 ~ 568.70 50 569 OH 0=S=0 HsC~N \

CH3,, _O N
\ NiN /N
171 ~ 554.67 63 555 OH 0=S=0 HsCiN \

Le A 32 733-Foreign Countries Ex. No. Structure ~~ o ~ HPLC MZ + H

\0 N-'~=
\ NiN /N
172 ~ ~H 582.73 50 583 OH O=S=0 ' ~N' \ I
CHI O CHI
~O N
\ NiN /N

173 ~ off 637.76 30 638 0 o=s=o O~N~ /
~--" \ ~
j H3 ° CH

O N
\ \ ~N / N ., -N

O=S=O
I74 554.67 70 555 N~CH3 OH

Le A 32 733-Foreign Countries Ex. No. Structure ~~ ~ HPLC MZ + H

'\ 3 O N
\ NiN / N
~3 O=S=O
~ 75 568.70 44 569 N
N~CH3 OH

Le A 32 733-Ausland Table 4:
Ex. No. Structure . ~~ ot) HPLC MZ+H

~O N
\ Ni'N / N
176 I ~ 477.59 82 478 O=S=O
H C'O

\5 O CH3 O N
\ NiN / N
177 ~ 491.61 89 492 O=S=O
H5C~0 3 O CHs O N
NON ~ N , O=S=O
178 505.64 88 506 N
O
H3C CHs Le A 32 733-Ausland Ex. No. Structure ~~ oll HPLC MZ+H

~O N i ~N
\ ~ ,N /
"N
179 ~ / 513.62 47 514 .~. N O=~=O
N~'N

CHa O CH3 ~O N
\ NiN /N
180 CH 504.66 83 505 H C'N N

~O N
NiN /N
181 ~ / 552.70 83 553 CH3 O= ~ =O
N N

Le A 32 733-Ausland MW HPLC MZ~H
Ex. No. Structure (glrool]
O ~
O N i NiN ~ N

182 O= ~ =O 492.60 72 493 N
H3Cw N
OH

O N
N/N / N

O=S=O
N
183 593.75 52 594 N
c N
CA 02309332 2000-OS-09 .

Le A 32 733-Ausland Ex. No. Structure MW HPLC MZ+H
O
O N
\ NiN / N
~ 84 CH3 504.66 82 505 O=S=O
N
~3 ~C~N' CH3 '~3 l'0 N
~ iN / N
-N

185 O= ~ =O
582.75 59 583 N
N
~S

Le A 32 733-Ausland Ex. No. Structure ~~ o ~ HPLC MZ+H
\a O CH3 O N
\ NiN / N

O=S=O
186 566.68 60 567 N
N
~O
~3 O CH3 O N
\ NON / N

O=S=O
187 579.73 30 580 N
N~ , ~N~

Le A 32 733-Ausland Ex. No. Structure MW HPLC MZ+H
(g/molj O
O N
\ ~ iN / N
-N
188 O- ~'-O ~ 548.63 73 549 N
O CHs \O N
\ '~ ~N / N
-N
_ _ CH3 189 O ~ O
548.63 72 549 N
N~N
N

Le A~32 733-Ausland Ex. No. Structure MW HPLC MZ+H
~g/mol~
~3 O CH3 \O N
\ yN/N / N
/
~3 190 O- ~ -O 559.67 54 560 N
~O
HCS\\

l\ O N
\ ~ iN / N
'N
191 511.60 70 512 OH O=S=O CH3 N

CH3 p CH3 ~O N i ~N
\_ ,N /
N .

CH 580.76 68 581 N / S=O 3 "-N

Le A 32 733-Ausjand Ex. No. Structure j~o,olj MW HPLC MZ+H
' 3 O CH3 l'0 N
\ NiN / N
193 ~ ~' 476.60 89 477 O=S=O
I
H3C~N~N~CH3 ~O N
\ NiN /N
194 I / 583.71 80 584 O=S=O
OH
H3C~../O
~/
\s O CH3 O N
NON / N
195 I \ 505.64 84 506 O=S=O
H3C~N~OH

Le A 32 733-Ausland Ex. No. Structure (~ oli HPLC MZ+H
O
O N
\ NiN / N
196 ~ / 518.68 40 519 ~3 O=S=O CH3 H3C~N~/N~CH

~3 l\0 N
\ NiN / N
CH
O=S=O 3 528.68 82 ? 529 N
N

Le A 32 733-Ausland Ex. No. Structure ~~ o~~ HPLC MZ+H
\s O CHs O N
\ jy~N / N

O=S=O
I
198 N 566.68 63 567 c~
N
H3C~0 f 3 O CH3 l\ O N
\ ~ ~N / N
-N
199 CH3 553.69 87 554 O=S=O
I
N
HO
~3 O CH3 O N
\ \ iN / N
200 I _N
/ 491.61 84 492 O=S=O
I
H3C~N~OH

Le A 32 733-Foreign Countries Table 5 ,-, Ex. No. Structure MW HPLC MZ+
~3 0 CH3 \0 N
\ \ iN / N
'N

201 0 = ~ =0 516.67 87 517 N
N
~3 0 CH3 0 N ~\N
~ ,N /
'N

202 0 = ~ =0 502.64 84 503 N

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+
~3 ~ CH3 0 N ~\
\ ~ ~N / N
~N

203 0 = ~ =0 516.67 87 517 N
N
~3 0 C
0 N ~\
\ NON /N
C~3 204 0 - ~ -0 538.67 91 539 N
H3C~N ~ \
3 ~ C'H3 O N
\ \ ~N / N
~N
205 ~ 533.7 85 534 O=S=O
~~rH3 N
Fi3C~N~N~CH3 Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+
..--.-__ -.

\ NON /N

206 0 = ~ =0 518.68 77 519 N
H3C wN CH3 I

\3 0 CH3 \ \ ~N / N
-N

O =S =0 207 566.73 92 567 N
H 3C ~N
\

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+
~3 0 CH3 0 N ~\
\ ~ ~N / N
I N

0 =S =0 208 552.7 87 553 N
N~CH3 I~
~3 0 CHa 0 N ~\
\ ~ ~N / N
I -N
_ _ CH3 209 0 - ~ -0 506.63 52 507 N
N ' H3C~
OH

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+
g 0 CH3 \ W ~N / N
'N
_ _ CH3 210 0 - ~ -0 560.72 62 561 N

N
O J
3 O ~3 O N ~\
\ \ ~N / N
'N
211 ~3 568.7 88 569 O=S=O
N

N~
OH

0 N ~\
\ W iN / N
'N
212 p=S=0 CH3 582.73 89 583 N
\ /CH3 N(~
OH

Le A 32 733-Foreign Countries Ex. No. Structure MW IiPLC MZ+
\3 0 CH3 0 N ~\
\ ~ iN / N
_N
213 CH3 580.71 83 581 0 =S=0 N
I \ ~0 / NJ
~3 0 CH3 \0 N
\ \ /N / N
~N
I
_ _ CH3 214 0- ~ -0 518.64 89 519 N
N

~3 0 CH3 \0 N ~ \
\ ~ ~N / N
'N
215 ~ / 4b3.5b 90 464 0=S=0 I
H3C ~N OOH

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+

O N ~ \N
\ ~ ~N /
'N
216 ~ ~ 548.71 78 549 ~3 0=S=0 HO~N~N~CH3 H3~J
\s O CHa O N ~\
\ NON / N
217 ~ 490.63 87 491 ~3 0=S=0 H3C~N~N~CH3 0 CI~3 O N
\ NON /N
218 ~ ~ 532.71 93 533 CH3 O= i =0 \N ~/N ~C H 3 ~C H

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+
3 ~ 'rH3 '0 N
\ ~ ~N / N
'N
_ _ CH3 219 0- ~ -0 564.71 91 565 N
N
\s 0 CHa 0 N ~\
\ '~ ~N / N
'N
_ _ CH3 220 0- ~ -0 556.73 92 557 N
N

Lx A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+
g 0 CH3 [\0 N ~ \
\ ~. ~N / N
-N
221 ~ / 516.67 92 517 0=S=0 N

N
wCH3 0 N ~\
\ /N ~ N
222 I ~ N 504.66 83 505 CH3 0=S=0 H3C ~N ~N ~CH3 ~3 O CH3 O N
\ NON / N ..
223 ( ~ 558.75 90 559 O=S=O
~N,~N CH3 Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+

[\0 N
NON /N
224 ~ ~ 532.71 86 533 0=S=0 ~ H3 HsC I N~,/~/NwCH3 0 N ~\
NiN /N
225 ~ 572.78 68 573 iH3 0=i-p ~N~N

~3 0 CH3 O N ~\
y /N / N
~ ~N

226 O=SAN ~ H3 582.73 87 583 HO
H3C\
N

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+

\0 N
\ N iN / N
227 ( ~ 548.71 85 549 0=S=0 H3C_N OH ~CH3 ~N
\.-CH3 O N ~ \N
\ NON /
594.78 97 595 ~3 0 ~ -0 H3C"'~
'~ N '_ ~3 O CH3 O N
\ ~ iN / N
'N
229 ~ 590.75 90 591 O=S=O
HsC~ ~ OH
'O
N, /

Ix A 32 733-Foreign Countries Ex. No. Stnzcture MW HPLC MZ+
~3 O CH3 \0 N
\ \ iN / N
-N

0 =S =0 230 N 530.69 95 531 N

~3 0 CH3 \0 N
\ '~ /N / N
-N

231 0 =S =0 542.71 88 543 N
N

O N ~ \N
NON /
232 ~ / 552.7 91 553 O=S=O
f Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+

\ ~ ~N / N
'N
233 I / 534.68 65 535 0=S=0 ~ Ha HO~N~N~CH3 \O N ~ \
\ \ /N / N
'N
234 ~ 520.66 83 521 '~3 0-S=0 OH
HsC-N~ CHs - ~N
~CH3 O N ~\
\ ~ /N ~ N
-N
235 ~ ~ 530.69 89 531 O=S=O

Le A 32 733-Fore~~n Countries Ex. No. Structure MW HPLC MZ+

t\0 N
\ ~ ~N / N
'N

236 0 =S =0 542.71 ?0 543 N
N

\ NiN /N
/

0 =S=0 I
237 N 580.71 81 581 c N
\ ( , H3C,0 Le A 32 733-Forei;e_n Countries ' - 228 -Ex. No. Structure MW HPLC MZ+

O N
\ \ ~N / N
'N
238 / 504.66 81 505 O=S=O
I
H3C~N~N.~CH3 I

~0 N
\ ~ ~N / N
-N

239 0=S=0 551.67 86 552 N
N
N~
O CH3 , O N
\ \ ~N / N
-N
240 / 518.68 85 519 O=S=O
I
H3C~N~N~CH3 ~CH3 '' Le A 32 733-Foreign CounL~ies .

Ex. No. Structure MW HPLC MZ+
\a 0 CHs \ NON /N
241 C H 3 502.64 85 503 0=S=0 I
N
N

\3 0 CH3 O N
\ \ iN / N
-N
242 CH3 580.76 79 581 O=S=O
I
N
H3CnN~\/ /
HaCJ

L.e A 32 733-Foreisn Countries Table 6 Ex. No. Structure MW HPLC MZ+H
\a 0 CH3 0 N ~\
\ ~ iN / N
'N
243 ~ 477.5869 86 478 0=S=0 I
N
~ _0~CH3 \3 0 CH3 0 N ~i\
\ ~ iN / N
~N
244 ~ / 495.605 62 496 0 =S =0 N
\
CH3 O CHs ~O N i \ ~ iN / N
-N
245 / 51 ( .6044 50 512 O=S=O
I
N
\ ~ ~CH3 O

L,e A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
' 3 p CH3 '\0 N
\ NiN /N
/
246 0 =S =0 C H a 564.495 40 565 I
N
CI
/
CI \

0 N ~\
\ ~ iN / N
~N

247 0 = i =0 555.658 61 556 N

~CH3 O~CH

\s 0 CH3 \ ~ iN / N
-N
248 CH3 497.5773 60 498 0=S=0 I
N \
/

I

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H

N
N
NON /
/
249 ~, 581.6963 77 582 oho~~
'O' ~ /N
//
~9 \s O CHa O N ~ \N
~ ~N /
~N
/ '1 250 O=S=O CH3 557.6303 76 558 I
N \
H3C~0 / O
I
O~ CH3 N
\ ~ ~N / N
-N

251 0 =S =0 539.615 74 540 N

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
' 3 O CH3 '~0 N ~i \
\ ~ ~N / N
~N
252 C H 3 515.5677 64 516 0 =S =0 N \
/' ~0 ~3 0 CHI
0 N ~ \N
\ N ~N /
253 CH 472.5266 38 473 0 =S =0 N
Ow ~CHa N
, '\0 N ~ \
\ ~ iN / N
-N
254 ~ CH 459.5715 88 460 0=S=0 I
N

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
~3 0 CH3 0 N ~\
\ ~ ~N / N
~N

255 0= i =0 551.5486 78 552 N
F
0 -j-F
~F

I\0 N
\ ~ iN / N
-N
256 ~ 574.6824 59 575 0=S=0 N ~ ~ S_0 ~0 N i \ NON /N
/
257 CH 497.5773 40 498 0=S=0 N
OH

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
3 ~ CH3 /\O N ~ \
\ NON / N
258 ~ 459.5715 90 460 O=S=O
I
N
\3 0 CH3 \ ~ ~N / N
~N
259 CH3 473.5986 80 474 0=S=0 I
N

CHs O CHs ~O N
\ ~ ~N / N
'N
260 ~ 461.5439 83 462 O=S=O
I
N
O

Le A 32 733-Fore~Qn Countries Ex. No. Structure MW HPLC MZ+H
O ~a O N ~ \N
NON /
261 ~ ~ 503.6687 71 504 O=S=O
I
N
H3 'r'-~ ~-CH3 O
~O N
\ \ iN / N
'N
262 ~3 517.6086 71 518 O=~=O
N
ti3C~0 O
~3 0 CH3 0 N i \ \ /N / N
~N
263 ~ 511.6044 76 512 0-S~0 / CH3 I
N

~CH3 Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
' 3 ~ C1'13 /\O N ~-~\
\ ~ iN / N
'N
264 CH3 518.5989 74 519 0 =S =0 I
N
/
\ \
\3 0 Cfi3 \ ~ iN /N
'N
265 CH3 552.6573 91 553 0=S=0 I
N
N
~0 .
0 N ~\
\ NON /N
/

266 0 ~ 0 566.6844 71 567 N
j H3 N

' Ix A'32 733-Forei,~n Countries Ex. No. Structure MW HPLC MZ+H

O N ~\
\ NiN / N
/
267 ~3 567.6692 48 568 O=S=O
I O
N
~O~~s \

1~,0 N ~~\
\ ~ ~N / N
~N
268 / ~ 477.6084 90 478 O=S=O
I
N
S
CH3 0 CH3 , ~0 N i \ ~ iN /N
-N
269 / 569.6851 73 570 0 =S =0 I
H3C~N ~ \ O~CH3 / O~CH3 Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H

O N ~ \N
~ ~N /
I _N
270 CHa 651.766 65 652 O=S=O
I
~ I N ~ I
O=S=O
OH

~O N
\ ~ ~N / N
-N

O=S=O
271 I 541.6309 71 542 N
\ ~OH
O
H3C~
CH, 0 N ~ \N
NON /
272 cH, 607.6133 39 608 o=
F 0 ~ N
F- 1 '0 F

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
~3 N
\ \ iN / N
'N
273 ~3 511.6044 92 512 O= =O
OH
N

~O N i \ ~ ~N / N
~N
274 ~ / 589.7164 >95 590 O=S=O
O
HO~NyO
O CH

O N
\ NON / N , 275 ~ / 477.5869 >95 478 O=S=O
H3C~../N~'~'OH

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
O CH

O N ~ \N
NON /
276 ~ / 463.5598 64 464 O=S=O
~~~OH

3 ~ CH3 l\0 N ~ \N
\ N ~N /
277 ~ / 449.5327 >95 450 O=S=O
H 3C ~0 ~N
\3 0 CH3 \ ~ iN / N
-N
278 I / 507.6134 >95 508 0=S=0.
H3C ~0 ~N ~O,CH3 Le A 32 733-Forei~rn Countries Ex. No. Structure MW HPLC MZ+H
3 ~ CH3 /\0 N ~ \
\ ~ ~N / N
I _N

279 ~ =S 0 532.6232 >95 533 N
~N 0 ~3 0 CH3 0 N ~\
\ ~ ~N / N
I -N
_ CH3 280 0- ~ 0 560.6775 89 561 N
~N 0 H 3C' / , L,e A 32 733-Foreign Cowries Ex. No. Structure MW HPLC MZ+H
O ~s N
\N/N ~ N
281 CH3 636.8199 88 637 O= =O
~N~N
O
~3 O C1"~3 N ~\
\ 1. ~N / N
'N
282 CH 476.5585 50 477 O=S=O
I
,N
N
OJ
CH3 O CH3 , ~O N i \ \ iN / N
_N
283 CHa 489.5981 93 490 O=S=O
I
N
HO

Le A 32 733-Forei; n~ Countries Ex. No. Structure MW HPLC MZ+H
\3 C~ CH 3 0 N' Y
\ NON' /N
I /
284 ~ OH 622.7928 68 623 0=S=0 /
~N ~N \

~0 N
\ ~ ~N / N
I ~N
285 ~ 608.7657 >95 609 0=S=0 ~N ~N / I
O
J
~3 0 CHs 0 N ~\
\ ~N / N
~N
/ , 286 p=S=p ~H3 583.6873 85 584 I F
N ~ \
OH

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H

O N
\ \ iN / N
'N
287 ~ 51 I .6044 >95 S I 2 O=S=O
\ N
HO
O C~
O N
\ NiN / N
/
288 O=S=o ~H' 541.6309 >95 542 \ N
H3C'O I / r.
OH
\3 0 CHa \ \ /N /N
_N .

0=S =0 289 ~ 541.6309 >95 542 N
HsW 0 /
OH

Le A 32 733-Foreign Countries ~ -246-Ex. No. Structure MW HPLC MZ+H
O CHa O N
\ \ iN / N
-N
290 ~ O=~=O ~' 571.6574 73 572 O \ N
/
HO
,O

\a 0 CHa \ ~ iN / N
"N
_ _ CH3 291 ~ 1 ~ 569.6851 83 570 N
HaC 0 \
CI H i0 O N
\ ~ ~N / N
~N

O=S=O
292 I 597.7393 89 598 N
~C~O
O
HOC ~CH~

Le A 32 733-Foreign Countrics Ex. No. Structure MW HPLC MZ+H
cHa O
~O N
\ ~ iN / N
'N
O= =O
293 581.6963 76 582 N
~O /
O~
~3 O N
\ ~ iN / N
'N

O=S=O
294 , 609.7504 83 610 N
~O
OwCH3 ~3 ~ CH3 0 N' Y\
\ ~ ~NI / N
'N

0 =S =0 295 I 609.7504 77 610 N

O
~CH3 Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
~9 0 CHa 0 N ~N
N ~N' /
/

296 0=S\ 0 583.7122 82 584 N
CH, , OwCH3 \3 0 CHs 0 N ~ \N
\ NON /
/

0=S=0 297 611.7227 88 612 N
\
~0 /

~CH3 ~3 ~ CH3 \O N
\ \ /N / N
'N

298 O=S~O 571.6574 89 572 N
H3Cw0~0 O~
~3 Le A 32 733-Foreign Countries Ex. No. Stcvcture MW HPLC MZ+H
\s O CHa 0 N ~ \N
\ ~N /
~N

299 0=S=0 567.6692 81 568 N

~CH3 \s O CHa O N- Y \
\ ~ i'N /N
_N
O= =O
300 627.7221 82 628 N
I \

H3C O~O /
CH3 ~~0~[' ~ O~C
~3 O CH3 O N
\ NON / N

O=S=O
301 - I 661.7396 64 662 N
I\
O O /
O~CH3 Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H

~O N
\ NiN / N
(/
O=S=O
302 , 599.668 77 600 N
O
~C~O/\/O
O~

0 N ~\
\ \ iN /N
_N
_ CH3 303 0 ~ 0 555.658 83 556 N
I\

O~CH

CHs 0 CHa ~0 NI Y\
N
\ NON /

0=~=0 304 N 654.7916 60 655 ~ ' /
H3C~N' v0 ~CH~
HOC

I,e A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
~3 0 CIi3 0 N ~ \N
I \ N ~N /

0=S=0 305 626.7374 86 627 N
CH3 ~ H3 N
~0 ~CH3 ~a 0 CHI
O N_ Y\
\ \ iN / N
N
_ _ CHI
306 ~ ~ 627.7221 82 628 N
H~CVO O /
O O
~CH~
,3 O
l\ ~ J 3 O N' Y\
\ \ iN / N
~N
_ ~3 307 0 ~ 0 583.7122 8l 584 N
\
H3C~0 O~CH3 Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
' 3 CH3 ''O N ~ \
\ \ ~N / N
_N
~3 O= =O
308 631.7568 29 632 N
I Oi~3 \ O
/
~a 0 CHa N
\ ~ iN~ / N
N
CHI
309 0 =0 569.6851 60 570 \ N
HOC 0 ~ /
CHs 0~
CHI
~ ~~a N' Y \
\ ~ iIN /N
I N
~3 310 O =o . 597.7393 62 598 \ N
HaC O I /
H C' O~CH

Le A 32 733-Forei,g~n Countries Ex. No. Structure MW HPLC MZ+H
~O N i \ ~ iN / N
'N
~3 311 °_ _~ 581.6963 87 582 \ N
~O
O~
a CHs N ~ \
\ ~ iN / N
'N
CHI
312 ° _ =0 609.7504 71 610 \ N

~CHa O ~
~N
'N
313 °_~_° ~ 633.7291 47 634 N
° ~ /
H~C~O
°~CH, L.e A 32 733-Forei;~n Countries Ex. No. Structure MW HPLC MZ+H
\s 0 CHs 0 N ~N
\ NON /
/

O=S=0 314 ~ 570.629 59 571 N
O, 0 O
Hz~'~ ~CHa ~O N~~
\ ~ iN / N
N
315 °-~-° 633.7291 35 634 N
HaCiO / ~ O ~ /
O~CNa a CHa O N
\ \ ~N / , ~N
_ ~3 316 ~ ~ ° 583.7122 51 584 HaC CHa Le A 32 733-Forei~~n Countries Ex. No. Structure MW HPLC MZ+H
o CH~

\ ~. ~N / N
N

317 0- -0 611.7227 51 612 \ N
/

O~CH3 H' Ha ~O N ~' \ ~ iN / N
N
_ _ CHI
318 0- -~ 571.6574 75 572 \ N
HaC w0 ~/0 ~CH~
13 O '(~3 O N
NON ~ N , ~3 O=S=O
319 N 603.7026 64. 604 O
~3 Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
CHa O
O NI Y\N
N~1N /
/
320 O=s=o ~3 567.6692 74 568 N
O~

O N
\ \ iN / N
-N
_ CH3 321 O ~ O 597.652 88 598 \ N
O
O
~CH3 O O
' 3 ~ C.H3 I\O N' Y\
\ \ iNJ / N
N
CHa 322 0= i=o 627.7221 80 628 \ N
HoCa~O~ ~ /

CHa O 0~
CHa Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
N~
N~N
\ \ iN
..
323 0=~=0 oN' 647.7562 47 648 \ N
0~0 / OwCN~

N
\ \ iN / N
'N
CHI
324 0 ~ =0 555.658 43 556 ~ N
HOC 0 ~ /
O~CH~
~~ ~O l~a O N
NiN / N , /
CHI
O= =O
325 654.7916 54 655 N
~ ' /
H C~N_ v 0 O~
CHI
HOC

Le A 32 733-Foreign Countries Ex. No. Structure MW HPGC MZ+H
, H~
0 N i \ N~ /N

326 0 ~ =o cH' 624.7214 71 625 N

GN

~c H, ~° l~, ~O N
\ ~ ~N / N
N
CHI
O- =O
327 689.8375 42 690 0 o I , o~
H.,, "' H
H
° CH
O N~ , \ NiN /N
328 ~ _° ~' 583.7122 40 584 \ N
O
H3C~
°~CH~

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H
O CHa O N~N
NON /
/
~3 O-S=O
329 555.658 49 556 N
~C~O ~ /
O~
~3 CN3 O CH Chifal ~O N
\ \ iN / N
'N
330 ~ ~ 525.6315 83 526 O=S=O
N
OH
0 '.H Chlfal, \ ~ iN / N
'N
331 ~ 525.6315 71 526 0=S=0 N
OH

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H

~O N i \ N/N / N
332 ~3 555.658 91 556 O=S=O
.~ N

OH
\s O CHs O N
\ ~ iN / N
~N
333 CH3 477.5869 76 478 O=S=O
N
HO
~CH3 ~0 N
\ ~ ~N / N
'N
334 ~ / 478.5745 62 479 O =S =O
H2N ~N OOH

Le A 32 733-Foreign Countries Ex. No. Structure MW HPLC MZ+H

~O N i \ NON / N
'~3 335 O= ~ =O 490.6292 42 491 N
~N1 3 Chla Le A 32 733-Foreign countries Example 336 2-[2-Ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazol[5,1-f][1,2,4]triazine-4-one hydrochloride trihydrate H3C~O HN ~ N
\ ~N.N /

O=S=O
N
CI x 3 H20 H
J

If the free base from Example 19 is crystallized from a mixture of an organic solvent and dilute aqueous hydrochloric acid, a hydrochloride trihydrate is obtained.
m.p.:218°C
Water content: 9.4% (K. Fischer) Chloride content: 6.1 %
Example 337 2-[2-Ethoxy-5-{4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-fJ[1,2,4]triazine-4-one dihydrochloride Le A 32 733-Foreign countries H3C~
O=S=O -Ha N
x 2 HC.
N
HCJ

0.35 g (0.712 mmol) of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazine-4-one are suspended in 8 ml of ether and dichloromethane is added until a homogeneous solution is formed. 24 ml of a 1M solution of HCl in ether are added and the mixture is stirred at room temperature for 20 minutes and filtered off with suction. This gives 372 mg (99%) of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,i-f][1,2,4]triazine-4-one dihydrochloride.
200 MHz 1H-NMR (DMSO-d6): 0.96, t, 3H; 1.22, t, 3H; 1.36, t, 3H; 1.82, sex., 2H;
2.61, s, 3H; 2.88, m, 2H; 3.08, m, 6H; 3.50, m, 2H; 3.70, m, 2H; 4.25, quart., 2H;
7.48, d, 1 H; 7.95, m, 2H; 11.42, s, 1 H; 12.45, s, 1 H.

Claims

claims

1. 2-Phenyl-substituted imidazotriazinones of the general formula (I) in which R1 represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, R2 represents straight-chain alkyl having up to 4 carbon atoms, R3 and R4 are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to 8 carbon atoms, or represents a straight-chain or branched alkyl chain having up to 10 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of trifluoromethyl, trifluoromethoxy, hydroxyl, halogen, carboxyl, benzyloxycarbonyl, straight-chain or branched alkoxycarbonyl having up to 6 carbon atoms and/or by radicals of the formulae -SO3H, -(A)a-NR7R8, -O-CO-NR7R8, -S(O)b-R9, -P(O)(OR10)(OR11), in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or SO2, R7, R7', R8 and R8' are identical or different and each represents hydrogen, or represents cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms, a 5- to 6-membered unsaturated, partially unsaturated or saturated, optionally benzo-fused heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, where the abovementioned ring systems are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, nitro, trifluoromethyl, trifluoromethoxy, carboxyl, halogen, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms or by a group of the formula -(SO2)c-NR12R13, in which c represents a number 0 or 1, R12 and R13 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms, or R7, R7', R8 and R8' each represent straight-chain or branched alkoxy having up to 6 carbon atoms, or represents straight-chain or branched alkyl having up to 8 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, halogen, aryl having 6 to 10 carbon atoms, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms or by a group of the formula -(CO)d-NR14R15, in which R14 and R15 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and d represents a number 0 or 1, or R7 and R8 and/or R7' and R8' together with the nitrogen atom form a 5- to 7-membered saturated heterocycle which may optionally contain a further heteroatom from the group consisting of S and O or a radical of the formula -NR16, in which R16 represents hydrogen, aryl having 6 to 10 carbon atoms, benzyl, a 5- to 7-membered aromatic or saturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and O
which is optionally substituted by methyl, or represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl, R9 represents aryl having 6 to 10 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms, R10 and R11 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and/or the alkyl chain listed above under R3/R4 is optionally substituted by cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or by a 5- to 7-membered partially unsaturated, saturated or unsaturated, optionally benzo-fused heterocycle which may contain up to 4 heteroatoms from the group consisting of S, N
and O or a radical of the formula -NR17, in which R17 represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl or alkoxy having in each case up to 4 carbon atoms, or represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl and straight-chain or branched alkoxy having up to 6 carbon atoms, and where aryl and the heterocycle are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of nitro, halogen, -SO3H, straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy and/or by a radical of the formula -SO2-NR18R19, in which R18 and R19 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms, and/or R3 or R4 represents a group of the formula -NR20R21, in which R20 and R21 have the meanings of R18 and R19 given above and are identical to or different from them, and/or R3 or R4 represents adamantyl, or represents radicals of the formulae or represents cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or represents a 5- to 7-membered partially unsaturated, saturated or unsaturated, optionally benzo-fused heterocycle which may contain up to 4 heteroatoms from the group consisting of S, N and O, or a radical of the formula -NR22, in which R22 has the meaning of R16 given above and is identical to or different from it, or represents carboxyl, formyl or straight-chain or branched acyl having up to 5 carbon atoms, and where cycloalkyl, aryl and/or the heterocycle are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, triazolyl, trifluoromethyl, trifluoromethoxy, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro and/or by groups of the formulae -SO3H, -OR23, (SO2)e NR24R25, -P(O)(OR26)(OR27), in which e represents a number 0 or 1, R23 represents a radical of the formula represents cycloalkyl having 3 to 7 carbon atoms, or represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms which is optionally substituted by cycloalkyl having 3 to 7 carbon atoms, benzyloxy, tetrahydropyranyl, tetrahydrofuranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, carboxyl, benzyloxycarbonyl or phenyl which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkoxy having up to 4 carbon atoms, hydroxyl and halogen, and/or alkyl which is optionally substituted by radicals of the formulae -CO-NR28R29 or -CO-R30, in which R28 and R29 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 8 carbon atoms, or R28 and R29 together with the nitrogen atom form a 5- to 7-membered saturated heterocycle which may optionally contain a further heteroatom from the group consisting of S and O, and R30 represents phenyl or adamantyl, R24 and R25 have the meanings of R18 and R19 given above and are identical to or different from them, R26 and R27 have the meanings of R10 and R11 given above and are identical to or different from them and/or cycloalkyl, aryl and/or the heterocycle are optionally substituted by straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl, carboxyl, by a 5- to 7-membered heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, or by groups of the formula -SO2-R31, P(O)(OR32)(OR33) or -NR34R35, in which R31 represents hydrogen or has the meaning of R9 given above and is identical to or different from it, R32 and R33 have the meanings of R10 and R11 given above and are identical to or different from them, R34 and R35 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl or by straight-chain or branched alkoxy having up to 4 carbon atoms, or R34 and R35 together with the nitrogen atom form a 5- to 6-membered saturated heterocycle which may contain a further heteroatom from the group consisting of S and O, or a radical of the formula -NR36, in which R36 represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 7 carbon atoms or straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl, or R3 and R4 together with the nitrogen atom form a 5- to 7-membered unsaturated or saturated or partially unsaturated, optionally benzo-fused heterocycle which may optionally contain up to 3 heteroatoms from the group consisting of S, N and O, or a radical of the formula -NR37, in which R37 represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, trifluoromethyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, or by groups of the formula -(D)f -NR38R39, -CO-(CH2)g -O-CO-R40, -CO-(CH2)h-OR41 or -P(O)(OR42)(OR43), in which g and h are identical or different and each represents a number l, 2, 3 or 4, and f represents a number 0 or 1, D represents a group of the formula -CO or -SO2, R38 and R39 are identical or different and each has the meaning of R7 and R8 given above, R40 represents straight-chain or branched alkyl having up to 6 carbon atoms, R41 represents straight-chain or branched alkyl having up to 6 carbon atoms, R42 and R43 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or R37 represents a radical of the formula -(CO)i -E, in which i represents a number 0 or 1, E represents cycloalkyl having 3 to 7 carbon atoms or benzyl, represents aryl having 6 to 10 carbon atoms or a 5- to 6-membered aromatic heterocycle having up to 4 heteroatoms from the group consisting of S, N and O, where the abovementioned ring systems are optionally mono- or polysubstituted by identical or different constituents selected from the group consisting of nitro, halogen, -SO3H, straight-chain or branched alkoxy having up to 6 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy, or by a radical of the formula -SO2-NR44R45, in which R44 and R45 have the meaning of R18 and R19 given above and are identical to or different from them, or E represents radicals of the formulae and the heterocycle listed under R3 and R4, which is formed together with the nitrogen atom, is optionally mono- or polysubstituted, if appropriate also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro and groups of the formulae -P(O)(OR46)(OR47), = NR48 or ~ (CO)j NR49R50 in which R46 and R47 have the meanings of R10 and R11 given above and are identical to or different from them, R48 represents hydroxyl or straight-chain or branched alkoxy having up to 4 carbon atoms, j represents a number 0 or 1, and R49 and R50 are identical or different and have the meanings of R14 and R15 given above, and/or the heterocycle listed under R3 and R4, which is formed together with the nitrogen atom, is optionally substituted by straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, halogen, carboxyl, cycloalkyl or cycloalkyloxy having in each case 3 to 8 carbon atoms, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, or by a radical of the formula -SO3H, -NR51R52 or P(O)OR53OR54, in which R51 and R52 are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, R53 and R54 are identical or different and have the meanings of R10 and R11 given above, and/or the alkyl is optionally substituted by aryl having 6 to 10 carbon atoms which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, hydroxyl, straight-chain or branched alkoxy having up to 6 carbon atoms, or by a group of the formula -NR51'R52', in which R51' and R52' have the meanings of R51 and R52 given above and are identical to or different from them, and/or the heterocycle listed under R3 and R4, which is formed together with the nitrogen atom, is optionally substituted by aryl having 6 to 10 carbon atoms or by a 5- to 7-membered saturated, partially unsaturated or unsaturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, optionally also attached via a nitrogen function, where the ring systems for their part may be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, or R3 and R4 together with the nitrogen atom form radicals of the formulae R5 and R6 are identical or different and each represents hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, hydroxyl or represents straight-chain or branched alkoxy having up to 6 carbon atoms, and their salts, hydrates, N-oxides and isomeric forms.

2-Phenyl-substituted imidazotriazinones of the general formula (I) according to Claim 1 in which R1 represents straight-chain or branched alkyl having up to 3 carbon atoms, R2 represents straight-chain alkyl having up to 3 carbon atoms, R3 and R4 are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to 6 carbon atoms, or represents a straight-chain or branched alkyl chain having up to 8 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, benzyloxycarbonyl, straight-chain or branched alkoxycarbonyl having up to 5 carbon atoms, and by radicals of the formulae -SO3H, -(A)a-NR7R8, -O-CO-NR7'R8', -S(O)b-R9, -P(O)(OR10)(OR11), in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or SO2, R7, R7', R8 and R8' are identical or different and each represents hydrogen, or cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, piperidinyl and pyridyl, where the abovementioned ring systems are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, nitro, trifluoromethyl, trifluoromethoxy, carboxyl, fluorine, chlorine, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a group of the formula -(SO2)c-NR12R13, in which c represents a number 0 or 1, R12 and R13 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or R7, R7', R8 and R8' each represent straight-chain or branched alkoxy having up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 7 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, phenyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a group of the formula -(CO)d-NR14R15, in which R14 and R15 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and d represents a number 0 or 1, or R7 and R8 and/or R7' and R8' together with the nitrogen atom form a pyrrolidinyl, morpholinyl, piperidinyl or triazolyl ring or radicals of the formulae in which R16 represents hydrogen, phenyl, benzyl, morpholinyl, pyrrolidinyl, piperidinyl, piperazinyl or N-methylpiperazinyl, or represents straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl, R9 represents straight-chain or branched alkyl having up to 3 carbon atoms, R10 and R11 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and/or the alkyl chain listed under R3/R4 is optionally substituted by cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, pyridyl, quinolyl, pyrrolidinyl, pyrimidyl, morpholinyl, furyl, piperidinyl, tetrahydrofuranyl or by radicals of the formulae in which R17 represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl or alkoxy having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl and straight-chain or branched alkoxy having up to 4 carbon atoms, and where phenyl and the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, -SO3H, straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms, hydroxyl, and/or by a radical of the formula -SO2NR18R19, in which R18 and R19 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and/or R3 or R4 represents a group of the formula -NR20R21, in which R20 and R21 have the meanings of R18 and R19 given above and are identical to or different from them, and/or R3 or R4 represents adamantyl, or represents radicals of the formulae or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl, morpholinyl, oxazolyl, thiazolyl, quinolyl, isoxazolyl, pyridyl, tetrahydrofuranyl, tetrahydropyranyl or represents radicals of the formulae in which R22 has the meaning of R16 given above and is identical to or different from it, or represents carboxyl, formyl or straight-chain or branched acyl having up to 3 carbon atoms, and where cycloalkyl, phenyl and/or the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, triazolyl, trifluoromethyl, trifluoromethoxy, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 5 carbon atoms, nitro and/or by groups of the formulae -SO3H, -OR23, (SO2)e NR24R25, -P(O)(OR26)(OR27), in which e represents a number 0 or 1, R23 represents a radical of the formula represents cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl or cycloheptyl, represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms which may optionally be substituted by cyclopropyl, cyclopentyl, cyclohexyl, benzyloxy, tetrahydropyranyl, tetrahydrofuranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, benzyloxycarbonyl or phenyl which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkoxy having up to 3 carbon atoms, hydroxyl, fluorine and chlorine, and/or where alkyl is optionally substituted by radicals of the formulae -CO-NR28R29 or -CO-R30, in which R28 and R29 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms, or R28 and R29 together with the nitrogen atom form a morpholinyl, pyrrolidinyl or piperidinyl ring, and R30 represents phenyl or adamantyl, R24 and R25 have the meanings of R18 and R19 given above and are identical to or different from them, R26 and R27 have the meanings of R10 and R11 given above and are identical to or different from them and/or cycloalkyl, phenyl and/or the heterocycles are optionally substituted by straight-chain or branched alkyl having up to 4 carbon atoms which is optionally substituted by hydroxyl, carboxyl, pyridyl, pyrimidyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, triazolyl or by groups of the formula -SO2-R31, -P(O)(OR32)(OR33) or -NR34R35, in which R31 has the meaning of R9 given above and is identical to or different from it, R32 and R33 have the meanings of R10 and R11 given above and are identical to or different from them, R34 and R35 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl or straight-chain or branched alkoxy having up to 3 carbon atoms, or R34 and R35 together with the nitrogen atom form a morpholinyl, triazolyl or thiomorpholinyl ring or a radical of the formula in which R36 represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 5 carbon atoms or straight-chain or branched alkyl having up to 4 carbon atoms which is optionally substituted by hydroxyl, or R3 and R4 together with the nitrogen atom form a morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl ring, or a radical of the formula in which R37 represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or represents straight-chain or branched alkyl having up to 5 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, trifluoromethyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by groups of the formula -(D)f -NR38R39, -CO-(CH2)g -O-CO-R40, -CO-(CH2)h -OR41 or -P(O)(OR42)(OR43), in which g and h are identical or different and each represents a number 1, 2 or 3, and f represents a number 0 or 1, D represents a group of the formula -CO or -SO2, R38 and R39 are identical or different and have the meanings of R7 and R8 given above, R40 represents straight-chain or branched alkyl having up to 4 carbon atoms, R41 represents straight-chain or branched alkyl having up to 4 carbon atoms, R42 and R43 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, or R37 represents a radical of the formula -(CO)i-E, in which i represents a number 0 or 1, E represents cyclopentyl, cyclohexyl, cycloheptyl, benzyl, phenyl, pyridyl, pyrimidyl or furyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of vitro, fluorine, chlorine, -SO3H, straight-chain or branched alkoxy having up to 4 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy or by a radical of the formula -SO2-NR444R45, in which R44 and R45 have the meanings of R18 and R19 given above and are identical to or different from them, or E represents radicals of the formulae and the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally mono- to trisubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 5 carbon atoms, nitro and groups of the formulae -P(O)(OR46)(OR47), or ~(CO)j NR49R50 in which R46 and R47 have the meanings of R10 and R11 given above and are identical to or different from them, R48 represents hydroxyl or straight-chain or branched alkoxy having up to 3 carbon atoms, j represents a number 0 or 1, and R49 and R50 are identical or different and have the meanings of R14 and R15 given above, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 5 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a radical of the formula -SO3H, -NR51R52 or -P(O)OR53OR54, in which R51 and R52 are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms, R53 and R54 are identical or different and have the meanings of R10 and R11 given above, and/or the alkyl is optionally substituted by phenyl which for its part may be mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, hydroxyl, straight-chain or branched alkoxy having up to 4 carbon atoms, or by a group of the formula -NR51'R52', in which R51' and R52' have the meanings of R51 and R52 given above and are identical to or different from them, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by phenyl, pyridyl, piperidinyl, pyrrolidinyl or tetrazolyl, optionally also attached via a nitrogen function, where the ring systems for their part may be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 5 carbon atoms, or R3 and R4 together with the nitrogen atom form radicals of the formulae R5 and R6 are identical or different and each represents hydrogen, hydroxyl or represents straight-chain or branched alkoxy having up to 4 carbon atoms, and their salts, hydrates, N-oxides and isomeric forms.

3. 2-Phenyl-substituted imidazotriazinones of the general formula (I) according to Claim 1 in which R1 represents straight-chain or branched alkyl having up to 3 carbon atoms, R2 represents straight-chain alkyl having up to 3 carbon atoms, R3 and R4 are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to 4 carbon atoms, or represents a straight-chain or branched alkyl chain having up to 6 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, straight-chain or branched alkoxycarbonyl having up to 4 carbon atoms, and/or by radicals of the formulae -SO3H, -(A)a-NR7R8; -O-CO-NR7'R8', -S(O)b-R9, -P(O)(OR10)(OR11), in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or SO2, R7, R7', R8 and R8' are identical or different and each represents hydrogen, or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl,~
piperidinyl and pyridyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, nitro, carboxyl, fluorine, chlorine, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a group of the formula -(SO2)c-NR12R13, in which c ~represents a number 0 or 1, R12 and R13 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, or R7, R7', R8 and R8' each represent methoxy, or represent straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, phenyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a group of the formula -(CO)d-NR14R15, in which R14 and R15 are identical or different and each represents hydrogen, methyl or ethyl, and d ~represents a number 0 or 1, or R7 and R8 and/or R7' and R8' together with the nitrogen atom form a morpholinyl, piperidinyl or triazolyl ring or radicals of the formulae ~
in which R16 represents hydrogen, phenyl, benzyl, morpholinyl, pyrrolidinyl, piperidinyl, piperazinyl or N-methylpiperazinyl, or represents straight-chain or, branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl, R9 represents methyl, R10 and R11 are identical or different and each represents hydrogen, methyl or ethyl, and/or the alkyl chain listed under R3/R4 is optionally substituted by cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, morpholinyl, furyl, tetrahydrofuranyl, or by radicals of the formulae in which R17 represents hydrogen, hydroxyl, formyl, acetyl or alkoxy having up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl or straight-chain or branched alkoxy having up to 3 carbon atoms, and where phenyl and the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, -SO3H, straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, hydroxyl, and/or by a radical of the formula -SO2NR18R19, in which R18 and R19 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and/or R3 or R4 represents a group of the formula -NR20R21, in which R20 and R21 have the meanings of R18 and R19 given above and are identical to or different from them, and/or R3 or R4 represents adamantyl, or represents radicals of the formulae or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl, morpholinyl, oxazolyl, thiazolyl, quinolyl, isoxazolyl, pyridyl, tetrahydrofuranyl, tetrahydropyranyl, or represents radicals of the formulae in which R22 has the meaning of R16 given above and is identical to or different from it, or represents formyl or acetyl, and where cycloalkyl, phenyl and/or the heterocycles are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, triazolyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 4 carbon atoms, nitro, and/or by groups of the formulae -SO3H, -OR23, (SO21)e NR24R25, -P(O)(OR26)(OR27), in which e ~represents a number 0 or 1, R23 ~represents a radical of the formula represents cyclopropyl, cyclopentyl, cyclobutyl or cyclohexyl, represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by cyclopropyl, cyclohexyl, benzyloxy, tetrahydropyranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, benzyloxycarbonyl or phenyl which for its part may be mono- or disubstituted by identical or different substituents selected from the group consisting of methoxy, hydroxyl, fluorine or chlorine, and/or where alkyl is optionally substituted by radicals of the formulae -CO-NR28R29 or -CO-R30, in which R28 and R29 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or R28 and R29 together with the nitrogen atom form a morpholinyl, pyrrolidinyl or piperidinyl ring, and R30 represents phenyl or adamantyl, R24 and R25 have the meaning of R18 and R19 given above and are identical to or different from them, R26 and R27 have the meanings of R10 and R11 given above and are identical to or different from them and/or cycloalkyl, phenyl and/or the heterocycles are optionally substituted by straight-chain or branched alkyl having up to 3 carbon atoms, which is optionally substituted by hydroxyl, carboxyl, pyridyl, pyrimidyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyi, triazolyl or by groups of the formula -SO2-R31, P(O)(OR32)(OR33) or -NR34R35, in which R31 represents methyl, R32 and R33 have the meanings of R10 and R11 given above and are identical to or different from them, R34 and R35 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl or methoxy, or R34 and R35 together with the nitrogen atom form a morpholinyl, triazolyl or thiomorpholinyl ring or a radical of the formula in which R36 represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 3 carbon atoms or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl, or R3 and R4 together with the nitrogen atom form a morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl ring, or a radical of the formula in which R37 represents hydrogen, hydroxyl, formyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by groups of the formula -(D)f NR38R39, -CO-(CH2)g-O-CO-R40, -CO-(CH2)h-OR41 or -P(O)(OR42)(OR43), in which g and h are identical or different and each represents a number 1 or 2, and f represents a number 0 or 1, D represents a group of the formula -CO or -SO2, R38 and R39 are identical or different and have the meanings of R7 and R8 given above, R40 represents straight-chain or branched alkyl having up to 3 carbon atoms, R41 represents straight-chain or branched alkyl having up to 3 carbon atoms, R42 and R43 are identical or different and each represents hydrogen, methyl or ethyl, or R37 represents a radical of the formula -(CO)i-E, in which i ~represents a number 0 or 1, E ~represents cyclopentyl, benzyl, phenyl, pyridyl, pyrimidyl or furyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, -SO3H, straight-chain or branched alkoxy having up to 3 carbon atoms, hydroxyl, or by a radical of the formula -SO2-NR44R45, in which R44 and R45 have the meanings of R18 and R19 given above and are identical to or different from them, or E ~represents radicals of the formulae and the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally mono- to trisubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or groups of the formulae -P(O)(OR46)(OR47), =NR48 or ~(CO)i NR49R50 in which R46 and R47 have the meanings of R10 and R11 given above and are identical to or different from them, R48 represents hydroxyl or methoxy, j represents a number 0 or 1, and R49 and R50 are identical or different and have the meanings of R14 and R15 given above, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, cyclopropyl, cycloheptyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a radical of the formula -SO3H, -NR51R52 or P(O)OR53OR54, in which R51 and R52 are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, R53 and R54 are identical or different and have the meanings of R10 and R11 given above, and/or the alkyl is optionally substituted by phenyl which for its part may be mono- to disubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, hydroxyl, methoxy, or by a group of the formula -NR51'R52', in which R51' and R52' have the meanings of R51 and R52 given above and are identical to or different from them, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by phenyl, pyridyl, piperidinyl, pyrrolidinyl or tetrazolyl, if appropriate also attached via a nitrogen function, where the ring systems for their part may be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, or R3 and R4 together with the nitrogen atom form radicals of the formulae R5 and R6 are identical or different and each represents hydrogen, hydroxyl or represents straight-chain or branched alkoxy having up to 3 carbon atoms, and their salts, hydrates, N-oxides and isomeric forms.

4. 2-Phenyl-substituted imidazotriazinones of the general formula (I) according to Claim 1 in which R1 represents methyl or ethyl, R2 represents ethyl or propyl, R3 and R4 are identical or different and each represents a straight-chain or branched alkyl chain having up to 5 carbon atoms which is optionally substituted up to two times by identical or different substituents selected from the group consisting of hydroxyl and methoxy, or R3 and R4 together with the nitrogen atom form a piperidinyl, morpholinyl, thiomorpholinyl ring, or a radical of the formula in which R37 represents hydrogen, formyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by groups of the formulae -(D)f-NR38R39 or -P(O)(OR42)(OR43), in which f represents a number 0 or 1, D represents a group of the formula -CO, R38 and R39 are identical or different and each represents hydrogen or methyl, R42 and R43 are identical or different and each represents hydrogen, methyl or ethyl, or R37 represents cyclopentyl, and the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally mono- or disubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or groups of the formulae -P(O)(OR46)(OR47) or -(CO)i NR49R50, in which R46 and R47 are identical or different and each represents hydrogen, methyl or ethyl, j represents a number 0 or 1, and R49 and R50 are identical or different and each represents hydrogen or methyl and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, carboxyl, or by a radical of the formula P(O)OR53OR54, in which R53 and R54 are identical or different and each represents hydrogen, methyl or ethyl, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by pyrrolidinyl or piperidinyl attached via nitrogen, R5 represents hydrogen, and R6 represents ethoxy or propoxy, and their salts, hydrates, N-oxides and isomeric forms.

5. A 2-phenyl-substituted imidazotriazinone according to Claim 1 wherein R1 is methyl, R2 is n-propyl, the group NR3R4 forms a six-membered heterocycle containing a radical of the formula NR37 in which R37 is ethyl, the sulphonyl moiety is in the 5-position of the phenyl group, R5 is hydrogen and R6 is ethoxy in the 2-position of the phenyl group.

6. 2-Phenyl-substituted imidazotriazinones according to any one of Claims 1 to 5 having the following structures:

7. The compound 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one or a pharmaceutically acceptable salt thereof or a hydrate thereof or a hydrate of a pharmaceutically acceptable salt thereof.

8. The compound 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one in the form of a hydrochloride salt or a hydrate of a hydrochloride salt.

9. The compound 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one in the form of the monohydrochloride trihydrate.

10. 2-Phenyl-substituted imidazotriazinones of the general formula (I) according to any one of Claims 1 to 9 and pharmaceutically acceptable salts and hydrates thereof for the treatment of cardiovascular or cerebrovascular disorders or disorders of the urogenital system.

11. A pharmaceutical composition comprising a 2-phenyl-substituted imidazotriazinone according to any one of Claims 1 to 9, or a pharmaceutically acceptable salt or hydrate thereof, together with pharmacologically acceptable formulating agents.

12. A composition according to Claim 11 for the treatment of cardiovascular or cerebrovascular disorders or disorders of the urogenital system.

13. A composition according to Claim 11 for the treatment of erectile dysfunction.

14. Use of a 2-phenyl-substituted imidazotriazinone according to any one of Claims 1 to 9, or a pharmaceutically acceptable salt or hydrate thereof, for the treatment of cardiovascular or cerebrovascular disorders or disorders of the urogenital system.

15. Use of a 2-phenyl-substituted imidazotriazinone according to any one of Claims 1 to 9, or a pharmaceutically acceptable salt or hydrate thereof, for the treatment of erectile dysfunction.

16. Use of a 2-phenyl-substituted imidazotriazinone according to any one of Claims 1 to 9 or a pharmaceutically acceptable salt or hydrate thereof for the preparation of a pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disorders and disorders of the urogenital system.

17. Use according to Claim 16 for the preparation of a pharmaceutical composition, for the treatment of erectile dysfunction.

18. A pharmaceutical composition comprising 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one monohydro-chloride trihydrate, together with pharmacologically acceptable formulating agents.

19. Use of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one monohydrochloride trihydrate, for the treatment of cardiovascular or cerebrovascular disorders or disorders of the urogenital system.

20. Use of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one monohydrochloride trihydrate, for the treatment of erectile dysfunction.

21. ~Use of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one monohydrochloride trihydrate, in the manufacture of a pharmaceutical composition for the treatment of cardiovascular or cerebrovascular disorders or disorders of the urogenital system.

22. ~Use of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one monohydrochloride trihydrate, in the manufacture of a pharmaceutical composition for the treatment of erectile dysfunction.

23. ~A process for preparing 2-phenyl-substituted imidazotriazinones of formula (I) according to Claim 1, which process comprises reacting a compound of the general formula (V) in which R1, R2, R5 and R6 are as defined in Claim 1, with an amine of general formula (VI) HNR3R4 ~~(VI) in inert solvent, wherein R3 and R4 are as defined in Claim 1, followed, if required, by converting an obtained compound of formula (I) into a pharmaceutically acceptable salt, or a hydrate thereof, or a hydrate of a pharmaceutically acceptable salt thereof.

24. ~A process according to Claim 23 wherein the compound of formula (V) is obtained by reacting a compound of the general formula (II) in which R1 and R2 are each as defined in Claim 23 and L represents straight-chain or branched alkyl having up to 4 carbon atoms, with a compound of the general formula (III) in which R5 and R6 are each as defined in Claim 23, in a two-step reaction in the systems ethanol and phosphorus oxytrichloride/dichloroethane to form a compound of the general formula (IV) in which R1, R2, R5 and R6 are each as defined above, followed by reaction with chlorosulphonic acid to give the compound of the general formula (V).

25. Compounds of formula (V) wherein R1 represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, R2 represents straight-chain alkyl having up to 4 carbon atoms, and R5 and R6 are identical or different and each represents hydrogen straight-chain or branched alkyl having up to 6 carbon atoms or hydroxyl, or represents straight-chain or branched alkoxy having up to 6 carbon atoms.

26. Compounds according to Claim 25 in which R1 represents straight-chain or branched alkyl having up to 3 carbon atoms, R2 represents straight-chain alkyl having up to 3 carbon atoms and R5 and R6 are identical or different and each represents hydrogen, hydroxyl or straight-chain or branched alkoxy having up to 4 carbon atoms.

27. Compounds according to Claim 25 in which R5 and R6 are identical or different and each represents straight-chain or alkoxy having up to 3 carbon atoms.

28. Compounds according to Claim 25 in which R1 represents methyl or ethyl, R2 represents ethyl or propyl, R5 represents hydrogen and R6 is ethoxy or propoxy.

29. ~A process for preparing 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one which comprises reacting 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride with N-ethyl-piperazine.

30. A process according to Claim 29 which comprises the further step of crystallizing the product from a mixture of an organic solvent and dilute aqueous hydrochloric acid to obtain the product in the form of the hydrochloride trihydrate.