CA2108899A1 - Use of oxazolo-[2,3-a]-isoindole and imidazo-[2,1-a]- isoindole derivatives as antiviral medicaments, as well as new oxazolo-[2,3-a]-isoindole derivatives - Google Patents

Abstract

2108899 9216207 PCTABS00016 The invention concerns the use of oxazolo-[2,3-a]isoindole and iminazo[2,1-a]isoindole derivatives as antiviral drugs, as well as optically active derivatives, new oxazolo-[2,3-a]isoindole derivatives, a method for preparing them and drugs containing these compounds. In particular, the subject matter of the invention is the use of oxazolo-[2,3-a]isoindole and imidazo[2,1-a]isoindole derivatives of general formula (I) to produce antiviral drugs. In formula (I), X stands for an oxygen atom or a sulphur atom, the imino group =NH or a =N-C1-C5 alkylimino group, Y stands for an oxygen atom or the group NR7, wherein R7 is a hydrogen atom or a C1-C6 alkyl residue or a C1-C6 acyl residue, R is a hydrogen atom, a straight-chain or branched, saturated or unsaturated aliphataic residue containing 1-9 carbon atoms, possibly substituted by phenyl, or a phenyl ring possibly substituted one or more times, or a carbocyclic or heterocyclic ring, R1 and R2 stand for a hydrogen atom, a straight-chain or branched, saturated or unsaturated aliphatic residue with 1 to 6 carbon atoms, R3-R6 stand for hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylmercapto, amino, C1-C6 alkylamino, di-C1-C6 alkylamino, halogen, cyano, hydroxy, carboxy, aminocarbonyl, substituted aminocarbonyl or C1-C6 alkoxycarbonyl. The invention also concerns their tautomers, enantiomers, diastereomers and physiologically acceptable salts.

Description

210889g Boehringer Mannheim GmbH 3477/o~/
Use of oxazolo~2,3-a~-isoindol~ and imidazo-~l-a7-isoindole derivatives as antivirsl medi-caments as well a~ new oxazolo-~ ~3- ~ -isoindole derivatives ~he pre~ent invention concerns the use of o~azolo-~ -s7-isoindole and imidazo-~,1-s7-isoindole derivatives as antiviral medicament~, a~ well as ne~
opticaIl~-active derivatives and new oxazolo-/~,3-a7-is~indole derivatives, processe~ for their prepar-ation and medicaments which contain thesc compounds.
Ihe ~se of oxazolo~ 3-s7-isoindole and imidazo-/~,1-~ -isoindole derivatives as medicaments i~
described in several publications Thus~ derivatives of these ~ubstance classes are des~ribed in J~ Qrg.
Chem~ 55, 3~88,. 1990, as inhibitor~ of ~amms-butyrobetaine hgdrox~lase. ~urthermore, the following pharmacolo~ical actions are de~cribed:
a) appetite suppre~sor.action in US 3,994,920 and ~0 US 3,935,218, b) treatment of g~triti~ i~ US 3,966,955, c) anti-dffpre~ive action in US 3,935~219~ US
3,900,.494~ US 3~898~226, US 3,898,231, US 3,885,037~ :~
US 3,867,~394~. US 3,867,394 and US 3, 76~ ,178..

2.5 d~ diuretic action in US 3,9359218, US 3,898t226, US 3,898, 231, US 3,885~037 and US 3,867,394, e) ant~h~pergl~caemic action in US 3,928,597, ~.

" 2108~9

-3-f) anorexic action i~ US 3,898,226,. US 3,898,.231 ~nd US 3,885~037, g) anti-inf~ammstor~ action i~ ~ 480350 ~nd . .
.US 3,408~35~, h) ~algesic actio~ in C~ 48~35Q~ CH 482l697, C~ 48~,~24 and ~.481~123, i) blood pre~sure-si~king a~tion in C~ 48~-,350, C~ 481~124 and CH 481~123, )~.~pasmol~tic action in CH.48Q,~50~. CH 481,124 and ~0C~ 481,12~, .
k) tranquiliser a~d sedative action in CH 480,350 -and CH 481tl23, 1) antitussive action in CH 480,35~, CH 481,124 and CH 481,123 a~d m) rheumatic acti~n in.CH 482,697 The oxazolo-/~,3-~7-isoi~do].e and imidazo~
isoindole derivative~ of the genera~ formula I also .:
possess~ in part, a certain potential as intermediate products for the preparation of stru~turally similar 2D classes of compounds~ ~hese intermediat~ products are described in C~ 201,499, Aust. J. Chem., 35, 2307, I982; US 4,0I8,765; GB 1,225,411; U~ 3,925,359;
US 3,929,766; US 3,910,947; US 3,9~5,994; J~ Med. Chem~
18, 177r 1975; J. Org~ Chem~ 40, 382,1975; D~ 1~795,785;
GB 1,.322,339; US ~,663,532; GB 1,258,946; FR 7457;
DE 2,106,.694; GB 1$225,411; GB 1,232,469, GB lt225,413;
FR 1,580,180; FR 1,580,184, FR lt571,331; US 3,454,592;

` 21088~9 US 3,44~,572; SA 6,801,724; J, Org~ Chem, 34,- 1720, 1969; SA 6,8~1~872;: U~ 3,~79,733~
~ h~ ~gnthesis of the compounds of the general formula I is described, inter alia, in J. Heteroc~cl, Chem, 26, 1441~ ~989; Gazz.. Chim~ Ital, 155 (:12, part B~, 653" 1985, Bull, ~oc~ Chim, Belg~ 95,~ 197, ~986;
J~ Chem, Soc~, Perkin ~ra~s~ l~ 8099. 1985; J, Org~
Chem~,.45t 4049,; 1980; US 3,867,4l; ~E 2,332,232;
US 3,.65~7,?2l;. U~ ~,5Q~,863; GB ~Q59,175,. J~ 0~, Chem, . .
10 34,. 165, 1969; US 3,403j164; J_ ~g~ Chem~ 2874, 1968; US 3,3~6,3~6;: US 3,334~13,i ~L 6,613,264; J, Org, Chem, 32,,2l80" 1967; J, Org~ Chem, 32~ 2185,196? and Belg~ 659~530, The in~e~tion concerns the use of oxazolo-/~,3-a7-isoindal~ and imidazo-~,l-a7-isoindole derivatives of the general formula. I

~"r~ ~4 ~

~ ~ R5 ( ) 3 R

for the prepar~tion of medicaments with a~tiviral action~ whereb~ ~ can be an ox~gen or sulphur atom, 20 the imino group =NH or sn =N-Cl-C5-alk~limino group, - -. ~ can be an oxygen atom or the gro~p NR7, where~ R7 signifies a hydrogen atom or a ~-C6-alk~l or Cl-C6-ac~l rsdical, R signifies a h~drogen atom9 a str~ight-chained or.branched? s~turated or unsaturated -~ -5-aliphatic radical with 1 - 9 C-atoms, which can be substituted by phenyl~ or a Cl-C6-alkoxy~Cl-C6-a~kyl or Cp-C6-a;Dk~lmercapto-cL-c6-alkyl radical, or signifies a phenyl ring which is possibly substituted on~ or more.time~. b~ ~-C6-alk~ 6-~lkox~r Cl-~6-k~lmer~pto" C~-C6-~lkylsulphiD~l, Cl-C6-sIk~l-sul~hongl~ C2-C6_~1ken~l~ a~-~6-slkynyl~ C2-C6-a-lken~102~ C~-C6-slken~lmercapto, C2 C6-a~k~nylox~
.C~_C6alkyn~1mer~apto~ ami~ a~ - aIk~sm~no~ di--10 C~ C6-a}k~lamino~ Cl-C6-alk~lcarbQn~lamino,,~Cl-C6-alkglaminocarbon~l, CL C.6-~lkox~carbonyl~ hg~rox~
benzyloxyt phen~lme-D~ptOE~ phenylox~ nitro~ cyano~ .
h~logen, trifluorometh~. azido~ form~lamino, carbo~gI ;`~.:
or pheD~,; or signifies a mono-, bi- or tricgclic `
carbocyclic ring with 7 - 15 C-atoms or a heteroc~clic mono-,~ bi- or tric~clic ring s~stem with, in each ca~e~
5 or 6 ring atoms s~d, per ring s~stem, csn contain 1 - 4 or t - 5 heteroatoms, respectively, whereby the heteroatoms are nitroge~ sulphur or oxygen~
20. signifies a hgdrogen atom, a strsight-chained or -~
branched, saturated or unsaturated a~iphstic radical with 1 - 6 ~-atoms or C~-C6-alkoKg, Cl-C6-alk~lmercaptot Cl-C6-alk~lsulphongl t Cl-C~-alkglsulphongl~ smino, C~-C6-aikglamino~ di-Cl-C6-alk~laminot sulphonamido, Cl-C6-alkox~carbon~l~ trif~uoromethyl~ carboxyl~
halogen, hydroxylt nitro, cyano, azido, phen~l or benz~lox~, R2 ha$ the same meaning as Rl, whereby the radicals. Rl and R2, independently of one another, can ` 2108899 be the ssme or different, ~3 signifies h~droge~
6 lk~l~ Cl-C6-alkox~, CI-C6-alk~lmercspto, amino" ~-C6-alkylamino~ di-Cl-G6-alkylamino, halogen, c~ano, hydrox~l,. carboxgl~ Cl-C6-alkoxycarbon~
aminocarbon~l" ~1-C6-alk~laminocarbongl or di-Cl-C6--- a-lk~lami~ocarbon~, R4~ R5, ~6 ha~e the same me~-ning as R3, whereb~ th~ radicals R~ R4, R5 and R6, i~depe.~dentl~ of one anQther,; can be the s~me or dif~rent" a~-well as their tsutomers~ ~n~tiomers, lQ diastereomers and ph~siologicall~ compatible salts~
~or the case that r is an oxggen atom and R~ and R2 do not simultaneously signif~ h~dro~e~ atoms~ it i8 ~
8 question of new oxazolo~ 3-_7-isoindole derivative~ -which are also the subject of th~ present invention.
~he compounds of the formula I hsve hitherto onl~ -been kn~wn in the form of their racemate~r lt has now bee~ 3h~wn that the opticall~-active derivatives possess-a hi~her effectiveness than the corresponding racemic mixtures so that the present invention also .2~ refers to the the new R_ and S enantiomers, ~ he compounds of the formula I displa~ valuable pharmacological properties. In particular,. the~ are suitable for the therap~ and prophglax~is of infections which are caused by DNA viruses, such as e~g herpes simple~ virus, cytome~alovirus~ papillomaviruses, the varicella zoster virus or Epstein-Barr virus-or RN~ viruses~ such as togavi~uses or especiall~ retro-.
~iruses, such as the oncoviruses H~LV-I and IIr.as 21~8~9 well as the lentiviruses visna and human immu~e deficiencg virus HIV-l and -2.
~ he compounds of the formula I appear to be e~pecisllg suitable for the treatment of the clinical 5 manifestations of the retroviraI ~IV infection in humans,~ as well as of the persistent general lgmph-adenopathg (PG~), the adva~ce~stage of thë.~IDS-r~lsted comple~ (ARC) and the clinicall~ com~lete - p~cture o~ AIDS. .
~he.compou~ds of the general formula I posse~s an outstanding antiviral action and are especiallg suitab~e for the tre~tment of viral or retrovirsl ~.
infections. Viral infection~ of mammals,. especiallg - of humans,~ are wide ~pread.. In spite of intensive 15 efforts, it has hitherto not been succassful to make ~.
available chemotherapeutics which interfere cau~all~ :- or sgmptomaticall~ with the.virall~ or retrovirall~
cau æ d appearances of diseases with recognis~ble substantial success. At present, it is not possible to cure certain viral di~eases, ~uch as for e~ample the acquired immune deficienc~ syndrome (AIDS)S .. the~ ~IDSDrelated complex (ARC) and their preliminar~
stages, herpes, cgtomegalovirus (CMV),. influenza and other vîrus infe~;tions or chemotherapeuticall~
~5 fa.vourablg to influence their ~mptoms. At present, for e~ample~ for the treatment of AID5 there is available almost exclusivel~ 3'-szido-3'-deox~-th~midine (AZ~), known as Zidovudine or ~etrovirR.

-8- 21088~9 Hawever,~AZT i8. characterised by a very nsrrow therapeutic spectrum or bg verg severe to~icities 8 read~ ap~earing in the therapeutic ra~ge (Hir~ch, M,S., (1988) J~ Infec:, Dis~ 157,, 427-431~ ~he ~ompound~
5 .of the gener~l formula I do not possessthese di~ad-~a~ta~es.. They act antivirall~ without being cgtotoYic in pharmacologicall~ rel.evant do.~es~ ..
It could now be demonstrated th~t compou~ds o~
the genera~l.fo.rmuls I in~ibit the multiplication of . .
lQ of DN~ and RN~ viruses, respectivelg, at the ~tsg~ of the virus-~pacific ~NA and RN~ ~ra~scri~tio~, -respectivel~.. Via the inhibition of the enzgme ~;
reverse transcriptsse, the substance~ csn influenc~ -~
the multiplication of retroviruses (cf. Proc_ Natl, ~cad, Sci, U5~ 83, 1911~ 1986 or Nsture 325~ 773, 1987), Since a very great need exists for chemothera-peutics which interfere as specificallg as pos~lble with retrovirslly-c~used disesse~ or their s~mptoms without i~fluencing the normallg occur~ing na.tural 20 bod~ functions, the said compounds could bs advant-age.ous1g used prophglacticallg or therapeuticsllg in the treatment of diseases in which a retrovir~l infectio~ is of pathophgsiological,. s~mptomatic or c~inicaI releva~ce.
The sepa~tion of the racem&tes into the enanti~-mer~ csn be carried out anal~ticallg, semipreparativelg - a~d preparativelg chromatographicallg on suitable oFticall~-active phas~ with usual blutions agent~

` ` 2108~9 g As opticall~-ac~i~e.pha~es., there a.re. suitable, for example, opti.call~-active pol~acrglamides or pol~-meth.acrg~amides.~ in some cases also on ~ilica. ~el (e-.g~ ~hiraS.pher (R) of Merck, Chiralp~k ( ) 0~/OP
of Baker)~ cellulo.se esters/carbamates (e~g~ Chirscel(~) QB/Q~ of Baker.~Daicel.~, phase~ based on c~c-~ode~t~i~
or crown ether.~ (e g~ Crownpsk (R) Qf.Dsicel) or microcr~s.tslline cellul~se triac.etate (Merc~
.. An..a~iphatic radical means a straight-chainea or 0 branched 81k~1~, s-lken~l or slk~n~l ~adical with 1 - 9,, pre~erabl~ 2 --7 carbon atom~, such as e~g. the.propgl~
isoprop~lr but~l, isobut~l, pentyl, hex~l or hept~l :
radical. As unsatursted rsai;~als, there come into question C2-C7-a-lken~l and alk~l radicsls,; prefer-sbiy C2-~5, such a~ e~g~ all~l,; dimeth~lall~1t buten~l, is-o.bute~l,. pentenyl or prop~n~l rsdical~
An sliph~tic radical.which can be ~ubstituted b~
phen~I is especiall~ a phen~l-C~-~6-~Ik~l group, such as e~g~ the benz~ phe~eth~l~ phen~lprop~l or phe~
butyl radical, If R signifi~s a phen~l ring~. this csn be sub-stituted one, two or three times.. Independentl~ of o~e an~*her~ the substituents can ~tand in the o-,. m- or p-position~ ~
A carbocgclic ring with 7 - 15 C-~toms can be mono-, bi- or tric~clic and, per ring, ca~, in each case, ha~e 5 or 6 C-atoms~ Thi9 ri~g can be saturated, unsatura.ted, partly ~aturated or aromatic. Bg wa~ of `- 2108~99 example are mentioned the following ring sgstems~
ths naphthyl" anthracengl, phenanthren~lr fluoren~
indengl,, inda~n~l, acena~hthglen~l, norborn~
sdama-~t~l.ring or C3-~7-c~cloaIk~l or C5-G8-c~clo-alkengI. gro~p~
~ he heterocgc3~ic mo~o--, bi. or tricyclic ring sys.tem~ contain, per ri~g s~stem, 5 or 6 carbon atoms,.
whereby 1 - 4 or 1 --5 C-atoms, respective~y, can be rep~aced b~ th~ hetero2toms ox~gen~ ~ulphur and/or ...
1~ nitrogen.. The ~ing systems can be arom~tI~, pa-rtl~
or completeIy hydrogenated. The following ring s~stems can be mention~d b~ wa~ of example: the p~ridine, p~rimidine, p~.ridszine, pgrazine, triazine, pyrrole, p~razole, imidszole,. triazole, thiszole~ oxazole, isoxsz~le,; oxadiazole, furazane" fura~ thiophene,.
indols, quinoline~ isoquinoline., cu~arone~ thio-naphthene,; benzoxszoler benzthiazole~ indazole, benzimidazole~ benztriazole, chromene ~ ph~halazine~
quinazoline, quinoxaline~ meth~leneaioxgbenze~e,.
carbazole,~acridine" phenoxa~ine~ phenothiazine, phenazine or purine s~tem,. wherebg the unsa tura ted or arom~tic carbo- or heterocycles ca~ be partly or completeI~ hgdrogena ted.
R preferabl~ signifies unsubstituted phen~l or - 25 phen~l substituted ~nce or twice by C~-C6-al*~l;
Cl-C6-alkoxy ~ CJ-C6_alkylmercapto, Cl-C6-alk~l_ sulphingl~ Cl-C6-alk~lsulphonyl, C2-C6-alke~
C2-C6-alkyngl, C3~ 6-alkeny-loxy, Cl-C6-alkglamino, 2lnss~s Cl-C6-dialkylamino, Cl-C6-alkglcarbon~lamino ~ Cl-C6~
alk~laminocarbon~l, Cl-C6-alkox~carbon~l, amino, :`
hgdroxyl~ nitro, azido, trifluoromethgl, c~ano or halogen~ The previously mentioned "aIk~l" parts .5 preferablg oontain in the definitions in question up to 4, especiallg up to 3 C-atoms~
Carbocgclic rings are preferabl~ biphen~l, naphthyl, anthracengl, inde~l, fluoren~l, ace- .
n~phthylengl,.phe-nanthren~l~-.norborn~l,. adamantgl, .~.... ...
:~0 C3--C6-c~cloalkgl, C.5-C8-cgcloalkeng,l, Heterocyclic ring sgste~s are preferablg p~rrole, imidazole, furan, thiophene, pyridine, p~rimidine, thiazole,. triazine, indole, quinoline, isoquinoline, cumaro~e, thionaphthe~e~ be~zimidazole, quinazoline, methylenedioxgbenzene,. ethylenediox~benzene, carbazole, scridine and phenothiazi~e.
For the radicals Rl and R2 are preferred hyd~ogen, C L-C6-alkgl,~ C2-C6-aIke~ C2~C6~alk~Y~Ylr Cl~C6~
alkox~, Cl-C6-alkylmercapto~ Cl-C6walkglami~o~ Cl-C6-alkoxgcarbongl,~ trifluoromethyl, amino, halogen,hydroxyl, c~ano and azido, wherebg the "alk~l" parts in the pre~iouslg mention~d definitio~s preferabl~
contain up to 4, e~pecially up to 3 C-atoms.
Preferred ~ubsti.tuents for R3~ R4, ~5 a~d R6 are hgdrogen, Cl-C6-aIkyl~ Cl-C6-alkox~ r C~-C6-alkgl-mercapto, carboxyl, Cl-C6-alkoxgcarbon~l,. halogen, cgano and hgdroxyl, whereby the "alkyl" part~ in the 108~!~9 pre~iously mentioned definition~ preferablg contain ~`
up to 4, especiall~ up to 3 C-atoms.
X is preferabl~ ox~ge~ or sulphur. By halogen is ~enerall~ to be under~tood fluorine, chlorine, bro~ine ~-and iodine, preferabl~ fluorine, chlorine and bro~ine~
Y is prefera~l~ oxygen Qr -~R7, whereb~ for ~7 there comes into question hydrogen ~r the C~-C6-alk~
or C~-C6-scy~ radical. B~ acgl radics~, one under- -~
~tands especially the C iC6-alk~lcarbonyl radical. ~;
~h~ "alk~l'r parts preferably contain up to 4, ospeciall~ up to 3 C-atoms~
E~peciall~ preferred radicals for R are C3-C5-alkyl, phe~yl~ phenyl mono- or ~isubstituted b~
Gl-C6-~lk~ C6-alkox~, trifluorometh~l or halogen, naphth~l, anthra~n~l, i~dan~ fur~, thienyl~
pgridJl~ indol~ ui~olin~l.
~ or Rl and R2, independentl~ of o~e another, there are especiall~ preferred hydrogen~ methglr eth~l~ isoprop~l, trifluorometh~l~ methox~, ethox~
and halogen~ whereby chlorine and bromine are especisllg preferred for halogen, ~ or R~" R4,~ R5 an~ R6, ami~ocarbo~l, meth~l, eth~l and isoprop~l are e~peciall:y preferred.
EspecialIb preferred are compounds of the general for~ula I in which R, Rl, X and Y have the above-~iven meani~g a~d R2, R3~ R4, R5 and R6 are e~ual to - h~drogen, meth~l~ eth~l~ chlorine~ bromine~ methox~

' ~ 210~99 or ethox~, whereb~ R2 to R6 above all represent hgdrogen.~.
.The medicaments containing at least one compound of the formula I for the treatment of viral or retro-. 5 virs~ infections or o~ di~eases c~used bg these ca~be administered enterall~ or par.enterall~ in liquid or solid fQrm~ ~here hereb~ come into ~uestion the u~ual forms Qf admini~tration, such a~ for e~sm~le tsblets, ca~sul~-s, dragees; syrup~ solution~-or }~ su~pension~ ~g inje.ction medium, water is preferabl~
used which co~tsins the additive~. usual in the case of injection solution~,; such as ~tabilising sgents,.
solubili~ing agents sna buffers~. Such additives are e.g~ tartrste and citrate buffers, ethanol, comple~
15 formers, such as ethylene.diami~e-tetrsacetic acid ~nd its non-toxic salts, high molecu~ar po~mer~,.
s.uch as liquid pol~eth~lene oxide~ for ViSC08it~
regulation. ~iquid carrier materials or injection solutions must be sterile and are preferabl~ filled into ampoules~ Solid carrier materials are, for example, stsrch, lactose, ma~nitol, meth~l cellulose~
tal.c, highLg dispersed silicic acid~, high molecular fatt.~ acids~ such as stearic acid,~ gelatine, agar-agar, .~
. . calciu~ phosphate., magnesium ~.tearate9 animal ~nd :-:
vegetable fats, solid high molecular pol~mers, such as pol~ethylene gl~col, etc. Compositions suitable ~or oral.~ministr~tio-n can,. if desired, contain ~-flavouring or sweetening m~terial~ ~

? 2 ~ O ~ ~ 9 9 For th~ prepara.tion ~ ph~iologicallg compatible salts, compcullds of the farmula I, which car~;~ 8 basic group" are reacted with inorganic or organic acids" .
such a~ e~g.. with h~drochloric acid,. hg~ar~bromic acid, 5 ~ulphuric acid~l phosphoric acid,. fumsric acid, ~uccinic acid" tar~aric acid,S citric acid t~ lactic acid ~r maleic acid, and the a.cid-addition ~alt~ isolated~
If the compQunds.of th~ formuls I contain ~n acid g~ou~ en o.n~ obt~in~ the ph~s~-ol-ogicsll~-cQm~stibl~
lD sslta b~ reaction with sl~ali mets~ or alkaIine ea~th metal h~droxide, such as e..g. sodi~m h~droxidet potas&ium hgdroxide or calcium h~droxide,~or with other basic group9, such as a~ines, e.g~ trieth~lsmine.
The dossging can depend upo~ ~arious factors,. ~uch 89 mode of administration, ~pecie~, age or individual s.tate of health~ The compounds according to the invention are usuall~ admini~tered in amou~ts of 0~I--I00 m~, prefer~blg of Q~2 - 80 mg per da~ and per kg of bod~ weight_ It is preferred to di~ide up 2~ the daiI~ dose into 2 - 5 administrations, whereb~, in the case of each admi~istratio~ t~ 1 - 2 tabl~ts with an active material ~te~t ~f 0~5 - 50~ mg are admini~tered. The. tablets can 81so be retardedt whereb~ the number of administrations per day is ~ 25 ~educéd to ~.- 3. The ac~ive material content of the retarded tablets. can smount to 2 - 1000 mg. The acti~a msterial can also be given b~ conti~uous infusion, 2108~99 -15- ,~
wherebg the,amounts of 5 - lOQO mg per ~a~ normallg . ~u~fice, The. medicsments containing at lea~t one.compound of the formu~a I are prepsred. in that one mixes a compound of the formula I with usual pharma:csutical adJuv~nts snd works up to medicin~l forms.,.'such as ~g~ tablets,, dragees,. capsules or solution~. ~hese medicina~ forms are made. up into packaging unit~
r.~ad~'~for`'sale'and p'rovided with ~n appropriat~- `
instruction, e.g~ in_the form of a psc~aging leaflet or printed instructions on the packa~ing from which follows the use for the treatment of ~ rsl or retro-~iral infect~ons or of disea~es caused by these infecti~ns~
The compound~ of the general formula I according to the inve~tion are prepared according to proces~e~
~nown ~rom the litsrature in that one reacts possiblg ; ~
substituted benzoic acid derivatives of the general ~`:
formula II ` :.

RR2 ~ ~ (II), in ~hich R, Rl and R2 have the above-given meaning and ~ i~ equal to -COQ~ or C~N, with substituted or unsubstituted ethanolami~e or ethylenediamine of - the general formul~ III

2108~9 . ~III) ,.
~E2 \ R5 ~6 in which Y~ R~, ~4,.R5 and ~6 have the given mea~i~g,.
in ~ suitable i~ert 90~ent at room ~emperature to r.eflux temperatur~ pos~ in the presence of - i ~;; cat~ tical smounts of scid~ 8~g.. p--to-luenesul~?hot~
acid, and. pos~ib~;y subsequentl~ converts compound~ c~f the formula I int~ other compounds of the formu~a I
and subsequentl~ pu~ifie~ chrom~tographicall~ or b~
recrg~talliæatio~. Racemstes can be separated into lQ the antip-odes by chromatogrsph~ o~ suitable opticall~--sctive phases~ e.g~ cellulose t~iacet3te.
~ he subseque~t conversion of compounds of the formula I into other compounds of the formula I
co~cerns the preparation of oxazolo-~ ~3-a7isoindole ~;
15 or imidazo~ 7-isoindole derivatives with :~ ~ S
or N-alk~limine~ Compounds with ~ = S are prepared ~g reaction of compounds of the formula I,in which X
signi~ies an oxggen atom~ with sulphur group-transferring compounds, such as 8. g, ~BWe`9$0n I S
rea~ent. Compound~ with X = N-alk~limino are prepared b~ reaction of the corre~ponding imino compounds of the genera~ formula I with al~lami~es according to per ~e known methods.

21088~9 The benzoic acid derivatives of the gener~l formula II are also known from the literature ~nd are prepared e~g~ by Friedel-Crsfts ac.~lation of ~
sub~.tituted or u~substituted phthalic ac.id anh~dride with possibly ~ubstituted arenes i~ the pre~ence of a Iewi~ acid (e.g. sluminium chloride) or b~ reaction of Grignard reage~t~.of the general formula IV
R-MgB~ (IV), -- in which R, with ths exce~*ion of hydrogen, has the.
above-gi~en meani~,.with phth~lic acid anh~dride, which is possibl~ substituted, in suitable inert solvent~ at low temperature~..
- ~he processe~ for the prepsration of the compou~d~
of the gener~l formula I according to the inventio~ .
csn also be taken from the pstent applications or literature references given in the prior art~
In the meaning of the pres~t i~vention~ apa~t from the compounds mentioned in the~E~ample~ a~d those gi~en b~ combination of all meanings of the substituents mentioned in the claims~ the following compOunds of the for~ula I come into question which can be pre~ent as racsmic mixture or in opticallg-sctive form or ~s pure R- and S_enàntiomers.
Compounds of the formula I 9 in which Y ~ig~ifies an ox~gen atom are especiall~ the following;
1, 8,9b-dimethgl-2,~-dih~drooxazolo-/~,3-a7~isoindol- ~:
5(9bH)-o~e 21088~9 2. 8-chloro-9b-phengl-2,3-dihgdrooxazolo~ 7_ isoindol~5(9bH)-one 8-fluoro-9b-(4-~ethglphen~).-2,3-dihgdrooxazolo-~,.3-a7-isoindol-59~bH~-one ..5 4~ 8-chloro-9b-(3-m~th~.lphen~..1.~-2,3-dih~droox~zolo-/~,3-a7-isoindol-5(9bH~-one 5~ 3-methy~-9b-(4-ethylphèng~)-2,~-dih~drooxaz~
/~,3-~ -isoindol-5(9bH)-one -; - 6. 9b-~.3-dimeth~lpheng.~ ,.3-dihgdrooxazo~o- <-. 10 /~3--7-isoin~le-;5(9bH)-~hiQne~
7, 8-chloro-9b-(3,~4-dimethglphengl.)-2,3-dih~.dro-oxszolo-/~,.3-a7-isoind~5(9bH)-thio~e :~
8, 2-eth~1-9b-{?,5-dimeth~lphenyl)-2,3-dihgdrooxsz~lo~
-87--i~oindol-5(9bH2-One 15 9. 8-chlo-ro-9b-(3-trifluorometh~lphen~ 2,~-dih~aro-oxazolo-/~,3-s~--isoindol-5(9bE~-One 10. 6-methox~.-9b-(4-trifluQrome~h~lphengl)-2,,3 dihgdrooxazolo~ 3-a7-isoindol-5(9bH)-on~
11. 9b-(4-hgdrQx~pehn~ 2~3 dihgdrooxazolo~ 3-a7-20iso.indole-5(9bH)-thione 12. 8-chloro-9b-(3-hgdroxgphengl)-2,3-dihgdrooxazolo-/~,3-s~ oindol-~(.9bH~-one 13. 7-methylmerca~to-9b-(4-ethox~phen~ 2,3-dih~dro-o~azolo~ 37-isoindol-5(9bH~-one -25 14. 9-methgl_9b-(3-methox~phen~ 253-dihgdrooxazolo-/~,3-s7-isoindol-5-(9b~)-one 15~ 8-fluoro-9b-(.3-~luorophen~ 2,3-dih~drooxazolo-~ -a7-isoindol-5(9bH)-one 16. 9b-(4-chlorophen~,1.)-2,,3-dih~drooxazolo~
isoind'ole-5(9bH.2-thione 17~-8-m~th~-L-9b-(3'-me.th~lsulphon~lphen~ 2~3-dîh~dro-OXaZOl.Q - /~, 3- ~ -isoindol-5(9bH')-o~e 5- 1~.. 8-chIoro-9b-phen~ 3-dih~drooxaz~lo--~2,3 i~oindol-5(9bH.~-one l-oxide~
19~ 8-chloro.-9b-benz~1-2,~3-di~hydrooxszolo-~,.3-~ -i~o~ndol-5(9b~)-one ' - 2~., 2.,2-dime,thgl-9b-phe'n,~th~l-2,.3-~ih~rooxazolo~ ~ ~' lQ - ~ ,~-~7-isoindol * (9b~-on~ , -~
21, 9b-(3-meth~lmercaptophenglS,-2,3-dihydroo~azolo- ..
/~,3'-e3.-i~oindol-5(9b~)-one - ''' 22~ 9b-(3-metb~-laminophen~1~-2,,3-dih~drooxazolQ- -' t~`,3-_7-isoindol-5(9bH~-On~
23, 9b-(3-azidophenyl~-2~3-dih~drooxazolo-~ ,3-a7- ' isoindol-5(9.b~I~-one , -24~ 8-me.th~l-9b-ell~1-2~3-dihydrooxazolo- ~ ~3-_7,~
isoindol-5(9bHS-One 25~. 8-chloro-9b-(3,,5-dimeth~lphen~ 2,3-dih~dro- '~
Ox~zolo-/~',3- ~ ~isoindol-5(9bH)-o~e 26~ 8-me*h~l-9b-(1-~aphthgl)-2,.3-dihydrooxazolo-/~,3-a7-isoindol--5(9bH)-on~
27. 9b-(anthracen-~ 2,,3-dih~drooxazolo-~,3-s7- - ~-~
i~oindole_5(9b~)-one 28~' 9b-(a~thr~cen-9-~1)-2~3-dih~drooxazolo-/~,3-a7-isoindol-5(9b~ one 29~ 9b-(inden-1-~1)-2~,3-dih~drooxazolo-/~,3-~ -5(9b~)-one . .,.

~" 2108899 30~ 9b-{inden-3-g.l)-2~3-dih~drooxazolo~ 3- ~ -isoindol-5(9bH.).-one 31_ 9b-(inden-4~1)_2.~3-dihgdrooxaz~lo-~isoin&~-5(9bH:~-thione 32, 9b-(phenanthren-~ _2,-.~-dih~drooxazolo-/~,3- ~ -isoindo~-5(9bE~-one.
33; 9b-(phenanthre~-9-~1)-2,3-dih~droo~azolo-f~3~
isoindol-5(9bH)-one. . ..
....... ~-.~. 34.~ 9~-~c~c~lohexen-~-gl.)-2,3-dihydroaxazolo-~, 3.-.a7~-~Q isoindole-5(9bE~.-thione . :~
35~ 9b-(2-furyl)-2.~3-dihydrooxazolo-/~,3-~ -iso~ndol~-~(9bH).-thion~
36~ 9b-(3-furyl)-2,.~-dih~drooxazolo-~,3-a7-isoindol- .~
5(9bH)-one ~.
37~ 9b-(2-thien~1)-2,?3-dih~droox~zolo-/~,3-_7-iso~
i~dole-5(9bH~_thione 38~ 9b-c~-thi~n~ 2~3-dih~drooxazolo-/~3-a7-i~
.. indol-5(9b~)-0~e:
39~ 9b-(p~rimidi~-4.-~-2~3-dih~drooxazolo-/~, 3-A7-isoindol-5(9bH.. ) o~e 40, 9b-(thiazol-?-gl)-2~3-dih~drooxazolo-/~3 i~olndol-5(9b~ One 41, 9b-(thiszol-4-~1)-2,.3-dihydrooxazol~ ,3_a7-isoindole-5(9bH)-thione -- ~5 42~ 9b-(indol-3-~1)-2,3-dihgdroox.azolo-~,3-a7-isoi~dol-5(9bH)-one ~ 43~ 9b-(indol-7-yl)-2,3-dihgdrooxazolo~ -a7-.. isoindol-5(9bH.)-one -" 2108~9 44, 9b- (quinolin-4-~1)-2,3-dihgdrooxazolo-~,3-~ -isoindol-5(9bH)-one 45~-9b-(quinolin-5-y-1)-2,j3-dihgdrooxazolQ-/~,3-~ -isoindole-5~9bH~-thione.
- 5 46~ 9b-~benzimidazol-4-gl.~-2,3-dihydrooxszolo~
isoindol-5(9bH~;-one. . . 47~ 9b-(carbazol-i-gl)-2,.3-dihydrooxazolo-/~,3-a~7-~s~indol-5(9bE.. ~-~ne .
- - 48~ 9~J-~c~rbazol-4-~1.)-2~3-dih~dr~ox~zolo ~ ~,3 ~ - -isoindole-5(9bH.~-thion~ .
49_ 9b-(phenothiazin~ 2,3-dih~drooxazolo-/~,3-s7- `.
isoi~dole-5(9bH)-thione ~.
50, 9b-(phenothiazin-4-~1)-2~.3-dih~drooxazolo-.
/~,3-a7-isoindol-5(9bH.~-one .:~
51~ 9b-(4-quinazolin-4-gl3-2,3-dihydrooxazolo;- - . ~ ,3-a7-isoindol-5(9b~)-One 52. 8-chloro-9b-(inden-3-~ 2,3-dih~drooxazolo- ~
/~,3-~ -isoindol-5(9b~)-one . .
53. 8-methgl-9b-(is.oqui~olin-1-gl)-2,3-dihydro- .
o~azolo-~,3-s7-isoindole-5(9bH)-~hio~
54~ 9-methoxg-9b-(7-naphthyl)-2,.~-dihydrooxazolo-~ a7-isoindol-5(9bH)-One 55. 9b-(cumaron-3-gl)-2~3-dihydrooxazolo-~,3-a7-isoïndol-5(9b~)-one C~mpounds of the formula I, in which Y signifies the group -NR, are especiall~ the following:
lo 8~9b-dimethyl-2,~ dih~droimidazo~ ~-isoindol~
5(9bH)-one - -" 2108~9 2;..8-chloro-9b-pheng1-2,3-dihydroimidazo- ~ ,1- ~ -i~oindol-5(9bH)-one 3. 8-fluoro-9b-(4-methylphen~I)-2,3-dihgdroimidazo-~ isoi~dol-5(9bH~-One -5 4~ 8-chloro-9b-(3-meth~lphen~1~-2,3-dihgdroimidazo-~ 7-isoindol-5(9bH~-one . ~-~
5~ 3-meth~1-9b-C4-ethglphen~1~-2,3-dih~droimidazo-/~ ,.l-a7-i~olnd~1-5(9bH.'),-One 6, 9b-(2,3-dim~th~lphen~12_233-dih~droimidazo-~
I0 isoindole-5(.9bH)-thione~
7 8-chloro-9b-(3,?4-dimeth~lphen~1)-2,3-dihgdro-imidazo-/~,l- ~ -isoindole-5(9b~)-thion~
8~ 2-ethyl-9b-(2,.5 dimethglphe~ 2,3-dih~dro-imidazo-~ ~ isoindol-5(9bH)-One ~-~5 9 8-chloro-9b-(3-trifl~orometh~lphen~;1)-2,3-dihgdro-imid~zo-~ ,}- ~ -isoindol-5(9bH)-one 10. 6 methox~-9b-~4-trifluorometh~lphen~1)-2~3-dih~dro-imidazo~ l-a7-isoindol-5(9bH)-one 11~ 9b-(4-h~dr~x~phen~ 2,.3-dihgdroimidazo-/~,L- ~ _ 20 isoi~dole-5(9b~)-thione 12~ 8-chloro-9b-(3-h~drox~phenyl)-2,3-dihydro-imidazo-~ ,l-a7-isoindol-5(~9bH)-one 13 7-methglmercapto-9b-(4-ethox~phen~1)-2,~-dih~dro-imidazo-~ ,1-~ -isoindol-5(9bE)-one 2.5 14 9-meth~1-9b-(3-methox~phen~1)-2,3-dih~droimidazo-~',1--_7--isoindol-5(9b~)-one 15~ 8-fluoro-9b-(3-fluoropheny1)-2,3-dih~droimidazo-~ ,l-a7-isoindol-5(9bE)-One " ` 2108~99 16~ 9b-(4-ch~orophen~1~-2,3~dihydroimidazo~ a7- ::
isoindole-5(9bH)-thione 17. 8-meth~1-9b-(3-methglsulphon~lphen~ 2~3-dih~drO-imidazo~ isoindol-5(9bH:2-one . 5 18. 8-chloro-9b-phen~ 2~3-dih~droimid~
isoindol-5(9bH~-one l-o~ide 19,. 8-chlc~ro-9b-benz~L-2.,.3-dihgdroimida zo~
i~o~r~do~L-5(9bH)-Gne ~-20.. 2,2-dimethg1~9b-ph~t~gl~ 2,3-dih~dr~imidaæo~
/~ 7-isoindol-5(9bH)-O~e - -210 9b-(3-meth~lmercaptophen~1)-2~3 dih~droimiaaæo- . -:
/~,1-87--isoindol-5(9b~)-o~e 2Z, 9b-(~-meth~laminoph~ 2,3-dihydroimid~zo- ~;
~,1-~7-isoindo~--5(9bH.)-one 15. 23~ 9b-(3-~zidophenyl)-2"3~dih~droimidazQ-~,l-s7-i~oi~dol-5(9b~ one.
24~ 8-methgl-9b-all~1-2~.3-dih~droimidaz i~oindol-5(9bH~-0~e 25~ 8-chloro-9b-~9.5-dimethglphen~l) 2S3-dih~dro- :
, 20 imidazQ~ l s7-isoi~dol-5(9bH)-~ne 26~ 8-meth~-9b~ nsphthyl)-2,~-dlhydroimidazo-~ s7-isoindol-5(9bH)-One 27~ 9b (anthracen~l-yl)-~,3-dih~droimidszo-/~,1 a7-isoindole-5(9bH:)-thione 28, 9b--(anthracen-9-~ 2 j.3-dihgdr~imidazo~ a7 isoindol-5(9bH)-o~e 29, 9b-~inden~ 1)-2,3-dih~droimidazo-/~ a7-isoindol-5(9b~)-one --2108~9 ~0, 9b-(inden-3-~1)~2 ~3-dih~droimid~zo-.
isoindol--5(9BH.~-one 31_ 9b-( inden-4~ 2~3-dihgdroimidszo~ a~--isoin~ 5(9bH.~-t~ione.
5 32:~ 9b-(phensnthren~ 2~-dih~droimidazo~
isoindol-5(9bE~-one.
9b-(phenanthren-9~ 2~-dihgdroimid~z~
isoindol-5(9bH)-~ne .,........ .. ~-34, ~b-(c~olohexen-~ 2~3-.~ ro.imid.a~
1~ isoindole-5~9b~ thi~ne 35, 9b-(2-fur~l.)-2~.3-dih~droimid~zo~7-iso~ndole~
5~9bE)-thione 36, 9b-{3-fur~ 2~3-dih~droimid~zo~1-a7-i~oi~dol-5(.9b~.~_v~
37~ 9b-(2-thien~ 2"~-dih~droimidazo~ isQ--indole-5(9bH)-thione 38~ 9b-S3-thiengl)-2,3-dihgdroimidaz~ s7-i~o-indal-~(9bH).-on~
39~ 9b-(pgrImidin-4-gl)~2~3-dihydroi~ids.z~91-~ -isoindo~-5(9bH) one 40, 9b-(thiazol-2-~1) 2~3~dihgdroimidaza~
isoindol-5(9b~)-one 41, 9b-(thiazol-4-~ 2,~3-dihydroimidazo~ 7-isoindole-5(9bH)~thione -- 25 42,-9b-(indol-3--~1)-2,3-dih~droimidszo /~,l- ~ -isoindol-5(9b~)-one.
~ 43. 9b-(indol-7-y1~-2~3-dih~droimidazo-~ ,1-a7-isoindol-5(9bH)-one ~ 2108899 ~
-25- ~ ;
44~ 9b-(~uinolin-4~ 2,~-dihgdroimid~zo~
isoi~do~-5(9bH)-One ~.
- 45~. 9b--(quinolin-5~ _2,3-dih~droimidaz~
isoindole-5(9b~ thione 46~ 9b-(be~zimid~zol-4-~1)-2,3-dihgdroimidszo-/~,1-a7-i~indol-5(9bH,)-one 47_ 9b-(ca~bazol-1-yl)-2~3-dih~droimid~zo-~ ,1- 7-isoind~l-5(9bH?-one 48~ 9b-~arbazol-4~ 2,3-dih~d~oi~idazo~ a7 1~ isoi~dale-5(9b~-thione 49, 9b-(phenothiazin-1-yl)-2r3-dih~droimid~zo~
/~1- ~-isoifido~e-5(9b~)-thion~
5~. 9b-(phe~othiazi~-4~ 2~3-dihydroimid~
~ sindo1-5(9b~)-o~e I~ 51. 9b-(4-~uinazolin-4-~1) 2t.3-dih~droimidazo- :~
~ isoindol-5(9b~)-o~e 52 8-chloro-9b~ den-3~ 2,~-dih~droimidszo-~ oindol-5~9b~ one 5~ 8-meth~1-9b-(isoquinolin-1-gl)-2~3-dih~dro imidazo-~ ,1- ~-isoindole-5(9b~)-thione 54~ 9-metho~-9b~ naphth~ 2~3-dih~droimidazo-~ isoindol-5(9bH)-on~
55r 9b-.(cumaron-~-yl)-2,~dih~droimidazo-~ ,1-a7-isoindol-5(9b~)-One Example 1 9b~ Na ~th~1)-2~-dih~drooxazolo-~ ~ -isoindol-5(9b~I)-onQ

`~ 2108899 2................ 76 g (1~ mmol) 2-(1-naphtho~ benzoic acid ~,~
were diss.olved in 100 ml xglene and~ after sddition of 1~.22 ~ (20 mmol) ethanolamine,., a~ well ~s of a c~talgtic amou~t of p-toluenesulphonic acid, hested und~.r reflux for l.h o~ a water separator~ ~he solvent was then removed in a vacuum and the residue recrgstalli~ed ~rom ethan~ ield 2.1 g t70~ of theorg)~, m.p.~ 144 - 146C~
- ~he 2-(1-naphthogl)-be~z.oic acid.use~ wss-prepared , ~?~`
b~ ~low dropwise additio~ of l-nsphthgl m~gnesium ... ~ . . . .
bromide in ether/toluene 4/1 ~ -10C to a solution of phthalic acid a~h~dride in toluene, after 2 h~urs post-stirring additicn of sat. ~ Cl solution,.
ex~rsction with ethyl acetate,~ shskin~ out of the ~thy-l ester phase w,ith 2~ soda solution snd renewed e~traction of the scidified ~oda phase with eth~l acet~te~ Yield after recrgstallisation from eth~nol :
64~ of theor~, m~p, 170C~
~he?foll~wlng compounds,were prepared ~nalogousl~
to Examp~le, 1:
1,1 9b-(snthracen-9-~1) 2,3-dihgdrooxazolo-~ ,3-87-isoindol-5(9bH)-one; m,p~ 205-206C; gield 45 from 2-(9-anthrace~o~ benzoic acid s~d ethanolamine 1~2 7,.8-dichloro-9b~ naphth~1)-2,.~-dih~droo~azolo-/~',3- ~ -isoindol-5(9bH)-one; m.p, 165-172C;
gield: 45~

`''.

"` 2108~99 ::

~' --27--from 4,~-dichloro-2-~enzoylbenzoic acid and e thanolamine -1~3 9b-(2-thieny1)-~ 3-dihgdrooxazolo-/~, 3-87--i50-indol-5(9bH)-one; m~p.. 101-104C
-5 from 2-(2-thieno~l)-be~zoic acid and ethanolamine (64% ~ield)` ~:
1~4 9b-(2-fur~1)-2"3-dihgdrooxszolo- ~ ,3- ~-isoindol- :
5(9b~ ne;
~rom 2-(2-~uro~l)-benzoic acid and etha~o~amine;
_ 10 1,5 8-metho~-9b-phen~1-2,3-dihgdrooxszol~ 3-~7-isoindol-5( 9b~ -One;
from 4-methoY~-2-benzoglb~nzoic acid and ethanolamine 1~6 8-chloro-9b-phen~1-2,~-dih~d~ooxazolo-/~,3 ~5 i~oindol-5(9b~)-One; m~p. 112-114C, from 4-chloro-2-benzoylbenzGic ~cid ~ud etha~
amine (58~ gield) 1,7 8-meth~l-9b-phengl 2~3-dihgdrooxazo~ 3-a7-isoindol-5(9b~)-o~; m.p. 103-104C; ~ie7d 6~
from 4-meth~l-2-benzoglbenzoic acid and ethanol-smin~
1~8 8-trifluQromethyl-9b-phe~gl-2,3-dih~drooxszolo-a~ -isoindol-5(9b~.)-one;
f~om 4-trifluoromethgl-2-benzoylb~nzoic acid and e thanolamine 1~9 9b-(4-p~ridgl)-2 ,3-dih~drooxazolo-~, 3-s~-iso-indol-5(9bH)-one; m~p.. 115-118~

; 21088~9 from 2-(4-p~ridoyl~-benzoic acid and ethano~amine (62~ ~ield) l~10 9b-meth~-2,.3-dih~droox~zolo-~,3-s7~isoindol-5(9b~-one; oil; ~ield 61~ .
from 2-Ecet~1benzoic scid snd ethan~7amin~
9b-bu~ 2,~-dihydrooxazolo-~:,3-a7-isoi~dol-5(9b~)-o~e, ~il; ~ield 53~
from 2-but~lbenzoic acid and e.thanolami~e .12 9b-phengl-2~3-dih~drQox~zQlo~ 3~ isoind ~0 5~9bH)_one; m.. p~ 148-150C, from 2-benzoglbenzoic acid and ethanol~mine.
(75~ gicld~
1,13 9b-(4-fluorophen~L)_2,.3-dih~drooxazolo-/~,3-a7-iqoindol-5(9bH~-one, m~p_ lQ~-lC4C; ~ield 64%
from (4-fiuorobenzo~ be~z~ic acid and etha~ol-amine 1 14 9b-(3-meth~lphen~1~-2"3-dihydr.ooxazolo-/~,3-s~ -isoindol-5(9bH)-one; m~p~ 79-85C;. ~iela 45 f~om 2-(.~;meth~lbenzo~l~-be~zoic acid s~d ethanolamine 1,15 9b-(3-chlorophe~ 2,.3-dih~drooxazolo-~,3-a7- ~.
i~oindol-5(9bH3-one; m,p.. 95-96C.; ~leld.72 from ~-(3-chlor~b~nzo~ benzoic acid ~d ethanolamine: ~
2,5 1,16 9b-~3-m~thoxgphen~ 2,3-dih~drooxazolo-~,7_~7_ ~:
isoindol-5(9b~)-one; m..p~ 120-121C; ~ield 62 from 2-(3-methox~benzogl.)-b~nzpic.2cid and e thanolamine t . 2108~9 ~17 9b-~3-trifluorophen~ 2,~-dihydroox~zolo-/~,3-_7-i~oindol-5(9bH~-one;- mr~ 97-98~C, ~iel~ 46 from 2-(3-triflu~robenzo~ benzoic aci~ and ethanol~mine 1~18 9b-(~5-di~ethylphe~ 2,3-dih~drooxszolo-~,3- ~-isoindol-5t9bH~-one; - ~:
from 2~ 5-dimeth~lbenzogl)-benzoic aci~ and ~ ~thanolamin~- -1,19 9b-:(3,~-dic~l-orophen~1~_2~-dihydrooxa~olo-3~ indol-5(9bH)-on~; m.p~ 158-159~C;
~ieI~ 70~
from 2-(3,5-dichlorobenzo~1) b~nz~ic acid and e.tha~olsmine 1,20 9b-(4-ind~ 2,3-dihydroox~zQlo-/~,3-~7_ isoindol-5~9bH)-One; m_p.. 153-157G, ~ield ~9%
from 2-(4-ind~o~l)-be~zoic acid s~d eth3nol~mi~
1-,21 9b-(5-tetralin~ 2,.~-dih~droox~zolo-/~7 ~_~7_ isoi~dol-5(9b~)-o~e;-from 2-(5-tetral;no~ b~z~c acid and etha~ol-smi~
1,22 9b-(2-be~zothiophen~1~2,3-dihgdroo~zolo ~ -a7 isoindol-5(9bH)-one;
from 2-~2-benzothiopheno~ benzoic 8Ci~ a~d ethanolamine 1~23 9b-(2-benzofura~ 2,.3-dihydrooxazolo~
i~oindol-5(9bH)-one, 1 2~08~9 .. ~
from 2-(2-benzofura~o~ benzoi~ ~cid and e thano lami~e 1~24 9b-(3-indolgl)-2.,3-dihydrooxazolo-~,3 isoirldol~(9b~)-one; m.p_ 210-2l3C;~ ~iel~ 39 from 2-(3-indolo~ benzoi~ acid. and: ethanol--~m*~e 1~25 9b--(4-quinolin~ 2,3-dih~d;rooxazol~ ,3 isoindol-5(~bH~--o~;
'J.~ ' ,J, from 2 (4-quinolino~ bepz~ic ao-i;d ~nd etha~ol-1~ smi~e-- ~
1~26 9b~ isoqui~olin~1)-2"3-dih~drooxa~olo-~,3-s7-isoindol-5(9bH.~-O~e;
from 2-(1-i~oquinolino~ be~zc~ic acid and e than~lamine 1~ 1,27 9b-phen~ 2,3-d~h~droo~ zolo-~,3-a7-isoindol-5(9bH)-imine; m~p~ 109--111C; ~ie}d.47 from 2-benzQ~lbenzonitrile a~d ethanolamine 1,28 9b-phengl-3-isoprop~1-2,3-dih~drooxazolo ~ ,~-~7-~,~ .
isoindol-5(9b~)-one; oil / ~ 72~ = +248~7 (CHCl~) from 2-benzo~lbenzoic acid and S-(+)-valinol (73~ ~ield) 1~29 (t~- a~d (-~-9b-phengl-2~ meth~l-2,3-dih~dro-ox~olo~ ,3-~ -isoi~dol-5(9bH)-one;
m,p, 147C? ~ ~_720 = +137 (CHC13) and m.p~ 154C,, / ~ D - -26~ (CHCl~), from 2-benzo~lbenzoic acid and R~ amino-2-p~opanol. a~ter sepa~ation on cel~ulo~e triscetate with methanol~wa.ter 7.3 1,30 (*)--and (-)~9b phen~i-2-methgl-2,3-dih~dro-o~azolo~ 3~ isoindol-5(9bH~-one;
. 5 m.p~ 154~C, / ~ 720_ +261~1 (CHC13~ and m~p~ 147C, / ~ 720= 137 (CEC13) ~rom 2-benzQ~lbenzoic acid snd S~(+) ~-amino-2-pro~anol after separation o~ ~P 18 with m~thanol/
- ~ w~ter-6:4 ~0 1,~1 9b-phen~1-2S,3-dimeth~1-2~.3-dih~drooxazolo~ 7-isoindol-5(gb~)-one; m.~. 76C, from 2-benzo~lbe-nzoic acid and (+/-)-2-smino-3-butanol ~ 1_32 (+)-9b-phen~1-3-meth~1-2,3-dihydrooxazolo I5 /~3-_~-isoi~dol-5(9bH)-one~;
m.~p~ 140-141C; ~ - ~13.3 (CHC13) from 2-benzo~lbenzoic acid ~nd S-(~)-2-ami~o-- 1-prapano~
~D
1,33 (-~-9b-pheng1-3-m~th~1-2,3-dih~drooxazolo- :~
/2~3 a7-isoi~dQ~ 5(9b~)-One;
m.p, 142~143C~ ~ ~ 20 _ -318,5 (CHC13) from 2-benzo~lbenzoic acid and R~ 2-amino-l-propa~ol 1.34 9b-phen~1-2?2-dimeth~1-2,3~dihydrooxazolo-/~.3-a7-isoi~dol 5(9b~)-one; m.p~ 149G
from 2-be~zo~lbenzoic acid and 3-~mino-2-methgl-2-propanol (85~ ~ield) ~i 2108~99 -~2 1..35 (~2-9b-phen~ -methox~car.bon~1-2?~-dih~dro-oxazolo~ s7-isoindol-5(9bH)-one; m~p~
--- from 2-benzo~lbenzoic acid a~d -~erine methgl e~ter 1..~6 9b-phengl-2~3-dih~drooxazolo-~ t 3-a~-isoindole-5(9bH2-o~e;
from 2-be~zo~lbenzonitrile and etha~olsmine E~ample 2 9b-phen~}-2~3-dih~drooxazol-a-/~3-a7-isoindole- -~0 ~(9b~)-thione 1,9 g (7~.5 mmol) 9b-phen~1-2,3-dihgdrooxazolo-,3-a7-isoindo~in-5(9bH)-one (Ex~mple 1.12) in lOQ ml abs. dioxan~ were mixed with 3~8 g (9~4 mmol) :-~wesso~'s re~gent /~ bis-(4-metho~phengl)-1,3-15 dithia-2,4-diphosphetane-2,4 disu~phid~ snd sti~re~ -for 5 h a~ 60C (~IC cOntrol)..
A~ter cooli~g, it wa~ filtered off from precip_ itate, the filtrste evaporated in 8 vacuum a~d the residue purified bg flssh co~umn chromstograph~ with heptane/meth~l eth~l ketone 6/1 as eluent.
Exam~
Enantiomer ~e~earation of rac-8-chloro-9b-phen~1-2 ~L~
dih~drooxazolo-/2 ~ ~-a7-i so 1ndol-5(gbH)-one (Example 1~6) on cellulo~e triscetate ~or the ~eparation of the antipodes, 200 mg of the racemate were dis~olved i~ 15 ml sthanol, applied to 8 column with 50 mm internal diameter and 300 mm length (corre~ponding to 250 g cellulose triacetate, :" 2108~99 . j, , .
--3~
15-25 grain size, Merck 16326~ and eluted with ethanol (flow 7..5 ml/min, a~out 1, 5 bar) ~
~eak I ~eak I:E:
UV detectio~ /n~Z 254 254 . 5 /--OL 7~ ~.114~8 -115.2 --- -- 1). .
m. p~ /~C~ : 8~-91 89-91 ~ he enantiomers were rec~g~tall i~ed from eth~nol~
~ E~antiomer purit~ according to ~IPIC in each case > ~9_~; ee~
~ample 4 . .~ w - - -9b-Phen~l-2 ,~3-d h ~d~im da ZQ- ~l-a7-isoindol-5(9b~1)-one 5~0 g (22 mmol~ 2-b~zoglbenzoic scid ~ere di~olve~ i~ lQ0- ml toluene a~d, after sdaitio~ ~f 1.5 6,.6 g (llO mm~l) eth~lenedi~nine, a~ well as of a catal~tic amount of p-to~uenesul~honic acid, heated under reflux for 1 ~ h on a wster separator. ~h~
- ~o1v~nt wa ~ then remove~ in a v~cuum and the residu~
recr~stallised from ethano1.. Yield 3~5 g (6~ of 20 theorg ), m~p.. 152-l54C, Exampl~e 5 ~-~cet~l 9b- phen~L-2~-dih~dr.oimidazo~ a7- . :
isoindo -~9bH~-one.
1 g (4 mm~l~ o~ the compo.und obtained in Ex~mple 4 were stirred with lO.ml acetic scid anhydride for 8 h at room temperature. One pours on to water, filters off with suction the residue which precipitates out and washe~ the cr~stals with ether.. Yield: 1,1 g . ~34- 21n8~99 (92~ of theor~), m.p_ 171-173~
.. . . ..
F~s 1e 6 ~~Meth~I~2~=~b~9r~=3~-dih~droimidazO~ .7-i~oindol-5(9bH ~-obe 5 I g C4 mmol~ of the compound.obtsiDed in Example.

4 were dis~ol~ed in 5 ml.DMF and mixed with ~5 ml methJl.iodide and~ g NaH (100 pe.rcent) ~fter fpur hours s.tirring, 0~5 ml meth~l iodide and 0~13 g .. NaH (10~ percen.t.).wer.e.agai.~ saded thereto. ~fter a .. ......... -~
IQ. further 2 h, tho reaction so~ution ~8-~ sdded to water~
ex*racted with e~th~l acetate,l dried sna the solvent evap~rsted off in a vacuum_ ~fter column chromato- ....
graph~ on silics gel (elution sgent: eth~l scet~te/ .
iQohexane~ L:2), on~ collects the desired fractions ~`
ana cr~tallise~ the residue from isohe~ane snd B
few drops of ethanol.. Yield: 0~59 g (56% of the~r~
m.p~.. 119-12i~C..
E~ample 7 Inhi~ition of ~IV reverse. tran~cript~se (R~) b~ :~
deriva.tives o~ 9b-phen~1-2,.3-dih~drooxa-zolo-/~3-a~-isoindol-5(9bH)-one and 9b-phen~1-2,3-dih~droimidazo-/~ ~l-a7-isaindol-5(~bH)-one.
~he screening test ~stem contains the purified RT from ~ l, which wa~ expres~ed b~ gene-technol-25 o~ical method.s in E coli, as well a~ th~ components .. -of the initiation complex, such a~ the ~n vitro - transcripts o~ the ~ TR's with the neighbouring primer binding ~ite as template and an 18mer oligo-nucleotide complem~ntarg to the p~imer bindin~; site a~ primer.. ~here was measu~ed the ~ 3 ~ th~midine-

5'-triphosphste inCorporatiQn by counting in the ~-counter.. In the ~ollowing Table ia ~iven the IC50 5 vslue for the investigated.compounds. ~hi~.~alue corresponds to that concentration of the te~t sub~tancè which bring~ about an inhibition of the reverse trsnscriptas.e. activitg of 50~..
~esu~t~
_ , 10 - ~substsnce~ c~ - inhibition of the -: :.
. HIV-R~ .:
. . IC50 _ M_7 ~:
_ . _ , .
9b-phen~2,.~-dih~drooxszolo- -6 .
. /~3~ isoindol-5(9bHi-one 6.1 x 10 .
..
7,8-dichIoro-9b-phen~1-2,3-dihydrooxazolo~ ,3- ~ -i~o- 14~1 x 10-6 .~.
indol-~9b~-one . ..
9b-(1-naphthyl)-2,3-dihydro-oxazolo~ a~7-isoindol- 1~8 x 10-5 ~:
2D 5-(9bE)-one _ . _ 9b-(~-msthglphen~1~-2,3-dihydroo~azolo-/2~3-a7-iso- 7.9 x 10 6 indol-5(9bH)-one _ _ 8-chloro-9b-phenyl-2,3-dih~drooxazolo-/~,3-~ -iso- 5.. 7 x 10 6 indol-5(9bH)-one . . _ 9b-(3-chlorophenyl)-2,3- . ..
dih~drooxazoIo-/2,3-a7-iso- 2.1 x 10 6 indol-5(9bH)-one . ~

21088~
~ -36-, .
substsnce inhibition of the . HIV-R~
IG50 _M_7 , _ ~
9b-(3~5-dichIorophen~ .
2,3-dihgdrooxazolo-~,3-~7 2.. 2 ~ 10 6 i~oindol-5(9bH~-one . .
., .
9b-(3-indol~ 2~3-dih~dro-oxazolo-/2,3-~-isoindol- 7~3 ~ 10-6 5(9bH)-one . ........................... . ~ ~

~ _ ' .

21 08~99 -46-~

~ he present invention Goncerns the use of oxa~olo-~,.3-~ -isoindole and imidazo~
isoindole derivatives as ant~v$ral medicsmen~s, as ~ 5 well as new opticallg-active derivatives, as well a~
- new oxazolo-/~,3- ~-isoindote derivatives, processes ~or their preparation snd medicsments which contain these compounds.~
- The subaect of the inve~tion i~ especiall~ the ~ :
lQ use of oxszoIo~ 3-a~isoindole and imidazo-/~ a7 isoindole derivatives of the general ~ormula I --~

~3 ~ 5 for the preparstion of medicPment~ with antiviral ..
action, whcrebg X can be an ox~gen or sul~h~lr 8tom, the imino group =NH or an =N-Gl-C5-alk~limino group, Y can be an ox~gen atom or the group NR , whereby R7 signifies a h~dro~en atom or a C~-G6-~lk~l or Cl-C6-ac~l radical~ R signifies a h~dro~en atom, a straight-chained or branched~ saturated or unsat-urated ali~hatic radical with 1 - 9 C-atoms, which can be substituted b~ phen~l, or a phen~l ring which is possibl~ substituted one or more times, - 2108~99 or repre.sents a csrbocyclic or heterocgclic rin~, R~, R2 signif~ 8 hgdrogen atom, a straight-chai~ed or branched,; saturated or unsaturated aliphatic :~
radical with I.- 6 C-atoms, R~ - R6:h~drogent Cl-~6- :.
5 alkyl, C i C6-alkox~, C i C6-aIk~lmercaptoy amino, :-C~-G6--alkglamino~di-Cl C6-alk~lamino, halo~en, c~ano~.h~drox~l" carboxgl,. aminocarbon~l, substituted - :
aminocarbongl or C~-C6-alkoxgcarbongl, as well as their .t~tomers, e.nsat~omerQ, diseastereomers and --~
ph~siologicall~ compstible ~alts, ~
....

Amended pa~e 5 of the German.text.
aminocarbonyl, Cl-C6-alk~laminocarbongl or di-C iC6-alk~laminocarbon~l, R4, R5, R6 have the same meaning .
as R3, whereb~ the radicals R~, ~4, R5 ana R6~ ;
independentl~ of one.ano*her, can be the same or different, a~ well as. their tautomers" enantiomers,dias.tareomers a~d ph~siQlog~callg compstible salt~..
For the cas.e that ~ is an oxggen atom,.Rl and R2 do nQt simults~eousl~ signif~.~gdrogen.atom~..and or R2 do no:t signifg lower alk~ alkoxy, smino, 10 .halogenj.nitro~snd tri~luorometh~ it-is--a ~ue~-tion~
of new oxazolo-/~,3-~-isoindole derivatives which are sl~.o the subJect of the present invention. -~ h~ compounds of the formula I have hitherto onl~ been known in the farm of their racem~tes. It hs~ now been ~h~wn that the op~ticall~-active derivatives po~$e~s a higher effectiveness th~n the correspo~ding rscemic mixtures so that the present invention ~lao refer~ to the new R_ snd 5-ensnti~mer~
~he. compound~.of the formu~a I displa~ valuable ph~rmacological properties~ In particular, the~ are ~uitable for the therap~ snd prophyl~xis of infections which are caused by DNA viruse~, such a~ e.g. herpes simplex. virus, c~tomegalo~irus, papillomaviruses, the vsricella zoster virus or ~ stein-Barr virus or RNA vlruses, such as. togaviruses or especiallg retroviruses,. such as the oncoviruses HT~V-~ and II, : ~: 210~9~

as well as the lentiviru~e~ and human immun2. ;
deficiency virus HIV-l and -2 ~ he compounds of ths formula I sppear to be especisllg suitable for the treatment o~ the clinical -5 manifestation~ of the ret~oviral HIV infection in humans,l a~ we~l as of the persistent general lymph-sde~opath~ (~GL)-, the advsnced ~tage of the A~DS_ related co~ple~ (~R~) and the cIinicsll~ complste pictu~e of A~IE~. . -~............................ .

~ . ~1 08~9 ~5~
Amende~ pages 35 and 36 of the German text 5_ Oxazolo-,/~ -a7-i~oindole derivati~e~i of th~
generaI.formu~a Ia R~ :
Rl R O ~ R4 ~ N ~ ~5 in which ~ can ~ ~n ox~gen Qr sul~hur atom, the imino ~roup 3NH~ or an ~-Cl-C5~ glimino ~roup, R signifies 8 hg~rogcn stom, a straight-chained or branched,. saturate~ or u~s~turated aliphstic radical with 1 - ~ G-stom~;whic~ c~ ~æ substitutsd b~
ph~yl, or a Cl-G6-~lkox~ 6 ~lky I 6 ~0 alk~lmercapto~ 6-slk~l radical, o~ signifie~i a phen~1 rin~ which i~i po~sibl~ substituted one ~r mor~
times by-C~-~6-aIkyl~ ~-C6-alk~xy, C.i~6-sIk~
ercapto G: L~6~ IkglsulEhing~ ~6-alkY ph C6-alkeng~l ~ G2-C6Dfllk~n~l ~ C2-C6 15 ~ G6-al~kenylme:~Capto~ G~-G6-a~ynglox~,~ C2~6-a~
amino, di-Gl-C~;~lk~lsmino, C~1~6-alkg 1c~rbon~1~mino 9, C1~6-alkyl~mlnocarbonyl~ G~ slkoxycarbonyl, h~drox~l, b~nz~loxy,. phen~lmercapto, ph~ lox~, nitro, - c~ano, h~logen, trif-uoromethyl~ szido, form~lamino, 20 carbo~cgll or phen~l, or sig~ifies a mono-, bi--or tricgclic carboc~clic ring with 7 - 15 C-~toms or - a heteroc~clic mono--, b~--or tric~clic ring s~stem 2108~9 with, in each ¢ase, 5 or 6 rin~ a~om~ and, per ring ~gstem, can contain L- 4 or 1 - 5 heterostoms, r~3spectively, whereb~ the heteroatoms are nitrogen, ~ulE~hur or oxygen,. ~1 signifies a straight-chai~ed or.
5 branched u~saturated alipha tic ~adical with up to 6 C-Qtoms" G'1-~6-~lkglmercapto, C i C6-~lk~lsul~hin~l,.
C'l-G6--slk~I~ulphon~ 6-sl~glamino,~ di~I~6-aIl~lamino " sulphonamido ~ C~ 6-a~oxg~-carbon~l "
. carbox~l~ h~dr~x~ cga~n, a~i~or phe~l or be~z~lox~, 0 R2 siE~nifi~5 a h~d~ogsn atom or. has; the same meanîng Rl, R3 signifies h~drogen, C1~6~11~1, Cl-C6- .
~ ox~,CL-G6-all~lmercapto, amino, Cl-C6~11~1amino~
di-CiC~ a~k~lsmino, halogen9 c~ano,. h~dro~ carbo~l, C.~-C6-~lkox~carb~n~lp sminocsrbonyl~ Ci(~6-elk~lamino-15 csrbonyl or- di-aiG6-alk~laminocsrbongl, R4~ 5, R6 have the same meaning ~s R~, whereb~ the radic~ls R~, R4, R5 snd ~6, independentl~ of one another, can be the same or different9 a~ well as their tsutomer~,~
enantiomers, diastereomers and physiolQgicell~
2~ compatible ~alts.

6. R_ and S oxazo~o-/~,~-a7-isoindole and R_ and S-imida zo~ 7- ~

2108~99 ~2 Amended pages. ~8 and 39 of the German text signifi.e$ a mono-,.bi- or tric~clic carbocgclic ring with 7 - 15 C-atoms or a heteroc~clic ~ona-,. bi- or tric~clic ring s~stem with~ in each case,. 5 or 6 ri~g atom~ and, per rin~ sgstemy. can contain 1 - 4 o~ 1 - 5 heteroatoms., res.pectivel~, whereb~ the heteroatoms a.re nitrogen, ~ulphur or ox~en,. ~1 signif.ies a h~drpgen atom, a strai~ht-chsined ~r ..branched,-~a.t.urated or unsaturated sliphatic.~adical.
with 1 - 6 C_atoms or. ~ -~6-slk~x~,.Cl-~6-alkg~-.10 mercspto~.Cl-~6-alk~ls.ulphin~l, Cl-G6-~lk~lsulphon~l r ami~o r Cl-c6-all~lami~lo ~ di-C L-C6-alkglamino sulphonamido,. C i G6-alkox~carbon~l, trifluorometh~l~
c~ox~ halogen, hgdrox~l, nitror c~ano,. azido, phen~1 or benzylox~ 2 hss the same me~ning as Rl, whereb~ the. radicals Rl a~d R2, indepe~dentl~ af one another, ca~ be the same or different, R3 ~ignifie~
h~drogen~ C~-C6-alk~l, Gl-C6-aikox~, C i ~6-alk~l-mercaptoS amino, Cl-C6-alkglami~o, di-Cl-C6-alk~lami~o, halogen, c~ano, h~droxyl, carbox~l~ Cl-C6-alkoxy-carbon~l~ aminocarbongl, Cl-C6-alk~laminocarbon~l or di-Cl-C~-alk~laminocarbon~l, R4, R5, R6 have the same mesning as R3~ whereb~ the radicals R~, R~, R5 and R6,.
independentl~ of one another~ can be the same ar .
.different, as well as their tautomers, diastereomer~
and ph~iologicall~ compatible salts.

- 7. Medicaments containing at least one compound of the for~ula I or Ia according to claim 5 or 6, - 2108~9 besides pharmacolo~icall~ compatible adjuvant or carrier materials.

8. U~e o~ compounds of the formula I or Ia according to claim 5 or 6 for the preparation of medicaments !,~
for the treatment of viral or retroviral infections or of diseases caused bg these infections, such as ~IDS or ~RC. -

9~ Process for the preparation of medicaments ~~- contai~ing ~t least one`compoù~`of the formula I or ~
DO Ia ~ccordin~ to claim 5 or 6, besides usu~l carrier .
or adjuvant materials, characterised in that one mixes a compound o~ the formula I or Ia with the carrier or adjuvant materials and works up to appropriate forms of adm~nistration.

Claims (9)

1. Patent Claims I. Use of oxazolo-[2,3-a]-isoindole and imidazo-[2,1-a]-isoindole derivatives of the general formula I
   
   (I)?
   for the preparation of medicaments with antiviral action, whereby X can be an oxygen or sulphur atom, the imino group =NH or an =N-C1-C5-alkylimino group, Y can be an oxygen atom or the group NR7, whereby R7 signifies a hydrogen atom or a C1-C6-alkyl or C1-C6-acyl radical, R signifies a hydrogen atom, a straight-chained or branched, saturated or unsaturated aliphatic radical with 1-9 C-atoms, which can be substituted by phenyl, or a C1-C6-alkoxy-C1-C6-alkyl or C1-C6-alkylmercapto-C1-C6-alkyl radical or signifies a phenyl ring which is possibly substituted one or more times by C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylmercapto, C1-C6-alkylsulphinyl, C1-C6-alkylsulphonyl, C2-C6 alkenyl, C2-C6-alkynyl, C2-C6-alkenyloxy, C2-C6-alkenylmercapto, C2-C6-alkynyloxy, C2-C6-alkynylmercapto, amino, C1-C6-alkylamino, di-C1-C6-alkylamino, C1-C6-a1kylcarbonylamino, C1-C6-alkylaminocarbonyl, C1-C6-alkoxycarbonyl, hydroxyl, benzyloxy, phenylmercapto, phenyloxy, nitro, cyano, halogen, trifluoromethyl, azido, formylamino, carboxyl or phenyl, or a mono-, bi- or tricyclic carbocyclic ring with 7 - 15 C-atoms or a heterocyclic mono-, bi-or tricyclic ring system with, in each case, 5 or 6 ring atoms and, per ring system, can contains 1 - 4 or 1 - 5 heteroatoms, respectively, whereby the heteroatoms are nitrogen, sulphur or oxygen, R1 signifies a hydrogen atom, a straight-chained or branched, saturated or unsaturated aliphatic radical with 1 - 6 C-atoms or C1-C6-alkoxy, C1-C6-alkyl, mercapto, C1-C6-alkylsulphinyl, C1-C6-alkylsulphonyl, amino, C1-C6-alkylamino, di-C1-C6-alkylamino, sulphonamido, C1-C6-alkoxycarbonyl, trifluoromethyl, carboxyl, halogen, hydroxyl, nitro, cyano, azido, phenyl, or benzyloxy, R2 has the same meaning as R1, whereby the radicals R1 and R2, independently of one another, can be the same or different, R3 signifies hydrogen, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkyl-mercapto, amino, C1-C6-alkylamino, di-C1-C6-alkyl-amino, halogen, cyano, hydroxyl, carboxyl, C1-C6-alkoxycarbonyl, aminocarbonyl, C1-C6-alkylamino-carbonyl or di-C1-C6-alkylaminocarbonyl, R4, R5, R6 have the same meaning as R3, whereby the radicals R3, R4, R5 and R6, independently of one another, can be the same or different, as well as their tauromers, enantiomers, diastereomers and physio-logically compatible salts.
2. 2. Use according to claim 1, characterised in that R signifies a carbocyclic ring with 7 - 15 C-atoms selected from the group naphthyl, enthracenyl, phenanthrenyl, fluorenyl, indenyl, indanyl, ace-naphthylenyl, norbornyl, adamantyl ring or a C3-C7-cycloalkyl or C5-C8-cycloalkenyl group, whereby these can be partly hydrogenated or fully hydrogenated.
3. 3. Use according to claim 1, characterised in that R signifies a heterocyclic mono-, bi or tricyclic ring selected from the group pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, ozadiazolyl, furazanyl, furanyl, thiophenyl, indolyl, quinolinyl, isoquinolinyl, cumaronyl, thionsphthenyl, benzoxazolyl, benzthiazolyl, indazolyl, benzimidazolyl, benztriazolyl, chromenyl, phthalazinyl, quinazolinyl, quinoxalinyl, methylene-dioxybenzolyl, carbazolyl, acridinyl, phenoxazinyl, phenothiazinyl, phenazinyl or purine group, whereby the heterocycles can be partly or completely hydrogenated.
4. 4, Use according to claim 1, characterised in that X signifies an oxygen or sulphur atom and Y signifies an oxygen atom or -NR7, whereby R7 can be hydrogen or C1-C6-alkyl or C1-C6-acyl radical and R signifies unsubstituted phenyl or phenyl substituted once or twice by C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkyl-mercapto, C1-C6-alkylsulphinyl, C1-C6-alkylsulphonyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-alkenyloxy, C1-C6-alkylamino, C1-C6-dialkylamino, C1-C6-alkyl-carbonylamino, C1-C6-alkylaminocarbonyl, C1-C6-alkoxycarbonyl, amino, hydroxyl, nitro, azido, trifluoromethyl, cyano or halogen, or signifies biphenyl, naphthyl, anthracenyl, indenyl, fluorenyl, acenaphthylenyl, phenanthrenyl, norbornyl, adamantyl, C3-C6-cycloalkyl, C5-C8-cycloalkenyl, or signifies pyrrolyl, imidazolyl, furanyl, thiophenyl, pyridinyl, pyrimididinyl, thiazolyl, triazinyl, indolyl, quinolinyl, isoquinolinyl, cumaronyl, thionaphthenyl, benzimidazolyl, quinazolinyl, methylenedioxy-benzolyl, ethylenedioxy benzolyl, carbazolyl, acridinyl or phenothiazinyl, and R1 and R2 signify hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, C1-C6-alkylmercapto, C1-C6-alkylamino, C1-C6-alkoxycarbonyl, trifluoromethyl, amino, halogen, hydroxyl, cyano and azido, R3, R4, R5 and R6 signify hydrogen, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkyl-mercapto, carboxyl, C1-C6-alkoxycarbonyl, halogen, cyano and hydroxyl.
5. 5. Oxazole-[2,3-a]-isoindole derivatives of the general formula I
   
   (I), in which X can be an oxygen or sulphur atom, the imino group =NH or an =N-C1-C5-alkylimino group, Y
   signifies an oxygen atom, R signifies a hydrogen atom, a straight-chained or branched, saturated or unsaturated aliphatic radical with 1 - 9 C-atoms, which can be substituted by phenyl, or a C1-C6-alkoxy-C1-C6-alkyl or C1-C6-alkylmercapto-C1-C6-alkyl radical, or signifies a phenyl ring which is possibly substituted one or more times by C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylmercapto, C1-C6-alkylsulphinyl, C1-C6-alkylsulphonyl, C2-C6-alkenyl, C2-C6-alkynyl, C2-C6-alkenyloxy, C2-C6-alkenyl-mercapto, C2-C6-alkynyloxy, C2-C6-alkynylmercapto, amino, C1-C6-alkylamino, di-C1-C6-alkylamino, C1-C6-alkylcarbonylamino, C1-C6-alkylaminocarbonyl, C1-C6-alkoxycarbonyl, hydroxyl, benzyloxy, phenyl-mercapto, phenyloxy, nitro, cyano, halogen, tri-fluoromethyl, azido, formylamino, carboxyl or phenyl, or signifies a mono-, bi- or tricyclic carbocyclic ring with 7 - 15 C-atoms or a hetero-cyclic mono-, bi- or tricyclic ring system with, in each case, 5 or 6 ring atoms and, per ring system, can contain 1 - 4 or 1 - 5 heteroatoms, respectively, whereby the heteroatoms are nitrogen, sulphur or oxygen, R1 signifies a straight-chained or branched, saturated or unsaturated aliphatic radical with 1 - 6 C-atoms or C1-C6-alkoxy, C1-C6-alkylmercapto, C1-C6-alkylsulphinyl, C1-C6-alkyl-sulphonyl, amino, C1-C6-alkylamino, di-C1-C6-alkyl-amino, sulphonamido, C1-C6-alkoxycarbonyl, trifluoro-methyl, carboxyl, halogen, hydroxyl, nitro, cyano, azido, phenyl or benzyloxy, R2 signifies a hydrogen atom or has the same meaning as R1, R3 signifies hydrogen, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkyl-mercapto, amino, C1-C6-alkylamino, di-C1-C6-alkylamino, halogen, cyano, hydroxyl, carboxyl, C1-C6-alkoxy-carbonyl, aminocarbonyl, C1-C6-alkylaminocarbonyl or di-C1-C6-alkylaminocarbonyl, R4, R5, R6 have the same meaning as R3, whereby the radicals R3, R4, R5 and R6, independently of one another, can be the same or different, as well as their tautomers, enantiomers, diastereomers and physiologically compatible salts.
6. 6. R- and S-oxazolo-[2,3-a]-isoindole and imidazo-[2,1-a]-isoindole derivatives of the general formula I
   
   (I), in which X can be an oxygen or sulphur atom, the imino group =NH or an =N-C1-C5-alkylimino group, Y can be an oxygen atom or the group NR7, whereby R7 signifies a hydrogen atom or a C1-C6-alkyl or C1-C6-acyl radical, R signifies a hydrogen atom, a straight-chained or branched, saturated or unsaturated aliphatic radical with 1 - 9 C-atoms, which can be substituted by phenyl, or a C1-C6-alkoxy-C1-C6-alkyl or C1-C6-alkylmercapto-C1-C6-alkyl radical or signifies a phenyl ring which is possibly substituted one or more times by C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkylmercapto, C1-C6-alkylsulphinyl, C1-C6-alkylsulphonyl, C2-C6-alkenyl, C2-C6-alkynyl, C2-C6-alkenyloxy, C2-C6-alkenylmercapto, C2-C6-alkynyloxy, C2-C6-alkynyl-mercapto, amino, C1-C6-alkylamino, di-C1-C6-alkyl-amino, C1-C6-alkylcarbonylamino, C1-C6-alkylamino-carbonyl, C1-C6-alkoxycarbonyl, hydroxyl, benzyloxy, phenylmercapto, phenyloxy, nitro, cyano, halogen, trifluoromethyl, azido, formylamino, carboxyl or phenyl, or a mono-, bi- or tricyclic carbocyclic ring with 7 - 15 C-atoms or a heterocyclic mono-, bi- or tricyclic ring system with, in each case, 5 or 6 ring atoms and, per ring system, can contain 1 - 4 or 1 - 5 heteroatoms, respectively, whereby the heteroatoms are nitrogen, sulphur or oxygen, R1 signifies a hydrogen atom, a straight-chained or branched, saturated or unsaturated aliphatic radical with 1 - 6 C-atoms or C1-C6-alkoxy, C1-C6-alkyl-mercapto, C1-C6-alkylsulphinyl, C1-C6-alkylsulphonyl, amino, C1-C6-alkylamino, di-C1-C6-alkylamino, sulphonamido, C1-C6-alkoxycarbonyl, trifluoromethyl, carboxyl, halogen, hydroxyl, nitro, cyano, azido, phenyl or benzyloxy, R2 has the same meaning as R1, whereby the radicals R1 and R2, independently of one another, can be the same or different, R3 signifies hydrogen, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkyl-mercapto, amino, C1-C6-alkylamino, di-C1-C6-alkyl-amino, halogen, cyano, hydroxyl, carboxyl, C1-C6-alkoxycarbonyl, aminocarbonyl, C1-C6-alkylamino-carbonyl or di-C1-C6-alkylaminocarbonyl, R4, R5, R6 have the same meaning as R3, whereby the radicals R3, R4, R5 and R6, independently of one another, can be the same or different, as well as their tautomers, diastereomers and physiologically compatible salts.
7. 7. Medicaments containing at least one compound of the formula I according to claim 5 or 6, besides pharmacologically compatible adjuvant and carrier materials.
8. 8. Use of compounds of the formula I according to claim 5 or 6 for the preparation of medicaments for the treatment of viral or retroviral infections or of diseases caused by these infections.
9. 9. Process for the production of medicaments containing at least one compound of the formula I
   according to claim 5 or 6, besides pharmaceutically usual carrier and adjuvant materials, characterised in that one mixes a compound of the formula I with the carrier or adjuvant materials and works up to appropriate forms of administration.