IE914100A1 - Optically-active thiazoloisoindolinone derivatives with¹antiviral action - Google Patents
Optically-active thiazoloisoindolinone derivatives with¹antiviral actionInfo
- Publication number
- IE914100A1 IE914100A1 IE410091A IE410091A IE914100A1 IE 914100 A1 IE914100 A1 IE 914100A1 IE 410091 A IE410091 A IE 410091A IE 410091 A IE410091 A IE 410091A IE 914100 A1 IE914100 A1 IE 914100A1
- Authority
- IE
- Ireland
- Prior art keywords
- active
- thiazoloisoindolinones
- optically
- dihydrothiazolo
- a7isoindol
- Prior art date
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
The present invention relates to optically active thiazoloisoindolinones of general formulae (I) and (II) where: R is a hydrogen atom or a straight-chained or branched, saturated or unsaturated aliphatic radical with 1-7 carbon atoms which may also be substituted by phenyl, or a phenyl ring which may be singly or multiply substituted by C1-C4-alkyl, C1-C4-alkoxy, hydroxy, trifluoromethyl, C1-C4-alkyl sulphonyl or a halogen; n is 0, 1 or 2; and their pharmacologically acceptable salts and tautomers. The object of the invention also includes medicaments containing the compounds of formula (I) or (II) and their use for the production of medicaments to treat viral or retroviral infections.
Description
-2The present invention is concerned with optically-active thiazoloisoindolinone derivatives and with pharmaceutical compositions containing them, as well as with the use thereof for the production of pharmaceutical compositions with anti-viral action.
I^us, according to the present invention, there are provided optically-active compounds of the general formulae: wherein R is a hydrogen atom or a straight-chained or branched, saturated or unsaturated aliphatic radical containing up to 7 carbon atoms, which can be substituted by phenyl, or is a phenyl radical which is optionally substituted one or more times by C^-C^-alkyl, C^-C^-alkoxy, hydroxyl, trifluoromethyl, C^-C^-alkylsulphonyl or halogen, for example fluorine, chlorine or bromine, and n is 0, or 2, as well as the pharmacologically acceptable salts and tautomers thereof.
In Federal Republic of Germany Patent Application P 40 35 309.7 ate described the corresponding racemates of these thiazoloisoindolinones. -3Surprisingly, we have now found that the optically-active forms possess a higher pharmacological effectiveness than the racemates. In particular, we have found that the new compounds of the general formulae I and II are effective in smaller dosages in comparison with the racemates and are characterised by a better therapeutic index.
In U.S. Patent Specification No. 3,334,113 is described, inter alia, 9b-phenyl-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one as inflammation-inhibiting 3nd anticonvulsive medicament.
Further derivative of thiazoloisoindolinone with similar action and lower toxicity are known from Swiss Patent Application No. CH-469,?33 (3 = alkyl; n = 0) and from Belgian Patent Application No. 659,523 or U.S. Patent Specification No. 3,646,022.
In U.S. Patent Specification No. 2,860,935 and Belgian Patent Application No. 564,592, thiazoloisoindolinones are used for the stabilisation and as contrast agents for photographic emulsions.
Apart from in the mentioned Patent Applications, the synthesis of the racemic compounds is also described in J. Org. Chem., 50, 1506/1965, as well as in J. Org. Chem., 54 , 165/1969.
The separation of the racemates into the enantiomers can be carried out analytically, by semipreparative methods or by preparative chromatoIE 914100 -I). graphy on appropriate optically-active phases with the use of conventional elution agents. As opticallyactive phases, there can be used, for example, optically-active polyacrylamides or polymethacrylamides, and, in some cases, also silica gel (for example Chitaopher^ of Merck or Chiralpak OT/OP of Baker', cellulose esters/carbamates (for example (r) Ghitacel 03/CY of Baker/Daicel), phases based on cyclodextrin or on crown ethers (for example ffi) Grownpakk? of Daicel) or microcrystalline cellulose triacetate (Merck).
The compounds of general formulae I and II display an outstanding antiviral action and can, therefore, be used especially well for the treatment of viral and retroviral infections. Viral infections of mammals and especially of humans are widespread. In spite of intensive efforts, hitherto it has not been possible to make available chematherapeutics which interfer causatively or symptomatically with occurances of diseases caused virally or retrovirally with recognisable success. At present, it is not possible to cure or chemotherapeutically to influence favourably the symptoms of certain viral diseases, for example acquired immune deficiency syndrome (AIDS), the AIDS-related complex (ARC) and the preliminary stages thereof, herpes virus, cytomegalovirus (CMV), influenza virus and other viral infections. At present, for example, for the treatment of AIDS, there is almost exclusively available 5'-azido-5’deoxythymidine (AZT), which is known as zidovudine or Retrovir However, AZT is characterised by a very narrow therapeutic range and by very severe toxicities which already occur in the therapeutic range (see M.S. Hirsch, J. Infect. Dis., 157, 427-451/1988). The compounds of general formulae I and II do not possess these disadvantages. They act antivirally without being cytotoxic in the pharmacologically relevant doses.
The compounds according to the present invention can be used for the therapy and prophylaxis of infections which are caused by DNA viruses, for example herpes simplex virus, cytomegalovirus, papillomavirus, varicella zoster virus and EpsteinBarr virus, and by RNA viruses, for example togaviruses, andespecially by retroviruses, for example oncoviruses HTLV I and II, as well as the lentiviruses visna and human deficiency virus HIV 1 and 2.
The compounds of general formulae I and II appear to be especially well suited for the treatment of the clinical manifestations of retroviral infections in humans, for example persistent, generalised lymphadenopathy (PG-L) , the advanced stage of the AIDSrelated complex (ARG) and the clinically complete manifestation of AIDS. -6»e have now been able to demonstrate that compounds of general formulae I and II inhibit the multiplication of DNA and RNA viruses at the stage of the virus-specific DNA and RNA transcription.
Via the inhibition of the enzyme reverse transcriptase, the compounds can influence the multiplication of retroviruses (cf. Proc. Natl. Acad. Sci. USA, 85, 1911/1986 and Nature, 525, 775/1987).
Since a very great need exists for chemotherapeutics which interfere as specifically as possible with diseases caused by retroviruses or with the symptoms thereof without influencing the normally occurring natural body functions, the said compounds could be advantageously used prophylactically or therapeutically for the treatment of diseases in which a retroviral infection is of pathophysiological, symptomatic or clinical relevance.
In general formulae I and II, R is a straightchained or branched, saturated or unsaturated aliphatic radical and especially an alkyl radical with up to 7 and preferably up to 4 carbon atoms, for example a methyl, ethyl or isopropyl radical.
The aliphatic radical can also be substituted by a phenyl radical so that R represents a phenylalkyl radical, for example a benzyl radical. The unsaturated radicals can be C2-C7-alkenyl or alkynyl radicals. Furthermore, R can be a phenyl ring which can be unsubstituted or substituted one or more times. The phenyl radical is preferably substituted once or twice. The substituents can be, for example, methyl, ethyl, methoxy, ethoxy or methylsulphonyl radicals.
R is preferably a phenyl radical which can be substituted once, twice or three times by the following radicals: C^-C^-alkyl, especially methyl, ethyl, n-propyl or isopropyl; halogen, especially fluorine, chlorine or bromine; trifluoromethyl; hydroxyl; C^-C^-alkoxy, especially methoxy or ethoxy. Especially preferred are those derivatives which carry a substituent in the 3-position of the phenyl ring. Disubstituted phenyl radicals are preferably the derivatives which are substituted in the 2,3-, ,5-, 5,4-, 2,4- or 2,5-positions.
In the meaning of the present invention, optically-active compounds of general formula I are preferred.
Pharmaceutical compositions which contain at least one compound of general formula I or II can be administered enterally or parenterally in liquid or solid form. There can hereby be used the conventional forms of administration, for example tablets, capsules, dragees, syrups, solutions and suspensions. As injection medium, it is preferred to use water which contains the additives usual in the case of injection solutions, for example stabilising agents, solubilising agents and buffers. Such additives include, for -8example, tartrate and citrate buffers, ethanol, complex formers (such as ethylenediamine-tetraacetic acid and the non-toxic salts thereof), high molecular weight polymers (such as liquid polyethylene oxide) for viscosity regulation. Liquid carrier materials for injection solutions must be sterile and are preferably filled into ampoules. Solid carrier materials include, for example, starch, lactose, mannitol, methyl cellulose, talc, highly dispersed silicic acids, high molecular weight fatty acids (for example stearic acid), gelatine, agar-agar, calcium phosphate, magnesium stearate, animal and vegetable fats, solid high molecular weight polymers (for example polyethylene glycols) and the like.
Compositions suitable for oral administration can, if desired, contain flavouring or sweetening agents .
Pharmacologically acceptable salts of compounds of general formulae I and II are acid-addition salts with inorganic and organic acids, for example hydrochloric acid, hydrobromic acid, nitric acid, phosphoric acid, acetic acid, oxalic acid, fumaric acid, maleic 3cid and succinic acid.
Phe dosage can depend upon various factors, such as mode cf administration, species, age and individual state of health. Phe compounds according to the present invention are usually administered in amounts of from 0.1 to 100 mg and preferably of from 0.2 to 80 mg per day and per kg of body weight, It is -9preferred to divide up the daily dose into 2 to 5 administrations, whereby, in each case, the are administered 1 or 2 tablets with a content of active material of 0.5 to 500 mg. The tablets can also be retarded, whereby the number of administrations per day can be reduced to 1 to 5. The content of active material of the retarded tablets can be from 2 to 1000 mg. The active material can also be given by continuous infusion, in which case amounts of from 5 to 1000 mg per day normally suffice.
The racemates of the compounds according to the present invention of general formulae I and II can be prepared according to the instructions given in the patent applications and literature references mentioned in the prior art and can be separated chromat©graphically on appropriate optically-active phases .
Apart from the compounds mentioned in the following Examples and those obtained by the combination of all of the meanings given in the claims for the substituents, within the meaning of the present invention, there are also included the following compounds of general formula I: 1. (3)-2,3- dihydrothiasolo/2,3-9.7isoindol-5(9bH)one 2. (R)-9b-methyl-2,3-dihydrothiazolo/2,3-a7isoindol5(9bK)-one -ίο3. (H)-9b-phenyl-,2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one 4. (3)-9b-(4-methylphenyl)-2,3-dihydrothiazolo/2,5-a7isoindol-5(9t»H) - one . (3)-9b-(3-raethylphenyl)-2, 5-dihydrothiasolo/2,3-a,7isoindol-5(9bH) - one 6. (3)-9b-(4-ethylphenyl)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one 7. (3)-9b-(2,4-dimethylphenyl)-2,3-dihydrothiazolo /2,3-a7isoindol-5(9bH)-one 8. (3)-9b-(3,4_dimethylphenyl)-2,3-dihydrothiazolo /2,3-a7isoindol-5(9bH)-one 9. (3)-9b-(2,5-dimethylphenyl)-2,3-dihydrothiazolo /2,3-a7isoindol-5(9bH)-one. . (3)-9b-(3-trifluoromethylphenyl)-2,3-di hydrothiazolo/2,3-a7isoindol-5(9bE)-one 11. (3)-9b-(4-trifluoromethylphenyl)-2,3-dihydrothiaz olo/2 ,3-a7isoindol-5(9bH)-one 12. (3)-9b-(4-hydroxyphenyl)-2,3-dihydrothiazolo/2,3-a,7isoindol-5(9bH) - one 13. (3)-9b-(3-hydroxyphenyl)-2,3-dihydrothiazolo/2,3-a7-5(9b3)-one 14. (3)-9b-(4-ethoxyphenyl)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9t>H) -one . (3) -9b-( 3-nie thoxy phenyl) -2,3-dihydrothiazolo/2,3-a7iscindol-5(9bH)-one 16. (3)-9b - (3-fluorophenyl)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one -ιιι?. (R)-9b-(4-chlorophenyl)-2,3-dihydrothiazolo(/2,5-a7isoindol-5(9bH)-one 18. (R)-9b-(4-bromophenyl)-2,5-dihydrothiazolo/2,5-£7i3o’indol-5(9bH) - one 19. (R)-9b-(4-methylsulphonylphenyl)-2,3-dihydrothiazolo/2,5-a7isoindol-5(9bH)-one 2C. (R)-9b-phenyl-2,3-dihydrothiazolo/2,3-a7isoindol5(9bH)-one 1-oxide.
Furthermore, the following compounds of general formula II can also be considered: 1. (S)-2,3-dihydrothiazolo/2,3-a7isc mdol-5(9bH)-one 2. (S)-9b-methyl-2, 3-dihydrothiaz olo/2,3-a7isoindol5(9bH)-one 3. (8)-9b-phenyl-2,3-dihydrothiazolo/2,3-a7isoindol5(9bH)-one 4. (3)-9b-(4-methylphenyl)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one . (8)-9b-(3-methylphenyl)-2,3-dihydrothiazolo/2,3-a7i3Oindol-5(9bH)-one 6. (3)-Qb-(4-ethyIpheny1)-2, 3-dihydrothiazolo/2,3-a7iaoindol-5(9bH)-one 7. (8)-9b-(2,4-dimethyIphenyl)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one 8. (3)-9b-(3,4-dimethyIphenyl)-2,3-dihydrothiasolo/2,3-a7isoindol-5(9bH)-one 9. (3)-93-(2,5-dimethyIphenyl)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one -121C. (3)-9b-(3-triflu or ometh.yl phenyl)-2,3-dihydrothiasolo/2,3-a7isoindol-5(9bH)-one 11. (3)-9b-(4-trifluoromethylphenyl)-2,3-dihydrothiazolo/2,5-a.7i3oindol-5(9hH) - one 12. (3)-9b-(4-hydroxyphenyl)-2,3-dihydrothiasolo72 ,3-a7isc i ndol-5(9b'i) - one . (3) -9b-(3-hydroxy phenyl') -2,3 -dihydro thia zolo/2,3-a7isoin^ol-5(9bH)-one 14. (3)-9b-(4-ethoxyphenyl)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one . (3)-9b-(3-methoxyphenyl)-2,3-dihydrothiazolo/2,5-a7isoindol-5(9bH)-one 16. (S)-9b-(3-fluorophenyl)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one 17. (3)-9b-(4-chlorophenyl;-2,3-dihydrothiasolo/2,3-a7isi. ίiidol-5(9bH)-one 18. (3)-9b-(4-bromophenyl)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one 19. (3)-9b-(4-methyIsulphorylpheny1)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one 2C. (3)-9b-phenyl-2,3-dihydrothiazolo/2,5-a7isoindol (9bH)-one 1-oxide.
The following Examples are given for the purpose of illustrating the present invention: -13Example 1.
Enantiomer separation of rac-9b-phen.yl-2,5-dihydrothiazolo/2,5-a7isoindol-5(9bH)-one on cellulose triacetate.
For the separation of the antipodes, 500 mg of the racemate were dissolved in 10 ml of ethanol, applied to a column of 50 mm internal diameter and 30C mm length (containing 250 g of cellulose triacetate, 15 - 25 grain size, Merck 16326) and eluted with ethanol (flow 7.5 ml/min., about 1.5 bar). Peak I: UV detection at 254 nm; run time: 130 minutes; /‘9_7ρ°= -542°; m.p. 99 - 100°C; absolute configuration: (S)-form Peak II: UV detection at 254 nm; run time: 165 minutes; /9_7q° = +344°; m.p. 99 - 100°0; absolute configuration: (R)-form.
The enantiomers were recryst3llised from ethanol. The following racemates were separated on cellulose triacetate analogously to Example 1: 1.1 rac-9b-(4-methylphenyl)-2,3-dihydrothiazolo/_2,3-a7isoindol-5(9bH) - one 1.2 rac-9b-(3-methylpheny1)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bH)-one 1.3 rac-9b-(3,4-dimethylpheny1)-2, 5-dihydΓ0thiazolo/2, 3-a7isoindol-5(9t>H) - one 1.4 rac-9b-(3,4-dichlorophenyl)_2,3-dihydrothiazolo/2,3-a7iscindol-5(9bH)-one 1.5 rac-9b-(2,3-dimethylpheny1)-2,5-dihydrothiazolo/2,3-a/isoindol-5(9bH)-one -lit1.6 rac-9b-(3-chlorophenyl)-2,3-dihydrothiazolo/2,3-a_7i3Oindol-5(9bH) - one; methanol/20^ water as elution agent; recrystallised from ethanol 1.7 rac-9b-(5,5-dimethylphenyl)-2,3-dihydrothiazolo/2,3-a7isoindol-5(9bK)-one; meth3nol/2O?< water as elution agent; recrystallised from ethanol. ' example run time peak I run time peak XI , ,- 720 L α-7τ> m.p. °C i 1 105 -275 oil l ί 1 104 +270 oil 1.2 155 -294 84-88 190 +288 84-88 1.5 150 -241 oil 180 +231 oil 1.4 155 -242 oil 185 +231 oil 1.5 120 -239 oil 175 +235 oil 1.6 95 -5C3 107-109 150 +507 107-109 1.7 105 -516 170-174 155 +519 170-174 Example 2. Enantiomer separation of rac-9b-phenyl-2,3-dihydro- thiazolo/2, 5-a7isoindol- 5(9bH)-one on Chinacel OB.
For separation on a semi-preparative scale, 2 ml of a cold saturated solution of the racemate in a -15mixture of isopropanol/hexane (50:70 v/v) were applied to the optically-active phase and eluted with the said solvent mixture (C’niracel OB of Baker/Daicel; column 10 mm internal diameter and 5CC mm length; flow 1 ml/minute; 10 (um grain size). The run times were 12 and 17 minutes, respectively. The data were comparable with those of the enantiomers isolated according to Example 1.
Example 5.
Inhibition of reverse transcriptase (RT) by (R)and (S)-9b-phenyl-2,5~dihydrothiazolo/2t5-a7~ isoindol-5(9bH)-one.
The screening test system contains the purified KT from HIV-1, which was expressed by gene-technological methods in Escherichia coli, as well as the components of the initiation complex, such as the in vitro transcripts of the HIV-LTK's with the neighbouring primer binding site as template and an 18mer oligonucleotide as primer complementary to the primer binding site. The /"^H7-thymidine-5’-triphosphate incorporation was measured by counting in a β-counter The results obtained are given in the following Table: -ISTable compound inhibition of the KIV-RT ic5o 3’-asido-3'-desoxythymidine-5'-triphosphate /ΛΖΤ-ΤΡ7 6.0 x 106 (R)-9b-phenyl-2,3-dihydro- thiazolo^2,3-a7isoindol·- 5(9bH)-one 0.4 x IO6 (3)_9b_phenyl-2,3-dihydrothiazolo/2,3-a7isoindol5(9bH)-one 26.5 x 106 Έ914100
Claims (8)
1. Optically-active thiazoloisoindolinones of the general formulae: (II) (I) wherein R is a hydrogen atom or a straight-chained or branched, saturated or unsaturated aliphatic radical containing up to 7 carbon atoms, which can optionally be substituted by phenyl, or is a phenyl ring which is optionally substituted one or more times by C^-C^-alkyl, C^-C^-alkoxy, hydroxyl, trifluoromethyl, C^-C^-alkylsulphonyl or halogen and n is Ο, 1 or 2, as well as the pharmacologically acceptable salts and tautomers thereof.
2.O Cptically-active thiazoloisoindolinones according to claim 1, wherein R is a hydrogen atom or a saturated or unsaturated, straight-chained or branched aliphatic radical containing up to 7 carbon atoms.
3. 5. Cptically-active thiazoloisoindolinones according to claim 1, wherein R is a C^-Cy-alkyl radical which can be substituted by a phenyl radical. -184. Optically-active thiazoloisoindolinones according to claim 1, wherein R is a phenyl radical which is substituted once, twice or three times by alkyl, halogen or hydroxyl. 5. Optically-active thiazoloisoindolinones according to claim 1, wherein the optionsl halogen substituent in a phenyl radical R is fluorine, chlorine or bromine
4. 6. Cptically-active thiazoloisoindolinones according to claim 1 selected from the following compounds: 9b-phenyl-2,5-dihydr othiazol 0^/2,5-a7isoindol5(9bH)-one 9b-(4-methylphenyl)_2,5-dihydrothiazolo/2,5-a7isoindol-5(9bH)-one 9b-(5-methylpheny1)-2,5-dihydrothi3zolo/2,5-a7isoindol-(5(9bH)-one 9b-(5,4-dimethylphenyl)-2,5-dihydrothiazolo/2,5-a7isoindol-5(9bH)-one 9b-(5,4-dichlorophenyl)-2,5-dihydrothiaz olo/2,5-a7isoindol-5(9bH)-one 9b-(2,5-dimethylpheny1)-2, 5-dihydrothiaz olo/2,5-a7isoindol-5(9bH)-one 9b-(3-chlorophenyl)-2,5-dihydrothiazolo/2.5-a7-isoindol-5(9bH)-one 9b-(5,5-dimethylphenyl)-2,5-dihydrothiazolo/2,5-a7isoind ol-5(.9 bH) - one.
5. 7. Cptically-active thiazoloisoindolinones according to claim 1 which are hereinbefore specifically exemplified. -198. Process for the preparation of optically-active thiazoloisoindolinones according to claims 1—7, characterized in that the corresponding racemate is separated by chromatography on optically-active phases into the optically-active compound of formula I or II.
6. 9. Optically-active thiazoloisoindolinones according to claim 1 whenever prepared by the process according to claim 8.
7. 10. Pharmaceutical compositions containing at least one compound of general formula I or II according to any of claims 1 to 7 and 9, together with pharmacologically acceptable carriers and adjuvants.
8. 11. The use of compounds of general formula I or II according to any of claims 1 to 7 and 9 for the production of pharmaceutical compositions with antiviral action.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4037674A DE4037674A1 (en) | 1990-11-27 | 1990-11-27 | New 2,3-di:hydro:thiazolo:isoindolone derivs. |
| DE19914122418 DE4122418A1 (en) | 1991-07-06 | 1991-07-06 | Optically active thiazolo:isoindolinone derivs. - are antiviral agents, effective against diseases caused by DNA and by RNA viruses, and by retrovirus(es), esp. HIV |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IE914100A1 true IE914100A1 (en) | 1992-06-03 |
Family
ID=25898790
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE410091A IE914100A1 (en) | 1990-11-27 | 1991-11-26 | Optically-active thiazoloisoindolinone derivatives with¹antiviral action |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0559815B1 (en) |
| JP (1) | JPH06502634A (en) |
| CN (1) | CN1062732A (en) |
| AT (1) | ATE127467T1 (en) |
| AU (1) | AU8910491A (en) |
| CA (1) | CA2095255A1 (en) |
| DE (1) | DE59106440D1 (en) |
| ES (1) | ES2079850T3 (en) |
| IE (1) | IE914100A1 (en) |
| IL (1) | IL100119A0 (en) |
| PT (1) | PT99609A (en) |
| WO (1) | WO1992009606A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4129779A1 (en) * | 1991-09-07 | 1993-03-11 | Boehringer Mannheim Gmbh | NEW TRICYCLIC THIAZOLE AND OXAZOLE DERIVATIVES AND MEDICINAL PRODUCTS CONTAINING THEM |
| WO2002066479A1 (en) * | 2001-02-23 | 2002-08-29 | Banyu Pharmaceutical Co.,Ltd. | Novel isoindole derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH433321A (en) * | 1964-02-11 | 1967-04-15 | Geigy Ag J R | Process for the preparation of new, condensed heterocyclic compounds |
| CH469733A (en) * | 1965-07-27 | 1969-03-15 | Geigy Ag J R | Process for the preparation of new, condensed heterocyclic compounds |
-
1991
- 1991-11-21 IL IL100119A patent/IL100119A0/en unknown
- 1991-11-22 AT AT92902580T patent/ATE127467T1/en not_active IP Right Cessation
- 1991-11-22 AU AU89104/91A patent/AU8910491A/en not_active Abandoned
- 1991-11-22 DE DE59106440T patent/DE59106440D1/en not_active Expired - Fee Related
- 1991-11-22 EP EP92902580A patent/EP0559815B1/en not_active Expired - Lifetime
- 1991-11-22 JP JP4500305A patent/JPH06502634A/en active Pending
- 1991-11-22 CA CA002095255A patent/CA2095255A1/en not_active Abandoned
- 1991-11-22 WO PCT/EP1991/002205 patent/WO1992009606A1/en active IP Right Grant
- 1991-11-22 ES ES92902580T patent/ES2079850T3/en not_active Expired - Lifetime
- 1991-11-26 IE IE410091A patent/IE914100A1/en unknown
- 1991-11-26 PT PT99609A patent/PT99609A/en not_active Application Discontinuation
- 1991-11-27 CN CN91111914A patent/CN1062732A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| IL100119A0 (en) | 1992-08-18 |
| EP0559815B1 (en) | 1995-09-06 |
| AU8910491A (en) | 1992-06-25 |
| PT99609A (en) | 1992-10-30 |
| ES2079850T3 (en) | 1996-01-16 |
| ATE127467T1 (en) | 1995-09-15 |
| CN1062732A (en) | 1992-07-15 |
| CA2095255A1 (en) | 1992-05-28 |
| EP0559815A1 (en) | 1993-09-15 |
| DE59106440D1 (en) | 1995-10-12 |
| WO1992009606A1 (en) | 1992-06-11 |
| JPH06502634A (en) | 1994-03-24 |
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