GB2060611A - 2,3-Dihydro-4H-1- benzothiopyran-4-ones and 2,3- dihydro-1H-inden-1-ones - Google Patents

2,3-Dihydro-4H-1- benzothiopyran-4-ones and 2,3- dihydro-1H-inden-1-ones Download PDF

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GB2060611A
GB2060611A GB8023925A GB8023925A GB2060611A GB 2060611 A GB2060611 A GB 2060611A GB 8023925 A GB8023925 A GB 8023925A GB 8023925 A GB8023925 A GB 8023925A GB 2060611 A GB2060611 A GB 2060611A
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phenyl
lower alkyl
dihydro
hydrogen
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ER Squibb and Sons LLC
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Priority claimed from US06/064,653 external-priority patent/US4228177A/en
Priority claimed from US06/066,726 external-priority patent/US4218461A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/45—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by at least one doubly—bound oxygen atom, not being part of a —CHO group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
    • C07C49/747—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

New 2,3-dihydro-3-(1H-imidazol- 1-ylmethylene)-4H-1-benzothiopyran- 4-ones are provided having the general formula <IMAGE> wherein R<1> and R<2> each is hydrogen, lower alkyl, halogen, lower alkoxy, lower alkylthio, phenyl-lower alkyl, phenyl or substituted phenyl; R<3> and R<4> each is hydrogen, lower alkyl, lower alkoxy, halogen, hydroxy, lower alkylthio, phenyl, or phenyl-lower alkyl and 2,3-dihydro-2-[(1H-imidazol-1 yl)-methylene]-1H-inden-1-ones are provided having the general formula <IMAGE> wherein R<5>, R<6>, R<7>, R<8>, R<9> and R<10> may be the same or different and each is hydrogen, lower alkyl, halogen, lower alkoxy, lower alkylthio, phenyl-lower alkyl, phenyl or substituted phenyl. The above compounds and their salts are useful as antifungal and antibacterial agents.

Description

SPECIFICATION 2,3-Dihydro-4H-1 -benzothiopyran-4-ones and 2,3-dihydro-1 H-inden-1 -ones This invention provides 2,3-dihydro-3-(1 H-imidazol-1 -ylmethylene)-4H-1 -benzothiopyran-4-ones, 2,3-dihydro-2-[( 1 H-imidazol-1 -yl)methylene]-1 H-inden-1 -ones and the acid addition salts of these compounds having the general formulae:
The symbols R1, R2, R3 and R4 have the following meaning in formula I and throughout the specification.
R' and R2 each is hydrogen, lower alkyl, phenyl-lower alkyl, halogen, lower alkoxy, lower alkylthio, phenyl or substituted phenyl wherein the phenyl group bears one halogen, hydroxy, lower alkoxy, lower alkyl, lower alkylthio, cyano or nitro group; R3 and R4 each is hydrogen, halogen, lower alkyl, phenyl, phenyl-lower alkyl, hydroxy, lower alkoxy or lower alkylthio.
The symbols R5, R6, R7, R8, R9 and R'O have the following meaning in formula IA and throughout the specification.
R5, R6, R7, R8, P9 and R'O may be the same or different and are hydrogen, lower alkyl, phenyl-lower alkyl, halogen lower alkoxy, lower alkylthio, phenyl or substituted phenyl wherein the phenyl group bears one halogen, hydroxy, lower alkoxy, lower alkyl, lower alkylthio, cyano or nitro group.
The new compounds of formulae I and IA and their salts are antifungal and antibacterial agents.
In formulae I and IA the lower alkyl groups include straight or branched chain hydrocarbon groups containing 1 to 7 carbon atoms. Examples of the type of groups contemplated are methyl, ethyl, propyl, isopropyl, etc. The lower alkoxy and loweralkylthio groups include such lower alkyl groups bonded to an oxygen or sulfur, respectively, e.g., methoxy, ethoxy, propoxy, butoxy, t-butoxy, methylthio, ethylthio, propylthio, butylthio, isobutylthio. In all of these radicals the C,C4, especially the C1-C2 members, are preferred.
The halogens are the four common halogens, chlorine and bromine being preferred in that order.
Preferred embodiments of the invention are compounds of formula I wherein R1 and R2 are hydrogen, and R3 is hydrogen and R4 is hydrogen or 6-halo, preferably 6-chloro. Other preferred embodiments of the invention are compounds of formula IA wherein one of R5 and R6 is hydrogen and the other is hydrogen, lower alkyl, such as methyl, phenyi, or mono- or di-halo-phenyl, wherein halo is preferably chloro, and R7 and/or R9 are hydrogen or halo, such as chloro, and R8 and R10 are hydrogen.
When RX, R2, R5, R6, R7, R8, P9 and R' are phenyl then unsubstituted phenyl is preferred.
The new compounds of formula I are formed by the following series of reactions.
A 2,3-dihydro-4H-1 -benzothiopyran-4-one of the formula
[either commercially available or produced analogous to the procedure described in the literature, e.g., Beilsteins Handbuch der Organischen Chemie, Band 17 (ElI 336 and E III/IV 4960)], is made to react with alkyl formate of the formula
at room or elevated temperature in the presence of a condensing agent, e.g., metal alcoholate. The resulting compound of the formula
in which M represents metals such as sodium, potassium or the like, is neutralized and then reacted with imidazole of the formula
to give compounds of formula I.
A preferred method for preparing products of formula I is the reaction of the hydroxymethylene compound of formula IV (M = H) with carbonyl-bis-imidazole or thionyl-bis-imidazole of the formula
wherein A represents -CO- or -SO-.
The new compounds of formula IA are formed by the following series of reactions.
A 2,3-dihydro-1 H-inden-4-one of the formula
is made to react with alkyl formate of the formula
at room or elevated temperature in the presence of a condensing agent, e.g., metal alcoholate. The resulting compound of the formula
in which M represents metals such as sodium, potassium or the like, is neutralized and then reacted with imidazole of the formula
in which R" represents hydrogen, metals such as sodium, potassium or the like, or carbonylimidazole or thionylimidazole, to give compounds of formula IA.
A preferred method for preparing products of formula IA is the reaction of the hydroxymethylene compound of formula VIII (M = H) with the carbonyl-bis-imidazole or the thionyl-bis-imidazole of the formula
wherein A represents -CO- or -SO-.
The compounds of formulae I and IA form salts which are also part of this invention. The salts include acid-addition salts, particularly the non-toxic, physiologically acceptable members. The compounds of formula I form salts by reaction with a variety of inorganic and organic acids providing acid addition salts including, for example hydrohalides (especially hydrochloride and hydrobromide), sulfate, nitrate, borate, phosphate, oxalate, tartrate, maleate, citrate, acetate, ascorbate, succinate, benzensulfonate, methanesulfonate, cyclohexane-sulfamate and toluene-sulfonate.The acid addition salts frequently provide a convenient means for isolating the product, e.g., by forming and precipitating the salt in the appropriate medium in which the salt is insoluble, then after separation of the salt, neutralizing with a base, such as barium hydroxide or sodium hydroxide, to obtain the free base of formulae I and IA. Other salts may then be formed from the free base by reaction with an equivalent of acid having the desired anion.
The compounds of formula I and IA and their salts may be used as antimicrobial agents, particuiarly as antifungal agents, and can be used to combat infections in various mammalian species, such as mice, rats, dogs, guinea pigs and the like, due particularly to organisms such as Candida albicans as well as organisms such as Trichomonas vaginalis or Trichophyton mentagrophytes. For example, a compound or mixture of compounds of formula I and IA or physiologically acceptable acid addition salts thereof can be administered orally to an infected animal, e.g., to a mouse, in an amount of about 5 to 25 mg/kg/day in 2 to 4 divided doses.These may be conventionally formulated in a tablet, capsule or elixir containing about 10 to 250 mg per dosage unit, by compounding the active substance or substances with a conventional excipient, vehicle, binder, preservative, flavor, etc. as called for by accepted pharmaceutical practice. Preferably they are applied topically e.g., intravaginally in a lotion or in a conventional cream base at a concentration of about 0.01 to 3 percent by weight for a period of 3 to 7 days, 2 to 4 times daily.
The invention thus provides an antimicrobial composition comprising a compound of the invention and a pharmaceutically acceptable carrier therefor.
The following examples are illustrative of the invention. They represent particularly preferred embodiments and also serve as models for the preparation of other members of the group. All temperatures are on the Celsius scale.
EXAMPLE 1 2,3-Dihydro-3-( 1 H-imidazol- 1 -ylmethylene)-4H- 1 -benzothiopyran-4-one a) 2,3-Dihydro-3-(hydroxymethylene)-4H-1 -benzothiopyran-4-one From 9.2 g of sodium (0.4 mol) and 160 ml of absolute methanol there is prepared sodium methanolate. Then the surplus of methanol is evaporated in vacuo and 200 ml of dry benzene and 32.6 g of ethyl formate (0.44 mol) are added to the dry residue. While stirring and passing nitrogen through the mixture, there are added 32.8 g of 2,3-dihydro-4H-1 -benzothiopyran-4-one, dissolved in 1 60 ml of dry benzene dropwise to it to keep the reaction temperature in the range from 0 to 50C. All components become dissolved and after that, the sodium salt of the 2,3-dihydro-3-(hydroxymethylene)4H-1 -benzothiopyran-4-one precipitates.After allowing the reaction mixture to stand overnight at room temperature, 400 ml of water are added for dissolving the sodium salt. The aqueous layer is separated from the organic solvent and, after agitating twice with ether and treatment with charcoal, it is acidified with half-concentrated aqueous hydrochloric acid. The oily title compound is extracted with chloroform, dried with sodium sulphate and after evaporation of the solvent, distilled in vacuo. b.p. 0.3 mm, 1341380; yield: 32.9 g (85.6%).
b) 2,3-Dihydro-3-(1 H-imidazol-1 -ylmethylene)-4H- 1 -benzothiopyran-4-one To 8.7 g of 2,3-dihydro-3-(hydroxymethylene)-4H-1 -benzothiopyran-4-one (0.045 mol), dissolved in 200 ml of benzene are added 8 g of carbonyl bis-imidazole (0.05 mol) while stirring at room temperature for about 1 2 hours. Then the clear solution is evaporated in vacuo, the residue treated with water and the product extracted with chloroform. After the solvent is again distilled off, the oily residue is agitated with ether until the 2,3-dihydro-3-(1 H-imidazol-1 -ylmethylene)-4H-1 -benzothiopyran becomes crystalline. Yield: 9.4 g. Recrystallization from absolute ethanol gives 8.7 g (79.8%) of compound; m.p. 139--1400C.
EXAMPLE 2 6-Chloro-2,3-dihydro-3-( l H-imidazol- 1 -ylmethyleneJ4H-benzo[b]thiopyran-4-one a) 6-Chloro-2,3-dihydro-3-(hydroxymethylene)-4H-benzo[b]thiopyran-4-one Following the procedure according to Example 1 a, 6-chloro-2,3-dihydro-4H-1 -benzothiopyran-4one is reacted with sodium methanol to obtain the above compound, m.p. 103-1 040C (ligroin).
b) 6-Chloro-2,3-dihydro-3-( 1 H-imidazol- 1 -ylmethylene)-4H-benzo[b]thiopyran-4-one Following the procedure according to Example 1 b, 6-chloro-2,3-dihydro-3-(hydroxymethylene)4H-benzo[b]-thiopyran-4-one is reacted with carbonyl-bis-imidazole to obtain the title compound, m.p.
139-141 C (acetonitrile).
EXAMPLES 3 to 22 The following additional compounds shown in Column II of Table A set out below are produced by the procedure of Example 1, by substituting for 2,3-dihydro-4H-1 -benzothiopyran-4-one the compound shown in Column I of Table A below.
TABLE A
Column 1 Column II Ex. R4 R R4 R No. (position) (position) R R (position) (position) R R 3. CH3(6) H H H # 4. C2H5(7) H CH3 H as in column 1 5. C6H5(8) H C6H5 H 6. CH3(6) CH3(7) H H 7. CH3O(3) CH3O(5) C2H5 Br 8. Cl(5) H CH2O H 9. Br(7) H CH3S Cl 10. C2H5(6) CH25(7) C6H5CH2 Br 11. C2H3(8) H P-OH-C6H4 H 12. Br(5) Br(6) O-C2H5O-C6H5 H 13. H CH3(5) m-C2H5O-C6H5 Br TABLE A (Continued)
Column 1 Column II Ex. R4 R R4 R No. (position) (position) R R (position) (position) R R 14. Cl(6) Cl(7) p-CH2S-C6H4 Cl # 15. Br(6) Br(7) o-CN-C6H4 H as in Column 1 16. OH(7) H p-NO2-C6H4 H 17. C6H7S(6) C2H5OC2H4 Cl 18. H C2H5O(7) C6H5OC2H4 Br 19. OH(6) OH(7) C6H5C2H4 H 20. Cl(8) H C6H5H3S H 21. C2H5S(7) H H Cl 22. C6H5CH2(7) H H H EXAMPLE 23 2,3-Dihydro-2-ft 1 H-imidazol- 1 -yl)methylenel- 1 H-in den- 1-one a) 2,3-Dihydro-2-(hydroxymethylene)-1 H-inden-1-one The above starting material is prepared according to W. S. Johnson, J. M. Anderson and W. E.
Shelberg, J. of the Am. Chem. Soc., Vol. 66, 218-222 (1944) and Vol. 67, 1745-1754 (1945). A quite similar procedure is described by P. Schenone, G. Bignardi (a). and S. Morasso, J. Heterocyclic Chem. 9, 1345 (1972). M.p. 110-112 C, yield 71%.
b) 2,3-Dihydro-2-[(1 H-imidazol- 1 -yl)-methylene]--1 H-inden- 1 -one 9.6 g of 2,3-dihydro-2-(hydroxymethylene)-1 H-inden-1 -one (0.06 mol) are suspended in 1 50 ml of benzene. While stirring 11.5 g of carbonyl-bis-imidazole (0.072 mol) are added and the reaction mixture is warmed to about 70-750C for a short time to get the components dissolved. If required, the solution is filtered clear and then allowed to stand at room temperature for 17 hours. The crystallized product is filtered off, washed with benzene and dried.Treatment with 100 ml of water and drying in the desiccator over P205 furnishes the 2,3-dihydro-2-[(1 H-imidazol-1 -yl)-methylene] 1 H-inden-1 -one which after recrystallization from ethylacetate melts at 183-1 850C, yield 10 g (79%).
EXAMPLE 24 2,3-Dihydro-2-lC 1 H-imidazol- 1 -yl)methylenej-3-phenyl- 1 H-inden-1-one a) 2,3-Dihydro-2-(hydroxymethylene)-3-phenyl-1 H-inden-1 -one The above starting material is prepared using the literature method mentioned in Example 23a the said starting material melts at 135-1 370C (ethyl acetate). Yield 92%.
b) 2,3-Dihydro-2-[(1 H-imidazol- 1 -yl)-methylene]-3-phenyl- 1 H-inden- 1 -one Following the procedure according to Example 1, except reacting 2,3-dihydro-2 (hydroxymethylene)-3-phenyl-1 H-inden-1-one with carbonyl-bis-imidazole, the title compound is produced, m.p. 204-2060C (ethanol); yield 72%.
EXAMPLE 25 6-Chloro-3-(4-chlorophenyl)-2,3-dihydro-2-[( 1 H-imidazol- 1 -yI)methylene]- 1 H-inden- 1 -one a) 6-Chloro-3-(4-chlorophenyl)-2,3-dihydro-2-(hydroxymethylene)-1 H-inden-1 -one The above starting material is prepared according to the literature method of Example 23a, m.p.
122-1 240C (absolute ethanol), yield 89%.
b) 6-Chloro-3-(4-chlorophenyl)-2,3-dihydro-2-[( 1 H-imidazol-1 -yl)methylene]-1 H-inden- 1 -one Following the procedure according to the method of Example 23b except reacting 6-chloro-3-(4 chlorophenyl)2,3-dihydro-2-(hydroxymethylene)- 1 H-inden- 1-one with carbonyl-bis-imidazole, the title compound is produced, m.p. 204-2050C (absolute ethanol); yield 63%.
EXAMPLE 26 4,6-Dichloro-3-92,4-dichlorophenyl)-2,3-dihydro-2-[(1 H-imidazol- 1 -yl)methylenel- 1 H-inden- 1-one a) 4,6-Dichloro-3-(2,4-dichlorophenyl)-2,3-dihydro-2-(hydroxymethylene)-1H-inden-1-one The above starting material is prepared following the procedure of Example 23a m.p.
189-191 0C (ethylacetate); yield 75%.
b) 4,6-Dichloro-3-(2,4-dichlorophenyl)-2,3-dihydro-2-[(1 1 H-irnidazol-1 -yl)-methylene]-1 H- inden-1 -one 11.2 g of 3,6-dhloro-3-(2,4-dichlorophenyl)-2,3-dihydro-2-(hydroxymethylene)-1 H-inden-1-one (0.03 mol) are suspended in 150 ml of benzene. After addition of 5.4 g of carbonyl-bis-imidazole (0.033 mol) both reaction components dissolve at room temperature. Stirring is continued at room temperature for about 2 hours. The precipitated product is worked up as described in Example 23b, m.p.
191 960C (absolute ethanol); yield 5.9 g. An additional crop of 4.0 g (m.p. 193-1 950C) is obtained by evaporation of the mother liquor and treated of the residual product with water and ether. Total yield 9.9 g (78%).
EXAMPLES 27 to 46 The following additional compounds shown in Column II of Table B set out below are produced by the procedure of Example 23, by substituting for 2,3-dihydro-2-(hydroxymethylene)-1 H-inden-1 -one the compound shown in Column I of Table B below.
BALE B
Column 1 Column II Ex.
No. R5 R6 R7 R8 R9 R10 R5 R6 R7 R8 R9 R10 27. CH3 H H H H H # 28. H H Cl H C2H5 H as in Column 1 29. H H H H Cl H 30. H H CH3 H CH3 H 31. C2H5 Br CH2O H CH3O H 32. CH3O H H Cl H H 33. CH2S Cl H H H Br 34. C6H5CH2 Br H C2H5 C2H5 C2H5 35. p-OH-C6H4 H H H C2H5 H 36. o-CH3-C6H4 H H H Br Br TABLE B (Continued)
Column 1 Column II Ex.
No. R5 R6 R7 R8 R9 R10 R5 R6 R7 R8 R9 R10 37. m-C2H@O-C6H4 Br H H H CH3 # 38. p-CH2S-C6H4 Cl H H Cl Cl as in Column 1 39. o-CN-C6H4 H H H Br Br 40. p-NO2-C6H4 H H H H C6H5 41. C2H5OC2H4 Cl H H C2H7S H 42. C6H5OC2H4 Br CH3 C2H5O H H 43. C6H2C2H4 H H C6H4 C6H5 H 44. C6H5 H CH3O H Cl H 45. H Cl H H C2H5S H 46. H H H H C6H5CH2 H

Claims (28)

1. A compound of the formula
wherein R1 and R2 each is hydrogen, lower alkyl, halogen, lower alkoxy, lower alkylthio, phenyl-lower alkyl, phenyl or substituted phenyl wherein the phenyl bears one halogen, hydroxy, lower alkoxy, lower alkyl, lower alkylthio; cyano or nitro group; R3 and R4 each is hydrogen, lower alkyl, lower alkylthio, lower alkoxy, halogen, phenyl, hydroxy, or phenyl-lower alkyl; a compound of the formula
wherein R5, R6, R7, R6, R9 and R10 may be the same or different and each is hydrogen, lower alkyl, halogen, lower alkoxy, lower alkylthio, phenyl-lower alkyl, phenyl or substituted phenyl, wherein the phenyl bears one halogen, hydroxy, lower alkoxy, lower alkyl, lower alkylthio, cyano or nitro group; or such a compound in non-toxic physiologically acceptable acid addition salt form.
2. A compound according to claim 1 of the formula
wherein R' and R2 each is hydrogen, lower alkyl, halogen, lower alkoxy, lower alkylthio, phenyl-lower alkyl, phenyl or substituted phenyl, wherein the phenyl bears one halogen, hydroxy, lower alkoxy, lower alkyl, lower alkylthio, cyano or nitro group; R3 and R4 each is hydrogen, lower alkyl, lower alkylthio, lower alkoxy, halogen, phenyl, hydroxy, or phenyl-lower alkyl; or such a compound in non-toxic physiologically acceptable acid addition salt form.
3. The compound as defined in claim 2 wherein R1 and R2 are hydrogen.
4. The compound as defined in claim 2 wherein one of R3 and R4 is halogen and the other is hydrogen.
5. The compound as defined in claim 4 wherein one of R3 and R4 is chlorine.
6. The compound as defined in any one of claims 2 to 5 in the form of its hydrochloride salt.
7. The compound as defined in claim 2 having the name 2,3-dihydro-3-(1 H-imidazol-1 ylmethylene)-4H-1 -benzothiopyran-4-one or its hydrochloride salt.
8. The compound as defined in claim 2 having the name 6-chloro-2,3-dihydro-3-(1 H-imidazol-1 ylmethylene)-4H-benzo[b]thiopyran-4-one.
9. An antimicrobial composition comprising a compound as defined in Claim 2 and a pharmaceutically acceptable carrier therefor.
10. A method for treating bacterial or fungal infections in mammals which comprises administering to a mammalian host an effective amount of a compound as defined in Claim 2.
11. A compound according to claim 1 of the formula
wherein R5, R6, R7, R8, R9 and R'O may be the same or different and each is hydrogen, lower alkyl, halogen, lower alkoxy, lower alkylthio, phenyl-lower alkyl, phenyl or substituted phenyl wherein the phenyl bears one halogen, hydroxy, lower alkoxy, lower alkyl, lower alkylthio, cyano or nitro group; or such a compound in non-toxic physiologically acceptable acid addition salt form.
12. The compound as defined in claim 11 wherein R5 and R6 are hydrogen.
13. The compound as defined in claim 11 wherein one of R5 and R6 is lower alkyl, phenyl, or phenyl containing one or two halo substituents and the other is hydrogen.
14. The compound as defined in claim 13 wherein one of R7, R6, R9 and R10 is chlorine and the remainder hydrogen.
1 5. The compound as defined in any one of claims 11 to 14 in the form of its hydrochloride salt.
16. The compound as defined in claim 11 having the name 2,3-dihydro-2-[(1 H-imidazol-1yl)methylene]-1 H-inden-1 -one or its hydrochloride salt.
17. The compound as defined in claim 11 having the name 6-chloro-2,3-dihydro-2-(1 H-imidazol1 -ylmethylene)-1 H-inden-1 -one.
1 8. The compound as defined in claim 11 having the name 2,3-dihydro-2-(1 H-imidazol-1 ylmethylene)-3-phenyl-1 H-índen-1 -one.
1 9. The compound as defined in claim 11 having the name 6-chloro-3-(4-chlorophenyl)-2,3dihydro-2-(1 H-imidazol-1 -ylmethylene)-1 H-inden-1 -one.
20. The compound as defined in claim 11 having the name 4,6-dichloro-3-(2,4-dichlorophenyl)2,3-dihydro-2-(1 H-imidazol- 1 -ylmethylene)-1 H-inden- 1-one.
21. The compound as defined in claim 11 having the name 2,3-dihydro-2-(1 H-imidazol-1 ylmethylene)-3-methyl-1 H-inden-1 -one.
22. The compound as defined in claim 11 having the name 4-chloro-2,3-dihydro-2-(1 H-imidazol1 -ylmethylene)-1 H-inden-1 -one.
23. An antimicrobial composition comprising a compound as defined in claim 11 and a pharmaceutically acceptable carrier therefor.
24. A method for treating bacterial or fungal infections in mammals which comprises administering to a mammalian host an effective amount of a compound as defined in ciaim i i.
25. A compound according to claim 1 as named or shown in any dfthe Examples.
26. A compound according to any one of claims 1-8, 1 1-22 and 25 for use in the treatment of bacterial and fungal infections in mannals.
27. A composition according to claim 9 or 23 in the form of a tablet, capsule, elixir, lotion or cream.
28. A composition according to claim 9, 23 or 27, including a preservative or flavor.
GB8023925A 1979-08-08 1980-07-22 2,3-Dihydro-4H-1- benzothiopyran-4-ones and 2,3- dihydro-1H-inden-1-ones Withdrawn GB2060611A (en)

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US06/064,653 US4228177A (en) 1979-08-08 1979-08-08 2,3-Dihydro-3-(1H-imidazol-1-ylmethylene)-4H-1-benzothiopyran-4-ones
US06/066,726 US4218461A (en) 1979-08-15 1979-08-15 2,3-Dihydro-2-[(1H-imidazol-1-yl)-methylene]-1H-inden-1-ones

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