CA1257281A - Antiviral and anti-tumor cyclohexadienone compositions - Google Patents

Antiviral and anti-tumor cyclohexadienone compositions

Info

Publication number
CA1257281A
CA1257281A CA000497725A CA497725A CA1257281A CA 1257281 A CA1257281 A CA 1257281A CA 000497725 A CA000497725 A CA 000497725A CA 497725 A CA497725 A CA 497725A CA 1257281 A CA1257281 A CA 1257281A
Authority
CA
Canada
Prior art keywords
formula
compound
compounds
compositions
acetone
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA000497725A
Other languages
French (fr)
Inventor
Kenneth M. Snader
Tatsuo Higa
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Harbor Branch Oceanographic Institution Inc
Original Assignee
Harbor Branch Oceanographic Institution Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US06/744,620 external-priority patent/US4921873A/en
Priority claimed from US06/772,330 external-priority patent/US4708962A/en
Application filed by Harbor Branch Oceanographic Institution Inc filed Critical Harbor Branch Oceanographic Institution Inc
Application granted granted Critical
Publication of CA1257281A publication Critical patent/CA1257281A/en
Expired legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D303/00Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02Compounds containing oxirane rings
    • C07D303/12Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
    • C07D303/32Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/12Ketones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425Thiazoles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/51Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
    • C07C45/511Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups
    • C07C45/515Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups the singly bound functional group being an acetalised, ketalised hemi-acetalised, or hemi-ketalised hydroxyl group
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61Preparation 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
    • C07C45/65Preparation 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 splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61Preparation 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
    • C07C45/67Preparation 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
    • C07C45/68Preparation 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
    • C07C45/70Preparation 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 by reaction with functional groups containing oxygen only in singly bound form
    • C07C45/71Preparation 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 by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/78Separation; Purification; Stabilisation; Use of additives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/603Unsaturated compounds containing a keto groups being part of a ring of a six-membered ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/647Unsaturated compounds containing a keto groups being part of a ring having unsaturation outside the ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/687Unsaturated compounds containing a keto groups being part of a ring containing halogen
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/703Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
    • C07C49/713Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups a keto group being part of a six-membered ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/753Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/757Unsaturated compounds containing a keto groups being part of a ring containing —CHO groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Emergency Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

ABSTRACT OF THE DISCLOSURE
Antitumor compounds and compositions may be used to treat cancerous cachexia caused by the pre-sence of a tumor in a host; the compounds have the formula:

wherein R is:

Description

- ~25~2~31 Field of the Invention This invention relates to new cyclohexadienone derivatives which have useful antiviral and antitumor activity. More particularly, this invention relates to cyclohexadienone derivatives with antiviral and antitumor activities which are derived from marine organisms, i.e. red alg 2 .

Backqround of the Invention Viral diseases inflict man, plants, insects, and animals. The prevention and control of viral diseases have important health and economic implications.
Vlral diseases contribute to inflictions in humans including common colds, herpes and cancer and the importance of their control is obvious. Also important is control of viral diseases in animals for economic reasons as well as the ability of such animals to become virus reservoirs or carriers which facilitate the spreading of viral diseases to humans. Viral plant diseases have been known to have a disruptive effect on the cultivation of fruit 3l~S ;72~

trees, tobacco and various vegetables. Insect viral diseases are also of interest because of the insects' abili-ty to transfer viral diseases to humans.
The preven-tion and control of viral diseases is thus of prime importance to man and considerable research has been devoted -to an-tiviral measures.
Certain methods and chemical compositions have been developed which aid in inhibiting, con-trolling or destroying viruses but new methods and antiviral chemical composi-tions are needed.
U.S. Pa-ten-t Nos. 4,162,308 and 4,162,309 to Calvin and Ellis describe that wa-ter soluble extrac-ts from marine red algae have been found to be effec-tive to inhibit the growth of certain herpes viruses.
U.S. Paten-t 4,162,308 describes wa-ter soluble ex-tracts from marine red algae selected from a group consisting of Turnerella mertensiana, Schizymenia epiphy-tica, Turnerella pennyi and mixtures thereof as effective to inhibit the grow-th of herpes simplex virus, type 1 and type 2, and herpes zoster, and to relieve -the pain caused by infec-tion attributable -to such viruses.
U.S. Patent 4,162,309 describes the use of wa-ter soluble extrac-ts from marine red algae selected from a group consisting of Neodilsea americana and Neodilsea integra and mixtures thereof -to inhibit the growth of herpes simplex virus, type 1 and type 2, and herpes zoster, and to relieve the pain caused by infec-tion at-tributable to such viruses.

~,. ..

~25~

Crews et al in "Bio-Active Monoterpenes Erom Red Seaweeds", Phytochemis-try Vol. 23, No. 7, pp.
:L449-1~51, Pergamon Press Ltd., Great Britain, 1984, describe the bioactivi-ty of seaweed derived mono-terpenes. Crews et al disclose halogenated mono--terpenes which are extracted from red algae Chondrococcus hornemanni with methylene chloride.
The halogentated monoterpenes are shown to be bioactive in various applica-tions and biotoxic against insec-ts.
In addition -to the water soluble red algae ex-tractions described in the above noted U.S. Paten-t applications to Calvin and Ellis and the halogena-ted monoterpenes of Crews et al other compounds have been isolated from red algae and marine organisms known as sea hares which are mollusks which diet on red algae. these compounds include halogenated chamigrenes and have been described in various literature references including P. J. Scheuer, Ed.
Marine Natural Products, Volume 1 (Martin) and Volume 5 (Erickson) Academis Press, 1978; 1983.
The presen-t inventors have also developed compounds prepared from red algae and extracts of sea hares, which diet on red algae, comprising certain halogenated chamigrenes which show an-tiviral ac-tivity and certain cyclohexadienone compounds which show antiviral and antitumor activity.

. , -, . ~.;, The present inventors have also developed compounds prepared from red algae and extracts of sea hares, which diet on red algae, comprising certain halogenated chamigrenes which show anti-tumor activity.
Prevention, control of the growth and regression of tumors in mammals is also of importance to man. Considerable research has been devo-ted -to oncology and antitumor measures. The term tumor refers to abnormal masses of new tissue grow-th which is discordant with the economy of the -tissue of origin or the host's body as a whole. Tumors are common in a variety of mammals and -the preven-tion, control of the growth and regression of tumors in mammals is important to man.
Tumors inflect mammals and man with a variety of disorders and conditions including various forms of cancer and resultant cancerous cachexia.
Cancerous cachexia refers to the symptomatic disco~ ort that accompanies the inflection of a mammal with a tumor. These symptoms include weakened condition of the inflicted mammal as evidenced by, for example, weight loss. The serious-ness of cancer is well known, e.g., cancer is second only -to heart and vascular diseases as a cause of dea-th in man.

~.

-` ~L2~72~3~

Considerable research and resources have been devoted to oncology and antitumor measures including chemotherapy. While certain met~lods and chemical compositions have been developed which aid in inhibiting, remitting or controlling the growth of tumors new methods and antitumor chemical compositions are needed.

It has now been found that certain cyclohexadienone compounds derived from extracts of red algae possess useful antiviral and antitumor activity.

Summary of the Invention It is therefore an object of the invention to provide novel compositions which are useful as antiviral and antitumor agents and a process for producing such novel antiviral and antitumor compositions.
It is an aaditional object of the invention to provide a method for inhibiting viruses and tumors utili~ing novel antiviral and antitumor compositions, respectively.
Additional objects and advantages of the invention will be set forth, in part, in tne description whicn follows and in part will be obvious from this description, or may be learned by the practice of the invention. The objects and advantages of the invention are realized and cbtained by means of the compositions, processes, methods, ana ~ZS7281 the combinations particularly pointed out herein.
To achieve the objects in accordance with the purposes of the invention, as embodied and fully described here, the invention comprises a compound of the general formula (I):

Rl X R2 R~
~0 wherein both R1 groups are the same or different and are hydrogen or a lower alkyl group, X is lower alkyl, hydroxyl, lower acyloxy, lower alkoxy, fluoro, chloro, bromo or iodo group, and R2 is hydroxy, a lower acyloxy group, a halogenated lower acyloxy group or halogen.
In preferred embodiments of the invention, R1 is a methyl group, R2 is an acetyloxy group, and xl is methyl, chloro, or bromo.
In a more preferred embodiment of the invention, the invention comprises a compound of the formula:
CH~ Cl OCCH~
H3C - ~ ~ /

II.

12S7~81 As embodied and fully described ~erein, the invention also comprises an antiviral or antitumor composition comprising, as active ingreaient, an effective antiviral or antitumor amount o~ one or more o~ the compounds according to Formula I or preferably Formula II and a non-toxic pharmaceutically acceptable carrier or diluent.
As embodied and broaaly described herein, the invention also comprises a process to produce the 1~ compounds of Fo~rmula I co~prising the steps of:
collect~ng red alga; contacting the alga with a suitable organic solvent to obtain an extract; and isolating a compound of Formula I. Pre~erably, the process comprises the steps of: collecting red alga, particularly Desmia hornemanni; contacting the alga with a suitable organic first solvent to obtain extract; removing the solvent containing a derivative of the first compouna of For~ula I, preferably an alcohol derivative of Formula II; isolating the derivative of Formula II by conventional means, preferably chromatography; and acetylating the alcohol aerivative to yield the compoun~ of Formula II.
As embodie~ and fully describec herein, tke invention further comprises a methoa ror inhibiting viruses or tumors comprisina contacting a virus or tumor wi~h an effective antiviral or antitumor amount of one or more compositions of Formula I or preferably Formula II.
- 30 In accordance witn the purposes of the invention, as embodied and fully described herein, .
: . .

~2S72~

the invention further comprises a compound of the general formula (III):
R~
R~ ~ R

~0 III
wherein R is:
Xl OCH3 o oR2 oR2 X2 R2 / ~ CHR2 / ~ \R2 X R2 / ~ CHR2 I ~CH2 ~ ~ N____,_CONH2 Y X ~2 ~ ; or ~ ~

wherein Xl is an oxygen, x2 is hydrogen, halogen, lower alkyl group or alkylsulfenyl group, sulfur or an imine group; Y is oxygen or sulfur; Z is oxygen, sulfur or an imine group; wherein both Rl groups are the same and are hydrogen or a lower alkyl group; R2 is hydrogen or a lower alkyl group; and n is from 1 to 5.
In preferred embodiments of the invention, Rl and R2 are methyl groups, and Xl and Y are oxygen.
In a more preferred embodiment of the invention, the invention comprises compounds of the Formulae:

~L~5~2~3~
- g CH3 OC~3CH3 OCH3 OCH3 H3C ~ CH~H3C ~ c~3 1~0 \,~0 N3C ~ ~ c~3 H3C
O O
VI VII

As embodied and fully described herein, the invention also comprises an antitumor composition 15comprising, as active ingredient, an effective antitumor amount of one or more of the compositions according to Formula I or III or preferably one of ` Formula IV, V, VI or VII and a non-toxic pharmaceutically acceptable carrier or diluent.
20As embodied and broadly described herein, the invention also comprises a process to produce the compound of Formula III comprising the steps of:
collecting red alga; contacting the alga with a suitable organic solvent to obtain an extract; and 25synthesizing and isolating a compound of Formula III.
As embodied and fully described herein, the invention further comprises a method for inhibiting tumors comprising contacting a tumor with an effective antitumor amount of one or more compositions of Formula 30I or III or preferably one of ~S~B~
--lV-Formula IV, V, VI, or VII.

As embodied and broadly described herein the invention also comprises a method for treating cancerous cachexia comprising inhibiting, remitting or controlling the growth of tumors or tumor cells which syptomatically cause the conditions o~ cancerous cachexia.

It is to be understood that both the foregoing general and the following detailed description are exemplary and explanatory only and are not intended to be restrictive of the invention as claimed.
DETAILE DESCRIPTION OF THE PREFERRED
E INVENTION

Reference will now be made in detail to the present preferred embodiments of the invention, examples of which are illustrated in the following example section.
In accordance with the invention, a compound is provided of the formula:
Rl X ~2 R~
~0 S7Z~3~

wherein both R1 groups are the same or different and are hydrogen or a lower alkyl group, X is a lower alkyl, hydroxyl, lower acyloxy, lower alkoxy, fluoro, chloro, bromo or iodo group, and R2 is hydroxy, a lower acyloxy group, a halogenated lower acyloxy group or a halogen.
Preferably, the lower alkyl and acyloxy groups have from one to five carbon atoms, more preferably from one to three carbon atoms, and most 10 preferably, the lower alkyl group is methyl and the lower acyloxy group is acetyloxy.
Preferably, X is a methyl, chloro or bromo group, more preferably, X is a chloro group.
More particularly, a preferred embod-iment of the invention comprises a compound of thestructure II as indicated below:

CH3 Cl OCCH3 II
Another preferred embodiment of the invention comprises a compound of the formula as indicated below:
CH3 Cl Br H3C ~
~`0 ~57Z~3 In accordance with the invention an antiviral composition is provided comprising as active incredient an effective antiviral amount of one or more of the compounds described above and identified by Formulas I and II anà a non-tcxic pharmaceutically acceptable carrier or ciluent.
While erfective amounts may vary, as conditions in which the antiviral compositions are used vary, a minimal dosage required for activity is senerally ~etween 50 and 200 microgram against 25-80 plaque-forming units o~ virus. Useful exa~ples of non-toxic pharmaceutically acceptable carriers or diluents include, but are not limited to, the following: ethanol; dimethyl sulfoxide; and glycerol.
In accordance with the invention, a process to produce a compound according to Formula I
comprises the steps of: collecting red alga, particularly Desmia hornemanni (also known as Chondrccoccus hornemanni); contacting ~he alga witn a suitable organic solvent to obtain an ex~ract of the solvent; and isolating a compound accoraing to Formula I.
A detailed description and explanation of a preferred embodiment o~f the process of t:ne invention to produce the compound accordinS to For~ula I is as follows. Red alca, Desmia horr.emanni is collected at Cape Zampa, Okinawa. The alga is then contacted with acetone (a first solvent) to obtain an acetone e:c ract from the red alga. The acetone extract is then concentrated by evapor2tion through either heat or reduced pressure and the acetone .esidue is . ~., ~ , .
..~i,,, ~ j 8~

contacted with methylene chloride to obtain a methylene chloride extract.
While acetone and methylene chloride are the presently preferred choices for first and second solvents, other suitable soivents may be substituted for acetone and/or methylene chloride. A suitabie first solvent should be capable of extracting a compound according to Formula I from other components of the red alga. Suitable first solvents which may be substituted for acetone include, but are not limited to, the following organic solvents: methyl ethyl ketone; ethyl acetate; methanol; ethanol; and methyl isobutyl ketone. A suitable second solvent should be capable of extracting and separating the compound of Formula I from other components that may be present in the first solvent extract. Suitable second solvents which may be substituted for methylene chloride include, but are not limited to, the following organic solvents: chloroform;
trichloroethylene; hexane; and lower alkanes.
Different ratios of first to second solvents may be used in the invention as would be known to those skilled in the art.
The methylene chloride extract is removed and concentrated by evaporation of the methylene chloride solvent by either gentle heating or reduced pressure. An alcohol derivative of the compound of Formula II is isolated from the methylene chloride extract by chromatography.
An~ suitable chromatography techniaue may be used, but it has been found that first subjecting the ~l2S~ .

. methylene chloride extract to chromatography on a silica gel column, by eluting with hexane-acetone in an approximate ml. ratio of 7:3 hexane to acetone to obtain a major fraction of the alcohol derivative of Formula II and then further separating the major fraction on a thin layer chromatography grade silica gel column by flash chromatography yields the pure : alcohol derivative of the compound according to Formula II. Other eluents and columns may be substituted as would be known to those skilled in the art.
The alcohol derivative of the compound of Formula II was found to decompose at room temperature in two hours so it is important to carry out the next step as soon as possible.

The alcohol derivative of the compound of Formula II is acetylated with acetic anhydride and pyridine mixture in a ml. ratio of approximately l:l of acetic anhydride to pyridine for about ten minutes. ~hile a mixture of acetic anhydride and pyridine is the present preferred choice of acetylation agents other suitable agents may be substituted such as, for example isopropenyL acetate and acetyl chloride substituted for acetic anhydride;
and N-methyl morpholine and N-methyl pyrrolidine `substituted for pyridine. The ~xcess acet c anhydride and pyridine is removed by evaporation to yield pure compound according to ormula II.
In accordance with the present invention, virus cells are inhibited in growth or killed by a method comprisinc contacting a virus with an effective antiviral amount of one or more compounds according to Formulas I and/or II. The minimal effective amount as stated above is generally from 50 to lC0 micrograms for 25 to 80 plaque forming units of virus cells. The compound of Formulas I and II are active ~or inhibiting or killing a diverse range of viruses including, but not limited tot the RNA viruses, vesicular-stomatitis (herein "VSV), arenaviruses, coronaviruses, influenza viruses and the DNA viruses, herpes simplex-I (herein "HSV-I"), other herpes viruses, adenoviruses and papovaviruses.
The effectiveness of the compositions o~ the invention for inhibiting virus cells indicates that the compositions of Formulae I and II should also be useful in controlling viral infections in host animals and plants which are caused bv a virus which is thus inhibited or destroyed. Viral infections which may be controlled by utilizins compositions of the present invention include, but are not limited to, those caused by RNA viruses such as arenaviruses, coronaviruses, reoviruses, influenza viruses, and viral infections caused by the D~A viruses such as herpes viruses, adenoviruses and papova viruses. The invention may also be useful in controlling common viral infections of plants.
In accordance with the invention, a compounds is provided of the formula:

~2572~3~

R~ Rl \~O

III
wherein R is:

Xl OCH3 o oR2 oR2 X2 R /~ CHR2 F;2 XR2 ;~ ~ 2 ~R2 /~\ ; or ~CONH2 ~25~281 wherein X1 is an oxygen, x2 is hydrogen, halogen, lower alkyl group or alkylsulfenyl group, sulfur or an imine group; Y is oxygen or sulfur; Z is oxygen, sulfur or an imine group; wherein both Rl groups are the same and are hydrogen or a lower alkyl group; R2 is H or a lower alkyl group; and n is from 1 to 5.
Preferably, the lower alkyl groups have from one to five carbon atoms, more preferably from one to three carbon atoms, and most preferably, the lower alkyl group is methyl.
Preferably, Xl and Y are oxygen.
More particularly, a preferred embodiment of the invention comprises a compound of the structure IV, V, VI or VII as indicated below:

CH3 OCH3 CH3 Q~H3 OCH3 H3C ~ CH2 H3C ~ X CH3 ~0 ~0 IV V

25 H3C~Q--CH3 H3C

VI VII
In accordance with the invention an 30 antitumor composition is provided comprising as active ingredient an effective antitumor amount of ~2~72 one or more of the co~pounds ~escribed above and identi~ied by Formulas I - VII and a non-toxic pharmace~tically acceptable carrier or diluent.
~hile e~fective amounts may vary, as conditions in which the antitumor compositions are used vary, a minimal dosage required for activity is generally between 1 and 100 micrograms against 10~ tumor cells. Useful examples o~ non-toxic pharmaceutically acceptable carriers or diluents lnclude, b~t are not limited to, th~ following: ethanol; dimethyl sulfoxide; and glycerol.
In accordance with the invention, a process to produce a compound according to Formula III
comprises the step of: collecting red alga, particularly Desmia hornemanni (also know~ as Chondrococcus hornemanni); contacting the alga with a suit`able organic solvent to obtain an extract of the solvent; and synthesi7ing and isolating a compo~nd according to Formula III.
~0 A detailed description and explanation of a preferred embodiment of the process of the invention for producing a compound according to Formula III is as follows. Red alga, Desmia hornemanni is collected at Cape Zampa, Okina~a. The alsa is then contacted with acetone (a ~irst solvent) to obtain an acetone extract from the red alga. The ace~one extract is then concentrated by evaporation through either heat or reduced pressure and the acetone residue contacted with methylene chloride to obtain a methylene chloride extract.
~hile acetone and methylene chloride are the .

~25'72~3~

presently preferred choices for first and second solvents, other suitable solvents may be substituted for acetone and/or methylene chloride. A suitable first solvent should be capable of extracting a compound according to Formuia I from other components of the red alga. Suitable first solvents which may be substituted for acetone include, but are not limited to, the following polar organic solvents:
methyl ethyl ketone; ethyl acetate; methanol;
ethanol; and methyl isobutyl ketone. A suitable second solvent should be capable of extracting and separating the compound of Formula I from other components that may be present in the first solvent extract. Suitable second solvents which may be substituted for methylene chloride include, but are not limited to, the following organic solvents:
chloroform; trichloroethylene; hexane; and lower alkanes. Different ratios of first to second solvents may be used in the invention as would be 20, known to those skilled in the art.
The methylene chloride extract is removed and concentrated by evaporation of the methylene chloride soLvent by either gentle heating or reduced pressure. An alcohol derivative (VIII) of a compound according Formula I is isolated from the methylene chloride extract by chromatography.
The alcohol derivative has the following Formula: ~ Cl ~, ; o~.
1 ~
~0 ~T ~ I

~ 2 .

.

Any suitable chromatography technique may be used, but it has been found that first subjecting the methylene chloride extract to chromatography on a silica gel column, by eluting with hexane-acetone in an approximate ml. ratio of 7:3 hexane to acetone to obtain a major fraction containing a compound of Formula VIII and then further separating the major fraction on a thin Layer chromatography grade silica gel column by flash chromatography yields pure Formula VIII. Other eluents and columns may be lS substituted as would be known to those skilled in the art. The compound of Formula VIII was found to decompose at room temperature in two hours so it is important to carry out the next synthesis steps as soon as possible.
To prepare the preferred e~.bodiments of the invention according to Formula IV, V, VI and VII the following synthesis steps are taken to prepare these compounds from the compound of Formula VIII and IX.
Compounds according to formula I~ and V are ~5 synthesized from a halogen derivative of the compound ~5~2~

of Formula I having the Formula:

~ ~ ~Bs O

IX
wherein X3 is Cl or Br.
A compound of Formula IX is obtained by isolating a vola~ile oil fraction from the methylene chloride extract subjected to chromatography as described above for obtaining the alcohol derivative of Formula I (Formula VIII), and obtaining from said volatile oil fraction a halogen derivative of the compound of Formula I having the Formula IX.
The halogen derivative IX is treated with a base such as potassium hydroxide in methanol ~e.g.
10% KOH-methanol) to yield (a~ter isolation, e.g., separation by thin layer chromatography) a major amount or a ketal of formula V and a minor amount of a vinyl ether of Formula IV.
A compound according to Formula VI is obtained by hydrolysis of the ketal of Formula V
with, for example, methanol and hvdrochloric acid (e.g. 1:1 by volume of MeOH: 5N HCl).
A compound according to Formula VII is synthesized by treating a compound of Formula VIII, obtained as described above, with a base such as potassium hydroxide and dioxane (e.g. 1:1 by volume of 1~ KOH in H20: dioxane).
In accordance with the present invention, tumors and ~umor cells are inhibited by a method comprising contacting a tumor with an effective antitumor amount of one or more compositions according to Formul~e I - VII. The minimal effective amount as stated above is generally from 1 to 100 micrograms for 105 tumor cells. The compound of Formulae I - VII are active for inhibiting a diverse range of tumors including, but not limited to human lung, colon and mammary tumors such as lung carcinoma A549, ileocecal adenocarcinoma HCT-8, and human breast carcinoma MCF-7.
The effectiveness of the compositions of the invention for inhibiting tumors indicates that the compositions of Formulae I - VII should also be useful in controlling tumors in host animals.
It is therefore apparent that the compositions of the invention, the pr-ocesses for producing the compositions of the invention and the methods for utilizing the compositions of the invention to inhibit viruses and tumors are effective for inhibiting or destroying viruses and tumors and therefore controlling diseases, disorders and symptomatic discomfort caused by or related to such viruses anG tumors in fulfillment of the objects of the invention.

E~AMPLES

The invention will now be illustrated by examples. The examples are not intended to be limiting of the scope of the present invention. In ~:2S'728 ~, .
conjunction with the detailed and general description above, the examples provide further understanding of the present invention and outline a process for producing compositions of the invention.
S The following examples represent preferred embodiments of the compositions, processes and methods of the invention for satisfying the stated objects of the invention. The starting materials and reagents in the examples whose method of preparation are not indicated, are commercially available from sources known to the art such as chemical supply houses.

lS Preparation of Compounc (1):
C~
~ QC~

~
(1) 2000 grams of red alga Desmia hornemanni were co~lected and placed in a 5000 ml. vessel and 2000 mls. of acetone was added to the vessel and the mixture was vigorously agitated to produce a slurry.
The slurry was f iltered to provide an acetone extract. The acetone extract was concentrated under vacuum at room temperature and admixed with 100 mls. of methylene chloride ln a separatory funnel. The methylena chloride fraction was removea and concentrateQ to give 13.2 gms of ~257Zi3 crude oil.
The methylene chloride extract was subjected to chromatography on a silica gel column, by eluting with 7:3 hexane-acetone. A major fraction containing the alcohol derivative of Compound (l) illustrated below as Compound (X):

~,~ I t,~

~ o ~ X) was further separated on a thin layer chromatography grade silica gel column by flash chromatography to obtain the pure compound of Formula VIIX, t ~2l-87~2 (C 1.29, CH2Cl2) The compo~nd of Formula VIII was immediately subjected to acetylation by admixing lO0 milligrams of the compound of Compound ~X) with 0.1 ml. of acetic anhydride and 0.1 ml. of pyridine. Excess acetic anhydride and pyridine was removed by evaporation with gencle heating and under reduced pressure to give an oil which was further purified by chromatography on silca gel using an eluting solvent of l:l of hexane: ethylacetate to give a pure yellow oil of ~ormula II []2l-56.8 (C 0~84, CHCl2).
The absolute configura~ion of t~e compound is not .yet known.

~5'7~81 ~ 25 -Preparation of Compound (2) and (3) CH3 OCH3 CH3 O~H3 OCH3 H3C~CH2 H3ct--~CH3 ~0 ~o
(2) (3) 2000 grams of red alga Desmia hornemanni were collected and placed in a 5000 ml. vessel and 2000 mls. of actone was added to the vessel and the mixture was vigorously agitated to produce a slurry.
The slurry was filtered to provide an acetone extract. The acetone extract was concentrated under vacuum at room temperature and admixed with 100 mls. of methylene chloride in a separatory funnel. The methylene chloride fraction was removed and concentrated to yield 13.2 gms. of crude oil.
The methylene chloride extractwas subjected to chromatography ona silica gel column, by eluting with 7:3 hexane-acetone. A volatile oil fraction was obtained which contained a halogen derivative of Formula I illustrated below as Formula IX (wherein X3 is Cl or Br):

:`g ~2S~

Br .. ~0 IX
A sample of a compound (Y) of Formula IX
(47.2 mg) was treated with 10% KOH-MeOH at room temperature for 30 minutes giving a reaction mixture with two major spots on a tlc plate (CHC13). The mixture was separated by a preparative tlc with chloroform to give ketal Composition (3) (Rf=Q.3, 18.3 mg 53.4~), anà vinyl ether Composition (2) (Rf=0.5, 8.3 mg, 28.6~) Ketal (3) has the following characteristics: oil, ~max (EtOH) 235 nm (~ 7900);
IR (film) 2960, 2830, 1660, 1635, 1470, 1370, 1270, 1190, 1175, 1150, 1110, 1055, 870 cm 1; lH NMR
(CC14) ~7.03 (lH, d, J=3.2 Hz), 6.65 (lH, dd, J=10.0, 3.2Hz), 6.00 (lH, d, J=10.0 Hz), 3.06 (6H, s), 1.50 (3H,s), 1.30 (6H,s).
Vinyl ether (2) had the followin~
characteristics: oil,~max (EtOH) 235 (~ 6000), 218 nm (~ 14000); IR (film) 2960, 1665, 1625, 158~, 1400, 1285, 1080, 840 cm 1; lH NMR (CC14)~6.97 (lH, d J=3.2 Hz), 6.53 (lH, dd, J=10.0 Hz), 6.00 (lH, d, J=10 Hz), 5.31 (lH, d, J=2.0Hz), 4.25 (lX, d, J=2.0 Hz)~ 3.53 (3H, s), 1.30 (6H, s).

.
Alternatively, ketal (3) can be produced by treating a sample (9.3 mg) of Compound (Y) in S N
methanolic KOH (1 ml) allowing it to stand at room temperature for ?O hours. Arter aading 5.0 ml. water the mixture was extracted with CH2C12. The CH2C12 solution was dried over sodium sulfate and concentrated to give ketal (3) (6.4 mg, 87-97%).

Preparation of Compound (4):

CH3 o H3C~CH3 ~o (4) Ketal ( 3) ( 6.9 mg) produced according to the procedures of either Examples 2 or 3 was dissloved in 0.1 ml of MeOH and 0.1 ml of 5 N HCl. After standing for 10 min the solution was extracted with CHC13 to give 4.5 mg (79.4%) of (4) as an oil with the following characteristics: max (EtOH) 205 ( 7500), 234 nm ~ 9200); IR (film) 2980, 2940, 2875, 1695, 1665, 1630, 1600, 1400, 1360, 1260, 935, 840 cm~l;
H NMR (CDC13) 7.50 (lH, d, J=3.0 Hz), 6.77 (lh, dd, J=10.0, 3.0 Hz), 6.12 (lH, d, J=10.0 Hz)~ 2.50 (3H, S), 1.33 (6H, s).
EXAMPLE 5 Preparation of epoxide Compound (5):

H3C ~
~`b (5) ~25~728~ .

~.

A mixture o~ Compound (X) (157.8 mg), 2 ml of 1~ KOH/H2O, and 2 ml of dioxane was heated under reflux for two hours. After removing dioxane in vacuo the reaction mixture was extracted with chloroform. The extract was separated on a silica gel column with chloroform to give 62 mg of starting material and 31.8 mg (46.8%) of epoxide (5) as a light yellow oil witn the following characteristics:
[~]D8 31.2 (c 0.64, MeOH); IR (film) 2975, 2925, 2875, 1670, 1630, 1470, 1~20, 1255, 1240, 1130 91S, 105, 880, 820, 800 cm 1; lH NMR~6.57 (lH, dd, J=9.0, 2.0 Hz), 6.37 (lH, dd, J-2.0, 0.4 Hz), 5.92 (lH, d, J=9.0 Hz), 3.62 (lH, m), 2.83 (lH, dd, lS J=6.8, 4.3 Hz), 2.26 (lH, dd, J-6.8, 2.0 Hz), 1.25 (3H, s), 1.18 (3H, s).

Example 6 Preparation Gf Composi.ion (6) ~ ~Br ~ O
(6) 2000 grams of red alga Desm-a hornemanni were collected and placed in a 5000 ml. vessel and ~Q00 mls. of acetone was added to the vessel and the mixture was viyorously agitated to produce a slurry.

~2S~728~

The slurry was filtered to provide an acetone extract. The acetone extract was concentrated under vacuum at room temperature and admixed with 100 mls. of methylene chloride in a separatory funnel. The methylene chloride fraction was removèd and concentrated to yield 13.2 gms. of crude oil.
The methylene chloride extract was subjected to chromatography on a silica gel column, by eluting with 7:3 hexan-acetone. A volatile oil fraction was obtained which contains a composition (6).

EXAMPLES 7 and 8 Preparation of compounds (7) and (8):
CH3 Cl c~3 ~CH
H3C ~ CH2 H3C

(7) (8) To 0.34 grams of the oil of Compound (6) 10~ KOH in dry methanol (1 ml.) was slowly added with stirring. The mixture was allowed to stand at room temperature for 30 minutes. The mixture was chromatographed on a silica gel column by eluting with 15:2 hexane/acetone to give 33.8 mg.of (7) and 190 mg. of a mixture containing (8). Further separation of a 110 mg.portion of the mixture on a Lobar Si-60 column with 6:1 hexane/ethyl acetate gave 34.3 mg of (8).

~L257~B~

~, Composition (7~ was a light yellow oil; IR
(~ilm) 3260, 3060, 2975, 2940, 2875, 2110, 1665, 1630, 1975, 1400, 1380, 1360, 1305, 125;, 118~, 1135, 1085, 985, 950, 930, 910 and 840 cm 1, Composition (8) ~as a light yellow oil; IR
(film) 3050, 2970, 2940, 2870, 1670, 1640, 1480, 1400, 1380, 1360, 1250, 1200, 1170, 113~, 1020, 960, 910, 840 cm~l.

A~1TIVIRAL AND ANTITUMOR ACTIVITIES O~ THE
.
COMPO~NDS OF THE INVENTIO~i _ _ The following assay method was utilized to illustrate the antiviral effectiveness of compound (1).
- Day 1:
1) Remove 7~ cm2 culture flasks from ~ incubator (these were pl~ted the previous week).
2) Aspirate medium.
3) ~lash with 10 ml PBSA or Puck's Saline.
4) Aspirate.
5) ~ash a second time with 10 ml PBSA or Puck's Saline.
6) Aspirate.
7) Aàd 2 ml trypsin/~DTA. Incubate until cells detach (10-20 min).
8) Once detached, shake vigcrously and immediately add 8 ml medium and shake again.
~) Cour.t cells. (To 0.5 ml cell ~, suspension add 0.1 ml trypan blue.
~ait 5-10 minutes. Count 4 corner squares and middle square of 5 x 5 array in hemocytometer. ~lue cells are dead. Total count per 10 ml in culture flask = ~ live cells x 6 x 105~.
1~) Maintain cell line by adding 3 x 106 cells to another 75 cm2 culture flask. Bring to 30 ml with fresh 1~
medlum.
11) For assay, add 1 x 106 cells to each well (6 wells per culture dish). Bring each well to 2 ml with fresh medium.
12) Incubate overnight at 37 C.
15 Day 2:
1) Aspirate me~ium.
2) Add 0.5 of medium containing 200 pfu HSV-I.
3) Incubate 102 hr with a s~all amount of shaking.
4) Add 2 ml MC-4000 to each well.
5) Place disks on surface and push through (1 mg/disc, 0.5 mg/disc, 0.25 mg/disc, etc. for crude extracts).
6) Incu~ate 48 hr. (making sure dishes remain level).
Dav 4 1) Add 2 ml neutral red medium.
2) Incubate overnight.
3~ Day 5:
1) Read wells, Q . g . compounà of Formula II

~iLZ~i7~

~, 16 (~+) where 16 indicates zone of cytotoxicity as the diameter in mm (6 mm ~o 16 mm) and (++) indicates the inhibition of plaque formation:
complete inhibition (++~), a few plaques around the outside of well (++), definite inhibition (+), questionable inhibition (+/-), no inhibition (-J, and no conclusion due to complete cytotoxicity.
Day 7:
8egin cycle again at Day 1.
II RECIPES
CULTURE MEDIU~I
1 L GIBC0 MEM (pius non-essential a.a.'s with Earle's Salts).
2.2 g NaHCO3 50 ml calf serum 105 units penicillin 50 mg streptomycin SOO ml CULTURE MEDIUM made to nalf volume (twice as concentrated) 500 ml v/w 4000 cps methyl cellulose NEUTRAL RED MEDIUM
tALWAYS MA~E FRESH) 500 ml CULTURE MEDIUM made to hal~ volume (twice as concentratedJ
500 ml 4% v/w 15 c~s methyl cellulose 100 mg neutral red from stock solution P~CK'S G SALINE SOLUTIO~J
to 1 L distilled H20 add:
8.00 g NaCl 0.40 g-KCI
0.lS g KH2PO4 0.29 9 Na2HPo4.7H2o 2.0 ml 1% phenol red 1.10 g glucose autoclave TRYPSIN-EDTA
for 1 L:
~dissolve" 2g DIFCO 1-250 trypsin plus 0.2 EDTA in 100 ml PUCK'S SALINE.
sterile filter.
ado to 900 ml sterile PUCK'S SALINE.
PBSA
to 1 L distilled H2U Add:
8.00 G NaCl 0.20 g RCl 5 2HP4'7H2 0.25 g K~2pO4 autoclave The results at Day 5 for Composition (1) indicates definite âr.tiviral activity 16(++) for the compound. compound (1~ shows antiviral activity in minimal effective amounts of from 50 to 100 micrograms for 25 to 80 plaque forming units of virus cells.

The foilowing assay method was utilized to ~2~

illustrate the antitumor effectivenes~ of compounds 1-7.
L1210 And P3~8 MOUSE LEUKEMIA CELL;
ILEOCECAL ADENO CARCINOMA HCT-8; AND LUNG
CARCINOMA A549; CITOXICITY ASSAY 24-~1ELL
P~ATE SCR~ENING ASSAY AND TUBE ASSAY PROTOCOL
MATERIALS UTILIZED
Media - Dulbeccos with glucose and pyruvate ~Biologos, Inc) with 10% horse serum, (Biologos, Inc) and 1.0 ug/ml gentamicin (Gibco).
Cells - L1210 and P-388 mouse leukemia cells tAmerican Type Culture Collection) in media at a concentration of 5x104 cells/ml. Sterile 24-well culture plates ~Nunc) for screening or 12 x 75mm glass culture tubes (3ecton-Dickinson) for tube assay. Microdispenser with 1 to 5 ul increments (Drummond Scientific Co. Broomall PA).
Finnpipette with 5 to 50 ul increments and Finnpipette with 5~ to 200 ul increments.
PROCED~RE
1. A sample of the composition to ~e assayed is added to each well or tube in an amount of from ~00 ug/~l and 100 ug/ml for screening. For DDC of known active compounds use log concentrations from lQ0 ug/ml to .01 ug/ml for range-finding assay; when range has been determine~, use five concentrations between highest an~ lowest active concentrations.

2. Add 2.0 ml of 5 ~ 104 cell suspension in media to each ~ell or tube. Tubes are loosely covered with parafilm.

~s~

3. Incubate in 5% CO2 incubator 48 hou-s.

4. Visually read plates with inverted microscope, comparing with solvent control. Assign activity as follows:

0 = 90 -100% of control growth 1~ = 75 - 89% of control growth 2+ = 50 - 74% of control growth 3+ = 25 - 49% of control growth 4+ = 25% of control growth Repeat all positive samples using tube assay.

5. For Tube assays - Mix tube well on vortex and remove 0.5 ml aliquot and add to 9.5 ml nf diluent fluid (Isoton - Coulter) in Accuvette (Coulter) and - mix well by inversion immediately before counting, taking care not to produce excessive bubbles. Count on Coulter Counter (Counter is set to count 0.5 ml of the solution; therefore counts may be converted to cell/ml in original assay tube by multiplying count by 4~.

Positive control - Vinblastine or Vincristine in aqueous solution.

Final conc. or Vinblastine or Vincristine ~ontrol (use 2 ul/assay) 3~
Solution Conc.

~572 Solution Conc. Amt added Final Conc. in test 10 mg/ml 2 ul 10 ug/ml 1 mg/ml 2 ul 1 ug~ml 10' O~l mg/ml 2 ul 0.1 ug/ml 0.01 mg/ml 2 ul 0.001 ug/ml Notes:
For solvents other than water, allow solvent to evaporate from tube or well in hood.

Chloroform and butanol cannot be usea in the plastic 24-well plates - use glass tubes.
Always run a solvent control in duplicate in the last two wells of each plate or four tubes for each rack of 72 or less tubes. Also run four wells or tubes with media and cells only per run of pla~es or tubes. Whell using volumes of a~ueous solutions greater than 200 ul, dry sample and bring up to desirea concentratiorl in meaia.
The results of the above assay show compounds of rormulae II, V, VI and VII are cytotoxic ~2S;'728 U

1n vitro against P-388 murine leukemia cells showing estimated ID50's (aose which kills 50% of the cells) of 37, 70, 70 and 5 micrograms per milliliter respectively. Compounds IV, V, VI and VII are cytotoxic ~n vitro against L-1210 murine leukemia cells showing 15~, 17%, 41% and 25% surviv~l at 200 micrograms per milliliter respectively. Compound VII
shows an estimated ID50 of 0 7 micrograms per milliliter against L-1210 murine leukemia cells. The following table summarizes these results.

TABLE
.__ CompositionTest Cells at (ID 50) ~-388 A549 HCT-8 -15 ug/ml ~0 ug/ml 10 ug/ml 2S ug/ml 30 ug/ml 20 ug/ml 310 ug~ml 30 ug/rlll 30 ug~ml S ug/ml 5 ug/ml 5 uy/ml 510 ugJml 1 ug/ml S uy/ml 60.5 ug/ml 5 ug/ml 5 ug/ml 7i ug/ml 3 ug/ml 0.3 ug/ml ~25~
-- 3~ --8 5 ug/ml 5 ug/ml 3 ug/ml The scope of the present invention is not limited by the description, examples, and suggested uses herein and modifications can be made without àeparting from the spirit of the invention. For example, it may be notea that other derivatives of the cyclohexadienones of example 1 such as a fluorinated cyclohexadienone may possess antiviral or antitumor activity analogous to those preferred embodiments described above. ~urther, the compositions described herein may have other useful applications such as, for example, analgesic applications. ThUs, it is intended that the present invention cover th~ modifications an~ variations of this invention provided that they come within the scope of.the appended claims ana their equivalents.

Claims (12)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:
1. A compound according to the formula:

wherein R is :

wherein X1 is =O or =S, X is -H, -R3, -SR3 or halo-gen, Y is -O- or -S-, R1 is -R3, R2 is -H or -R3, R3 is lower alkyl and n is an integer from 1 to 5.
2. A compound according to claim 1, wherein R
is:

3. A compound according to claim 1, wherein R
is:

4. A compound according to claim 1, wherein R
is:

5. A compound according to claim 1, wherein R
is:

6. A compound according to claim 1, wherein R
is:

7. A pharmaceutical composition comprising, as an active ingredient, an effective antitumor amount of one or more of the compounds of claim 1, and a non-toxic, pharmaceutically acceptable carrier or diluent.
8. A pharmaceutical composition comprising, as an active ingredient, an effective antitumor amount of one or more of the compounds of claim 2, and a non-toxic, pharmaceutically acceptable carrier or diluent.
9. A pharmaceutical composition comprising, as an active ingredient, an effective antitumor amount of one or more of the compounds of claim 3, and a non-toxic, pharmaceutically acceptable carrier or diluent.
10. A pharmaceutical composition comprising, as an active ingredient, an effective antitumor amount of one or more of the compounds of claim 4, and a non-toxic pharmaceutically acceptable carrier or diluent.
11. A pharmaceutical composition comprising, as an active ingredient, an effective antitumor.
amount of one or more of the compounds of claim 5, and a non-toxic, pharmaceutically acceptable carrier or diluent.
12. A pharmaceutical composition comprising, as an active ingredient, an effective antitumor amount of one or more of the compounds of claim 6, and a non-toxic, pharmaceutically acceptable carrier or diluent.
CA000497725A 1984-12-17 1985-12-16 Antiviral and anti-tumor cyclohexadienone compositions Expired CA1257281A (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US772,330 1977-02-25
US68227884A 1984-12-17 1984-12-17
US682,278 1984-12-17
US06/744,620 US4921873A (en) 1984-12-17 1985-06-14 Antiviral and antitumor cyclohexadienone compositions
US744,620 1985-06-14
US06/772,330 US4708962A (en) 1984-12-17 1985-09-04 Antiviral and antitumor cyclohexadienone compositions

Publications (1)

Publication Number Publication Date
CA1257281A true CA1257281A (en) 1989-07-11

Family

ID=27418399

Family Applications (1)

Application Number Title Priority Date Filing Date
CA000497725A Expired CA1257281A (en) 1984-12-17 1985-12-16 Antiviral and anti-tumor cyclohexadienone compositions

Country Status (3)

Country Link
EP (1) EP0205576A1 (en)
CA (1) CA1257281A (en)
WO (1) WO1986003738A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW200829234A (en) * 2007-01-08 2008-07-16 Golden Biotechnology Corp Antrodia camphorata isophorone extract

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4162309A (en) * 1978-04-10 1979-07-24 Calvin Natasha I Water soluble extracts of certain marine red algae and processes for use thereof

Also Published As

Publication number Publication date
EP0205576A1 (en) 1986-12-30
WO1986003738A1 (en) 1986-07-03

Similar Documents

Publication Publication Date Title
US4808590A (en) Antiviral, antitumor and antifungal compositions and their methods of use
Goda et al. Inhibitors of prostaglandin biosynthesis from Dalbergia odorifera
US4708962A (en) Antiviral and antitumor cyclohexadienone compositions
US4859782A (en) Misakinolide compositions and their derivatives
FI62316C (en) FOERFARANDE FOER FRAMSTAELLNING AV DI- ELLER TRISUBSTITUERADE ESTRAR AV DAUNORUBICINDERIVAT VILKA AER ANVAENDBARA VID BEHANDLING AV TUMOERER
CA1257281A (en) Antiviral and anti-tumor cyclohexadienone compositions
JP2005179339A (en) New compound and medicinal composition
US4921873A (en) Antiviral and antitumor cyclohexadienone compositions
EP0272810A2 (en) Antitumor and antiviral alkaloids
EP0208714B1 (en) Antiviral chamigrene derivative
US5578646A (en) Pharmaceutically acceptable anthracene compounds
US4801606A (en) Antiviral compositions
US4755529A (en) Guaiazulene derivatives and their methods of use
JP2988937B2 (en) Novel antitumor and antiviral compositions from marine sources
US4847246A (en) Antiviral compositions derived from fireflies and their methods of use
US4801607A (en) Antiviral furanoditerpenoids
JPH01117881A (en) Antitumor and viral alkaroid
US4946869A (en) Avarol, process for its production, pharmaceutical compositions thereof, and antiviral use of the same
Nikolaeva et al. Isolation and Immunomodulant Activity of Gentiabavaroside from Gentiana barbata.
US4942180A (en) Antitumor chamigrene derivatives and their methods of use
US3840560A (en) Derivatives of 3-chloro-1,2-propanediol having antifertility activity
JPS62501357A (en) Antiviral and antitumor cyclohexadienone compositions
JP2021535223A (en) Bioactive compounds
EP0285302A1 (en) Sesquiterpenoid isocyanide composition and its methods of use
KR20050022711A (en) Acer mono leaf extracts and Phenolic compounds isolated thereof having hepatoprotective activity

Legal Events

Date Code Title Description
MKEX Expiry