4-AMINO DERIVATIVES OF MYCOPHENOLIC ACID WITH IMMUNOSUPPRESSANT ACTIVITY

Abstract: The disclosed derivatives of mycophenolic acid represented by formula (I) are therapeutic agents advantageous in the treatment of disease states indicated for mycophenolic acid and/or mycophenolate mofetil and other imunosuppressant agents.

Description: 4-AMINO DERIVATIVES OF MYCOPHENOLIC ACID WITH IMMUNOSUPPRESSANT ACTIVITY Field of the Invention The present invention relates to mycophenolic acid in which the 4-hydroxy group has been replaced by amino substituents. The invention is also directed to formulations and methods for treatment. Background Information and Related Disclosures Mycophenolic acid ("MPA") iε a weakly active antibiotic found in the fermentation broth of Penicillium brevicompactum, having the following structure. Mycop enolie Acid MPA and certain related compounds, such as mycophenolate mofetil (the morpholinoethyl ester of MPA) , having the following structure: have more recently been described aε having particularly advantageous properties as immunosuppressant drugs. Various derivatives of mycophenolic acid, their synthesis and uses in the treatment of autoimmune disorders, psoriasiε, inflammatory diseaεes, including, in particular, rheumatoid arthritiε, tumors, viruseε, and for treatment of allograft rejection, are described in U.S. Patentε Nos. 4,686,234; 4,725,622; 4,727,069; 4,748,173; 4,753,935; 4,786,637; 4,808,592; 4,861,776; 4,868,153; 4,948,793; 4,952,579; 4,959,387; 4,992,467; 5,247,083; and U.S. Patent Application Serial No. 07/927,260, filed August 7, 1992. As immunosuppressive agents, the previouεly described esters and derivatives of mycophenolic acid are useful in treating auto-immune related disorders, glomerulonephritiε and hepatitis, and in preventing allograft rejection. As anti-inflammatory agents, they are useful in treating rheumatoid arthritis. As anti-tumor agents, they are useful in treating solid tumors and malignancies of lymphoreticular origins. See alεo U.S. Patents No. 3,825,571 and 3,853,919; Japanese Pat. No. J 01290667; J. Med. Chem. , 33(2), 833-8 (1990); Austr. J. Chem. , 31(2), 353-64, (1978); and J. Anfcijbiot., 29(3), 275-85, 286-91 (1976). The disclosed compounds are described as having anti-tumor, immunosuppressive, anti-viral, anti-arthritic and/or anti-psoriatic activities. The article by J.W. Patterεon and G. Huang, Chemical Communications, 1579 (1991) describes synthetic methodology of interest with respect to εuch compoundε. The above-cited patents, publications, and the references/ publications referenced therein, are all incorporated herein by reference. SUMMARY OF THE INVENTION One aεpect of the invention concerns compounds represented by Formula I: Formula I wherein: R 1 iε hydrogen or lower alkyl; R 2 iε hydrogen, lower alkyl, -C(0)R 3 , -C(0)NRR 5 , -C0 2 R 6 , or -S0 2 R 3 where: R 3 iε hydrogen, lower alkyl, halo lower alkyl or optionally εubεtituted phenyl; R 4 iε hydrogen, lower alkyl or optionally substituted phenyl; R 5 is hydrogen, lower alkyl or optionally substituted phenyl; R 6 iε lower alkyl or optionally substituted phenyl; and R 7 is hydrogen, lower alkyl, optionally substituted phenyl, or - (CH 2 ) m -N=Y, wherein: m is an integer from two to four; and Y is lower alkylene of four to six carbon atoms or lower alkylene of three to five carbon atoms and one member that is -0-, -S-, or -N(R 8 ) - where R 8 is hydrogen or lower alkyl; are useful as therapeutic agentε, particularly for immunosuppressive, anti- inflammatory, anti-tumor, anti-viral and anti-psoriatic indications. In another aspect, the invention relates to a pharmaceutical composition containing a therapeutically effective amount of a compound of Formula I admixed with at least one pharmaceutically acceptable excipient. In still another aspect, the invention relates to a method of treating immune, inflammatory, tumor, proliferative, viral and psoriatic diεorderε in a mammal by adminiεtering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt thereof. In yet another aspect, the invention relates to the methods of preparation of compounds of Formula I. DETAILED DESCRIPTION OF THE INVENTION Definitions and General Parameters The following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein. As used herein, the term "alkyl" referε to a fully saturated monovalent radical of one to twelve carbon atoms containing only carbon and hydrogen, and which may be a cyclic, branched or straight chain radical. Thiε term iε further exemplified by radicalε such aε methyl, ethyl, t-butyl, pentyl, cyclopentyl, cyclohexyl, heptyl, cycloheptyl and adamantyl. The term "lower alkyl" refers to a monovalent alkyl radical of one to εix carbon atoms. This term iε further exemplified by such radicals aε methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, t-butyl, i-butyl (or 2-methylpropyl), isoamyl, pentyl, cyclopentyl, i-pentyl, hexyl and cyclohexyl. The term "halo" refers to fluoro and chloro, unless otherwise specified. The term "halo lower alkyl" refers to a lower alkyl radical substituted with one or more chlorine or fluorine atomε. This term iε further exemplified by εuch radicalε aε trichloromethyl, trifluoromethyl, dichloromethyl, fluoromethyl, difluoro-chloro-methyl, 3-chloropropyl and 4-trifluoro-2-chloro-butyl. The term "halomethyl" refers to a methyl radical substituted with one or more chlorine and/or fluorine atoms. This term is further exemplified by εuch radicals aε trichloromethyl, trifluoromethyl, dichloromethyl, fluoromethyl and difluoro-chloro-methyl. The term "lower alkylene" refers to a divalent alkyl radical of one to εix carbon atoms. This term is further exemplified by such radicals aε methylene, ethylene, n-propylene, i-propylene, n-butylene, t-butylene, i-butylene (or 2-methylpropylene) , isoamylene, pentylene, and n-hexylene. The term "alkoxy" means the group -OR wherein R is lower alkyl. The term "lower alkanol" means an alcohol of the formula ROH where R is a lower alkyl. This term is further exemplified by εuch alcohols as methanol, ethanol, n-propanol, i-propanol, n-butanol, t-butanol, i-butanol (or 2-methylpropanol) , pentanol, n-hexanol. The moiety "-N=Y" as defined represents a heterocycle radical εuch as pyrrolidino, piperidino, hexamethyleneimino, imidazolidino, thiazolidino, morpholino, thiomorpholino, piperazino, thiopentamethyleneimino, and the like. The term "optionally subεtituted phenyl" refers to phenyl and mono-, di-, or tri-substituted phenyl, wherein the optional substituents are lower alkyl, lower alkoxy, hydroxy, trifluoromethyl, or halo. This term iε further exemplified by εuch radicalε aε 2-chlorophenyl, 2-trifluoromethylphenyl, 4-methoxyphenyl, 4-chlorophenyl. 3,4-dimethoxyphenyl, 2-chloro-3,4-dimethoxyphenyl, 4-hydroxyphenyl, -methylphenyl, 3-t-butyIpheny1, and 4-hexyIpheny1. The term "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances in which said event or circumstance occurs and instanceε in which it does not. For example, "optionally substituted phenyl" means that the phenyl may or may not be substituted and that the deεcription includeε both unsubstituted phenyl and phenyl wherein there is substitution: "optionally" followed by "converting the free base to the acid addition salt" means that such conversion may or may not be carried out in order for the procesε described to fall within the invention, and the invention includes those processeε wherein the free base iε converted to the acid addition salt and those procesεes in which it is not. A "pharmaceutically acceptable salt" may be any salt derived from an inorganic or organic acid or base. Salts may be derived from acids or bases. The acid addition saltε are derived from inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid (giving the sulfate and bisulfate salts) , nitric acid, phosphoric acid and the like, and organic acids εuch as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethaneεulfonic acid, εalicylic acid, p-toluenesulfonic acid and the like. The base addition salts are derived from inorganic bases such aε sodium hydroxide, potassium hydroxide, lithium hydroxide, ammonia, calcium hydroxide, magnesium hydroxide and the like. Cations derived from organic baseε include those formed from primary, secondary and tertiary amines, such as isopropylamine, diethylamine, trimethylamine, triethylamine, pyridine, cyclohexylamine, ethylene diamine, monoethanolamine, diethanolamine, triethanolamine and the like. As used herein, the term "inert organic solvent" or "inert solvent" means a solvent inert under the conditions of the reaction being described in conjunction therewith (including, for example, benzene, toluene, acetonitrile, tetrahydrofuran, diethyl ether, chloroform, methylene chloride, pyridine, xylene, dimethylformamide, 1,4-dioxane, dichloromethane, and the like) . As used herein, the term "treatment" or "treating" means any treatment of a disease in a mammal, and includes: (i) preventing the disease, that is, causing the clinical symptoms of the disease not to develop; (ii) inhibiting the diseaεe, that iε, arresting the development of clinical symptoms; and/or (iii) relieving the disease, that is, causing the regression of clinical symptoms. As used herein, the term "effective amount" means a dosage sufficient to provide treatment. This will vary depending on the patient and the treatment being effected. Unless specified to the contrary, the reactions deεcribed herein take place at atmospheric pressure over a temperature range from about -20°C to about 100°C, more preferably from about 10°C to about 50°C, and most preferably at about room temperature. Isolation and purification of the compounds and intermediateε deεcribed herein can be effected, if deεired, by any suitable separation or purification procedure εuch as, for example, filtration, extraction, crystallization, column chromatography, thin-layer chromatography or thick-layer chromatography, or a combination of theεe procedureε. Specific illustrations of suitable separation and isolation procedures can be found by reference to the exampleε hereinbelow. However, other equivalent εeparation or iεolation procedures can, of course, alεo be used. Nomenclature The compounds of Formula I will be named using the numbering syεtem illuεtrated below: The compoundε of the preεent invention are prepared aε the E (or Entgegen) configurational iεomer. Following are exampleε of how εome repreεentative compoundε of Formula I are named. The compound of Formula I where R 1 , R 2 and R 7 are hydrogen is named " (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4- methyl-4-hexenoic acid". The compound of Formula I where R 1 and R 2 are hydrogen, and R 7 is methyl iε named "methyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate" . The compound of Formula I where R 1 and R 2 are hydrogen, and R 7 iε morpholinoethyl iε named "2- (morpholin-4-yl)ethyl (E) -6- (l,3-dihydro-4- amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl- -hexenoate" . The compound of Formula I where R 1 is hydrogen, R 2 is methyl, and R 7 is hydrogen is named " (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl- 3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid". The compound of Formula I where R 1 iε hydrogen, R 2 is -C(0)R 3 , R 3 iε -CF 3 , and R 7 iε hydrogen iε named " (E) -6- [l,3-dihydro-4- (trifluoroacetyl) amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoic acid". The compound of Formula I where R 1 is hydrogen, R 2 is -C(0)NRR 5 where R 4 and R 5 are methyl, and R 7 is hydrogen iε named " (E) -6- (l,3-dihydro-4- [3,3-dimethylureido] -6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid". The compound of Formula I where R 1 iε hydrogen, R 2 iε -C(0)NRR 5 where R 4 iε hydrogen and R 3 iε 4 -methoxyphenyl , and R 7 iε hydrogen iε named " (E) -6- (l,3-dihydro-4- [3- (4 -methoxyphenyl) -ureido] -6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid". PREPARATION OF COMPOUNDS OF FORMULA I The compounds of Formula I are prepared from a common intermediate, the (E) -6- (l,3-dihydro-4-isocyanato-6-methoxy-7-methyl-3-oxoisobenzofuran- 5-yl) -4-methyl-4-hexenoate esters of Formula (7), the structure of which is shown below: where R 7 is lower alkyl. The compounds of Formula (7) are then converted to the compounds of Formula I by several different εynthetic pathwayε, depending on the deεired substitution at the 4-position and the definition of R 7 . Many of the eεterification routeε and/or final esterification steps for the esterε of the 4-εubεtituted derivativeε of mycophenolic acid are deεcribed in U.S. Patent Noε. 4,686,234; 4,725,622; 4,727,069; 4,748,173; 4,753,935; 4,861,776; and the pending application entitled "Direct Esterification of Mycophenolic Acid", Serial No. 07/911635, filed July 10, 1992 (by inventors working in the εame research organization as that of the present applicants, and subject to an obligation of asεignment to the same assignee as in the present application) all previously incorporated herein by reference. By εubstituting the acids of Formula I for mycophenolic acid or its acid derivativeε aε deεcribed in the above referenceε, the esterification routes and/or final stepε described may likewise be used. Starting Materials Mycophenolic acid is commercially available, for example from Ajinomoto Company Incorporated of Tokyo, Japan. It can be made, for example, as described in U.S. Patent No. 4,452,891, incorporated herein by reference. Preoaration of Intermediateε of Formula (7) The preparation of a compound of Formula (7) is shown in Reaction Scheme I below. REACTION SCHEME I CO C23 C 3 CO C5} C6} C 7. ) where R 7 is lower alkyl. Preparation of Coπrpoundε of Formula (2) Mycophenolic acid, the compound of Formula (1) , is commercially available. Mycophenolic acid iε reacted with a large excess of an alcohol of the formula R 7 OH, where R 7 is lower alkyl, preferably methanol, with catalytic amounts of an acid catalyst, (such as methane sulfonic acid, sulfuric acid, hydrochloric acid and p-toluene sulfonic acid) , preferably p-toluene-sulfonic acid) . The reaction iε carried out in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 1 to 7 days, preferably about 24 hours. The reaction product, a lower alkyl ester of mycophenolic acid, a compound of Formula (2) where R 7 iε lower alkyl, is isolated and purified by conventional means. Preparation of Compounds of Formula (3) A compound of Formula (2) , where R 7 is lower alkyl, in an inert solvent, preferably chloroform or dichloromethane, is reacted with a slight excess, preferably about 1.1 molar equivalents, of a εulfonic anhydride, (εuch aε a halo lower alkyl εulfonic anhydride, halomethyl εulfonic anhydride, or halosulfonic anhydride, or preferably trifluoromethane εulfonic anhydride or fluoroεulfonic anhydride) or a sulfonyl halide, (such aε trifluoromethyl sulfonyl bromide, preferably trifluoromethyl sulfonyl chloride) , in the presence of about 1 to 3 molar equivalents, preferably about 2 molar equivalents, of a tertiary organic base, preferably pyridine. The reaction is carried out in the temperature range from about -20°C to 20°C, preferably at about 0°C, for about 15 to 45 minutes, preferably about 30 minutes. The trifluoromethyl sulfonyl reaction product, a compound of Formula (3) where R 7 is lower alkyl, iε isolated and purified by conventional means. Preparation of Compounds of Formula (4) A compound of Formula (3), where R 7 is lower alkyl, is reacted with about 1 to 3 molar equivalents, preferably about 1.85 molar equivalents, of potasεium cyanide, in the presence of a catalytic amount of a triarylphosphine palladium complex, preferably tetrakiε(triphenylphosphine) palladium, in an organic solvent, preferably 1,4-dioxane. The reaction iε carried out in the temperature range from about 70°C to 130°C, preferably at about the reflux temperature of 1,4-dioxane, for about 10 to 30 hourε, preferably about 18 hourε. The cyano reaction product, a compound of Formula (4) where R 7 is lower alkyl, is isolated and purified by conventional means, preferably with extraction by an organic solvent and column chromatography. Preparation of Compounds of Formula (5) A compound of Formula (4) , where R 7 is lower alkyl, is hydrolyzed by reacting it with about 1 to 10 molar equivalents, preferably about 4 molar equivalents, of an inorganic base (e.g., sodium hydroxide, lithium hydroxide, or potassium hydroxide, preferably sodium hydroxide,) in a large exceεε of a protic εolvent, preferably about a 3:2 water:methanol εolution. The reaction is carried out in the temperature range from about 40°C to 130°C, preferably at about reflux, for about 1 to 3 hourε, preferably about 2 hours. The reaction solution is distilled to remove approximately 30% of the volume of solvent added, and an additional amount of about 1 to 1.6 molar equivalents, preferably about 1.3 molar equivalents, of an inorganic base (e.g., sodium hydroxide, lithium hydroxide, or potasεium hydroxide, preferably εodium hydroxide,) is added, and the reaction is continued in the temperature range from about 40°C to 130°C, preferably at about reflux temperature, for about 1 to 3 days, preferably about 2 days. The reaction product, E-6- (1,3-dihydro-4-carboxy-6-methoxy-7-methyl-3-oxoisobenzofuran- 5-yl) -4-methyl-4-hexenoic acid, the compound of Formula (5), is isolated and purified by conventional meanε. Alternatively, the compound of Formula (5) may be prepared by reacting a corresponding compound of Formula (3) with a catalytic amount of 1,1' -Bis (diphenylphoεphine) ferrocene palladium dichloride in a large excesε of an alkanol (preferably methanol) in an organic solvent (preferably trimethyl formamide) with a slight exceεε, preferably 1.01 molar equivalentε, of an organic baεe (preferably triethylamine) , under a carbon monoxide atmoεphere of increaεed pressure of about 400-1000 PSI, preferably at about 600 PSI. The reaction product, which iε a dieεter of a compound of Formula (5) , is then hydrolyzed by reacting it with about 1 to 10 molar equivalents, preferably about 4 molar equivalents, of an inorganic base, preferably aqueous lithium hydroxide, in a large excesε of a protic solvent, preferably 4:1 methanol/water solution. The solution iε heated to a temperature range from about 30°C to 80°C, preferably from about 50°C to 60°C, for about 1 to 10 hourε, preferably for about 2 to 6 hourε. The reaction product, E-6- (l,3-dihydro-4-carboxy-6-methoxy-7- methyl-3-oxo-5-iεbenzofuranyl) -4-methyl-4-hexenoic acid, the compound of Formula (5), is isolated and purified by conventional means. Preparation of Compounds of Formula (6) E-6- (l,3-dihydro-4-carboxy-6-methoxy-7-methyl-3-oxo-5- isbenzofuranyl) -4-methyl-4-hexenoic acid, the compound of Formula (5), is reacted in a large excess of a lower alkanol of the formula R 7 OH, preferably methanol, with catalytic amounts of an acid catalyst, preferably p-toluene-sulfonic acid. The reaction is carried out in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 4 hourε to 3 dayε, preferably about 24 hours. The reaction product, a corresponding lower alkyl ester compound of Formula (6) where R 7 is lower alkyl, is isolated and purified by conventional means. Preparation of Compounds of Formula (7) A compound of Formula (6) , where R 7 is lower alkyl, is reacted with about 1 to 3 molar equivalents, preferably about 2 molar equivalents, of an organic base, preferably triethylamine, in a large excess of an organic solvent, preferably dimethylformamide, and about 1 to 2 molar equivalents, preferably about 1.3 molar equivalentε, of an alkyl or phenyl haloformate or of a dialkyl or diphenyl halophosphate, preferably diphenyl chlorophosphate, in the temperature range from about -20°C to 20°C, preferably at about 0°C. The reaction mixture is allowed to warm to the temperature range from about 0°C to 40°C, preferably at about 20°C, and maintained there for about 0.5 to 2 hours, preferably about 1 hour. The reaction mixture iε recooled to the temperature range from about -20°C to 20°C, preferably at about 0°C, a large excess of sodium azide added, and the temperature preferably maintained at about 0°C for about 10 to 30 hours, preferably about 18 hours. The 4-isocyanato reaction product, a compound of Formula (7) where R 7 is lower alkyl, is isolated and purified by conventional means. Alternatively, a compound of Formula (6) iε reacted with about 1 to 3 molar equivalentε, preferably about 2 molar equivalentε, of an organic base, preferably triethylamine, in a large excess of an organic solvent, preferably dimethylformamide, and with a slight exceεε, preferably 1.2 molar equivalentε, of a diphenyl or dialkyl phoεphoroazide, preferably diphenyl phoεphoroazide, in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 12 to 36 hourε, preferably for about 24 hours. The iεocyanato reaction product, a compound of Formula (7) where R 7 iε lower alkyl, is isolated and purified by conventional means. Preparation of Compounds of Formula I where R'. R 2 . and R 7 are all Hydrogen The compounds of Formula I where R 1 , R 2 , and R 7 are all hydrogen (designated aε compoundε of Formula IA) are prepared from the compoundε of Formula (7) aε shown in Reaction Scheme II below. REACTION SCHEME II C7D IA where R 7 is lower alkyl. Preparation of Formula IA A compound of Formula (7) , where R 7 iε lower alkyl, is reacted with about 1 to 20 molar equivalents, preferably 10 molar equivalents, of an inorganic baεe, preferably lithium hydroxide monohydrate, in a protic εolvent, preferably 3:10 water:1,4-dioxane. The reaction iε carried out in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 1 to 3 hourε, preferably about 2 hours. The reaction product, (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl- 4-hexenoic acid, the compound of Formula IA, iε isolated and purified by conventional means, preferably column chromatography. Preparation of Compounds of Formula IB The compounds of Formula I where R 1 iε hydrogen and R 2 iε -C(0)NR 4 R 5 (deεignated as compoundε of Formula IB) are prepared from the compoundε of Formula (7) aε εhown in Reaction Scheme III below. REACTION SCHEME III C7} IB Preparation of Formula IB A compound of Formula (7) where R 7 iε lower alkyl iε reacted with a large exceεε of an amine of the formula HNR 4 R 5 , where R 4 and R 5 are aε defined in the Summary of Invention, for example, methylamine, dimethyla ine, methylphenylamine, ammonia, and the like, in an inert organic εolvent, preferably tetrahydrofuran. The reaction iε carried out in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 30 minuteε to 2 hours, preferably about 1 hour. The reaction product, a 4-ureido ester of Formula IB where R 7 iε lower alkyl, is isolated and purified by conventional means. Preparation of Formula IB where R 7 is hydrogen An ester of Formula IB where R 7 is lower alkyl is hydrolyzed by reacting with about 1 to 10 molar equivalents, preferably about 4 molar equivalentε of an inorganic baεe, preferably aqueous lithium hydroxide, in a large excesε of an organic εolvent, preferably 4:1 methanol/water. The solution is heated to a temperature range from about 30°C to 80°C, preferably from about 50°C to 60°C, for about 1 to 10 hours, preferably for about 2 to 6 hourε. The reaction product, a 4-ureido acid compound of Formula IB where R 7 is hydrogen, is isolated and purified by conventional means. Preparation of Compounds of Formula I where R' is Hydrogen and R 2 iε -C(0)R 3 The compoundε of Formula I where R 1 iε hydrogen and R 2 is -C(0)R 3 (deεignated as compounds of Formula IC) , are prepared from the compoundε of Formula IA as shown in Reaction Scheme IV below. REACTION SCHEME IV IA IA' IC where R 7 is lower alkyl. Preparation of Compounds of Formula IA . a Compound of Formula I wherein R 1 and R 2 are hydrogen, and R 7 is lower alkyl (E) -6- (1,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5- yl) -4-methyl-4-hexenoic acid, the compound of Formula IA, is esterified with a lower alkanol of the formula R 7 OH, as described in the preparation of a compound of Formula (2) to give the reaction product, a lower alkyl ester of (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoisobenzofuran- 5-yl) -4-methyl-4-hexenoic acid, a compound of Formula IA . Preparation of Compounds of Formula IC where R 7 iε Lower Alkyl A compound of Formula IA iε reacted in a large excess of an inert organic εolvent, preferably dichloromethane, with about 1 to 6 molar equivalentε, preferably about 2.5 molar equivalentε, of an anhydride of the formula (R 3 C(0)) 2 0, or an acyl chloride of the formula R 3 C(0)C1, where R 3 is as defined in the Summary of the Invention. The reaction is carried out in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 30 minutes to 2 hourε, preferably about 1 hour. The reaction product, an a ido ester of Formula IC where R 7 iε lower alkyl, iε isolated and purified by conventional means, preferably by recrystallization. Preparation of Formula IC where R 7 is Hydrogen A compound of Formula IC where R 7 is lower alkyl is hydrolyzed aε deεcribed in the preparation of a compound of Formula IB where R 7 iε hydrogen to give a 4-amido compound of Formula IC where R 7 is hydrogen. Preparation of Compounds of Formula I where R' is Lower Alkyl and R 2 is -C(Q)R 3 The compounds of Formula I where R 1 is lower alkyl and R 2 is -C(0)R 3 (designated as compoundε of Formula ID) are prepared from the compoundε of Formula IC where R 7 iε lower alkyl as shown in Reaction Scheme V below. REACTION SCHEME V IC ID where R 7 is lower alkyl. Preparation of Formula ID wherein R' and R 7 are Lower Alkyl A compound of Formula IC where R 7 is lower alkyl is reacted in the presence of about 1 to 10 molar equivalents, preferably about 4.5 molar equivalentε, of a mild baεe, preferably potaεεium carbonate, and with about 1 to 10 molar equivalents, preferably about 4 molar equivalents, of a lower alkyl bromide or iodide, preferably an iodide, in an inert organic solvent, preferably dimethylformamide. The reaction is carried out in the temperature range from about 0°C to 40°C, preferably at about 20°C, for about 12 to 48 hourε, preferably about 24 hours. The organic layer is dried, and then concentrated to an oil, to give an amide ester of Formula ID where R 1 and R 7 are both lower alkyl. Preparation of Formula ID wherein R' is Lower Alkyl and R 7 is Hydrogen A compound of Formula ID where R 7 is lower alkyl is hydrolyzed as described in the preparation of a compound of Formula IB to give a carboxylic acid of Formula ID where R 7 is hydrogen. Preparation of Compounds of Formula I where R' is Lower Alkyl, and R 2 and R 7 are Hydrogen The compounds of Formula I where R 1 is lower alkyl, and R 2 and R 7 are hydrogen (deεignated as compounds of Formula IE) , are prepared from the compounds of Formula ID where R 7 is hydrogen as shown in Reaction Scheme VI below. REACTION SCHEME VI ID IE Preparation of Formula IE where R 1 iε Lower Alkyl An amido eεter of Formula ID iε hydrolyzed by reacting with about 1 to 10 molar equivalentε, preferably about 4 molar equivalentε of an inorganic baεe (for example sodium hydroxide, preferably lithium hydroxide), in a large excess of an organic solvent, preferably 4:1 methanol/water. The solution iε heated to a temperature range from about 50°C to 100°C, preferably from about 60°C to 80°C, for about 4 to 24 hourε, preferably for about 12 hourε. The reaction product, a 4-alkylamino acid compound of Formula IE, iε iεolated and purified by conventional means. Preparation of Compoundε of Formula I where R 7 is Lower Alkyl. Optionally The compounds of Formula I where R 7 is lower alkyl, optionally substituted phenyl, or -(CH 2 ) m -N=Y (i.e., ester derivatives) may be prepared from the corresponding compounds of Formula I where R 7 is hydrogen, including compounds of Formulae IA, IB, IC, ID, and IE, by conventional meanε, for example aε deεcribed in the preparation of a compound of Formula (2) . Preferred Preparation of Eεterε of Formula I where R 7 is -(CH,) m -N--Y In a preferred procedure, a compound of Formula I where R 7 is hydrogen is esterified with an heterocyclic a inoalkyl alcohol of the formula R 7 OH, where R 7 is - (CH 2 ) m -N=Y, in which m and Y are aε defined in the Summary of the Invention, by the direct esterification procedure described in the pending application entitled "Direct Esterification of Mycophenolic Acid", Serial No. 07/911635, filed July 10, 1992. In the direct esterification route, an acid compound of Formula I where R 7 iε hydrogen iε eεterified by refluxing in an inert organic εolvent capable of azeotropic removal of water (such as toluene, xylene, or a mixture thereof) in the presence of a slight excess (between 1.01 to 1.20 molar equivalents, and preferably, 1.05 to 1.06 molar equivalentε) of a heterocyclic aminoalkyl alcohol of the formula HO(CH 2 ) m -N=Y. Water generated by the reaction is removed azeotropically. For example, with toluene as the solvent: 1) the reaction takes place with (a) a reaction time of 20 to 120 hourε, preferably 50 to 100 hours and most preferably 100 hours and (b) an initial pot temperature range of 114 to 120°C increaεing to a final pot temperature range of 118 to 130°C, preferably an initial pot temperature range of 115 to 118°C increasing to a final pot temperature range of 118 to 125°C, each depending on solute concentration and atmospheric pressure, and most preferably an initial pot temperature of 116°C increasing to a final pot temperature of 121°C with a ratio of the acid compound of Formula I (where R 7 is hydrogen) to toluene of lgm:2ml at one atmosphere of presεure. The reaction product, a compound of Formula I where R 7 iε - (CH 2 ) m -N=Y, iε isolated and purified by conventional means. Salts of Compoundε of Formula I Some of the compounds of Formula I may be converted to corresponding baεe addition salts by virtue of the presence of a carboxylic acid group. The conversion is accomplished by treatment with a εtoichiometric amount of an appropriate baεe, such as potassium carbonate, sodium bicarbonate, ammonia, ethylenedia ine, monoethanolamine, diethanolamine, triethanolamine and the like. Typically, the free acid iε dissolved in a polar organic solvent such as ethanol, methanol or ethyl acetate, and the base added in water, ethanol, methanol or isopropanol. The temperature is maintained at about 0°C to 50°C. The resulting salt precipitates spontaneously or may be brought out of solution with a leεε polar εolvent. The baεe addition εaltε of the compoundε of Formula I may be decomposed to the corresponding free acids by treating with at least a stoichiometric amount of a εuitable acid, εuch aε hydrochloric acid or εulfuric acid, typically in the preεence of aqueouε εolvent, and at a temperature of between about 0°C and 50°C. The free acid form iε iεolated by conventional meanε, such aε extraction with an organic solvent. By virtue of the presence of an amine group in the 4-poεition, εome of the compounds of Formula I may be converted to the acid addition salts by the substitution of an organic or inorganic acid for the base in the above procedure. The acid salts can be decomposed to the corresponding free bases by similar treatment with an appropriate base. Preferred Processes In summary, compounds of Formula I are prepared according to the following last steps: A proceεε for preparing compoundε of Formula I, F o r mu l a I wherein : R 1 iε hydrogen or lower alkyl ; R 2 iε hydrogen, lower alkyl , -C (0) R 3 , -C (0) NR 4 R 5 , -C0 2 R 6 , or -S0 2 R 3 where : R 3 iε hydrogen, lower alkyl, halo lower alkyl or optionally εubstituted phenyl; R 4 is hydrogen, lower alkyl or optionally subεtituted phenyl; R 5 is hydrogen, lower alkyl or optionally subεtituted phenyl; R 6 iε lower alkyl or optionally substituted phenyl; and R 7 is hydrogen, lower alkyl, optionally subεtituted phenyl, or -(CH 2 ) m -N=Y, wherein: m iε an integer from two to four; and Y iε lower alkylene of four to εix carbon atomε or lower alkylene of three to five carbon atomε and one member that iε -O-, -S-, or -N(R 8 ) - where R 8 iε hydrogen or lower alkyl; or a pharmaceutically acceptable salt thereof, which comprises: a) reacting a compound of Formula I wherein R 7 is lower alkyl, optionally substituted phenyl, or - (CH 2 ) m -N=Y, with an inorganic base to form a compound of Formula I wherein R 7 is hydrogen; or b) reacting a compound of Formula I wherein R 7 is hydrogen with a compound of the formula R 7 OH to form a compound of Formula I wherein R 7 is lower alkyl, optionally substituted phenyl, or - (CH 2 ) m -N=Y, wherein: m is an integer from two to four; and Y is lower alkylene of four to six carbon atomε or lower alkylene of three to five carbon atoms and one member that iε -0-, -S-, or -N(R 8 )- where R 8 iε hydrogen or lower alkyl; or c) reacting a compound of Formula I wherein R 1 is H, R 2 is C(0)R 3 wherein R 3 is H, and R 7 is lower alkyl, with a compound of the formula HNR 4 R 5 to form a compound of Formula I wherein R 1 iε hydrogen; R 2 is -C(0)NR 4 R 5 , where R 4 and R 5 are independently hydrogen, lower alkyl or optionally subεtituted phenyl; and R 7 iε lower alkyl; or d) reacting a compound of Formula I wherein R 1 and R 2 are H with a compound of the formula (R 3 C(0) 2 0 or R 3 C(0)Cl to form a compound of Formula I wherein R 1 is hydrogen; R 2 iε -C(0)R 3 , where R 3 is lower alkyl, halo lower alkyl or optionally substituted phenyl; and R 7 is lower alkyl, optionally substituted phenyl, or - (CH 2 ) m -N=Y, ; or e) reacting a compound of Formula I wherein R 1 is H, R 2 is C(O)R 3 and R 7 iε lower alkyl, with a compound of the formula R'X, where R 1 iε lower alkyl and X is iodine or bromine, to form a compound of Formula I wherein: R 1 is lower alkyl; R 2 is -C(0)R 3 , where R 3 is lower alkyl, halo lower alkyl or optionally substituted phenyl; and R 7 is lower alkyl; or f) reacting a compound of Formula I to form a pharmaceutically acceptable salt of a compound of Formula I; or g) reacting a pharmaceutically acceptable salt of a compound of Formula I to form the corresponding free compound of Formula I; or h) reacting a pharmaceutically acceptable salt of a compound of Formula I to form another pharmaceutically acceptable salt of a compound of Formula I. Preferred Compounds Among the family of compoundε of the preεent invention, one preferred category includeε the compoundε where R 1 is hydrogen. Within thiε category a preferred group includeε the compounds where R 2 is hydrogen or -C(0)R 3 . One preferred εubgroup within this group includes compounds in which R 2 iε hydrogen. One preferred claεs within this εubgroup includes compounds in which R 7 iε hydrogen, lower alkyl, or morpholinoethyl. Another preferred εubgroup of thiε group includeε compounds in which R 2 iε -C(0)R 3 where R 3 iε halomethyl, eεpecially where R 3 iε -CF 3 . One preferred class within this subgroup includes compounds in which R 7 is hydrogen, lower alkyl, or morpholinoethyl. Yet another preferred εubgroup of this group includes compoundε in which R 2 iε lower alkyl, eεpecially where R 2 is methyl. One preferred clasε within this subgroup includes compounds in which R 7 is hydrogen, lower alkyl, or morpholinoethyl. Another preferred subgroup of this group includeε compoundε in which R 2 iε -C(0)NRR 5 . One preferred class within thiε group includeε compounds in which R 4 and R 5 are independently hydrogen or lower alkyl, especially where they are both methyl. One preferred subclaεε within thiε claεε includeε compoundε in which R 7 iε hydrogen, lower alkyl, or morpholinoethyl. At present the most preferred compounds are: (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5- yl) -4-methyl-4-hexenoic acid; and E-6- (l,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid. Utility. Testing and Administration General Utility The compounds of the present invention, the pharmaceutically acceptable saltε thereof and pharmaceutical compositions therewith (collectively the "compounds" for purposes of the following description) are useful as immunosuppresεive agents, anti-inflammatory agentε, anti- tumor agents, anti-proliferative agentε, anti-viral agentε and anti- pεoriatic agents in mammals, whether domeεtic (cattle, pigs, sheep, goats, horses) , pets (cats, dogs), or preferably humans. The compounds are inhibitors of inosine monophosphate dehydrogenase (IMPDH) and thuε inhibit de novo purine εynthesiε; they have anti-proliferative effectε (e.g., againεt εmooth muscle cells and both B and T lymphocytes) and inhibit antibody formation and the glycoεylation of cell adhesion moleculeε in ly phocyteε and endothelial cellε. Aε immunosuppresεive agentε, the compoundε are uεeful in treating auto-immune related diεorders, for example: Type I Diabetes Mellitus; Inflammatory Bowel Diεeaεe (e.g., Crohn<ε Diεeaεe and Ulcerative Colitis) ; Systemic Lupus Erythematoεus; Chronic Active Hepatitis; Multiple Sclerosis; Grave's Diεeaεe; Hashimoto<s Thyroiditis; Behcet s Syndrome; Myasthenia Gravis; Sjogren<ε Syndrome; Pernicious Anemia; Idiopathic Adrenal Insufficiency; and Polyglandular Autoimmune Syndromes Type I and II. The compounds are alεo useful as therapeutic immunosuppreεεive agentε in the treatment of Aέthma, Immunohemolytic Anemia, Glomerulonephritiε, and Hepatitiε. Preventative uεeε of the compoundε aε immunosuppressive agents include the treatment of allograft rejection, for example, in cardiac, lung, pancreatic, renal, liver, skin and corneal allografts, and prevention of Graft vs. Host Diseaεe. The compoundε are useful for inhibiting proliferative responseε to vaεcular injury, for example, εtenoεiε following an inεult to a blood veεεel wall in poεt-angioplaεty reεtenoεis, and post-cardiac by-pasε εurgery reεtenosiε. The compoundε are uεeful as anti-inflammatory agentε, for example, in treating Rheumatoid Arthritiε, Juvenile Rheumatoid Arthritis and Uveitiε. Aε anti-tumor agentε, the compoundε are uεeful in treating εolid tumors and malignancies of lymphoreticular origin. For example, the compounds' utility for treatment of solid tumorε includeε: cancers of the head and neck, including squamouε cell carcinoma; lung cancer, including εmall cell and non-small cell lung carcinoma; mediastinal tumors; eεophageal cancer, including εquamouε cell carcinoma and adenocarcinoma; pancreatic cancer; cancer of the hepatobiliary εyεtem, including hepatocellular carcinoma, cholangiocarcinoma, gall bladder carcinoma and biliary tract carcinoma; small intestinal carcinoma, including adenocarcinoma, sarcoma, lymphoma and carcinoidε; colorectal cancer, including colon carcinoma and rectal carcinoma; metastatic carcinoma; cancers of the genitourinary syεtem, including ovarian cancer, uterine sarcoma, and renal cell, ureteral, bladder, prostate, urethral, penile, testicular, vulvar, vaginal, cervical, endometrial, and fallopian tube carcinoma; breaεt cancer; endocrine εyεtem cancer; εoft tiεεue εarcomaε; malignant meεotheliomaε; skin cancer, including εquamous cell carcinoma, basal cell carcinoma and melanoma; cancer of the central nervous εyεtem; malignant bone tumorε; and plaεma cell neoplasms. As anti-tumor agents for the treatment of malignancies of lymphoreticular origin, the compoundε are uεeful in treating, for example: Lymphomas and Leukemias, including B, T and promonocyte cell line malignancies, Mycoses Fungoides, Non-Hodgkinε Lymphoma, Malignancieε of Burkitt Lymphoma Cells and other EBV-transformed B-lymphocyteε, Lymphomas resulting from Epεtein-Barr viral infections in allograft recipientε. Chronic Lymphocytic Leukemia, Acute Lymphocytic Leukemia and Hairy Cell Leukemia. Aε anti-viral agents, the compounds are useful in treating, for example: retroviruses, including Human T-leukemia Viruses, Types I and II (HTLV-1 and HTLV-2) , Human Immuno Deficiency Viruses, Types I and II (HIV-1, HIV-2) and, Human Nasopharyngeal Carcinoma Virus (NPCV) and in treating Herpes Viruεeε, including EBV infected B-lymphocytes, CMV infection, Herpeε Virus Type 6, Herpeε Simplex, Types 1 and 2, (HSV-1, HSV-2) and Herpes Zoster. As anti-pεoriatic agentε, the compoundε are useful in treating, for example, psoriasis and pεoriatic arthritis. Testing Activity testing is conducted aε deεcribed in the following referenceε, and by modifications thereof. General anti-inflammatory, anti-viral, anti-tumor, anti-psoriatic and/or immunosuppresεive activity iε associated with the inhibition of Inosine 5' -Monophosphate Dehydrogenase ("IMPDH") . In vitro asεayε measuring the inhibition of IMPDH, for example, by determining the level of NADH formation according to the method of Anderson, J.H. and Sartorelli, A.C., J". Bio2. Chem., 243:4762-4768 (1968) are predictive of such activity. Initial animal screening tests to determine anti-inflammatory activity potential include the adjuvant arthritis asεay, e.g., according to the method of Pearson, Proc. Soc. Exp. Biol . Med. , 91:95-101 (1956). Also, in vitro testε, for example thoεe using synovial explantε from patients with rheumatoid arthritis, Dayer, et al., J. Exp. Med. , 145:1399-1404 (1977) , are useful in determining whether compounds exhibit anti- inflammatory activity. Autoimmune activity is determined, for example, utilizing experimental allergic encephalomyelitis, by a modification of a procedure initially described by Grieg, et. al., J. Pharmacol . Exp. Ther. , 173:85 (1970) . Human clinical trials for efficacy in the treatment of asthma are conducted, e.g., as described by Erzurum, Leff, Cochran, et al. "Lack of benefit of methotrexate in severe, steroid-dependent asthma. A double- blind, placebo controlled study." Ann. Int. Med. , 114:353-360 (1991). Activity to prevent the rejection of organ or tissue allografts in experimental animalε iε determined, for example, as described by Hao, et al., J. Immunol . , 139:4022-4026 (1987). In addition, U.S. Patent No. 4,707,443 and EP 226062, incorporated herein by reference, also describe assays for activity in prevention of allograft rejection by detection of IL-2R levels. Human clinical trials to establiεh efficacy in preventing rejection of solid organ transplants (such as renal) are conducted, e.g., as described by Lindholm, Albrechtεen, Tufveson, et al., "A randomized trial of cyclosporin and predniεolone versuε cycloεporin, azathioprine and prednisolone in primary cadaveric renal transplantation, " Transplantation, 54:624-631 (1992). Human clinical trials for graft vs. host disease are conducted, e.g., as described by Storb, Deeg, Whitehead, et al., "Methotrexate and cyclosporin compared with cyclosporin alone for prophylaxis of acute graft versuε hoεt disease after marrow transplantation for leukemia." New England J. Med. , 314:729-735 (1986). Immunoεuppreεεive activity iε determined by both in vivo and in vitro procedures. In vivo activity is determined, e.g., utilizing a modification of the Jerne hemolytic plaque asεay, [Jerne, et al., "The agar plaque technique for recognizing antibody producing cells," Cell-bound Antibodies, Amos, B. and Kaprowεki, H. editorε (Wistar Institute Press, Philadelphia) 1963, p. 109] . In vitro activity is determined, e.g., by an adaptation of the procedure deεcribed by Greaves, et al., "Activation of human T and B lymphocytes by polyclonal mitogens," .Nature, 248:698-701 (1974). Anti-viral activity is determined, for example, by the procedure described by Smee, et al. ["Anti-Herpeεviruε Activity of the Acyclic Nucleoεide 9- (l,3-Dihydroxy-2-Propoxymethyl)Guanine, " Antimicrobial Agentε and Chemotherapy, 23 (5) :676-682 (1983)3, or as described by Planterose ["Antiviral and cytotoxic effects of mycophenolic acid," Journal of General Virology, 4:629 (1969)] . Anti-viral activity can likewise be determined by measurement of reverse transcriptaεe activity, for example, according to the method deεcribed by Chen et al., Biochem. Pharm. , 36:4361 (1987). Human clinical trialε for anti-HIV efficacy (together with clinical treatment εcenarioε) are described and cited, for example, by Sande, et al., "Antiretroviral Therapy for Adult HIV-Infected Patients," JAMA, 270 (21) :2583-2589 (1993). A large scale clinical trial can be conducted, e.g., as described by Volberding, P.A., et al. "Zidovudine in asymptomatic human immunodeficiency virus infection: a controlled trial in persons with fewer than 500 CD4 positive cells per cubic millimeter, " New England J. Med. , 322 (14) :941-949 (1990). A smaller scale (Phase I) clinical trial can be conducted, e.g., as described by Browne, et al., "2' ,3' -Didehydro-3' - deoxythymidine (d4T) in Patients with AIDS or AIDS-Related Complex: A Phase I Trial," J. Infectious Diseases, 167:21-29 (1993). Tests for syεtemic activity in pεoriaεiε can be carried out, for example, as described by Spatz, et al. , "Mycophenolic acid in psoriaεis," British Journal of Dermatology, 98:429 (1978) . Tests for anti-tumor activity can be performed, for example, as described by Carter, et al. ["Mycophenolic acid: an anticancer compound with unuεual propertieε, " Mature, 223:848 (1969)]. In vitro activity for treating stenosiε iε demonεtrated, for example, by inhibiting the proliferation of εmooth muscle cells, as eεtablished by the following human arterial smooth muscle cell proliferation assay. Human smooth muscle cells are grown in culture. A test group is treated with the teεt compound added at selected concentrationε in fresh media. Both groups receive 2μCi tritiated thymidine ( 3 HTdR) , a radioisotope label. After 24 hours, the cellε are harvested and the amount of label incorporated into DNA is counted by scintillation; this is compared for the test and control groups, the amount being proportional to cell proliferation. Inhibition of smooth muscle proliferation iε established when the test group has a lower radioisotope count than the control group. The concentrations of test compound required to inhibit proliferation by 50% (the IC 50 ) , and to inhibit proliferation by more than 95% are determined. In vivo activity for treating stenoεiε iε demonεtrated, for example, in rat and pig modelε for arterial εtenoεis. In the rat model, a test group is treated with the test compound, starting 6 days before and continuing for 14 days after injury to the left carotid artery; the test group iε compared to a control group receiving vehicle without the test compound. Injury iε achieved by a gentle perfuεion of air through a 10 mm long εection of the left artery. The right artery iε left intact. Arterial croεε-εectionε (10 μm) axe taken from both the left and right arterieε of each εubject, and the area of the vessel wall (endothelium, intima, media) is meaεured, The amount of vaεcular proliferation is calculated by subtracting the mean area of the intact, right carotid artery from the mean area of the injured, left carotid artery. Reduction in vascular proliferation iε eεtablished when the test group shows lesε proliferation than the control group. Human clinical trials for restenoεiε after coronary angioplasty are conducted, e.g., as described by Serruys, Rutεch, Heyndrickx, et al., "Prevention of reεtenoεis after percutaneouε tranεluminal coronary antioplaεty with thromboxane A^receptor blockade: a randomozed, double- blind, placebo-controlled trial." Circulation, 84:1568-80 (1991). Administration The compounds of Formula I are adminiεtered at a therapeutically effective doεage, e.g., a dosage sufficient to provide treatment for the disease states previously described. Administration of the compounds of the invention or the pharmaceutically acceptable salts thereof can be via any of the accepted modes of adminiεtration for agents that serve similar utilities. The compoundε can be uεed both prophylactically (e.g., to prevent allograft rejection) and therapeutically. While human dosage levels have yet to be optimized for the compounds of the invention, generally, a daily dose iε from about 0.01 to 100.0 mg/kg of body weight, preferably about 0.1 to 64.3 mg/kg of body weight, and moεt preferably about 0.3 to 43.0 mg/kg of body weight. Thuε, for adminiεtration to a 70 kg person, the dosage range would be about 0.7 mg to 7 g per day, preferably about 7.0 mg to 4.5 g per day, and most preferably about 21 mg to 3.0 g per day. The amount of active compound administered will, of course, be dependent on the subject and disease state being treated, the severity of the affliction, the manner and schedule of administration (e.g., oral administration one day prior to cancer chemotherapy and intravenous adminiεtration during cancer chemotherapy) and the judgment of the prescribing physician. In employing the compounds of thiε invention for treatment of the above conditions, any pharmaceutically acceptable mode of administration can be uεed. The compounds of Formula I can be adminiεtered either alone or in combination with other pharmaceutically acceptable excipients, including solid, semi-solid, liquid or aerosol dosage forms, such as, for example, tablets, capsules, powders, liquids, injectableε, suspenεionε, εuppositories, aerosols or the like. The compounds of Formula I can alεo be administered in sustained or controlled release dosage forms, including depot injectionε, oεmotic pumpε, pillε, tranεdermal (including electrotransport) patches, and the like, for the prolonged administration of the compound at a predetermined rate, preferably in unit dosage forms suitable for single administration of precise dosages. The compositions will typically include a conventional pharmaceutical carrier or excipient and a compound of Formula I or a pharmaceutically acceptable salt thereof. In addition, these compositionε may include other medicinal agentε, pharmaceutical agentε, carrierε, adjuvants, etc., such as multidrug reεiεtance modifying agentε, steroids, immunosuppressants εuch aε cyclosporine A, azathioprene, rapamycin, FK-506, brequinar, leflunomide and vincryεtine. Generally, depending on the intended mode of adminiεtration, the pharmaceutically acceptable compoεition will contain about 0.1% to 90%, preferably about 0.5% to 50%, by weight of a compound or salt of Formula I, the remainder being suitable pharmaceutical excipients, carriers, etc. One preferred manner of administration for the conditions detailed above iε oral, uεing a convenient daily doεage regimen which can be adjusted according to the degree of affliction. For such oral adminiεtration, a pharmaceutically acceptable composition is formed by the incorporation of any of the normally employed excipients, such as, for example, mannitol, lactose, εtarch, povidone, magneεium εtearate, εodium εaccharine, talcum, celluloεe, croεcarmelloεe sodium, glucose, gelatin, sucrose, magnesium carbonate, and the like. Such compositions take the form of solutionε, suspensions, tablets, diεpersible tablets, pills, capsules, powders, sustained release formulations and the like. Preferably the compositions will take the form of a pill or tablet and thus the composition will contain, along with the active ingredient, a diluent such aε lactoεe, εucrose, dicalcium phosphate, or the like; a lubricant such as magnesium stearate or the like; a disintegrant such as croscarmellose εodium or the like; and a binder such as starch, gum acacia, polyvinylpyrrolidine, gelatin, cellulose and derivativeε thereof, and the like. Liquid pharmaceutically administrable compositions can, for example, be prepared by dissolving, dispersing, etc. an active compound as defined above and optional pharmaceutical adjuvants in a carrier, such as, for example, water, saline, aqueous dextrose, glycerol, glycols, ethanol, and the like, to thereby form a solution or εuεpension. If desired, the pharmaceutical composition to be administered may alεo contain minor amounts of nontoxic auxiliary εubεtanceε εuch as wetting agentε, suspending agents, emulsifying agentε, or εolubilizing agents, pH buffering agents and the like, for example, sodium acetate, sodium citrate, cyclodextrine derivativeε, polyoxyethylene, εorbitan monolaurate or εtearate, etc. Actual methodε of preparing εuch dosage forms are known, or will be apparent, to those skilled in thiε art; for example, εee Remington ' s Pharmaceutical Sciences, Mack Publiεhing Company, Eaεton, Pennsylvania, 15th Edition, 1975. The composition or formulation to be adminiεtered will, in any event, contain a quantity of the active compound in an amount effective to alleviate the εymptomε of the subject being treated. Dosage forms or compositions containing active ingredient in the range of 0.005% to 95% with the balance made up from pharmaceutically acceptable carrier may be prepared. For oral adminiεtration, a pharmaceutically acceptable compoεition iε formed by the incorporation of any of the normally employed excipients, such as, for example pharmaceutical grades of mannitol, lactose, starch, magneεium stearate, talcum, povidone, cellulose derivativeε, croscarmellose sodium, glucose, sucrose, magnesium carbonate, sodium saccharin, talcum and the like. Such compositions take the form of εolutions, suspensions, tablets, capsules, powders, sustained release formulations and the like. Such compositions may contain 0.01%-95% active ingredient, preferably 0.1-50%. For a εolid dosage form containing liquid, the solution or εuεpenεion, in for example propylene carbonate, vegetable oils or triglycerides, iε preferably encapεulated in a gelatin capsule. Such ester solutions, and the preparation and encapsulation thereof, are disclosed in U.S. Patents Nos. 4,328,245; 4,409,239; and 4,410,545. For a liquid dosage form, the solution, e.g. in a polyethylene glycol, may be diluted with a sufficient quantity of a pharmaceutically acceptable liquid carrier, e.g. water, to be easily measured for adminiεtration. Alternatively, liquid or εemi-εolid oral formulations may be prepared by dissolving or dispersing the active compound or salt in vegetable oils, glycols, triglycerides, propylene glycol esterε (e.g. propylene carbonate) and the like, and encapsulating these solutionε or εuεpenεionε in hard or soft gelatin capsule shells. Other useful formulations include thoεe εet forth in U.S. Patents Nos. Re. 28,819 and 4,358,603. Parenteral adminiεtration iε generally characterized by injection, either εubcutaneouεly, intramuεcularly or intravenouεly. Injectableε can be prepared in conventional for ε, either as liquid solutions or suspensions, εolid forms suitable for solution or suspension in liquid prior to injection, or as emulsions. Suitable excipients are, for example, water, saline, dextrose, glycerol, ethanol or the like. In addition, if deεired, the pharmaceutical compoεitions to be administered may also contain minor amounts of non-toxic auxiliary subεtanceε εuch aε wetting or emulsifying agentε, pH buffering agents, solubility enhancerε, and the like, εuch as for example, sodium acetate, polyoxyethylene, sorbitan monolaurate, triethanolamine oleate, cyclodextrinε, etc. A more recently devised approach for parenteral administration employs the implantation of a slow-releaεe or sustained-release syεtem, such that a constant level of dosage is maintained. See, e.g., U.S. Patent No. 3,710,795. The percentage of active compound contained in εuch parenteral compositions iε highly dependent on the εpecific nature thereof, aε well aε the activity of the compound and the needs of the subject. However, percentages of active ingredient of 0.01% to 10% in solution are employable, and will be higher if the composition is a solid which will be subsequently diluted to the above percentages. Preferably the composition will compriεe 0.2-2% of the active agent in εolution. Formulationε of the active compound or a εalt may alεo be adminiεtered to the respiratory tract as an aerosol or solution for a nebulizer, or aε a microfine powder for inεufflation, alone or in combination with an inert carrier εuch aε lactoεe. In εuch a caεe, the particleε of the formulation have diameters of less than 50 microns, preferably less than 10 microns. EXAMPLES The following exampleε are given to enable those skilled in the art to more clearly understand and to practice the present invention. They should not be considered as limiting the scope of the invention, but merely as being illustrative and representative thereof. EXAMPLE 1 Preparation of Compounds of Formula (2) IA. Preparation of (2) where R 7 is Methyl A solution of 15.1 g (47.1 mmol) of (E) -6- (l,3-dihydro-4-hydroxy-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid (mycophenolic acid) and 0.7 g (3.7 mmol) of p-toluenesulfonic acid in 400 ml of methanol was allowed to stand at room temperature for 3 dayε. The mixture was concentrated under reduced presεure to approximately 75 ml and then partitioned between aqueous sodium bicarbonate and ethyl acetate. The organic phase waε further waεhed with brine and then dried over εodium εulfate. Concentration of the organic phaεe under reduced pressure gave 15.4 g (46.0 mmol, 98%) of methyl (E) -6- (l,3-dihydro-4-hydroxy-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate as a white solid, mp 104-105°C. EXAMPLE 2 Preparation of Compoundε of Formula (3) 2A. Formula (3) where R 7 iε Methyl To a 0°C solution of 4.59 g (13.7 mmol) of methyl (E) -6- (1,3-dihydro- 4-hydroxy-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate and 2.22 ml (27.4 mmol) of pyridine in 100 ml of methylene chloride waε added 2.55 ml (15.1 mmol) of trifluoromethane sulfonic anhydride dropwise. After 30 minutes, the reaction mixture was poured into IN aqueous sodium hydrogen εulfate. This mixture was extracted with dichloromethane, and the organic phase waε further washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated under reduced preεεure. Trituration of the reεidue with hexane gave 5.7 g (12.2 mmol) of methyl (E) -6- (1,3-dihydro-4-trifluoromethylεulfonyloxy-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate aε a white solid, mp 53-55°C. EXAMPLE 3 Preparation of Compounds of Formula (4) 3A. Formula (4) where R 7 is Methyl A nitrogen-flushed mixture of 5.8 g (12.4 mmol) of methyl (E)-6-(l,3- dihydro-4-trifluoromethylεulfonyloxy-6-methoxy-7-methyl-3-oxoiεobenzofuran- 5-yl) -4-methyl-4-hexenoate, 1.5 g (23.0 mmol) of potassium cyanide, and 1.11 g (0.96 mmol) of tetrakis(triphenylphoεphine) palladium in 100 ml of 1,4-dioxane waε heated at reflux for 18 hourε. Upon cooling, the mixture waε partitioned between water and ethyl acetate. The organic phase was waεhed with water εix timeε, with brine once, and then dried over magneεium εulfate. The solvent was evaporated under reduced pressure and the reεulting solid was stirred with hexane for 18 hours and then filtered off. This solid was further purified by silica gel chromatography using 5:4 hexane:ethyl acetate to give 4.0 g (11.7 mmol) of methyl (E)-6-(l,3- dihydro-4-cyano-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4- hexenoate, p 87-88°C. EXAMPLE 4 Preparation of a Compound of Formula (5) A mixture of 4.0 g (11.7 mmol) of methyl (E) -6- (l,3-dihydro-4-cyano- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl- -hexenoate and 1.86 g (46.5 mmol) of sodium hydroxide in 100 ml of 3:2 water:methanol was heated at reflux for 2 hourε. The resulting homogenous solution was diεtilled until 30 ml of distillate was recovered. An additional 0.6 g (15 mmol) of sodium hydroxide was added to the reaction εolution and it was refluxed for 2 days. Upon cooling the solution was partitioned between IN aqueous HCI and ethyl acetate. The organic phase was waεhed twice with water, once with brine, and then dried over magneεium εulfate. The εolvent waε evaporated under reduced preεεure to give a εolid. This εolid waε εtirred with hexane and then filtered off to give 3.88 g (11.1 mmol) of (E)-6-(l,3- dihydro-4-carboxy-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4- hexenoic acid as a white solid, mp 172-174°C. EXAMPLE 5 Preparation of Compounds of Formula (6) 5A. Formula (6) where R 7 is Methyl A solution of 3.88 g (11.1 mmol) of (E) -6- (l,3-dihydro-4-carboxy-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid and 0.2 g (1.0 mmol) of p-toluene εulfonic acid in methanol (60 ml) waε εtirred at room temperature for 8 hourε. The εolvent waε evaporated under reduced preεsure. The residue waε dissolved in ethyl acetate, and thiε εolution waε waεhed twice with water, once with brine, and dried over magneεium εulfate. The εolvent was evaporated under reduced presεure to give a εolid which was recrystallized from ethyl acetate to give 3.37 g (9.3 mmol) of methyl (E) -6- (l,3-dihydro-4-carboxy-6-methoxy-7-methyl-3-oxoisobenzofuran- 5-yl) - -methyl-4-hexenoate as a white εolid, mp 169-170°C. EXAMPLE 6 Preparation of Compoundε of Formula (7) 6A. Formula (7) where R 7 is Methyl To a stirred, 0°C solution of 6.0 g (16.6 mmol) of methyl (E)-6-(l,3- dihydro-4-carboxy-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4- hexenoate in 150 ml of dimethylformamide waε added 4.62 ml (33.1 mmol) of triethylamine followed by drop-wiεe addition of 4.5 ml (21.8 mmol) of diphenylchlorophoεphate. The mixture waε allowed to stir at room temperature for 1 hour and then recooled to 0°C, and treated with 10.8 g (166 mmol) of εodium azide. This mixture was εtirred for 24 hours at 0°C and then partitioned between aqueous εodium hydrogen sulfate and ethyl acetate. The organic phaεe was washed four times with water, dried over magneεium sulfate, and concentrated under reduced presεure. The reεidue was triturated with hexane to give 5.8 g of methyl (E) -6- (l,3-dihydro-4- isocyanato-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4- hexenoate. A small sample was further purified by rapid silica gel chromatography with an eluant of 1:1 hexane:ethyl acetate followed by recrystallization from hexane-ethyl acetate to give purified methyl (E) -6- (1,3-dihydro-4-iεocyanato-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4- methyl-4-hexenoate, mp 95-101°C. EXAMPLE 7 Preparation of Compoundε of Formula I 7A. Formula IA where R 1 . R 2 and R 7 are Hydrogen 2.0 g (5.5 mmol) of methyl (E) -6- (l,3-dihydro-4-carboxy-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate, the compound of Formula (6) , was treated as in the procedure in Example 6A above, to give methyl E-6- (l,3-dihydro-4-isocyanato-6-methoxy-7-methyl-3-oxoisobenzofuran- 5-yl) -4-methyl-4-hexenoate, the methyl ester of Formula (7). Instead of purifying the resulting residue as deεcribed in Example 6A, above, it waε rediεεolved in 50 ml of 1,4-dioxane and treated with 16 ml of water and 2.0 g (47.7 mmol) of lithium hydroxide monohydrate. The mixture waε stirred at room temperature for 2 hours and then partitioned between aqueous IN sodium hydrogen sulfate and ethyl acetate. The organic phase was washed twice with water, once with brine, and was dried over magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by chromatography on silica gel, using 50:40:1 hexane:ethyl acetate:acetic acid aε eluant to give 1.28 g (4.0 mmol) of (E)-6-(l,3- dihydro-4-amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4- hexenoic acid aε a white εolid, mp 130-131°C. 7B. Alternate Svntheεis of Formula IA where R'. R 2 and R 7 are Hydrogen Similarly, following the procedures of Example 7A above, but replacing the methyl eεter of (E) -6- (1,3-dihydro-4-carboxy-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate with other lower alkyl (e.g., ethyl, t-butyl, pentyl, and cyclopentyl) esters of (E)-6-(l,3- dihydro-4-carboxy-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl- - hexenoate, which may all be prepared by the methods described in Examples 1 through 6 above, (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5- yl) -4-methyl-4-hexenoic acid is obtained. EXAMPLE 8 Preparation of Compounds of Formula I 8A. Formula IA where R 1 and R 2 are hydrogen, and R 7 is methyl To a εolution of 2.5 g (7.8 mmol) of (E) -6- (l,3-dihydro-4-amino-6- methoxy-7-methyl-3-oxoi8θbenzofuran-5-yl) -4-methyl-4-hexenoic acid in 50 ml (1.234 mol) of methanol was added 0.125 g (0.66 mmol) of p-toluene sulfonic acid monohydrate. The solution was stirred at room temperature for 2 days and then concentrated to a small volume. The residue was partitioned between water and ethyl acetate. The organic layer was dried over magnesium εulfate and concentrated to a εolid. Recryεtallization of thiε solid from hexane-ethyl acetate gave 2.48 g of methyl (E) -6- (l,3-dihydro-4- amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate, mp 91-93°C. 8B. Formula IA where R 1 and R 2 are hydrogen, varying R 7 Similarly, following the procedures of Example 8A above, but replacing methanol with the following lower alkanols and optionally εubεtituted phenolε (other compounds of the formula R 7 OH) (which may be commercially obtained or prepared by methods known to those skilled in the art) : ethanol, n-propanol, isopropanol, t-butanol, iεoamyl alcohol, phenol, 2-chlorophenol, 2-trifluoromethylphenol, and 2-chloro-3,4-dimethoxyphenol; there are obtained the following respective compoundε: ethyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; n-propyl (E) -6- (1,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; isopropyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; t-butyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; iεoamyl (E) -6- (1,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; phenyl (E) -6- (1,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) - -methyl-4-hexenoate; 2-chlorophenyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7- methyl-3-oxoiεobenzo ' furan-5-yl) -4-methyl-4-hexenoate; and 2-chloro-3,4-dimethoxyphenyl (E) -6- (1,3-dihydro-4-amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl- -hexenoate. EXAMPLE 9 Preparation of Compoundε of Formula I 9A. Formula IA where R' and R 2 iε hydrogen, and R 7 is Morpholinoethyl 7g (0.02 moles) of (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid and toluene (25ml) are warmed gently to form a εolution. A εlight exceεε (1.05 molar equivalentε) of 2-morpholinoethanol (3g, 0.021 moleε) and toluene (25ml) are added. The reaction mixture is stirred for half an hour and then heated to reflux at an initial pot temperature of 117°C (which increaseε a few degrees during reflux) under a Dean-Stark trap for 80 hours. The reaction mixture is cooled, washed with water (2 X 15ml) , 10% aqueouε εodium bicarbonate (2 x 15ml) and finally with water (15ml) . The toluene layer is stripped to a volume of about 20ml in vacuo. n-hexane (30ml) iε added and the reεulting εlurry is aged at room temperature for 2 hourε. The product iε filtered, washed with n-hexane (ca. 10 ml) and dried in vacuo at 60°C to yield 2- (morpholin-4-yl)ethyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate. 9B. Formula IA where R' and R 2 are hydrogen, varying R 7 Similarly, following the procedures of Example 9A above, but replacing morpholinoethanol with the following heterocyclic aminoalkyl alcohols (other compoundε of the formula R 7 OH) (which may be commercially obtained or prepared by methods known to those εkilled in the art) : 2- (pyrrolidin-1-yl)ethanol, 2- (piperidin-1-yl)ethanol, 2- (thiazolidin-3-yl)ethanol, 3- (morpholin-4-yl)propanol, 4- (morpholin-4-yl)butanol, 2- (imidazolidin-1-yl)ethanol, and 2- (2-methyl-1,2-pyrazolidin-1-yl)ethanol; there are obtained the following reεpective compoundε: 2- (pyrrolidin-1-yl)ethyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) - -methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- (1,3-dihydro-4-amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) - -methyl- -hexenoate; 4- (morpholin-4-yl)butyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- (1,3-dihydro-4-amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) - -methyl-4-hexenoate; and 2- (2-methyl-1,2-pyrazolidin-1-yl)ethyl (E) -6- (1,3-dihydro-4-amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. EXAMPLE 10 Preparation of Compounds of Formula (I) 10A. Formula IB where R 1 is Hydrogen. R 2 is -C(Q)NR 4 R 5 . where R 4 . R 5 and R 7 are all Methyl A solution of 0.65 g (1.8 mmol) of methyl (E) -6- (1,3-dihydro- - isocyanato-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl- -hexenoate in 10 ml of tetrahydrofuran was treated with 5 ml of a solution of 40% dimethylamine in water. After 1 hour the reaction was partitioned between water and ethyl acetate. The organic phase was washed with water three times, dried over magneεium εulfate, and concentrated under reduced pressure to give 0.4 g of methyl (E) -6- [l,3-dihydro-4- (3,3-dimethylureido) - 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate, mp 116-118°C. 10B. Formula IB where R' is Hydrogen. R 2 is -C(Q)NR 4 R 5 . and R 7 is Methyl. varying R 4 and R 5 Similarly, following the procedures of Example 10A above, but replacing dimethylamine with the following compoundε of the formula HNR 4 R 5 where R 4 and R 5 are as defined in the Summary of the Invention (which may be commercially obtained or prepared by methods known to those skilled in the art) : methylamine, ammonia, diethylamine, ethylamine, ethylmethylamine, diphenylamine, phenylamine, methyIpheny1amine, butylpropylamine, and 2-chlorophenylamine; there are obtained the following respective compoundε: methyl (E) -6- (1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) - -methyl-4-hexenoate; methyl (E) -6- (1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl- 3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (1,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate, methyl (E) -6- (1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (l,3-dihydro-4- (3-butyl-3-propyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) - -methyl-4-hexenoate; and methyl (E) -6- (1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl- -hexenoate. EXAMPLE 11 Preparation of Compounds of Formula (I) 11A. Formula IB where R' is hydrogen. R 2 is -C(Q)NRR 5 , where R 4 and R 5 are methyl. and R 7 is hydrogen To a solution of 0.3 g (0.74 mmol) of methyl (E) -6- [l,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- 4-hexenoate in 7.4 ml of 4:1 methanol:water was added 0.13 g (2.96 mmol) of lithium hydroxide monohydrate. The solution was heated at 50-60°C for 4 hourε. Upon cooling, the reaction was partitioned between aqueous εodium hydrogen εulfate and ethyl acetate. The organic layer was washed with brine, dried over magnesium εulfate, and concentrated to (E)-6-[l,3- dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - 4-methyl-4-hexenoic acid. Recryεtallization from hexane-ethyl acetate gave 0.27 g (0.7 mmol) of (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid, mp 170-190°C. 11B. Formula IB where R 1 and R 7 are Hydrogen and R 2 is -C(Q)NRR 5 , varying R 4 and R 5 Similarly, following the procedure of Example 11A above, but replacing methyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7- ethyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate with: methyl (E) -6- (1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (l,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl- -hexenoate; methyl (E) -6- (1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (1,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (l,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (1,3-dihydro-4- (3-butyl-3-propyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (1,3-dihydro-4- [3- (2-chlorophenyl)ureido] -6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; there are obtained the following respective compounds: (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- (1,3-dihydro-4-ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5- yl) - -methyl-4-hexenoic acid; (E) -6- [l,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; and (E) -6- [1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid. EXAMPLE 12 Preparation of Compoundε of Formula (I) 12A. Formula IB where R 1 iε Hydrogen, R 2 is -C(0)NR 4 R 5 , and R 7 is Methyl. varying R 4 and R 5 By following the procedure of Example 8A above, but replacing E-6- (1,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl- 4-hexenoic acid with: E-6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- (1,3-dihydro-4-ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl- -hexenoic acid; (E) -6- [l,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; and (E) -6- [1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; there are obtained the following reεpective compoundε: methyl E-6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; methyl (E) -6- [l,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; methyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; methyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; methyl (E) -6- [1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; methyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; methyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; and methyl (E) -6- [l,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate. 12B. Formula IB where R' is hydrogen, R 2 is -C(Q)NR 4 R 5 . varying R 4 . R 5 and R 7 Similarly, following the procedure of Example 12A above, but replacing methanol with the following lower alkanols or optionally substituted phenols (other compounds of the formula R 7 OH) (which may be commercially obtained or prepared by methods known to those skilled in the art) : ethanol, n-propanol, isopropanol, t-butanol, iεoamyl alcohol, phenol, 2-chlorophenol, 2-trifluoromethylphenol, and 2-chloro-3,4-dimethoxyphenol; there are obtained the following reεpective compounds: ethyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; iεopropyl (E) -6- [l,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; iεoamyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl- -hexenoate; ' phenyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] - -methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- 4-hexenoate,- ethyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate,- n-propyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] - -methyl-4-hexenoate; iεopropyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; isoamyl (E) -6- [l,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7- ethyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; ethyl (E) -6- (1,3-dihydro-4-ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) - -methyl-4-hexenoate; n-propyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl- -hexenoate; iεopropyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl- -hexenoate; t-butyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl- -hexenoate; isoamyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; phenyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) - -methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- (1,3-dihydro-4-ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) - -methyl-4-hexenoate; ethyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; isopropyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; iεoamyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; 2-chlorophenyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7- ethyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; ethyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; isopropyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3-' oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; isoamyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate,- 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; ethyl (E) -6- [1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; iεopropyl (E) -6- [1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; isoamyl (E) -6- [1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [l,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- [1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-ethyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] - -methyl-4- hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-ethyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] - -methyl-4- hexenoate; ethyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [l,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; iεopropyl (E) -6- [l,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; t-butyl (E) -6- [l,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; isoamyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl- 3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl¬ s'oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl- 4-hexenoate; ethyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; iεopropyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [l,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; iεoamyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl- -hexenoate; phenyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; -chlorophenyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl- -hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate,• 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; ethyl (E) -6- [1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; iεopropyl (E) -6- [1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; isoamyl (E) • 6- [1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- [1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl- -hexenoate; 2-trifluoromethylphenyl (E) -6- [l,3-dihydro-4- (3-methyl- 3-phenyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4- hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-phenyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] - -methyl-4- hexenoate; ethyl (E) -6- [l,3-dihydro-4- (3-butyl-3-propyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (3-butyl-3-propyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; iεopropyl (E) -6- [1,3-dihydro-4- (3-butyl-3-propyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [l,3-dihydro-4- (3-butyl-3-propyl)ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; iεoamyl (E) -6- [1,3-dihydro-4- (3-butyl-3-propyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [l,3-dihydro-4- (3-butyl-3-propyl)ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate,- 2-chlorophenyl (E) -6- [1,3-dihydro-4- (3-butyl-3-propyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (3-butyl- 3-propyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (3-butyl- 3-propyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; ethyl (E) -6- [l,3-dihydro-4- (3- ( -chlorophenyl)ureido) -6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate,- isopropyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy- 7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; isoamyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; -chlorophenyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-trifluoromethyIpheny1 (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoate; and 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoate. EXAMPLE 13 Preparation of Compoundε of Formula (I) 13 . Formula IB where R' iε Hydrogen, R 2 iε -C(0)NRR 5 , and R 7 is Morpholinoethyl. varying R 4 and R 5 Similarly, by following the procedure of Example 9A above, but replacing E-6- (1,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl- -hexenoic acid with: E-6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl- -hexenoic acid; (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [l,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] - -methyl- -hexenoic acid; (E) -6- [1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; and (E) -6- [1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; there are obtained the following respective compounds: 2- (morpholin-4-yl)ethyl E-6- [1,3-dihydro-4- (3,3-dimethylureido) -6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-ethyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4- hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- [l,3-dihydro-4- (3-phenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; and 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-phenyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate. 13B. Formula IB where R' is Hydrogen, R 2 iε -C(Q)NRR 5 , varying R 4 . R 5 and E Similarly, following the procedure of Example 13A above, but replacing morpholinoethanol with the following heterocyclic aminoalkyl alcoholε (other compounds of the formula R 7 OH) (which may be commercially obtained or prepared by methodε known to thoεe εkilled in the art) : 2- (pyrrolidin-1-yl)ethanol; 2- (piperidin-1-yl)ethanol; 2- (thiazolidin-3-yl)ethanol; 3- (morpholin-4-yl)propanol; 4- (morpholin-4-yl)butanol; 2- (imidazolidin-1-yl)ethanol; and 2- ( -methyl-1,2-pyrazolidin-1-yl)ethanol; there are obtained the following respective compoundε: 2- (pyrrolidin-1-yl)ethyl (E) -6- [l,3-dihydro-4- (3,3-dimethylureido) -6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate,- 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) - 6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [l,3-dihydro-4- (3,3-dimethylureido) -6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6- methox -7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) - 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (2-methyl-l,2-pyrazolidin-l-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- 4-hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [l,3-dihydro-4- (3-methyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [l,3-dihydro-4- (3-methyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] - -methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [l,3-dihydro-4- (3-methyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (2-methyl-1,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] - -methyl-4- hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- (1,3-dihydro-4-ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- (l,3-dihydro-4-ureido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate,- 2- (2-methyl-l,2-pyrazolidin-1-yl)ethyl (E) -6- (1,3-dihydro-4-ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [l,3-dihydro-4- (3,3-diethyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E)-6- [1,3-dihydro-4- (3,3-diethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido- 6-methoxy-7-methy. -3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (2-methyl-1,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-diethyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [l,3-dihydro-4- (3-ethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [l,3-dihydro-4- (3-ethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (2-methyl-l,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-ethyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-ethyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-ethyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [l,3-dihydro-4- (3-methyl- 3-ethyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-ethyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-ethyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-ethyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4- hexenoate; 2- (2-methyl-l,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl-3-ethyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl- -hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido- 6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; 2- (2-methyl-1,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3,3-diphenyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- 4-hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] - -methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-phenyl)ureido-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (2-methyl-l,2-pyrazolidin-1-yl)ethyl (E) -6- [l,3-dihydro-4- (3-phenyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-phenyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-phenyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-phenyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-phenyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-phenyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl- 3-phenyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (2-methyl-l,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-methyl-3-phenyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl- -hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-butyl- 3-propyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-butyl- 3-propyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (3-butyl- 3-propyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (3-butyl- 3-propyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [l,3-dihydro-4- (3-butyl- 3-propyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3-butyl- 3-propyl)ureido-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (2-methyl-1,2-pyrazolidin-1-yl)ethyl (E) -6- [l,3-dihydro-4- (3-butyl- 3-propyl)ureido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro- - (3- (2-chlorophenyl)ureido) -6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate; 3- (morpholin-4-yl) ropyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate; and 2- (2-methyl-l,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (3- (2-chlorophenyl)ureido) -6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate. EXAMPLE 14 Preparation of Compounds of Formula (I) 14A. Formula IC where R' is Hydrogen, R 2 is -C(0)R 3 , where R 3 is -CF,. and R 7 is Methyl To a solution of 0.5 g (1.5 mmol) of methyl (E) -6- (1,3-dihydro-4- amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) - -methyl- -hexenoate in 5 ml of dichloromethane waε added 0.5 ml (3.5 mmol) of trifluoroacetic anhydride. After 1 hour the reaction waε partitioned between water and dichloromethane. The organic layer waε waεhed twice with water, dried over magneεium εulfate, and concentrated to a εolid. Recryεtallization of thiε solid from hexane-ethyl acetate gave 0.520 g of methyl (E) -6- [1,3-dihydro- 4- (trifluoroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate aε a white εolid, mp 107-109°C. 14B. Formula IC where R' iε Hydrogen. R 2 iε -C(Q)R 3 . where R 3 is Methyl, and R 7 is Methyl Similarly, following the procedures of Example 14A above, but replacing trifluoroacetic anhydride with acetyl chloride, the following compound was obtained: methyl (E) -6- [l,3-dihydro-4-acetamido-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] - -methyl-4-hexenoate, mp 177-179°C. 14C. Formula IC where R' is Hydrogen. R 2 iε -C(Q)R 3 , where R 3 is Hydrogen, and R 7 is Methyl A solution of methyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate (0.32 g, 1 mmol) in 3 ml formic acid was cooled to 0°C and treated with 0.45 g of carbonyldiimidazole. After 1 hour water was added and the precipitate collected by filtration. This material was recryεtallized from iεopropanol to give 0.24 g of methyl (E) -6- [l,3-dihydro-4-formamido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - 4-methyl-4-hexenoate, aε a white solid, mp 187-189°C. 14D. Formula IC where R' is Hydrogen. R 2 is -C(Q)R 3 . and R 7 is Methyl. varying R 3 Similarly, following the procedures of Example 14A above, but replacing trifluoroacetic anhydride with other compoundε of the formula (R 3 C(0)) 2 0 or of the formula R 3 C(0)C1, where R 3 iε as defined in the Summary of the Invention, (which may be commercially obtained or prepared by methods known to those skilled in the art) : there are obtained the following compounds: methyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; methyl (E) -6- [l,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; methyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate and methyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate. EXAMPLE 15 Preparation of Compounds of Formula (I) 15A. Formula IC where R 1 is Hydrogen. R 2 is -C(Q)R 3 , where R 3 iε -CF,. and R 7 iε Hydrogen Similarly, by following the procedure of Example 11A above, but εubstituting methyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl) -amino-6-methox - 7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate and methyl (E) -6- [1,3-dihydro-4-acetamido-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoate for methyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate, the following compoundε were obtained: (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid, mp 140-141°C; and (E) -6- [l,3-dihydro-4-acetamido-6-methoxy-7-methyl-3-oxoiεobenzofuran- 5-yl] -4-methyl-4-hexenoic acid, mp 206-210°C. 15B. Formula IC where R 1 is Hydrogen, R 2 iε -C(Q)R 3 . and R 7 is Hydrogen, varying R 3 Similarly, following the procedure of Example 15A above, but replacing methyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate with: methyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl- -hexenoate; methyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; methyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; and methyl (E) -6- [l,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; there are obtained the following compounds: (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (fluoroacetyl) mino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; and (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid. EXAMPLE 16 Preparation of Compounds of Formula (I) 16A. Formula IC where R' iε Hydrogen. R 2 is -C(0)R 3 . where R 3 iε -CF,, and R 7 iε Methyl Similarly, by following the procedure of Example 8A above, but replacing E-6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl-4-hexenoic acid with: methyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl- -hexenoate; methyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; methyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; methyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; and methyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; there are obtained the following respective compounds: methyl E-6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl- -hexenoate, methyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; methyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; methyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; and methyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl) -amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate. 16B. Formula IC where R' iε Hydrogen. R 2 is -C(0)R 3 . varying R 3 and R 7 Similarly, following the procedure of Example 16A above, but replacing methanol with the following lower alkanols and optionally substituted phenols (other compounds of the formula R 7 0H) (which may be commercially obtained or prepared by methods known to those εkilled in the art) : ethanol, n-propanol, isopropanol, t-butanol, isoamyl alcohol, phenol, 2-chlorophenol, 2-trifluoromethylphenol, and 2-chloro-3,4-dimethoxyphenol; there are obtained the following respective compounds: ethyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7-methyl- 3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; n-propyl (E) -6- [l,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; iεopropyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; iεoamyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl- -hexenoate; 2-chlorophenyl (E) -6- [l,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy- 7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino- 6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoate; ethyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7-methyl- 3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] - -methyl-4-hexenoate; iεopropyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [l,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; isoamyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7-methyl- 3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy- 7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- 4-hexenoate; ethyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; isopropyl (E) -6- [l,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl¬ s'oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; iεoamyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl- 3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; 2-chlorophenyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] - -methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; ethyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; isopropyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; isoamyl (E) 6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy- 7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-trifluoromethylρhenyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoate; ethyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy- 7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; iεopropyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy- 7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; isoamyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate,- phenyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- [l,3-dihydro-4- (fluorodichloroacetyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate, • 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl- -hexenoate; and 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoate. EXAMPLE 17 Preparation of Compounds of Formula (I) 17A. Formula IC where R 1 is Hydrogen. R 2 iε -C(Q)R 3 . where R 3 is -CF,. and R 7 is Morpholinoethyl Similarly, by following the procedure of Example 9A above, but replacing E-6- (1,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5- yl) -4-methyl-4-hexenoic acid with: (E) -6- [l,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl] - -methyl- -hexenoic acid; (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] - -methyl-4-hexenoic acid; and (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; there are obtained the following reεpective compoundε: 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; and 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl) - amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate. 17B. Formula IC where R' iε Hydrogen. R 2 iε -C(Q)R 3 , varying R 3 and R 7 Similarly, following the procedure of Example 17A above, but replacing morpholinoethanol with the following heterocyclic aminoalkyl alcoholε (compoundε of the formula R 7 0H) (which may be commercially obtained or prepared by methodε known to those skilled in the art) : 2- (pyrrolidin-1-yl)ethanol, 2- (piperidin-1-yl)ethanol, 2- (thiazolidin-3-yl)ethanol, 3- (morpholin-4-yl)propanol, 4- (morpholin-4-yl)butanol, 2- (imidazolidin-1-yl)ethanol, and 2- (2-methyl-l,2-pyrazolidin-1-yl)ethanol; there are obtained the following respective compounds: 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [l,3-dihydro-4- (trifluoroacetyl)amino- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl- -hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino- 6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino- 6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methy1-4-hexenoate; 2- (2-methyl-l,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino- 6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [l,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl- 4-hexenoate; 2- (2-methyl-1,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (difluoroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- 4-hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino- 6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; 2- (2-methyl-l,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (fluoroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl- -hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino- 6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate; 2- (2-methyl-1,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (trichloroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4- methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methy1-4-hexenoate; and 2- (2-methyl-l,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (fluorodichloroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl-4-hexenoate. EXAMPLE 18 Preparation of Compoundε of Formula (I) 18A. Formula ID wherein R' is Methyl. R 2 is -C(0)R 3 . where R 3 is -CF3. and R 7 is Methyl To a solution of 0.35 g (0.82 mmol) of methyl (E) -6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4- methyl- -hexenoate in 4 ml of dimethylformamide was added 0.47 g (3.40 mmol) of potassium carbonate and 0.23 ml (3.69 mmol) of iodomethane. The mixture was εtirred for 24 hourε and then partitioned between ethyl acetate and water. The organic layer waε waεhed with water, dried over magneεium sulfate, and concentrated under reduced presεure to give methyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate, an oil, NMR: δ 5.22-5.17 (multiplet ("m"), 2H) ; 5.10-5.04 (broad triplet, IH) ; 3.81 (singlet ("s") , 3H) ; 3.62 (s, 3H) ; 3.42-3.27 (m, 5H) ; 2.45-2.25 (m, 5H) ; 1.75 (s, 3H) . 18B. Formula I wherein R' is Lower Alkyl. R 2 is -C(Q)R 3 . where R 3 iε -CF3, and R 7 is Methyl Similarly, following the procedures of Example 18A above, but replacing iodomethane with the following compounds of the formula R'Br or R'l where R 1 is lower alkyl (which may be commercially obtained or prepared by methodε known to thoεe εkilled in the art) : iodoethane or bromoethane, and iodoiεopropane or bromoisopropane; there are obtained the following respective compoundε: methyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; and methyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-iεopropyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate. EXAMPLE 19 Preparation of Compoundε of Formula (I) 19A. Formula ID wherein R' is Methyl. R 2 is -C(Q)R 3 , where R 3 is -CF3. and R 7 is Hydrogen Methyl (E) -6- [1,3-dihydro-4- (trifluoroacetylmethyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate, the amount of oil yielded in Example 18A above, was suεpended in 8.2 ml of 4:1 methanol:water and 0.138 g (3.28 mmol) of lithium hydroxide monohydrate was added. The mixture was heated at 50-60°C for 4 hourε. Upon cooling the reaction waε partitioned between aqueous sodium hydrogen sulfate and ethyl acetate. The organic layer waε washed with brine, dried over magnesium εulfate, and concentrated to give (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N- methyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoic acid, mp 159-160°C. 19B. Formula ID wherein R' is Lower Alkyl. R 2 is -C(0)R 3 . where R 3 is -CF3. and R 7 is Hydrogen Similarly, following the procedureε of Example 19A above, but replacing methyl (E) -6- [1,3-dihydro-4- (trifluoroacetylmethyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate with: methyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; and methyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) -N-iεopropyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; there are obtained the following reεpective compoundε: (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; and (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-iεopropyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid. 19C. Formula ID wherein R 1 is Lower Alkyl, R 2 is -C(Q)R 3 . where R 3 is -CF3. and R 7 is Methyl Similarly, by following the procedure of Example 8A above, but replacing E-6- (1,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5- yl) -4-methyl-4-hexenoic acid with: (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; and (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-isopropyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; there are obtained the following compoundε: methyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; methyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; and methyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-isopropyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate. 19D. Formula ID wherein R' is Lower Alkyl, R 2 is -C(Q)R 3 . where R 3 is -CF3. and R 7 is varied Similarly, following the procedure of Example 19C above, but replacing methanol with the following lower alkanolε and optionally substituted phenols (other compoundε of the formula R 7 OH) (which may be commercially obtained or prepared by methods known to those skilled in the art) : ethanol, n-propanol, isopropanol, t-butanol, iεoamyl alcohol, phenol, 2-chlorophenol, 2-trifluoromethylphenol, and 2-chloro-3,4-dimethoxyphenol; there are obtained the following reεpective compoundε: ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; iεopropyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; isoamyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-methyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-methyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran- 5-yl] -4-methyl-4-hexenoate; ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; iεopropyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; t-butyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate,- iεoamyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; phenyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate,- 2-chlorophenyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-ethyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-ethyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5- yl] -4-methyl-4-hexenoate; ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-iεopropyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; n-propyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-isopropyl)amino- 6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; isopropyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-isopropyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; t-butyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) -N-iεopropyl)amino- 6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate; iεoamyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-iεopropyl)amino- 6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4-hexenoate; phenyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-iεopropyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) - N-isopropyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2-trifluoromethylphenyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-iεopropyl)amino-6-methoxy-7-methyl-3-oxoiεobenzo uran-5-yl] -4-methyl-4- hexenoate; and 2-chloro-3,4-dimethoxyphenyl (E) -6- [1,3-dihydro- 4- (N- (trifluoroacetyl) -N-iεopropyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate. 19E. Formula ID wherein R' iε Lower Alkyl, R 2 iε -C(0)R 3 . where R 3 is -CF3, and R 7 is morpholinoethyl Similarly, by following the procedure of Example 9A above, but replacing E-6- (1,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5- yl) -4-methyl-4-hexenoic acid with: (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; and (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-iεopropyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid; there are obtained the following compounds: 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N- methyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-ethyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4- hexenoate; and 2- (morpholin-4-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-iεopropyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate. 19F. Formula ID wherein R 1 iε Lower Alkyl. R 2 iε -C(Q)R 3 . where R 3 is -CF3. and R 7 is varied Similarly, following the procedure of Example 19FE above, but replacing morpholinoethanol with the following heterocyclic aminoalkyl alcoholε (other compounds of the formula R 7 OH) (which may be commercially obtained or prepared by methods known to those εkilled in the art) : 2- (pyrrolidin-1-yl)ethanol; 2- (piperidin-1-yl)ethanol; 2- (thiazolidin-3-yl)ethanol; 3- (morpholin-4-yl)propanol; 4- (morpholin-4-yl)butanol; 2- (imidazolidin-1-yl)ethanol; and 2- (2-methyl-1,2-pyrazolidin-1-yl)ethanol; there are obtained the following respective compounds: 2- (pyrrolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-methyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate,- 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-methyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-methyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-methyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-methyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4- hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) N-methyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (2-methyl-l,2-pyrazolidin-l-yl)ethyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran- 5-yl] -4-methyl-4-hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) - N-ethyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-ethyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-ethyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 3- (morpholin-4-yl) ropyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-ethyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-ethyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) N-ethyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- - hexenoate; 2- (2-methyl-1,2-pyrazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5- yl] -4-methyl-4-hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) - N-iεopropyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-isopropyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-iεopropyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4- hexenoate; 3- (morpholin-4-yl)propyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-isopropyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4- hexenoate; 4- (morpholin-4-yl)butyl (E) -6- [l,3-dihydro-4- (N- (trifluoroacetyl) - N-iεopropyl)amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] -4-methyl- - hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) - N-isopropyl)amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4- hexenoate; and 2- (2-methyl-l,2-pyrazolidin-l-yl)ethyl (E) -6- [1,3-dihydro- 4- (N- (trifluoroacetyl) -N-iεopropyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate. EXAMPLE 20 Preparation of Compounds of Formula (I) 20A. Formula IE wherein R' is Methyl. and R 2 and R 7 are Hydrogen Similarly, by following the procedure of Example 11A above, but εubεtituting (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl- -hexenoic acid for methyl (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoate gave (E) -6- (1,3-dihydro-4- methylamino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid, mp 121-124°C. 20B. Formula IE where R' is Lower Alkyl, and R 2 and R 7 are Hydrogen Similarly, following the procedure of Example 20A above, but replacing (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-methyl)amino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoic acid with: (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-ethyl)amino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; and (E) -6- [1,3-dihydro-4- (N- (trifluoroacetyl) -N-iεopropyl)amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl] - -methyl-4-hexenoic acid; there are obtained the following reεpective compoundε: (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; and (E) -6- (l,3-dihydro-4-iεopropylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) - -methyl-4-hexenoic acid. EXAMPLE 21 Preparation of Compounds of Formula (I) 21A. Formula IE wherein R' iε Lower Alkyl, R 2 iε Hydrogen and R 7 iε Methyl Similarly, by following the procedure of Example 8A above, but replacing E-6- (1,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoisobenzofuran-5- yl) -4-methyl-4-hexenoic acid with: (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid and (E) -6- (l,3-dihydro-4-isopropylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; there are obtained the following respective compounds: methyl E-6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; methyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; and methyl (E) -6- (l,3-dihydro-4-iεopropylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid. 21B. Formula IE where R 2 is Hydrogen, varying R' and R 7 Similarly, following the procedure of Example 21A, above, but replacing methanol with the following lower alkanols and optionally εubεtituted phenols (other compounds of the formula R 7 OH) (which may be commercially obtained or prepared by methods known to those εkilled in the art) : ethanol, n-propanol, isopropanol, t-butanol, isoamyl alcohol, phenol, 2-chlorophenol, 2-trifluoromethylphenol, and 2-chloro-3,4-dimethoxyphenol,• there are obtained the following respective compounds: ethyl (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; n-propyl (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; isopropyl (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; t-butyl (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; iεoamyl (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; phenyl (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- (l,3-dihydro-4-methylamino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4- hexenoate,- ethyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; n-propyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; iεopropyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; t-butyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; iεoamyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; phenyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2-chloro-3,4-dimethoxyphenyl (E) -6- (1,3-dihydro-4-ethylamino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) - -methyl-4-hexenoate; ethyl (E) -6- (l,3-dihydro-4-iεopropylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; n-propyl (E) -6- (l,3-dihydro-4-iεopropylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; iεopropyl (E) -6- (l,3-dihydro-4-isopropylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; t-butyl (E) -6- (l,3-dihydro-4-iεopropylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; iεoamyl (E) -6- (l,3-dihydro-4-iεopropylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; phenyl (E) -6- (1,3-dihydro-4-isopropylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2-chlorophenyl (E) -6- (l,3-dihydro-4-isopropylamino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2-trifluoromethylphenyl (E) -6- (l,3-dihydro-4-isopropylamino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate and 2-chloro-3,4-dimethoxyphenyl (E) -6- (l,3-dihydro-4-iεopropylamino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. EXAMPLE 22 Preparation of Compounds of Formula (I) 22A. Formula IE wherein R 1 is Lower Alkyl, R 2 is hydrogen, and R 7 iε Morpholinoethyl Similarly, by following the procedure of Example 9A, above, but replacing E-6- (1,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl-4-hexenoic acid with: (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl-4-hexenoic acid; (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid and (E) -6- (l,3-dihydro-4-isopropylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid; there are obtained the following respective compounds: 2- (morpholin-4-yl)ethyl E-6- (l,3-dihydro-4-methylamino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl- -hexenoate; 2- (morpholin-4-yl)ethyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid; and 2- (morpholin-4-yl)ethyl (E) -6- (l,3-dihydro-4-iεopropylamino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid. 22B. Formula IE where R 2 iε Hydrogen, varying R' and R 7 Similarly, following the procedure of Example 22A above, but replacing morpholinoethanol with the following heterocyclic lower alkanolε (other compoundε of the formula R 7 OH) (which may be commercially obtained or prepared by methodε known to those εkilled in the art) : 2- (pyrrolidin-1-yl)ethanol, 2- (piperidin-1-yl)ethanol, 2- (thiazolidin-3-yl)ethanol, 3- (morpholin-4-yl)propanol, 4- (morpholin-4-yl)butanol, 2- (imidazolidin-1-yl)ethanol and 2- (2-methyl-1,2-pyrazolidin-1-yl)ethanol; there are obtained the following respective compounds: 2- (pyrrolidin-1-yl)ethyl (E) -6- (l,3-dihydro-4-methylamino-6-methoxy- 7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- (1,3-dihydro-4-methylamino-6-methoxy- 7-methyl-3-oxoiεobenzofuran-5-yl) - -methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- (l,3-dihydro-4-methylamino-6-methoxy- 7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- (1,3-dihydro-4-methylamino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl- -hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- (l,3-dihydro-4-methylamino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (2-methyl-l,2-pyrazolidin-l-yl)ethyl (E) -6- (1,3-dihydro-4- methylamino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4- hexenoate; 2- (pyrrolidin-1-yl)ethyl (E) -6- (1,3-dihydro-4-ethylamino-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7- ethyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- (1,3-dihydro-4-ethylamino-6-methoxy- 7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- (l,3-dihydro-4-ethylamino-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- (1,3-dihydro-4-ethylamino-6-methoxy- 7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (2-methyl-l,2-pyrazolidin-1-yl)ethyl (E) -6- (1,3-dihydro-4- ethylamino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4- hexenoate,- 2- (pyrrolidin-1-yl)ethyl (E) -6- (1,3-dihydro-4-iεopropylamino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (piperidin-1-yl)ethyl (E) -6- (1,3-dihydro-4-iεopropylamino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (thiazolidin-3-yl)ethyl (E) -6- (1,3-dihydro-4-iεopropylamino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; 3- (morpholin-4-yl)propyl (E) -6- (l,3-dihydro-4-isopropylamino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 4- (morpholin-4-yl)butyl (E) -6- (1,3-dihydro-4-iεopropylamino-6- methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; 2- (imidazolidin-1-yl)ethyl (E) -6- (l,3-dihydro-4-isopropylamino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate; and 2- (2-methyl-1,2-pyrazolidin-1-yl)ethyl (E) -6- (l,3-dihydro-4- isopropylamino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4- hexenoate. EXAMPLE 23 Preparation of Compounds of Formula (I) where R 2 is -CO-.R 6 22A. Preparation of (E) -6- (1.3-dihvdro-4-methoxycarbonylammo-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid A solution of methyl (E) -6- (l,3-dihydro-4-iεocyanato-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate (1.0 g) in 10 ml methanol waε heated to reflux for 4 hours and then evaporated to dryness. The residue was recrystallized from acetone/hexane to give 0.41 g of methyl (E) -6- (l,3-dihydro-4-methoxycarbonylamino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate. The ester (0.35 g) and 0.05 g of LiOH-^O in 9 ml 2:1 MeoH-HjO was heated at reflux for 4 hours. The mixture was acidified, extracted with ethyl acetate, and the organic layer waε dried over MgS0 4 . The organic layer waε concentrated and the residue was further purified by silica gel chromatography (eluant 60:40:2 hexane:ethyl acetate:acetic acid) to give 0.21 g of (E) -6- (1,3-dihydro-4- methoxycarbonylamino-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl) -4-methyl- 4-hexenoic acid, mp 155-158°C. 23B. Formula I where R 2 is -C0,R 6 Similarly, following the procedure of Example 23A above, but replacing methanol with other alkanolε of Formula R*0H, other carbamates of Formula I are prepared. EXAMPLE 24 Preparation of Compounds of Formula (I) where R 2 is -SOiR 3 22A. Preparation of ( E) -6- ( 1.3-dihvdro-4-methylsulfonamido-6-methoxy-7- methyl-3-oxoisobenzofuran-5-yl) - -methyl-4-hexenoic acid To a solution of 0.66 g of methyl (E) -6- (l,3-dihydro-4-amino-6- methoxy-7-methyl-3-oxoiεobenzofuran-5-yl) -4-methyl- -hexenoate in 5 ml dichloromethane was added 0.24 ml of pyridine and 0.5 g of methanesulfonic anhydride. After 1 hour the mixture was partitioned between water and dichloromethane. The organic layer waε dried over MgS0 4 , and concentrated to give crude methyl (E) -6- (l,3-dihydro-4-methylεulfonamido-6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoate. Thiε material waε purified by εilica gel chromatography with 1:1 hexane-ethyl acetate. The purified eεter waε then treated with 0.1 g LiOH-H 2 0 in 10 ml 1:1 methanol:H 2 0 and the mixture refluxed for 1.5 hourε. After cooling, the mixture waε partitioned between dilute aqueouε HCI and ethyl acetate. The organic layer was dried over MgSO, and concentrated. The reεidue was purified on silica gel (eluant 80:80:4 EtoAc:hexane:acetic acid) to give 0.12 g of (E) -6- (l,3-dihydro-4-methylεulfonamido-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) - -methyl-4-hexenoic acid, mp 170-176°C. 24B. Formula I where R 2 is -SO..R 3 Similarly, following the procedure of Example 24A above, but replacing methanesulfonic anhydride with other sulfonating agentε, other sulfonamides of Formula I are prepared. EXAMPLE 25 Thiε example illuεtrates the preparation of a representative pharmaceutical formulation for oral adminiεtration containing an active compound of Formula I, e.g., (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl- 3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid. Ingredients Quantity per tablet, mgs. Active Compound 200 Lactose, spray-dried 148 Magneεium εtearate 2 The above ingredients are mixed and introduced into a hard-shell gelatin capsule. Other compoundε of Formula I, εuch aε thoεe prepared in accordance with Exampleε 8-24, can be uεed aε the active compound in the preparation of the orally administrable formulations of thiε example. EXAMPLE 26 This example illustrates the preparation of another representative pharmaceutical formulation for oral administration containing an active compound of Formula I, e.g., (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid. Ingredientε Quantity per tablet, mgs. Active Compound 400 Cornstarch 50 Lactose 145 Magneεium εtearate 5 The above ingredientε are mixed intimately and pressed into single scored tablets. Other compounds of Formula I, εuch as those prepared in accordance with Examples 8-24, can be used aε the active compound in the preparation of the orally adminiεtrable formulations of thiε example. EXAMPLE 27 Thiε example illuεtrateε the preparation of a repreεentative pharmaceutical formulation containing an active compound of Formula I, e.g., (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5- yl) - -methyl-4-hexenoic acid. An oral suspenεion is prepared having the following composition. Ingredients Active Compound Fumaric acid Sodium chloride Methyl paraben Granulated sugar Sorbitol (70% εolution) Veegum K (Vanderbilt Co.) Flavoring Coloringε Diεtilled water q.s. Other compounds of Formula I, such as those prepared in accordance with Exampleε 8-24, can be uεed aε the active compound in the preparation of the orally adminiεtrable formulations of thiε example. EXAMPLE 28 Thiε example illustrates the preparation of a representative pharmaceutical formulation for oral administration containing an active compound of Formula I, e.g., (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl- 3-oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid. An injectable preparation buffered to a pH of 4 iε prepared having the following compoεition: Ingredientε Active Compound 0.2 g Sodium Acetate Buffer Solution (0.4 M) 2.0 ml HCL (IN) q.ε. to pH 4 Water (diεtilled, sterile) q.s. to 20 ml Other compoundε of Formula I, εuch aε those prepared in accordance with Exampleε 8-24, can be uεed as the active compound in the preparation of the injectable formulations of this example. EXAMPLE 29 This example illuεtrateε the preparation of a repreεentative pharmaceutical formulation for topical application containing an active compound of Formula I, e.g., (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl- 3-oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid. Ingredientε gramε Active compound 0.2-10 Span 60 2 Tween 60 2 Mineral oil 5 Petrolatum 10 Methyl paraben 0.15 Propyl paraben 0.05 BHA (butylated hydroxy aniεole) 0.01 Water q.s. to 100 All of the above ingredients, except water, are combined and heated to 60°C with stirring. A εufficient quantity of water at 60°C iε then added with vigorouε εtirring to emulεify the ingredientε, and water then added q.s. 100 g. Other compounds of Formula I, such as those prepared in accordance with Examples 8-24, can be uεed as the active compound in the preparation of the topical formulations of thiε example. EXAMPLE 30 This example illustrateε the preparation of a repreεentative pharmaceutical formulation containing an active compound of Formula I, e.g., (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3-oxoiεobenzofuran-5- yl) -4-methyl-4-hexenoic acid. A εuppository totalling 2.5 grams is prepared having the following composition: Ingredients Active Compound 500 mg Witepsol H-15 * balance ("triglycerides of saturated vegetable fatty acid; a product of Riches-Nelson, Inc., New York, N.Y.) Other compounds of Formula I, εuch aε those prepared in accordance with Examples 8-24, can be used aε the active compound in the preparation of the εuppoεitory formulationε of thiε example. EXAMPLE 31 In Vitro Determination of Therapeutic Activity (Aε an Anti-Inflammatory, Anti-Viral, Anti-Tumor, Anti-Pεoriatic and/or Immunoεuppreεεive Agent) Utilizing the Inhibition of IMP Dehydrogenaεe Aεεay Thiε aεεay iε a modification of the method of Anderson, J.H. and Sartorelli, A.C., Jour. Biol . Chem, 243:4762-4768 (1968) . It measures the formation of NADH {X___ = 340 nm, e340 = 6,220 M^cπr 1 ) as Inoεine 5 ' -monophosphate ("IMP") is converted to Xanthosine 5' -monophosphate ("XMP") by the human Type II IMP dehydrogenaεe ("IMPDH") . Compounds are diεεolved and diluted in DMSO, and reaction solutions containing compoundε at 0, 0.01, 0.10, 1.0, 10, and lOOμM are prepared in diεpoεable methacrylic plastic microcuvets ( 'UV-transparent' plastic, 1 cm pathlength, 1.5 ml capacity) . The solutions (0.5-1 ml) contain the following: 0.1 M TrisHCL, pH 8.0; 0.1 M KCL; 3.0 mM EDTA; 100 μg/ml BSA; 0.05 mM IMP; 0.10 mM NAD; 10% DMSO; 5-15 nM IMPDH (0.003-0.010 units/ml; one unit of enzyme catalyzeε the formation of one μmol NADH per minute at 40°C at εaturating subεtrate concentrationε - 200 μM IMP and 400 μM NAD) . Reactions are performed at 40°C and initiated by the addition of enzyme. Mycophenolic acid (IC^ - 0.02μM) serveε aε the positive control. The reactions are monitored at 340 nm for 10 minutes in a UV/V S spectrophotometer, and rate data are collected. The 50% inhibitory value ("ICjo") is determined by fitting the fractional activitieε relative to control to the following equation on a Macintosh computer by the program Systat: Fractional activity = HSΑX/ { {X/IC 50 ) n +l) . X is the concentration of the compound, and the term n accounts for deviationε of the data from a εimple competitive inhibition model. The compounds of the present invention inhibit IMPDH when tested by this method, indicating their activity as anti-inflammatory, anti-viral, anti-tumor, anti-pεoriatic and/or immunoεuppreεεive agentε, as shown in the below table. Compoundε of Formula I were tested as shown below. R 1 R 2 R 3 R 4 R 5 R 7 R 8 IC^μM) 48 CF, >100 >100 27.6 22.3 0.154 In Vi tro Determination of Immunosuppressive Activity Utilizing Responses of Human Peripheral Blood Lymphocytes to T- and B-cell Mitogens This procedure iε a modification of a procedure initially deεcribed by Greaveε, et al. ["Activation of human T and B lymphocyteε by polyclonal mitogenε," Nature, 248:698-701 (1974)] . Human mononuclear cellε ("PBL") are εeparated from heparinized whole blood by denεity gradient centrifugation in Ficoll-Plaque (Pharmacia) . After washing, 2 x 10 5 cells/well are cultured in microtiter plates with RPMI 1640 supplemented with 5% fetal calf εerum, penicillin and εtreptomycin. PHA (Sigma) at 10 μg/ml is then added. Test materials are tested at concentrations between 10 4 and 10^, by addition to the culture at time 0. Cultures are set up in quadruplicate and incubated at 37°C in a humidified atmosphere with 7% C0 2 for 72 hours. A pulse of 0.5 μCi/well of ^-thymidine is added for the laεt 6 hourε. Cellε are collected on glaεε fiber filterε with an automatic harvester and radioactivity is meaεured by standard scintillation procedureε. The 50% inhibitory concentration ("ICio") for mitogenic εtimulation iε determined graphically. To evaluate differential effectε on T- and B-lymphocyteε, different mitogenε are uεed: PWM (Sigma) at 20 μg/ml and Staphylococcuε Protein A bound to Sepharose (SPA) (Sigma) 2 mg/ml or 14 μg/ml of Protein A. The compounds of the present invention εhow immunoεuppreεεive activity when tested by thiε method. EXAMPLE 33 Determination of Immunoεuppreεεive Activity Utilizing the Hemolvtic Plague Forming Cell Assay This procedure is a modification of "The agar plaque technique for recognizing antibody producing cellε," a procedure initially deεcribed by Jerne et al., [Cellbound Antibodies, Amos and Kaprowski editorε (Wiεtar Inεtitute Press, Philadelphia, 1963) , p. 109] . Groups of 5-6 adult C578B1/6 male mice were sensitized with 1X10 8 sheep red blood cells ("SRBC") and simultaneouεly treated with an oral doεage form of the teεt material in an aqueouε vehicle. Animals in a control group receive the same volume of vehicle. Four dayε after SRBC inoculation, spleens are dispersed in loose Ten Broeck homogenizers. The number of nucleated cellε ("WBC") iε determined and the εpleen cell suspenεion iε mixed with SRBC, guinea pig complement and agar solution at 0.5% concentration. Aliquots of the above mixture (0.1 ml) are dropped on four separate quadrants of a Petri dish and are covered with cover εlips. After two hours incubation at 37°C, areas of hemolysiε around plaque-forming cellε ("PFC") are counted with a dissecting microscope. Total WBC/εpleen, PFC/εpleen and PFC/10 6 WBC ("PPM") are calculated for each mouεe εpleen. Geometric means of each treatment group are then compared with the vehicle-treated control group. The compounds of the present invention show immunosuppreεεive activity when teεted by thiε method, aε εhown in the below table. While the preεent invention haε been described with reference to the specific embodiments thereof, it should be understood by those skilled in the art that variouε changeε may be made and equivalents may be substituted without departing from the true spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation, material, composition of matter, process, procesε step or stepε, to the objective, εpirit and εcope of the preεent invention. All εuch modificationε are intended to be within the εcope of the claimε appended hereto.

Claims: WHAT IS CLAIMED IS: 1. A compound represented by the formula: wherein: R 1 iε hydrogen or lower alkyl; R 2 iε hydrogen, lower alkyl, -C(0)R 3 , or -C(0)NR 4 R 5 , where R 3 is halomethyl, and R 4 and R 5 are independently hydrogen, lower alkyl, or optionally subεtituted phenyl; and R 7 is hydrogen, lower alkyl, optionally substituted phenyl, or - (CH 2 ) πl -N=Y, wherein: m iε an integer from two to four; and Y iε lower alkylene of four to six carbon atoms or lower alkylene of three to five carbon atoms and one member that is -0-, -S-, or -N(R 8 )-, where R 8 iε hydrogen or lower alkyl; or a pharmaceutically acceptable salt thereof. 2. The compound or salt of Claim 1 wherein R 1 is hydrogen. The compound or salt of Claim 2 wherein R 2 is hydrogen or -C(0)R 3 - 4. The compound or salt of Claim 3, wherein R 2 iε hydrogen and R 7 iε hydrogen, namely (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoic acid; or wherein R 2 is hydrogen and R 7 is morpholinoethyl, namely 2- (morpholin-4-yl)ethyl (E) -6- (l,3-dihydro-4-amino-6-methoxy-7-methyl-3- oxoisobenzofuran-5-yl) -4-methyl-4-hexenoate; or wherein R 2 is -C(0)R 3, R 3 is -CF 3 and R 7 iε hydrogen, namely (E) - 6- [1,3-dihydro-4- (trifluoroacetyl)amino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid; or wherein R 2 iε -C(0)R 3 , R 3 iε -CF 3 , and R 7 is morpholinoethyl, namely 2- (morpholin-4-yl)ethyl (E) -6- [l,3-dihydro-4- (trifluoroacetyl)amino- 6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl] -4-methyl-4-hexenoate. 5. The compound or salt of Claim 2 wherein R 2 iε methyl and R 7 iε hydrogen, namely (E) -6- (l,3-dihydro-4-methylamino-6-methoxy-7-methyl-3- oxoiεobenzofuran-5-yl) -4-methyl-4-hexenoic acid. 6. The compound or salt of Claim 20 wherein R 4 and R 5 are both methyl, namely (E) -6- [1,3-dihydro-4- (3,3-dimethylureido) -6-methoxy-7- methyl-3-oxoiεobenzofuran-5-yl] -4-methyl-4-hexenoic acid. 7. A pharmaceutical composition comprising a pharmaceutically acceptable non- oxic excipient and a therapeutically effective amount of a compound or salt of Claim 1. 8. A method of treatment for immune, inflammatory, tumor, proliferative, viral or psoriatic disorders in a mammal, comprising administering a therapeutically effective amount of a compound or salt of Claim l to a mammal in need thereof. A compound represented by the formula: wherein: R 7 is lower alkyl; and R 10 is -0S0 2 CF 3 , -OS0 2 F, -CN, -COjH, or -NCO. 10. A process for preparing compounds of Formula I, Formula I wherein: R 1 is hydrogen or lower alkyl; R 2 is hydrogen, lower alkyl, -C(0)R 3 , -C(0)NRR 5 , -C0 2 R 6 , or -S0 2 R 3 where: R 3 is hydrogen, lower alkyl, halo lower alkyl or optionally subεtituted phenyl; R 4 iε hydrogen, lower alkyl or optionally εubstituted phenyl; R 5 is hydrogen, lower alkyl or optionally subεtituted phenyl; R 6 is lower alkyl or optionally subεtituted phenyl; and R 7 iε hydrogen, lower alkyl, optionally substituted phenyl, or - (CH 2 )_.-N=Y, wherein: m is an integer from two to four; and Y iε lower alkylene of four to six carbon atoms or lower alkylene of three to five carbon atoms and one member that is -0-, -S-, or -N(R 8 )- where R 8 iε hydrogen or lower alkyl; or a pharmaceutically acceptable εalt thereof, which compriεeε: a) reacting a compound of Formula I wherein R 7 iε lower alkyl, optionally εubstituted phenyl, or - (CH 2 ) m -N=Y, with an inorganic baεe to form a compound of Formula I wherein R 7 iε hydrogen; or b) reacting a compound of Formula I wherein R 7 iε hydrogen with a compound of the formula R 7 0H to form a compound of Formula I wherein R 7 iε lower alkyl, optionally εubεtituted phenyl, or - (CH 2 ) m -N=Y, wherein: m iε an integer from two to four; and Y iε lower alkylene of four to εix carbon atomε or lower alkylene of three to five carbon atoms and one member that is -O-, -S-, or -N(R 8 )- where R 8 iε hydrogen or lower alkyl; or c) reacting a compound of Formula I wherein R' is H, R 2 is C(0)R 3 wherein R 3 is H, and R 7 is lower alkyl, with a compound of the formula HNRR 5 to form a compound of Formula I wherein R 1 is hydrogen; R 2 is -C(0)NR 4 R 5 , where R 4 and R 5 are independently hydrogen, lower alkyl or optionally subεtituted phenyl; and R 7 is lower alkyl; or d) reacting a compound of Formula I wherein R' and R 2 are H with a compound of the formula (R 3 C(0) 2 0 or R 3 C(0)C1 to form a compound of Formula I wherein R 1 is hydrogen; R 2 is -C(0)R 3 , where R 3 iε lower alkyl, halo lower alkyl or optionally εubεtituted phenyl; and R 7 iε lower alkyl, optionally εubstituted phenyl, or - (CH 2 ) m -N=Y, ; or e) reacting a compound of Formula I wherein R 1 is H, R 2 iε C(0)R 3 and R 7 iε lower alkyl, with a compound of the formula R'X, where R' is lower alkyl and X is iodine or bromine, to form a compound of Formula I wherein: R' is lower alkyl; R 2 iε -C(0)R 3 , where R 3 is lower alkyl, halo lower alkyl or optionally subεtituted phenyl; and R 7 iε lower alkyl; or f) reacting a compound of Formula I to form a pharmaceutically acceptable εalt of a compound of Formula I; or g) reacting a pharmaceutically acceptable salt of a compound of Formula I to form the corresponding free compound of Formula I; or h) reacting a pharmaceutically acceptable salt of a compound of Formula I to form another pharmaceutically acceptable salt of a compound of Formula I.

Inventors: SJOGREN ERIC B, SJOGREN, ERIC, B.
Applicants: SYNTEX INC, SYNTEX (U.S.A.) INC.
Application year: 1995
Main classification: C07D307
IPC codes: A61K31, A61P17, A61P29, A61P35, A61P37, C07D307, C07D405, C07D417