SUBSTITUTED INDOLES AND AZAINDOLES AS ANGIOTENSIN II ANTAGONISTS

Abstract: Compounds of formula (I), (II), or (III) wherein: R<1> is lower alkyl when R<2> is V; or R<2> is lower alkyl when R<1> is V; wherein: V is (A); R<3> is hydrogen or lower alkyl; X is hydrogen, lower alkyl, halogen, -C(O)CF3, -CO2R<4>, or -C(O)NR<5>R<6>; Y is hydrogen, lower alkyl, lower alkoxy, hydroxy, halogen, or -CO2R<4>; Z is hydrogen, lower alkyl, lower alkoxy, or halogen; with the proviso that Y and Z cannot be attached to the nitrogen atom in formula (II); in which R<4> is hydrogen or lower alkyl; R<5> is hydrogen, lower alkyl, or -CH2CO2R<4>; R<6> is hydrogen or lower alkyl; or R<5> and R<6> taken together with the nitrogen to which they are attached represent a heterocycle; R<7> is (B); (C); (D); (E); (F); (G); (H) or (J); in which: R<8> is -CO2H or 1H-tetrazol-5-yl; and W is oxygen, sulfur, or -NR-, wherein R is hydrogen or lower alkyl; and the pharmaceutically acceptable salts thereof, exhibit useful pharmacological properties, and are particularly useful as angiotensin (II) antagonists.

Description: SUBSTITUTED INDOLES AND AZAINDOLES AS ANGIOTENSIN II ANTAGONISTS BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to substituted indole, azaindole and tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one compounds and derivatives thereof, useful as angiotensin II antagonists, particularly effective in the control of smooth and cardiac muscle contraction, especially for the treatment of cardiovascular disorders such as hypertension and congestive heart failure. Additionally, the compounds of the present invention are useful for the treatment of chronic renal failure and disorders of the alimentary tract, and have procognitive, anxiolytic and antidepressant activities. Related Disclosures The renin-angiotensin system is a fundamental physiological mechanism for regulating blood pressure in mammals. Angiotensinogen is secreted into the bloodstream by the liver. Angiotensinogen is then cleaved by the protease renin to yield the decapeptide angiotensin I, which in turn is hydrolyzed by angiotensin converting enzyme (ACE) to the octapeptide angiotensin II. Angiotensin I is inactive in the cardiovascular system, but angiotensin II has numerous cardiovascular-renal activities. For example, it stimulates the adrenal cortex to secrete aldosterone, which causes the kidneys to retain sodium and water, increasing blood pressure. It causes vasoconstriction. It also facilitates neurotransmission in the sympathetic nervous system. The effects of angiotensin II, such as arteriolar vasoconstriction, contraction of gastro-intestinal smooth muscle, aldosterone secretion, glycogenolysis, alteration of renal function and CNS effects, are mediated by the activation of specific angiotensin II receptors on smooth and cardiac muscle, adrenal medulla, brain, liver and kidney. Angiotensin II receptors are categorized into subtypes, for example the AT-1 and AT-2 subtypes. It is evident that disease states associated with activation of angiotensin II receptors could be usefully treated by compounds possessing angiotensin II antagonist activity. Various angiotensin II receptor antagonists are known. See, for example, U.S. Patent Nos. 4,333,943, 4,880,804, 5,053,329, 5,124,335, and European Patents 0245 637, 0253 310, and 0 291 969, and also Wong et al., Hypertension 15:459 (1990), J. Pharmacol . Exp . Ther. 256:211 (1990), and Chiu et al., Biochem. Biophys. Res . Comm. 165:196-203 (1989). SUMMARY OF THE INVENTION A first aspect of the present invention relates to compounds of the Formula (I) , (II) and (III) : CD (II CHI) wherein: R 1 is lower alkyl when R 2 is V; or R 2 is lower alkyl when R l is V; wherein: V is: R 3 is hydrogen or lower alkyl; X is hydrogen, lower alkyl, halogen, -C(0)CF 3 , -C0 2 R 4 , or -CfOJNR- 6 ; Y is hydrogen, lower alkyl, lower alkoxy, hydroxy, halogen, or Z is hydrogen, lower alkyl, lower alkoxy, or halogen; with the proviso that Y and Z cannot be attached to the nitrogen atom in Formula (II); in which R 4 is hydrogen or lower alkyl; R 5 is hydrogen, lower alkyl, or -CHjCOjR 4 ;; R 6 is hydrogen or lower alkyl; or R s and R 6 taken together with the nitrogen to which they are attached represent a heterocycle; R 7 is: in which; R 8 is -C0 2 H or lH-tetrazol-5-yl; and W is oxygen, sulfur, or -NR-, wherein R is hydrogen or lower alkyl; and the pharmaceutically acceptable salts thereof. A second aspect of this invention relates to pharmaceutical compositions containing at least one compound of Formula (I), (II) or (III), and one or more pharmaceutically acceptable excipients. A third aspect of this invention relates to methods for treating angiotensin II receptor-related disorders in a mammal by administering an effective amount of a compound of Formula (I), (II) or (III), or a composition containing a compound of Formula (I), (II) or (III), to the mammal. In one embodiment, the angiotensin II receptor-related disorder treated is a cardiovascular disease, more particularly hypertension or congestive heart failure. In another embodiment, the angiotensin II receptor-related disorder treated is chronic renal failure or disorders of the alimentary tract. In yet another embodiment, the invention relates to methods for treating cognitive disorders, anxiety and depression. A fourth aspect of the invention relates to methods for the preparation of the compounds of Formula (I), (II) and (III). A fifth aspect of the invention relates to intermediates of the Formula (1), (2) and (3), shown below: CO C2} C3) wherein R 3 , X, Y, and Z are as defined above; R 1 is lower alkyl when R 9 is V; or R 9 is lower alkyl when R 1 is V; where V is: where R 10 is where W is as defined above. DETAILED DESCRIPTION OF THE INVENTION Definitions As used herein: "Alkyl" means a branched or unbranched saturated hydrocarbon chain containing 1 to 12 carbon atoms, such as methyl, ethyl, propyl, tert-butyl, n-hexyl, n-octyl, n-decyl, and the like. "Lower alkyl" means a branched, unbranched, or cyclic saturated hydrocarbon chain, optionally substituted by cycloalkyl, containing 1 to 10 carbon atoms, such as methyl, ethyl, propyl, isopropyl, tert-butyl, butyl, n-hexyl, n-decyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, 2-cyclohexylethyl, 2-cyclohexylpropyl, and the like. "Cycloalkyl" means a saturated monovalent monocyclic hydrocarbon radical containing 3-8 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. "Lower alkoxy" means the group -O-R wherein R is lower alkyl is as defined above. The definition "R 5 and R 6 taken together with the nitrogen to which they are attached is a heterocycle" as used herein is intended to include saturated monovalent monocyclic radicals containing 3-7 carbon atoms and one nitrogen atom, such as azetidine, azolidine, piperidine, 4-methylpiperidine, hexamethyleneimine, heptamethyleneimine, and the like. The term "halo" means fluoro, bromo, chloro or iodo, unless otherwise indicated. The terms "inert organic solvent" or "inert solvent" mean a solvent inert under the conditions of the reaction being described in conjunction therewith [including, for example, benzene, toluene, acetonitrile, tetrahydrofuran ("THF"), dimethylformamide ("DMF"), chloroform ("CHCl 3 "), methylene chloride (or dichloromethane or "CH 2 C1 2 "), diethyl ether, ethyl acetate, acetone, methylethyl ketone, methanol, ethanol, propanol, isopropanol, tert-butanol, dioxane, pyridine, and the like] . Unless specified to the contrary, the solvents used in the reactions of the present invention are inert solvents. The compounds of Formula (I), (II) and (III) form base addition salts by virtue of the presence of a lH-tetrazol-5-yl group, and/or the presence of - C0 2 H group. The term "pharmaceutically acceptable salt" means any salt derived from an inorganic or organic base chosen not to be biologically or otherwise undesirable. The term "pharmaceutically acceptable cation" means the cation of such base addition salts. The cations derived from inorganic bases include sodium, potassium, lithium, ammonium, calcium, magnesium and the like. Cations derived from organic bases include those formed from primary, secondary and tertiary amines, such as isopropylamine, diethylamine, trimethylamine, pyridine, cyclohexylamine, ethylene diamine, monoethanolamine, diethanolamine, triethanolamine and the like. "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances in which it does not. For example, "optionally followed by converting the free acid to the base addition salt" means that said conversion may or may not be carried out in order for the process described to fall within the invention, and the invention includes those processes wherein the free base is converted to the acid addition salt and those processes in which it is not. The term "mammal" includes humans and all domestic and wild mammals, including, without limitation, cattle, horses, swine, sheep, goats, dogs, cats, rabbits, and the like. The term "treatment" as used herein covers any treatment of a disease in a mammal, particularly a human, and includes: (i) preventing the disease from occurring in a subject which may be predisposed to the disease but has not yet been diagnosed as having it; (ii) inhibiting the disease, i.e. arresting its development; or (iii) relieving the disease, i.e. causing regression of the disease. The term "a disease-state that is alleviable by treatment with an angiotensin II antagonist" as used herein is intended to cover all disease states which are generally acknowledged in the art to be usefully treated with angiotensin II antagonists in general, and those disease states which have specifically been found to be usefully treated by the specific compounds of our invention, the compounds of Formula (I), (II) and (III). Such disease states include, but are not limited to, cardiovascular disorders such as hypertension and congestive heart failure, chronic renal failure, cognitive and affective disorders, and disorders of the alimentary tract, for example inflammatory bowel disease. The term "q.s." means adding a quantity sufficient to achieve a stated function, e.g., to bring a solution to the desired volume (i.e., 100%). The term "effective amount" means a dosage sufficient to provide treatment for the disease state being treated. This will vary depending on the patient, the disease and the treatment being effected. The naming and numbering of the compounds of the present invention are illustrated below. The tetrazole group is illustrated with the hydrogen atom at the 1-position. However, the tetrazole group is tautomeric, and consequently the hydrogen may be present at any of the 1-, 2-, 3- and 4-positions. Examples of the group V are shown below: 1. The above structure is named as 2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl. 2. 3 2 The above structure is named as follows: where W is oxygen, it is named as t3-(lH-tetrazol-5-yl)furan-2-yl]phen- 4-ylmethyl; where W is sulfur, it is named as {3-(lH-tetrazol-5-yl)thiophen-2- yl]phen-4-ylmethyl; and where W is NH, it is named as [3-(lH-tetrazol-5-yl)pyrrol-2-yl]phen-4- ylmethyl. 3. The above structure is named as follows: where W is oxygen, it is named as [3-(lH-tetrazol-5-yl)benzofuran-2- yl]phen-4-ylmethyl; where W is sulfur, it is named as (3-(lH-tetrazol-5-yl)benzothiophen-2- yl]phen-4-ylmethyl; and where W is NH, it is named as [3-(lH-tetrazol-5-yl)indol-2-yl]phen-4- ylmethyl. 4. The above structure is named as 2-(lH-tetrazol-5-yl)indol-l-yl]phen-4- ylmethyl. A compound of Formula (I) is numbered as follows: CD The compound of Formula (I) where X is -CO,H, Y and Z are hydrogen, R 1 is n-butyl, and R 2 is 2"-(lH-tetrazol-5-yl)biρhenyl-4'-ylmethyl (that is, where R 2 is V, where V is as defined above, in which R 7 is 2-(lH-tetrazol-5-yl)phenyl) , is named: 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4 • -ylmethy1]indole-3- carboxylic acid. The compound of Formula (I) where X and Z are hydrogen, Y is 7-CO. j H, R 1 is 2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl, and R 2 is ethyl, is named: 2-ethyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-7-carboxylic acid. The compound of Formula (I) where Y and Z are hydrogen, X is -CO^, R 1 is n-butyl and R 2 is [2-(lH-tetrazol-5-yl)thiophen-3-yl]phen-4-ylmethyl (that is, where R 2 is V, where V is as defined above, in which R 7 is 2-(lH-tetrazol-5- yl)thiophene), is named: 1-(n-butyl)-2-[(2-(lH-tetrazol-5-yl)thiophen-3-yl)phen-4- ylmethyl]indole-3-carboxylic acid. A compound of Formula (II) is numbered as follows: (ID The compound of Formula (II) where X, Y and Z are hydrogen, R 1 is n- butyl and R 2 is 2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl, is named: 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl- '-ylmethyl]-1H- pyrrolo[2,3-b]pyridine; or alternatively may be named as: 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]—7-azaindole. A compound of Formula (III) is numbered as follows: The compound of Formula (III) where X is hydrogen, Rl is n-butyl, R2 is 2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl, and R3 is methyl, is named: 1-(n-butyl)-6-methy1-2-[2"-(lH-tetrazol-5-yl)biphenyl-4 • -ylmethyl]- 4,5,6,7-tetrahydro-lH-pyrrolo[2,3-c]ρyridin-7-one. The compound of Formula (III) where X is -C0 2 H, Rl is cyclohexylmethyl, R2 is 2"-(lH-tetrazol-5-yl)biphenyl-4"-ylmethyl, and R3 is hydrogen, is named: 1-(cyclohexylmethyl)-2-[2"-{lH-tetrazol-5-yl)biphenyl-4 ■ -ylmethyl]- 4,5,6,7-tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one-3-carboxylic acid. Preferred Embodiments Among the family of compounds of the present invention, one preferred category includes the compounds of Formula (I) where R 2 is 2"-(lH-tetrazol-5- yl)biphenyl-4'-ylmethyl, X is -C0 2 R 4 and Z is hydrogen. Within this category one preferred group includes the compounds where R 1 is a branched or unbranched saturated hydrocarbon, especially where R 4 is hydrogen, and more especially where R * is n-butyl. Another preferred group includes the compounds where R 1 is a branched or unbranched saturated hydrocarbon substituted by cycloalkyl, especially where R 4 is hydrogen, and more especially where R 1 is cyclopropylmethyl or cyclohexylmethyl. Another preferred category includes the compounds of Formula (II) where R 2 is 2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl, X is -CO,R 4 and Z is hydrogen. Within this category one preferred group includes the compounds where R 1 is lower alkyl of three to eight carbon atoms, and R 4 is hydrogen, especially where R 1 is n-butyl and Y is hydrogen. A third preferred category includes the compounds of Formula (III) where R 2 is 2"-(lH-tetrazol-5-yl)biphenyl-4*-ylmethyl, X is -C0 2 R 4 , R 1 is lower alkyl of three to eight carbon atoms, and R 4 is hydrogen, especially where R 1 is n- butyl, R 3 is hydrogen, and Y is hydrogen. A fourth preferred category includes the compounds of Formula (I) where R 1 is lower alkyl and R 2 is V. Within this category one preferred group includes the compounds where R 7 is not 2-(lH-tetrazol-5-yl)phenyl, especially where X is -CO-jR 4 and Z is hydrogen, and more especially where R 1 is n-butyl and R 4 is hydrogen. A fifth preferred category includes the compounds of Formula (I) where R 1 is V and R 2 is lower alkyl. Within this category one preferred group includes the compounds where R 7 is not 2-(lH-tetrazol-5-yl)phenyl, especially where X is -C0 2 R 4 and Z is hydrogen, and more especially where R 1 is n-butyl and R 4 is hydrogen. Another preferred group within this category includes the compounds where R 7 is 2-(lH-tetrazol-5-yl)phenyl and X is halogen, -C(0)CF 3 , or -C(0)NR 5 R 6 , especially where R 1 is n-butyl, X is -C(θ)CF 3 , Y is 7-fluoro, and Z is hydrogen. A sixth preferred category includes the compounds of Formula (II) where R 1 is lower alkyl and R 2 is V Within this ςategory one preferred group includes the compounds where R 7 is not 2-{lH-tetrazol-5-yl)phenyl, especially where X is -CO^ and Z is hydrogen, and more especially where R 1 is n-butyl and R 4 is hydrogen. A seventh preferred category includes the compounds of Formula (II) where R 1 is V and R 2 is lower alkyl. Within this category one preferred group includes the compounds where R 7 is not 2-(lH-tetrazol-5-yl)phenyl, especially where X is -CO- j R 4 and Z is hydrogen, and more especially where R 1 is n-butyl and R 4 is hydrogen. An eighth preferred category includes the compounds of Formula (III) where R 1 is lower alkyl and R 2 is V, especially where X is -C0 2 R 4 and Z is hydrogen, and more especially where R 1 is n-butyl and R 4 is hydrogen. A ninth preferred category includes the compounds of Formula (III) where R 1 is V and R 2 is lower alkyl. Within this category one preferred group includes the compounds where R 7 is not 2-(lH-tetrazol-5-yl)phenyl, especially where X is -C0 2 R 4 and Z is hydrogen, and more especially where R 1 is n-butyl and R 4 is hydrogen. At present, the most preferred compounds are: l-n-butyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4 * -ylmethyl]-5-chloroindole- 3-carboxylic acid; l-n-butyl-2-f2"-(lH-tetrazol-5-yl)biρhenyl-4'-ylmethyl]-3- trifluoroacetylindole; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl- '-ylmethyl]-indole-3- carboxylic acid; and 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl- '-ylmethyl]indole-7- carboxylic acid. PREPARATION OF COMPOUNDS OF FORMULA (I), (II) and (III) I. Preparation of Compounds of Formula (Xa) The compounds of Formula (I) where R 1 is lower alkyl and R 2 is V, identified as Formula (la) , may be prepared from the intermediates of Formula (11) or (12), the preparation of which is shown below in Reaction Scheme I. Reaction Scheme I O 5} ?} sn C-- B OH 2 C 0D C11D 12D where R 1 is lower alkyl, and R 10 , X, Y and Z are as defined in the Summary of the Invention. Starting Materials The substituted aniline starting materials of Formula (4) are commercially available, for example from Aldrich Chemical Company. Alternatively, the substituted aniline compounds of Formula (4) can be prepared from commercially available substituted anilines by conventional means. The reactant of Formula (6), N-methyl-N-methoxy-p- bromophenylacetylamide, used in step 2 of Reaction Scheme I, may be prepared according to the general method described in Nahm, S. and Weinreb, S. Tet. Lett. 22:3815-3818 (1981). Most preferably, this amide is prepared as follows: C13 1 D ce;. Step 1 of the preparation of N-methyl-N-methoxy-p-bromophenylacetylamide (6) uses p-bromophenylacetic acid, the starting material of Formula (13), which is commercially available, for example, from Aldrich Chemical Company. Initially, oxalyl chloride is added to an eguimolar amount of p- bromophenylacetic acid (13) in an inert solvent, preferably methylene chloride, at about room temperature, with a catalytic amount of dimethylformamide. The mixture is stirred for about 30 minutes, after which the product, p-bromophenylacetyl chloride (14), is isolated by conventional means. Then p-bromophenylacetyl chloride (14) is dissolved in an inert solvent, preferably methylene chloride, cooled, and reacted with N-methyl-O- methylhydroxylamine hydrochloride in the same inert solvent, preferably methylene chloride, in the presence of a tertiary amine, preferably triethylamine. The product, N-methyl-N-methoxy-p-bromophenylacetylamide (6), is isolated by conventional means. The 2-cyanobromobenzene used in step 6 of Reaction Scheme I is commercially available, i.a., from Aldrich. The trialkyl tin azide used in step 8 is prepared as described in Kricheldorf and Leppert, Synthesis, pp 329-330 (1976). Preparation of Compounds of Formula (5) To prepare a compound of Formula (5), a compound of Formula (4) is reacted with about 1-2 molar equivalents, preferably about 1 molar equivalent, of di-t-butyldicarbonate in an inert solvent (such as ether, dichloromethane, or tetrahydrofuran, preferably tetrahydrofuran) . The reaction is carried out at a temperature of about 60°C to 100°C, preferably at about 80°C, for about 2 to 6 hours, preferably 4 hours. When the reaction is substantially complete the t-butyl-carbamate of Formula (5) is isolated by conventional means. Preparation of Compounds of Formula (7) To prepare a compound of Formula (7), a compound of Formula (5) is first reacted with about 2 molar equivalents of a strong base (such as a butylli hium, preferably sec-butyllithium), in an ethereal solvent (such as diglyme, ether, or tetrahydrofuran, preferably tetrahydrofuran), at a temperature of about -30 β C to -50°C, preferably at about -40°C. After addition of the base, the temperature is lowered to about -70°C to -100°C, preferably at about -75 β C. To the lithium dianion thus formed is added about 1 to 1.5 molar equivalents, preferably about 1 molar equivalent, of the compound of Formula (6) (N-methyl-N-methoxy-p-bromophenylacetylamide) in an ethereal solvent, preferably tetrahydrofuran, maintaining the temperature at about -80°c to - 50 β C, preferably at about -60°C, for about 5 minutes to 1 hour, preferably about 10 minutes. When the reaction is substantially complete an uncyclized intermediate is isolated by conventional means, and dissolved in an inert aprotic solvent (such as ether, tetrahydrofuran, or methylene chloride; preferably methylene chloride), and about 0.1 to 2 molar equivalents, preferably about 1 molar equivalent, of trifluoroacetic acid is added. The reaction is carried out at about room temperature, for about 5 minutes to 1 hour, preferably about 30 minutes. When the reaction is substantially complete the t-butylcarboxyindole of Formula (7) is isolated by conventional means. Preparation of Compounds of Formula (8) To prepare a compound of Formula (8), a compound of Formula (7) is reacted with an excess of a base (such as potassium hydroxide, ammonium hydroxide, or sodium hydroxide; preferably sodium hydroxide) in water and an organic solvent (such as methanol, propanol, or ethanol; preferably ethanol), at a temperature of about 50°C to reflux, preferably at about reflux, for 4 to 10 hours, preferably about 6 hours. When the reaction is substantially complete the 2-(p-bromophenyl-methyl)indole of Formula (8) is isolated by conventional means. Preparation of Compounds of Formula (9) where R 1 is lower alkyl To prepare a compound of Formula (9) where R' is lower alkyl, a compound of Formula (8) is first reacted with 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of an alkali metal hydride (such as lithium hydride, potassium hydride, or sodium hydride; preferably sodium hydride) in a polar βolvent (such as ace amide, DMSO (dimethyl sulfoxide), or DMF (dimethylformamide); preferably DMF). The reaction is carried out at a temperature of -10 β C to 20°C, preferably about 0°C, for about 5 minutes to 1 hour, preferably about 10 minutes. The anion thus formed is then reacted with about 1 to 1.5 molar equivalents, preferably about 1 molar equivalent, of a lower alkyl halide, preferably a lower alkyl iodide, for about 15 to 60 minutes, preferably about 30 minutes. When the reaction is substantially complete the 1-lower alkyl-2-(p-bromophenylmethyl)indole of Formula (9) where R 1 is lower alkyl is isolated by conventional means. Preparation of Compounds of Formula (10) where R 1 is lower alkyl To prepare a compound of Formula (10) where R * is lower alkyl, a compound of Formula (9) where R 1 is lower alkyl is first reacted with 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of an alkyl lithium base, preferably n-butyllithium, in an ethereal solvent (such as ether, monoglyme, or tetrahydrofuran; preferably tetrahydrofuran). The reaction is carried out at a temperature of -100°C to -50°C, preferably about -70°C, for about 5 minutes to 1 hour, preferably about 15 minutes. The anion thus formed is then reacted with about 1 to 2 molar equivalents, preferably about 1.5 molar equivalents, of an alkyl borate (such as triethyl borate, trimethyl borate, or tributyl borate, preferably tributyl borate), allowing the reaction mixture to warm to about 0°C. When the reaction is substantially complete the 2-[4'-(dihydroxyboron)phenylmethyl]-indole of Formula (10) where R 1 is lower alkyl is isolated by conventional means. Preparation of Compounds of Formula (11) where R 1 is lower alkyl To prepare a compound of Formula (11) where R 1 is lower alkyl, a compound of Formula (10) where R 1 is lower alkyl is reacted with 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of a compound of the Formula R 10 Halo (where R 10 is as defined-in the Summary of the Invention, and Halo is chloro, bromo, or iodo), preferably R 10 Br (for example a 1-cyano- 2-halobenzene, preferably l-cyano-2-bromobenzene), and a transition metal catalyst (such as di-[triphenyl phosphine] palladium chloride, palladium on carbon, or tetrakisftriphenylphoβphine] palladium, preferably tetrakis[triphenylphosphine] palladium). The reaction is carried out in an inert βolvent (such as tetrahydrofuran, ethanol, and/or toluene; preferably a mixture of toluene and ethanol), in the presence of an excess of a mild base (such as sodium or potassium carbonate, or sodium bicarbonate, preferably sodium carbonate). The reaction is carried out at a temperature of 60°C to reflux, preferably at about reflux for 6 to 48 hours, preferably about 24 hours. When the reaction is substantially complete the indole of Formula (11) where R 1 is lower alkyl is isolated by conventional means, Preparation of Compounds of Formula (12) where R 1 is lower alkyl and X is -CO-H To prepare a compound of Formula (12) where R * is lower alkyl and X is - CO-H, a compound of Formula (11) where R 1 is lower alkyl is reacted with 1 to 3 molar equivalents, preferably about 1.5 molar equivalents, of phosgene. The reaction is carried out in an inert solvent (such as ether, methylene chloride, or tetrahydrofuran; preferably tetrahydrofuran) at -20°C to 10°C, preferably about 0°C, for about 8 to 48 hours, preferably overnight. When the reaction is substantially complete the 3-carboxyindole of Formula (12) where R 1 is lower alkyl and X is -C0 2 H is isolated by conventional means. Preparation of Compounds of Formula (12) where R 1 is lower alkyl and X ii - CO j R 4 To prepare a compound of Formula (12) where R 1 is lower alkyl and X is - COjR 4 , in which R 4 is lower alkyl, the solution of a compound of Formula (12) where X is -COCl in dichloromethane, prepared as shown above, is cooled to 0 to 10°C, preferably about 5°C, and reacted with an alcohol of formula R 4 OH, where R 4 is lower alkyl. When the reaction is substantially complete, the 3-(carbo-loweralkoxy)indole derivative of Formula (12), where R 1 is lower alkyl and X is -C0 2 R 4 , in which R 4 is lower alkyl, is isolated and purified by conventional means, preferably chromatography. Preparation of Compounds of Formula (12) where R 1 is lower alkyl and X is - CONR 5 R' To prepare a compound of Formula (12) where R 1 is lower alkyl and X is - CONR 5 R 6 , in which R s and R* are as defined in the Summary of the Invention, the procedure shown above is followed, substituting an amine of formula R 5 R 6 H for the alcohol of formula R 4 OH. Preparation of Compounds of Formula (12) where R l is lower alkyl and X is - COCF 3 To prepare a compound of Formula (12) where R 1 is lower alkyl and X is - COCF 3 , a compound of Formula (11) where R 1 is lower alkyl is reacted with 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of trifluoroacetic anhydride. The reaction is carried out in an aprotic solvent (such as ether, tetrahydrofuran, or DMF; preferably DMF) at -10°C to 20°C, preferably about 0°C, for about 5 to 30 minutes, preferably about 10 minutes. When the reaction is substantially complete the 3-trifluoroacetylindole of Formula (12) where R' is lower alkyl and X is -C0CF 3 is isolated by conventional means. Preparation of Compounds of Formula (12) where R 1 is lower alkyl and X is Halo To prepare a compound of Formula (12) where R l is lower alkyl and X is halo, a compound of Formula (11) where R 1 is lower alkyl is reacted with 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of an N-halosuccinimide. The reaction is carried out in an aprotic solvent (such as ether, tetrahydrofuran, or DMF; preferably DMF) at 0°C to 30°C, preferably about 20°C, for about 5 to 30 hours, preferably about 16 hours. When the reaction is substantially complete the 3-halo compound of Formula (12) where R 1 is lower alkyl and X is halo is isolated by conventional means. Alternative Preparation of Compounds of Formula (11) Alternatively, compounds of Formula (11) may also be prepared as shown below in Reaction Scheme IA. Reaction Scheme IA C15D C1B3 C17) cm wherein R 1 is lower alkyl and R 10 , Y and Z are as defined above in the Summary of -the Invention. Star ing Materials The starting compounds of Formula (15) are commercially available from, for example, the Aldrich Chemical Company. The starting compound of Formula (17) is commercially available from, for example, Lancaster Chemicals, or may be prepared as shown in Example 17, or from compounds of Formula (20) or (28) by means well known in the art, for example by reducing (20) to an alcohol and converting it to a leaving group, for example methanesulfonate, bromo, and the like. Preparation of Compounds of Formula (16) To prepare a compound of Formula (16) where R * is lower alkyl, a compound of Formula (15) where R 1 is lower alkyl is first reacted with about 1 molar equivalent of n-butyl lithium. The reaction is carried out in an aprotic solvent (such as ether, tetrahydrofuran, preferably tetrahydrofuran) mixed with hexamethylphosphoramide (10%) at -10°C to 5°C, preferably about -5°C, for about 30 minutes. The resultant anion is then reacted with 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of tributyl tin chloride, for about 1 hour at about room temperature. When the reaction is substantially complete the compound of Formula (16) where R 1 is lower alkyl is isolated by conventional means. Preparation of Compounds of Formula (11) To prepare a compound of Formula (11) where R 1 is lower alkyl, a compound of Formula (16) where R * is lower alkyl is reacted with 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of a compound of the Formula (17) (where R 10 is as defined in the Summary of the Invention), and a transition metal catalyst (such as di-[triphenyl phosphine] palladium chloride, palladium on carbon, or tetrakis[triphenylphosphine] palladium, preferably tetrakis[triphenylphosphine] palladium). The reaction is carried out in an inert solvent (such as tetrahydrofuran, ether, dimethoxyethane; preferably tetrahydrofuran), at a temperature of 50°C to reflux, preferably at about reflux for 30 minutes to 8 hours, preferably about 2 hours. When the reaction is substantially complete the indole of Formula (11) where R 1 is lower alkyl is isolated by conventional means. II. Alternative Preparation of Compounds of Formula (la) Compounds of Formula (la) where X is -C0 2 H may also be prepared from the intermediates of Formula (12a) (a compound of Formula (12) where X is -C0 2 H), the preparation of which is shown below in Reaction Scheme IB. REACTION SCHEME IB ( 20 ) (21) C12a wherein R 1 is lower alkyl and R 10 , Y and Z are as defined above in the Summary of the Invention. Starting Materials The compounds of Formula (18) are commercially available, for example, from Aldrich Chemical Company. Alternatively, they may be prepared conventionally, for example by the methods described in Synthesis, Vol. 10, p 871 (1991), or Organic Preparations and Procedures, No. 2, Vol. 4, p 297 (1970). The reactant of Formula (20) where R 10 is 2-cyanophenyl used in Step 2 of Reaction Scheme IA may be prepared as follows: (22) (23) (24) (20) The reactant of Formula (20) where R 10 is a 2-cyanoheterocycle used in Step 2 of Reaction Scheme IA may be prepared as follows: (25) (26) (27) (28) (20) where R 10 is as defined in the Summary of the Invention. Preparation ' of Compounds of Formula (23) Step 1 of the preparation of the 4-substituted aldehyde of Formula (20) involves reaction of 4-bromobenzaldehyde (22) (which is commercially available, for example, from Aldrich Chemical Company) with ethylene glycol in an inert solvent, preferably toluene, at reflux temperature for about 2 hours in the presence of an acid catalyst, preferably p-toluene sulfonic acid, after which the ethylene ketal of Formula (23) is isolated by conventional means. Preparation of Compounds of Formula (24) A solution of the compound of Formula (23) in a dry ethereal solvent, preferably tetrahydrofuran, is cooled to -60°C, and an equivalent amount of n-butyllithium (preferably in hexane) is added. The mixture is then stirred at -70°C for 30 minutes, after which time a suspension is formed. To the suspension at -70°C is then added tributylborate. The mixture is stirred for additional 3 hours as it gradually warms to θ°C, after which the dihydroxyborane derivative of Formula (24) is isolated by conventional means. Preparation of Compounds of Formula (20) A compound of Formula (20) is then obtained by stirring a mixture of a compound of Formula (24), 2-bromobenzonitrile, tetrakis(triphenylphosphine)palladium(0) , and sodium carbonate in an inert solvent, preferably toluene, at reflux temperature for 24 hours. The compound of Formula (20) is then isolated by conventional means. Preparation of Compounds of Formula (26) An appropriate 2-cyano substituted heterocyclic compound (25) is first reacted with tert-butyl-4-fluorobenzoate in the presence of potassium carbonate in a polar solvent such as dimethylβulfoxide at about 110°C for about 24-60 hours, preferably for about 48 hours. The compound of Formula (26) is then isolated by conventional means. Preparation of Compounds of Formula (27) A compound of Formula (26) is hydrolysed under acid conditions by dissolving (26) in excess acetic acid/hydrogen bromide mixture, and stirring for 10 minutes, after which the compound of Formula (27) is isolated by conventional means. Preparation of Compounds of Formula (28) The preparation of a compound of Formula (28) from the corresponding compound of Formula (27) may be accomplished by reacting the compound of Formula (27) with a reducing agent, for example sodium borohydride, in an inert solvent, preferably aqueous tetrahydrofuran, for about 20 minutes. A compound of Formula (28) is then isolated by conventional means. Preparation of Compounds of Formula (20) The compound of Formula (20) may be prepared by reacting the corresponding compound of Formula (28) with an oxidizing agent, for example activated manganese dioxide, in an inert solvent, preferably tetrahydrofuran, for about 16 hours. A compound of Formula (20) is then isolated by conventional means. Preparation of Compounds of Formula (19) To prepare a compound of Formula (19), a compound of Formula (18) is first added to a suspension of NaH in an inert solvent preferably DMF in an ice bath. To the thickened suspension, about 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of a lower alkyl halide of formula R'Halo, where Halo is chloro, bromo, or iodo, is added at 0°C. The mixture is then stirred at about 0-30°C, preferably at about room temperature for about 6 to 20 hours, preferably about 10 hours. When the reaction is substantially complete, the 3-carboxyindole of Formula (19) where R 1 is lower alkyl is isolated by conventional means. Preparation of Compounds of Formula (21) To prepare a compound of Formula (21), diisopropylamine in an inert solvent, preferably tetrahydrofuran, is first cooled to -50°C under argon. To this solution n-butyllithium is added and the temperature of the solution is adjusted to -40°C. A compound of Formula (19) is then added to this solution under continuous stirring for about 1 hour, after which a compound of Formula (21) is isolated by conventional means. Preparation of Compounds of Formula (12a) *•* To prepare a compound of Formula (12a), a compound of Formula (21) is reacted with triethylsilane and boron trifluoride etherate in an inert solvent such as methylene chloride. The mixture is stirred for 6 to 10 hours at room temperature. The compound of Formula (12a) thus prepared is isolated by conventional means. III. Preparation of Compounds of Formula (lb) The compounds of Formula (I) where R 1 is V and R 2 is lower alkyl, identified as Formula (lb), are prepared from the intermediates of Formula (34), the preparation of which is shown below in Reaction Scheme II. Reaction Scheme II C29.) 30) C31D 32} 33 C 173 C 34 wherein R 2 is lower alkyl, L is a leaving group, preferably bromo or tosyl, and R 10 , Y and Z are as defined above in the Summary of the Invention. Starting Materials o-Nitrotoluene derivatives of Formula (29) where Y and Z are chosen from, for example, hydrogen, halo, lower alkoxy, and hydroxy, are commercially available, for example from Aldrich Chemical Company. Alternatively, as is well known in the art, the o-nitrotoluene derivatives of Formula (29) where Y is -CO-jH can be prepared from commercially available o-nitrotoluenes appropriately substituted by carboxyl. Such acids may be converted by methods well known in the art to produce compounds where Y is an ester or an amide. Preparation of Compounds of Formula (17) The compounds of Formula (17) used in step 5 (and elsewhere) may be prepared by a number of known methods. For example, where R 10 is 2- cyanopheny1: C353 where Halo is bromo or iodo. Equimolar amounts of 2-bromobenzonitrile and 4-methylphenylboronic acid are combined with tetrakis[triphenylphosphine] palladium, toluene, sodium carbonate and ethanol and refluxed vigorously, with stirring for 6 to 12 hours, preferably overnight. The mixture is allowed to cool to 10 to 30°C, preferably ambient temperature and hydrogen peroxide is added. The mixture is stirred, extracted with ether, washed with water, and dried over magnesium sulphate to produce an oil, 4-methyl-2'-cyano-biphenyl, a compound of Formula (35. To this oil, equimolar amounts of N-bromosuccinimide and azaisobutylnitrile are added, in a nonpolar solvent (such as ether, cyclohexane, or carbon tetrachloride; preferably carbon tetrachloride), and the mixture is heated under reflux for 1 to 4 hours, preferably 2 hours. The mixture is cooled and filtered, and the solvent is extracted to yield 4-(bromomethyl)-2'-cyanobiphenyl. A method of preparing the starting compound of Formula (35 where R 10 is 2-cyanofuran is shown below: 353 The formyl group is introduced conventionally, e.g. formation of an anion using a hindered base, for ' example lithium diethylamide, and quenching with dimethylformamide. The bromofσrmyl compound is reacted with 4-methylphenylboronic acid as shown above, and the resultant formyl compound converted to cyano conventionally, for example with hydroxylamine hydrochloride/acetic anhydride. Alternatively, compounds of Formula (28), prepared as shown above, may be converted to the corresponding 4-bromomethyl or 4-tosylmethyl derivatives by means well known in the art. Certain substituted indoles of Formula (32), used in step 4 of Reaction Scheme II, are also available commercially, e.g, 2-methylindole, indole-2- carboxylic acid, and indole-3-propanoic acid, from Kawaken Fine Chemicals Co., Ltd., Tokyo, Japan. Preparation of Compounds of Formula (30) To prepare a compound of Formula (30), a compound of Formula (29) is reacted with an equivalent amount of N,N-dimethylformamide dimethylacetal in an aprotic βolvent (such as ether, tetrahydrofuran, or DMF; preferably DMF). The reaction is carried out at a temperature of 100°c to about reflux, preferably about reflux temperature, for about 24 to 100 hours, preferably about 72 hours. When the reaction is substantially complete the nitrostyrene derivative of Formula (30) is isolated by conventional means. Preparation of Compounds of Formula (31) where R 2 is lower alkyl To prepare a compound of Formula (31) where R 2 is lower alkyl, a compound of Formula (30) is reacted with 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of an acyl halide of formula R'COCl, where R 1 is lower alkyl, in the presence of excess of a tertiary base (such as triethylamine or pyridine, preferably pyridine). The reaction is carried out in a chlorinated organic solvent (such as chloroform, 1,2-dichloroethane, or dichloromethane, preferably dichloromethane), at a temperature of 20°C to reflux, preferably at about reflux temperature, for about 5 to 72 hours, preferably about 24 hours. The product of this reaction is isolated by conventional means, and is dissolved in a mixture of an inert solvent (such as DMF, tetrahydrofuran, or dioxane, preferably dioxane) and water, and the resulting mixture is heated at 50°C to reflux, preferably at about reflux, for 8 to 24 hours, preferably 16 hours. When the reaction is substantially complete the nitrophenyl derivative of Formula (31) where R 2 is lower alkyl is isolated and purified by conventional means, preferably chromatography. Preparation of Compounds of Formula (32) where R 2 is lower alkyl To prepare a compound of Formula (32) where R 2 is lower alkyl, a compound of Formula (31) where R 2 is lower alkyl is reacted with 2 to 20 molar equivalents, preferably about 11 molar equivalents, of a reducing metal (such as nickel, iron, or zinc dust, preferably zinc dust) in an acid solvent (such as propanσic acid, butanoic acid, or acetic acid, preferably acetic acid) . The reaction is carried out at a temperature of about 60 to 100°C, preferably at about 90°C, for about 8 to 32 hours, preferably about 16 hours. When the reaction is substantially complete the indole derivative of Formula (32) where R 2 is lower alkyl is isolated and purified by conventional means, preferably chromatography. Preparation of Compounds of Formula (33) where R 2 is lower alkyl and X is -CO-H To prepare a compound of Formula (33) where R 2 is lower alkyl and X is - CO_ , a compound of Formula (32) where R 2 is lower alkyl is reacted with 1 to 3 molar equivalents, preferably about 1.5 molar equivalents, of phosgene. The reaction is carried out in an inert solvent (such as ether, methylene chloride, or tetrahydrofuran; preferably tetrahydrofuran) at -20°C to 10°C, preferably about 0 β -5C, for about 8 to 48 hours, preferably overnight. When the reaction is substantially complete, water is added and the 3-carboxyindole derivative of Formula (33) where R 2 is lower alkyl and X is -C0 2 H is isolated and purified by conventional means, preferably chromatography. Preparation of Compounds of Formula (33) where R 2 is lower alkyl and X is - CO 2 R To prepare a compound of Formula (33) where R 2 is lower alkyl and X is - CO j R 4 , in which R 4 is lower alkyl, the solution of a compound of Formula (33) where X is -COCl in dichloromethane, prepared as shown above, is cooled to 0 to 10°C, preferably about 5°C, and reacted Vith an alcohol of formula R 4 OH, where R 4 is lower alkyl. When the reaction is substantially complete, the 3-(carbo-loweralkoxy)indole derivative of Formula (33), where R 2 is lower alkyl and X is -COjR 4 , in which R 4 is lower alkyl, is isolated and purified by conventional means, preferably chromatography. Preparation of Compounds of Formula (33) where R 2 is lower alkyl and X is - CONR^l' To prepare a compound of Formula (33) where R 2 is lower alkyl and X is - CONR'R 6 , in which R 3 and R* are as defined in the Summary of the Invention, the procedure shown above is followed, substituting an amine of formula R 5 R 6 NH for the alcohol of formula R 4 OH. Preparation of Compounds of Formula (33) where R 2 is lower alkyl and X is - COCF j To prepare a compound of Formula (33) where R 2 is lower alkyl and X is - COCF 3 , a compound of Formula (32) where R 2 is lower alkyl is reacted with 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of trifluoroacetic anhydride. The reaction is carried out in an aprotic solvent- (such as ether, tetrahydrofuran, or DMF; preferably DMF) at -10°C to 20°C, preferably about 0°C, for about 5 to 30 minutes, preferably about 10 minutes. When the reaction is substantially complete the 3-trifluoroacetylindole of Formula (33) where R 2 is lower alkyl and X is -COCF 3 is isolated by conventional means. Preparation of Compounds of Formula (33) where R 2 is lower alkyl and X is Halo To prepare a compound of Formula (33) where R 2 is lower alkyl and X is halo, a compound of Formula (32) where R 2 is lower alkyl is reacted with 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of an N-halosuccinimide. The reaction is carried out in an aprotic solvent (such as ether, tetrahydrofuran, or DMF; preferably DMF) at 0°C to 30°C, preferably about 20°C, for about 5 to 30 hours, preferably about 16 hours. When the reaction is substantially complete the 3-halo compound of Formula (33) where R 2 is lower alkyl and X is halo is isolated by conventional means. Preparation of Compounds of Formula (34) where R 2 is Lower Alkyl and X is Hydrogen, Halo, -COCF,, -COΛ 4 or -CONR 5 R < To prepare a compound of Formula (34) where R 2 is lower alkyl and X is hydrogen, halo, -COCF 3 , -CO-J-t 4 or -CONR * !* 6 , a compound of Formula (32) where X is hydrogen or a compound of Formula (33) where X is halo, -COCF 3 , -C0 2 R 4 or - CONR--R 6 , is reacted with about 1 molar equivalent of an alkali metal hydride, preferably sodium hydride, at -5°C to 20°c, preferably about 0°C. The reaction is carried out in a polar solvent (such as tetrahydrofuran, DMSO, or DMF, preferably DMF), for about 10 minutes to 2 hours, preferably about 30 minutes. The anion thus formed is then reacted with about 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of a compound of Formula (17), allowing the temperature to rise to about 20°C When the reaction is substantially complete, the indole derivative of Formula (34) where R 2 is lower alkyl and X is -C0.-JR 4 is isolated and purified by conventional means, preferably chromatography. IV. Alternative Preparation of Compounds of Formula (lb) The compounds of Formula (lb) jaay also be prepared from the intermediates of Formula (39) where R 2 is lower alkyl, the preparation of which is shown below in Reaction Scheme III. Reaction Scheme III is the preferred procedure for preparing compounds of Formula (lb) in which Y is at the 7-position, especially where Y is -CO.-R 4 , where R 4 is lower alkyl. This is because a substituent at the 7 position may sterically hinder the desired coupling to the 1-position of the indole. In Reaction Scheme III, this problem is avoided because the V moiety is attached to the nitrogen before the formation of the fused heterocycle. Reaction Scheme III 3 D C3BD C37} where R 2 is lower alkyl, and R 10 , Y and Z are as defined in the Summary of the Invention. Preparation of Compounds of Formula (36) where R 2 is lower alkyl To prepare a compound of Formula (36) where R 2 is lower alkyl, a compound of Formula (31) where R 2 is lower alkyl is reacted with about 1 to 5 molar equivalents, preferably about 1.5 molar equivalents, of ethylene glycol. The reaction is carried out in an aromatic solvent (such as benzene, xylene, or toluene; preferably toluene), in the presence of an acid catalyst, preferably p-tolueneβulfonic acid, refluxing for 8 to 20 hours, preferably about 12 hours. When the reaction is substantially complete, the ethylene ketal derivative of Formula (36) where R 2 is lower alkyl, is isolated and purified by conventional means, preferably chromatography. Preparation of Compounds of Formula (37) where R 2 is lower alkyl To prepare a compound of Formula (37) where R 2 is lower alkyl, a compound of Formula (36) where R 2 is lower alkyl is hydrogenated in the presence of a transition metal catalyst. The reaction is carried out in a polar solvent (such as ethyl acetate, methanol, or ethanol, preferably ethanol), under hydrogen, in the presence of a transition metal catalyst (such as di[triphenylphoβphine]palladium chloride, palladium on carbon, or tetrakis[triphenylphosphine]palladium, preferably palladium on carbon), at about room temperature for about 2 to 24 hours, preferably about 6 hours. When the reaction is substantially complete, the phenylamino derivative of Formula (37) where R 2 is lower alkyl, is isolated and purified by conventional means. Preparation of Compounds of Formula (38) where R 2 is lower alkyl To prepare a compound of Formula (38) where R 2 is lower alkyl, a compound of Formula (37) where R 2 is lower alkyl is reacted with about 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of a 4- halomethyl-2'-cyanobiphenyl compound (or a 4-tosylmethyl-2'-cyanobiphenyl compound) in the presence of about 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of a base (such as lithium carbonate, sodium carbonate, or potassium carbonate, preferably potassium carbonate). The reaction is carried out in a polar solvent (such as tetrahydrofuran, DMSO, or DMF, preferably DMF), at about 70-100°C, preferably about 80-90°C, for 6-48 hours, preferably about 16 hours. When the reaction is substantially complete, the ketal derivative of Formula (38) where R 2 is lower alkyl is isolated and purified by conventional means, preferably chromatography. Preparation of Compounds of Formula (39) To prepare a compound of Formula (39) where R 2 is lower alkyl, a compound of Formula (38) where R 2 is lower alkyl is dissolved in an organic solvent (such as dimethoxyethane, ether, or tetrahydrofuran, preferably tetrahydrofuran) containing an excess of a mineral acid (such as sulfuric acid, phosphoric acid, or hydrochloric acid, preferably hydrochloric acid) is stirred at 20-80°C, preferably about 40°C, for 1-5 hours, preferably about 2 hours. When the reaction is substantially complete, the indole derivative of Formula (39) where R 2 is lower alkyl, is isolated and purified by conventional means, preferably chromatography. V. Preparation of Compounds of Formula (Ha) The compounds of Formula (II) where R l is V and R 2 is lower alkyl, identified as Formula (Ha), are prepared from the intermediates of Formula (44), the preparation of which is shown below in Reaction Scheme IV. Reaction Scheme IV C 23 C - 3} C 4 3 wherein R 2 is lower alkyl, and R 10 , Y and Z are as defined in the Summary of the Invention. Starting Materials The 2-amino-3-methylpyridine derivatives of Formula (40) are commercially available, for example from Aldrich. Alternatively, as is well known in the art, acid, ester, alkoxy, alkyl and halo substituted 2-amino-3- methylpyridine compounds of Formula (40) can be prepared by conventional means from commercially available substituted pyridines, e.g., by halogenation, nucleophilic substitution, etc. Step 1 - Preparation of Compounds of Formula (41) To prepare a compound of Formula (41), a compound of Formula (40) is reacted with about 1-2 molar equivalents, preferably about 1 molar equivalent, of di-t-butyldicarbonate in an inert solvent (such as ether, dichloromethane, or tetrahydrofuran, preferably tetrahydrofuran) . The reaction is carried out at a temperature of about 60°C to 100°C, preferably at about 80°C, for about 5 to 30 hours, preferably about 12 hours. When the reaction is substantially complete the t-butylcarbamate derivative of Formula (41) is isolated and purified by conventional means, preferably recrystallization. Step 2 - Preparation of Compounds of Formula (42) To prepare a compound of Formula (42), where R 2 is lower alkyl, a compound of Formula (41) is first reacted with about 2 molar equivalents of a strong base (such as a butyllithium, preferably sec-butyllithium) , in an ethereal solvent (such as diglyme, ether, or tetrahydrofuran, preferably tetrahydrofuran), at a temperature of about -30°C to -70°C, preferably at about -50°C, for about 1-60 minutes, preferably about 10 minutes. To the lithium dianion thus formed is added about 1 to 1.5 molar equivalents, preferably about 1.1 molar equivalents, of an N-methoxy-N- methyl(lower-alkyl)amide of the formula R 2 C(0)N(OCH 3 )CH 3 , in an ethereal solvent, preferably tetrahydrofuran, maintaining the temperature at about - 80°C to -50°C, preferably at about -60°C, for about 5 minutes to 1 hour, preferably about 10 minutes. When the reaction is substantially complete the t-butylcarboxyazaindole of Formula (42) is isolated and purified by conventional means, preferably recrystallization. Step 3 - Preparation of Compounds of Formula (43) To prepare a compound of Formula (43J", where R 2 is lower alkyl, a compound of Formula (42) is dissolved in an inert aprotic solvent (such as ether, tetrahydrofuran, or methylene chloride; preferably methylene chloride), and about 0.1 to 2 molar equivalents, preferably about 1 molar equivalent, of trifluoroacetic acid is added. The reaction is carried out at about room temperature, for about 4-48 hours, preferably about 16 hours. When the reaction is substantially complete the azaindole of Formula (43) is isolated by conventional means, preferably chromatography. Step 4 - Preparation of Compounds of Formula (44) To prepare a compound of Formula (44) where R 2 is lower alkyl, a compound of Formula (43) where R 2 is lower alkyl is reacted with about 1 molar equivalent of an alkali metal hydride, preferably sodium hydride, at 10°C to 40°C, preferably about 20°C. The reaction is carried out in a polar solvent, (such as tetrahydrofuran, DMSO, or DMF, preferably DMF) , for about 5 minutes to 2 hours, preferably about 20 minutes. The anion thus formed is then reacted with about 1 to 1.5 molar equivalents, preferably about 1.2 molar equivalents, of a 4-halomethy1-2'-cyanobiphenyl compound or 4-tosylmethyl-2*- cyanobiphenyl, allowing the temperature to rise to about 20°C. When the reaction is substantially complete, the azaindole derivative of Formula (44) where R 2 is lower alkyl is isolated and purified by conventional means, preferably chromatography. VI. Preparation of Compounds of Formula (lib) The compounds of Formula (II) wherein R 1 is lower alkyl and R 2 is V as defined in the Summary of the Invention, identified as Formula (lib), may be prepared from the intermediates of Formula (11a), the preparation of which is shown below in Reaction Scheme IVA. REACTION SCHEME IVA C45} 5D C 7) C 8D C49} where R 1 is lower alkyl, and R 10 , Y and Z are as defined in the Summary of the Invention. Starting Materials —- In step 1, the compounds of Formula (45) are commercially available, for example from the Aldrich Chemical Company. Step 1 - Preparation of Compounds of Formula (46) To prepare a compound of Formula (46), a compound of Formula (45) is reacted with about 1-1.5 molar equivalents, preferably about 1.1 molecular equivalents, of dimethylamine hydrochloride and excess paraformaldehyde. The reaction is carried out in an inert solvent (such as propanol, butanol, preferably butanol), at about reflux temperature, for about 30 minutes. When the reaction is substantially complete, the derivative of Formula (46) is isolated and purified by conventional means. Step 2 - Preparation of Compounds of Formula (47) To prepare a compound of Formula (47), a compound of Formula (46) is reacted with about 2 molar equivalents, of hexamethylenetetramine in propionic acid as a solvent. The reaction is carried out at about reflux temperature, for about 1-6 hours, preferably about 3 hours. When the reaction is substantially complete, the compound of Formula (47) is isolated and purified by conventional means. Step 3 - Preparation of Compounds of Formula (48) To prepare a compound of Formula (48), a compound of Formula (47) is reacted with a suitable oxidizing agent (for example, chromium trioxide, silver oxide, potaββium permanganate, preferably potassium permanganate) in an inert βolvent, for example acetone. When the reaction is substantially complete, the compound of Formula (48) is isolated and purified by conventional means. Step 4 - Preparation of Compounds of Formula (49) The compounds of Formula (49) are prepared in the same manner as shown for the compounds of Formula (19) in Reaction Scheme IB above. Step 5 - Preparation of Compounds of Formula (50) The compounds of Formula (50) are prepared in the same manner as shown for the compounds of Formula (21) in Reaction Scheme IB above. Step 6 - Preparation of Compounds of Formula (11a) The compounds of Formula (11a) are prepared in the same manner as shown for the compounds of Formula (12a) in Reaction Scheme IB above. VII. Preparation of Compounds of Formula (III) The compounds of Formula (III) where R * is V and R 2 is lower alkyl are prepared from the intermediates of Formula (56) or (57), the preparation of which is shown below in Reaction Scheme V. Reaction Scheme V where R 2 is lower alkyl . and R 3 and R 10 are as defined in the Summary of the Invention. Starting Materials In step 1, the compounds of Formula (51), where R 2 is lower alkyl, are 1-tosylmethyliβocyanide derivatives of the formula: Such compounds are commercially available, for example from Aldrich. Alternatively, as is well known in the art, the compounds of Formula (51) can be prepared by conventional means from 1-tosylmethyisocyanate, as described in van Leuβen and Poβsel, Tet. Lett . 1975:3487-3488 (1975). Preparation of Compounds of Formula (52) To prepare a compound of Formula (52) where R 2 is lower alkyl, methylbutadiene-1-carboxylate is reacted with about 1-1.5 molar equivalents, preferably about 1.1 molecular equivalents, of an optionally substituted 1- tosylmethyliso-cyanide of Formula (51), and about 1-1.5 molar equivalents, preferably about 1.1 molecular equivalents, an alkali metal hydride, preferably sodium hydride. The reaction is carried out in an organic solvent mixture (such as tetrahydrofuran, DME, and/or dry DMSO and anhydrous ether, preferably a mixture of dry DMSO and anhydrous ether), initially at a temperature about 0°C for about 1 hour, and then at 10-40°C, preferably about 20°C, for about 2-12 hours, preferably about 6 hours. When the reaction is substantially complete, the pyrrole derivative of Formula (52) where R 2 is lower alkyl is isolated and purified by conventional means, preferably chromatography. Preparation of Compounds of Formula (53) To prepare a compound of Formula (53) where R 2 is lower alkyl, a compound of Formula (52) where R 2 is lower alkyl is reacted with about 1-2 molar equivalents, preferably about 1.5 molar equivalents, of an alkali metal hydride, preferably sodium hydride, at -10°C to 20°C, preferably about 0°C. The reaction is carried out in a polar solvent, (such as tetrahydrofuran, DMSO, or DMF, preferably DMF), for about 10 minutes to 2 hours, preferably about 30 minutes. The anion thus formed is then reacted with about 1 to 1.5 molar equivalents, preferably about 1.2 molar equivalents, of a 4-halomethy1-2'-cyanobiphenyl compound or 4-tosylmethyl-2'-cyanobiphenyl, allowing the temperature to rise to about 20 β C. When the reaction is substantially complete, the pyrrole derivative of Formula (53) where R 2 is lower alkyl is isolated and purified by conventional means, preferably chromatography. Preparation of Compounds of Formula (54) To prepare a compound of Formula (54) where R 2 is lower alkyl, a compound of Formula (53) where R 2 is lower alkyl is hydrogenated in the presence of a transition metal catalyst. The reaction is carried out in a polar βolvent (such as ethyl acetate, methanol, or ethanol,* preferably ethanol) under hydrogen, in the presence of a transition metal catalyst (such as di[triphenylphosphine]palladium chloride, palladium on carbon, or tetrakis[triphenylphosphine]palladium, preferably palladium on carbon), at about room temperature for about 2 to 16 hours, preferably about 4 hours. When the reaction is subβtantially complete, the pyrrole derivative of Formula (54) where R 2 is lower alkyl is isolated and purified by conventional means. Preparation of Compounds of Formula (55) To prepare a compound of Formula (55), a compound of Formula (54) is reacted with an excess of a base (such as potaββium hydroxide, ammonium hydroxide, or sodium hydroxide; preferably sodium hydroxide) in water and an organic solvent (such as methanol, propanol, or ethanol; preferably methanol), at a temperature of about 50°C to reflux, preferably at about reflux, for 2 to 10 hours, preferably about 4 hours. When the reaction is substantially complete the pyrrole derivative of Formula (55) is isolated by conventional means. Preparation of Compounds of Formula (56) To prepare a compounds of Formula (56) where R 2 is lower alkyl, a compound of Formula (55) is reacted with about 1-2 molar equivalents, preferably about 1.5 molar equivalents, of ethyl chloroformate, in the presence of 1-10 molar equivalents, preferably about 1.5 molar equivalents, of a tertiary amine, preferably triethylamine. The reaction is carried out in a solvent mixture of water and a water-miβcible organic solvent (such as tetrahydrofuran, methylethyl ketone, or acetone, preferably acetone), for about 30 minutes to 4 hours, preferably about 1 hour, at a temperature of about -10 β C to 20°C, preferably at about 0°C. The reaction mixture is then reacted with 1-3 molar equivalents, preferably about 1.5 molar equivalents, of an alkali metal azide (such as lithium azide, potassium azide or sodium azide, preferably sodium azide), for about 30 minutes to 4 hours, preferably about 1 hour, preferably maintaining the temperature at about 0°C. When the reaction is substantially complete, the product is isolated by conventional means, and dissolved in an organic βolvent (βuch aβ benzene, xylene, or toluene, preferably toluene) and heated for 30 minutes to 2 hours, preferably about 1 hour, at 60 to 120°C, preferably about 100°C. When the reaction is subβtantially complete, the product is isolated by conventional means, and reacted with an excess of a Lewis acid (such as titanium tetrachloride, aluminum trichloride or boron trifluoride-diethylether complex, preferably boron trifluoride-diethylether complex) in an organic solvent (such as tetrahydrofuran, DME or anhydrous ether, preferably anhydrous ether), for about 30 minutes to 4 hours, preferably about 2 hour, at a temperature of 0- 30°C, preferably about 10°C. When the reaction is substantially complete the tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one of Formula (56) is isolated by conventional means, preferably crystallization. Preparation of Compounds of Formula (57) To prepare a compounds of Formula (57) where R 2 is lower alkyl, a compound of Formula (56) is first reacted with about 1-1.5 molar equivalents, preferably about 1.1 molar equivalents, of an alkyl lithium base, preferably n-butyllithium, in an ethereal solvent (such as ether, monoglyme, or tetrahydrofuran; preferably tetrahydrofuran ^ ) . The reaction is carried out at a temperature of -100°C to -50°C, preferably about -70°C, for about 5 minutes to 1 hour, preferably about 15 minutes. The anion thus formed is then reacted with about 1 to 2 molar equivalents, preferably about 1.5 molar equivalents, of an alkyl halide of formula R * *Hal, where Hal is chloride, bromide or iodide, preferably iodide, and allowed to warm to about room temperature. The reaction is continued for 4-30 hours, preferably about 16 hours. When the reaction is subβtantially complete the substituted tetrahydro-lH-pyrrolo[2,3- c]pyridin-7-one of Formula (57), where R 2 is lower alkyl, is isolated by conventional means, preferably chromatography. VIII.Preparation of (III) where R l is Lower Alkyl and R 2 i« V The compounds of Formula (III) where R l is lower alkyl and R 2 is V may be prepared as shown in Reaction Scheme I, replacing the phenyl compounds of Formula (4) by appropriately substituted tetrahydropyridin-2-one compounds. PREPARATION OF COMPOUNDS OF FORMULA (I), (II) AND (III) The preparation of the compounds of Formula (I), (II) and (III) from the appropriate intermediates is shown below. It should be understood that the various βubβtituents defined as X may be introduced before conversion of the cyano group to carboxy. However, the various subβtituents defined as X may be introduced into the ring before or after the conversion of the cyano group to tetrazole. Additionally, compounds where X is -C0 2 H can be converted to compounds where X is, for example, -C0 2 R 4 , -CONR 5 R 6 , etc, at any stage of the syntheses. Preparation of Compounds of Formula (I) A. Preparation of (I) where R l is Lower Alkyl and R 2 is 2"-(lH-tetrazol-5- yl)biph«nyl- '-ylmethyl The compounds of Formula (I) where R' is lower alkyl and R 2 is V, identified as Formula (la), may be prepared from the intermediates of Formula (11), (12) or (12a) as shown below in Reaction Scheme VI. REACTION SCHEME VI (la) where R 1 , R 7 , X, Y and Z are as defined in the Summary of the Invention. Preparation of Compounds of Formula (la) where R* is lH-tetrazol-5-yl To prepare a compound of Formula (la where R 8 is lH-tetrazol-5-yl, a compound of Formula (11), (12) or (12a) is reacted with about 1-10 molar equivalents, preferably about 5 molar equivalents, of a trialkyl tin azide, preferably tributyltin azide, in an inert solvent (βuch aβ hexane, benzene, or xylene, preferably xylene). The reaction is carried out at a temperature of 80-150°C, preferably at about reflux temperature, for about 8-48 hours, preferably about 20 hours. The mixture is then cooled to about 0°C, and an acid (such as potassium fluoride-tetrafluoroboric acid/diethyl ether complex, βulfuric acid, or hydrochloric acid, preferably hydrochloric acid or potaββium fluoride-tetrafluoroboric acid/diethyl ether complex) is added, and stirred for an additional 5-60 minutes, preferably about 15 minutes. When the reaction is substantially complete the indole of Formula (la) is isolated and purified by conventional means. Preparation of Compounds of Formula (la) where R 8 is carboxy To prepare a compound of Formula (la) where R 8 is carboxy, a compound of Formula (11) or (12) is reacted with a base by means well known in the art to hydrolyse the cyano group to a carboxy group. B. Preparation of (I) where R 1 is V and R 2 is lower alkyl The compounds of Formula (I) where R 1 is V and R 2 is lower alkyl, identified as Formula (lb), are prepared from the intermediates of Formula (34) or (39), as shown below in Reaction Scheme VII. Reaction Scheme VII (lb) where R 2 is lower alkyl, and R 7 , X, Y and Z are as defined in the Summary of the Invention. Preparation of Compounds of Formula (lb) where R 8 is lH-tetrazol-5-yl To prepare a compound of Formula (lb) where R 8 is lH-tetrazol-5-yl, a compound of Formula (34) or (39), where R 2 is lower alkyl, is reacted with a trialkyl tin azide, preferably tributyltin azide, as described above in Reaction Scheme VI. When the reaction is substantially complete the indole of Formula (lb) where R 8 is lH-tetrazol-5-yl is isolated and purified by conventional means. *- Compounds of Formula (lb) where X and Y are both -C0--R 4 , where R 4 is lower alkyl, can be prepared by the above procedure. Conventional base hydrolyβis of these compounds gives compounds of Formula (lb) where X and Y are both -CO j H. Heating of the dicarboxylic compounds at about their melting point gives compounds where X is hydrogen and Y is -CO,H. Preparation of Compounds of Formula (II) A. Preparation of (II) where R 1 is V and R 2 is Lower Alkyl The compounds of Formula (II) where R 1 is V and R 2 is lower alkyl, identified as compounds of Formula (Ha), are prepared from the intermediates of Formula (44), as shown below in Reaction Scheme VIII. REACTION SCHEME VIII (Ha) where R 2 is lower alkyl, and R 7 , X, Y and Z are as defined in the Summary of the Invention. Preparation of (Ha) where R 2 is lower alkyl and R 8 is lH-tetrazol-5-yl To prepare a compound of Formula (Ha) where R 2 is lower alkyl and R 8 is lH-tetrazol-5-yl, a compound of Formula (44), where R 2 is lower alkyl, is reacted with a trialkyl tin azide, preferably tributyltin azide, as described above in Reaction Scheme VI. The reaction mixture is then preferably acidified with potaββium fluoride-tetrafluoroboric acid/diethyl ether complex, and stirred for about 8-24 hourβ, preferably about 12 hours. When the reaction is substantially complete the azaindole of Formula (II) is isolated and purified by conventional means, preferably chromatography. Preparation of (Ha) where R 2 is lower alkyl, R* is lH-tβtrazol-5-yl, and X is To prepare a compound of Formula (Ha) where R 2 is lower alkyl, R 8 is lH-tetrazol-5-yl, and X is -CO^ or -CONR 5 R 6 , a compound of Formula (Ha) where R 2 is lower alkyl, R* is lH-tetrazol-5-yl_, and X is hydrogen is first reacted with phosgene as described above in Reaction Scheme I to give a compound of Formula (Ha) where X is -COjH. This compound is then converted to compounds where X is -CO-- 4 or -CONR 5 R 6 as described above. B. Preparation of (II) where R 1 is Lower Alkyl and R 2 is V The compounds of Formula (Hb) where R 1 is lower alkyl, R 2 is V, and X is -CO- j H, are prepared from the intermediates of Formula (11a), as shown below in Reaction Scheme VIHA. REACTION SCHEME VI HA where R 1 is lower alkyl, and R 7 , X, Y and Z are as defined in the Summary of the Invention. Preparation of (lib) where R 2 is lower alkyl and R 8 is lH-tetrazol-5-yl To prepare a compound of Formula (lib) where R 2 is lower alkyl and R 8 is lH-tetrazol-5-yl, a compound of Formula (11a), where R 1 is lower alkyl, is reacted with a trialkyl tin azide, preferably tributyltin azide, as described above in Reaction Scheme VI. The reaction mixture is then preferably acidified with potasβium fluoride-tetrafluoroboric acid/diethyl ether complex, and stirred for about 8-24 hourβ, preferably about 12 hours. When the reaction is substantially complete the azaindole of Formula (Hb) is isolated and purified by conventional means, preferably chromatography. Preparation of Compounds of Formula (HI) A. Preparation of (III) where R 1 is V and R 2 is Lower Alkyl The compounds of Formula (III) where R 1 is V and R 2 is lower alkyl, identified as compounds of Formula (Ilia), may be prepared from the intermediates of Formula (56) or (57), as shown below in Reaction Scheme IX. Reaction Scheme IX (Ilia) where R 2 is lower alkyl. and R 3 and R 7 are as defined in the Summary of the Invention. Preparation of (Ilia) where R 2 is lower alkyl and R 8 is lH-tetrazol-5-yl To prepare a compound of Formula (Ilia) where R 2 is lower alkyl and ~~ .~ is lH-tetrazol-5-yl, a compound of Formula (56) or (57), where R 2 is lower alkyl, is reacted with a trialkyl tin azide, preferably tributyltin azide, as described above in Reaction Scheme VI. The reaction mixture is then preferably acidified with potassium fluoride-tetrafluoroboric acid/diethyl ether complex, and stirred for about 8-24 hours, preferably about 12 hours. When the reaction is βubβtantially complete the tetrahydro-lH-pyrrolo[2,3- c]pyridin-7-one of Formula (Ilia) iβ iβolated and purified by conventional means, preferably chromatography. Preparation of (Ilia) where R 2 is lower alkyl, R s is lH-tetrazol-5-yl, and X is -CO j R 4 or -COMlfR' To prepare a compound of Formula (Ilia) where R 2 is lower alkyl, R 8 is lH-tetrazol-5-yl, and X is -COjR 4 or -CO R 5 R 6 , a compound of Formula (Ilia) where R 2 is lower alkyl, R 8 is lH-tetrazol-5-yl, and X is hydrogen is first reacted with phosgene as described above in Reaction Scheme I to give a compound of Formula (Ha) where X is -C0 2 H. This compound is then converted to compounds where X is -CO--R 4 or -CONR- s R £ as described above. B. Preparation of (III) where R 1 is Lower Alkyl and R 2 is V The compounds of Formula (HI) where R 1 is lower alkyl and R 2 is V, identified as compounds of Formula (IHb), may be prepared as shown in Reaction Scheme I, replacing the phenyl compounds of Formula (5) by appropriately subβtituted tetrahydropyridin-2-one compounds, and converting the cyano group to carboxy or lH-tetrazol-5-yl as shown above. Preparation of Compounds of Formula (I), (II) or (III) where X is lower alkyl The preparation of compounds of Formula (I), (II) or (III) where X is lower alkyl may be accomplished by appropriately modifying the starting materials of the above Reaction Schemes. For example, starting with the compound of Formula (31), βubβtituted by lower alkyl alpha to the carbonyl of the keto βidechain, and following the procedures of Reaction Schemes III and VII, a compound of Formula (I) where X is lower alkyl is obtained. Likewise, starting with the compound of Formula (40) substituted by lower alkyl at the 3-position of the ring, and following the procedures of Reaction Schemes IV and VIII, a compound oiTFormula (II) where X iβ lower alkyl iβ obtained. Likewise, starting with the compound of Formula (52) subβtituted by lower alkyl at the 3-position of the ring, and following the procedures of Reaction Schemes V and IX, a compound of Formula (HI) where X is lower alkyl iβ obtained. Preparation of Compounds of Formula (I), (II) or (III) where X is halo The preparation of compounds of Formula (I), (II) or (III) where X is halo may be accomplished by halogenating an appropriate intermediate in the above Reaction Schemes. For example, reacting a compound of Formula (32) with N-chlorosuccinimide gives compound (32) substituted at the 3-position by chlorine. Following the procedures of Reaction Schemes II and VI, compounds of Formula (I) where X is chloro are obtained. Similarly, reacting a compound of Formula (39) with N-chlorosuccinimide gives compound (39) substituted at the 3-position by chlorine. Following the procedures of Reaction Schemes III and VII, compounds of Formula (I) where X is chloro are obtained. Similarly, other compounds of Formula (I), (II) and (III) where X is halo are obtained. Isolation and Purification of the compounds Isolation and purification of the compounds and intermediates described herein can be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, extraction, crystallization, column chromatography, thin-layer chromatography, thick-layer chromatography, preparative low or high-pressure liquid chromatography or a combination of these procedures. Specific illustrations of suitable separation and isolation procedures can be had by reference to the Examples hereinbelow. However, other equivalent separation or isolation procedures could, of course, also be used. Salts of Compounds of Formula (I), (II) and (III) The compounds of Formula (I), (II) and (III) may be converted to a corresponding base addition salt by virtue of the presence of the acidic tetrazole group, and in some instances because of the presence of a carboxyl group. Such salts may be prepared from either inorganic or organic bases. Salts derived from inorganic bases include, but are not limited to, the sodium, potasβium, lithium, ammonium, calcium, magnesium, ferrous, zinc, copper, manganouβ, aluminum, ferric, and manganic salts, and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary and tertiary amines, substituted amines including naturally- occurring substituted amines, and cyclic amines, including isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, tromethamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, N-alkylglucamines, theobromine, purines, piperazine, piperidine, N- ethylpiperidine, and the like. The conversion is preferably accomplished by treatment of the free compound in an inert organic solvent with a stoichiometric amount of an appropriate base in an inert organic solvent (such as methanol or ethanol, preferably methanol) at a temperature of about 0-50°C, preferably ambient temperature. The resulting salt may be brought out of solution with a lees polar solvent, by lyophilization of the solution, or by βimply evaporating the βolvent. The compounds of Formula (II) may be converted to a corresponding acid addition salt by virtue of the presence of a tertiary nitrogen atom. The conversion is accomplished by treatment with at least a stoichiometric amount of an appropriate acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids βuch aβ acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, βuccinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzole acid, cinnamic acid, mandelic acid, menthanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like. Typically, the free base is dissolved in an inert organic solvent such as diethyl ether, ethyl acetate, chloroform, ethanol or methanol and the like, and the acid added in a similar βolvent. The temperature iβ maintained at 0°-50°C. The reβulting βalt precipitates spontaneously or may be brought out of solution with a less polar solvent. In Bummary, the compounds of the present invention are made by the procedures outlined below: 1. A process for preparing compounds of the Formula (I), wherein: R 1 is lower alkyl; R 2 is V; wherein: ~~ V is: X is hydrogen, lower alkyl, halogen, -C(0)CF 3 , -C0 2 R 4 , or -C(0)NR 5 R 6 ; Y is hydrogen, lower alkyl,' lower alkoxy, hydroxy, halogen, Z iβ hydrogen, lower alkyl, lower alkoxy, or halogen; wherein R 4 is hydrogen or lower alkyl; R s iβ hydrogen, lower alkyl, or -CH 2 CO-jR 4 ;; R* is hydrogen or lower alkyl; or R 5 and R 6 taken together with the nitrogen to which they are attached represent a heterocycle; in which; R 8 is lH-tetrazol-5-yl; and W is oxygen, sulfur, or -NR-, wherein R is hydrogen or lower alkyl; comprises: reacting a compound of the formula: where R 1 is lower alkyl, and R 10 , X, Y and Z are as defined in the Summary of the Invention; with a trialkyl tin azide followed by treatment with an acid. 2. A process for preparing compounds of the Formula (I), wherein: R 1 is V; wherein V is aβ defined above; R 2 iβ lower alkyl; and X, Y and Z are aβ defined above; comprises: reacting a compound of the formula: where R 2 iβ lower alkyl, and R 10 , X, Y and Z are as defined in the Summary of the Invention; with a trialkyl tin azide followed by treatment with an acid. 3. A proceβs for preparing compounds of the Formula (II), wherein: R 1 is V; wherein V is aβ defined above; R 2 iβ lower alkyl; and X, Y and Z are aβ defined above; with the proviβo that Y and Z cannot be attached to the nitrogen atom; comprises: reacting a compound of the formula: where R 2 is lower alkyl and R 10 , X, Y and Z are as defined in the Summary of the Invention; with, a trialkyl tin azide followed by treatment with an acid. 4. A procesβ for preparing compounds of the Formula (II), wherein: R 1 iβ lower alkyl; wherein V iβ aβ defined above; and X, Y and Z are aβ defined above; with the proviβo that Y and Z cannot be attached to the nitrogen atom; comprises: reacting a compound of the formula: where R 2 iβ lower alkyl and R !0 , X, Y and Z are aβ defined in the Summary of the Invention; with a trialkyl tin azide followed by treatment with an acid. 5. A process for preparing compounds of the Formula (III), wherein: R 1 is_V; wherein V iβ as defined above; R 2 is lower alkyl; R 3 is hydrogen or lower alkyl; and X is as defined above; comprises: reacting a compound of the formula: where R 2 is lower alkyl, and R 10 and X are as defined in the Summary of the Invention; with a trialkyl tin azide followed by treatment with an acid. 6. A process for preparing compounds of the Formula (I), (II) or (III), wherein: R l and R 2 are different and are either lower alkyl or V; R 3 , R 4 , V, X, Y and Z are as defined above; comprises: reacting a compound of the formula: (I) (II) CUD where R 9 is aβ defined in the Summary of the Invention; with a base. v 7. A proceββ for preparing compounds of the Formula (I), (II) or (III), wherein: R 1 and R 2 are different and are either lower alkyl or V; X is -CO-^l 4 or -ClOJNR-^-t*; and R 3 , R 4 , V, Y and Z are as defined above; comprises: reacting a compound of the formula: where X is hydrogen; with phosgene, optionally followed by an alcohol of formula R 4 OH, where R 4 iβ lower alkyl, or an araine of formula R S R 6 NH, where R 5 and R 6 are aβ defined in the Summary of the Invention. 8. Alternatively, a process for .preparing compounds of the Formula (I), (II) or (III), wherein R 1 , R 2 , R 3 , X, Y and Z are as defined in the Summary of the Invention, constitutes: (a) reacting the compound of Formula (I), (II) or (III) with a base to give a pharmaceutically acceptable base addition salt; or (b) reacting a base addition salt of a compound of Formula (I), (II) or (III) with an acid to give the corresponding free acid; or (c) converting a base addition salt of a compound of Formula (I), (II) or (HI) to another pharmaceutically acceptable base addition salt of Formula (I), (II) or (HI). Utility and Administration A. General Utility The compounds of the present invention, and the pharmaceutically acceptable salts thereof, exhibit useful pharmacological properties in mammals, including use as cardiovascular agents, such as for treating hypertenβion, congestive heart failure, and chronic renal diβease. In view of the local role of the renin angiotensin system in smooth muscle in the alimentary tract and in the brain, the compounds are also useful for treating disorders of the brain such as cognitive disorders, including mood disorders such aβ anxiety and depression, as well as disorders of the alimentary tract, including motility and secretory disorderβ and inflammatory bowel diβease. The compounds of the present invention may also be used to treat chronic renal failure, glaucoma, as well as neuroblastoma^ and other growth disorderβ. The ability of the compounds of Formulae (I), (II) and (HI) to effectively inhibit the binding of angiotensin II to its receptors can be determined by a variety of in vitro and in vivo assays that are known to those of ordinary skill in the art. In particular, assays which inhibit the response of isolated smooth muscle and cardiac muscle to angiotensin II, and assays which inhibit hypertensive responβeβ to angiotenβin II in animal modelβ are predictive of therapeutic utility. B. Testing In vitro assays for determining binding of the present compounds at angiotensin II receptors follow a method which is essentially that described by Gunther, J. Biol . Chem. 259:7622 (1984) and Whitebread et al., Biochem. Biophys. Res. Comm. 163:284 (1989). This method employs [ 125 I]-Sar* He 8 AH in membrane preparations from rat liver (AT-1 receptors) and bovine cerebellum (AT-2 receptors). Binding affinity of a test compound to angiotensin II receptor sites is thus demonstrated. In vitro functional assays for determining antagonist activity of the present compounds at receptors for angiotensin follow a method which iβ essentially that described by Chiu et al., J. Pharmacol . Exp . Ther. 252:711 (1990) and Kamikawa et al., Gastroenterology 88:706 (1985). Isolated ring segments of_ rabbit thoracic aorta and isolated segments of guinea pig ileum are exposed to angiotensin II with and without test compounds, and a contractile response is evoked. Inhibition of contraction demonstrates angiotensin II receptor antagonist activity of the test compound. In order to evaluate the in vivo anti-hypertensive activity of the present compoundβ, male normotensive rats are subjected to complete left renal artery ligation essentially as described by Wong et al., J. Pharmacol . Exp . Ther. 252:726-732 (1990), and a test compound is administered. Lowering of blood pressure demonstrates in vivo hypotensive activity of the test compound. In addition, in vivo testing can be conducted on conscious normotensive rats to which angiotensin II and a test compound are administered. In vivo activity iβ demonstrated by inhibition of the pressor response to angiotenβin II by the test compound. Cognition enhancing activity iβ determined using a modification of the Morriβ Water Maze spatial learning-memory assay (e.g., see Morris, R.M.G, J. Neurosci . Methods 1984, Vol. 11, pp 47-60). This procedure tests rats in six trials daily for two consecutive days, recording the time to find a hidden platform. The cognitive enhancement asβay iβ described in Example 20. C. General Administration In applying the compounds of this invention to treatment of the above conditions, any pharmaceutically acceptable mode of administration can be used, 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, powdera, liquids, suspensions, suppositories, aerosols or the like, or in sustained or controlled release dosage forms 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 an active compound of formula (I), (II) or (II) or the pharmaceutically acceptable salts thereof. In addition, these compositions may include other medicinal agents, pharmaceutical agents, carriers, adjuvants, etc., e.g. antihypertenβive agents βuch aβ angiotensin converting enzyme (ACE) inhibitors, beta-blocking agents and diuretics; bronchodilating agents and an iasthmatics; steroids; antiinflammatories; and non-steroidal antiinflammatories (NSAIDs). Generally, depending on the intended mode of administration, the pharmaceutically acceptable composition will contain about 0.1% to 90%, preferably about 0.5% to 50%, by weight of a pharmaceutically active compound of this invention, the remainder being suitable pharmaceutical excipients, carriers, etc. 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 of administration and the judgment of the prescribing physician. However, an effective dosage is in the range of about 0.1 mg to about 100 mg/kg of body weight, preferably about 1 mg to 10 mg/kg. For an average 70 kg human, this would amount to about 7 mg to 7 g per day, or preferably 70-700 mg per day. The preferred manner of administration for the conditionβ detailed above iβ oral, using a convenient daily dosage regimen which can be adjusted according to the degree of affliction. For such oral administration, a pharmaceutically acceptable, non-toxic composition is formed by the incorporation of any of the normally employed excipients, such as, for example, mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, glucose, gelatin, sucrose, magnesium carbonate, and the like. Such compositions take the form of solutions, suspensions, tablets, pills, capsules, powders, sustained release formulations and the like. Preferably the compositionβ will take the form of a pill or tablet and thus the composition will contain, along with the active ingredient, a diluent βuch aβ lactose, sucrose, dicalcium phosphate, or the like; a lubricant such as magnesium stearate or the like; and a binder such as starch, gum acacia, polyvinylpyrrolidine, gelatin, cellulose and derivatives 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 suspension. If desired, the pharmaceutical composition to be administered may also contain minor amounts of nontoxic auxiliary substances βuch aβ wetting agents, emulsifying agents, or solubilizing agents, pH buffering agents and the like, for example, sodium acetate, sodium citrate, cyclodextrine derivatives, sorbitan monolaurate, triethanolamine sodium acetate, triethanolamine oleate, etc. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Penneylvania, 15th Edition, 1975. The compoβition or formulation to be administered will, in any event, contain a quantity of the active compound(s) in an amount effective to alleviate the symptoms of the subject being treated. Doβage forme or compositions containing active ingredient (compounds of formula (I), (II) or (HI)) in the range of 0.005% to 95% with the balance made up from non-toxic carrier may be prepared. For oral administration, a pharmaceutically acceptable non-toxic composition is formed by the incorporation of any of the normally employed excipients, such as, for example pharmaceutical grades of mannitol, lactoβe, starch, magnesium stearate, talcum, cellulose derivatives, glucose, sucrose, magnesium carbonate, and the like. Such compositions take the form of solutions, suspensions, tablets, capsules, powders, sustained releaβe formulationβ and the like. Such compositions may contain 0.01%-95% active ingredient, preferably 0.1-50%. For a solid dosage form, the solution or suspension, in for example propylene carbonate, vegetable oils or triglycerides, is preferably encapsulated in a gelatin capsule. Such diester 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 administration. Alternatively, liquid or semi-solid oral formulations may be prepared by dissolving or disperβing compounds of Formula (I), (II) or (III) or their salts in vegetable oils, glycols, triglycerideβ, propylene glycol esters (e.g. propylene carbibate) and the like, and encapsulating these solution or suspension in hard or soft gelatin capsule shells. Other useful formulations include those set forth in U.S. Patents Nos. Re. 28,819 and 4,358,603. The formulation can be administered in a single unit dosage form for continuous treatment or in a single unit dosage form ad libitum when relief of symptoms is specifically required. Parenteral administration is generally characterized by injection, either subcutaneouβly, intramuscularly or intravenously. Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution or suspenβion in liquid prior to injection, or as emulsionβ. Suitable excipients are, for example, water, saline, dextrose, glycerol, ethanol or the like. In addition, if desired, the pharmaceutical compositions to be administered may also contain minor amounts of non-toxic auxiliary subβtanceβ such as wetting or emulsifying agents, pH buffering agents, solubility enhancers, and the like, such as for example, sodium acetate, sorbitan monolaurate, triethanolamine oleate, cyclodextrins, etc. A more recently devised approach for parenteral administration employe the implantation of a slow-release or sustained-release system, 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 βuch parenteral compositions iβ highly dependent on the βpecific nature thereof, aβ well aβ 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 comprise 0.2-2% of the active agent in solution. Nasal administration is generally characterized by inhalation of the compoundβ of formula (I), (II) or (III) alone or in combination with other pharmaceutically acceptable excipients. Formulations of compounds of formula (I), (II) or (II) may also be administered to the respiratory tract as an aerosol or solution for a nebulizer, or aβ a microfine powder for insufflation, alone or in combination with an inert carrier βuch as lactose, for the treatment of reversible airways obstruction and asthma. In such a case, the particles of the formulation have diameters of lesβ than 50 microns, preferably less than 10 microns. Pharmaceutical compositions suitable for the treatment of glaucoma may be prepared by mixing the active compound with a non-toxic pharmaceutical organic carrier, or with a pharmaceutically acceptable inorganic carrier. Typical of such pharmaceutically acceptable carriers are, for example, water, mixtures of water and water-miscible solvents such as lower alkanols or vegetable oils, glycerol, polyalkylene glycols, hydroxyethyl cellulose, ethyl oleate, carboxymethyl cellulose, polyvinylpyrrolidone, other polymers water miβcible βuch aβ cellulose derivatives (methylcellulose, carboxymethylcellulose alkaline derivative, hydroxymethylcellulose, hydroxyethylcelluloβe) and other conventionally employed acceptable carriers. The pharmaceutical composition may also contain non-toxic auxiliary substances such aβ emulsifying, preserving, wetting, bodying agents and the like, as for example, polyethylene glycols 200, 300, 400, and 600; carbowaxes 1,000, 1,500, 4,000, 6,000 and 10,000; a polyanionic polymer, e.g. a carboxyvinylpolymer having a molecular weight of from about 4,000 to about 6,000,000; antibacterial components such as quaternary ammonium compounds, phenylmercuric salts known to have cold sterilizing properties and which are non-injurious in use; thimeroβol, methyl and propylparaben, benzylic alcohol, phenylethanol; buffering ingredientβ and iβotonic agents such as alkali metal chloride, borate, acetate, gluconate buffers; antioxidant agents such as sodium metabisulfite, butylated hydroxyaniβole, butylated hydroxytoluene and other conventional ingredientβ βuch as sorbitan monolaurate, triethanolamine oleate, polyoxyethylene sorbitan monopalmitate, dioctyl alkali metal sulfosuccinate, monothioglycerol, ethylenediamine tetraacetic and the like. EXAMPLES The following preparations and examples are given to enable those skilled in the art to more clearly understand and practice the present invention. They should not be considered as a limitation on the scope of the invention, but merely aβ being illustrative and repreaentative of the preferred embodiments of the present invention. Unless specified to the contrary, these preparations and examples are carried out under an inert atmosphere, for example nitrogen or argon. PREPARATION 1 Preparation of Compounds of Formula (5) A. Preparation of (5) where Y and Z are hydrogen A solution of o-toluidine (25 g) , di-t-butyldicarbonate (56g) in tetrahydrofuran (250 ml) was refluxed for 4 hours. The reaction mixture was poured onto ice water/dilute sodium bicarbonate solution and extracted twice with ether. The organic layer was then washed with brine and dried over magnesium sulfate. The solvent was evaporated under reduced pressure; crystallization of the residue from hexane gave 2-methylphenyl-t- butylcarbamate (42 g), a compound of Formula (5), m.p. 82-83°C. B. Preparation of (5), varying Y and Z Similarly, following the procedures of Preparation IA above, but replacing o-toluidine with: 2,3,5-trimethylmethylaniline; 2,4-dimethylmethylaniline; 2,6-dimethylmethylaniline; 4-fluoro-2-methylaniline; 4-chloro-2-methylaniline; and 4-methoxy-2-methylaniline; the following intermediates of Formula (5) were prepared: 2,3,5-trimethylphenyl-t-butylcarbamate; 2,4-dimethylpheny1-t-butylcarbamate; 2,6-dimethylpheny1-t-butylcarbamate; 2-methyl-4-fluorophenyl-t-butylcarbamate; 2-methyl-4-chlorophenyl-t-butylcarbamate; and 2-methyl-4-methoxyphenyl-t-butylcarbamate. C. Preparation of (5), varying Y and Z Similarly, following the procedures of Preparation IA above, but replacing o-toluidine with: 3-methoxy-2-methylaniline; 5-hydroxy-2-methylani1ine; 6-fluoro-2-methylaniline; and 6-chloro-2,4-dimethylaniline; the following exemplary intermediates of Formula (5) are prepared: 3-methoxy-2-methylphenyl-t-butylcarbamate; 5-hydroxy-2-methylphenyl-t-butylcarbamate; 6-fluoro-2-methylphenyl-t-butylcarbamate; and 6-chloro-2,4-dimethylphenyl-t-butylcarbamate. PREPARATION 2 Preparation of Compounds of Formula (7) A. Preparation of (7) where Y and Z are hydrogen A βolution of 2-methylpheny1-t-butylcarbamate (5.0 g), prepared, for example, as described in Preparation 1, in tetrahydrofuran (100 ml) was cooled to -40°C under argon. s-Butyllithium (37 ml) was added dropwise, maintaining the temperature at -45° to -35°C. After addition of the s-butyllithium, the temperature of the mixture was lowered to -75°C, producing an orange solution. A solution of N-methyl-N-methoxy-p-bromophenylacetylamide (5.8 g) (Formula (6), prepared, e.g. as described in Reaction Scheme I), in tetrahydrofuran (50 ml) was then added dropwise, maintaining the temperature at below -65°C. After stirring for 10 minutes, the reaction was quenched with water and ether. The mixture was poured onto ice, extracted twice with ether, the organic layer dried over sodium sulphate, and the solvent evaporated to afford an oil. The oil was dissolved in methylene chloride (150 ml) and trifluoroacetic acid (5 ml) was added. The solution was stirred for 30 minutes at room temperature. The mixture was poured onto dilute sodium bicarbonate solution, extracted with ether, the organic layer dried over magnesium sulphate, and the solvent evaporated to produce an oil. The oil was further purified by silica gel chromatography eluting with 15% ethyl acetate in hexane, to give t-butyl 2-(p-bromophenylmethyl)indole-l-carboxylate (6.0 g), a compound of Formula (7), aβ an oil. B. Preparation of (7), varying Y and Z Similarly, following the procedureβ of Preparation 2A above, but replacing 2-methylphenyl-t-butylcarbamate with other compounds of Formula (5), the following intermediates of Formula (7) were prepared: t-butyl-(p-bromophenylmethyl)-5,7-dimethylindole-l-carboxylate; t—butyl—(p-bromophenylmethyl)-5-methylindole—1-carboxylate; t-butyl-(p-bromophenylmethyl)-7-methylindole-l-carboxylate; t-butyl-(p-bromophenylmethyl)-5-fluoroindole-1-carboxylate; t-butyl-(p-bromophenylmethyl)-5-chloroindole-l-carboxylate; and t-butyl-(p-bromophenylmethyl)-5-methoxyindole-l-carboxylate. C. Preparation of (7), varying Y and Z Similarly, following the procedures of Preparation 2A above, but **. replacing 2-methylphenyl-t-butylcarbamate with other compounds of Formula (5), the following exemplary intermediates of Formula (7) are prepared: t-butyl 2-(p-bromophenylmethyl)-4-methoxyindole-1-carboxylate; t-butyl 2-(p-bromophenylmethyl)-6-hydroxyindole-l-carboxylate; t-butyl 2-(p-bromophenylmethyl)-7-fluoroindole-1-carboxylate; and t-butyl 2-(p-bromophenylmethyl)-7-chloro-5-methylindole-l-carboxylate. PREPARATION 3 Preparation of Compounds of Formula (8) A. Preparation of (8) where Y and Z are hydrogen A mixture of t-butyl 2-(p-bromophenylmethyl)indole-1-carboxylate (7) (6.0 g) (prepared, e.g., as described in Preparation 2), 10% sodium hydroxide in water (20 ml), and ethanol (150 ml), was heated under reflux for 6 hours. The mixture was then poured onto a mixture of ice water/dilute brine and extracted twice with ethyl acetate. The extract was washed with brine and dried over magnesium sulphate. The solvent was evaporated under reduced pressure to produce an oil, which then crystallized. The material was recrystallized from methyl t-butyl ether to give 2-(p-bromophenylmethyl)indole (2.2 g), a compound of Formula (8), m.p. 136°C. B. Preparation of (8), varying Y and Z Similarly, following the procedures of Preparation 3A above, but replacing t-butyl 2-(p-bromophenylmethyl)indole-1-carboxylate with other compounds of Formula (7), the following intermediates of Formula (8) were prepared: 2-(p-bromophenylmethyl)-5,7-dimethylindole; 2-(p-bromophenylmethyl)-5-methylindole; 2-(p-bromophenylmethyl)-7-methy1indole; 2-(p-bromophenylmethyl)-5-fluoroindole; 2-(p-bromophenylmethyl)-5-chloroindole; and 5-methoxy-2-(p-bromophenylmethyl)indole. C. Preparation of (8), varying Y and Z Similarly, following the procedures of Preparation 3A above, but replacing t-butyl 2-(p-bromophenylmethyl)indole-l-carboxylate with other compoundβ of Formula (7), the following exemplary intermediates of Formula (8) are prepared: 2-(p-bromophenylmethyl)-4-methoxyindole; 2-(p-bromophenylmethyl)-5-methoxyindole; 2-(p-bromophenylmethyl)-5-methylindole; 2-(p-bromophenylmethyl)-6-hydroxyindole; 2-(p-bromophenylmethyl)-7-fluoroindole; and 2-(p-bromophenylmethyl)-7-chloro-5-methylindole. PREPARATION 4 Preparation of Compounds of Formula (9) A. Preparation of (9) where R 1 is n-Butyl and Y and Z are Hydrogen A mixture of sodium hydride (0.32 g) in DMF (50 ml) was cooled in an ice bath. A solution of 2-(p-bromophenylmethyl)-indole (2.0 g), prepared, e.g., aβ described in Preparation 3, in DMF, was added, and the mixture stirred for 10 minutes. 1-Iodobutane (0.9 ml) in DMF was added dropwise, and the mixture stirred for 30 minutes. It was then poured into cold dilute HC1 and extracted with ether. The extract was washed three times with cold water, dried over magnesium sulphate, and the βolvent evaporated to afford an orange-red oil, 1- (n-butyl)-2-(p-bromophenylmethyl)indole (2.5 g) , a compound of Formula (9). B. Preparation of (9), varying R 1 , Y and Z Similarly, following the procedures of Preparation 4A above, but optionally replacing 2-(p-bromophenylmethyl)indole with other compounds of Formula (8), and optionally replacing iodobutane with other lower alkyl halides, the following intermediates of Formula (9) were prepared: 1-(iβopentyl)-2-(p-bromophenylmethyl)indole; l-ethyl-2-(p-bromophenylmethyl)indole; l-methyl-2-(p-bromophenylmethyl)indole; 1-(n-pentyl)-2-(p-bromophenylmethyl)indole; 1-(n-butyl)-2-(p-bromophenylmethyl)-5,7-dimethylindole; 1-(n-butyl)-2-(p-bromophenylmethyl)-5-methylindole; 1-(n-butyl)-2-(p-bromophenylmethyl)-7-methylindole; 1-(n-butyl)-2-(p-bromophenylmethyl)-5-fluoroindole; 1-(n-butyl)-2-(p-bromophenylmethyl)-5-chloro-indole; l-iβopropyl-2-(p-bromophenylmethyl)indole; l-cyclopropylmethyl-2-(p-bromophenylmethyl)indole; l-cyclopropylmethyl-2-(p-bromophenylmethyl)-5-fluoroindole; l-cyclopropylmethyl-2-(p-bromophenylmethyl)-5-chloroindole; l-cyclopropylmethyl-2-(p-bromophenylmethyl)-6-methoxyindole; l-cyclohexylmethyl-2-(p-bromophenylmethyl)indole; 1-(n-propyl)-2-(p-bromophenylmethyl)indole; 1-(n-octyl)-2-(p-bromophenylmethyl)indole; 1-(n-butyl)-5-methoxy-2-(p-bromophenylmethyl)-3-trifluoroacetylindole; and 1-(n-butyl)-5-methoxy-2-(p-bromophenylmethyl)-indole. C. Preparation of (9), varying R 1 , Y and Z Similarly, following the procedures of Preparation 4A above, but optionally replacing 2-(p-bromophenylmethyl)indole with other compoundβ of Formula (8), and optionally replacing iodobutane with other lower alkyl halides, the following exemplary intermediates of Formula (9) are prepared: l-ethyl-2-(p-bromophenylmethyl)indole; 1-(2-propyl)-2-(p-bromophenylmethyl)indole; 1-(n-hexyl)-2-(p-bromophenylmethyl)indole; 1-(n-butyl)-2-(p-bromophenylmethyl)-4-methoxyindole; 1-(n-butyl)-2-(p-bromophenylmethyl)-5-methoxyindole; 1-(n-butyl)-2-(p-bromophenylmethyl)-5-methylindole; 1-(n-butyl)-2-(p-bromophenylmethyl)-6-hydroxyindole; 1-(n-butyl)-2-(p-bromophenylmethyl)-7-fluoroindole; and 1-(n-butyl)-2-(p-bromophenylmethyl)-8-chloro-5-methylindole. PREPARATION 5 Preparation of Compounds of Formula (10) A. Preparation of (10) where R 1 is n-Butyl and Y and Z are Hydrogen To a cold (-70°C) stirring solution of 1-(n-butyl)-2-(p- bromophenylmethyl)indole (9) (10.0 g), prepared, e.g., as described in Preparation 4, in tetrahydrofuran (150 ml) was added dropwise n-butyl lithium (18 ml, 2.5 M) , and stirring was continued for 15 minutes. Tributyl borate (12.5 ml) in tetrahydrofuran was then added dropwise and the reaction was allowed to warm to 0°C. It was then quenched with 10% HCl (60 ml) (pH 2-3) and stirred for 15 minutes at 20°C. The reaction mixture was extracted three times with ether, the extract washed with water, dried with magnesium sulfate, and the solvent was evaporated to produce an oil, l-(n-butyl)-2-[4*- (dihydroxyboron)phenylmethyl]indole (7.8 g), a compound of Formula (10). B. Preparation of (10), varying R 1 , Y and Z Similarly, following the procedures of Preparation 5A above, but replacing l-(n-butyl)-2-(p-bromophenylmethyl)indole with other compounds of Formula (9), the following intermediates of Formula (10) were prepared: 1-(iβopentyl)-2-[4'-(dihydroxyboron)phenylmethyl]indole; l-ethyl-2-[4*-(dihydroxyboron)phenylmethyl]indole; l-methyl-2-[4'-(dihydroxyboron)phenylmethyl]indole; 1-(n-pentyl)-2-[4'-(dihydroxyboron)phenylmethyl]indole; 1-(n-butyl)-2-[4'-(dihydroxyboron)phenylmethyl)-5,7-dimethylindole; 1-(n-butyl)-2-[4'-(dihydroxyboron)phenylmethyl]-5-methylindole; 1-{n-butyl)-2-[4'-(dihydroxyboron)phenylmethyl]-7-methylindole; 1-(n-butyl)-2-(4'-(dihydroxyboron)phenylmethyl]-5-fluoroindole; 1-(n-butyl)-2-[4'-(dihydroxyboron)phenylmethyl]-5-chloro-indole; l-iβopropyl-2-[4'-(dihydroxyboron)phenylmethyl]indole; l-cyclopropylmethyl-2-(4'-(dihydroxyboron)phenylmethyl]-indole; l-cyclopropylmethyl-2-(4'-(dihydroxyboron)phenylmethyl]-5-fluoroindole; l-cyclopropylmethyl-2-[4'-(dihydroxyboron)phenylmethyl]-5-chloroindole; l-cyclopropylmethyl-2-[4'-(dihydroxyboron)phenylmethyl]-6-methoxyindole; l-cyclohexylmethyl-2-[4'-(dihydroxyboron)phenylmethyl]-indole; l-(n-propyl)-2-[4*-(dihydroxyboron)phenylmethyl]indole; 1-(n-octyl)-2-[4'-(dihydroxyboron)phenylmethyl]indole; 1-(n-butyl)-5-methoxy-2-(4 • -{dihydroxyboron)phenylmethyl]-3- trifluoroacetylindole; and *. 1-(n-butyl)-5-methoxy-2-[4 • -(dihydroxyboron)phenylmethyl]-indole. C. Preparation of (10), varying R 1 , Y and Z Similarly, following the procedures of Preparation 5A above, but replacing l-(n-butyl)-2-(p-bromophenylmethyl)indole with other compounds of Formula (9), the following exemplary intermediates of Formula (10) are prepared: l-ethyl-2-[4 • -(dihydroxyboron)phenylmethyl]indole; 1-(2-propyl)-2-[4'-(dihydroxyboron) henylmethyl]indole; 1-(n-hexyl)-2-[4'-(dihydroxyboron)phenylmethyl]indole; 1-(n-butyl)-2-[4'-(dihydroxyboron)phenylmethyl]-4-methoxyindole; 1-(n-butyl)-2-[4'-(dihydroxyboron)phenylmethyl]-5-methoxyindole; 1-(n-butyl)-2-[4'-(dihydroxyboron)phenylmethyl]-5-methylindole; 1-(n-butyl)-2-[4'-(dihydroxyboron)phenylmethyl]-6-hydroxyindole; 1-(n-butyl)-2-[4'-(dihydroxyboron)phenylmethyl]-7-fluoroindole; and 1-(n-butyl)-2—[4'-(dihydroxyboron)phenylmethyl]-7-chloro-5-methylindole. PREPARATION 6 Preparation of Compounds of Formula (11) A. Preparation of (11) where R l is n-Butyl and Y and Z are Hydrogen l-(n-Butγl)-2-[4 * -(dihydroxyboron)phenylmethyl]indole (10), (14.0 g), prepared, e.g., as described in Preparation 5, was dissolved in a mixture of toluene (200 ml), ethanol (40 ml), and 2M sodium carbonate (40 ml). To this mixture was added l-cyano-2-bromobenzene (5.8 g) and tetrakis[triphenyl phosphine] palladium (0.6 g), and the combined mixture refluxed with vigorouβ stirring for 24 hourβ. The reaction mixture waβ then poured onto water and the layers separated. The organic layer was dried over magnesium sulphate, and the solvent removed under reduced presβure to afford an oil, which waβ further purified by βilica gel chromatography eluting with 10% ethyl acetate in hexane, to yield l-(n-butyl)-2-(2 n -cyanobiphenyl-4'-ylmethyl)indole (8.1 g), a compound of Formula (11), m.p. 64-68 c C. B. Preparation of (11), varying R 1 , Y and Z Similarly, following the procedures of Preparation 6A above, but replacing l-(n-butyl)-2-[4'-(dihydroxyboron)phenyl-methyl]indole with other compoundβ of Formula (10), the following intermediates of Formula (11) were prepared: l-(isopentyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)indole; l-ethyl-2-(2"-cyanobiphenyl-4*-ylmethyl)indole; l-methyl-2-(2"-cyanobiphenyl-4 • -ylmethyl)indole; 1-(n-pentyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)indole; 1—(n-butyl)-2-(2 M -cyanobiphenyl-4'-ylmethyl)-5,7-dimethylindole; 1-(n-butyl)-2-(2"-cyanobipheny1-4 ' -ylmethyl)-5-methylindole; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-7-methylindole; 1-(n-but l)-2-(2"-cyanobiphenyl-4*-ylmethyl)-5-fluoroindole; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-5-chloro-indole; l-isopropyl-2-(2"-cyanobiphenyl-4'-ylmethyl)indole; l-cyclopropylmethyl-2-(2"-cyanobiphenyl-4'-ylmethyl)-indole; l-cyclopropylmethyl-2-(2"-cyanobiphenyl-4 * -ylmethyl)-5-fluoroindole; l-cyclopropylmethyl-2-(2"-cyanobiphenyl-4*-ylmethyl)-5-chloroindole; l-cyclopropylmethyl-2-(2"-cyanobiphenyl-4'-ylmethyl)-6-methoxyindole; l-cyclohexylmethyl-2-(2"-cyanobiphenyl-4*-ylmethyl)indole; 1-(n-propyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)indole; 1-(n-octyl)-2-(2"-cyanobipheny1-4'-ylmethyl)indole; 1-(n-butyl)-5-methoxy-2-(2"-cyanobipheny1-4'-ylmethyl)-3- trifluoroacetylindole; and 1-(n-butyl)-5-methoxy-2-(2"-cyanobipheny1-4'-ylmethyl)-indole. C. Preparation of (11), varying R 1 , Y and Z Similarly, following the procedures of Preparation 6A above, but replacing l-(n-butyl)-2-[4'-(dihydroxyboron)phenyl-methyl]indole with other compounds of Formula (10), the following exemplary intermediates of Formula (11) are prepared: l-ethyl-2-(2"-cyanobipheny1-4'-ylmethyl)indole; 1-(2-propyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)indole; 1-(n-hexyl-2-(2"-cyanobipheny1-4'-ylmethyl)indole; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-4-methoxyindole; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-5-methoxyindole; 1-(n-butyl)-2-(2 n -cyanobiphenyl-4'-ylmethyl)-5-methylindole; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-6-hydroxyindole; l-(n-butyl)-2-(2"-cyanobipheny1-4'-ylmethyl)-7-fluoroindole; and 1-(n-butyl)-2-(2"-cyanobipheny1-4'-ylmethyl)-7-chloro-5-methylindole. PREPARATION 7 Preparation of Compounds of Formula (12) A. Preparation of (12) where R 1 is n-Butyl, X is -CO-H, and Y and Z are Hydrogen To a solution of l-(n-butyl)-2-(2"-cyanobiphenyl-4"-ylmethyl)indole (11) (5.0 g) , prepared e.g., as described in Preparation 6, in tetrahydrofuran (100 ml) at 0°C was added phosgene solution (10 ml, 20% in toluene) dropwise. The reaction was kept at 0°C overnight. Water (20 ml) was then added and the mixture stirred for 20 minutes. The layers were separated, the aqueous phase extracted with ether, then the combined organic layers washed with dilute sodium hydroxide. The aqueous layer waβ acidified at 0°C with dilute HCl, and the resultant precipitate was filtered off and washed with water and air dried, to yield l-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)indole-3- carboxylic acid (2.4 g), a compound of Formula (12), m.p. 186-188°C. B. Preparation of (12) where R l is n-Butyl, X is -COCF,, and Y and Z are Hydrogen *- To a solution of 1-(n-butyl)-2-(2"-cyanobipheny1-4'-ylmethyl)indole (11) (0.9 g), prepared e.g., aβ deβcribed in Preparation 6, in dimethylformamide (20 ml) at 0°C was added trifluoroacetic anhydride (0.4 ml) dropwise. The reaction waβ βtirred for 10 minutes, and poured into ice/water. The precipitate was filtered off, washed with water, and recrystallized from ether/hexane, to give l-(n-butyl)-2-(2"-cyanobiphenyl-4--ylmethyl)-3- trifluoroacetylindole (0.85 g), a compound of Formula (12). C. Preparation of (12), varying R 1 , Y and Z Similarly, following the procedures of Preparation 7A or 7B above, but replacing 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)indole with other compoundβ of Formula (11), the following intermediates of Formula (12) were prepared: l-(iβopentyl)-2-(2"-cyanobiphenyl-4 * -ylmethyl)indole-3-carboxylic acid; l-ethyl-2-(2"-cyanobiphenyl-4 ■ -ylmethyl)indole-3-carboxylie acid; l-methyl-2-(2"-cyanobipheny1-4'-ylmethyl)indole-3-carboxylie acid; 1-(n-pentyl)-2-(2"-cyanobipheny1-4'-ylmethyl)indole-3-carboxylic acid; 1-(n-butyl)-2-(2"-cyanobipheny1-4"-ylmethyl)-5,7-dimethylindole-3- carboxylic acid; l-(n-butyl)-2-(2"-cyanobiphenyl-4 * -ylmethyl)-5-methylindole-3-carboxylic acid; 1-(n-butyl)-2-(2"-cyanobiphenyl-4*-ylmethyl)-7-methylindole-3-carboxylic acid; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-5-fluoroindole-3-carboxylic acid; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-5-chloro-indole-3- carboxylic acid; l-iβopropyl-2-(2"-cyanobipheny1-4'-ylmethyl)-indole-3-carboxylic acid; l-cyclopropylmethyl-2-(2"-cyanobiphenyl-4."-ylmethyl)-indole-3-carboxylic acid; l-cyclopropylmethyl-2-(2"-cyanobiphenyl-4'-ylmethyl)-5-fluoroindole-3- carboxylic acid; l-cyclopropylmethyl-2-(2"-cyanobiphenyl-4'-ylmethyl)-5-chloroindole-3- carboxylic acid; l-cyclopropylmethyl-2-(2"-cyanobiphenyl-4 ■ -ylmethyl)-6-methoxyindole-3- carboxylic acid; l-cyclohexylmethyl-2-(2"-cyanobiphenyl-4'-ylmethyl)indole-3-carboxylic acid; 1-(n-propyl)-2-(2"-cyanobipheny1-4'-ylmethyl)-indole-3-carboxylic acid; 1-(n-octyl)-2-(2"-cyanobipheny1-4'-ylmethyl)-indole-3-carboxylic acid; and 1-(n-butyl)-5-methoxy-2-(2"-cyanobiphenyl-4'-ylmethyl)-indole-3- carboxylic acid. D. Preparation of (12), varying R 1 , Y and Z Similarly, following the procedures qf Preparation 7A or 7B above, but replacing l-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)indole with other compounds of Formula (11), the following exemplary intermediates of Formula (12) are prepared: l-ethyl-2-(2"-cyanobiphenyl-4'-ylmethyl)indole-3-carboxylic acid; l-(2-propyl)-2-(2"-cyanobiphenyl- '-ylmethyl)indole-3-carboxylic acid; l-(n-hexyl-2-(2"-cyanobiphenyl-4'-ylmethyl)indole-3-carboxylic acid; 1-(n-butyl)-2-(2"-cyanobiphen 1-4'-ylmethyl)-4-methoxyindole-3- carboxylic acid; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-5-methoxyindole-3- carboxylic acid; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-5-methylindole-3-carboxylic acid; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-6-hydroxyindole-3- carboxylic acid; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-7-fluoroindole-3-carboxylic acid; 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-3-trifluoroacetyl-7- fluoroindole; and 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)-7-chloro-5-methylindole-3- carboxylic acid. PREPARATION 8 Preparation of Compounds of Formula (19) and (49) A. Preparation of (19) where R 1 is n-Butyl, X is -CO-H, and Y and Z are Hydrogen To a suspension of 34.1 g NaH (60% dispersion) in 300ml DMF in an ice/methanol bath waβ added dropwise over 45 minutes a solution of 55 g indole-3-carboxylic acid in 250 ml DMF. The mixture was stirred for 30 minutes after completion of the addition, after which a further 100 ml of DMF was added. To the grey thick βuspenβion thus produced was added 40.8 ml of 1- iodobutane at 0°C, and the mixture stirred at room temperature overnight. The suspension then waβ poured into 2 liter of ice water and acidified with 1 N HCl, extracted with ethyl acetate three times, washed twice with water, and dried (MgS0 4 ). The solid material was stirred with ethyl ether and filtered, giving 1-(n-butyl)indole-3-carboxylic acid, 65.4 g. B. Preparation of (19) varying R 1 , Y, and Z Similarly, following the procedures of Preparation 8A above, but replacing 1-iodobutane with methyl iodide, the following intermediate of Formula (19) was prepared: l-methylindole-3-carboxylic acid. C. Preparation of (49) varying R 1 , Y, and Z Similarly, following the procedures of Preparation 8A above, but optionally replacing 1-iodobutane with other lower alkyl halides, and replacing indole-3-carboxylic acid with 7-azaindole-3-carboxylic acid, the following intermediates of Formula (49) are prepared: l-methyl-7-azaindole-3-carboxylic acid; and 1-(n-butyl)-7-azaindole-3-carboxylic acid. PREPARATION 9 Preparation of Compound of Formula (20) A. Preparation of (20) where R 1 * is 2-Cyanophenyl A mixture of 100 g 4-bromobenzaldehyde, 40 ml ethylene glycol, 800 ml of toluene and a catalytic amount of p-toluenesulfonic acid was refluxed for 2 hours, removing water with a Dean-Stark trap. The mixture was then cooled and poured into cold dilute potassium carbonate solution, extracted three times with ether and dried (MgS0 4 ). Solvent was removed under reduced pressure, giving 118 g of 4-bromobenzaldehyde ethylene ketal (23) aβ a βolid. The ketal (23) waβ dissolved in 200 ml of dry tetrahydrofuran. To this solution waβ added a solution of 260 ml of 2.5M of n-butyllithium (in hexane) in 1 liter of dry tetrahydrofuran under argon, and stirred at -70°C for 30 minutes. To the suspension thus formed tributylborate (184 ml) was added dropwise over 15 minutes. The mixture was stirred for 3 hours as it gradually warmed to 0°C, and kept at 0°C in an ice bath. The mixture was poured into 10% HCl, stirred for 1 hour, extracted with diethylether three times, and washed with cold 1M NaOH. The NaOH extracts were cooled in ice and acidified to pH 2 with dilute HCl. The product was washed with water and dried, giving 4-(dihydroxyboron)benzaldehyde, (72g), a compound of Formula (24). The boron compound (24) (65.6 g) and 2-bromobenzonitrile (84 g) were placed into a 3 liter 3-neck flask fitted with a mechanical stirrer containing 20 g of tetrakis(triphenylphosphine)palladium(0) , 1 liter of toluene, 480 ml of 2M sodium carbonate solution and 240 ml ethanol. The mixture was gently refluxed under argon with rapid stirring for 24 hours. A further 3g of triphenylphosphine waβ added and the mixture was continued to reflux overnight. While it waβ still warm 200 ml of water and 300 ml of tetrahydrofuran was added to the mixture. The organic layer was separated while warm, and the aqueous layer was extracted with ethyl acetate. The organic extracts were combined and dried (MgSO . The solid material was recrystallized from a mixture of ethyl acetate and methylene chloride, to yield 55 g of 2-formyl-2'-cyanobiphenyl (99+% pure). PREPARATION 10 Preparation of Compounds of Formula (21) and (50) A. Preparation of (21) where R 1 is n-Butyl, R 1 * is 2-Cyanophenyl, and Y and Z are Hydrogen To a 3 liter 3-neck flaβk waβ added 1 liter of dry tetrahydrofuran and 48.4 ml diisopropylamine. The mixture was cooled to -50°C under argon, and 216 ml of 1.6M of n-butyllithium (in hexane) waβ added dropwise over 5 minutes. The mixture was then allowed to warm to -10°C, and then recooled to -40 β C. A solution of 30 g of l-butylindole-3-carboxylic acid in 100 ml dry tetrahydrofuran was added dropwise over 5 minutes. The solution was stirred at -40° to -30°C for 1 hour, and.then recooled to -70°C. At once was added 28.61 g of 2- ormyl-2'-cyanobiphenyl, and the mixture was stirred at -70°C under argon for 2 hours. The mixture then was warmed to -20°C and 500 ml of water was added while stirring. Ethyl acetate was then added to the mixture and the aqueous layer separated, which was extracted three times with ethyl acetate. The ethyl acetate extracts were combined, washed with 1 N HCl, and dried (MgS0_,) . The solvent was removed under reduced pressure, and the resulting material recrystallized from a mixture of ethyl acetate and hexane, to yield 36.4 g of l-(n-butyl)-2-[l-hydroxy-l-(2"-cyanobiphenyl-4'- yl)methyl]indole-3-carboxylic acid. B. Preparation of (21) varying R 1 , R 1 ', Y, and Z Similarly, following the procedures of Preparation 10A above, but optionally replacing l-butylindole-3-carboxylic acid with other compounds of Formula (19), and replacing 2-formyl-2'-cyanobiphenyl acid with other compounds of Formula (20), the following intermediates of Formula (21) were prepared: 1-(n-butyl)-2-[1-hydroxy-l-(2-cyanothiophen-3-yl)phen-4-ylmethyl]indole- 3-carboxylic acid; methyl 1-(n-butyl)-2-[1-hydroxy-l-(2-cyanothiophen-3-yl)phen-4- ylmethyl]indole-3-carboxylate; 1-(n-butyl)-2-(1-hydroxy-l-(2-cyanofuran-3-yl)phen-4-ylmethyl])indole-3- carboxylic acid; 1-(n-butyl)-2-[1-hydroxy-l-(2-cyanobenzothiophen-3-yl)phen-4- ylmethyl]indole-3-carboxylic acid; 1-(n-butyl)-2-[1-hydroxy-l-(2-cyanobenzofuran-3-yl) hen-4- ylmethyl]indole-3-carboxylic acid; 1-(n-butyl)-2-[1-hydroxy-l-(2-cyanoindol-l-yl)phen-4-ylmethyl]indole-3- carbσxylic acid; l-methyl-2-(2-cyanothiophen-3-yl)ρhen-4-ylmethyl)indole; and l-methyl-2-(1-hydroxy-l-(2-cyanothiophen-3-yl)phen-4-ylmethyl]indole-3- carboxylic acid. C. Preparation of (50) varying R 1 , R 1 ', Y, and Z Similarly, following the procedures of Preparation 10A above, but replacing l-butylindole-3-carboxylic acid with other compounds of Formula (49), and replacing 2-formyl-2'-cyanobiphenyl acid with other compounds of Formula (20), the following intermediates of Formula (50) are prepared: l-methyl-2-[1-hydroxy-l-(2"-cyanobiphenyl-4'-yl)methyl]-7-azaindole-3- carboxylic acid; *- 1-(n-butyl)-2-[1-hydroxy-l-(2"-cyanobipheny1-4'-yl)methyl]-7-azaindole- 3-carboxylic acid; 1-(n-butyl)-2-[1-hydroxy-l-(2-cyanothiophen-3-yl)phen-4-ylmethy1]-7- azaindole-3-carboxylic acid; methyl 1-(n-butyl)-2-[1-hydroxy-l-(2-cyanothiophen-3-yl)phen-4- ylmethyl]-7-azaindole-3-carboxylate; 1-(n-butyl)-2-[1-hydroxy-l-(2-cyanofuran-3-yl)phen-4-ylmethyl]-7- aza)indole-3-carboxylic acid; 1-(n-butyl)-2-[1-hydroxy-l-(2-cyanobenzothiophen-3-yl)phen-4-ylmethyl]- 7-azaindole-3-carboxylic acid; 1-(n-butyl)-2-[1-hydroxy-l-(2-cyanobenzofuran-3-yl)phen-4-ylmethyl]-7- azaindole-3-carboxylic acid; 1-(n-butyl)-2-[1-hydroxy-l-(2-cyanoindol-l-yl)phen-4-ylmethyl]-7- azaindole-3-carboxylic acid; l-methyl-2-(2-cyanothiophen-3-yl)phen-4-ylmethyl)indole; and l-methyl-2-(1-hydroxy-l-(2-cyanothiophen-3-yl)phen-4-ylmethyl]-7- azaindole-3-carboxylic acid. PREPARATION 11 Preparation of Compounds of Formula (11a) and (12a) A. Preparation of (12a) where R l is n-Butyl, R 1 ' is 2-Cyanophenyl, and Y and Z are Hydrogen To a solution of 36.4 g of l-(n-butyl)-2-[l-hydroxy-l-(2"-cyanobiphenyl- 4'-yl)methyl]indole—3-carboxylic acid, obtained for example as in Preparation 10, 150 ml of triethylsilane and 1.5 liters of methylene chloride at ' 0°C was added dropwise 284 ml of BF 3 etherate over 20 minutes. The mixture waβ then warmed to room temperature, stirred for 7 hours, and poured slowly into 1 liter of saturated aqueous bicarbonate βolution. The basic mixture was acidified with concentrated HCl until pH 2 was attained. The methylene chloride layer was separated, and the remaining material waβ extracted two times with methylene chloride. The methylene chloride extracts were combined and dried (MgS0 4 ) . The solid material was recrystallized from a mixture of methylene chloride and hexane to yield 22.9 g of l-(n-butyl)-2-[2"- cyanobipheny1-4'-ylmethyl]indole-3-carboxylie acid. B. Preparation of (12a) varying R 1 , R 1 *, Y, and Z Similarly, following the procedures of Preparation HA above, but replacing 1-(n-butyl)—2-[1-hydroxy-l-(2"-cyanobipheny1-4'-yl)methyl]indole-3- carboxylic acid with other compounds of Formula (21), the following intermediates of Formula (12a) were prepared: 1-(n-butyl)-2-[(2-cyanothiophen-3-yl)phen-4-ylmethyl]indole-3-carboxylic acid; -methyl l-(n-butyl)-2-[(2-cyanothiophen-3-yl)phen-4-ylmethyl]indole-3- carboxylate; 1-(n-butyl)-2-[(2-cyanofuran-3-yl)pheo-4-ylmethyl])indole-3-carboxylic acid; 1—(n-butyl)-2-[(2-cyanobenzothiophen-3-yl)phen-4-ylmethyl]indole-3- carboxylic acid; 1-(n-butyl)-2-[(2-cyanobenzofuran-3-yl)phen-4-ylmethyl]indole-3- carboxylic acid; 1-(n-butyl)-2-[(2-cyanoindol-l-yl)phen-4-ylmethyl]indole-3-carboxylic acid; and l-methyl-2-[(2-cyanothiophen-3-yl)phen-4-ylmethyl]indole-3-carboxylic acid. C. Preparation of (11a) varying R 1 , R", Y, and Z Similarly, following the procedures of Preparation HA above, but replacing 1-(n-butyl)-2-(1-hydroxy-l-(2"-cyanobiphenyl-4*-yl)methyl]indole-3- carboxylic acid with other compounds of Formula (50), the following intermediates of Formula (11a) are prepared: l-methyl-2-[2"-cyanobipheny1-4'-ylmethyl]-7-azaindole-3-carboxylic acid; l-cyclopropylmethyl-2-[2"-cyanobiphenyl-4 • -ylmethyl]-7-azaindole-3- carboxylic acid; l-cyclohexylmethyl-2-[2"-cyanobipheny1-4'-ylmethyl]-7-azaindole-3- carboxylic acid; 1-(n-butyl)-2-[2"-cyanobiphenyl-4'-ylmethyl]-7-azaindole-3-carboxylic acid; 1-(n-butyl)-2-[ (2-cyanothiophen-3-yl)phen-4-ylmethyl)-7-azaindole-3- carboxylic acid; methyl 1-(n-butyl)-2-[ (2-cyanothiophen-3-yl)phen-4-ylmethyl]-7- azaindole-3-carboxylate; 1-(n-butyl)-2-[ (2-cyanofuran-3-yl)phen-4-ylmethyl]-7-aza)indole-3- carboxylic acid; 1-(n-butyl)-2-[ (2-cyanobenzothiophen-3-yl)phen-4-ylmethyl]-7-azaindole- 3-carboxylic acid; 1-(n-butyl)-2-( (2-cyanobenzofuran-3-yl)phen-4-ylmethyl]-7-azaindole-3- carboxylic acid; 1-(n-butyl)-2-[ (2-cyanoindol-l-yl)phen-4-ylmethyl]-7-azaindole-3- carboxylic acid; and l-methyl-2-((2-cyanothiophen-3-yl)phen-4-ylmethyl]-7-azaindole-3- carboxylic acid. PREPARATION 12 Preparation of Compounds of Formula (26) A. Preparation of (26) where R 1 ' is 2-Cyanoindole A mixture of 3.0 g (0.02 mol) of 2-cyanoindole, 4.2g (0.02 mol) of tert- butyl-4-fluorobenzoate, and 5.5g (0.04 mol) of potassium carbonate in 30 ml dimethyl sulfoxide was heated at 110°C for 48 hours. The reaction was poured onto ice-water and extracted twice with ethyl acetate. The organic extracts were combined, washed with water and dried pver magnesium sulfate. Evaporation yielded a dark oil which was flash chromatographed on silica gel, eluting with ethyl acetate-hexane 1:9 to give 3.6g (0.011 mol) of l-[4-(tert- butoxycarbόnyl)phenyl]-2-cyanoindole as an oil. B. Preparation of (26), varying R 1 ' Similarly, following the procedures of Preparation 12A above, but replacing 2-cyanoindole with other compounds of Formula (25), the following intermediates of Formula (26) were prepared: 3-[4-(tert-butoxycarbonyl)phenyl]-2-cyanothiophene; 3-[4-(tert-butoxycarbonyl)phenyl]-2-cyanofuran; 3-[4-(tert-butoxycarbonyl)phenyl]-2-cyanobenzofuran; and 3-[4-(tert-butoxycarbonyl)phenyl]-2-cyanobenzothiophene. PREPARATION 13 Preparation of Compounds of Formula (27) A. Preparation of (27) where R is 2-Cyanoindole 3.6g (0.011 mol) of l-[4-(tert-butoxycarbonyl)phenyl]-2-cyanoindole was dissolved in 40 ml of acetic acid and 10 ml of 30% hydrogen bromide in acetic acid was added dropwise. After stirring for 10 minutes, the slurry was poured onto 200 g of ice-water, and the resulting precipitate was filtered, washed with water and air-dried, to give 2.8g (0.0107 mol) of l-(4-carboxyphenyl)-2- cyanoindole, m.p., 128-131°C. B. Preparation of (27), varying R 1 ' Similarly, following the procedures of Preparation 13A above, but replacing l-[4-(tert-butoxycarbonyl)phenyl]-2-cyaπoindole with other compounds of Formula (26), the following intermediates of Formula (27) were prepared: 3-(4-carboxyphenyl)-2-cyanothiophene; 3-(4-carboxyphenyl)-2-cyanofuran; 3-(4-carboxyphenyl)-2-cyanobenzofuran; and 3-(4-carboxyphenyl)-2-cyanobenzothiophene. PREPARATION 14 Preparation of Compounds of Formula (28) A. Preparation of (28) where R 1 * is 2-Cyanoindolβ 2.8g (0.0107 mol) of l-(4-carboxyphenyl)-2-cyanoindole was dissolved in 100 ml tetrahydrofuran and cooled in an ice-bath. 1.5 ml (0.01 mol) of triethylamine was added, followed by the dropwise addition of 1.1 ml (0.01 mol) ethyl chloroformate. After stirring for 20 minutes the precipitate was removed by filtration and a solution of 1.2g (0.1 mol) sodium borohydride in 60 ml tetrahydrofuran-water 3:1 was added dropwise to the filtrate. After stirring an additional 20 minutes, 5 ml of 10% hydrochloric acid waβ added, and the mixture extracted with ethyl acetate. The extract was dried over magnesium sulfate and evaporated to an oil. The oily material was chromatographed on silica gel, eluting with ethyl acetate-hexane 7:3 to give 1.5g (0.006 mole) of l-[4-(hydroxymethyl)phenyl]-2-cyanoindole aβ an oil. B. Preparation of (28), varying R 1 ' Similarly, following the procedures of Preparation 14A above, but replacing l-(4-carboxyphenyl)-2-cyanoindole with other compounds of Formula (27), the following intermediates of Formula (28) were prepared: 3-[4-(hydroxymethyl)phenyl)-2-cyanothiophene; 3-[4-(hydroxymethyl)phenyl]-2-cyanofuran; 3-[4-(hydroxymethyl)phenyl]-2-cyanobenzofuran; and 3-[4-(hydroxymethyl)phenyl]-2-cyanobenzothiophene. PREPARATION 15 Preparation of Compounds of Formula (20) A. Preparation of (20) where R 1 ' is 2-Cyanoindole l.Og (0.0038 mole) of 2-cyano-l-[4-(hydroxymethyl)phenyl]- indole was dissolved in 150 ml tetrahydrofuran, 10.Og of activated manganese dioxide was added, and the mixture stirred at room temperature for 16 hours. The reaction was filtered and the filtrate evaporated to an oil, which was crystallized from a mixture of methyl-t-butyl ether and hexane 1:1 to give 0.63g (0.0026 mole) of J^(4-formylphenyl)-2-cyanoindole as an oil. B. Preparation of (20), varying R 1 ' Similarly, following the procedures of Preparation 15A above, but replacing 2-cyano-l-(4-(hydroxymethyl)phenyl]- indole with other compounds of Formula (28), the following intermediates of Formula (20) were prepared: 3-(4-formylphenyl)-2-cyanothiophene; 3-(4-formylphenyl)-2-cyanofuran; 3-(4-formylphenyl)-2-cyanobenzofuran; and 3-(4-formylphenyl)-2-cyanobenzothiophene. PREPARATION 16 Preparation of Compounds of Formula (16) A. Preparation of (16) where R 1 is n-Butyl A solution of n-butyl lithium in hexane (1.6M, 12.9 ml) was added dropwise to a cooled (-5 β C) solution of 3.25 g of 1-n-butylindole in a mixture of THF and hexamethylphosphoramide (9:1), keeping the reaction temperature below 5°C. After the addition waβ completed, the reaction mixture was stirred for half a hour at -5°C and then 5.85 g of tributyl tin chloride in THF was added dropwise at -5°C. The reaction mixture was allowed to warm to room temperature and stirred for 0.45 hour, quenched with water and extracted with hexane. The organic layer was then washed with brine dried and concentrated, yielding 8.4 g of l-n-butyl-2-(tributyltin)indole, a compound of Formula (16), B. Preparation of (16), varying R 1 , Y and Z Similarly, following the procedures of Preparation 16A above, but replacing 1-n-butylindole with other compounds of Formula (15), the following intermediates of Formula (16) are prepared: l-methyl-2-(tributyltin)indole; l-isopropyl-2-(tributyltin)indole; 1-cyclopropylmethy1-2-(tributyltin)indole; l-cyclohexylmethyl-2-(tributyltin)indole; and l-octyl-2-(tributyltin)indole. PREPARATION 17 Preparation of Compounds of Formula (17) A. Preparation of (17) where R 1 ' is 3-Cyanothiophen-2-yl A mixture of 2-(4-methylphenyl)-3-cyanothiophene (1.5 g, 7.5 mmol), N- bromoβuccinimide (1.34 g, 7.5 mmol), and azabicyclononane (20 mg) in carbon tetrachloride was irradiated with UV light for one hour. The reaction mixture waβ cooled, and the solid filtered off. The filtrate was concentrated, and the residue purified by flash chromatography, eluting with 5% ethyl acetate/hexane, to yield 2-(4-bromomethylphenyl)-3-cyanothiophene 1.4 g, m.p. 68-75 (slightly impure, used as such). B. Preparation of (17), varying R u Similarly, following the procedures of Preparation 17A above, but replacing 2-( -methylphenyl)-3-cyanothiophene with other similar compounds, the following intermediates of Formula (17) were prepared: 3-(4-bromomethylphenyl)-2-cyanothiophene; 3-(4-bromomethylphenyl)-2-cyanofuran; 4'-(bromomethy1)-2"-cyanobipheny1; 3-(4-bromomethylphenyl)-2-cyanobenzofuran; and 3-(4-bromomethylphenyl)-2-cyanobenzothiophene. PREPARATION 18 Preparation of Compounds of Formula (11) from (17) A. Preparation of (11) where R l * is 3-Cyanothiophen-2-yl A mixture of 2-[4-(bromomethyl)phenyl]-3-cyanothiophene (1.41 g, 5.0 mmol), l-(n-butyl)-2-(tributyltin)indole (2.7 g, 0.0048 mmol), and tetrakis- (triphenylphoβphine)palladium (0) (0.12g) in tetrahydrofuran (25ml) waβ heated at reflux for 2 hours. The reaction was cooled, diluted with ethyl acetate, and treated with 20ml of 20% potasβium fluoride for 15 minutes. The solid was removed by filtration through a celite pad and the organic layer was separated, washed with brine, dried (Na 2 S0 4 ) and concentrated. The residue was purified by flash chromatography, eluting with 3% ethyl acetate/hexane, to yield 1-(n-butyl)-2-((3-cyanothiophen-2-yl)phen-4-ylmethyl]indole, 1.5 g (81%) as an oil. *. B. Preparation of (11), varying R l , R 1 ', Y and Z Similarly, following the procedures of Preparation 18A above, but optionally replacing 2-[4-(bromomethyl)phenyl]-3-cyanothiophene with other compounds of Formula (17), and optionally replacing 1-(n-butyl)-2- (tributyltin)indole with other compounds of Formula (16), the following intermediates of Formula (11) were prepared: 1-(n-butyl)-2-[(2-cyanothiophen-3-yl)phen-4-ylmethyl]indole; 1-(n-butyl)-2-[ (2-cyanofuran-3-yl)phen-4-ylmethyl] )indole; 1-(n-butyl)-2-[ (2-cyanobenzothiophen-3-yl)phen-4-ylmethyl]indole; 1-(n-butyl)-2-( (2-cyanobenzofuran-3-yl)phen-4-ylmethyl]indole; 1-(n-butyl)-2-[ (2-cyanoindol-l-yl)phen-4-ylmethyl]indole; and l-methyl-2-[(2-cyanothiophen-3-yl)phen-4-ylmethyl]indole. PREPARATION 19 Preparation of Compounds of Formula (30) A. Preparation of (30) where Y is 3-Methoxycarbonyl and Z is Hydrogen A solution of methyl 3-methyl-2-nitrobenzoate (29) (51 g) in N,N- dimethylformamide dimethylacetal (100 ml) and DMF (250 ml) was refluxed for 72 hours. The mixture was allowed to cool to room temperature, and was poured into ice water. The precipitate was filtered off, affording 3-carboxymethyl- β-(N,N-dimethylamino)-2-nitrostyrene (34 g), a compound of Formula (30), m.p. 124-126 e C. B. Preparation of (30) where Y is 4-Methoxycarbonyl and Z is Hydrogen Similarly, following the procedures of Preparation 19A above, but replacing methyl 3-methyl-2-nitrobenzoate with methyl 4-methyl-3- nitrobenzoate, the following intermediate of Formula (30) was prepared: 4-carboxymethyl-β-(N,N-dimethylamino)-2-nitrostyrene, m.p. 126-127°C. C. Preparation of (30), varying Y and Z Similarly, following the procedures of Preparation 19A above, but replacing methyl 3-methyl-2-nitrobenzoate with other compounds of Formula (29), the following exemplary intermediates of Formula (30) are prepared: 3-methoxy-β-(N, -dimethy1 mino)-2-nitrostyrene; 4-fluoro-β-( ,N-dimethylamino)-2-nitrostyrene; 5-carboxymethyl-β-(N, -dimethylamino)-2-nitrostyrene; 6-methyl-β-(N,N-dimethylamino)-2-nitrostyrene; and 4-chloro-3-methyl-β-(N,N-dimethylamino)-2-nitrostyrene. PREPARATION 20 Preparation of Compounds of Formula (31) A. Preparation of (31) where R 2 is n-Butyl, Y is 3-Methoxycarbonyl, and Z is Hydrogen A mixture of 3-carboxymethyl-β(N, -dimethylamino)-2-nitrostyrene (30) (34 g) (prepared, e.g., as described in Preparation 19), valeryl chloride (19 ml), and pyridine (16 ml) in dichloromethane (400 ml) was refluxed for 24 hours. The mixture was allowed to cool to room temperature, washed twice with water, and βolvent removed under reduced pressure. The residual dark oil was dissolved in dioxane (150 ml) and water (75 ml) and heated under reflux for 16 hours. The mixture waβ then cooled to room temperature, diluted with water and extracted with ether. The ether extract waβ washed with dilute HCl, followed by aqueous sodium bicarbonate and brine, dried over sodium sulfate and the solvent evaporated. Chromatography on silica gel, eluting with 20% ethyl acetate/hexane, afforded methyl 2-nitro-3-(hexan-2-one)benzoate (17.3 g), a compound of Formula (31), as an oil. B. Preparation of (31) where R 2 is n-Butyl, Y is 4-Methoxycarbonyl and Z is Hydrogen Similarly, following the procedures of Preparation 20A above, but replacing 3-carboxymethyl-β(N, -dimethylamino)-2-nitrostyrene with 4- carboxymethyl-β-(N,N-dimethyl * smino)-2-nitrostyrene, the following intermediate of Formula (31) was prepared: methyl 3-nitro-4-(hexan-2-one)benzoate, m.p. 63-64°C. C. Preparation of (31), varying R 2 , Y and Z Similarly, following the procedures of Preparation 20A above, but optionally replacing 3-carboxymethyl-β(N,N-dimethylamino)-2-nitroetyrene with other compoundβ of Formula (30), and optionally replacing valeryl chloride with other lower acyl halides, the following exemplary intermediates of Formula (31) are prepared: methyl 2-nitro-3-(butan-2-one)benzoate; methyl 2-nitro-3-(pentan-2-one)benzoate; methyl 2-nitro-3-(octan-2-one)benzoate; 1-(3-methoxy-2-nitrophenyl)hexan-2-one; 1-(4-fluoro-2-nitrophenyl)hexan-2-one; 1-(5-carboxymethyl-2-nitrophenyl)hexan-2-one; l-(6-methyl-2-nitrophenyl)hexan-2-one; and 1-(4-chloro-3-methyl-2-nitrophenyl)hexan-2-one. PREPARATION 21 Preparation of Compounds of Formula (32) A. Preparation of (32) where R 2 is n-Butyl, Y is 7-Methoxycarbonyl, and Z is Hydrogen A mixture of methyl 2-nitro-3-(hexan-2-one)benzoate (31) (17.3 g) (prepared, e.g., aβ described in Preparation 20), and zinc dust (50 g) in acetic acid (200 ml) was stirred at 90°C for 16 hours. The mixture was filtered and the filtrate was diluted witlTwater and extracted twice with ethyl acetate. The ethyl acetate extract was washed twice with water, then with aqueous sodium bicarbonate, and finally brine, dried over sodium sulfate and the solvent evaporated under reduced presβure. Chromatography of the residue on silica gel, eluting with 10% ethyl acetate/hexane, afforded methyl 2-(n-butyl)indole-7-carboxylate (11.5 g), a compound of Formula=(32), aβ an oil. B. Preparation of (32) where R 2 is n-Butyl, Y is 6-Methoxycarbonyl, and Z is Hydrogen Similarly, following the procedures of Preparation 21A above, but replacing methyl 2-nitro-3-(hexan-2-one)benzoate with methyl 3-nitro-4-(hexan- 2-one)benzoate, the following intermediate of Formula (32) was prepared: methyl 2-(n-butyl)indole-6-carboxylate, m.p. 76-77°c C. Preparation of (32), varying R 2 , Y and Z Similarly, following the procedures of Preparation 21A above, but replacing methyl 2-nitro-3-(hexan-2-one)benzoate with other compounds of Formula (31), the following exemplary intermediates of Formula (32) are prepared: methyl 2-ethylindole-7-carboxylate; methyl 2-(n-propyl)indole-7-carboxylate; methyl 2-(n-hexyl)indole-7-carboxylate; 2-(n-butyl)-7-methoxyindole; 2-(n-butyl)-6-fluoroindole; methyl 2-(n-butyl)indole-5-carboxylate; 2-(n-butyl)-4-methylindole; and 2-(n-butyl)-6-chloro-7-methylindole. PREPARATION 22 Preparation of Compounds of Formula (33) A. Preparation of (33) where R 2 is n-Butyl, X is 3-Methoxycarbonyl, Y is 7-Methoxycarbonyl, and Z is Hydrogen A solution of phosgene in toluene (37 ml, 1.9M) was added to a solution of methyl 2-(n-butyl)indole-7-carboxylate (32) (11.5 g) (prepared, e.g., as described in Preparation 21), at 5°C in dichloromethane (75 ml). The solution waβ stirred at room temperature for 16 hours, cooled in an ice bath, and treated with methanol (20 ml). Water was added, and the dichloromethane layer waβ separated and solvent evaporated under reduced pressure. Chromatography on silica gel, eluting with 20% ethyl acetate/hexane, afforded dimethyl 2-(n- butyl)indole-3,7-dicarboxylate (7.4 g), a compound of Formula (33), as an oil. B. Preparation of (33) where R 2 is n-Butyl, X is 3-Chloro, Y is 7-Methoxycarbonyl, and Z is Hydrogen To a solution of methyl 2-(n-butyl)indole-7-carboxylate (32) (0.3 g) in 6 ml of dimethylformamide at room temperature was added N-chlorosuccinimide (0.17 g). The solution waβ βtirred at room temperature for 16 hours, then water waβ added, and the mixture extracted -with ether. The extract was separated and solvent evaporated under reduced pressure, to give methyl 2-(n- butyl)-3-chloroindole-7-carboxylate, a compound of Formula (33) where X iβ chloro, as an oil. C. Preparation of (33), varying R 2 , Y and Z Similarly, following the procedures of Preparation 22A above, but optionally replacing methyl 2-(n-butyl)indole-7-carboxylate with other compounds of Formula (32), and optionally replacing phosgene with trifluoroacetic anhydride, the following exemplary intermediates of Formula (33) are prepared: dimethyl 2-ethylindole-3,7-dicarboxylate; dimethyl 2-(n-propyl)indole-3,7-dicarboxylate; dimethyl 2-(n-hexyl)indole-3,7-dicarboxylate; dimethyl 2-(n-butyl)indole-3,6-dicarboxylate. methyl 2-(n-butyl)indole-3-trifluoroacetyl-7-carboxylate; methyl 2-(n-butyl)-7-methoxyindole-3-carboxylate; methyl 2-(n-butyl)-6-fluoroindole-3-carboxylate; dimethyl 2-(n-butyl)indole-3,5-dicarboxylate; methyl 2-(n-butyl)-4-methylindole-3-carboxylate; and methyl 2-(n-butyl)-6-chloro-7-methylindole-3-carboxylate. PREPARATION 23 Preparation of Compounds of Formula (34) A. Preparation of (34) where R 2 is n-Butyl, X is 3-Methoxycarbonyl, Y is 7-Methoxycarbonyl, and Z is Hydrogen Dimethyl 2-(n-butyl)indole-3,7-dicarboxylate (33) (4.5 g) (prepared, e.g., as described in Preparation 22), in DMF (40 ml) was treated with sodium hydride (0.7 g of 60% mineral oil dispersion) at 0°C, and the resulting mixture was stirred for 30 minutes at 0°C. 2'-(Cyano)biphenyl-4-ylmethyl bromide (4.4 g) was added and the mixture was allowed to come to room temperature. Water was added and the mixture was extracted with ethyl acetate. The ethyl acetate extract was washed with water, brine, then dried over sodium sulfate and evaporated under reduced pressure. Chromatography on silica gel, eluting with 25% ethyl acetate-hexane, afforded dimethyl 2-(n- butyl)-l-(2"-cyanobiphenyl-4'-ylmethyl)indole-3,7-dicarboxylate (1.7 g) , a compound of Formula (34), as a white solid. B. Preparation of (34) where R 2 is n-Butyl, Y is 6-Methoxycarbonyl, and X and Z are Hydrogen Similarly, following the procedures of Preparation 23A above, but replacing dimethyl 2-(n-butyl)indole-3,7-dicarboxylate with methyl 2-(n- butyl)indole-6-carboxylate, the following intermediate of Formula (34) was prepared: methyl 2-(n-butyl)-1-(2"-cyanobiphenyl-4*-ylmethyl)indole-6-carboxylate. C. Preparation of (34) where R 2 is n-Butyl, Y is 7-Methoxycarbonyl, X is Chloro, and Z is Hydrogen Similarly, following the procedures of Preparation 23 above, but replacing dimethyl 2-(n-butyl)indole-3,7-dicarboxylate with methyl 2-(n- butyl)-3-chloroindole-7-carboxylate and βtirring the reaction mixture overnight at room temperature, the following intermediate of Formula (34) was prepared: methyl 2-(n-butyl)-3-chloro-l-(2"-cyanobiphenyl-4'-ylmethyl)indole-7- carboxylate. D. Preparation of (34), varying R 2 , Y and Z Similarly, following the procedures of Preparation 23A above, but replacing dimethyl 2-(n-butyl)indole-3,7-dicarboxylate with other compounds of Formula (32) or (33), the following exemplary intermediates of Formula (34) are prepared: dimethyl 2-ethyl-l-(2"-cyanobiphenyl-4'-ylmethyl)indole-3,7- dicarboxylate; dimethyl 2-(n-propyl)-l-(2"-cyanobiphenyl-4'-ylmethyl)-indole-3,7- dicarboxylate; dimethyl 2-(n-hexyl)-1-(2"-cyanobipheny1-4 ■ -ylmethyl)-indole-3,7- dicarboxylate; dimethyl 2-(n-butyl)-1-(2"-cyanobipheny1-4'-ylmethyl)indole-3,6- dicarboxylate; 2-(n-butyl)-7-methoxy-l-(2"-cyanobipheny1-4'-ylmethyl)indole; 2-(n-butyl)-6-fluoro-1-(2"-cyanobipheny1-4'-ylmethyl)indole; methyl 2-(n-butyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)-7-methoxyindole-3- carboxylate; methyl 2-(n-butyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)-6-fluoroindole-3- carboxylate;. dimethyl 2-(n-butyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)-indole-3,5- dicarboxylate; methyl 2-(n-butyl)-1-(2"-cyanobiphenyl-4 ■ -ylmethyl)-4-methylindole-3- carboxylate; and methyl 2-(n-butyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)-6-chlθro-7- methylindole-3-carboxylate. PREPARATION 24 Preparation of Compounds of Formula (36) A. Preparation of (36) where R 2 is Ethyl, Y is 3-Methoxycarbonyl, and Z is Hydrogen A solution of methyl 2-nitro-3-(hexan-2-one)benzoate (31) (1.0 g), ethylene glycol (0.4 g), and p-toluenesulfonic acid (50 mg) in toluene (20 ml) was heated under reflux (120-125°C) for 12 hours. Water formed during the course of reaction was removed using a Dean-Stark separator. The reaction mixture was cooled and diluted with ethyl acetate (100 ml) and the resulting solution washed sequentially with sodium bicarbonate solution (5%), water and brine. The ethyl acetate layer was dried over magnesium βulfate and solvent waβ evaporated under reduced pressure. The residue was chromatographed on silica gel, eluting with 20% ethyl acetate-hexane, to give l-(3- methoxycarbonyl-2-nitrophenyl)butan-2-one ethylene ketal (1.17 g), a compound of Formula (36), as an oil. B. Preparation of (36) where Y is 3-methoxycarbonyl, varying R 2 and Z Similarly, following the procedures of Preparation 24A above, but replacing methyl 2-nitro-3-(hexan-2-one)benzoate with other compounds of Formula (31), the following exemplary intermediates of Formula (36) are prepared: 1-(3-methoxycarbonyl-2-nitro-5-methylphenyl)butan-2-one ethylene ketal; l-(3-methoxycarbonyl-2-nitrophenyl)pentan-2-one ethylene ketal; l-(3-methoxycarbonyl-2-nitrophenyl)hexan-2-one ethylene ketal; l-(3-methoxycarbonyl-2-nitrophenyl)octan-2-one ethylene ketal; l-(3-methoxy-2-nitrophenyl)butan-2-one ethylene ketal; l-(4-fluoro-2-nitrophenyl)butan-2-one ethylene ketal; l-(5-carbomethoxy-2-nitrophenyl)butan-2-one ethylene ketal; l-(6-methyl-2-nitrophenyl)butan-2-one ethylene ketal; and l-(5-chloro-6-methyl-2-nitrophenyl)butan-2-one ethylene ketal. PREPARATION 25 Preparation of Compounds of Formula (37) A. Preparation of (37) where R 2 is Ethyl, Y is 3-Methoxycarbonyl, and Z is Hydrogen To a solution of l-(3-methoxycarbonyl-2-nitrophenyl)butan-2-one ethylene ketal (36) (1.12 g) (prepared, e.g., as described in Preparation 24), in absolute ethanol (50 ml) was added palladium on carbon (150 mg, 10%), and the mixture stirred under hydrogen at atmospheric presβure and room temperature for 6 hours. The reaction mixture waβ passed through a Celite pad to remove catalyst, and the pad was washed with methylene chloride. The combined filtrate and washings were concentrated under reduced presβure to give l-(2- amino-3-methoxycarbonyl-phenyl)butan-2-one ethylene ketal (0.98 g), a compound of Formula (37), aβ a colorless oil. B. Preparation of (37) where Y is 3-methoxycarbonyl, varying R 2 and Z Similarly, following the procedures of Preparation 25A above, but replacing l-(3-methoxycarbonyl-2-nitrophenyl)butan-2-one ethylene ketal with other compoundβ of Formula (36), the following exemplary intermediates of Formula (37) are prepared: l-(3-methoxycarbonyl-2-amino-5-methylphenyl)butan-2-one ethylene ketal; l-(3-methoxycarbonyl-2-aminophenyl)pentan-2-one ethylene ketal; l-(3-methoxycarbonyl-2-aminophenyl)hexan-2-one ethylene ketal; l-(3-methoxycarbonyl-2-aminophenyl)octan-2-one ethylene ketal; l-(3-methoxy-2-aminophenyl)butan-2-one ethylene ketal; l-(4-fluoro-2-aminophenyl)butan-2-one ethylene ketal; l-(5-carbomethoxy-2-aminophenyl)butan-2-one ethylene ketal; 1—(6-methyl-2-aminophenyl)butan-2-one ethylene ketal; and l-(5-chloro-6-methyl-2-aminophenyl)butan-2-one ethylene ketal. PREPARATION 26 Preparation of Compounds of Formula (38) A. Preparation of (38) where R 2 is Ethyl, Y is 3-Methoxycarbonyl, and Z is Hydrogen A mixture of l-(2-amino-3-methoxycarbonylphenyl)butan-2-one ethylene ketal (37) (0.7 g) (prepared, e.g., as described in Preparation 25), 2'- (cyano)biphenyl-4-yl-methylbromide (0.826 g) and potassium carbonate (0.41 g) in dimethylformamide (20 ml) waβ heated at 80-90°C for 16 hours under an inert atmosphere. The reaction mixture was concentrated under reduced pressure, and the residue obtained was diluted with ethyl acetate (100 ml) , washed twice with cold water, and then brine. The solvent was removed under reduced presβure and the residue waβ chromatographed on silica gel, eluting with 20% ethyl acetate/hexane, to give l-[2-(2''-cyanobiphenyl-4'-ylmethylamino)-3- methoxycarbonylphenyl]butan-2-one ethylene ketal (0.52 g), a compound of Formula (38), as an oil. B. Preparation of (38) where Y is 3-methoxycarbonyl, varying R 2 and Z Similarly, following the procedures of Preparation 26A above, but replacing l-(2-amino-3-methoxycarbonylphenyl)butan-2-one ethylene ketal with other compoundβ of Formula (37), the following exemplary intermediateβ of Formula (38) are prepared: 1-[2-(2"-cyanobiphenyl-4 ■ -ylmethylamino)-3-methoxy-carbonyl-5- methylphenyl]butan-2-one ethylene ketal; l-[2-(2"-cyanobipheny1-4'-ylmethylamino)-3-methoxy- carbonylphenyl]pentan-2-one ethylene ketal; 1-[2-(2"-cyanobiphenyl-4'-ylmethylamino)-3-methoxy-carbonylphenyl]hexan- 2-one ethylene ketal; 1-[2-(2"-cyanobipheny1-4'-ylmethylamino)-3-methoxy-carbonylphenyl]octan- 2-one ethylene ketal; 1-[2-(2"-cyanobiphenyl-4'-ylmethylamino)-3-methoxy-phenyl)butan-2-one ethylene ketal; l-[2-(2"-cyanobipheny1-4'-ylmethylamino)-4-fluoro-phenyl)butan-2-one ethylene ketal; 1-[2-(2"-cyanobipheny1-4'-ylmethylamino)-5-methoxycarbonylphenyl)butan- 2-one ethylene ketal; 1-[2-(2"-cyanobipheny1-4'-ylmethylamino)-6-methyl-phenyl)butan-2-one ethylene ketal; and -- 1-(2-(2"-cyanobipheny1-4'-ylmethylamino)-5-chloro-6-methylphenyl)butan- 2-one ethylene ketal. PREPARATION 27 Preparation of Compounds of Formula (39) A. Preparation of (39) where R 2 is Ethyl, Y is 7-Methoxycarbonyl, and Z is Hydrogen A βolution of l-[2-(2"-cyanobiphenyl-4'-ylmethylamino)-3- methoxycarbonylphenyl]butan-2-one ethylene ketal (38) (0.5 g) (prepared, e.g., as described in Preparation 26), in tetrahydrofuran (50 ml) containing hydrochloric acid (2N, 5ml) was stirred at 40°C for 2 hours. The reaction mixture was cooled and diluted with methylene chloride (100 ml), and the resulting solution was carefully neutralized with cold ammonium hydroxide solution. The organic layer waβ separated, and the aqueous layer was extracted twice with methylene chloride. The combined methylene chloride extracts were washed with water and brine and then dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue was chromatographed on βilica gel, eluting with 20% ethyl acetate/hexane, to give methyl 2-ethyl-l-(2"-cyanobiphenyl-4'-ylmethyl)indole-7-carboxylate (0.41 g), a compound of Formula (39), an oil. B. Preparation of (39), varying R 2 , Y and Z Similarly, following the procedures of Preparation 27A above, but replacing 1-(2-(2"-cyanobipheny1-4'-ylmethylamino)-3- methoxycarbonylphenyl]butan-2-one ethylene ketal with other compounds of Formula (38), the following exemplary intermediates of Formula (39) are prepared: methyl 2-(n-propyl)-1-(2"-cyanobipheny1-4'-ylmethyl)-indole-7- carboxylate; methyl 2-(n-butyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)indole-7-carboxylate; methyl 2-(n-hexyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)indole-7-carboxylate; 2-(n-butyl)-7-methoxy-l-(2"-cyanobiphenyl-4'-ylmethyl)indole; 2-(n-butyl)-6-fluoro-1-(2"-cyanobipheny1-4'-ylmethyl)indole; methyl 2-(n-butyl)-1-(2"-cyanobipheny1-4*-ylmethyl)indole-5-carboxylate; 2-(n-butyl)-4-methy1-1-(2"-cyanobipheny1-4'-ylmethyl)indole; and 2-{n-butyl)-5-chloro-4-methyl-l-(2"-cyanobiphenyl-4'-ylmethyl)indole. PREPARATION 28 Preparation of Compounds, of Formula (41) A. Preparation of (41) where Y and Z are Hydrogen A solution of 2-amino-3-methylpyridine (10.8 g) and di-tert-butyl dicarbonate (21.8 g) in tetrahydrofuran was heated under reflux for 12 hours. Evaporation afforded a solid, which was recrystallized from ether- tetrahydrofuran to yield 2-(t-butoxycarbonylamino)-3-methylpyridine (10.2 g), a compound of Formula (41), m.p. 132-133°C. B. Preparation of (41), varying Y and Z Similarly, following the procedures of Preparation 28A above, but replacing 2-amino-3-methylpyridine with other compounds of Formula (40), the following exemplary intermediates of Formula (41) are prepared: 2-(t-butoxycarbonylamino)-3-methyl-4-methoxypyridine; 2-(t-butoxycarbonylamino)-3,5-dimethylpyridine; 2-(t-butoxycarbonylamino)-3-methyl-5-fluoroρyridine; and 2-(t-butoxycarbonylamino)-3,4-dimethyl-6-chloropyridine. PREPARATION 29 Preparation of Compounds of Formula (42) A. Preparation of (42) where R 2 is n-Butyl and Y and Z are Hydrogen A solution of 2-(t-butoxycarbonylamino)-3-methylpyridine (41) (5.3 g) (prepared, e.g, as described in Preparation-28) , in tetrahydrofuran (100 ml) was cooled to -50°C and a solution of sec-butyllithium (46 ml of 1.3 M in cyclohexane) was added. After 10 minutes, the dark solution was treated with N-methoxy-N-methylvaleramide (4.4 g) and the resulting solution was stirred 10 minutes. The mixture was diluted with ether, washed with water, dried over sodium sulfate and evaporated. Crystallization of the residue from hexane afforded l-[2-(t-butoxycarbonylamino)-pyridin-3-yl]hexan-2-one (4.3 g) , a compound of Formula (42), as a white solid m.p. 66-67 °C. B. Preparation of (42), varying R 2 , Y and Z Similarly, following the procedures of Preparation 29A above, but replacing 2-(t-butoxycarbonylamino)-3-methylpyridine with other compounds of Formula (41), the following exemplary intermediates of Formula (42) are prepared: 1-(2-(t-butoxycarbonylamino)pyridin-3-yl]butan-2-one; l-[2-(t-butoxycarbonylamino)pyridin-3-yl]pentan-2-one; 1-[2-(t-butoxycarbonylamino)pyridin-3-y1]octan-2-one; 1-[2-(t-butoxycarbonylamino)pyridin-3-yl)hexan-2-one; 1-[2-(t-butoxycarbonylamino)-4-methoxypyridin-3-yl]hexan-2-one; 1-(2-(t-butoxycarbonylamino)-5-methylpyridin-3-yl]hexan-2-one; 1-[2-(t-butoxycarbonylamino)-5-fluoropyridin-3-yl]hexan-2-one; and 1-[2-(t-butoxycarbonylamino)-6-chloro-4-methylpyridin-3-y1]hexan-2-one. PREPARATION.30 Preparation of Compounds of Formula (43) A. Preparation of (43) where R 2 is n-Butyl and Y and Z are Hydrogen A solution of l-[2-(t-butoxycarbonylamino)pyridin-3-yl]hexan-2-one (42) (4.2 g) (prepared, e.g, as described in Preparation 29), in dichloromethane (25 ml) and trifluoroacetic acid (10 ml) was stirred at room temperature overnight. The solution was concentrated under vacuum and the residue was partitioned between aqueous ammonium hydroxide and ether. The ether layer was waβhed with brine, dried, and the solvent was evaporated. The residue was further purified by silica gel chromatography, eluting with 30% ethyl acetate- hexane, to give 2-(n-butyl)-7-azaindole (2.9 g) , a compound of Formula (43), as an oil, which crystallized on standing to a solid, m.p. 46-47°C. B. Preparation of (43), varying R 2 , Y and Z Similarly, following the procedures of Preparation 30A above, but replacing l-(2-(t-butoxycarbonylamino)pyridin-3-yl]hexan-2-one with other compoundβ of Formula (42), the following exemplary intermediates of Formula (43) are prepared: 2-ethyl-7-azaindole; 2-(n-propyl)-7-azaindole; 2-(n-hexyl)-7-azaindole; 2-(n-butyl)-4-methoxy-7-azaindole; 2-(n-butyl)-6-methyl-7-azaindole; 2-(n-butyl)-4,6-dimethyl-7-azaindole; 2-(n-butyl)-5-fluoro-7-azaindole; and 2-(n-butyl)-6-chloro-4-methyl-7-azaindole. PREPARATION 31 Preparation of Compounds of Formula (44) A. Preparation of (44) where R 2 is n-Butyl and Y and Z are Hydrogen A solution of 2-(n-butyl)-7-azaindole (43) (0.87 g) (prepared, e.g., as described in Preparation 30), in DMF (30 ml) was treated with sodium hydride (0.26 g of 60% mineral oil dispersion) at 20°C and the resulting mixture was stirred 20 minutes at room temperature, then cooled to 0°C. 2'-(Cyano)bipheny1-4-ylmethyl bromide (1.47 g, 6 mmol) was added and the mixture waβ allowed to come to room temperature. Water was added and the mixture was extracted with ethyl acetate. The ethyl acetate extract was washed with water and brine, dried over sodium sulfate and evaporated. Chromatography on βilica gel, eluting with 25% ethyl acetate/hexane, afforded 2-(n-butyl)-1-(2"-cyanobipheny1-4'-ylmethyl)-lH-pyrrolo[2,3-b]pyridine (1.13 g), a compound of Formula (44), aβ a white βolid, m.p. 86-88°C. B. Preparation of (44), varying R 2 , Y and Z Similarly, following the procedureβ of Preparation 31A above, but replacing 2-(n-butyl)-7-azaindole with other compoundβ of Formula (43), the following exemplary intermediates of Formula (44) are prepared: 2-ethyl-l-(2"-cyanobiphenyl-4 τ -ylmethyl)-lH-pyrrolo[2,3-b]pyridine; 2-(n-propyl)-1-(2"-cyanobipheny1-4'-ylmethyl)-IH-pyrrolo(2,3-b]pyridine; 2-(n-hexyl)-1-(2"-cyanobiphen 1-4'-ylmethyl)-lH-pyrrolo[2,3-b]pyridine; 2-(n-butyl)-1-(2"-cyanobipheny1-4'-ylmethyl)-4-methoxy-lH-pyrrolo[2,3- b]pyridine; 2-(n-butyl)-1-(2"-cyanobipheny1-4'-ylmethyl)-6-methyl-lH-pyrrolo[2,3- b]pyridine; 2-(n-butyl)-1-(2"-cyanobipheny1-4'-ylmethyl)-4,6-dimethyl-lH- pyrrolo[2,3-b]pyridine; 2-(n-butyl)-l-(2"-cyanobiphenyl-4'-ylmethyl)-5-fluoro-lH-pyrrolo[2,3- b]pyridine; and 2-(n-butyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)-6-chloro-4-methyl-lH- pyrrolo[2,3-b]pyridine. PREPARATION 32 Preparation of Compounds of Formula (52) A. Preparation of (52) where R 2 is n-Butyl To a cold (0°C) suspension of NaH (5.4 g, 60% suspension in mineral oil) in anhydrous ether (180 ml) was added dropwise a mixture of 1-n- butyltoβylmethyliβocyanide (29 g) and methyl butadienecarboxylate (12.2 ml) in anhydrous ether (180 ml) and dry dimethyl sulfoxide (90 ml) under an inert atmosphere. The reaction mixture was first stirred at 0°C for 1 hour and then slowly brought to room temperature and the stirring continued for an additional 6 hours. The reaction mixture was then cooled to 0°C and cautiously poured onto aqueous saturated ammonium chloride solution (200 ml). The organic layer waβ separated, and the aqueous layer was thoroughly extracted with ethyl acetate. The combined ether and ethyl acetate extracts were sequentially washed with saturated ammonium chloride solution in cold water, and then brine, and dried with magnesium sulfate. The solvent was removed under vacuum and the residue purified by column chromatography on silica gel, eluting with 15% ethyl acetate/hexane, to afford methyl 3-[2-(n- butyl)pyrrol-4-yl]acrylate as a yellow oil (15.32 g), a compound of Formula (52), which crystallized on standing to a solid, m.p. 65-67°C. B. Preparation of (52), varying R 2 Similarly, following the procedures of Preparation 32A above, but replacing 1-n-butyltosylmethylisocyanide with other compounds of Formula (51), the following exemplary intermediates of Formula (52) are prepared: methyl 3-(2-ethylpyrrol-4-yl)acrylate; methyl 3-[2-(2-n-propyl)pyrrol-4-yl]acrylate; and methyl 3-[2-(n-hexyl)ρyrrol-4-yl]acrylate. PREPARATION 33 Preparation of Compounds of Formula (53) A. Preparation of (53) where R 2 is n-Butyl Methyl 3-[2-(n-butyl)pyrrol-4-yl]acrylate (52) ( 6.2 g) (prepared, e.g., as described in Preparation 32), in DMF (200 ml) was treated with sodium hydride (1.8 g of 60% mineral oil dispersion) at 0°C, and the resulting mixture was stirred for 30 minutes at 0°C. 2*-(Cyano)biphenyl-4-ylmethyl bromide (9.8 g) was added, and the mixture allowed to come to room temperature. Water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate extract was washed with water, brine, dried over sodium βulfate and evaporated. The reβidue was chromatographed on silica gel, eluting with 25% ethyl acetate/hexane, affording methyl 3-[2-(n-butyl)-l-(2"- cyanobiphenyl-4'-ylmethyl)ρyrrol-4-yl]acrylate (9.17 g), a compound of Formula (53), as an oil. B. Preparation of (53), varying R 2 Similarly, following the procedures of Preparation 33A above, but replacing methyl 3-[2-(n-butyl)pyrrol-4-yl]acrylate with other compounds of Formula (52), the following exemplary intermediates of Formula (53) are prepared: 3-[2-ethyl-l-{2"-cyanobipheny1-4'-ylmethyl)pyrrol-4-yl]acrylate; 3-[2-(n-propyl)-1-(2"-cyanobipheny1-4'-ylmethyl)pyrrol-4-y1]acrylate; and 3-[2-(n-hexyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)ρyrrol-4-yl]acrylate. PREPARATION 34 Preparation of Compounds of Formula (54) A. Preparation of (54) where R 2 is n-Butyl To a solution of methyl 3-[2-(n-butyl)-l-(2"-cyanobiphenyl-4'- ylmethyl)pyrrol-4-yl]acrylate (53) (6.0 g) (prepared, e.g., as described in Preparation 33), in methylene chloride (200 ml) was added 5% palladium on carbon (1 g), and the resulting mixture was stirred under hydrogen at room temperature at atmospheric pressure for 4 hours. The reaction mixture was filtered through a Celite pad to remove catalyst, and evaporation of the filtrate gave methyl 3-[2-(n-butyl)-l-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4- yljpropionate (6.0 g), a compound of Formula (54), as an oil. B. Preparation of (54), varying R 2 Similarly, following the procedures of Preparation 34A above, but replacing methyl 3-[2-(n-butyl)-l-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4- yl]acrylate with other compounds of Formula (53), the following exemplary intermediates of Formula (54) are prepared: methyl 3-[2-ethyl-l-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4- yljpropionate; v methyl 3-[2-(n-propyl)-l-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4- yl]propiqnate; and methyl 3-[2-(n-hexyl)-l-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4- yljpropiσnate. PREPARATION 35 Preparation of Compounds of Formula (55) A. Preparation of (55) where R 2 is n-Butyl To a solution of methyl 3-[2-(n-butyl)-l-(2"-cyanobiphenyl-4'- ylmethyl)pyrrol-4-yl]propionate (54) (5.8 g) (prepared, e.g., as described in Preparation 34), in methanol (100 ml) was added 10% sodium hydroxide solution (35 ml), and the resulting solution was gently heated under reflux for 4 hours. After cooling to 0°C, the solution was acidified to pH 6 with hydrochloric acid solution (6N), and the product thoroughly extracted into methylene chloride. The combined methylene chloride extracts were washed with cold water, brine, and then dried with magnesium sulfate. Removal of the solvent under vacuum gave 3-[ (2-(n-butyl)-l-(2"-cyanobiphenyl-4*- ylmethyl)pyrrol-4-yl]propionic acid (5.51 g), a compound of Formula (55), as a slightly pinkish gum. B. Preparation of (55), varying R 2 Similarly, following the procedures of Preparation 35A above, but replacing methyl 3-[2-(n-butyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4- yl]propionate with other compounds of Formula (54), the following exemplary intermediates of Formula (55) are prepared: 3-[2-ethyl-l-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4-yl]propionic acid; 3-[2-(n-propyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4-yl]propionic acid; and 3-[2-(n-hexyl)-1-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4-yl]propionic acid. PREPARATION 36 Preparation of Compounds of Formula (56) A. Preparation of (56) where R 2 is n-Butyl To a suspension of 3-[(2-(n-butyl)-l-(2"-cyanobiphenyl-4*- ylmethyl)pyrrol-4-yl]propionic acid (55) (5.5 g) (prepared, e.g., as described in Preparation 35), in water (8 ml) waβ added acetone (40 ml), and the solution waβ cooled to 0°C. To this solution was slowly added triethylamine (2.6 ml) in acetone (20 ml), and the resulting reaction mixture was stirred for 20 minutes at 0°C. A solution of ethyl chloroformate (20 mmol) in acetone (20 ml) was then slowly added while stirring at 0°C. After stirring for an additional 1 hour at 0°C, a solution of sodium azide (1.48 g) in water waβ added dropwise, and stirring was continued for 1 hour at 0°C. The reaction mixture was then poured onto crushed ice, and the product thoroughly extracted into ethyl acetate. The combined extracts were washed with cold water, brine, then dried with magnesium sulfate The solvent waβ removed under reduced preββure, and the reβidue dissolved in toluene (50 ml). The toluene solution was heated for 1 hour on a steam bath, excluding moisture. Removal of the solvent under reduced pressure gave a crude isocyanate (5.42 g, 14.2 mmol). The crude isocyanate obtained above was dissolved in anhydrous ether (200 ml) and boron trifluoride-diethyl ether complex (2.0 ml) was added and the resulting mixture was stirred at 10°C for 2 hours under an inert atmosphere. The reaction mixture was treated with ice, then diluted with saturated ammonium chloride solution (50 ml). The ether layer was separated, and the aqueous layer was thoroughly extracted with methylene chloride. The combined organic extracts were washed with brine, dried with magnesium sulfate and evaporated under reduced pressure. The crude product was crystallized from ethyl acetate to give 2-(n-butyl)-l-(2"-cyanobipheny1-4'-ylmethyl)- 4,5,6,7-tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one (4.37 g), a compound of Formula (56), m.p. 98-100°C. B. Preparation of (56), varying R 2 Similarly, following the procedures of Preparation 36A above, but replacing 3-[(2-(n-butyl)-l-(2"-cyanobiphenyl-4'-ylmethyl)pyrrol-4- yl]propionic acid with other compounds of Formula (55), the following exemplary intermediates of Formula (56) are prepared: 2-ethyl-l-(2"-cyanobipheny1-4'-ylmethyl)-4,5,6,7-tetrahydro-lH- pyrrolo[2,3-c]pyridin-7-one; 2-(n-propyl)-1-(2"-cyanobipheny1-4'-ylmethyl)-4,5,6,7-tetrahydro-lH- pyrrolo[2,3-c]pyridin-7-one; and 2-(n-hexyl)-1-(2"-cyanobiphenyl-4 • -ylmethyl)-4,5,6,7-tetrahydro-lH- pyrrolo[2,3-c]pyridin-7-one. PREPARATION 37 Preparation of Compounds of Formula (57) A. Preparation of (57) where R 2 is n-Butyl and R 3 is Methyl A solution of 2-(n-butyl)-l-(2"-cyanobiphenyl-4'-ylmethyl)-4,5,6,7- tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one (56) (1.15 g) (prepared, e.g, as described in Preparation 36), in dry tetrahydrofuran (100 ml) waβ cooled to - 70°C under an argon atmosphere. To this stirring solution -was added n-butyllithium (2.1 ml, 1.6M in hexane) and the resulting solution was stirred for 15 minutes at -70°C, and then methyl iodide (0.4 ml) was added. The solution was slowly warmed to room temperature, stirred overnight, and then quenched with ammonium chloride. The mixture was then concentrated under vacuum, diluted with methylene chloride, washed with cold water, brine, and then dried over magnesium sulfate. Solvent, was removed under reduced presβure, and the reβidue purified by silica gel chromatography, eluting with ethyl acetate/hexane, to yield 2-(n-butyl)-6-methy1-1-(2"-cyanobipheny1-4'- ylmethyl)-4,5,6,7-tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one (1.018 g), a compound of Formula (56), as a gum. B B.. PPrreeppaarraattiioonn ooff ((5577)),, vvaarryyiinngg RR 2* aanndd R" Similarly, following the procedures of Preparation 37A above, but replacing 2-(n-butyl)-l-(2"-cyanobipheny1-4'-ylmethyl)-4,5,6,7-tetrahydro-lH- pyrrolo[2,3-c]pyridin-7-one with other compounds of Formula (56), the following exemplary intermediates of Formula (57) are prepared: 2-ethyl-6-methyl-l-(2"-cyanobiphenyl-4'-ylmethyl)-4,5,6,7-tetrahydro-lH- pyrrolo[2,3-c]ρyridin-7-one; 2-(n-propyl)-6-methyl-l-(2"-cyanobiphenyl-4'-ylmethyl)-4,5,6,7- tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one; 2-(n-hexyl)-6-methyl-l-(2"-cyanobiphenyl-4'-ylmethyl)-4,5,6,7- tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one; 2-(n-butyl)-6-ethyl-l-(2"-cyanobiphenyl-4*-ylmethyl)-4,5,6,7-tetrahydro- lH-pyrrolo[2,3-c]pyridin-7-one; and 2-(n-butyl)-6-(n-butyl)-1-(2"-cyanobipheny1-4'-ylmethyl)-4,5,6,7- tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one. PREPARATION 38 Preparation of Compounds of Formula (47) Step 1. Preparation of (46) where Y and Z are Hydrogen To 40 ml of n-butyl alcohol waβ added 1.18 g of 7-azaindole, 0.88 g of dimethylamine hydrochloride and 0.33 g of paraformaldehyde, and the mixture refluxed for 30 minutes. The clear βolution was then evaporated to dryness in vacuo, and 10 ml of 10% aqueous hydrochloric acid was added to the residue. The water layer was extracted with ether, and then made strongly basic with potasβium carbonate. The reβulting precipitate was filtered off, washed with ether and dried, yielding 1.42 g (81.1%) of 3-dimethylamino-7-azaindole, m.p. 144-152°C. Step 2. Preparation of (47) where Y and Z are Hydrogen A solution of 3-dimethylamino-7-azaindole (0.35 g) and hexamethylenetetramine (0.28 g) in 1.5 ml of 66% propionic acid was added dropwiβe to a refluxing βolution of 0.28 g of hexamethylenetetramine in 1 ml of the same solvent. The addition was carried out over a period of one hour and the solution was refluxed two hours more. On addition of 6 ml of water to the yellow solution and cooling, a white precipitate (0.16 g, 55%) of the aldehyde formed. The precipitate which melted at 211-213.5°C was recrystallized from water. White needles of 3-formyl-7-azaindole were obtained, m.p. 214.5-215°C. B. Preparation of (47), varying R 2 and 3 Similarly, following the procedures of Preparation 38A, Steps 1 and 2, but replacing 7-azaindole with other compounds of Formula (45), the following exemplary intermediates of Formula (47) are prepared: 3-formyl-5-methoxy-7-azaindole; 3-formyl-5-fluoro-7-azaindole; and 3-formyl-5-methyl-7-azaindole. EXAMPLE 1 Preparation of Compounds of Formula (la) A. Preparation of (la) where R l is n-Butyl, R 7 is 2-(lH-tetrazol-5- yl) henyl, X is -CO-H, and Y and Z are Hydrogen A mixture of l-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)indole-3- carboxylic acid (12) (0.35 g) (prepared e.g., as described in Preparation 18), xylene (20 ml), and tributyltin azide (2 ml) was heated under reflux for about 20 hours. The mixture was then cooled in an ice bath, HCl in ether was added, and the mixture was stirred for 15 minuteβ. The mixture was filtered and washed with ether to yield l-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]indole-3-carboxylic acid (0.34 g) , a compound of Formula (la), m.p. 200-203°C. B. Preparation of (la) where R 1 is n-Butyl, R 7 is (3-(lH-tetrazol-5- yl)thiophβn-2-yl, X is -CO-H, and Y and Z are Hydrogen A suspension of 0.3g (0.75 mmol) of 1-(n-butyl)-2-(3-cyanothiopheπ-2- yl)phen-4-ylmethyl)indole-3-carboxylic acid waβ heated in 1 ml of tributyltin azide for 1 hour at 140-145 β C. The resulting oil was cooled, diluted with ethyl acetate and stirred with potassium fluoride overnight. The solid was removed by filtration, and the filtrate washed with water and brine, and concentrated under reduced presβure. The resultant oil was purified by flash chromatography, eluting with 15% acetone in methylene chloride/1% acetic acid, yielding 1-(n-butyl)-2-[(3-(lH-tetrazol-5-yl)thiophen-2-yl)phen-4- ylmethyl]indole-3-carboxylic acid, which was purified by trituration with hexane/ethyl acetate, to give 175mg of product, m.p., 199.5-200°C. C. Preparation of (la) where R 1 is n-Butyl, Z is Hydrogen, varying R 7 , X and Y Similarly, following the procedures of Example IA or IB above, but replacing 1-(n-butyl)-2-(2"-cyanobiphenyl-4'-ylmethyl)indole-3-carboxylic acid or 1-(n-butyl)-2-(3-cyanothiophen-2-yl)phen-4-ylmethyl)indole-3-carboxylie acid with other compounds of Formula (11), (12), or (12a), the following compounds of Formula (la) were prepared: 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-3- trifluoroacetylindole, m.p. 223-225 β C; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-indole-3- carbonylaminoacetic acid, m.p. 234-237°C; • » l-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-indole-3- carbonylaminoacetic acid methyl ester, m.p. 140-144°C; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biρhenyl-4'-ylmethyl]-4- methoxyindole-3-carboxylic acid, m.p. 216-217°C; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphen 1-4'-ylmethyl]-6- methoxyindole-3-carboxylic acid, m.p. 221-222 β C; 1-(isopentyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3- carboxylic acid, m.p. 210-212 β C; l-ethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3-carboxylic acid, m.p., 234-237°C; l-methyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4 ■ -ylmethyl]indole-3- carboxylic acid, m.p., 231-232°C; 1-(n-pentyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3- carboxylic acid, m.p., 209-210°C; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-5,7- dimethylindole-3-carboxylic acid, m.p. 207~209°C; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4 ■ -ylmethyl]-5- methylindole-3-carboxylic acid, m.p. 207-209°C; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-7- methylindole-3-carboxylic acid, m.p., 218-219°C; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-5- fluoroindole-3-carboxylic acid, m.p., 216-219°C; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-5- chloroindole-3-carboxylic acid, m.p., 228°C; l-iβopropyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-indole-3- carboxylic acid, m.p. 174-175°C; l-cyclopropylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole- 3-carboxylic acid, m.p. 273-274°C; l-cyclopropylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-5- fluoroindole-3-carboxylic acid, m.p. 284-285°C; l-cyclopropylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-5- chloroindole-3-carboxylic acid, m.p. 275-276°C; l-cyclopropylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-6- methoxyindole-3-carboxylic acid, m.p. 252-253°C; l-cyclohexylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4 ■ -ylmethyl]indole- 3-carboxylic acid, m.p. 192-193°C; l-cyclohexylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-5- fluoroindole-3-carboxylic acid, m.p. 163-165°C; l-cyclohexylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-5- chloroindole-3-carboxylic acid, m.p. 137-142°C; 1-(n-propyl)-2-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]indole-3- carboxylic acid, m.p., 233-235°C; 1-(n-octyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-indole-3- carboxylic acid, m.p., 189-190°C. 1-(n-butyl)-5-methoxy-2-[2"-(lH-tetrazol-5-yl)biphenyl-4*-ylmethyl]-3- trifluoroacetylindole, m.p. 214-218°C; v 1-(n-butyl)-5-methoxy-2-[2"-(lH-tetrazol-5-y1)bipheny1-4'- ylmethyl]indole-3-carboxylic acid, m.p. 227°C; 1-(n-butyl)-2-[(2-(lH-tetrazol-5-y1)thiophen-3-yl)phen-4- ylmethyl]indole-3-carboxylic acid, m.p., 153.5-154.5°C; methyl 1-(n-butyl)-2-[ (2-(lH-tetrazol-5-yl)thiophen-3-yl)phen-4- ylmethyl]indole-3-carboxylate, m.p., 191.5-193°C; 1-(n-butyl)-2-[ (2-(lH-tetrazol-5-yl)furan-3-yl)phen-4-ylmethyl] )indole- 3-carboxylic acid, m.p., 160-162°C; 1-(n-butyl)-2-[(2-(lH-tetrazol-5-yl)benzothiophen-3-yl)phen-4- ylmethyl]indole-3-carboxylic acid, m.p., 160-164°C; 1-(n-butyl)-2-[(2-(lH-tetrazol-5-yl)benzofuran-3-yl)phen-4- ylmethyl]indole-3-carboxylic acid, m.p., 215-216.5°C; 1-(n-butyl)-2-[(2-(lH-tetrazol-5-yl)indol-1-yl)phen-4-ylmethyl]indole-3- carboxylic acid, m.p., 171-172°C; l-methyl-2-(2-(lH-tetrazol-5-yl)thiophen-3-yl)phen-4-ylmethyl)indole, m.p., 183°C; and l-methyl-2-[(2-(lH-tetrazol-5-yl)thiophen-3-yl)phen-4-ylmethyl)indole-3- carboxylic acid, m.p., 185.5-186°C. D. Preparation of (la), varying R l , X, Y and Z Similarly, following the procedures of Example IA above, but replacing 1-(n-butyl)-2-(2"-cyanobipheny1-4'-ylmethyl)-indole-3-carboxylic acid with other compounds of Formula (11) or (12),. the following exemplary compounds of Formula (la) are prepared: l-ethyl-2-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]indole-3-carboxylic acid; 1-(2-propyl)-2-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]indole-3- carboxylic acid; 1-{n-hexyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3- carboxylic acid; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-5- methylindole-3-carboxylic acid; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-6- hydroxyindole-3-carboxylic acid; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-7- fluoroindole-3-carboxylic acid; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-3- trifluoroacetyl-7-fluoroindole; 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-7-chloro-5- methylindole-3-carboxylic acid; 1-(n-butyl)-3-chloro-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]indole-3-carboxylic acid; and 1-(n-butyl)-3-methyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]indole-3-carboxylic acid. EXAMPLE 2 Preparation of Compounds of Formula (la) where X is -CONRUt* A. Preparation of (la) where R 1 is n-Butyl, R 7 is 2-(lH-tetrazol-5- yl)phenyl, X is 3-(N-piperidinocarbonyl), and Y and Z are Hydrogen A solution of l-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]indole-3-carboxylic acid (0.4 g) (prepared, e.g, as described in Example 1), and carbonyldiimidazole (0.2 g) in acetonitrile (10 ml) was heated under reflux for 1 hour Piperidine (0.14 ml) and triethylamine (0.2 ml) were added, and the mixture was heated under reflux overnight. The mixture was then poured onto cold dilute HCl and extracted twice with ethyl acetate. The extract was washed with sodium bicarbonate, dried over magnesium sulfate, and evaporated under reduced presβure to yield 1-(n-butyl)-3-(N- piperidinocarbonyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole (0.43 g), a compound of Formula (la), m.p. 127-130°C. B. Preparation of (la) where R 1 is n-Butyl, R 7 is 2-(lH-tetrazol-5- yl)phenyl, X is 3-(N-mβthylaminocarbonyl), and Y and Z are Hydrogen Similarly, following the procedures of Example 2A above, but replacing piperidine with methylamine, the following compound of Formula (la) was prepared: 1-(n-butyl)-3-(N-methylaminocarbonyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl- 4'-ylmethyl]indole, m.p. 166 β C. C. Preparation of (la), varying R 1 , X, Y and Z Similarly, following the procedures of Example 2A above, but optionally replacing 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3- carboxylic acid with other compounds of Formula (la) where X is -C0 2 H, and optionally replacing piperidine with alkylamines of the formula R-'R'-NH, the following exemplary compoundβ of Formula (la) are prepared: n-propyl l-methyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3- carboxylate; ethyl 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3- carboxylate; l-ethyl-3-(N-methylcarboxamido)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]indole-3-carboxylic acid; methyl 1-(2-propyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole- 3-carboxylate; and 1-(n-hexyl-3-(N-hexylcarboxamido)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4 ■ - ylmethyl]indole-3-carboxylic acid. EXAMPLE 3 Preparation of Compounds of Formula (lb) A. Preparation of (lb) where R 2 is n-Butyl, R 7 is 2-(lH-tetrazol-5- yl) henyl, X is 3-Mβthoxycarbonyl, Y is 7-Methoxycarbonyl, and Z is Hydrogen A βolution of dimethyl 2-(n-butyl)-l«-[2"-cyanobiphenyl-4'- ylmethyl]indole-3,7-dicarboxylate (1.7 g) (prepared, e.g., as deβcribed in Preparation 23), and tributyltin azide (2.4 g) in xylene (20 ml) waβ heated under reflux for 48 hours. The βolution waβ cooled to room temperature and then treated with a βolution of hydrochloric acid in ether. The resulting mixture was stirred for 30 minutes. Filtration afforded dimethyl 2-(n-butyl)- l-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3,7-dicarboxylate (1.6 g), a compound of Formula (lb), m.p. 188-189°C. B. Preparation of (lb) where R 2 is n-Butyl, R 7 is 2-(lH-tetrazol-5- yl)phenyl, X is 3-Methoxycarbonyl, and Z is Hydrogen, varying Y Similarly, following the procedureβ of Example 3A above, but replacing dimethyl 2-(n-butyl)-1-[2"-cyanobiphenyl-4'-ylmethyl]indole-3,7-dicarboxylate with other compoundβ of Formula (34), the following compounds of Formula (lb) were prepared: methyl 2-(n-butyl)-3-chloro-l-[2"-(lH-tetrazol-5-yl)bipheny1-4'- ylmethyl]indole-7-carboxylate; methyl 2-(n-butyl)-1-[2"-{lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole- 6-carboxylate; 2-(n-butyl)-7-methoxy-l-[2"-(lH-tetrazol-5-yl)bipheny1-4•- ylmethyl]indole; and 2-(n-butyl)-5-methoxy-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]indole. C. Preparation of (lb), varying R 2 , Y and Z Similarly, following the procedureβ of Example 3A above, but replacing dimethyl 2-(n-butyl)-1-[2"-cyanobiphenyl-4'-ylmethyl]indole-3,7-dicarboxylate with other compounds of Formula (34), the following exemplary compounds of Formula (lb) are prepared: dimethyl 2-ethyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole- 3,7-dicarboxylate; dimethyl 2-(n-propyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4*- ylmethyl]indole-3,7-dicarboxylate; dimethyl 2-(n-hexyl)-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethy1]indole-3,7-dicarboxylate; dimethyl 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)bipheny1-4'- ylmethyl]indole-3,6-dicarboxylate; methyl 2-(n-butyl)-1-[2"-(lH-tetrazo1-5-y1)bipheny1-4'-ylmethyl]-7- methoxyindole-3-carboxylate; methyl 2-(n-butyl)-l-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-6- fluoroindole-3-carboxylate;. dimethyl 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]- indole-3,5-dicarboxylate; methyl 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-4- methylindole-3-carboxylate; and — methyl 2-(n-butyl)-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-6- chloro-7-methylindole-3-carboxylate. κ EXAMPLE 4 Preparation of Compounds of Formula (lb) A. Preparation of (lb) where R 2 is n-Butyl, R 7 is 2-(lH-tβtraxol-5- yl)phenyl, X is 3-Carboxyl, Y is 7-Carboxyl, and Z is Hydrogen A mixture of dimethyl 2-(n-butyl)-l-[2"-(lH-tetrazol-5-yl)bipheny1-4'- ylmethyl]indole-3,7-dicarboxylate (1.5 g) (prepared, e.g., as described in Example 3), in water (35 ml) and 15% sodium hydroxide (5.3 ml) was heated under reflux for 2 hours. The resulting solution was cooled, acidified with hydrochloric acid and filtered to afford 2-(n-butyl)-l-[2"-(lH-tetrazol-5- yl)biphenyl-4'-ylmethyl]-3,7-dicarboxylic acid (1.3 g) , a compound of Formula (lb), as a white solid, m.p. 185-186°C. B. Preparation of (lb), varying R 2 , Y and Z Similarly, following the procedures of Example 4A above, but replacing dimethyl 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3,7- dicarboxylate with other compounds of Formula (lb) where X or Y is -C0 2 R 4 , where R 4 is lower alkyl, the following compounds of Formula (lb) were prepared: 2-(n-butyl)-3-chloro-l-[2"-(lH-tetrazol-5-yl)bipheny1-4'- ylmethyl]indole-7-carboxylic acid; and 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-6-carboxylic acid. C. Preparation of (lb), varying R 2 , Y and Z Similarly, following the procedures of Example 4A above, but replacing dimethyl 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3,7- dicarboxylate with other compounds of Formula (lb) where X is -C0 2 R 4 , where R 4 is lower alkyl, the following exemplary compounds of Formula (lb) are prepared: 2-ethyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-indole-3,7- dicarboxylic acid; 2-(n-propyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3,7- dicarboxylic acid; 2-(n-hexyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3,7- dicarboxylic acid; 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-3,6- dicarboxylic acid. 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-7- methoxyindole-3-carboxylic acid; 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-6- fluoroindole-3-carboxylic acid; 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-indole-3,5- dicarboxylic acid; 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-4- methylindole-3-carboxylic acid; and 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-6-chloro-7- methylindole-3-carboxylic acid. EXAMPLE 5 Preparation of Compounds of Formula (lb) A. Preparation of (lb) where R 2 is n-Butyl, R 7 is 2-(lH-tetrazol-5- yl) henyl, X and Z are Hydrogen, and Y is 7-Carboxyl 2-(n-Butyl)-1-[2"-(lH-tetrazol-5-yl)bipheny1-4 ■ -ylmethyl]indole-3,7- dicarboxylic acid ((lb) where X iβ -C0 2 H) (50 mg) (prepared, e.g., aβ described in Example 4), was heated in a 200°c oil bath for several minutes. The melt waβ cooled and cryβtallized from ether-hexane to afford 2-(n-butyl)- 1-[2"-(lH-tetrazol-5-yl)biρhenyl-4*-ylmethyl]indole-7-carboxylic acid (28 mg), a compound of Formula ((lb) where X iβ hydrogen), m.p. 205-206°C. B. Preparation of (lb), varying R 2 , Y and Z Similarly, following the procedureβ of Example 5A above, but replacing 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)bipheny1-4 • -ylmethyl]indole-3,7- dicarboxylic acid with other compoundβ of Formula (lb) where X is -CO- j H, the following exemplary compounds of Formula (lb) are prepared: 2-ethyl-l-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-indole-7- carboxylic acid; 2-(n-propyl)-1-[2 B -(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-7- carboxylic acid; 2-(n-hexyl)-1-[2"-(lH-tetrazol-5-y1)bipheny1-4'-ylmethyl]indole-7- carboxylic acid; 2-(n-butyl)-l-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]indole-6- carboxylic acid. 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-7- methoxyindole; 2-(n-butyl)-l-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-6- fluoroindole; 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-indole-5- carboxylic acid; 2-(n-butyl)-1-[2"-(lH-tetrazol-5-y1)bipheny1-4'-ylmethyl]-4- methylindole; and 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-6-chloro-7- ethylindole. EXAMPLE 6 Preparation of Compounds of Formula (lb) A. Preparation of (lb) where R 2 is Ethyl, R 7 is 2-(lH-tetrazol-5-yl)phenyl, X and Z are Hydrogen, and Y is 7-Mβthoxycarbonyl A solution of methyl 2-ethyl-l-[(2"-cyano)biphenyl-4'-yl)methyl]indole- 7-carboxylate (0.25 g) (39) (prepared, e.g., aβ deβcribed in Preparation 27), and tributyltin azide (1 ml) in xylene (15 ml) waβ heated under reflux (140- 150°C) for 48 hours under an inert atmosphere. The reaction mixture was cooled and poured into saturated potassium fluoride (20 ml), and tetrafluoroboric acid/diethylether complex (8 drops). The resulting mixture was stirred for 18 hours at room temperature and then concentrated under vacuum. The residue waβ diluted with water (50 ml), the pH of the solution was adjusted to 6 with glacial acetic acid, and the product was thoroughly extracted into methylene chloride. The combined methylene chloride extracts were washed with brine, then dried over magnesium sulfate and concentrated under vacuum. The residue obtained was chromatographed on silica gel, eluting with 5% methane/methylene chloride, to give methyl 2-ethyl-l-[2"-(lH-tetrazol- 5-yl)biphenyl-4'-ylmethyl]indole-7-carboxylate (0.165 g), a compound of Formula (lb), as a white βolid m.p. 180-182°C. B. Preparation of (lb), varying R 2 , Y and Z Similarly, following the procedureβ of Example 7A above, but replacing methyl 2-ethyl-l-[ (2"-cyano)biphenyl-4'-yl)methyl]indole-7-carboxylate with other compoundβ of Formula (39), the following exemplary compounds of Formula (lb) are prepared: methyl 2-(n-propyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole- 7-carboxylate; methyl 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4 • -ylmethyl]indole- 7-carboxylate; methyl 2-(n-hexyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole- 7-carboxylate; 2-(n-butyl)-7-methoxy-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]indole; 2-(n-butyl)-3-chloro-l-[2"-(lH-tetrazol-5-yl)biphenyl-4 ■ - ylmethyl]indole; 2-(n-butyl)-3-methyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]indole; 2-(n-butyl)-6- luoro-1-[2"-(lH-tetrazol-5-yl)biphenyl-4 • - ylmethyl]indole; methyl 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole- 5-carboxylate; 2-(n-butyl)-4-methyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4*- ylmethyl]indole; and 2-(n-butyl)-5-chloro-4-methyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]indole. EXAMPLE 1 Preparation of Compounds of Formula (lb) A. Preparation of (lb) where R 2 is Ethyl, R 7 is 2-(lH-tetrazol-5-yl)phenyl, X and Z are Hydrogen, and Y is 7-Carboxyl A βolution of methyl 2-ethyl-l-(2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]indole-7-carboxylate (lb) (0.12 g) (prepared, e.g, aβ deβcribed in Example 6), in βodium hydroxide βolution (15%, 0.5 ml), methanol (2 ml), and water (5 ml) waβ heated at 100°C for 3 hours. The reaction mixture was cooled and diluted with methylene chloride containing methanol (5%) and the reβulting βolution waβ acidified with hydrochloric acid (IN) . The organic layer was separated and the aqueous layer was extracted twice with methylene chloride. The combined methylene chloride extracts were washed with cold water and brine and then dried over magnesium sulfate. The solvent was removed under reduced presβure, and the crude product waβ crystallized from methanol to give 2- ethyl-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-7-carboxylic acid (0.109 g), a compound of Formula (lb), aβ a white solid m.p. 240-243°C. B. Preparation of (lb), varying R 2 , Y and Z Similarly, following the procedures of Example 7A above, but replacing methyl 2-ethyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'-yl)methyl]indole-7- carboxylate with other compounds of Formula (lb) where Y is -CO_R 4 , where R 4 is lower alkyl, the following exemplary compounds of Formula (lb) are prepared: 2-methy1-1-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]indole-7- carboxylic acid; 2-(n-propyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4 • -ylmethyl]indole-7- carboxylic acid; 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]indole-7- carboxylic acid; 2-(n-hexyl)-1-[2"-(lH-tetrazol-5-yl)bipheny1-4 ■ -ylmethyl]indole-7- carboxylic acid; and 2-(n-butyl)-l-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]indole-5- carboxylic acid. EXAMPLE 8 Preparation of Compounds of Formula (Ha) A. Preparation of (Ha) where R 2 is n-Butyl, R 7 is 2-(lH-tetrazol-5- yl) henyl, and X, Y and Z are Hydrogen A solution of 2-(n-butyl)-l-(2"-cyanobiphenyl-4'-ylmethyl)-lH- pyrrolo[2,3-b]pyridine (44) (0.25 g) (prepared, e.g, aβ described in Preparation 31), and tributyltin azide (1 ml) in xylene (10 ml) was heated under reflux for 48 hours under an inert atmosphere. The cooled solution was diluted with diethyl ether (100 ml), and aqueous saturated potasβium fluoride βolution (25 ml) and tetrafluoroboric acid/diethyl ether complex (0.5 ml) waβ added. The reβulting mixture waβ βtirred for 12 hourβ at room temperature and then concentrated under vacuum. The reβidue waβ diluted with water (50 ml), the pH of the βolution waβ adjusted to 6 with acetic acid, and the product was thoroughly extracted in methylene chloride. The combined methylene chloride extracts were washed with brine, dried over magnesium sulfate, and concentrated under vacuum. The residue obtained waβ chromatographed on βilica gel, eluting with 25% methanol-methylene chloride, to yield 2-(n-butyl)-l-[2"- (lH-tetrazol-5-yl)bipheny1-4'ylmethyl]-lH-pyrrolo[2,3-b]pyridine (0.2 g), a compound of Formula (II), aβ a white solid, m.p. 86-90 β C. B. Preparation of (II) where X is Hydrogen, varying R 2 , Y and Z Similarly, following the procedures of Example 8A above, but replacing 2-(n-butyl)-1-(2"-cyanobiρhenyl-4'-ylmethyl)-lH-pyrrolo[2,3-b]pyridine with other compounds of Formula (44), the following exemplary compoundβ of Formula (II) are prepared: 2-ethyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'ylmethyl]-lH-pyrrolo[2,3- b]pyridine; 2-(n-propyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4 ■ ylmethyl]-1H- pyrrolo[2,3-b]pyridine; 2-(n-hexyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4*ylmethyl)-lH-pyrrolo[2,3- b]pyridine; 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'ylmethyl)-4-methoxy-lH- pyrrolo[2,3-b]pyridine; 2-(n-butyl)-3-chloro-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'ylmethyl]-1H- pyrrolo[2,3-b]pyridine; 2-(n-butyl)-3-methyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'ylmethyl]-1H- pyrrolo[2,3-b]pyridine; 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'ylmethyl]-5-methyl-lH- pyrrolo[2,3-b]pyridine; 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4 ■ ylmethyl]-5-fluoro-lH- pyrrolo[2,3-b]pyridine; and 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'ylmethyl]-6-chloro-4- methyl-lH-pyrrolo[2,3-b]pyridine. EXAMPLE 9 Preparation of Compounds of Formula (lib) A. Preparation of (lib) where R 1 is n-Butyl, R 7 is 2-(lH-tetrazol-5- yl)phenyl, X is -COjH, and Y and Z are Hydrogen A mixture of l-(n-butyl)-2-[2"-cyanobiphenyl-4'-ylmethyl]-7-azaindole-3- carboxylic acid (11a) (0.35 g) (prepared e.g., as described in Preparation 11), xylene (20 ml), and tributyltin azide (2 ml) is heated under reflux for about 20 hours. The mixture is then cooled in an ice bath, HCl in ether added, and the mixture βtirred for 15 minutes. The mixture is filtered and washed with ether to yield l-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]-7-azaindole-3-carboxylic acid, a'compound of Formula (lib). B. Preparation of (lib) varying R 1 , X, Y x and Z Similarly, following the procedures of Example 8A above, but replacing 1-(n-butyl)-2-[2"-cyanobiphenyl-4'-ylmethyl]-7-azaindole-3-carboxylic acid with other compounds of Formula (11a), the following exemplary compounds of Formula (lib) are prepared: l-methyl-2-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-7-azaindole-3- carboxylic acid; l-cyclopropylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-7- azaindole-3-carboxylic acid; l-cyclohexylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-7- azaindole-3-carboxylic acid; 1-(n-butyl)-2-[(2-(lH-tetrazol-5-yl)thiophen-3-yl)phen-4-ylmethyl]-7- azaindole-3-carboxylic acid; methyl 1-(n-butyl)-2-[(2-(lH-tetrazol-5-yl)thiophen-3-yl)phen-4- ylmethyl]-7-azaindole-3-carboxylate; 1-(n-butyl)-2-[(2-(lH-tetrazol-5-yl)furan-3-yl)phen-4-ylmethyl]-7- aza)indole-3-carboxylic acid; 1-(n-butyl)-2-[(2-(lH-tetrazol-5-y1)benzothiophen-3-yl)phen-4-ylmethyl]- 7-azaindole-3-carboxylic acid; 1-(n-butyl)-2-[(2-(lH-tetrazol-5-yl)benzofuran-3-yl)phen-4-ylmethyl]-7- azaindole-3-carboxylic acid; 1-(n-butyl)-2-[(2-(lH-tetrazol-5-yl)indol-1-yl)phen-4-ylmethyl]-7- azaindole-3-carboxylic acid; and l-methyl-2-[(2-(lH-tetrazol-5-yl)thiophen-3-yl)phen-4-ylmethyl]-7- azaindole-3-carboxylic acid. EXAMPLE 10 Preparation of Compounds of Formula (Ilia) A. Preparation of (Ilia) where R 2 is n-Butyl, R 7 is 2-(lH-tβtraaol-5- yl)phenyl, and R 3 and X are Hydrogen A βolution of 2-(n-butyl)-l-(2"-cyanobiphenyl-4'-ylmethyl)-4,5,6,7- tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one (56) (300 mg) (prepared, e.g, aβ deβcribed in Preparation 36), and tributyltin azide (1 ml) in xylene (10 ml) was heated under reflux for 48 hours under an inert atmosphere. The cooled βolution waβ diluted with diethyl ether (100 ml), and aqueous saturated potaββium fluoride βolution (25 ml) and tetrafluoroboric acid/diethyl ether complex (0.5 ml) waβ added. The reβulting mixture waβ stirred for 12 hourβ at room temperature and then concentrated under vacuum. The reβidue waβ diluted - with water (50 ml), the pH of the βolution was adjusted to 6 with acetic acid, and the product waβ thoroughly extracted into methylene chloride. The combined methylene chloride extracts were washed with brine, then dried over magnesium sulfate and concentrated under reduced presβure. The reβidue obtained was chromatographed on silica gel, eluting with 25% methanol/methylene chloride, to yield 2-(n-butyl)-l-[2"-(lH-tetrazol-5- yl)biphenyl-4'-ylmethyl]-4,5,6,7-tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one (220 mg), a compound of Formula (Ilia), as a white solid, m.p. 181-183°C. B. Preparation of (Ilia) where R 2 is n-Butyl, R 7 is 2-(lH-tetrazol-5- yl) henyl, R 3 is Methyl, and X is Hydrogen Similarly, following the procedures of Example 10A above, but replacing 2-(n-butyl)-1-(2"-cyanobipheny1-4'-ylmethyl)-4,5,6,7-tetrahydro-lH- pyrrolo[2,3-c]pyridin-7-one with 2-(n-butyl)-6-methyl-l-{2"-cyanobiphenyl-4'- ylmethyl)-4,5,6,7-tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one (57), the following compound of Formula (Ilia) was prepared: 2-(n-butyl)-6-methyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]- 4,5,6,7-tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one, m.p. 90-95°C. C. Preparation of (Ilia), varying R 2 , R 3 and X Similarly, following the procedures of Example 10A above, but optionally replacing 2-(n-butyl)-1-(2"-cyanobipheny1-4'-ylmethyl)-4,5,6,7-tetrahydro-lH- pyrrolo[2,3-c]pyridin-7-one with other compounds of Formula (56) or (57), and optionally replacing methyl iodide with other lower alkyl halides, the following compounds of Formula (Ilia) are prepared: 2-methyl-6-methyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4 • -ylmethyl]-4,5,6,7- tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one; 2-ethyl-6-methyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4 ■ -ylmethyl]-4,5,6,7- tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one; 2-(n-propyl)-6-methyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]- 4,5,6,7-tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one; 2-(n-hexyl)-6-methyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]- 4,5,6,7-tetrahydro-lH-pyrrolo[2,3-c)pyridin-7-one; 2-(n-butyl)-6-ethyl-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]- 4,5,6,7-tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one; and 2-(n-butyl)-6-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]- 4,5,6,7-tetrahydro-lH-pyrrolo[2,3-c]pyridin-7-one. EXAMPLE 11 PREPARATION OF SALTS OF COMPOUNDS OF FORMULA (I), (II) and (III) A. Conversion of l-(n-butyl)-6-mβthoxy-2-[2"-(lH-tetrazol-5-yl)biphenyl- '- ylmethyl]-indole to its Potassium Salt 1-(n-Butyl)-6-methoxy-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]- indole (100 mg) , prepared, e.g, as described in Example 1, was dissolved in methanol (20 ml), and a solution of potassium hydroxide (4.65 ml, 0.1 M) in methanol was added. The solvent was evaporated to afford an oil, which was triturated with ethyl acetate to yield a white solid, potasβium 1-(n-butyl)-6- methoxy-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-indole as a foam. B. In a similar manner, all compounds of Formula (I), (II) or (III) may be converted to their base addition βalts by treatment with an appropriate base, for example, sodium bicarbonate, potasβium carbonate, lithium hydroxide, ammonium hydroxide, calcium hydroxide, magnesium hydroxide, and the like. Base addition salts derived from organic baseβ include those formed from primary, secondary and tertiary amines, βuch as iβopropylamine, diethylamine, trimethylamine, pyridine, cyclohexylamine, ethylene diamine, monoethanolamine, diethanolamine, triethanolamine, and the like. In Examples 12 through 16 the active ingredient is 1-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4*-ylmethyl]-indole-3-carboxylic acid. Other compounds of Formula (I), (II) or (III), and the pharmaceutically acceptable salts thereof, may be substituted therein. EXAMPLE 12 Composition for Oral Administration The composition contains: % wt./wt. Active ingredient 40% Lactose 59.5% Magnesium stearate 0.5% The two ingredientβ are milled, mixed and dispensed into capsules containing 125-250 mg each; one capsule would approximate a total daily dosage of 50-100 mg. EXAMPLE 13 Composition for Oral Administration The composition contains: % wt./wt. Active ingredient 50.0% Microcrystalline cellulose 45.0% Croβcarmelloβe sodium 2.0% PVP (polyvinylpyrrolidine) 2.0% Magnesium stearate 1.0% The first four ingredients above are combined and granulated using water aβ βolvent. The formulation is then dried, blended with the magnesium stearate, and formed into tablets (containing 50-100 mg of active compound) with an appropriate tableting machine. The compoundβ of the present invention may also be formulated in a solution for oral administration as follows: Active Ingredient 10 mg/ml Sucrose 10 mg/ml Sorbitol 100 mg/ml Sodium benzoate 10 mg/ml HCl or NaOH to adjust pH to 3 - 7; q.s. to 1 ml with H 2 0. EXAMPLE 14 Parenteral Formulation (IV) The composition contains: % wt./wt. Active ingredient 2.00% Propylene glycol 20.0% Polyethylene glycol 400 20.0% Polysorbate 80 1.0% 0.9% Saline solution qs ad 100 ml The active ingredient iβ dissolved in propylene glycol, polyethylene glycol 400 and polysorbate 80. A sufficient quantity of 0.9% βaline solution is then added with stirring to provide 100 ml. of the I.V. solution which iβ filtered through a 0.2 micron membrane filter and packaged under sterile conditions. EXAMPLE 15 Suppository Formulation The composition contains: % wt./wt. Active ingredient 5.0% Witepsol W 95.0% The ingredients are melted together and mixed on a steam bath, and poured into molds containing 1-2 g total weight. All of the above ingredients, except water, are combined and heated to 60°C with βtirring. A sufficient quantity of water at 60°C is then added with vigorous stirring to emulsify the ingredients, and water then added q.s. 100 g. EXAMPLE 17 Determination of Affinity for Angiotensin II Receptors Membranes of rat liver cells were homogenized (using.a Polytron P10 tissue disrupter, setting 10 for 5 or 10 sec bursts) in 10 volumes (w/v) Tris buffer (pH 7.4 at 4°C) of the following composition: Tris HCl (50 mM) and Na 2 EDTA (5 mM) . The homogenate was centrifuged at 500 x g and the supernatant retained. This procedure was repeated. The supernatant was rehomogenized and centrifuged at 30,000 to 48,000 x g, and the pellet resuspended in homogenizing buffer. Non-specific binding ^ as determined using human angiotensin II (1.0 μM). AT 1 and AT 2 binding sites were labelled with [ 12S I]- Sar 1 He 8 AH (0.01 nM; New England Nuclear). Incubations of test compound/ radiolabel, and AT 1 or AT 2 binding βites were terminated by vacuum filtration over Whatman GF/B glass fiber filters. After filtration, the filters were washed, dried and counted for radioactivity by liquid scintillation spectrometry with quench correction. The concentration of test compound producing 50% inhibition of specific radioligand binding waβ determined by iterative curve fitting and its inhibition dissociation constant (K calculated. 1-(n-Butyl)-2-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]indole-3- carboxylic acid was found active in this assay and has a pKi value of 7.7. EXAMPLE 18 ANGIOTENSIN RECEPTOR ANTAGONISM FUNCTIONAL ASSAYS (a) Isolated ring segments of rabbit aorta were set up in Krebs" physiological salt solution at 37°C, pH 7.4, under 1 g resting tenβion. The segments were exposed to 50 mM KC1 to evoke contraction. After thorough washing, cumulative concentration-effect curves to angiotenβin II were constructed. Then, teβt compounds were preincubated with the tissue and a second concentration-effect curve to angiotensin II was constructed. A dextral shift in the concentration-effect curve to angiotensin II, greater than that seen in appropriate time controlβ, waβ taken aβ antagonistic activity of the test compound. The compounds of the present invention were active as antagonists of angiotenβin II-mediated contraction in this assay. (b) Isolated segments of guinea pig ileum were set up in Krebs' physiological salt βolution at 37°C, pH 7.4, under 1 g reβting tenβion. Non- cumulative concentration-effect curves to angiotensin II were constructed using 0.5 log unit increases in concentration. Then, test compoundβ were pre- incubated with the tissue and a second concentration-effect curve to angiotensin II was constructed. A dextral shift in the concentration-effect curve to angiotensin II, greater than that seen in appropriate time controls, was taken aβ antagonistic activity of the test compound. 1-(n-Butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3- carboxylic acid was found active as an antagonist in this asβay. EXAMPLE 19 Determination of Antihypertensive Activity (a) Male normotensive rats were subjected to complete left renal artery ligation. Four to 8 days poet ligation, systemic blood pressure and heart rate were recorded via the left femoral artery from conscious rats housed in Bollman restraint cages. Test and control compounds were administered via the femoral vein. The rats were divided into test and control groups. For intravenous administration, the test group received the test compound (in a vehicle of Tween*80 [polyoxyethylene sorbitan monooleate] and normal saline) in a dose of 10 or 30 mg/kg, whereas the control group received the appropriate volume of vehicle. Blood presβure and heart rate were monitored for 4 hourβ, at which time captopril (3 mg/kg, iv) waβ administered to both groups as a positive control, and blood pressure and heart rate were recorded for a further 30 minutes. For oral administration, the test group received a dose of 10 or 30 mg/Kg of the test compound, whereas the control group received the appropriate volume of vehicle. Blood pressure and heart rate were monitored for 4 hours, at which time captopril (3 mg/kg, iv) was administered to both groups as a positive control and the same parameters were recorded for a further 30 minutes. The compounds of Formula (I), (II) and (HI) significantly lowered mean blood pressure when given by both the intravenous and oral routes. (b) Normotensive rate were βet-up for recording βyβtemic blood presβure and heart rate as described for renal hypertensive rats in (a) above. Angiotensin II (0.1 μg/kg, iv) was administered intravenously to both control and test groups at 15 and 30 minutes prior to administration of vehicle or test compound, which waβ administered by bolus injection or infusion. Angiotenβin II (0.1 μg/kg, iv) waβ then injected every 30 minutes for 4 hours. A final doβe of angiotensin II (1.0 μg/kg,. iv) was given at the end of the experiment. The compoundβ of the present invention inhibited significantly the pressor response to angiotensin II without causing sustained hypotension, demonstrating that the compounds possess angiotensin II blocking properties in vivo and that their hypotensive action is selective to angiotensin II-dependent hypotension. (The βyβtemic blood preβsure of normotensive rate iβ not angiotensin II-dependent. ) 1-(n-Butyl)-2-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]indole-3- carboxylic acid significantly blocked the pressor response to angiotensin II at an IV dose of 30 mg/Kg for 30 minutes. EXAMPLE 20 COGNITIVE ENHANCEMENT ASSAY The following describee a model to determine the cognitive enhancing effects of compoundβ of Formulae (I), (II) and (III). Sprague Dawley rate (240-260 g) were kept in the laboratory the night prior to teβting, and remained there throughout the experiment. The Morris Water Maze consists of a circular pool made from black perspex (122 cm diameter, 46 cm in height, with a 15 cm rim), filled with opaque water to a height of 35 cm. A hidden platform consisting of black plexiglass was placed 1-2 cm below the surface of the water. The pool was divided into four quadrants, arbitrarily corresponding to nor , south, east and west. The platform waβ located in the βouth quadrant, about 24 cm from the side. Objectβ of high contraβt were placed about the room to serve as spatial cues. A TV camera tracked the swim path of the rats, and the data thus obtained waβ examined to determine the time in seconds the rats took to find the platform (escape latency). Test trials were initiated by placing a rat into one of the four quadrants, facing the wall. Testing consisted of a block of six trials (starting firβt in the north quadrant, then east, south, west, north, and finally east) on each of two consecutive days. During each trial the rat was allowed 90 seconds to find the platform. When the rat succesβfully found the platform, it was given 30 seconds to "study" the spatial cues. When the rat failed to find the platform within 90 seconds, it was given a score of 90 seconds, and placed on the platform for 30 seconds. The following groups of 8 rats each were used: 1) vehicle-treated controlβ; 2) atropine treated-controlβ; 3) atropine pluβ test drug. Thus the studies were designed to determine whether the test drug could alleviate the cognitive deficit induced by atropine (30 mg/kg, ip) . Statiβtical tests were applied to test for heterogeneity of the learning curves, and separation of the learning curves. 1-(n-Butyl)-2-[2"-(lH-tetrazol-5-yl)bipheny1-4 • -ylmethyl]indole-3- carboxylic acid was active in this assay at 0.01 to 10 mg/Kg i.p.. EXAMPLE 21 Toxicit Rats were administered single oral doses of 30, 100 or 300 mg/Kg of 1- (n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3-carboxylic acid and observed for 3 days postdoβing. No mortality occurred at any of the doses given. While the present invention has been described with respect to specific embodiments thereof, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the true spirit and scope of the invention. All such modifications are intended to be within the scope of the claims appended hereto.

Claims: WHAT IS CLAIMED IS: A compound represented by the Formula (I), (II), or (III) CD (ID CUD wherein: R 1 is lower alkyl when R 2 is V; or R 2 is lower alkyl when R 1 is V; wherein: V is: R 3 is hydrogen or lower alkyl; X iβ hydrogen, lower alkyl, halogen, -C(0)CF 3 , -C0 2 R 4 , or -C(0)NR s R <s ; Y is hydrogen, lower alkyl, lower alkoxy, hydroxy, halogen, or -CO j R 4 ; Z is hydrogen, lower alkyl, lower alkoxy, or halogen; with the proviso that Y and Z cannot be attached to the nitrogen atom in Formula (II); in which R 4 is hydrogen or lower alkyl; R 3 is hydrogen, lower alkyl or -CH 2 C0 2 R 4 ; R 6 iβ hydrogen or lower alkyl; or R 5 and R 6 taken together with the nitrogen to which they are attached represent a heterocycle; R 7 is: in which; R 8 is -CO 2 H or lH-tetrazol-5-yl; and W is oxygen, sulfur, or -NR-, wherein R is hydrogen or lower alkyl; with the proviso that in Formulae (II) and (III), when R 1 is 2"-(lH-tetrazol- 5-yl)bipheny1-4"-ylmethyl and R 2 is lower alkyl, X cannot be hydrogen, lower alkyl or -COjR 4 ; and the pharmaceutically acceptable salts thereof. 2. The compound (I) of Claim 1 wherein R l is lower alkyl and R 2 is 2"- (lH-tetrazol-5-yl)biphenyl-4'-ylmethyl, or a pharmaceutically acceptable salt thereof. 3. The compound of Claim 2 wherein Z is hydrogen, or a pharmaceutically acceptable salt thereof. 4. The compound of Claim 3 wherein Y is hydrogen , or a pharmaceutically acceptable salt thereof. 5. The compound of Claim 4 wherein X is -C0 2 R 4 , or a pharmaceutically acceptable salt thereof. 6. The compound of Claim 5 wherein R 1 iβ n-butyl, R 4 is hydrogen, and Y iβ hydrogen, namely l-(n-butyl)-2-[2"-(lH-tetrazol-5-yl)biphenyl-4*- ylmethyl]indole-3-carboxylic acid, or a pharmaceutically acceptable βalt thereof. 7. The compound of Claim 5 wherein R 1 is methyl, ethyl, n-propyl, iβopropyl, n-pentyl, iβopentyl, n-octyl, cyclopropylmethyl or cyclohexylmethyl, and R 4 iβ hydrogen, namely reβpectively l-methyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3- carboxylic acid, _l-ethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4*-ylmethyl]indole-3-carboxylic acid, l-n-propyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3- carboxylic acid, l-isopropyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4 ■ -ylmethyl]indole-3- carboxylic acid, l-n-pentyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4 ■ -ylmethyl]indole-3- carboxylic acid, or l-isopentyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3- carboxylic acid, or l-n-octyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-3- carboxylic acid, l-cyclopropylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole- 3-carboxylic acid, or l-cyclohexylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole- 3-carboxylic acid, or a pharmaceutically acceptable salt thereof. 8. The compound of Claim 3 wherein Y is lower alkyl and X is -C0 2 R 4 , or a pharmaceutically acceptable salt thereof. 9. The compound of Claim 8 wherein Y is 5-methyl or 7-methyl, R 1 is n-butyl and R 4 is hydrogen, namely respectively l-n-butyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-5-methylindole- 3-carboxylic acid, or l-n-butyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-7-methylindole- 3-carboxylic acid, or a pharmaceutically acceptable salt thereof. 10. The compound of Claim 3 wherein Y is lower alkoxy and X is -CO- j R 4 , or a pharmaceutically acceptable salt thereof. 11. The compound of Claim 10 wherein Y is 5-methoxy or 6-methoxy, R 1 iβ n-butyl or eyelopropylmethyl and R 4 iβ hydrogen, namely l-n-butyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-5-methoxyindole- 3-carboxylic acid, or l-n-butyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-6-methoxyindole- 3-carboxylic acid, or l-cyclopropylmethyl-2-[2"-(lH-tetrazol-5-y1)bipheny1-4'-ylmethyl]-6- methoxyindole-3-carboxylic acid, or a pharmaceutically acceptable βalt thereof. ^ 12*. The compound of Claim 3 wherein Y iβ halogen and X is -CCjR 4 , or a pharmaceutically acceptable salt thereof. 13. The compound of Claim 12 wherein Y is 5-fluoro or chloro, R 1 is n- butyl, cyclopropylmethyl or cyclohexylmethyl and R 4 is hydrogen, namely l-n-butyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4 • -ylmethyl]-5-fluoroindole- 3-carboxylic acid, or l-n-butyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-5-chloroindole- 3-carboxylic acid, or l-cyelopropylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl- ■ -ylmethyl]-5- fluoroindole-3-carboxylic acid, or l-cyclopropylmethyl-2-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-5- chloroindole-3-carboxylic acid, or l-cyclohexylmethyl-2-[2 π -(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-5- fluoroindole-3-carboxylic acid, or l-cyclohexylmethyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-5- chloroindole-3-carboxylic acid, or a pharmaceutically acceptable βalt thereof. 14. The compound of Claim 2 wherein Y and Z are independently lower alkyl and X iβ -CO*jR 4 , or a pharmaceutically acceptable βalt thereof. 15. The compound of Claim 3 wherein X is C(0)CF 3 , or a pharmaceutically acceptable βalt thereof. 16. The compound of Claim 15 whrein R 1 is n-butyl, Y is hydrogen or 5- methoxy, namely l-n-butyl-2-[2"-{lH-tetrazol-5-yl)biphenyl-4*-ylmethyl]-3- trifluoroacetylindole, or l-n-butyl-5-methoxy-2-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-3- trifluoroacetylindole, or a pharmaceutically acceptable salt thereof. 17. The compound of Claim 4 wherein X is -C(0)NR S R S wherein R 5 iβ hydrogen, R* iβ methyl or -CH 2 CO^l 4 and R 4 iβ hydrogen or methyl, or a pharmaceutically acceptable βalt thereof. 18. The compound of Claim 17 wherein R 1 is n-butyl, namely l-n-butyl-2-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]-indole-3- carbonylaminoacetic acid, or l-n-butyl-2-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]-indole-3- carbonylaminoacetic acid methyl eβter, or a pharmaceutically aecepable βalt thereof. 19. The compound of Claim 1 wherein R 1 iβ lower alkyl and R 2 iβ [2-(lH- tetrazol-5-yl)thiophen-3-yl]phen-4-ylmethyl, or a pharmaceutically acceptable βalt thereof. 20. The compound of Claim 19 wherein X is hydrogen or -CO--R 4 wherein R 4 is hydrogen or lower alkyl, Y is hydrogen and Z is hydrogen, or a pharmaceutically acceptable salt thereof. 21. The compound of Claim 1 wherein R 1 is lower alkyl and R 2 is [3-(lH- tetrazol-5-yl)thiophen-2-yl]phen-4-ylmethyl, or a pharmaceutically acceptable βalt thereof. 22. The compound of Claim 21 wherein X is -C0 2 R 4 wherein R 4 is hydrogen, Y is hydrogen and Z is hydrogen, or a pharmaceutically acceptable βalt thereof. 23. The compound of Claim 1 wherein R * iβ lower alkyl and R 2 iβ [2-(lH- tetrazol-5-yl)furan-3-yl]phen-4-ylmethyl, or a pharmaceutically acceptable salt thereof. 24. The compound of Claim 23 wherein X is -C0 2 R 4 wherein R 4 is hydrogen, Y is hydrogen and Z is hydrogen, or a pharmaceutically acceptable salt thereof. 25. The compound of Claim 1 wherein R 1 is lower alkyl and R 2 is [2-(lH- tetrazol-5-yl)benzothioρhen-3-yl]phen-4-ylmethyl, or a pharmaceutically acceptable βalt thereof. 26. The compound of Claim 25 wherein X is -C0 2 R 4 wherein R 4 is hydrogen, Y iβ hydrogen and Z iβ hydrogen, or a pharmaceutically acceptable βalt thereof. 27. The compound of Claim 1 wherein R 1 is lower alkyl and R 2 is [2-(lH- tetrazol-5-yl)benzofuran-3-yl]phen-4-ylmethyl, or a pharmaceutically acceptable salt thereof. 28. The compound of Claim 27 wherein X is -C0 2 R 4 wherein R 4 is hydrogen, Y is hydrogen and Z is hydrogen, or a pharmaceutically acceptable salt thereof. 29. The compound of Claim 1 wherein R 1 is lower alkyl and R 2 is [2-(lH- tetrazol-5-yl)indol-l-yl]phen-4-ylmethyl, or a pharmaceutically acceptable salt thereof. 30. The compound of Claim 29 wherein X is -C0 2 R 4 wherein R 4 is hydrogen, Y iβ hydrogen and Z iβ hydrogen, or a pharmaceutically acceptable βalt thereof. 31. . The compound (I) of Claim 1 wherein R 1 is 2"-(lH-tetrazol-5- yl)biphenyl-4*-ylmethyl and R 2 is lower alkyl, or a pharmaceutically acceptable salt thereof. 32. The compound of Claim 31 wherein Z is hydrogen, or a pharmaceutically acceptable salt thereof. 33. The compound of Claim 32 wherein Y is hydrogen or -CO,R 4 , or a pharmaceutically acceptable salt thereof. 34. The compound of Claim 33 wherein X is hydrogen or -COjR 4 , or a pharmaceutically acceptable salt thereof. 35. The compound of Claim 34 wherein R 2 iβ ethyl or n-butyl, X is hydrogen or CO*jR 4 wherein R 4 is hydrogen or methyl, and Y is -C0 2 R 4 at the 7-position and R 4 for Y iβ hydrogen or methyl, namely 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole-7- carboxylic acid, or dimethyl 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)biphenyl-4'- ylmethyl]indole-3,7-dicarboxylate, or 2-(n-butyl)-1-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]indole-3,7- dicarboxylic acid, or methyl 2-(n-butyl)-l-[2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl]indole- 7-carboxylate, or 2-ethyl-l-[2"-(lH-tetrazol-5-yl)bipheny1-4'-ylmethyl]indole-7-carboxylic acid, or a pharmaceutically acceptable βalt thereof. 36. The compound (II) of Claim 1 wherein R 1 iβ 2"-(lH-tetrazol-5- yl)bipheny1-4'-ylmethyl and R 2 iβ lower alkyl, or a pharmaceutically acceptable βalt thereof. 37. The compound of Claim 36 wherein Z is hydrogen, or a pharmaceutically acceptable salt thereof. 38. The compound of Claim 37 wherein Y is hydrogen or -C0 2 R 4 , or a pharmaceutically acceptable salt thereof. 39. The compound of Claim 38 wherein X is halogen, -C(0)CF 3 or -C(0)NRR 6 , or a pharmaceutically acceptable salt thereof. 40. The compound (II) of Claim 1 wherein R 1 is lower alkyl and R 2 is 2"-(lH-tetrazol-5-yl)biphenyl-4'-ylmethyl, or a pharmaceutically acceptable βalt thereof. 41. The compound of Claim 40 wherein Z is hydrogen, or a pharmaceutically acceptable salt thereof. 42. The compound of Claim 41 wherein Y is hydrogen or -COjR 4 , or a pharmaceutically acceptable salt thereof. 43. The compound of Claim 42 wherein R 1 iβ n-butyl and X iβ hydrogen or -CO 2 4 , or a pharmaceutically acceptable βalt thereof. 44. The compound (III) of Claim 1 wherein R 1 is lower alkyl and R 2 is 2"-(lH-tetrazol-5-yl)biphenyl-4*-ylmethyl, or a pharmaceutically acceptable salt thereof. 45. The compound of Claim 44 wherein R 1 is n-butyl and X is hydrogen or -CO-Jt 4 , or a pharmaceutically acceptable salt thereof. 46. The compound (III) of Claim 1 wherein R 1 is 2"-(lH-tetrazol-5- yl)biphenyl-4'-ylmethyl and R 2 is lower alkyl, or a pharmaceutically acceptable salt thereof. 47. The compound of Claim 46 wherein X is halogen, -C(0)CF 3 or -C(0)NR J R 6 , or a pharmaceutically acceptable salt thereof. 48. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable βalt thereof, in admixture with one or more pharmaceutically acceptable non-toxic carriers. 49. A method for treating a mammal having a diβeaβe βtate that iβ alleviable by treatment with an angiotensin II antagonist, which comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of Claim 1, or a pharmaceutically acceptable salt thereof. 50. The method of Claim 49, wherein the disease state is hypertension or congestive heart failure. 51. The method of Claim 49, wherein the disease state is chronic renal failure or a disorder of the alimentary tract. 52. The method of Claim 49, wherein the.disease state is a cognitive disorder, anxiety or depression. 53. A proceββ for preparing compounds of the Formula (I), (II) and (III) wherein : R 1 is lower alkyl when R 2 is V; or R 2 is lower alkyl when R 1 is V; wherein: R 3 iβ hydrogen or lower alkyl; X iβ hydrogen, lower alkyl, halogen, -C(0)CF 3 , -CO-R 4 , or -C(0)NR s R 6 ; Y iβ hydrogen, lower alkyl, lower alkoxy, hydroxy, halogen, or Z is hydrogen, lower alkyl, lower alkoxy, or halogen; with the proviso that Y and Z cannot be attached to the nitrogen atom in Formula (II); in which R 4 is hydrogen or lower alkyl; R 5 iβ hydrogen, lower alkyl or -CH 2 C0 2 R 4 ; R 6 iβ hydrogen or lower alkyl; or R 5 and R 6 taken together with the nitrogen to which they are attached repreβent a heterocycle; in which; R 8 is -C0 2 H or lH-tetrazol-5-yl; and W is oxygen, sulfur, or -NR-, wherein R is hydrogen or lower alkyl; with the proviso that in Formulae (II) and (III), when R 1 is 2"-(lH-tetrazol- 5-yl)biphenyl-4'-ylmethyl and R 2 is lower alkyl, X cannot be hydrogen, lower alkyl or -CO-** 4 ; and the pharmaceutically acceptable salts thereof, comprising (a) reacting a compound of Formula (1), (2) and (3): C C2D C3D wherein R 3 , X, Y, and Z are aβ defined above; R 1 iβ lower alkyl when R' iβ V; or R* iβ lower alkyl when R 1 iβ V; where V is: where R 10 is: where W is as defined above, with the proviso that in Formula (2) and (3) when R 1 is 2"-cyanobipheny1-4'-ylmethyl and R 9 is lower alkyl, X cannot be hydrogen, lower alkyl or -CO-jR 4 , with a trialkyl tin azide followed by treatment with an acid to obtain a compound of Formula (I), (II), or (HI) wherein R 1 , R 2 , R 3 , R 4 , R s , R 6 , R 7 , X, Y, Z, V and W are as defined above and R 8 is lH-tetrazol-5-yl; or (b) reacting a compound of Formula (1), (2) or (3) with a base to obtain a compound of Formula (I), (II), or (III) wherein R 1 , R 2 , R 3 , R 4 , R s , R 6 , R 7 , X, Y, Z, V and W are aβ defined above and R 8 is -C0 2 H; or (c) reacting a compound of Formula (I), (II), or (III) wherein R 1 , R 2 , R 3 , R 7 , R 8 , Y, Z, V and W are aβ defined above and X iβ hydrogen, with phoβgene optionally followed by an alcohol of formula R 4 OH, where R 4 iβ lower alkyl, or an amine of formula ifa-VR, where R s and R 6 are as defined above, to form a compound of Formula (I), (II) or (III) wherein R 1 , R^R 3 - R 7 , R 8 , Y, Z, V and W are as defined above, X is -C0 2 R 4 or -C(0)NR s R and R 4 is lower alkyl and R 5 and R 6 are as defined above; or (d) reacting the compound of Formula (I), (II) or (III) with a base to give a pharmaceutically acceptable base addition salt; or (e) reacting a base addition βalt of a compound of Formula (I), (II) or (HI) with an acid to give the correβponding free acid; or " (f) converting a base addition salt of a compound of Formula (I), (II) or (HI) to another pharmaceutically acceptable base addition βalt of Formula (I), (II) or (III). 54. A compound of Formula (1), (2) and (3): O C2 3D wherein R 3 , X, Y, and Z are aβ defined above; R 1 iβ lower alkyl when R 9 iβ V; or R* iβ lower alkyl when R 1 iβ V; where V* iβ: where R 10 is: where W is aβ defined above, with the proviβo that in Formula (2) and (3) when R l iβ 2"-cyanobiphenyl-4'-ylmethyl and R 9 is lower alkyl, X can not be hydrogen, lower alkyl or -COjR 4 .

Inventors: CLARK ROBIN D, CLARKE DAVID E, FISHER LAWRENCE E, JAHANGIR ALAM, CLARK, ROBIN, D., CLARKE, DAVID, E., FISHER, LAWRENCE, E., JAHANGIR, ALAM
Applicants: SYNTEX INC, SYNTEX (U.S.A.) INC.
Application year: 1993
Main classification: C07D403
IPC codes: A61K31, A61P1, A61P7, A61P9, A61P13, A61P15, A61P25, A61P43, C07D209, C07D403, C07D405, C07D407, C07D409, C07D471