MX2008010043A - Hcv ns5b inhibitors - Google Patents

Abstract

The invention encompasses compounds of Formula (I) as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.

Description

INHIBITORS OF HEPATITIS C VIRUS NS5B DESCRIPTION OF THE INVENTION The hepatitis C virus (HCV) is a major human pathogen, infecting an estimated 170 million people worldwide - almost five times the number infected by the virus. human immunodeficiency virus type 1. A substantial fraction of these individuals infected with HCV develop serious progressive liver disease, including cirrhosis and hepatocellular carcinoma (Lauer, GM, alker, BDN Engl. J. Med. 2001, 345, 41-52) . HCV is a positive-strand RNA virus. Based on a comparison of the deduced amino acid sequence and extensive similarity in the 5 'untranslated region, HCV has been classified as a separate genus in the Flaviviridae family. All members of the Flaviviridae family have encapsidated virions that contain a positive-strand RNA genome that codes for all virus-specific proteins by translating a single uninterrupted open reading frame. Considerable heterogeneity is found within the nucleotide and amino acid sequence encoded throughout the HCV genome. At least six major genotypes have been characterized, and more than 50 subtypes have been described. The main genotypes of HCV differ in their distribution worldwide, and the clinical significance of the REF. : 195321 Genetic heterogeneity of HCV remains elusive despite several studies of the possible effect of genotypes on pathogenesis and therapy. The genome of single-stranded HCV RNA is approximately 9500 nucleotides long and has a single open reading frame (ORF) that codes for a single large polyprotein of about 3000 amino acids. In infected cells, this polyprotein is cut at several sites by cellular and viral proteases to produce the structural and non-structural proteins (NS). In the case of HCV, the generation of mature non-structural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B) is carried out by two viral proteases. The first is believed to be a metalloprotease and cuts at the NS2-NS3 junction; the second is a serine protease contained within the N-terminal region of NS3 (also known as NS3 protease) and mediates all subsequent cuts towards the 3 'end of NS3, both in cis, at the NS3-NS4A cut site and in trans, for the remaining NS4A-NS4B, NS4B-NS5A, NS5A-NS5B sites. The NS4A protein appears to have several functions, acting as a cofactor for the NS3 protease and possibly helping in the membrane location of NS3 and other viral replicase components. The complex formation of the NS3 protein with NS4A seems necessary for the processing events, increasing the proteolytic efficiency in all the sites.

The NS3 protein also exhibits nucleoside triphosphatase and RNA helicase activities. NS5B (also known as HCV polymerase) is an RNA-dependent RNA polymerase that is involved in the replication of HCV. The HCV NS5B protein is described in "Structural Analysis of the Hepatitis C Virus RNA Polymerase in Complex with Ribonucleotides (Bressanelli; S. et al., Journal of Virology 2 0 02, 3482-3492; and Defrancesco and Rice, Clinics in Liver Disease 2 0 0 3, 7, 211-242 Currently, the most effective HCV therapy uses a combination of alpha interferon and ribavirin, leading to prolonged efficacy in 40% of patients (Poynard, T. et al., Lancet 1 998, 352, 1426-1432) Recent clinical results demonstrate that pegylated alpha interferon is superior to unmodified alpha interferon as monotherapy (Zeuzem, S. et al., N. Engl. J. Med. 2 0 00, 343, 1666-1672 However, even with experimental therapeutic regimens that include combinations of alpha pegylated interferon and ribavirin, a substantial fraction of patients do not have a prolonged reduction in viral load, so there is a clear and important need to develop effective therapeutics for the treatment of HCV infection. The invention encompasses compounds and salts pharmaceutically acceptable compounds of formula I, and compositions and methods of treatment using these compounds. One aspect of the invention is a compound of the formula I I wherein: R1 is C02R5 or CONR6R7; R2 is furanyl, pyrrolyl, thienyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl or tetrazolyl and is substituted with 0-2 substituents selected from oxo, amino, alkylamino, dialkylamino, alkyl, (cycloalkyl) alkyl, hydroxyalkyl, (tetrahydrofuranyl) alkyl, (tetrahydropyranyl) alkyl, (C02R5) alkyl, (CON (R5) 2) alkyl, (COR9) alkyl, (alkylsulfonyl) alkyl and ((R9) alkyl) CON (R5); R3 is C5-7 cycloalkyl; R 4 is hydrogen, halo, hydroxy, alkyl or alkoxy; R5 is hydrogen, alkyl or cycloalkyl; R6 is hydrogen, alkyl, cycloalkyl, alkoxy or S02R8; R7 is hydrogen, alkyl or cycloalkyl; or NR6R7 taken together is pyrrolidinyl, piperidinyl, piperazinyl, N-alkylpiperazinyl, homomorpholinyl, homopiperidinyl, morpholinyl or thiomorpholinyl; R8 is alkyl, haloalkyl, cycloalkyl, amino, alkylamino, dialkylamino or phenyl; or R8 is pyrrolidinyl, piperidinyl, piperazinyl, N-alkylpiperazinyl, homomorpholinyl, homopiperidinyl, morpholinyl or thiomorpholinyl; R9 is pyrrolidinyl, piperidinyl, piperazinyl, N-alkylpiperazinyl, homomorpholinyl, homopiperidinyl, morpholinyl or thiomorpholinyl; and (a) it is a single link or a double bond, (b) it is a single link or a double bond, provided that at least one of (a) and (b) is a single link; or a pharmaceutically acceptable salt thereof. Another aspect of the invention is a compound of formula I selected from the group consisting of Another aspect of the invention is a compound of formula I wherein R1 is CONR6R7; R6 is S02R8; and R7 is hydrogen. Another aspect of the invention is a compound of the formula I wherein R3 is cyclohexyl. Another aspect of the invention is a compound of the formula I wherein R 4 is hydrogen. Another aspect of the invention is a compound of the formula I wherein R 4 is methoxy. For a compound of formula I, any range of R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, (a) and (b) can be used independently with the scope of any other variable. Unless otherwise indicated, these terms have the following meanings. "Alkyl" means a straight or branched chain alkyl group composed of 1 to 6 carbons. "Alkenyl" means a straight or branched chain alkyl group composed of 2 to 6 carbons with at least one double bond. "Cycloalkyl" means a monocyclic ring system composed of 3 to 7 carbons. "Hydroxyalkyl", "alkoxy" and other terms with a substituted alkyl portion include straight and branched isomers composed of 1 to 6 carbon atoms for the alkyl portion. "Haloalkyl" and "haloalkoxy" include all halogenated isomers of alkyl substituted with monohalo to alkyl substituted with perhalo. "Aryl" includes carbocyclic and heterocyclic aromatic substituents. The terms parentésicos and multiparentésicos try to clarify the relations of union for those skilled in the art. For example, a term such as ((R) alkyl) means an alkyl substituent further substituted with the R substituent. The invention includes all pharmaceutically acceptable salt forms of the compounds. The pharmaceutically acceptable salts are those in which the counterions do not contribute significantly to the physiological activity or toxicity of the compounds and as such function as pharmacological equivalents. These salts can be made according to common organic techniques employing commercially available reagents. Some anionic salt forms include acetate, acrylate, besylate, bromide, chloride, citrate, fumarate, glucouronat or, hydrobromide, hydrochloride, iodide, iodide, lactate, maleate, mesylate, nitrate, pamoate, phosphate, succinate, sulfate, tartrate, tosylate and xinofoato. Some forms of cationic salt include ammonium, aluminum, benzathine, bismuth, calcium, choline, diethylamine, diethanolamine, lithium, magnesium, meglumine, 4-phenylcyclohexylamine, piperazine, potassium, sodium, tromethamine and zinc. Some of the compounds of the invention possess asymmetric carbon atoms (e.g. structures below). The invention includes all stereoisomeric forms, including enantiomers and tereomer days as well as mixtures of diastereomers such as racemates. Some substances can be made using methods known in the art. The stereoisomeric mixtures of the related compounds and intermediates can be separated into individual isomers according to methods known in the art.

Synthetic Methods The compounds of the formula I can be made by methods known in the art including those described below. Some reagents and intermediates are known in the art. Other reagents and intermediates can be made by methods known in the art using readily available materials. The variables (for example, numbered sust i tuyent is "R") used to describe the synthesis of the compounds of formula I are intended only to illustrate how to elaborate and should not confused with variables used in the claims or in other sections of the description. The abbreviations used in the schemes generally follow conventions used in the art. The abbreviations used in the reaction schemes generally follow conventions used in the art. Some examples are the following: THF means tetrahydrofuran; D F means N, N-dimethylformamide; RCM means ring closure metasis; Boc means tert-butoxycarbonyl; TFA means trifluoroacetic acid; DMA means N, N-dime t i 1 a ce t ami da; PPh3 means triphenylphosphine; OAc means acetate; Me means methyl; COD (or cod) means 1,5-cyclooctadiene; dtbpy means 4, 4'-d i -tert-butyl-2,2'-bipyridine; dba means dibenzylideneacetone; Xanthos means 4,5-bis (diphenylphosphino) -9,9-dimethylxanthine; aq means aqueous; EtOH means ethanol; MeOH means methanol; TBTU means tet raf luroborate of 2 - (1 H-ben z or t r i a z o 1 -1 - i 1) - 1, 1, 3, 3 - 1 e t r ame t i lur onio; DMSO means dimethyl sulfoxide; HATU means hexafluorophosphate O- (7-a z aben z o t r i a z o 1 - 1 - i 1) - N,, N ', N 1 - 1 e t r ame t i luronio; EEDQ means 2-ethoxy-l-e-t-oxycarboni 1-l, 2-dihydr oquinol ina; WSC stands for 1 - [3 - (dime t i lamino) pr opi 1] - 3 - hydrochloride et i 1 ca rbodi imi da; DMAP means 4-dimethylaminopyridine; n-Bu means n-butyl; BEMP means 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine, polymer bound; DIPEA means diisopropylethylamine; and TEA means triet ilamine. Reaction scheme 1 Reaction scheme 2 Reaction scheme 3 Reaction scheme 4 Reaction scheme S Reaction scheme 6 Reaction scheme 9 Reaction scheme 10 Reaction scheme 11 Reaction scheme 12 Biological methods The compounds demonstrated activity against HCV NS5B as determined by the following HCV RdRp assays. Cloning, expression and purification of HCV NS5B RdRp. The cDNA encoding HCV NS5B protein genotype Ib was cloned into the expression vector pET21a. The protein was expressed with a C-terminal truncation of 18 amino acids to increase solubility. The line of competent cells of E. coli BL21 / DE3) was used for the expression of the protein. The cultures were made at 37 ° C for about 4 hours until the cultures reached an optical density of 2.0 to 600 nm. The cultures were cooled to 20 ° C and induced with 1 mM of IPTG. Fresh ampicillin was added to a final concentration of 50 μ? / P ?? and the cells were grown overnight at 20 ° C. The cell granules (3L) were used for purification to produce 15-24 mgs of purified NS5B. The lysis pH regulator consisted of 20 mM Tris-HCl, pH 7.4, 500 mM NaCl, 0.5% triton X-100, 1 mM DTT, lmM EDTA, 20% glycerol, 0.5 mg / ml lysozyme, 10 mM MgCl2, 15 g / ml deoxyribonuclease I and TM complete protease inhibitor tablets (Roche). After the addition of the lysis pH regulator, frozen cell pellets were resuspended using a tissue homogenizer. To reduce the viscosity of the sample, aliquots of lysate were sonicated on ice using a microtip attached to a Branson sonicator. The sonicated lysate was centrifuged at 100, 000 x g for 1 hour at 4 ° C and filtered through a filter unit of 0.2 μ? T? (Corning) The protein was purified using three sequential chromatography steps: Heparin sepharose CL-6B, polyU sepharose 4B and Hitrap SP sepharose (Pharmacia). Chromatography pH regulators were identical to the lysis pH regulator but did not contain lysozyme, deoxyribonulcease I, MgCl2 or protease inhibitor and the NaCl concentration of the pH regulator was adjusted according to the requirements to load the protein into the column . Each column was eluted with a gradient of NaCl that varied in length from 5-50 column volumes depending on the type of column. After the final chromatography step, the resulting purity of the enzyme is greater than 90% based on SDS-PAGE analysis. The enzyme was aliquoted and stored at -80 ° C. HCV enzyme assay NS5B RdRp standard. The HCV RdRp genotype Ib assays were run in a final volume of 60 μ? in 96-well plates (Costar 3912). The assay pH regulator is composed of 20 mM Hepes, pH 7.5, 2.5 mM KC1, 2.5 mM MgCl2, 1 mM DTT, 1.6 U RNase inhibitor (Promega N2515), 0.1 mg / ml BSA ( Promega R3961) and 2% glycerol. All compounds were serially diluted (3 times) in DMSO and further diluted in water such that the final concentration of DMSO in the assay was 2%. VHC RdRp genotype Ib enzyme was used at a final concentration of 28 nM. A polyA template at 6 nm was used and a biotinylated oligo-dT12 primer was used at a final concentration of 180 nM. The template was obtained commercially (Amersham 27-4110). Biotinylated primer is prepared by Sigma Genosys. 3H-UTP 0.6 pCi (0.29 μ total of UTP) was used. The reactions were initiated by the enzyme addition, incubated at 30 ° C for 60 minutes and stopped by adding 25 μ? of 50 mM EDTA containing SPA spheres (4 μg / μl, Amersham RPNQ 0007). Plates were read in a Packard Top Count NXT after more than 1 hour of incubation at room temperature. HCV enzyme assay NS5B RdRp modified. A modified enzyme assay was carried out essentially as described for the standard enzyme assay except for the following: the biotinylated oligo DT12 primer was precaptured in streptavidin-coated SPA spheres when mixing primer and spheres in pH-regulator assay. incubate at room temperature for 1 hour. Unbound primer was removed after centrifugation. The primer-bound spheres were resuspended in 20 mM Hepes pH buffer, pH 7.5 and used in the assay at final concentrations of 20 nM primer and 0.67 μ? / Μ? of spheres. The order of addition in the assay: enzyme (14 nM) was added to the diluted compound followed by the addition of a mixture of template (0.2 nM), 3 H-UTP (0.6 Ci, 0.29 μ?) And spheres bound to starter, to start the reaction; the concentrations given are final. The reactions were allowed to proceed for 4 hours at 30 ° C. The IC50 values for the compounds were determined using seven [I] different. The IC5o values were calculated from the inhibition using the formula y = A + ((B-A) / (l + ((C / x) AD))). FRET assay preparation. To carry out the VHC FRET screening assay, 96-well cell culture plates were used. The peptide FRET (Anaspec, Inc.) (Taliani et al., Anal.Bíochem, 1996, 240, 60-67) contains a fluorescence donor, EDANS, near one end of the peptide and one acceptor, DABCYL, near the other extreme. The fluorescence of the peptide is extinguished by transfer of intermolecular resonance energy (RET) between the donor and the receptor, but since the NS3 protease cuts the peptide the products are released from the cooling with RET and the fluorescence of the donor becomes apparent. The assay reagent was made as follows: 5x Promega luciferase cell culture lysis reagent (# E153A) diluted 1 x with dH20, 150 ml final NaCl, the FRET peptide diluted to 20 μ? final from a 2 mM supply solution. To prepare the plates, HCV replicon cells, with or without a Renilla luciferase reporter gene, were trypsinized and placed in each well of a 96-well plate. wells with titrated test compounds added in columns 3 to 12; columns 1 and 2 contained a control compound (inhibitor of HCV protease), and the lower row contained cells without compound. The plates were then placed in a C02 incubator at 37 ° C. Essays. After addition of the test compounds described above (FRET assay preparation, at various times the plate was removed and Alamar blue solution (Trek Diagnostics, # 00-100) was added per well as a measure of cell toxicity. After reading on a Cytoflour 4000 instrument (PE Biosystems), the plates were rinsed with PBS and then used for the FRET assay by the addition of 30 μl of the FRET peptide assay reagent described above (FRET assay preparation) per well. The plate was then placed on the Cytoflour 4000 instrument which had been set at 340 excitation / 490 emission, automatic mode for 20 cycles and the plate was read in a kinetic mode.Signually, the signal to noise using an analysis of endpoint after the readings was at least three times.Alternatively, after reading with alamar blue, the plates were rinsed with PBS, 50μ? of D EM (high glucose) was added without red faith nol and the plates were then used for luciferase assay using the Promega Dual-Glo Luciferase assay system. The analysis of the compound was determined by quantitation of relative HCV replicon inhibition and relative cytotoxicity values. To calculate the cytotoxicity values, the average alamar blue fluorescence signals from the control wells were established as 100% non-toxic. The individual signals in each of the compound test wells were then divided between the average control signal and multiplied by 100 to determine the percentage cytotoxicity. To calculate the inhibition values of the HCV replicon, an average background value of the two wells containing the highest amount of HCV protease inhibitor was obtained at the end of the test period. These numbers were similar to those obtained from Huh-7 naive cells. The background numbers were then subtracted from the average signal obtained from the control wells and this number was used. as 100% activity. The individual signals in each of the test wells of the compounds were then divided between the control values averaged after the subtraction of the bottom and multiplied by 100% to determine the percentage activity. The EC50 values for a protease inhibitor titration were calculated as the concentration that caused a 50% reduction in FRET or luciferase activity. The two numbers generated for the composite plate, percentage totoxicity and percentage activity were used to determine compounds of interest for further analysis. The representative data for the compounds of the formula I are reported in table 1. Table 1 A > 0.5 uA > 0.5 uM; B 0.001 μ? - 0.5 μ ?; CX0.02 μ? but an exact value was not determined; IC50 values were determined using the preincubation protocol. The EC50 values were determined using the FRET assay. In addition, the compounds described in the patent application of E.U.A. No .11 / 181639, filed on July 14, 2005, showed activity in these trials (see Table 2). Table 2 ?? twenty-one Pharmaceutical Compositions and Treatment Methods The compounds demonstrate activity against HCV NS5B and may be useful for treating HCV and HCV infection. Therefore, another aspect of the invention is a composition comprising a compound, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. Another aspect of the invention is a composition further comprising a compound having anti-HCV activity. Another aspect of the invention is a composition wherein the compound having anti-HCV activity is an interferon. Another aspect of the invention is where the Interferon is selected from interferon alpha 2B, pegylated interferon alpha, consensus interferon, interferon alpha 2A and lymphoblastoid tau interferon. Another aspect of the invention is a composition wherein the compound having anti-HCV activity is a cyclosporin. Another aspect of the invention is when the cyclosporin is cyclosporin A. Another aspect of the invention is a composition wherein the compound having anti-HCV activity is selected from the group consisting of interleukin 2, interleukin 6, interleukin 12, a compound which increases the development of a response to T helper cells type 1, interfering RNA, anti-sense RNA, Imiqimod, ribavirin, an inhibitor of inosine 5 '-monophosphate dehydrogenase, amantadite and rimantadine. Another aspect of the invention is a composition in which the compound having anti-HCV activity is effective in inhibiting the function of a target selected from HCV metalloprotease, HCV serine protease, HCV polymerase, HCV helicase, HCV NS4B protein, HCV, HCV assembly, HCV discharge, HCV NS5A protein, IMPDH and a nucleoside analogue for the treatment of HCV infection. Another aspect of the invention is a composition comprising a compound, or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier, a interferon and ribavirin. Another aspect of the. invention is a method for inhibiting the function of the HCV replicon comprising contacting the HCV replicon with a compound of the formula I or a pharmaceutically acceptable salt thereof. Another aspect of the invention is a method for inhibiting the function of the HCV NS5B protein comprising contacting the NS5B protein of HCV with a compound of the formula I or a pharmaceutically acceptable salt thereof. Another aspect of the invention is a method for treating an HCV infection in a patient, comprising administering to the patient a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof. Another aspect of the invention is a method for inhibiting the function of the HCV replicon. Another aspect of the invention is a method for inhibiting the function of the NS5B protein of HCV. Another aspect of the invention is a method for treating an HCV infection in a patient, comprising administering to the patient a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, in conjunction with (before, after or in conjunction with ) another compound that has anti-HCV activity. Another aspect of the invention is the method wherein the other compound that has anti-HCV activity is an interferon. Another aspect of the invention is the method wherein the interferon is selected from interferon alpha 2B, pegylated interferon alpha, consensus interferon, interferon alpha 2A and lymphoblastoid interferon tau. Another aspect of the invention is a method wherein the other compound having anti-HCV activity is a cyclosporin. Another aspect of the invention is when the cyclosporin is cyclosporin A. Another aspect of the invention is the method wherein the other compound having anti-HCV activity is selected from the group consisting of interleukin 2, interleukin 6, interleukin 12, a compound which increases the development of a response to T helper cells type 1, RNA interference, anti-sense RNA, Imiqimod, ribavirin, an inhibitor of inosine 5 '-monophosphate dehydrogenase, amantadite and rimantadine. Another aspect of the invention is the method in which the other compound having anti-HCV activity is effective to inhibit the function of a target selected from the group consisting of HCV metalloprotease, HCV serine protease, HCV polymerase, HCV helicase, NS4B protein of HCV, HCV entry, HCV assembly, HCV discharge, HCV NS5A protein, IMPDH and a nucleoside analogue for the treatment of an HCV infection. Another aspect of the invention is the method wherein the other compound having anti-HCV activity is effective to inhibit the function of the target in the life cycle of HCV which is not the NS5B protein of HCV. "Therapeutically effective" means the amount of agent required to provide a significant patient benefit as understood by practitioners in the field of hepatitis and HCV infection. "Patient" means a person infected with the HCV virus and suitable for therapy as it is understood by practitioners in the field of hepatitis and HCV infection. "Treatment", "therapy", "regime", "HCV infection" and related terms are used as understood by practitioners in the field of hepatitis and HCV infection. The compounds of this invention will generally be given as pharmaceutical compositions comprising a therapeutically effective amount of a compound or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier and may contain conventional excipients. A therapeutically effective amount is that which is required to provide a meaningful patient benefit. The pharmaceutically acceptable carriers are those carriers conventionally known to have acceptable safety profiles. The compositions encompass all common solid and liquid forms including capsules, tablets, pills and powders, as well as liquid suspensions, syrups, elixirs and solutions. The compositions are made using common formulation techniques, and conventional excipients (such as binding and wetting agents) and carriers (such as water and alcohols) are generally used for the compositions. The solid compositions are usually formulated in dosage units and compositions that provide about 1 to 1000 mg of the active ingredient per dose are those that are preferred. Some examples of doses are 1 mg, 10 mg, 100 mg, 250 mg, 500 mg and 1000 mg. Generally, other agents will be present on a unit scale similar to agents of that class used clinically. Typically, this is 0.25-1000 mg / unit. Liquid compositions are usually on unit dose scales. Generally, the liquid composition will be on a unit dose scale of 1-100 mg / mL. Some examples of doses are 1 mg / mL, 10 mg / mL, 25 mg / mL, 50 mg / mL and 100 mg / mL.

Generally, other agents will be present on a unit scale similar to agents of that class used clinically. Typically, this is 1-100 mg / mL. The invention encompasses all conventional modes of administration; oral and parenteral methods are preferred. Generally, the dosage regimen will be similar to other agents used clinically. Typically, the daily dose will be 1-10 mg / kg body weight daily. Generally, more compound is required orally and less parenterally. The specific dosage regimen, however, will be determined by a physician using correct medical judgment. The invention also encompasses methods in which the compound is given in combination therapy. That is, the compound can be used in conjunction with, but separately from, other agents useful for treating hepatitis and HCV infection. In these combination methods, the compound will generally be given in a daily dose of 1-100 mg / kg of body weight daily in conjunction with other agents. The other agents will generally be given in the amounts used therapeutically. The specific dosage regimen, however, will be determined by a physician using correct medical judgment. Some examples of suitable compounds for compositions and methods are listed in Table 2.

Table 2 Analytical HPLC and LC / MS were carried out using a Shimadzu-VP instrument using 220 nM UV detection and Waters Micromass. The NMR spectra were collected using Bucker DPX-300 MHz or DRX-500 MHz instruments. Intermediary 1 6- (Aminocarbonyl) -13-cyclohexyl-7H-indol [2, 1-a] benzazepine-10-carboxylic acid methyl ester. To a solution of 13-cyclohexyl-, 10-methyl ester of 7H-indole [2, 1-a] [2] benzaxepin-6,10-dicarboxylic ester, (1.10 g, 2.65 mmol) in DMF (7.0 mL) and DIPEA (1.85 mL, 10.6 mmol) was added TBTU (1.28 g, 3.97 mmol). The resulting solution was stirred at 22 ° C for 15 min. Ammonia (0.5M in dioxane, 21.2 mL, 10.6 mmol) was added and this solution was stirred at 22 ° C for 18 hours. 1M HC1 (50 mL) was added and the aqueous layer was extracted with CHCl3 (2x 50 mL). The organic phasedried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography on silica gel (4: 1, EtOAc: hexanes) of the concentrate gave the title compound (900 mg, 82%) as a yellow oil. MS m / z 415 (MH +), 1ti NMR (300 MHz, CDC13) d ppm 1.17-1.69 (m, 5H), 1.79 (m, 2H), 1.87-2.16 (m, 3H), 2.86 (m, 1 H ), 3.94 (s, 3H), 4.14 (broad m, 1 H), 5.72 (broad m, 1 H), 7.38 (s, 1 H), 7.46 (m, 2 H), 7.53 (dd, J = 7.6 , 8.4 Hz, 1 H), 7.61 (d, J = 7.6 Hz, 1 H), 7.74 (d, J = 8.4 Hz, 1 H), 7.87 (d, J = 8.4 Hz, 1 H), 8.29 (s) , 1 HOUR) . Intermediary 2 6-Cyano-13-cyclohexyl-7H-indole [2, 1-a] [2] benzaxepin-10-carboxylic acid methyl ester. To a solution of 6- (aminocarbonyl) -13-cyclohexyl-, 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (220 mg, 0.531 mmol) in dichloromethane (5.1 mL ) was added Burgess's Reagent (506 mg, 2.12 mmol). The resulting solution was stirred at 22 ° C for 6 hours. 1M HC1 (50 mL) was added and the aqueous layer was extracted with CHC13 (2 x 30 mL). The organic phase was dried over Na 2 SO 4, filtered and concentrated under reduced pressure to give the title (200 mg, 95%) as a yellow oil. MS m / z 397 (MH +), XH NMR (300 MHz, CDC13) d ppm 1.21-1.72 (m, 5H), 1.79 (m, 2H), 1.82-2.14 (m, 3H), 2.81 (m, 1H) , 3.96 (s, 3H), 4.47 (broad m, 1 H), 5.08 (wide m, 1 H), 7.42 (d, J = 8.4 Hz, 1H), 7.49-7.59 (m, 4 H), 7.78 ( d, J = 8.4 Hz, 1 H), 7.88 (d, J = 8 Hz, 1 H), 8.19 (s, 1 H). Intermediary 3 Methyl ester of 13-cyclohexyl-7H-indole [2, 1-a] [2] benzazepin-6,10-dicarboxylic acid. 13-cyclohexyl-, 7-indole [2, 1-a] [2] benzazepin-6,10-dicarboxylic acid dimethyl ester (98 mg, 0.23 mMole) was dissolved in 1.5 ml of THF and 0.24 ml of THF was added. 1.0M tetrabutylammonium hydroxide in methanol. The reaction was stirred at room temperature for 16 hours and then partitioned between ethyl acetate and 1N hydrochloric acid. The organic layer was washed with 1N hydrochloric acid, water, then brine and dried over magnesium sulfate to yield 93 mg (98%) of mono-acid product. XH NMR (500 MHz, CHLOROFORM-D) d ppm 8.29 (s, 1 H), 8.00 (s, 1 H) 7.88 (d, J = 8.55 Hz, 1 H), 7.74 (d, J = 8.55 Hz, 1 H) 7.58-7.65 (m, 1 H) 7.45-7.59 (m, 3 H) 5.67 (s, 1 H) 4.21 (s, 1 H) 2.84 (t, J = 12.05 Hz, 1 H) 1.99-2.18 (m, 3 H) 1.92 (d, 3 H) 1.77 (d, J = 7.63 Hz, 2 H) 1.40 (d, J = 12.51 Hz, 2 H) 1.17-1.31 (m, 6 H, trace Bu4NOH). MS m / z 416 (MH +). Intermediary 4 6-Chlorocarbonyl-13-cyclohexyl-7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester. Ester 13-cyclohexyl-, 10-methyl-7H-indole [2, 1-a] [2] benzazepin-6,10-dicarboxylic acid (1.50 g, 3.61 mols) was suspended in 30 ml of anhydrous dichloromethane. A solution of oxalyl chloride in dichloromethane (4.0 ml, 2.0M, 8.0 mMole) was added to the reaction. A catalytic amount of DMF (3 drops) was added. The reaction was briefly brought to reflux under nitrogen and allowed to cool and stir under nitrogen for 2.5 hours. The reaction volatiles were removed in vacuo. The residual oxalyl chloride was removed by azeotropic distillation with a mixture of benzene / dichloromethane to yield 1.59 g of a yellow solid. 1 H NMR (500 MHz, CHLOROFORM-D) d ppm 8.25 (s, 1 H) 8.22 (s, 1 H) 7.89 (d, J = 8.54 Hz, 1 H) 7.75-7.80 (m, 1 H) 7. 61-7.66 (m, 2 H) 7.57-7.61 (m, 1 H) 7.54 (dd, J = 5.95, 1.98 Hz, 1 H) 5.62-5.75 (m, J = 14.65 Hz, 2 H) 4.23 (s, 1 H), 3.96 (s, 3 H) 2.79-2.88 (m, 1 H) 1.99-2.17 (m, 3 H) 1.87-1.99 (m, 2 H) 1.77 (d, J = 7.63 Hz, 2 H) 1.31-1.68 (m, 3 H) 1.13-1-30 (m, 1 H). Intermediary 5 2- (Tetrahydro-2H-pyran-4-11) ethyl acetimidate hydrochloride. A 4-neck round bottom flask equipped with a pipette gas inlet tube connected to an anhydrous hydrogen chloride reading bottle and a gas outlet adapter to a bubbler containing ethanol was charged with 4-cyanomethyltetrahydropyran (970). mg, 775 mMole) and about 15 ml of anhydrous ethanol. The reaction was cooled with an ice bath and hydrogen chloride was bubbled in the reaction for 1 hour. The reaction was then capped with a rubber septum and placed in a freezer for 3 days. The reaction was taken out of the freezer, warmed to room temperature and the volatiles were removed in the vacuum of the reaction mixture, to obtain 1657 g of an amber oil. The oil was placed under nitrogen and placed in a freezer to crystallize overnight to a whitish solid. 1 H NMR (500 MHz, CHLOROFORM-D) d ppm 12.41 (s, 1 H) 11.52 (s, 1 H) 4.62 (q, J = 7.12 Hz, 2 H) 3.92 (dd, J = 11.44, 3.51 Hz, 2 H) 3.29-3.44 (ra, 2 H) 2.65 (d, J = 7.32 Hz, 2 H) 2.04-2.18 (m, 1 H) 1.54-1.63 (m, 2 H) 1.43-1.51 (ra, 4 H) 1.38-1.43 (m, 1 H). Intermediary 6 6-Hydroside 10-methyl ester of 13-cyclohexyl-7H-indole [2, 1-a] [2] benzazepin-6, 10-dicarboxylic acid. The 13-cyclohexyl-, 10-methyl ester of 7H-indole [, 21-a] [2] benzazepin-6, 10-dicarboxylic acid, (2.527 g, 6.08 mMole) was dissolved in 45 ml of DMF with hydroxybenzotriazole ( HOBt) (1.27 g, 9.4 mMoles). The coupling agent of 1- [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (1752 g, 9.14 mMol) was added to the reaction mixture. A bright yellow precipitate formed within 1 hour with stirring at room temperature and 50 ml of THF were added to dissolve the precipitate. The reaction was transferred by cannula to a stirred flask containing 2 mL of hydrazine (63.7 mMole) in 25 mL of THF and stirred for 3 hours at room temperature. The reaction was transferred to a 1 L Erlenmeyer flask and 500 ml of water was added with rapid stirring. A yellow precipitate was filtered, rinsed with water and dried under vacuum over phosphorus pentoxide. To produce 2,618 g (100%) of a light yellow solid. 1 H NMR (500 MHz, CHLOROFORM-D) d ppm 8.25 (s, 1 H) 7.85 (d, J = 8.54 Hz, 1 H) 7.73 (d, J = 8.55 Hz, 1 H) 7.57 (d, J = 7.63 Hz, 1 H) 7.48-7.54 (m, 1 H) 7.40-7.48 (m, 2 H) 7.30 (s, 1 H) 5.57 (s, 1 H) 4.17 (s, 1 H) 3.92 (s, 3 H ) 3.21 (s, 2 H) 2.76-2.90 (m, 1 H) 1.87-2.23 (m, 4 H) 1.47-1.82 (m, 3 H) 1.07-1.47 (m, 4 H); MS m / z 430 (MH +). Intermediary 7 Ester 13-cyclohexyl-3-methoxy-6- (phenylsulfonyl) -, ß-indole [2, 1-a] [2] benzazepine-10-carboxylic acid, tert-butyl ester. To a solution of methyl 3-cyclohexyl-2- (2-formyl-4-methoxyphenyl) -lH-indole-6-carboxylate (6.00 g, 13.8 mmol) in dioxane (28.0 mL) and BEMP (7.97 mL, 27.6 mmol) phenylvinylsulfone (27.6 g, 2.21 mmol) was added. Mix The resultant was stirred in a sealed tube in a microwave at 120 ° C for 15 minutes. The resulting solution was concentrated under reduced pressure. Chromatography on silica gel (CH2Cl2) of the concentrate gave the title compound (5.64 g, 70%) as a yellow oil. MS m / z 584 (MH +). 1 H NMR (500 MHz, CHLOROFORM-D) d ppm 1.18-1.33 (1 H, m), 1.34-1.45 (2 H, m), 1.49-57 (1 H, m), 1.64 (9 H, s), 1.74-1.82 (2 H, m), 1.90-2.09 (4 H, m), 2.73 (1 H, m), 3.93 (3 H, s), 4.38 (1 H, broad d), 5.08 (1 H, br D), 7.09 (1 H, d, J = 2.75 Hz), 7.12-7.18 (3 H, m), 7.22 (1 H, d, J = 7.45 Hz), 7.30 (1 H, s), 7.48 (1 H, d, J = 8.85 Hz), 7.54 (1 H, dd, J = 8.55, 1.22 Hz), 7.61 (2 H, m), 7.67 (1 H, d, J = 8.55), 8.01 (1 H, s). Intermediary 8 1,3-Cyclohexyl-3-methoxy-6- (tributylstannyl) -, 1,1-dimethyl ethyl ester of 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid. 13-Cyclohexyl-3- (methyloxy) -6- (tributyltin) -7H-indol [2, 1-a] [2] benzazepin-10-carboxylic acid 1,1-dimethylethyl ester. 13-Cyclohexyl-3-methoxy-6- (phenylsulfonyl) -, 1,1-dimethylethyl ester of 7H-indole [2, 1-a] [2] benzazepin-10- was dissolved. carboxyl (1.00 g, 1.71 mMoles) in 26 mL of benzene together with bis (tributyltin) (2.8 mL, 5.54 mMoles), tributyltin hydride (136 uL, 0.513 mMoles) and triethylamine (1.05 mL, 7.5 mMoles). The solution was bubbled for about 10 minutes with nitrogen and then the reaction 2, 2'-bisazoisobutyronitrile (AIBN) (96 mg, 0.58 mMoles) was added. The reaction was heated to reflux under nitrogen for 2 hours. The reaction was followed by LC-MS using the following CLAR conditions: Shimadzu Analytical CLAR using Discovery VP software:% A = 5% acetonitrile, 95% water, 10 mmol Ammonium Acetate% B = 95% acetonitrile, % water, 10 mmol Ammonium Acetate; % B Initial = 0; % B Final = 100; Gradient = 3 min .; Treatment time = 10 min.; Flow rate = 5 ml / min; Wavelength = 220 nm; Column = Waters Xterra, 3mm x 50mm, S7. To the reaction was added tributyltin hydride (0.45 mL, 1.7 mMole) and AIBN (95 mg, 0.58 mMole), the reaction was heated to reflux for 2 hours and analyzed for progress. AIBN (99 mg, 0.60 mMol) was added to the reaction and the reaction was heated to reflux for an additional 6 hours using a timer. The reaction was analyzed by LC-MS for progress and then tributyltin hydride (1.0 ml, 3.8 mMole) and AIBN (97 mg, 0.59 mMole) was added and the reaction was heated to reflux for 2 hours 20 min. The reaction was analyzed by LC-MS and AIBN (97 mg, 0.59 mMole) added to the reaction. The The reaction was heated for 1 hour under nitrogen at reflux and cooled and analyzed by LC-MS. Volatile materials were removed in vacuo from the reaction mixture and the reaction was purified by column chromatography using a Ci8 package of 190g of YMC GEL ODS-A, 120A spherical 75uM. The reaction residue (6.67 g of yellow oil) was dissolved in a minimum of dichloromethane and the solution was applied on the reverse phase column packed with 10% dichloromethane in acetonitrile. The initial elution was carried out using 10% dichloromethane in acetonitrile followed by elution with 15% dichloromethane in acetonitrile. Chromatography was monitored by TLC using a Whatman reverse phase MKC18F l "x3" 200 μM thick TLC plates eluting using 15% dichloromethane in acetonitrile. The observation of the compound was achieved by means of a UV lamp at 254 nm and iodine staining of the TLC plates. The product fractions were collected and the volatiles were removed in vacuo to yield 647 mg (52%) as a light yellow foam. 1 H NMR (500 Hz, CHLOROFORM-D) d ppm 0.71-0.83 (m, 9 H) 0.85-0.96 (m, 3 H) 0.95-1.08 (m, 6 H) 1.15-1.27 (m, 7 H) 1.27- 1.49 (m, 11 H) 1.53 (s, 5 H) 1.60-1.67 (m, 9 H9 1.68 - 1.82 (m, 2 H) 1.84-1.96 (m, 1 H) 1.96-2.16 (m, 3 H) 2.74 -2.91 (m, 1 H) 3.90 (s, 3 H) 4.16-4.40 (m, 1 H) 4.82-5.03 (m, 1 H) 6.72-6.90 (m, 2 H) 6.96 (dd, J = 8.55 Hz , 1 H) 8.04 (s, 1 H) LC-MS: Shimadzu Analytical CLAR using VP software:% A = 5% acetonitrile, 95% water, 10 mmol Ammonium Acetate; % B = 95% acetonitrile, 5% water, 10 mmol Ammonium Acetate; % Bnal = 0; % B Final = 100; Gradient = 3 min .; Execution time = 10 min; Flow rate = 5ml / min; Wavelength = 220 nm; Column = Waters Xterra, 3mm x 50mm, S7. Retention time = 4.2 min, MS m / z 734 (MH +). Intermediary 9 13-Cyclohexyl-3- (methyloxy) -6- (((5- (methyloxy) -2,5-dioxopentyl) amino) carbonyl) -7H-indole [2, 1-a] [2] benzazepine-10-carboxylate of methyl. 13-Cyclohexyl-3- (methyloxy) -10- ((methyloxy) carbonyl) -7H-indole [2, 1-a] [2] benzazepine-6-carboxylic acid (1.00 g, 2.24 mMole) was dissolved in 20 ml. of DMF together with l-hydroxy-7-azabenzotriazole (483 mg, 3.5 mMol). The reaction was placed under nitrogen, 1 - [3 - (dime ti 1 ami no) pr op i 1] - 3 -et ylburadiimide hydrochloride (663 mg, 3.5 mMoles) was added and the reaction was stirred for 1 hour at room temperature. ambient. 5-aminolevlic acid hydrochloride (608 mg, 3. 35 mMoles) to the reaction followed by di i s op op i 1 e t i 1 ami na (0.44mL, 2.5mMoles). The reaction was stirred overnight under nitrogen at room temperature. The volatiles were removed in vacuo and the residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The aqueous phase was extracted with ethyl acetate and the organic phases were combined, washed with brine and dried over magnesium sulfate. The volatiles were removed in vacuo to yield 1.47 g of crude product which was combined with 698 mg of a previous experiment. The crude product was purified by chromatography on silica gel eluting with a gradient of 10% ethyl acetate / dichloromethane to 25% ethyl acetate / dichloromethane to yield 1.64 g (84%) of the product as a yellow solid. 1 H NMR (500 MHz, CHLOROFORM-D) d ppm 1.12-1.30 (m, 1 H) 1.32-1.50 (m, 2 H) 1.77 (d, J = 9.16 Hz, 2 H) 1.89-1.99 (m, 1 H ) 1.99-2.18 (m, 3 H) 2.67 (t, J = 6.10 Hz, 2 H) 2.72-2.87 (m, 3 H) 3.67 (s, 3 H) 3.91 (s, 3H) 3.94 (s, 3 H) ) 4.15 (d, J = 19.23 Hz, 1 H) 4.31 (d, J = 34.79 Hz, 2 H) 5.62 (d, J = 12.82 Hz, 1 H) 6.70 (t, J = 4.12 Hz, 1 H) 6.96 (d, J = 2.44 Hz, 1 H) 7.08 (dd, J = 8.55, 2.75 Hz, 1 H) 7.33 (s, 1 H) 7.51 (d, J = 8.55 Hz, 1 H) 7.73 (d, J = 8.24 Hz, 1 H) 7.84 (d, J = 8.24 Hz, 1 H) 8.26 (s, 1 H); MS m / z 573 (MH +); MS m / z 571 (M-H) ~.

Intermediary 10 13-Cyclohexyl-3- (methyloxy) -10- (methyloxy) carbonyl) -7H-indole [2, 1-a] [2] benzazepine-6-carboxylic acid (1.50 g, 3.37 mMole) was dissolved in 32 ml of DMF together with 1-hydroxy-7-azabenzotriazole (697 mg, 5.1 mMoles). The reaction was placed under nitrogen, l- [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (967 mg, 5.04 mMole) was added and the reaction was stirred for 1.5 hours at room temperature. Aminoacetaldehyde dimethylacetal (0.44 mL, 4.1 mMole) was added to the reaction and the reaction was stirred at room temperature under nitrogen for 16 hours. The volatiles were removed in vacuo and the residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The aqueous phase was extracted with ethyl acetate and the organic phases were combined, washed with 0.1N hydrochloric acid after brine and dried over magnesium sulphate. The volatiles were removed in vacuo to yield 1.98 g of crude product which was used in the next reaction without purification. The crude acetal (1.4 g, 2.7 mMoles) was dissolved in 30 mL of acetone and 2 M hydrochloric acid (1.6 mL, 3.2 mMoles) and preheated to reflux and then allowed to stir for 2.5 hours before being briefly heated to reflux again and allowed to stir 1.5 hours more. 1N Hydrochloric acid (200 mL) was added to the reaction and a precipitate was filtered off which was rinsed with water and dried under vacuum to yield 1.14 g (87%) of crude product. The product was purified by chromatography on silica gel eluting with a gradient of 15% ethyl acetate in hexanes to 25% ethyl acetate in hexanes to yield 0.81 g (62%) of product as a yellow solid. 1 H NMR (500 MHz, CHLOROFORM-D) d ppm 1.25 (t, J = 7.17 Hz, 1 H) 1.31-1.48 (m, 2 H) 1.48-1.63 (m, 3 H) 1.77 (d, J = 9.46 Hz, 2 H) 1.86- 1.98 (m, 1 H) 1.98-2.16 (m, 3 H) 2.77-2.89 (m, 1 H) 3.91 (s, 3 H) 3.94 (s, 3 H) 4.18 (d, J = 14.04 Hz, 1 H ) 4.32 (d, J = 34.79 Hz, 2 H) 5.62 (d, J = 11.29 Hz, 1 H) 6.65 (s, 1 H) 6.97 (d, J = 2.75 Hz, 1 H) 7.09 (dd, J = 8.55, 2.75 Hz, 1 H) 7.35 (s, 1 H) 7.52 (d, J = 8.85 Hz, 1 H) 7.73 (d, J = 8.55 Hz, 1 H) 7.84 (d, J = 8.54 Hz, 1 H ) 8.26 (s, 1 H) 9.71 (s, 1 H). Shimadzu LC-MS discovery software; % A = 10% methanol, 90% water; 0.1% of TFA; % B = 90% methanol, 10% water, 0.1% Initial TFA% B = 50; % B Final = 100; Gradient = 5min; Execution time = 6 min; Flow Rate = 5ml / min; UV @ 220 nm; Column = Phenomenex Luna C18, lOu, 3.0 mm x 50 mm Product Retention Time = 4.2 min. MS m / z 487 (MH +).

Intermediary 11 Methyl ester of 13-cyclohexyl-6- [[(5-methoxy-2,5-dioxopentyl) amino] carbonyl] -TE-indole [2, 1-a] [2] benzazepine-10-carboxylic acid. 6- (Chlorocarbonyl) -13-cyclohexyl-, 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (499 mg, 1.15 mMole) was dissolved in 10 ml of anhydrous dichloromethane and added methyl 5-aminolevulinate hydrochloride (244 mg, 1.34 mMole) to the reaction mixture followed by 0.5 ml of pyridine (6.2 mMole). The reaction was stirred under nitrogen at room temperature for 40 hours. The volatiles were removed in vacuo and the residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic phase was washed with brine, dried over magnesium sulfate to yield 603 mg of crude product. The product was combined with 433 mg of a previous reaction run under the same conditions. The mixture was purified by column chromatography with silica eluting with a gradient of 20% ethyl acetate in dichloromethane to 20% ethyl acetate in dichloromethane produce 0.5 ml of pyridine 0.56 g (45%) of product. 1 H NMR (500 MHz, CHLOROFORM-D) d ppm 8.28 (s, 1 H) 7.87 (d, J = 8.55 Hz, 1 H) 7.74 (dd, J = 8.55, 1.22 Hz, 1 H) 7.59 (d, J = 7.93 Hz, 1 H) 7.43-7.56 (m, 3 H) 7.38 (s, 1 H) 6.71 (t, J = 4.12 Hz, 1 H) 5.65 (d, J = 10.99 Hz, 1 H) 4.31 (d , J = 27.16 Hz, 2 H) 4.14-4.23 (m, 1 H) 3.94 (s, 3 H) 3.67 (s, 3 H) 2.80-2.91 (m, 1 H9 2.01-2.16 (m, 3 H) 1.70 -2.00 (m, 3 H9 1.29-1.70 (m, 6 H) 1.14-1.31 (m, 2 H); MS m / z 543 (MH +), 560 (MNH4 +) Intermediary 12 13-Cyclohexyl-6- [2 [2- (tetrahydro-2H-pyran-4-yl) acetyl] hydrazide] -7H-indole [2, 1-a] [2] benzazepin-6,10-dicarboxylic acid. 13-Cyclohexyl-, 6- [2- [2- (tetrahydro-2H-pyran-4-yl) acetyl] hydrazide] of 7H-indole [2, 1-a] [2] benzazepin-6, 10-dicarboxylic acid was isolated as a by-product from the hydrolysis of ester 13-cyclohexyl-6- [5- [(tetrahydro-2-pyran-4-yl) methyl] -1,4,4-oxadiazol-2-yl] -, acid methyl? - Indole [2, 1-a] [2] benzazepine-10-carboxylic acid using the above CLAR conditions. The retention time was 6.9 minutes. 1 H NMR (500 MHz, CHLOROFORM-D) d ppm 11.64 (s, 1 H) 9.68 (d, J = 5.80 Hz, 1 H) 8.56 (s, 1 H) 7.92 (d, J = 8.54 Hz, 1 H) 7.78 (d, J = 8.24 Hz, 1 H) 7.65 (d, J = 7.63 Hz, 1 H) 7.46- 7.61 (m, 4 H) 5.84 (d, J = 14.95 Hz, 1 H) 4.18 (d, J = 14.34 Hz, 1 H9 3.93 (d, J = 10.99 Hz, 2 H) 3.37 (t, J = 11.44 Hz, 2 H) 2.79- 2.91 (m, 1 H) 2.44 (d, J = 6.71 Hz, 2 H ) 1.92-2.25 (m, 7 H) 1.76 (t, J = 11.29 Hz, 3 H) 1.67 (t, J = 9.92 Hz, 3 H) 1.53 (d, J = 10.99 Hz, 2 H) 1.32-1.50 ( m, 5 H) 1.15-1.28 (m, 1 H); MS m / z 542 (H +) Example 1 Methyl ester of 13-cyclohexyl-6- (1H-tetrazol-5-yl) -IR-indole [2.1-a] [2] benzazepine-10-carboxylic acid. To a solution of 6-cyano-13-cyclohexyl ester, 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (200 mg, 0.504 mmol) in toluene (2.0 mL) was added tributyltin azide (502 mg, 1.51 mmol). The resulting solution was stirred in a sealed tube in a microwave oven at 150 ° C for 30 minutes. 1M HC1 was added (15 mL) and the aqueous layer was extracted with CHC13 (2 x 30 mL). The organic phase was dried over Na 2 SO 4, filtered and concentrated under reduced pressure. Chromatography on silica gel (9: 1, EtOAc: methanol) of the concentrate gave the title compound (191 mg, 86%) as a yellow oil. MS m / z 440 (MH +), XH NMR (300 MHz, CD3OD) d ppm 1.18-1.69 (m, 5H), 1.79 (m, 2H), 1.86-2.15 (m, 3 H), 2.87 (m, 1 H), 3.94 (s, 3H, 4.52 (broad m, 1 H), 5.97 (wide m, 1 H), 7.49-7.54 (m, 3 H9, 7.62 (d, J = 7.6 Hz, 1 H), 7.68 (d, J = 8.4 Hz, 1 H), 7.75 (s, 1 H), 7.86 (d, J = 8.4 Hz, 1 H9, 8.38 (s, 1 H) Examples 2 and 3 13-Cyclohexyl-6- (2-ethyl-2H-tetrazol-5-yl) -5H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid and 13-cyclohexyl-6- (2- ethyl-2H-tetrazol-5-yl) -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid. To a solution of ester 13-cyclohexyl 1-6 - (1 H -tetrazo 1 -5-i 1), methyl of 7 H -indo 1 [2, 1 -a] [2] benz z epin-10-carboxy 1 i co (40 mg, 0.09 mmol) in DMF (1.0 mL) and cesium carbonate (60 mg, 0.18 mmol) Iodoethane (60 mg, 0.18 mmol) was added. The resulting mixture was heated at 60 ° C for 18 hours. Water (1 mL) was added and the mixture was heated at 60 ° C for an additional 8 hours. 1M HCl (15 mL) was added and the aqueous layer was extracted with CHC13 (2 x 30 mL). The organic phase was dried over Na 2 SO 4, filtered and concentrated under reduced pressure. This oil was purified by preparative reverse phase HPLC to give the title compounds. 7-H-id 1 [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-1- (2-ethyl-2H-tet razol-5-yl) -: mg, 49% yield MS m / z 454 (MH +), XH NMR (300 MHz, CD3OD) d ppm 1.17-1.66 (m, 5H), 1.68 (t, 3 H), 1.79 (m, 2 H9, 1.86-2.15 (m , 3 H), 2.88 (m, 1 H), 4.49 (broad m, 1 H), 4.70 (q, 2 H), 5.97 (broad m, 1 H), 7.47-7.58 (m, 3 H), 7.62 (d, J = 7.6 Hz, 1 H), 7.71 (d, J = 8.4 Hz, 1 H), 7.86 (d, J = 8.4 Hz, 1 H), 7.90 (s, 1 H), 8.41 (s, 1 H) Acid 5 H- i ndo 1 [2, 1 -a] [2] ben zaz ep in - 10 - ca rbox i 1 co, 13-cic 1 ohex i 1 - 6 - (2 - eti 1 - 2 H- 1 etrazo 1 - 5 - i 1) -: 11 mg, 27% yield MS m / z 454 (MH +), H NMR (300 mHz, CD3OD) d ppm 1.16-1.64 (m, 5H) , 1.68 (t, 3H), 1.79 (m, 2 H), 1.86-2.15 (m, 3H), 3.05 (m, 1 H), 3.68 (broad m, 1 H), 4.13 (broad m, 1 H) , 4.67 (q, 2 H), 7.31-7.39 (m, 2 H), 7.41-7.48 (m, 2 H9, 7.96 (t, J = 8.4, 8.4 Hz, 2 H), 8.20 (s, 1 H) , 8.38 (s, 1 H).

Example 4 13-Cyclohexyl-N- [(dimethylamino) sulfonyl] -6- [2-ethyl] -2H-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepine-10-carboxamide. To a solution of 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- (2-ethyl-2H-tetrazol-5-yl) - (87 mg, 0.19 mmol) ) in CH2C12 (1.0 mL) was added 2M oxalyl chloride (0.48 mL, 0.96 mmol). This solution was stirred at 22 ° C for 3 hours and then concentrated under reduced pressure. BEMP (0.22 mL, 0.76 mmol), CH2C12 (1.0 mL) and N, N-dimethylsulfamide (120 mg, 0.96 mmol) were added to the resulting oil. The resulting mixture was stirred for 6 hours at 22 ° C. 1M HC1 (15 mL) was added and the aqueous layer was extracted with CHCl3 (2 x 30 mL). The organic phase was dried over Na 2 SO 4, filtered and concentrated under reduced pressure. This oil was purified by reverse phase preparative HPLC to give the title compound (56 mg, 52%) as a yellow paste. MS m / z 561 (MH +), XH NMR (300 MHz, CD3OD) d ppm 1.16-1.64 (m, 5 H), 1.68 (t, 3 H), 1.80 (m, 2 H), 1.86-2.16 (m , 3H), 2.89 (m, 1 H), 3.09 (s, 6H), 4.52 (m wide, 1 H), 4.71 (q, 2 H), 5.97 (broad m, 1 H), 7.45-7.56 (m , 3 H), 7.61 (d, J = 7.6 Hz, 1 H), 7.69 (d, J = 8.4 Hz, 1 H), 7.83 (d, J = 8.4 Hz, 1 H), 7.87 (s, 1 H), 8.40 (s, 1 H), 8.69 (broad s, 1H). Example 5 13-Cyclohexyl-6- [2- (2-hydroxyethyl) -2H-tetrazol-5-yl] -7H-indole [2,1-a] [2] benzazepine-10-carboxylic acid. To a solution of 7-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (40 mg, 0.09 mmol) 13-cyclohexyl-6- (1H-tetrazol-5-yl) - methyl ester DMF (1.0 mL) and cesium carbonate (60 mg, 0.18 mmol) were added with 2-chloroethanol (15 mg, 0.18 mmol). The resulting mixture was heated at 60 ° C for 18 hours. Water (1 mL) was added and the mixture was heated at 60 ° C for an additional 8 hours. 1M HC1 (15 mL) was added and the aqueous layer was extracted with CHC13 (2 x 30 mL). The organic phase was dried over Na 2 SO 4, filtered and concentrated under reduced pressure. This oil was purified by preparative reverse phase HPLC to give the title compound (21 mg, 49% yield) as a yellow paste. MS m / z 470 (MH +), XH NMR (300 MHz, CD3OD) d ppm 1.18-1.69 (m, 5H), 1.79 (m, 2H), 1.86-2.15 (m, 3H), 2.89 (m, 1 H), 4.20 (broad m, 1 H), 4.32-4.56 (wide m, 2 H), 4.68-4.92 (broad m, 2H), 5.92 (wide m, 1 H), 7.48-7.58 ( m, 3 H), 7.61 (d, J = 7.6 Hz, 1 H), 7.66 (d, J = 8.4 Hz, 1 H), 7.75 (d, J = 8.4 Hz, 1 H), 7.90 (s, 1 H), 8.39 (s, 1 H). Examples 6 and 7 13-Cyclohexyl-6- [2- (cyclopropylmethyl) -2H-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepin-1-carboxylic acid and 13-cyclohexyl-6-acid [2- (cyclopropylmethyl) -2H-tetrazol-5-yl] -5H-indole [2,1-a] benzazepine-10-carboxylic acid. To a solution of 13-cyclohexyl-6- (1H-tetrazol-5-yl) -, 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (40 mg, 0.09 mole) DMF (1.0 mL) and cesium carbonate (60 mg, 0.18 mmol) was added (bromomethyl) cyclopropane (24 mg, 0.18 mmol). The resulting mixture was heated at 60 ° C for 18 hours. Water (1 mL) was added and the mixture was heated at 60 ° C for an additional 8 hours. HCl 1 (15 mL) was added and the aqueous layer was extracted with CHC13 (2 x 30 mL). The organic phase was dried over Na 2 SO 4, filtered and concentrated under reduced pressure.

This oil was purified by preparative reverse phase HPLC to give the title compounds. 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [2- (cyclopropylmethyl) -2H-tetrazol-5-yl] -: 22 mg, 50% yield. MS m / z 480 (MH +), XH NMR (300 MHz, CD3OD) d ppm 0.58 (m, 2 H), 0.70 (m, 2 H), 1.17-1.67 (m, 6H), 1.80 (m, 2 H ), 1.85-2.15 (m, 3H), 2.90 (m, 1 H), 4.42-4.58 (m wide, 3 H), 5.94 (wide m, 1 H), 7.49-7.54 (m, 3 H), 7.62 (d, J = 7.6 Hz, 1 H), 7.72 (d, J = 8.4 Hz, 1 H), 7.86 (d, J = 8.4 Hz, 1 H), 7.91 (s, 1 H), 8.49 (s, 1 HOUR) . 5H-Indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6-2- (cyclopropylmethyl) -2H-tetrazol-5-yl] -: 11 mg, 25% yield. MS m / z 480 (MH +), 1ti NMR (300 MHz, CD3OD) d ppm 0.50 (m, 2 H), 0.59 (m, 2 H), 1.19-1.69 (m, 6H), 1.81 (m, 2 H ), 1.85-2.15 (m, 3H), 3.10 (m, 1 H), 3.71 (m wide, 1 H), 4.18 (broad m, 1H), 4.49 (d, 2 H), 7.31-7.39 (m, 2 H), 7.42-7.49 (m, 2 H), 7.96 (t, J = 8.4, 8.4 Hz, 2 H), 8.20 (s, 1 H), 8.37 (s, 1 H). Examples 8, 9 and 10 13-Cyclohexyl-6- [2- [(tetrahydro-2-furanyl) methyl] -2H-tetrazol-5-yl] -5H-indol [2, 1-a] [2] benzazepine-10-carboxylic acid, acid 13-Cyclohexyl-6- [2- [(tetrahydro-2-furanyl) methyl] -2H-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid and -cyclohexyl-6- [1- [(tetrahydro-2-furanyl) methyl] -lH-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepin-1 O-carboxylic acid. To a solution of 7-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (40 mg, 0.09 mmol) 13-cyclohexyl-6- (1H-tetrazol-5-yl) - methyl ester in DF (1.0 mL) and cesium carbonate (60 mg, 0.18 mmol) was added 2- (bromomethyl) -tetrahydrofuran (30 mg, 0.18 mmol). The resulting mixture was heated at 60 ° C for 18 hours. Water (1 mL) was added and the mixture was heated at 60 ° C for an additional 8 hours. 1M HC1 (15 mL) was added and the aqueous layer was extracted with CHC13 (2 x 30 mL). The organic phase was dried over Na 2 SO 4, filtered and concentrated under reduced pressure. This oil was purified by reverse phase preparative HPLC to give the title compounds. 7H-Indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [2 [(tetrahydro-2-furanyl) methyl] -2H-tetrazol-5-yl] -: 22 mg, 48% yield S m / z 510 (MH +), XH NMR (300 MHz, CD3OD) d ppm 1.18-1.69 (m, 5H), 1.79 (m, 2H), 1.86-2.27 (m, 7H), 2.92 (m, 1 H ), 3.78 (m, 1 H), 3.93 (m, 1 H), 4.52 (broad m, 1 H), 4.54-4.87 (ra, 3 H), 5.98 (broad m, 1 H), 7.49-7.54 (m , 3 H), 7. 64 (d, J = 7.6 Hz, 1 H), 7.78 (d, J = 8.4 Hz, 1 H), 7.91 (d, J = 8.4 Hz, 1 H), 7.95 (s, 1 H), 8.49 (s) , 1 HOUR) . 5H-Indole [2,] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [2- [(tetrahydro-2-furanyl) methyl] -2H-tetrazol-5-yl] -: 10 mg , 22% yield. MS m / z 510 (MH +), XH NMR (300 MHz, CD3OD) d ppm 1.19-1.69 (m, 5H), 1.81 (m, 2H), 1.83-2.25 (m, 7H), 3.12 (m, 1 H ), 3.71 (broad m, 1 H), 3.83 (m, 1 H), 3.92 (m, 1 H), 4.15 (m wide, 1H), 4.51 (m, 1H), 4.62 (m, 1H), 4.73 (m, 1H), 7.32-7.38 (m, 2 H), 7.42-7.49 (m, 2 H), 7.98 (t, J = 8.4, 8.4 Hz, 2 H), 8.20 (s, 1 H), 8.38 (s, 1 H). 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [1- [(tetrahydro-2-furanyl) methyl] -lH-tetrazol-5-yl] -: 8 mg, 17% yield. MS m / z 510 (MH +), 1 H NMR (300 MHz, CD 3 OD) d ppm 1.19-1.70 (m, 5 H), 1.78 (m, 2 H), 1.84-2.26 (m, 7 H), 2.92 (m, 1 H), 3.80 (m, 1 H), 3.92 (m, 1H), 4.50 (m wide, 1 H), 4.55-4.87 (m, 3H), 5.97 (broad m, 1 H), 7.49-7.54 (m , 3 H), 7.65 (d, J = 7.6 Hz, 1 H), 7.78 (d, J = 8.4 Hz, 1 H), 7.90 (d, J = 8.4 Hz, 1 H), 7.94 (s, 1 H) ), 8.48 (s, 1 H). Examples 11, 12, 13 and 14 13-Cyclohexyl-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepin-10 acid -carboxylic acid, 13-cyclohexyl-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] -5H-indole [2, 1-a] [2] benzazepin-10-carboxylic acid, 13-cyclohexyl-6- [1- [(tetrahydro-2H-pyran-4-yl) methyl] -lH-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepin-10-carboxylic acid and 13-cyclohexyl-6- [1- [(tetrahydro-2 H -pyran-4-yl) methyl] -lH-tetrazol-5-yl] -5H-indole [2, 1] -a] [2] benzazepin-10-carboxylic acid. To a solution of 7-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (40 mg, 0.09 mmol) 13-cyclohexyl-6- (1H-tetrazol-5-yl) - methyl ester DMF (1.0 mL) and cesium carbonate (60 mg, 0.18 mmol) were added with 4- (bromomethyl) -tetrahydro-2H-pyran (31 mg, 0.18 mmol). The resulting mixture was heated at 60 ° C for 18 hours. Water (1 mL) was added and the mixture was heated at 60 ° C for an additional 8 hours. 1M HC1 (15 mL) was added and the aqueous layer was extracted with CHCl3 (2x30 mL). The organic phase was dried over Na 2 SO 4, filtered and concentrated under pressure reduced. This oil was purified by preparative reverse phase HPLC to give the title compounds. 7H-indole [2, la] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] -: 21 mg, 44% yield. MS m / z 524 (MH +), XH NMR (300 Hz, CD3OD) d ppm 1.18-1.69 (m, 6H), 1.79 (m, 2H), 1.86-2.20 (m, 7H), 2.91 (m, 1) , 3.39 (m, 2 H), 3.96 (m, 2 H), 4.52 (broad m, 3 H), 5.97 (broad m, 1 H), 7.48-7.54 (m, 3 H), 7.62 (d, J = 7.6 Hz, 1 H), 7.71 (d, J = 8.4 Hz, 1 H), 7.87 (d, J = 8.4 Hz, 1 H), 7.95 (s, 1 H), 8.39 (s, 1 H). 5H-Indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazole-5 il] -: 9 mg, 19% yield. MS m / z 524 (MH +), 1ti NMR (300 MHz, CD3OD) d ppm 1.19-1.69 (m, 6H), 1.81 (m, 2H), 1.83-2.21 (m, 7H), 3.10 (m, 1 H ), 3.42 (m, 2 H), 3.71 (broad m, 1 H), 3.98 (m, 2 H), 4.12 (broad m, 1H), 4.51 (m, 2H), 7.32-7.38 (m, 2 H) ), 7.42-7.49 (m, 2 H), 7.98 (t, J = 8.4, 8.4 Hz, 2 H), 8.20 (s, 1 H), 8.38 (s, 1 H). 7H-indole [2, la] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [1- [(tetrahydro-2H-pyran-4-yl) methyl] -lH-tetrazol-5-yl] -: 6 mg, 13% yield. MS m / z 524 (MH +), 1ti NMR (300 MHz, CD3OD) d ppm 1.18-1.69 (m, 6H), 1.79 (m, 2H), 1.86-2.20 (m, 7H), 2.90 (m, 1 H ), 3.59 (m, 2H), 3.89 (m, 2H), 4.52 (m wide, 1 H), 4.69 (m, 2H), 5.97 (broad m, 1 H), 7.48-7.54 (m, 3 H) , 7.62 (d, J = 7.6 Hz, 1 H), 7.71 (d, J = 8.4 Hz, 1 H), 7.87 (d, J = 8.4 Hz, 1 H), 7.94 (s, 1 H), 8.40 ( s, 1 H). 5H-indole acid [2, 1- a] [2] benzazepin-10-carboxylic acid, 13-cyclohexyl-6- [1- [(tetrahydro-2 H -pyran-4-yl) methyl] -lH-tetrazol-5-yl] -: 3 mg, 6% of performance. MS m / z 524 (MH +), XH NMR (300 MHz, CD3OD) d ppm 1.18-1.70 (m, 6H), 1.79 (m, 2H), 1.84-2.21 (m, 7H), 3.11 (m, 1 H ), 3.41 (m, 2H), 3.70 (broad m, 1 H), 4.01 (m, 2H), 4.12 (broad m, 1H), 4.52 (m, 2H), 7.32-7.38 (m, 2 H), 7.43-7.48 (m, 2 H), 7.99 (t, J = 8.4, 8.4 Hz, 2 H), 8.21 (s, 1 H), 8.36 (s, 1 H). Example 15 13-Cyclohexyl-N- [(dimethylamino) sulfonyl] -6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] -7H-indole [2, 1-] a] [2] benzazepin-10-carboxamide. To a solution of 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H- tetrazol-5-yl] - (100 mg, 0.19 mmol) in CH2C12 (1.0 mL) was added 2M oxalyl chloride (0.48 mL, 0.96 mmol). This solution was stirred at 22 ° C for 3 hours and then concentrated under reduced pressure. BEMP (0.22 mL, 0.76 mmol), CH2C12 (1.0 mL) and N, N-dimethylsulfamide (120 mg, 0.96 mmol) were added to the oil. resulting. The resulting mixture was stirred for 6 hours at 22 ° C. 1M HC1 (15 mL) was added and the aqueous layer was extracted with CHC13 (2 x 30 mL). The organic phase was dried over Na 2 SO 4, filtered and concentrated under reduced pressure. This oil was purified by preparative reverse phase HPLC to give the title compound (41 mg, 34%) as a yellow paste. MS m / z 631 (MH +), 1 H NMR (300 MHz, CD 3 OD) d ppm 1.17-1.71 (m, 6H), 1.78 (m, 2 H), 1.86-2.20 (m, 7H), 2.89 (m, 1H ), 3.11 (s, 6H), 3.40 (m, 2H), 3.97 (m, 2H), 4.52 (m wide, 3 H), 5.99 (broad m, 1 H), 7.49-7.55 (m, 3 H) , 7.62 (d, J = 7.6 Hz, 1 H), 7.69 (d, J = 8.4 Hz, 1 H), 7.85 (d, J = 8.4 Hz, 1 H), 7.92 (s, 1 H), 8.38 ( s, 1 H), 8.71 (broad s, 1 H). Example 16 13-Cyclohexyl-3-methoxy-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] -7H-indole [2,1-a] [2 ] benzazepin-10-carboxylic acid. 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-3-methoxy-6- [2- [(etrahydro-2H-pyran-4-yl) methyl] -2H- tetrazol-5-yl] - was made in a form analogous to 7H-indole [2, la] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [2- [(Tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] - (see above) to yield 110 mg (90% final yield stage) of a yellow solid. S m / z 555 (MH +), XH NMR (300 MHz, CD3OD) d ppm 1.18-1.69 (m, 6H), 1.81 (m, 2H), 1.92-2.38 (m, 7H), 2.89 (m, 1 H ), 3.46 (m, 2H), 3.95 (s, 3 H), 3.99 (m, 2H), 4.52 (m wide, 1 H), 4.56 (m, 2 H), 5.89 (broad m, 1 H), 7.05 (s, 1 H), 7.11 (d, J = 8.4 Hz, 1 H), 7.58 (d, J = 8.4 Hz, 1 H), 7.79 (d, J = 7.8 Hz, 1 H), 7.88 (d , J = 7.8 Hz, 1 H), 7.94 (s, 1 H), 8.44 (s, 1 H). Example 17 13-Cyclohexyl-N- [(dimethylamino) sulfonyl] -3-methoxy-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] -7H-indole [ 2, 1-a] [2] benzazepin-10-carboxamide. To a solution of 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-3-methoxy-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] ] -2H-tetrazol-5-yl] - (110 mg, 0.20 mmol) in CH2Cl2 (1.0 mL) was added 2M oxalyl chloride (0.50 mL, 1.00 mmol). This solution was stirred at 22 ° C for 3 hours and then concentrated under reduced pressure. BEMP (0.23 mL, 0.80 mmol), CH2C12 (1.0 mL) and N, N-dimethylsulfamide (124 mg, 1.00 mmol) to the resulting oil. The resulting mixture was stirred for 6 hours at 22 ° C. 1M HC1 (15 mL) was added and the aqueous layer was extracted with CHC13 (2 x 30 mL). The organic phase was dried over Na 2 SO 4, filtered and concentrated under reduced pressure. This oil was purified by reverse phase preparative HPLC to give the title compound (84 mg, 64%) as a yellow paste. MS m / z 661 (MH +), XH NMR (300 MHz, CD3OD) d ppm 1.18-1.69 (m, 6H), 1.79 (m, 2H), 1.93-2.40 (m, 7H), 2.89 (m, 1 H ), 3.09 (s, 6H), 3.42 (m, 2H), 3.93 (s, 3H), 3.96 (m, 2H), 4.52 (m wide, 1H), 4.56 (m, 2 H), 5.92 (wide m , 1 H), 7.05 (s, 1 H), 7.09 (d, J = 8.4 Hz, 1 H), 7.58 (d, J = 8.4 Hz, 1 H), 7.78 (d, J = 7.8 Hz, 1 H ), 7.86 (d, J = 7.8 Hz, 1 H), 7.90 (s, 1 H), 8.47 (s, 1 H), 8.69 (s broad, 1 H). Example 18 Methyl ester of 13-cyclohexyl-6- (4,5-dihydro-5-oxo-l, 3, 4-oxadiazol-2-yl) -7H-indole [2,1-a] [2] benzazepin-10 acid -carboxylic hydrazide (771 mg, 1.80 mMoles) 6-hydrazide 13-Cyclohexyl-, 10-methyl ester of 7-indol [2, 1-a] [2] benzazepin-6,10-dicarboxylic acid was partially dissolved in 18 ml of THF, diisopropylethylamine (DIEA) (0.34 mL, 1.95 mMole) was added and stirred for 5 minutes and then 1, 1 '-carbonyldiimidazole (CDI) (316 mg, 1.95 mMole) was added and the reaction was stirred overnight under nitrogen at room temperature. An additional 100 mg of CDI and 0.1 ml of DIEA were added to drive the reaction to the conclusion. The reaction was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic phase was washed with 0.1N hydrochloric acid, brine and dried over magnesium sulfate to yield 0.82 g of product. XH NMR (500 MHz, CHLOROFORM-D) d ppm 9.43 (s, 1 H), 8.20 (s, 1 H), 7.79 (d, J = 8.54 Hz, 1 H), 7.67 (d, J = 8.54 Hz, 1 H) 7.61 (d, J = 7.63 Hz, 1 H) 7.54 (t, J = 7.32 Hz, 1 H) 7.43-7.51 (m, 2 H) 7.41 (s, 1 H) 5.44 (d, - 13.43 Hz , 1 H) 4.00 (d, J = 15.87 Hz, 1 H) 3.90 (s, 3 H) 2.80 (t, J = 15.87 Hz, 1 H) 2.00-2.17 (m, 2 H) 1.89 (d, J = 41.20 Hz, 2 H) 1.51-1.80 (m, 3 H) 1.28-1.53 (m, 4 H) 1. 11-1.22 (m, 1 H); MS m / z 456 (MH +), MS m / z 454 (M-H). "Example 19 13-Cyclohexyl-6- (4,5-dihydro-5-oxo-1,3,4-oxadiazol-2-yl) -7H-indole [2, 1-a] [2] benzazepin-1-carboxylic acid . Ester 13-cyclohexyl-6- (4, 5-dihydro-5-oxo-l, 3, 4-oxadiazol-2-yl) -, 7-phi-indole methyl [2, 1-a] [2] benzazepin- 10-carboxylic acid (91 mg, 0.20 mMole) was suspended in 5 mL of acetic acid and 2.5 mL of 48% aqueous hydrobromic acid was added. The reaction was heated at 111 ° C for 4 hours. The reaction was cooled and a yellow precipitate was filtered off and rinsed with a small amount of acetic acid and then water. The product was dried under vacuum at room temperature to give 75 mg of product. X'H NMR (500 MHz, CHLOROFORM-D, MeOD) d ppm 8.17 (s, 1 H), 7.75 (d, J = 8.54 Hz, 1 H), 7.61 (d, J = 8.55 Hz, 1 H) 7.48 (d, J = 7.32 Hz, 1 H) 7.35-7.44 (m, 3 H9 7.30 (s, 1 H), 5.52 (d, J = 12.82 Hz, 1 H) 4.18 (d, J = 8.85 Hz, 1 H ) 2.65-2.78 (m, 1 H) 1.89-2.04 (m, 2 H) 1.71-1.85 (m, 1 H) 1.63 (d, J = 10.99 Hz, 2 H) 1.16-1.49 (m, 3 H) 1.11 (s, 2 H); MS m / z 442 (MH +). EXAMPLE 20 Methyl ester of 13-cyclohexyl acid 1-6 - [4,5-dihydro-5 -oxo-4- [(tetrahydro-2H-pyran-4-yl) methyl] -1,3,4-oxadiazole-2 -yl] -7H-indole [2, 1-a] [2] benzazepin-10-carboxylic acid. Ester 13-cic 1 -hexyl 1-6- (4,5-dihydro-5-oxo-1, 3-4-oxadi azo 1-2-i 1), 7-methyl-1-methyl acid [] 2, 1-a] [2] benzazepin-10 -carboxyi co (203 mg, 0.45 mMole) was dissolved in a mixture of 2 ml of DMF and 1 ml of THF with heating. To the reaction was added 4- (bromomethyl) tetrahydropyran (115 mg, 0.64 mMole), cesium carbonate (201 mg, 0.62 mMole) and sodium iodide (90 mg, 0.6 mMole) (95%). The reaction was capped and heated at 60 ° C overnight. The contents of the reaction were transferred to a 25 ml Erlenmeyer flask and water was added with rapid stirring. A bright yellow precipitate was filtered and rinsed with water and dried in the air to yield 236 mg of material (95%). 1ti NMR (500 MHz, CHLOROFORM-D) d ppm 8.32 (s, 1 H) 7.88 (d, J = 8.55 Hz, 1 H) 7.74 (dd, J = 8.55, 1.22 Hz, 1 H) 7.62 (d, J = 7.02 Hz, 1 H) 7.48-7.56 (m, 3 H) 7.43 (s, 1 H) 5.64 (d, J = 13.12 Hz, 1 H) 4.31 (d, J = 14.95 Hz, 1 H) 3.88-4.02 (m, 5 H) 3.67 (s, 2 H) 3.25-3.44 (m, 2 H) 2.77-2.87 (m, 1 H) 1.88-2.21 (m, 5 H) 1.70-1.82 (m, 2 H) 1.50 -1.70 (m, 4 H) 1.11-1.50 (m, 6 H); MS m / z 554 (MH +).

Example 21 13-Cyclohexyl-6- [4,5-dihydro-5-oxo-4 - [(tetrahydro-2H-pyran-4-yl) methyl] -1,4,4-oxadiazol-2-yl] -7H- acid indole [2, 1-a] [2] benzazepine-10-carboxylic acid. Ester 13-cyclohexyl-6- [4,5-dihydro-5-oxo-4- [(tetrahydro-2-pyran-4-yl) -methyl] -1,3,4-oxadiazol-2-yl] -, 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (225 mg, 0.41 mMole) was suspended in 5 ml of acetic acid and 2.5 ml of 48% aqueous hydrobromic acid was added. The reaction was heated at 100 ° C for 2 hours and then at 120 ° C for 1.5 hours and finally at 130 ° C for 3 more hours and then allowed to cool overnight. A yellow solid was filtered from the reaction mixture (55 mg) whose main component by HPLC analysis was the starting material. The filtrate was diluted with 50 ml of water and extracted with ethyl acetate. The organic phase was washed with water, then brine and dried over magnesium sulfate. The crude product residue was isolated by removal of volatiles at empty. The crude product was dissolved in an acetonitrile / DMF column and purified by reverse-phase HPLC under the following conditions: Shimadzu prep. CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% TFA; % B = 90% methanol, 10% water, 0.1% Initial TFA% B = 35; % B Final = 100; Gradient = 30 min; Run time = 40 min, Flow rate = 20 ml / min; Wavelength = 220 nm; Column = YMC Pro Pack 20 mm x 150 mm S5. XH NMR (500 MHz, CHLOROFORM-D) d ppm 8.40 (s, 1 H) 7.92 (d, J = 8.54 Hz, 1 H) 7.82 (d, J = 8.55 Hz, 1 H) 7.63 (d, J = 7.63 Hz, 1 H) 7.47-7.58 (m, 3 H) 7.44 (s, 1 H) 5.66 (d, J = 14.95 Hz, 1 H) 4.33 (d, J = 14.65 Hz, 4 H) 3.87-4.13 (m , 2 H) 3.72 (dd, J = 29.76, 5.95 Hz, 2 H) 3.26-3.52 (m, 2 H) 2.78-2.93 (m, 1 H) 2.14-2.26 (m, 1 H) 1.86-2.12 (m , 4 H) 1.31-1.84 (m, 9 H) 1.12-1.32 (m, 1 H); MS m / z 538 (M-H). Example 22 13-Cyclohexyl-6- [3- [(tetrahydro-2H-pyran-4-yl) methyl] -lH-1, 2,4-triazol-5-yl] -7H-indole [2, 1-a] [ 2] 10-carboxylic benzazepin. The synthesis of 7H-indole [2, 1-a] [2] benzazepin acid -carboxylic acid, 13-cyclohexyl-6- [3- [(tetrahydro-2 # -pyran-4-yl) methyl] -lfl-1,2,4-triazol-5-yl] - was carried out using the literature procedure: Kap-Sun Yeung, Michelle E. Farkas, John F. Kadow and Nicholas A. Meanwell; Tetrahedron Letters, 46 (2005) 3429-3432. In a 2 ml microwave ration tube, the following reagents were combined in 0.47 ml of n-butanol: 6-hydrazide of 13-cyclohexyl ester, 10-methyl ester of 7H-indole [2, 1-a] [2] ] benzazepin-6, 10-dicarboxylic (100 mg, 0.23 mMoles), 4-cyanomethyltetrahydropyran (88.3 mg, 0.71 mMoles), potassium carbonate (16.6 mg, 0.12 mMoles). The reaction was heated in a microwave at 150 ° C for 7 hours. The n-butyl ester intermediate was identified by LC / MS m / z 579 (MH +). The volatiles of the reaction were removed in vacuo and the crude reaction mixture was subjected to hydrolysis conditions of 10 ml of acetic acid, 5 ml of 48% aqueous hydrobromic acid at 80 to 100 ° C for 4 hours to produce the product final. Volatiles from the reaction mixture were removed in vacuo and the residue was dissolved in DMF / methanol for isolation by preparative HPLC using the following conditions: 2 injections of 2 ml in: Shimadzu prep. CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% TFA; % B = 90% methanol, 10% water, 0.1% TFA; % B Initial = 35; % B Final = 100; Gradient ^ 30 min; Execution time = 40 min; Flow Rate = 20 mi / min; Column = YMC Pro Pack 20 MI X 150 mm S5. Product peaks identified by LC / MS-MS m / z 442 (MH +) and combined to yield 25.2 mg. 1ti NMR (500 MHz, CHLOROFORM-D, MeOD) d ppm 8.35 (s, 1 H) 7.78 (d, J = 8.55 Hz, 3 H) 7.59-7.67 (m, 2 H) 7.53 (dd, J = 5.65, 3.51 Hz, 1 H) 7.44-7.49 (m, 1 H) 7.35-7.43 (m, 2 H) 5.89 (d, J = 15.26 Hz, 1 H9 4.29 (d, J = 14.34 Hz, 1 H9 3.84 (dd, J = 11.90, 3.05 Hz, 2 H) 2.80 (t, J = 11.44 Hz, 1 H) 2.63 (d, J = 7.32 Hz, 2 H) 1.60-2.18 (m, 8 H) 1.48-1.60 (m, 2 H) 1.08-1.41 (m, 6 H) Example 23 Methyl ester of 13-cyclohexyl-6- (3-methyl-1,2,4-oxadiazol-5-yl) -7H-indole [2,1-a] [2] benzazepine-10-carboxylic acid. The structure of the 1,2,4-oxadiazole ring can be synthesized according to the procedure of the Ying Wang and Regan L. Miller et al. Organic Letters 7 (5) 2005 p. 925-9258. 6- (Chlorocarbonyl) -13-cyclohexyl-, 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (250 mg, 0.58 mMole) was taken dissolved in 4.4 ml of anhydrous THF. Acetamide oxime (48 mg, 0.65 mMole) and diisopropylethylamine (0.2 mL, 1.15 mMole) were added to the reaction in a 5 mL microwave reactor tube. The reaction was capped under nitrogen and heated in a microwave at 150 ° C for 15 minutes. Additional acetamide oxime (12.8 mg, 0.17 mMole) was added and heated at 150 ° C for 10 minutes. The reaction was partitioned between ethyl acetate and 1N hydrochloric acid. The organic phase was then washed with 1 N hydrochloric acid, brine and dried over magnesium sulfate to yield 244 mg of crude product. Pure product (105 mg, 40%) was isolated from chromatography on silica gel eluting with dichloromethane. XH NMR (500 Hz, CHLOROFORM-D) d ppm 8.36 (s, 1 H) 7.92 (s, 1 H) 7.88 (d, J = 8.24 Hz, 1 H) 7.75 (d, J = 8.55 Hz, 1 H) 7.60-7.66 (m, 1 H) 7.47-7.59 (m, 3 H) 5.85 (s, 1 H) 4.48 (s, 1 H9 3.96 (s, 3 H) 2.85 (t, J = 11.75 Hz, 1 H) 2.44 (s, 3 H) 1.84-2.21 (m, 4 H) 1.77 (d, J = 7.93 Hz, 2 H) 1.31-1.48 (m, 3 H) 1.15-1.29 (m, 1 H); MS m / z 454 (MH +) Example 24 13-Cyclohexyl-6- (3-methyl-1,2,4-oxadiazol-5-7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid ester 13-cyclohexyl-6- (3- methyl-l, 2,4-oxadiazole-5- il) -, 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (97 mg, 0.21 mMole) was dissolved in 2.5 ml of pyridine together with lithium iodide (91 mg, 0.68 mMoles). The reaction was heated at 180 ° C for 2 hours in a microwave. The reaction volatiles were then removed in vacuo and the residue was partitioned between ethyl acetate and 1N hydrochloric acid. The organic phase was washed with 1 N hydrochloric acid, brine and dried over magnesium sulfate. Pure product (42 mg, 45%) was isolated by chromatography on silica gel by elution with 5% methanol in dichloromethane. ?? NMR (500 MHz, CHLOROFORM-D) d ppm 8.46 (s, 1 H) 7.88-8.02 (m, 2 H) 7.83 (d, J = 7.32 Hz, 1 H) 7.61-7.70 (m, 1 H) 7.48- 7.61 (m, 3 H9 5.89 (s, 1 H) 4.49 (s, 1 H9 2.86 (t, J = 11.44 Hz, 1 H9 2.47 (s, 3 H) 1.86-2.29 (m, 4 H) 1.78 (d, J = 7.63 Hz, 2 H) 1.31-1.51 (m, 2 H) 1.13-1.32 (m, 2 H); MS m / z 440 (MH +); MS m / z 438 (M-H) ~. Example 25 13-Cyclohexyl-N- [(dimethylamino) sulfonyl] -6- (3-methyl-1,2,4-oxadiazol-5-yl) -IR-indole [2, 1-a] [2] benzazepin-10- carboxamide. 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- (3-methyl-1,2,4-oxadiazol-5-yl) - (38 mg, 0.086 mMol) was placed in a 25 ml round bottom flask and 2 ml oxalyl chloride 2.0M in dichloromethane were added, followed by a drop of DMF. The reaction was briefly heated to reflux and then stirred at room temperature for 2 hours. The volatiles were removed in vacuo and the residual acid chloride was dissolved in 1 ml of anhydrous THF and the preformed anion of N, N-dimethylsulfamide prepared as follows was added dropwise over 7 minutes: N, N-dimethylsulfamide (35.9 mg, 0.289 mMole) was dissolved in 0.4 ml of anhydrous THF and 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,2,3-diazaphosphorine (62uL, 0.214 mMole) was added and the reaction was stirred for 10 minutes. minutes at room temperature under nitrogen. The reaction was allowed to proceed at room temperature under inert atmosphere for 1 hour. The reaction mixture was partitioned between 0.1 N hydrochloric acid and 30 mL ethyl acetate. The organic phase was washed with 0.1N hydrochloric acid, brine and dried over magnesium sulfate. The volatiles were removed in vacuo and the residue was dissolved in acetonitrile and purified by preparative HPLC using the following conditions to give 26.8 mg (57%) of the pure product as a yellow solid. Shimadzu prep. CLAR using Discovery VP software:% A = 10% acetonitrile, 90% water, 0.1% TFA% B = 90% acetonitrile, 10% water, 0.1% TFA; Initial B% = 30; % B Final = 100; Gradient = 15 min; Execution time = 25 min; Flow Rate = 25 ml / min; Wavelength = 220nm; Column = Phenonenex Luna 21.2 mm x 100 mm slO. ¾ NMR (500 MHz, CHLOROFORM-D) d ppm 8.60 (s, 1 H) 8.19 (s, 1 H) 7.89-7.95 (m, 2 H) 7.61-7.66 (m, 1 H) 7.50-7.61 (m, 3 H) 7.47 (dd, J = 8.55, 1.53 Hz, 1 H), 5.81 (s, 1H) 4.50 (s, 1 H) 3.08 (s, 6 H) 2.80-2.91 (m, 1 H) 2.45 (s) , 3 H) 1.84-2.18 (m, 4 H) 1.77 (d, J = 10.68 Hz, 2 H) 1.10-1.62 (m, 5 H9; MS m / z 546 (MH +) .Example 26 Methyl ester of 13-cyclohexyl-6- [3- [(methylsulfonyl) methyl] -1,2,4-oxadiazol-5-yl] -7H-indole [2,1-a] [2] benzazepin-10- carboxylic 6- (Chlorocarbonyl) -13-cyclohexyl-, 7-t-indol [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (776 mg, 1.79 mMole) was dissolved in 13 ml of anhydrous THF in a 20 ml microwave container. N-Hydroxy-2- (methylsulfonyl) ethanimidamide (308 mg, 2.02 mMole) was added to the reaction together with diisopropylethylamine (0.64 ml, 3.67 g. mMoles). The reaction was stirred for 5 minutes at room temperature and then heated in the microwave at 150 ° C for 15 minutes. The reaction was partitioned between 0.1N hydrochloric acid and ethyl acetate, washed with brine and dried over magnesium sulfate. The residue was chromatographed on silica gel and the product was eluted with ethyl acetate in dichloromethane to yield 287 mg (30%). XH NMR (500 MHz, CHLOROFORM-D) d ppm 1.13-1.23 (m, 1 H) 1.29-1.64 (m, 5 H) 1.77 (d, J = 9.77 Hz, 2 H) 1.87-2.00 (m, 1 H ) 2.04-2.17 (m, 2 H) 2.79-2.90 (m, 1 H) 3.23 (s, 3 H) 3.94 (s, 3 H) 4.47 (s, 2 H) 4.51 (d, J = 14.04 Hz, 1 H) 5.84 (d, J = 11.29 Hz, 1 H) 7.51-7.62 (m, 3 H) 7.62-7.67 (m, 1 H) 7.70-7.78 (m, 1 H) 7.88 (d, J = 8.24 Hz, 1 H) 7.99 (s, 1 H) 8.30 (s, 1 H); MS m / z 532 (MH +). Example 27 13-Cyclohexyl-6- [3- [(methylsulfonyl) methyl] -1,2,4-oxadiazol-5-yl] -β-indol [2, 1-a] [2] benzazepine-10-carboxylic acid. Ester-cyclohexyl-6- [3- [(methylsulfonyl) methyl] 1,2,4-oxadiazol-5-yl] -, 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (193 mg, 0.36 mMole) was dissolved in 3.6 ml of pyridine in a microwave tube. Lithium iodide (166 mg, 1.24 mMoles) was added and the reaction was placed under nitrogen and heated at 180 ° C in a microwave for 1 hour. The reaction was partitioned between ethyl acetate and 0.1N hydrochloric acid and brine was added to aid in phase separation. The organic layer was washed with a mixture of 0.12 N hydrochloric acid / brine, dried over magnesium sulfate and the volatiles were removed in vacuo to yield 180 mg of a brown solid. The crude reaction product was combined with 75 mg of crude reaction product from a pretest experiment and purified by chromatography on silica gel eluting with 5% methanol in dichloromethane to give 75 mg (29%) of product. A separate less pure fraction (13.6 mg) was further purified by preparative HPLC under the following conditions: Shimadzu prep. CLAR using Discovery VP software:% A = 10% acetonitrile, 90% water, 0.1% TFA; % B = 90% acetonitrile, 10% water, 0.1% TFA; Initial B% = 30; % B Final = 100; Gradient = 15 min; Execution time = 20 min; Flow rate = 25 ml / min; Wavelength = 220 nm; Column = Phenonenex Luna 21.2 mm x lOmm slO. Product retention time = 13.0 min, 5.9 mg of product recovered. 1R NMR (500 MHz, CHLOROFORM-D) d ppm 1.13-1.52 (m, 4 H) 1.53-1.85 (m, 3 H9 1. 86-2.23 (m, 4 H) 2.82-2.91 (m, 1 H) 3.29 (s, 3 H) 4.44-4.65 (m, 3 H) 5.89 (d, J = 12.21 Hz, 1 H) 7.52-7.65 ( m, 3 H) 7.64-7.70 (m, 1 H) 7.83 (d, J = 8.55 Hz, 1 H) 7.94 (d, J = 8.55 Hz, 1 H) 8.00 (s, 1 H) 8.39 (s, 1 H); MS m / z 518 (MH +). Example 28 13-Cyclohexyl-N- [(dimethylamino) sulfonyl] -6- [3- [(methylsulfonyl) methyl] -1,2,4-oxadiazol-5-yl] -7H-indole [2, 1-a] [2 ] benzazepin-1 O-carboxamide. 7H-Indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [3- [(methylsulfonyl) methyl] -1,2,4-oxadiazol-5-yl] - ( 75 mg, 0.13 mMoles) was dissolved in 1.5 ml of THF and carbonyldiimidazole (27.7 mg, 0.17 mMoles) was added. The reaction was stirred for 40 minutes at room temperature under a nitrogen atmosphere and then heated to reflux for 40 minutes. The reaction was cooled to room temperature under nitrogen and N, N-dimethylsulfamide (84 mg, 0.68 mMole) was added together with 22 uL (0.15 mMole) of DBU. The reaction it was stirred overnight (~ 16hr) at room temperature, then partitioned between ethyl acetate and 0.1N hydrochloric acid, washed with 0.1N hydrochloric acid, brine and dried over magnesium sulfate. The volatiles were removed in vacuo and the residue was purified by preparative HPLC under the following conditions: Shimadzu prep. CLAR using Discovery VP software:% A = 10% acetonitrile, 90% water, 0.1% TFA; % B = 90% acetonitrile, 10% water, 0.1% TFA; Initial B% = 30; % B Final = 100; Gradient = 15 min; Execution time = 20 min; Flow rate = 40 mi / min; Wavelength = 220 nm; Column = Waters Sunfire 30 mm x 100 mm S5. Product retention time = 13.3 min, 45.3 mg (51%) of product recovered. XH NMR (500 MHz, CHLOROFORM-D) d ppm 1.10-1.50 (ra, 3 H) 1.50-1.65 (m, 1 H) 1.69-1.83 (m, 2 H) 1.85-2.16 (m, 7 H) 2.79- 2.92 (m, 1 H) 3.07 (s, 6 H) 3.22 (s, 3 H) 4.51 (s, 3 H) 5.84 (d, J = 11.60 Hz, 1 H) 7.47 (d, J = 8.24 Hz, 1 H) 7.52-7.64 (m, 3 H) 7.63-7.69 (m, 1 H) 7.91 (d, J ^ 8.55 Hz, 1 H) 7.95 (s, 1 H) 8.13 (s, 1 H) 8.83 (s, 1 HOUR); MS m / z 624 (MH +). Example 29 6- (5-Amino-1,3,4-oxadiazol-2-yl) -13-cyclohexyl-7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester. To a suspension of 6-hydrazide of 13-cyclohexyl-, 10-methyl ester of 7 H-indo-1 [2, 1-a] [2] ben zaz ep in-6, 10-di caboxy 1 i co ( 1.01 g, 2.35 mMole) in 20 ml of 1,4-dioxane was added sodium bicarbonate (203 mg, 2.42 mMole) in 5.3 ml of water. The reaction was stirred for 20 minutes at room temperature and then cyanogen bromide (256 mg, 2.42 mMole) was added to the reaction. The reaction was capped and stirred for 18 hours at room temperature, after which cyanogen bromide (35 mg, 0.33 mMoles) was added. The reaction was stirred for a further 6 hours at room temperature. The reaction was filtered and rinsed with water and the precipitate was dried in vacuo to give 880 mg (82%) of product. 1 H NMR (500 MHz, CHLORIDE FORMO-D 6) d ppm 8.21 (s, 1 H) 7.93 (d, J = 8.55 Hz, 1 H) 7.63-7.69 (m, 2 H) 7.53-7.62 (m, 3 H ) 5.74 (d, J = 13.43 Hz, 1 H) 4.39 (d, J = 14.95 Hz, 1 H) 3.89 (s, 3 H) 2.73-2.87 (m, 1 H) 1.94-2.12 (m, 3 H) 1.84-1.94 (m, 1 H) 1.70 (d, J = 6.71 Hz, 2 H) 1.32-1.48 (m, 3 H) 1.06-1.18 (m, 1 H); MS m / z 455 (MH +), MS m / z 453 (M-H) ~.

Example 30 6- (5-Amino-1,3,4-oxadiazol-2-yl) -13-cyclohexyl-7H-indole [2,1-a] [2] benzazepine-10-carboxylic acid. 6- (5-amino-1,3,4-Oxadiazol-2-yl) -13-cyclohexyl-, 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (27.7) mg, 0.061 mMole) was suspended in 0.6 ml of THF and 0.2 ml of THF and 0.2 ml of tetrabutylammonium hydroxide in 1.0M methanol was added to the reaction. After the addition of the tetrabutylamine hydroxide solution the reaction became homogeneous. The reaction was stirred at room temperature for 16 hours resulting in only partial conversion of the product. The reaction was heated to 60 ° C for 2 hours then cooled and then 1N hydrochloric acid and DMF were added. The solution was injected in a preparative HLC to isolate 7.4 mg of product using the following conditions: Shimadzu prep. CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% TFA; % B = 90% methane, 10% water, 0.1% TFA; % B Initial = 35; % B Final% 100; Gradient = 30 min; Execution time = 50 miN; Flow rate = 20 mi / min; Column = YMC Pro Pack 20mm x 150mm S5. 1 H NMR (500 MHz, DMF) d ppm 12.90 (s, 1 H) 8.38-8.41 (m, 1 H) 7.70-7.78 (m, 3 H) 7.63-7.69 (ra, 1 H) 7.59-7.63 (m, 1 H) 7.43 (s, 2 H9 7.40 (s, 1 H) 5.91 (d, J = 17.09 Hz, 1 H) 4.51 (d, J = 12.82 Hz, 1 H) 2.03-2.22 (m, 3 H) 1.92 (t, J = 10.68 Hz, 1 H) 1.73 (d, J = 7.02 Hz, 2 H) 1.39-1.52 (m, 3 H) 1.18 (d, J = 12.82 Hz, 1 H) 0.84-0.91 (m, 1 H) Example 31 6- [5- [(Bromoacetyl) amino] -1,3,4-oxadiazol-2-yl] -13-cyclohexyl-7H-indole [2, 1-a] benzazepin-10-carboxylic acid methyl ester. Ester 6- (5-amino-l, 3, -oxadiazol-2-yl) -13-cyclohexyl-, 7-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (50.7 mg , 0.125 mMoles) was suspended in 1.0 ml of THF and pyridine (12 uL, 0.148 mMoles) was added. The reaction was cooled to 0 ° C under nitrogen and then brmoacetyl bromide (13 uL), 0.15 mMole) was added. The reaction stirred at 0 ° C for 1 hour and warmed to room temperature for 30 minutes. The reaction was divided between water and organic material consisting of ethyl acetate, THF and dichloromethane. The organic phase was washed with 0.1 N hydrochloric acid, brine and dried over magnesium sulfate to give 65 mg (90%) of product. 1 H NMR (500 MHz, DMSO-D6) d ppm 12.28 (s, 1 H) 8.25 (s, 1 H9 7.94 (d, J = 8.55 Hz, 1 H9 7.74 (d, J = 1.63 Hz, 1 H9 7.57 -7.70 (m, 5 H) 5.80 (d, J = 14.04 Hz, 1 H) 4.49 (d, J = 11.90 Hz, 1 H) 4.17 (s, 2 H) 3.90 (s, 3 H) 2.74-2.86 ( m, 1 H) 1.94-2.12 (m, 3 H) 1.82-1.95 (m, 1 H) 1.70 (d, J = 7.32 Hz 2 H) 1.36-1-50 (m, 3 H) 1.08-1.20 (m , 1 H); MS m / z 575 (MH +); MS m / z 573 (MH) ~ Example 32 Methyl ester of 13-cyclohexyl-6- [5- [(4-morpholinyl acetyl) amino] -1,3,4-oxadiazol-2-yl] -7H-indole [2,1-a] [2] benzazepin- 10-carboxylic acid Ester 6- [5- [(bromoacetyl) amino] -1,4,4-oxadiazol-2-yl] -13-cyclohexyl-, 7H-indole methyl ester [2, 1-] a] [2] benzazepin-10-carboxylic acid (62 mg, 0.11 mMol) was stirred in 1 ml of DMF and morpholine (28 uL, 0.32 mMol) was added to the reaction. A small fraction of sodium iodide was added to the reaction and the reaction was capped, stirred at room temperature for 16 hours. The reaction was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic layer was dried over magnesium sulfate and the volatiles were removed to give 67 mg of product. 1 H NMR (500 MHz, CHLOROFORM-D) d ppm 8.35 (s, 1 H) 7.86 (d, J = 8.55 Hz, 1 H) 7.74 (d, J = 8.54 Hz, 1 H) 7.58-7.66 (m, 2 H) 7.44-7.56 (m, 3 H) 5.81-5.98 (m, 1 H) 4.37-4.53 (m, 1 H) 3.94 (s, 3 H) 3.83 (s, 4 H) 2.69-2.87 (m, 5 H) 1.85-2.20 (m, 6 H) 1.34-1.86 (m, 14 H) 1.12-1.37 (m, 17 H) 0.74-0.94 (m, 9 H). The aliphatic region of NMR contains hydrocarbon (fat) contaminants not observed by HPLC; MS m / z 582 (MH +); MS m / z 580 (M-H) ". 13-Cyclohexyl-6- [5- [(4-orpholinylacetyl) amino] 1,3,4-oxadiazol-2-yl] -β-indole [2,1-a] [2] benzazepine-10-carboxylic acid . Ester 13-cyclohexyl-6- [5- [(4-morpholinyl acetyl) amino] 1, 3, 4-oxadiazol-2-yl] -, 7.9-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (60 mg, 0.10 mMole) was dissolved in 1 ml of anhydrous THF and potassium trimethylsilanoate (78 mg, 0.61 mMoles) was added. The reaction was capped and stirred at room temperature for 2.5 hours. Hydrochloric acid (6 mL of 0.1M) was added to the reaction and the product was extracted into ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The residue was triturated with hot diethyl ether to yield 18.7 mg (32%) of product as a yellow solid. ¾ M (500 MHz, DMSO-D6) d ppm 12.64 (s, 1 H) 11.55 (s, 1 H) 8.23 (s, 1 H) 7.91 (d, J = 8.55 Hz, 1 H) 7.72 (d, J) = 7.63 Hz, 1 H) 7.51-7.69 (m, 5 H9 5.79 (d, J = 13.12 Hz, 1 H) 4.48 (d, J = 12.21 Hz, 1 H) 3.55 (s, 4 H) 2.72-2.91 ( m, 1 H) 1.80-2.17 (m, 4 H) 1.61-1.81 (m, 2 H) 1.29-1.56 (m, 3 H) 1.03-1.22 (m, 1 H); MS m / z 568 (MH +) MS m / z 566 (MH) ~ Example 34 Methyl ester of 13-cyclohexyl-6- [5- (3-methoxy-3-oxopropyl) -2-oxazolyl] -β-indole [2,1-a] [2] benzazepine-10-carboxylic acid. Ester 13-cyclohexyl-6- [[(5-methoxy-2, 5 dioxopentyl) amino] carbonyl] -, 7H-indole [2, 1- a] [2] benzazepine-10-carboxylic acid methyl ester (0.25 g, 0.46 mMole) was dissolved in 4.6 ml of toluene and 93 uL of oxychloride was added of phosphorus. The reaction was heated to reflux for about 1.5 hours. The reaction was cooled and poured into an ice-cooled solution of saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated to yield 221 mg (92%) of the product. H NMR (500 MHz, CHLOROFORM-D) 5 ppm 8.38 (s, 1 H) 7.86 (d, J = 8.55 Hz, 1 H) 7.73 (d, J ^ 8.55 Hz, 1 H) 7.56-7.62 (m, 2 H) 7.42-7.54 (m, 3 H) 6.90 (s, 1 H) 5.93 (d, J = 12.51 Hz, 1 H9 4.36 (d, = 11.29 Hz, 1 H) 3.95 (s, 3 H) 3.69 ( s, 3 H9 3.03 (t, ^ 7.48 Hz, 2 H) 2.82-2.92 (m, 1 H) 2.69 (t, J = 7.48 Hz 2 H) 1.68-2.19 (m, 8 H) 1.49-1.61 (m, 1 H) 1.31-1.49 (m, 2 H) 1.14-1.31 (m, 2 H); MS m / z 525 (MH +). EXAMPLE 35 Methyl ester of 13-cyclohexyl-6- [5- [3- (4-morpholinyl) -3-oxopropyl] -2-oxazolyl] -TE-indole [2,1- a] [2] benzazepine-10-carboxylic acid . Ester 13-cyclohexyl-6- [5- (3-methoxy-3-oxopropyl) -2- oxazolyl] -, 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester (281 mg, 0.53 mMole) was dissolved in 3.5 ml of THF and 0.8 ml of 1.0 M tetrabutylamine hydroxide was added. in methanol to the reaction. The reaction was stirred at room temperature for 3.5 hours and cooled rapidly by dividing between 0.1 N hydrochloric acid and ethyl acetate. The organic phase was washed with brine and dried over magnesium sulfate. The volatile materials were removed and the sample was dried under vacuum to yield 232 mg (86%) of a yellow solid which was worked up without further purification. The yellow solid was suspended in 3 ml of dichloromethane and 2 ml of 2.0M oxalyl chloride in dichloromethane were added to the reaction followed by one drop of DMF. The reaction was stirred at room temperature under nitrogen for 3 hours 20 min. The volatiles of the reaction were removed in vacuo and the sample was dried under vacuum at room temperature for 2 hours 45 min. and then dissolved in 5 ml of dichloromethane and 0.15 ml (1.72 mMole) of morpholine was added. The reaction was stirred under a nitrogen atmosphere at room temperature for 2 days. The reaction was partitioned between ethyl acetate and 0.1N hydrochloric acid, washed with brine, dried over magnesium sulfate to yield 282 mg of residue. The reaction product was purified by silica column chromatography using gradient elution of 5% ethyl acetate / dichloromethane to 30% ethyl acetate. ethyl / dichloromethane to yield 157 mg (60%) of a yellow amorphous solid. XH NMR (500 MHz, CHLOROFORM-D) d ppm 8.38 (s, 1 H) 7.86 (d, J = 8.55 Hz, 1 H) 7.73 (d, J = 8.55 Hz, 1 H) 7.57-7.63 (m, 2 H) 7.45-7.53 (m, 3 H) 6.92 (s, 1 H) 5.92 (d, J = 13.43 Hz, 1 H) 4.37 (d, J = 14.04 Hz, 1 H) 3.95 (s, 3 H) 3.47 -3.76 (m, 6 H) 3.38 (d, J = 4.27 Hz, 2 H) 3.07 (t, J = 7.48 Hz, 2 H) 2.80-2.92 (m, 1 H) 2.65 (t, J = 7.48 Hz, 2 H) 1.87-2.19 (m, 5 H) 1.66-1.86 (m, 4 H) 1.50-1.66 (m, 2 H) 1.15-1.50 (m, 5 H); MS m / z 580 (MH +). Example 36 13-Cyclohexyl-6- [5- [3- (4-morpholinyl) -3-oxopropyl] -2-oxazolyl] -7H-indole [2, 1-a] benzazepine-10-carboxylic acid. Ester 13-cyclohexyl-6- [5- [3- (4-morpholinyl) -3-oxopropyl] -2-oxazolyl] -, 7H-indole methyl [2, 1-a] [2] benzazepin-10- carboxylic (22.4 mg, 0.039 mMole) and potassium trimethylsilanolate (75 mg, 0.19 mMole) were placed in a 1 gram jar with a magnetic stir bar and 0.4 ml anhydrous THF were added. The reaction was capped under nitrogen and stirred at room temperature for 22 hours. The reaction was acidified by the addition of acetic acid, diluted with acetonitrile and purified by preparative HPLC using the following conditions to yield 12.7 mg (57%) of product:% A = 10% acetonitrile, 90% water, 0.1 % of TFA; % B = 90% acetonitrile, 10% water, 0.1% TFA; Initial B% = 30; % B Final = 100; Gradient = 15 min; Execution time = 20 min; Flow Rate = 25 ml / min; Column = Phenomenex Luna 21.2 mm x 100 mm slO; XH NMR (500 MHz, CHLOROFORM-D) d ppm 8.52 (s, 1 H) 7.90 (d, ^ = 8.55 Hz, 1 H) 7.80 (dd,, 7 = 8.55, 1.22 Hz, 1 H) 7.65 (s, 1 H) 7.59-7.64 (m, 1 H) 7.44-7.56 (m, 3 H9 7.01 (s, 1 H) 5.88 (d, J = 13.43 Hz, 1 H) 5.46 (s, 4 H, H20 / H + peak) 4.40 (d, J = 13.12 Hz, 1 H) 3.51-3.69 (m, 6 H) 3.34-3.45 (m, 2 H) 3.10 (t, J = 7.32 Hz, 2 H) 2.82 -2.91 (m, 1 H) 2.66-2.73 (m, 2 H) I.98-2.19 (m, 3 H) 1.87-1.99 (m, 1 H) 1.70-1.85 (m, 2 H) 1.34-1.65 (m, 3 H9 1.15-1.34 (m, 3 H); MS m / z 566 (MH +) Example 37 13-Cyclohexyl-N- [(dimethylamino) sulfonyl] -6- [5- [3- (4-morpholinyl) -3-oxopropyl] -2-oxazolyl] -7H-indole [2,1-a] [2] benzazepin-10-carboxamide. 7-Indole-indol [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [5- [3- (4-morpholinyl) -3-oxopropyl] -2-oxazolyl] - (75 mg, 0.13 mMol) was dissolved in 1.5 ml of THF. Carbonyldiimidazole (28 mg, 0.17 mMole) was added to the reaction and the reaction was stirred under nitrogen at room temperature for 40 minutes and then heated to reflux for 40 minutes. The reaction was cooled under nitrogen and N, -dimethylsulfamide (84 mg, 0.68 mMole) was added to the reaction followed by DBU (22 uL, 0.15 mMole). The reaction was stirred overnight at room temperature. The reaction was partitioned between 0.1N hydrochloric acid and ethyl acetate. The organic phase was washed with 0.1 N hydrochloric acid, brine and dried over magnesium sulfate. The volatiles were removed in vacuo and the residue was purified by preparative HPLC under the following conditions: Shimadzu prep. CLAR using Discovery VP software:% A = 10% acetonitrile, 90% water, 0.1% TFA; % B = 90% acetonitrile, 10% water, 0.1% TFA; Initial B% = 30; % B Final = 100; Gradient = 12 min; Execution time = 22 min; Flow rate = 25 ml / min; Column = Waters Sunfire 19 x lOOmm S5; 49.6 mg (55%) of product was collected as an orange solid with retention time = 10.6 min; XH NMR (500 MHz, CHLOROFORM-D) d ppm 1. 09-1.32 (m, 1 H) 1.32-1.61 (m, 3 H) 1.68-1.87 (m, 2 H) 1.91-2.18 (m, 4 H) 2.69-2.79 (m, 2 H) 2.82-2.93 (m , 1 H) 3.05 (s, 6 H) 3.07-3.11 (m, 1 H) 3.14 (s, 1 H) 3.44 (d, J = 4.58 Hz, 2 H) 3.53-3.75 (m, 6 H) 4.40 ( d, J = 9.16 Hz, 1 H) 5.76 (d, J = 14.04 Hz, 1 H) 6.97 (s, 1 H) 7.49-7.57 (m, 3 H) 7.62 (d, J = 7.32 Hz, 1 H) 7.68 (d, J = 8.55 Hz, 1 H) 7.71 (s, 1 H) 7.92 (d, J = 8.55 Hz, 1 H) 8.49 (s, 1 H) 9.99 (s, 1 H); MS m / z 672 (MH +); S m / z 670 (M-H) ~. Example 38 13-Cyclohexyl-N- [(dimethylamino) sulfonyl] -6,7-dihydro-6- [5- [3- (4-morpholinyl) -3-oxopropyl] -2-oxazolyl] -5H-indole [2, 1 -a] [2] benzazepin-10-carboxamide. 7H-Indole [2, 1-a] [2] benzazepine-10-carboxamide, 13-cyclohexyl-N- [(dimethylamino) sulfonyl] -6- [5- [3- (4-morpholinyl) -3-oxopropyl] -2-oxazolyl] - (18 mg, 0.027 mMol) was dissolved in a mixture of 1.0 ml of THF, and 0.5 ml of methanol and 10% of palladium on carbon (7 mg) were added. The reaction was put under hydrogen (balloon atmosphere) and stirred at room temperature for 22 hours. The reaction was filtered through a plug of celite, and the celite was rinsed with methanol and THF. Volatile filtrate materials were removed in vacuo and the residue was dissolved in methanol and purified by preparative HPLC under the following conditions: Shimadzu prep. CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% TFA; % B = 90% methanol, 10% water, 0.1% TFA; % B Initial = 35; % B Final = 100; Gradient = 30 min; Execution time = 50 min; Flow rate = 20 mi / min; Column = YMC Pro Pack 20 mm x 150 mm S5; Product retention time = 29.4 min; ¾ RM (500 MHz, CHLOROFORM-D6) d ppm 1.19-1.32 (m, 1 H) 1.31-1.53 (m, 2 H) 1.68 (d, J L2.21 Hz, 1 H) 1.78 (d, J = 9.46 Hz, 2 H) 1.93 (d, J = 11.90 Hz, 1 H) 1.97-2.11 (m, 3 H) 2.55-2.75 (m, 2 H) 2.80-2.89 (m, 1 H) 2.89-3.14 (m, 10 H) 3.16-3.24 (m, 1 H) 3.33-3.61 (m, 3 H) 3.62-3.74 (m, 5 H) 3.84 (dd, 1 H) 4.06 (dd, .7 = 15.11, 5.95 Hz, 1 H) 4.80 (d, J = 15.26 Hz, 1 H) 6.89-6.95 (m, 1 H) 7.45 (d, J = 5.19 Hz, 4 H) 7.62 (d, J = 7.63 Hz, 1 H) 7.90 (d , J = 8.5 Hz, 1 H) 8.05 (s, 1 H) 9.68 (s, 1 H); MS m / z 674 (MH +). Example 39 Methyl ester of 13-cyclohexyl-6- [5- [(tetrahydro-2 H -pyran-4-yl) methyl] -1,3,4-oxadiazol-2-yl] -7H-indole] 2, 1-a] [2] benzazepin-10-carboxylic acid. ß-hydrazide of 13-cyclohexyl-, 10-methyl ester of 7H-indole [2, 1-a] [2] benzazepine-6, 10-dicarboxylic ester (720 mg, 1.68 mMole) and 2- (tetrahydroxy) hydrochloride Ethyl 2H-pyran-4-yl) acetimidate (422 mg, 2.05 mMol) was suspended in 5.2 mL of isopropanol and diisopropylethylamine (DIEA) (4.4 mL, 25.3 mMoles) was added to the reaction. The reaction was stirred for 10 minutes and heated to about 70 ° C under nitrogen for 2 hours before increasing the reaction temperature to 80 ° C. After 21 hours of heating, the HPLC analysis of the reaction showed a conversion of about 27% between cyclized alcohol and about 72% as an uncyclized intermediate. The reaction was transferred to a 20 mL microwave vessel and 5 mL of additional isopropanol were added to the reaction. The reaction was heated in a microwave at 150 ° C for 1 hour. The reaction volatiles were removed in vacuo and the residue was stirred in a separatory funnel with ethyl acetate and 1N hydrochloric acid. The reaction residue failed to adequately dissolve in the organic phase, therefore most of the aqueous phase was drained and dichloromethane was added. The pH of the organic phase was elevated by washing with saturated sodium bicarbonate. This stage seemed to help in the dissolution of the solid The organic phases were washed with brine and dried over magnesium sulfate to give 905 mg of a yellow-orange solid. Oxadiazole product (Rf = 0.55 in 25% ethyl acetate in dichloromethane) was isolated using column chromatography on silica gel eluting with a gradient of 10% ethyl acetate in dichloromethane at 30% ethyl acetate in dichloromethane. Product weight = 182 mg as a yellow solid. An analytically pure sample (164.6 mg) was obtained by trituration with hot methanol (2 ml) and rinsing with 2 ml of methanol at room temperature. 1 H NMR (500 MHz, CHLOROFORM-D) d ppm 7.88 (d, J = 8.24 Hz, 1 H) 7.63 (t, J = 3.36 Hz, 2 H) 7.46-7.58 (ra, 3 H) 5.94 (d, J = 7.32 Hz, 1 H) 4.46 (d, J = 11.29 Hz, 1 H) 3.86-4.01 (m, 5 H) 3.38 (t, J = 11.60 Hz, 2 H) 2.75-2.95 (m, 3 H) 2.00 -2.23 (m, 4 H) 1.88-2.00 (m, 1 H) 1.66-1.85 (m, 5 H) 1.51-1.66 (m, 2 H) 1.33-1.50 (m, 4 H) 1.13-1.31 (m, 1 HOUR); MS m / z 538 (MH +). Example 40 Methyl ester of 13-cyclohexyl-6- [5- [(tetrahydro-2H-pyran-4-yl) methyl] -1H-1, 2,4-triazol-3-yl] -7H-indole [2, 1] -a] [2] benzazepin-10-carboxylic acid. From the reaction mixture describing the preparation of 13-cyclohexyl-6- [5- [(tetrahydro-2H-pyran-4-yl) methyl] -1,3,4-oxadiazol-2-yl] - methyl ester of 7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid, the title compound- was isolated (Rf = 0.17 in 25% ethyl acetate in dichloromethane) from the gel column chromatography of silica to give 476 mg (53%) as a yellow solid. XH NMR (500 MHz, CHLOROFORM-D) d ppm 8.38 (s, 1 H) 7.75-7.90 (m, 2 H) 7.68 (d, J = 8.24 Hz, 1 H) 7.56-7.63 (m, 1 H) 7.50 -7.56 (m, 1 H) 7.41-7.50 (m, 2 H) 5.91 (d, J = 12.21 Hz, 1 H) 4.26 (d, J = 11.90 Hz, 1 H) 3.87-4.02 (m, 5 H) 3.33 (t, J = 11.29 Hz, 2 H) 2.87 (s, 1 H) 2.76 (s, 2 H) 1.84-2.17 (m, 6 H) 1.68-1.82 (m, 2 H) 1.30-1.66 (m, 8 H) 1.13-1.29 (m, 2 H); MS m / z 537 (MH +). Example 41 Methyl ester of 13-cyclohexyl-6- [l-methyl-5- [(tetrahydro-2H-pyran-4-yl) methyl] -lH-l, 2,4-triazol-3-yl] -7H-indole acid [2, 1-a] [2] benzazepin-10-carboxylic acid. Ester 13-cyclohexyl-6- [5- [(tetrahydro-2H-pyran-4-yl) methyl] -1H-1,2,4-triazol-3-yl] -, 7H-indole methyl methacrylate [2, 1-a] [2] benzazepine-10-carboxylic acid were dissolved in 3 ml of DMF. Iodomethane (39 uL, 0.62 mMole) was added to the reaction followed by sodium hydride (60% in mineral oil, 0.47 mMole). The reaction was capped under nitrogen and stirred at room temperature for 16 hours. The volatiles were removed in vacuo and the reaction was partitioned between ethyl acetate and saturated aqueous ammonium chloride. The aqueous was extracted with ethyl acetate. The organic fractions were combined and washed with saturated ammonium chloride, brine, dried over magnesium sulfate to obtain 174 mg of a yellow-brown solid. The chromatography residue on silica gel using 10% ethyl acetate in dichloromethane to obtain 100 mg (58%) of product. ¾ NMR (500 MHz, CHLOROFORM-D) d ppm 8.47 (s, 1 H) 7.85 (d, ^ 8.55 Hz, 1H) 7.67-7.76 (m, 2 H) 7.60 (dd, J = 5.19, 3.66 Hz, 1 H) 7.49-7.56 (m, 1 H) 7.41-7.49 (m, 2 H) 5.97 (d, J = 13.12 Hz, 1 H) 4.35 (d, = 14.04 Hz, 1 H) 3.90-3.98 (m, 5 H) 3.87 (s, 3 H) 3.37 (t, J = 11.44 Hz, 2 H) 2.84-2.93 (m, 1 H) 2.68 (d, < J = 7.02 Hz, 4 H) 2.68 (d, = 7.02 Hz, 2 H) 1.89-2.18 (m, 6 H) 1.67-1.83 (m, 2 H) 1.64 (d, J = 12.82 Hz, 2 H) 1.49-1.61 (m, 3 H) 1.32-1.48 ( m, 5 H) 1.14-1.31 (m, 3 H9.

Example 42 13-Cyclohexyl-6- [l-methyl-5- [(tetrahydro-2H-pyran-4-yl) methyl] -1H-1,2,4-triazol-3-yl] -7H-indole [2] acid 1-a] [2] benzazepin-1 O-carboxylic acid. Ester 13-cyclohexyl-6- [l-methyl-5- [(tetrahydro-2H-pyran-4-yl) methyl] -1H-1,2,4-triazol-3-yl] -, 7H-methyl-methyl Indole [2, 1-a] [2] benzazepine-10-carboxylic acid (94 mg, 0.17 mMol) was dissolved in 1.7 ml of anhydrous THF and potassium trimethylsilanolate (104 mg, 0.81 mMole) was added to the reaction. The reaction was capped under nitrogen and stirred at room temperature for 2 hours. The reaction was quenched with 1N hydrochloric acid and the product was extracted into ethyl acetate, washed with brine and dried over magnesium sulfate. The volatiles were removed in vacuo to give 89 mg of crude product. The product was purified by trituration with diethyl ether to yield 59 mg (64%). 1 H NMR (500 MHz, CHLOROFORM-D) d ppm 8.55 (s, 1 H) 7.89 (d, J = 8.55 Hz, 1 H) 7.78 (d, J = 8.55 Hz, 2 H) 7.61 (dd, J = 5.34 , 3. 51 Hz, 1 H) 7.51-7.58 (m, 1 H) 7.46 (dd, J = 5.49, 3.36 Hz, 2 H) 5.97 (d, J = 14.04 Hz, 1 H) 4.36 (d, J = 13.43 Hz, 1 H) 3.94 (dd, J = 11.44, 3.51 Hz, 2 H) 3.88 (s, 3 H) 3.38 (t, J = 11.29 Hz, 2 H) 2.83-2.96 (m, 1 H) 2.71 (d, J = 6.41 Hz, 2 H) 1.88-2.25 (m, 6 H) 1.76 (d, J = 11.60 Hz, 2 H) 1.65 (d, J = 11.90 Hz, 2 H) 1.30-1.59 (m, 6H) 1.16- 1.27 (m, 2 H); MS m / z 537 (MH +). Example 43 13-Cyclohexyl-N- [(dimethylamino) sulfonyl] -6- [1-methyl-5- [(tetrahydro-2H-pyran-4-yl) methyl] -1H-1, 2,4-triazol-3-yl ] -7H-indole [2, 1-a] [2] benzazepine-10-carboxamide. 7H-Indole [2, 1-a] [2] benzazepine-10-carboxylic acid, 13-cyclohexyl-6- [l-methyl-5- [(tetrahydro-2J / -pyran-4-yl) methyl] -lJi -l, 2,4-triazol-3-yl] - (58 mg, 0.11 mMol) was dissolved in 2 ml of dichloromethane containing 2.0 M oxalyl chloride. A drop of DMF was added to the reaction mixture and the reaction was stirred for 2.5 hours under nitrogen. The volatiles were removed in vacuo and the acid chloride was stored under nitrogen until needed. N, N- dimethylsulfamide (45.7 mg, 0.37 mMoles) was dissolved in 0.5 ml of THF and 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,2,3-diazaphosphorine (68.8 uL, 0.238 mMoles) was added. The reaction was stirred at room temperature for about 15 minutes and then the above acid chloride was dissolved in 1 ml of THF and added dropwise by means of a syringe. The reaction was capped under nitrogen and stirred for 2 hours at room temperature after which the progress of the reaction was monitored by HPLC. N, N-dimethylsulfamide (20 mg, 0.16 mMoles) and additional 2-tert-butylimino-2-diethylamino-l, 3-dimethylperhydro-l, 3, 2-diazaphosphorine (46 ul, moles) were added to the reaction in 0.3 mL of THF. The reaction was stirred for an additional 15.5 hours under nitrogen. The reaction was divided between ethyl acetate and 0.1 M citric acid, washed with 0.1M citric acid. The organic phase was washed with brine, dried over magnesium sulfate and the volatiles were removed in vacuo to give 125 mg of a brown oil. The product (4.3 mg, 6%) was isolated by preparative HPLC under the following conditions: Shimadzu prep. CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% TFA; %% = 90% methanol, 10% water, 0.1% TFA; % B Initial = 35; % B Final = 100; Gradient = 30 min; Execution time = 50 min; Flow rate = 20 ml / min; Wavelength = 220 nm; Column = YMC Pro Pack 20 mm x 150 mm S5. 1ti NMR (500 MHz, CHLOROFORM-D) d ppm 8.73 (s, 1 H) 8.27 (s, 1 H) 7.91 (d, J = 8.55 Hz, 1 H9 7.77-7.88 (m, 2 H) 7.58-7.65 (m, 1 H) 7.44-7.57 (m, 5 H) 5.81 (d, J = 14.34 Hz, 1 H), 4.41 (d, J = 13.12 Hz, 1 H) 3.91-4.04 (m, 7 H) 3.32-3.44 (m, 2 H) 3.13-3.23 (m, 1 H) 3.07 (s, 6 H) 2.81-2.95 ( m, 4 H) 1.85-2.16 (m, 7 H) 1.67- 1.83 (m, 3 H) 1.50-1.65 (m, 4 H) 1.15-1.51 (m, 8 H); MS m / z 643 (MH +) Example 44 13-Cyclohexyl-6- [5- [(tetrahydro-2H-pyran-4-yl) methyl] -1,4,4-oxadiazol-2-yl] -7H-indole [2, 1-a] [2 ] benzazepin-10-carboxylic acid. Ester 13-cyclohexyl-6- [5- [(tetrahydro-2H-pi ran-4-y1) met i] - 1, 3, 4-oxadi azo 1 - 2 - i 1] -, methyl 7 ff-indo 1 [2, 1-a] [2] benzazepin-10-carboxylic acid (156 mg, 0.29 mMole) was dissolved in anhydrous THF and potassium trimethylsilanolate (198 mg, 1.54 mMole) was added to the reaction. The reaction was capped under nitrogen and stirred at room temperature for 19 hours. The reaction was divided between ethyl acetate and 0.1N hydrochloric acid. The reaction was extracted with ethyl acetate and the organic phases were combined and washed with brine, dried over magnesium sulfate and the volatiles were removed in vacuo to yield 166 mg of crude material. About 87 mg of the crude reaction was dissolved in a methanol / acetonitrile / DMF mixture and subjected to purification with HPLC using the following conditions:% A = 10% acetonitrile, 90% water, 0.1% TFA; % B = 90% acetonitrile, 10% water, 0.1% TFA; Initial B% = 30; % B Final = 100; Gradient = lOmin; Execution time = 15 min; Flow rate = 25 ml / min; Column = Phenomenex Luna 21.2 mm x 100 mm slO; the retention time of 7 H-indole [2, la] [2] ben zaz ep i n-10-caboxy 1 i co, 13-cyclohexyl-6- [5- [(tetrahydro-2-pyran 4-yl) methyl] -1, 3, 4-oxadiazol-2-yl] - was 9.9 minutes. XH NMR (500 Hz, CHLOROFORM-D) d ppm 8.48 (s, 1 H) 7.91 (d, J = 8.55 Hz, 1 H) 7.80 (dd, J = 8.55, 1.53 Hz, 1 H) 7.61-7.68 (m , 2 H) 7.49-7.58 (m, 3 H9 5.96 (d, J = 13.12 Hz, 1 H) 4.48 (d, J = 8.24 Hz, 1 H) 3.96 (dd, J = 11.44, 3.20 Hz, 2 H) 3.33-3.44 (m, 3 H) 2.81-2.92 (m, 3 H) 2.01-2.20 (m, 4 H) 1.90-2.01 (m, 1 H) 1.65-1.84 (m, 4 H) 1.51-1.62 (m , 1 H) 1.32-1.52 (m, 5 H) 1.16-1.29 (m, 1 H); MS m / z 524 (MH +); MS m / z 522 (MH) ~.

Example 45 13-Cyclohexyl-6- (furan-3-yl) -TH-indole acid. { 2,1-a] [2] benzazepin-10-carboxylic acid. Step 1: Sodium hydride (44 mg of 95%, 1. 74 mmole) was added to a freezing solution of methyl 3-cyclohexyl-2- (2-vinylphenyl) lH-indole-6-carboxylate (0.500 mg, 1.34 mmol) in THF (6 mL). When the hydrogen evolution occurred, 2,3-dibromoprop-l-ene (402 mg, 2.01 mmol) was added in a single portion. Stirring was continued at 0 ° C for 2 hours and then at 22 ° C for 24 hours. The solution was concentrated and the residue was chromatographed on Si02 with petroleum ether-ethyl acetate (10: 1) using the vaporization technique to give 1- (2-bromoalyl) -3-cyclohexyl-2- (2-vinylphenyl) -lH-indol-6-carboxylic acid methyl ester (285 mg, 44.5%) as a gummy solid. MS m / z 479 (MH +). Step 2: Tetrakis (triphenylphosphine) palladium (0) (38 mg, 0.033 mmol) was added to a stirred and degassed mixture of 1- (2-bromoalyl) -3-cyclohexyl-2- (2-vinylphenyl) -lH-indole -6-methyl carboxylate (157 mg, 0.33 mmol), 3-furylboronic acid (54.5 mg, 0.49 mmol), LiCl (55 mg, 0.66 mmol) in ethanol (2 mL) and toluene (2 mL) containing aqueous sodium carbonate 1 (0.82 mL) , 0.82 mmoles). The mixture was heated under reflux for 1 hour, cooled and partitioned between ethyl acetate and water. The organic layer was washed (water, brine), dried over sodium sulfate and concentrated. The crude product was purified on a thick layer plate of silicic acid. The plate was eluted with hexanes-ethyl acetate (10: 1) to provide methyl 3-cyclohexyl-1- (furan-3-yl) -2- (2-vinylphenyl) -1H-indole-6-carboxylate as a gum (57 mg, 37%). MS m / z 466 (MH +); XH NMR (500 MHz, CHLOROFORM-D) d ppm 1.15-1.89 (m, 10 H) 2.42-2.53 (m, 1 H) 3.91 (s, 3 H) 4.25 (s, 1 H) 4.48 (d, J = 17.40 Hz, 1 H) 4.82 (d, J = 17.40 Hz, 1 H) 4.82 (d, J = 17.40 Hz, 1 H) .5.09-5.17 (m, 2 H9 5.69 (d, J = 17.70 Hz, 1 H ) 6.34-6.47 (m, 2 H), 7.18-7.23 (m, 2 H) 7.28 (t, J = 1.93 Hz, 1 H) 7.32 (t, J = 1.68 Hz, 1 H) 7.42 (t, J = 7.63 Hz, 1 H) 7.69 (d, J = 7.63 Hz, 1 H) 7.79-7.85 (m, 2 H) 8.00 (s, 1 H) Step 3: Grubb's second generation catalyst (lOmg) was added to a solution of methyl 3-cyclohexyl-l- (furan-3-yl) -2- (2-vinylphenyl) -lH-indole-6-carboxylate (47 mg) in methylene chloride (8 mL). The solution was stirred under reflux for 18 hours and concentrated to dryness The residue was purified on a preparative plate of silicic acid The plate was eluted with hexanes-ethyl acetate (10: 1) The band containing the product was extracted and the extract was concentrated. Purification in a second thick layer plate gave 13-cyclohexyl-6- (furan-3-yl) -7H-indole. { 2, 1-a] [2] benzazepin-10-carboxylate as a golden solid (17 mg, 39%). MS m / z 438 (MH +); XH NMR (300 MHz, CHLOROFORM-D) d ppm 1.11-2.16 (m, 10 H) 2.78-2.95 (m, 1 H) 3.94 (s, 3 H) 4.34-4.49 (m, 1 H) 5.00-5.15 ( m, 1 H) 6.60 (s, 1 H) 6.93 (s, 1 H) 7.38-7.45 (m, 4 H) 7.55 (d, J = 8.42 Hz, 1 H) 7.70 (dd,, 8.42, 1.46 Hz, 1 H) 7.81-7.88 (m, 2 H) 8.17 (s, 1 H). Step 4: A mixture of the above ester (17 mg) in THF (250 uL), methanol (250 uL) and 1.0 N NaOH (200 uL) was heated at 100 ° C in a microwave oven for 15 minutes. The resulting solution was cooled and acidified with dilute HCl to precipitate the title acid as a golden solid. MS m / z 424 (MH +). Example 46 13-Cyclohexyl-3-methoxy-6- (5- (3-methoxy-3-oxopropyl) -1,3-oxazol-2-yl) -7H-indole [2, 1-a] [2] benzazepin-10- methyl carboxylate. 13-Cyclohexyl-3- (methyloxy) -6- (((5- (methyloxy) -2,5- dioxopent il) amino) carbonyl) -7H-indole [2, 1-a] [2] benzazepin-10-carboxylic acid methyl ester (1.60g, 2.79 mMole) was suspended in 38 ml of toluene together with phosphorus oxychloride (0.58 mL , 6.34 mMoles). The mixture was refluxed under nitrogen for 3 hours, cooled and poured into a separatory funnel containing ice and saturated aqueous sodium bicarbonate solution. The aqueous mixture was extracted with ethyl acetate. The organic layer was washed sequentially with aqueous saturated bicarbonate, brine and dried over magnesium sulfate. The removal of volatile materials and vacuum drying yielded the title product in quantitative yield (1.55 g). 1 H NMR (500 MHz, CHLOROFORM-d) d ppm 1.27 (1 H, br S), 1.36-1.45 (2 H, m), 1.59 (2 H, br.s.), 1.78 (2 H, d , J = 9.77 Hz), 1.96 (1 H, br S.), 2.06 (2 H, br S.), 2.71 (2 H, t, J = 7.48 Hz), 2.81-2.90 (1 H, m ), 3.04 (2 H, t, J = 7.32 Hz), 3.70 (3 H, s), 3.95 (3 H, s), 3.98 (3 H, s), 4.37 (1 H, d, J = 11.60 Hz ), 5.93 (1 H, d, J = 12.51 (Hz), 6.91 (1 H, s), 7.02 (1 H, d, J = 2.75 Hz), 7.07 (1 H, dd, J = 8.70, 2.59 Hz ), 7.53 (2 H, s), 7.74 (1 H, d, J = 8.55 Hz), 7.85 (1 H, d, J = 8.55 Hz), 8.38 (1 H, s) HPLC analysis: Shimadzu Analytical CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; % B Initial = 50; % B Final = 100; Gradient = 5 min; Execution time = 6 min; Flow rate = 5 mi / min; Wavelength = 220 nm; Column ^ Phenomenex Luna 3.0 mm x 50mm S10; Retention Time = 4.48 min, purity 96%. Mass Spectrometry by flow injection: MS m / z 555 (MH +). Example 47 3- (2- (13-Cyclohexyl-3-methoxy-10- (methoxycarbonyl) -7H-indol [2, 1-a] [2] benzazepin-6-yl) -1,3-oxazol-5-yl acid propanoic. 13-Cyclohexyl-3-methoxy-6- (5- (3-methoxy-3-oxopropyl) -1, 3-oxazol-2-yl) -7H-indole [2, 1-a] [2] benzazepin-10 Methylcarboxylate (1.53 g, 2.92 mMol) was dissolved in 20 ml of THF and 5.8 ml of a 1.0M solution of tetrabutylammonium hydroxide in methanol was added. The reaction was stirred under nitrogen atmosphere for 2 hours until completion. The reaction was partitioned between ethyl acetate and 1N aqueous hydrochloric acid. The ethyl acetate layer was washed with 1 N hydrochloric acid and then the aqueous layers were combined and back-extracted with ethyl acetate. The organic layers are Combine and wash sequentially with 1 N hydrochloric acid, brine and dry over magnesium sulfate. The volatiles were removed in vacuo to yield an amorphous yellow solid / foam (1.54 g). XH NMR (500 MHz, CHLOROFORM-d) d ppm 1.21-1.31 (2 H, m), 1.32-1.50 (2 H, m), 1.56 (1 H, br S.), 1.72-1.82 (2 H, m), 2.01 (1 H, br. s.), 2.03-2.13 (3 H, m), 2.76 (2 H, d, J = 6.41 Hz), 2.80-2.89 (1 H, m), 3.13 (2 H, t, J = 6.26 Hz), 3.92 (3 H, s), 4.00 (3 H, s), 4.40 (1 H, d, J = 12.82 Hz), 5.81 (1 H, d, J = 16.17 Hz ), 6.92 (1 H, s), 7.01-7.09 (0 H, m), 7.03 (1 H, d), 7.07 (1 H, dd), 7.53 (1 H, d, J = 8.55 Hz), 7.73 (2 H, s), 7.86 (1 H, d, J = 8.55 Hz), 8.40 (1 H, s). CLAR Analysis: Shi adzu Analytical CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; 5B Initial = 50; % B Final = 100; Gradient = 5 min; Execution time = 6min; Flow rate = 5 ml / min; Wavelength = 220 nm; Column = Phenomenex Luna 3.0mm x 50mm S10. Retention time = 4.11 min, purity 97%. Mass spectrometry by flow injection: MS m / z 541 (MH +), m / z 539 (MH ~). Example 48 13-Cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1, 3-oxazol-2-yl) -7H-indole [, 2-a] [2] methyl benzazepin-10-carboxylate. 3- (2- (13-Cyclohexyl-3-methoxy-10- (methoxycarbonyl) -7-indole [2, 1-a] [2] benzazepin-6-yl) -1,3-oxazol-5-yl acid ) propanoic (1.522 g, 2.82 mMoles) was dissolved in 28 mL of THF and carbonyldiimidazole (548 mg, 3.38 mMoles) was added to the reaction. The reaction was stirred for 1 hour at room temperature under nitrogen and then heated to reflux under nitrogen for 1 hour. The reaction was cooled and morpholine (0.3 mL, 3.44 mMole) was added, the reaction was stirred under nitrogen for 2 hours. The volatiles of the reaction were removed in vacuo and the residue was partitioned between ethyl acetate and 1N aqueous hydrochloric acid. The aqueous material was extracted with ethyl acetate and the organic layers were combined and washed sequentially with 1N hydrochloric acid and brine, dried over magnesium sulfate to give 1.62 g of crude product. The title compound was purified by chromatography on silica gel eluting with a gradient of 50% ethyl acetate in dichloromethane to 65% ethyl acetate in dichloromethane to give 1.28 g (74%) of product as an amorphous yellow solid. 1 H NMR (500 MHz, CHLOROFORM-d) d ppm 1.27 (2 H, t, J = 7.17 Hz), 1.40 (1 H, t, J = 7.63 Hz), 1.53-1.62 (2 H, m), 1.78 ( 2 H, d, J = 10.99 Hz), 1.95 (1 H, br. S.), 2.05 (2 H, br. S.), 2.66 (2.

H, t, J = 7.48 Hz), 2.86 (1 H, td, J = 11.83, 3.51 Hz), 3.09 (2 H, t, J = 7.48 Hz), 3.36-3.44 (2 H, m), 3.56 ( 2 H, d, J = 4.27 Hz), 3.62 (2 H, br. S.), 3.64 (2 H, d, J = 2.75 Hz), 3.93 (3 H, s), 3.96 (3 H, s) , 4.38 (1 H, d, J = 12.21 Hz), 5.92 (1 H, d, J = 14.65 Hz), 6.92 (1 H, s), 7.02 (1 H, d, J = 2.75 Hz), 7.07 ( 1 H, dd, J = 8.85, 2.75 Hz), 7.55 (2 H, t, J = 4.27 Hz), 7.73 (1 H, d, J = 8.55 Hz), 7.85 (1 H, d, J = 8.24 Hz ), 8.38 (1 H, s). LC-MS: Shimadzu Analytical CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; % B Initial = 0; % B Final = 100; Gradient = 2 min; Execution time = 4 min; Flow rate = 5 mi / min; Wavelength = 220 nm; Column = Phenomenex Luna 3. Omm x 50mm S10. Retention time = 2.93 min, MS m / z 610 (MH +). Example 49 -Cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) oxopropyl) -1, 3-oxazol-2-yl) -6,7-dihydro-5H-indole [2,1-a] [2] Benzazepin-10-carboxylic acid methyl. 13-Cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3- oxopropyl) -1, 3-oxazol-2-yl) -7tf-indole [2, 1-a] [2] benzazepin-10-carboxylic acid methyl ester (610 mg, 1.00 mMol) (610 mg, 1.00 mMol) was dissolved in 15 ml of THF and 5 ml of methanol. To this reaction was added 83 mg of 10% palladium on carbon. The reaction was placed under a hydrogen atmosphere (1 atmosphere, balloon pressure) and stirred at room temperature for 22 hours. The reaction was filtered through a plug of celite and rinsed with THF. The volatiles were removed from the filtrate in vacuo to give 569 mg (93%) of the title compound as a yellow solid. LC-MS: Shimadzu Analytical CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; % B Initial = 50; % B Final = 100; Gradient = 3 min; Execution time = 4 min; Flow rate = 5 ml / min; Wavelength = 220 nM; column = Phenomenex Luna 3.0 mm x 50mm S10. Retention time = 2.55 min, MS m / z 612 (MH +). Example 50 13-Cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2] acid , 1-a] [2] benzazepin-10-carboxylic acid. 13-Cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2, 1-a] [2] Methyl benzazepin-10-carboxylate (560 mg, 0.92 mMol) was dissolved in THF and potassium trimethylsilanolate (585 mg, 4.56 mMoles) was added. The reaction was stirred under nitrogen atmosphere at room temperature for 20 hours. The reaction was added 1N aqueous hydrochloric acid. The reaction was extracted with ethyl acetate. The organic phase was washed with brine, dried over magnesium sulfate and the volatiles were removed in vacuo to give 585 mg of a yellow amorphous foam. LC-MS: Shimadzu Analytical CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; % B Initial = 50; % B Final = 100; Gradient = 5 min; Execution time = 6 min; Flow rate = 5 mi / min; Wavelength = 220nm; Column = Phenomenex Luna 3.0 itim x 50mm S10. Retention time: 4.05 min, MS m / z 598 (MH +), 1195 (2M + H) +. Chiral resolution of 13-cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7-dihydro-5H- acid Indole [2,1-a] [2] benzazepine-10-carboxylic acid. Conditions: Analytical column quiralpak AD-H, eleven 4. 6mm x 250mm, 5um; Mobile phase: 35% (0.1% of TFA) of methanol in carbon dioxide; Temperature = 35 ° C; flow rate = 2.0 ml / min for 16 min; Monitored UV @ 213 nm; Injection: 5 uL of a solution of approximately lmg / mL in ethanol. Retention time of isomer A: 5.96 min; Retention time of isomer B: 11.65 min. Chiral preparative separation: ChiralPak AD-H, 30mm x 250mm, 5 um; Mobile phase: 65% carbon dioxide, 35% methanol with 0.1% trifluoroacetic acid; temperature: 35 ° C; pressure: 150 bar; Flow rate: 70ml / min; UV: 213mm; Peak 1 Isomer A: 7.20 min. at 9.20 min; Isomer B of Peak 2: 12.4 min at 16.6 min. From 498 mg of racemate, 216 mg of Isomer A and 231 mg of Isomer B were obtained. Example 51 13-Cyclohexyl-3-ethoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2] acid , 1-a] [2] benzazepin-10-carboxylic acid. (Isomer A Quiral of Peak 1). XH NMR (500 MHz, CHLOROFORM-D) d ppm 1.20-1.52 (m, 3.3 H) 1.68 (t, J = 12.97 Hz, 1.1 H) 1.79 (d, J = 8.55 Hz, 2 H) 1.88-2.12 (m, 4 H) 2.46 (t, J = 7.32 Hz, 1.4 H) 2.71 (t, J = 7.63 Hz, 0.5 H) 2.79-2.88 (m, 1 H) 2.88-3.11 (m, 3.5 H) 3.15 (dd, J = 12.97, 5.95 Hz, 0.8 H) 3.19-3.31 (m, 1.4 H) 3.45-3.75 (m, 6.3 H) 3.84 (s, 0.7 H) 3.87-3.95 (m, 3 H) 3.94-4.03 (m, 0.5 H) 4.07 (dd, J = 15.11, 5.34 Hz, 0.8 H) 4.81 (d, J = 14.95 Hz, 0.9 H) 6.82-6.97 (m, 1.4 H) 6.97-7.04 (m, 1.5 H) 7.38 (t, J = 7.63 Hz, 1 H) 7.72-7.84 (m, 1 H) 7.85-7.93 ( m, 1 H) 7.98-8.08 (m, 0.7 H) 8.22 (s, 0.2 H). CLAR Analysis: Shimadzu Analyticial CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; % B Initial = 50; % B Final = 100; Gradient = 5 min; Execution time = 6 min; Flow rate = 5 mi / min; Wavelength = 220 nm; Column = Phenomenex Luna 3.0 mm x 50 mm S10; Retention time = 3.16 min, purity 98%. Mass Spectrometry by flow injection: MS m / z 598 (MH +), m / z 596 (MH ~). Example 52 13-Cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2] acid , 1- a] [2] benzazepin-10-carboxylic (chiral isomer B peak 2). CLAR analysis: Shimadzu Analytical CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; % B Initial = 50; % B Final = 100; Gradient = 5 min; Execution time = 6 min; Flow rate = 5 ml / min; Wavelength = 220 nm; Column = Phenomenex Luna 3.0 mm x 50mm S10. Retention time = 3.18 min, purity 99%. Mass Spectrometry by flow injection: MS m / z 598 (MH +), m / z 596 (MH ") Example 53 13-Cyclohexyl-N- ((dimethylamino) sulfonyl) -3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1, 3-oxazol-2-yl) -6, 7- dihydro 5H-indole [2,1-a] [2] benzazepin-10-carboxamide (Isomer B). 13-Cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2] 1- a] [2] benzazepin-10-carboxylic (Pico 2-Chiral B isomer) (100 mg, 0.17 mMole) was dissolved in 1.9 ml of anhydrous THF and carbonyldiimidazole (37.1 mg, 0.23 mMole) was added. The reaction was stirred under a nitrogen atmosphere at room temperature for 1 hour and heated to reflux for 1 hour under nitrogen. The reaction was cooled under nitrogen and dimethylsulfamide (145 mg, 1.17 mMole) and DBU (27.5 uL, 0.18 mMole) were added to the reaction. The reaction was heated to 50 ° C under a nitrogen atmosphere for 4 hours, then cooled to room temperature and analyzed by HPLC for progress. The reaction was heated for an additional 2.5 hours at 50 ° C and again monitored by HPLC. Dimethylsulfamide (100 mg) and DBU (27 uL) were added to the reaction and the reaction was heated to reflux for 3 hours under nitrogen. The heat was removed and the reaction was cooled to room temperature and stirred overnight. The reaction was partitioned between ethyl acetate and 1N aqueous hydrochloric acid and the aqueous phase was extracted with ethyl acetate. The organic phases were combined and washed sequentially with 1N aqueous hydrochloric acid, brine, then dried over magnesium sulfate. Removal of the volatiles in vacuo left 209 mg of crude product which was purified by reverse phase HPLC under the following conditions: Shimadzu prep. CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% TFA; % B = 90% methanol, 10% water, 0.1% TFA; % B Initial = 50; % B Final = 100; Gradient = 15 min; Execution time = 15 min; Flow rate = 45 ml / min; Column = Waters Sunfire 30mm x lOOmm; Peak collection 8.2 min to 9.1 min; the title compound was isolated as a colorless solid, 71.2 mg (60%). * H NMR (500 Hz, CHLOROFORM-D) d ppm 1.25 (q, J = 12.82 Hz, 1.2 H) 1.31-1.53 (m, 2.1 H) 1.58-1.85 (m, 3.2 H) 1.86-2.12 (m, 4.2 H) 2.54-2.76 (m, 2.1 H) 2.81-2.99 (m, 3.3 H) 2.99-3.12 (m, 7.3 H) 3.14-3.24 (m, 1 H) 3.34-3.61 (m, 3.1 H) 3.60-3.73 (m, 5.3 H) 3.72-3.82 (m, 0.9 H) 3.84 (s, 0.6 H) 3.90 (s, 2.5 H) 4.02 (dd, J = 14.95, 6.10 Hz, 0.9 H) 4.77-4.92 (m, 1.3 H) 6.78-6.87 (m, 1 H) 6.88-7.05 (m, 2 H) 7.30-7.51 (m, 1.2 H) 7.64 (dd, J = 8.39, 1.37 Hz, 0.8 H) 7.81-7.95 (m, 1.0 H) 8.01-8.21 (m, 1 H) 8.67 (s, 0.2 H) 9.86 (s, 0.8 H). CLAR Analysis: Shimadzu Analytical CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% TFA; % B = 90% methanol, 10% water, 0.1% TFA; % B Initial = 50; % B Final = 100; Gradient = 5 min; Execution time = 6 min; Flow rate = 5 ml / min; Wavelength = 220 nm; Column = Phenomenex Luna 3. Omm x 50mm S10. Retention time = 3.03 min; 99% purity. Mass spectrometry by flow injection: MS m / z 704 (MH +). Chiral Purity: Column Quiralacel OJ-H analytical column 4.6 mm x 250 mm; Mobile phase: 12% methanol in carbon dioxide; Temperature: 35 ° C; Flow rate: 2.0 ml / min for 40 min; UV monitoring = 213 nm; Injection: 5 uL of a solution of approximately lmg / mL in ethanol; Arrangement time: 32.5 min, purity = 100 'EE = 99.9%. Example 54 13-Cyclohexyl-N- ((dimethylamino) sulfonyl) -3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1, 3-oxazol-2-yl) -6,7 -dihydro-5H-indole [2, 1-a] [2] benzazepine-10-carboxamide (Isomer A). The same procedure used for the preparation of the above enantiomer except that 13-cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl acid) -6,7-dihydro-5H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid (Pico 1-Chiral A-isomer) was used as starting material. CLAR analysis: Shimadzu Analytical CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; % B Initial = 50; % B Final = 100; Gradient = 5 min; Execution time = 5 min; Flow rate = 5 mi / min; Wavelength = 220 nm; Column = Phenomenex Moon 3. O mm x 50mm S10. Retention time = 3.03 min, purity 99%; Mass spectrometry by flow injection MS m / z 704 (MH +), 726 (M + Na) +, m / z 702 (-H) ~. Chiral Test: Column: Chiralacel OJ-H analytical column 4.6mm x 250mm: Mobile phase: 12% methanol in carbon dioxide; temperature 35 ° C; flow rate: 2.0 ml / min for 40 min; UV monitoring = 213 nm; Injection: 5 uL of a solution of approximately lmg / mL in ethanol. Retention time: 27.1 min, purity = 100% EE > 99.9%. Example 55 13-Cyclohexyl-3-methoxy-6- (1,3-oxazol-2-yl) -7H-indol [2, 1-a] [2] benzazepin-10-carboxylic acid methyl ester. 13-Cyclohexyl-3- (methyloxy) -6- (((2-oxoethyl) amino) carbonyl) -7H-indole [2, 1-a] [2] benzazepin-10-carboxylic acid methyl ester (410 mg, 0.84 m oles) ) was dissolved in 10 mL of THF in a microwave reactor with stirring rod. Burgess reagent (602 mg, 2.53 mMoles) and (methoxycarbonylsulfamoyl) triethylammonium hydroxide were added, Inner salt was added to the reaction vessel. The reaction was placed under a nitrogen atmosphere and heated in a microwave for 1 minute at 100 watts. The reaction was monitored by HPLC and the additional Burgess reagent (200 mg, 0.884 mols) was added to the reaction. The reaction was heated further for 1 minute at a power of 100 watts. The reaction was partitioned between ethyl acetate and 1 N aqueous hydrochloric acid. The aqueous phase was extracted with ethyl acetate. The organic phases were combined and washed sequentially with 1N aqueous hydrochloric acid and brine, dried over magnesium sulfate and the volatiles were removed in vacuo to obtain 0.71 g of crude product. The title compound was purified by chromatography on silica gel eluting with a gradient of 0% ethyl acetate in dichloromethane to 15% ethyl acetate in dichloromethane to give 150 mg (38%) as a yellow solid. 1 H NMR (500 MHz, CHLOROFORM-d) d ppm 1.27 (1 H, br. S.), 1.32-1.50 (2 H, m), 1.57 (1 H, br. S.), 1.78 (2 H, d. , J = 9.77 Hz), 1.95 (1 H, br. S.), 2.07 (3 H, br. S.), 2.71-2.98 (1 H, m), 3.94 (3 H, s.), 3.97 ( 3 H, s), 4.43 (1 H, br. S.), 5.92 (1 H, br. S.), 7.03 (1 H, d, J = 2.44 Hz), 7.09 (1 H, dd, J = 8.70, 2.59 Hz), 7.29 (1 H, s), 7.55 (1 H, d, J = 8.55 Hz), 7.68 (2 H, d, J = 10.99 Hz), 7.74 (1 H, dd, J = 8.55 , 1.22 Hz), 7.86 (1 H, d, J = 8.55 Hz), 8.38 (1 H, s). CLAR Analysis: CLAR Analysis: Shimadzu Analytical CLAR using Discovery VP software:% A = 10% methanol, 90% water, 1 0. 1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; % B Initial = 50; % B Final = 100; Gradient = 5 min; Execution time = 6 min; Flow rate = 5 ml / min; Wavelength = 220 nm; Column = Phenomenex Luna 3.0 mm x 50mm S10. retention time = 4.43 min, purity 97%; Mass spectrometry by flow injection: MS m / z 469 (MH +). Example 56 13-Cyclohexyl-3-methoxy-6- (1, 3-oxazol-2-yl) -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid. 13-Cyclohexyl-3-methoxy-6- (1,3-oxazol-2-yl) -? H-indole [, 2-1-a] [2] benzazepin-10-carboxylic acid methyl ester (75.4 mg, 0.16 mMoles ) was dissolved in 2 mL of THF and potassium trimethylsilanolate (103 mg, 0.80 mMole) was added to the reaction. The reaction was stirred at room temperature under a nitrogen atmosphere for 19 hours. The reaction was partitioned between ethyl acetate and 1N aqueous hydrochloric acid. The organic phase was washed sequentially with 1N aqueous hydrochloric acid and brine, dried over magnesium sulfate and the The volatiles were removed in vacuo to give 68 mg (93%) of the title product as a yellow solid. 1 H NMR (500 MHz, CHLOROFORM-d) d ppm 1.18-1.33 (1 H, m), 1.36-1.45 (2 H, m), 1.58 (1 H, br. S.), 1.79 (2 H, d, J = 10.07 Hz), 1.96 (1 H, br. S.), 2.08 (3 H, br. S.), 2.88 (1 H, t, J = 12.05 Hz), 3.94 (3 H, s), 4.44 (1 H, br. S.), 6.00 (1 H, br. S.), 7.04 (1 H, d, J = 2.75 Hz), 7.09 (1 H, dd, J = 8.70, 2.59 Hz), 7.31 (1 H, s), 7.56 (1 H, d, J = 8.85 Hz), 7.65 (1 H, s), 7.68 (1 H, s), 7.82 (1 H, dd, J = 8.55, 1.22 Hz) , 7.90 (1 H, d, J = 8.55 Hz), 8.54 (1 H, s). CLAR Analysis: Shimadzu Analitical CLAR using Discovery VP Software:% A = 10% methanol, 90% water, 0.1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; % B Initial = 50; % B Final = 100; Gradient = 5 min; Execution time = 6 min; Flow rate = 5 mi / min; Wavelength = 220 nm; column = Phenomenex Luna 3. Omm x 50mm S10. Retention time = 3.83 min, purity 96%; Mass Spectrometry by flow injection MS m / z 455 (MH +), m / z 453 (M-H) ~. Example 57 13-Cyclohexyl-N- ((dimethylamino) sulfonyl) -3-methoxy-6- (1,3-oxazol-2-yl) -7H-indole [, 2-1-a] [2] benzazepine-10-carboxamide . 13-Cyclohexyl-3-methoxy-6- (1, 3-oxazol-2-yl) -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid (63 mg, 0.14 mMol) was dissolved in 1.7 ml of THF and carbonyldiimidazole (31 mg, 0.19 mMoles) was added. The reaction was stirred under a nitrogen atmosphere at room temperature for 1 hour and then heated to reflux for 1 hour. The reaction was cooled under nitrogen atmosphere and dimethylsulfamide (91 mg, 0.73 mMoles) was added followed by DBU (23 uL, 0.15 mMoles). The reaction was heated to 50 ° C under a nitrogen atmosphere for 4 hours, cooled under nitrogen and stirred at room temperature overnight. The reaction was partitioned between ethyl acetate and 1N aqueous hydrochloric acid. The organic phase was washed with brine, dried over magnesium sulfate and the volatiles were removed in vacuo to give 103 mg of a crude product as an amorphous yellow film. The crude product was dissolved in methanol and purified by preparative HPLC under the following conditions: Shimadzu prep. CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% TFA; % B = 90% methanol, 10% water, 0.1% TFA; % B Initial = 50; % B Final = 100; Gradient = 15 min; Execution time = 25 min; Flow rate = 25 ml / min; Column = Sunfire aters 19mm x 100mm; Peak Collection = 12.16min to 12. 96 min. ?? RN (500 MHz, CHLOROFORM-d) d ppm 1.23 (1 H, br. S.), 1.36-1.45 (2 H, m), 1.56 (1 H, br. S.), 1.78 (2 H, d, J = 10.07 Hz), 2.00 (2 H, br. S.), 2.07 (2, H, br. S.), 2.78-2.91 (1 H, m), 3.09 (6 H, s), 3.94 (3 H, s), 4.43 (1 H, br. S.), 5.91 (1 H, br. S.), 7.03 (1 H, d, J = 2.44 Hz), 7.10 (1 H, dd, J = 8.55 , 2.75 Hz), 7.50 (1 H, d, J = 1.53 Hz), 7.55 (1 H, d, J = 8.55 Hz), 7.65 (1 H, s), 7.69 (1 H, s), 7.89 (1 H, d, J = 8.55 Hz), 8.24 (1 H, s), 8.81 (1 H, br. S.). CLAR analysis: Shimadzu Analytical CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; % B Initial = 50; % B Final = 100; Gradient = 5 min; Execution time = 6 min; Flow rate = 5 mi / min; Wavelength = 220 nm; Column = Phenomenex Luna 3. Omm x 50mm S10. Retention time = 3.65 min, purity 93%; Mass spectrometry by flow injection: MS m / z 561 (MH +), m / z 559 (M-H) ~. Example 58 13-Cyclohexyl-N- ((dimethylamino) sulfonyl) -3-methoxy-6- (1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2.1-a] [2] benzazepin ~ l 0-carboxamide. 13-Cyclohexyl-N- ((dimethylamino) sulfonyl) -3-methoxy-6- (1,3-oxazol-2-yl) -7H-indole [2, 1-a] [2] benzazepine-10-carboxamide ( 45 mg, 0.08 mMoles) was dissolved in 3.8 mL of THF and 0.9 mL of methanol was added. 10% Palladium on carbon (13 mg) was added and the reaction was placed under an atmosphere (balloon) of 1 atmosphere of hydrogen and stirred at room temperature for 18 hours. The reaction was filtered through a plug of celite and the celite was rinsed using dichloromethane. Removal of the volatiles from the filtrate in vacuo gave 47 mg of material that was purified by preparative HPLC under the following conditions: Shimadzu prep. CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% TFA; % B = 90% methanol, 10% water, 0.1% TFA; % B Initial = 50; % B Final = 100; Gradient = 15 min; Execution time = 20 min; Flow rate = 25 ml / min; Column = Waters Sunfire 19mm x lOOmm; Peak collection = 10.09 min at 10.88 min. 33.7 mg (75%) of the title compound was obtained as a colorless solid. XH NMR (500 Hz, CHLOROFORM-D) d ppm 1.20-1.31 (m, 1.1 H) 1.31-1.52 (m, 2.1 H) 1.66 (d, J = 13.12 Hz, 1.1 H) 1.78 (d, J = 9.16 Hz , 2.0 H) 1.93 (d, J = 13.12 Hz, 1.1 H) 1.96-2.09 (m, 2.9 H) 2.82-2.98 (m, 2.2 H) 3.03-3.08 (m, 6.0 H) 3.11-3.19 (m, 1.0 H) 3.73-3.81 (m, 1.0 H) 3.84 (s, 1. 3 H) 3.90 (s, 1.8 H) 3.97-4.02 (m, 09. H) 4.05 (dd, J = 14.95, 5.80 Hz, 0.7 H) 4.75-4.85 (m, 0.4 H) 4.90 (d, J = 14.95 Hz, 0.6 H) 6.84 (d, J = 2.44 Hz, 0.4 H) 6.94 (dd, J = 8.55, 2.44 Hz, 0.5 H) 6.97-7.01 (ra, 1.2 H) 7.09-7.17 (m, 1.0 H) 7.32 -7.49 (m, 2.0 H) 7.64 (s, 0.6 H) 7.69 (s, 0.4 H) 7.78-7.87 (m, 1.2 H) 7.90 (d, J = 8.55 Hz, 0.4 H) 8.02 (s, 0.4 H) 8.42 (s, 0.5 H) 8.59 (s 0.4 H). CLAR analysis: Shimadzu Analytical CLAR using Discovery VP software:% A = 10% methanol, 90% water, 0.1% trifluoroacetic acid; % B = 90% methanol, 10% water, 0.1% trifluoroacetic acid; % B Initial = 50; % B Final = 100; Gradient = 5 min; Execution time = 6 min; Flow rate = 5 mi / min; Wavelength = 220 nm; Column = Phenomenex Luna 3.0 mm x 50mm S10. Retention time = 3.02 min, purity 99%; Mass Spectrometry by flow injection: MS m / z 563 (MH +), m / z 561 (M-H) ~. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (10)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. A compound characterized in that it has the formula I: I where: R1 is C02R5 or CONR6R7; R 2 is furanyl, pyrrolyl, thienyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl or tetrazolyl, and is substituted with 0-2 substituents selected from oxo, amino, alkylamino, dialkylamino, alkyl, (cycloalkyl) alkyl, hydroxyalkyl , (tetrahydrofuranyl) alkyl, (tetrahydropyranyl) alkyl, (C02R5) alkyl, (CON (R5) 2) alkyl, (COR9) alkyl, (alkylsulfonyl) alkyl and ((R9) alkyl) CON (R5); R3 is cycloalkyl of Cs_7; R 4 is hydrogen, halo, hydroxy, alkyl or alkoxy; R5 is hydrogen, alkyl or cycloalkyl; R6 is hydrogen, alkyl, cycloalkyl, alkoxy or S02R; R7 is hydrogen, alkyl or cycloalkyl; or NR6R7 taken together is pyrrolidinyl, piperidinyl, piperazinyl, N-alkylpiperazinyl, homomorpholinyl, homopiperidinyl, morpholinyl or thiomorpholinyl; R8 is alkyl, haloalkyl, cycloalkyl, amino, alkylamino, dialkylamino or phenyl; or R8 is pyrrolidinyl, piperidinyl, piperazinyl, N-alkylpiperazinyl, homomorpholinyl, homopiperidinyl, morpholinyl or thiomorpholinyl; R9 is pyrrolidinyl, piperidinyl, piperazinyl, N-alkylpiperazinyl, homomorpholinyl, homopiperidinyl, morpholinyl or thiomorpholinyl and (a) is a single bond or a double bond, (b) is a single bond or a double bond, so long as at least one from (a) AND (b) be a single link; or a pharmaceutically acceptable salt thereof.
2. 2. The compound according to claim 1, characterized in that R1 is CONR6R7; R6 is S02R8 and R7 is hydrogen.
3. 3. The compound according to claim 1, characterized in that R3 is cyclohexyl.
4. 4. The compound according to claim 1, characterized in that R4 is hydrogen.
5. 5. The compound in accordance with the claim 1 1, characterized in that R is methoxy.
6. 6. The compound according to claim 1, characterized in that it is selected from the group consisting of 13-cyclohexyl-6- (1H-tetrazol-5-yl) -7H-indole methyl ester [2, 1-a] [2] benzazepin-10-carboxylic acid; 13-cyclohexyl-6- (2-ethyl-2H-tetrazol-5-yl) -5H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-6- (2-ethyl-2H-tetrazol-5-yl) -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-N- [(dimethylamino) sulfonyl] -6- [2-ethyl] -2H-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepine-10-carboxamide; 13-cyclohexyl-6- [2- (2-hydroxyethyl) -2H-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-6- [2- (cyclopropylmethyl) -2H-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; and 13-cyclohexyl-6- [2- (cyclopropylmethyl) -2H-tetrazol-5-yl] -5H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-6- [2- [(tetrahydro-2-furanyl) methyl] -2H-tetrazol-5-yl] -5H-indole [2, 1-a] [2] benzazepin-10-carboxylic acid; 13-cyclohexyl-6- [2- [(tetrahydro-2-furanyl) methyl] -2H-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepin-10-carboxylic acid; 13-cyclohexyl-6- [1- [(tetrahydro-2- furanyl) methyl] -lH-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] -7H-indole [2, 1-a] benzazepine-10-carboxylic acid; 13-cyclohexyl-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] -5H-indole [2, 1-a] [2] benzazepin-10 acid -carboxylic; 13-Cyclohexyl-6- [1- [(tetrahydro-2H-pyran-4-yl) methyl] -lH-tetrazol-5-yl] -7H-indole [2, 1-a] [2] benzazepin-lG acid -carboxylic; 13-cyclohexyl-6- [1- [(tetrahydro-2H-pyran-4-yl) methyl] -lH-tetrazol-5-yl] -5H-indole [2,1-a] [2] benzazepin-10 acid -carboxylic; 13-cyclohexyl-N- [(dimethylamino) sulfonyl] -6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] -7H-indole [2, 1-] a] [2] benzazepin-10-carboxamide; 13-cyclohexyl-3-methoxy-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] -7H-indole [2, 1-a] [2 ] benzazepin-10-carboxylic acid; 13-cyclohexyl-N- [(dimethylamino) sulfonyl] -3-methoxy-6- [2- [(tetrahydro-2H-pyran-4-yl) methyl] -2H-tetrazol-5-yl] -7H-indole [ 2, 1-a] [2] benzazepin-10-carboxamide; methyl ester of 13-cyclohexyl-6- (, 5-dihydro-5-oxo-l, 3,4-oxadiazol-2-yl) -7H-indole [2, 1-] a] [2] benzazepin-10-carboxylic acid; 13-cyclohexyl-6- (4,5-dihydro-5-oxo-l, 3,4-oxadiazol-2-yl) -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-6- [4,5-dihydro-5-oxo-4- [(tetrahydro-2H-pyran-4-yl) methyl] -1,3,4-oxadiazol-2-yl] methyl ester -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-6- [4,5-dihydro-5-oxo-4- [(tetrahydro-2H-pyran-4-yl) methyl] -1,4,4-oxadiazol-2-yl] -7H- acid indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-6- [3- [(tetrahydro-2H-pyran-4-yl) methyl] -1H-1,2,4-triazol-5-yl] -7H-indole [2, 1-a] acid [2] benzazepin-10-carboxylic acid; 13-cyclohexyl-6- (3-methyl-1,2,4-oxadiazol-5-yl) -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester; 13-cyclohexyl-6- (3-methyl-1,2,4-oxadiazol-5-yl) -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-N- [(dimethylamino) sulfonyl] -6- (3-methyl-1,2,4-oxadiazol-5-yl) -7H-indole [2, 1-a] [2] benzazepin-10- carboxamide; methyl ester of 13-cyclohexyl-6- [3- [(methylsulfonyl) methyl] -1,2,4-oxadiazol-5-yl] -7H-indole [2,1-a] [2] benzazepin-10- carboxylic; 13-Cyclohexyl-6- [3- [(methylsulfonyl) methyl] -1,2,4-oxadiazol-5-yl] -7H-indole [2, 1-a] [2] benzazepin-10- acid carboxylic; 13-cyclohexyl-N- [(dimethylamino) sulfonyl] -6- [3- [(methylsulfonyl) methyl] -1,2,4-oxadiazol-5-yl] -7H-indole [2,1-a] [2 ] benzazepin-10-carboxamide; 6- (5-amino-1,3,4-oxadiazol-2-yl) -13-cyclohexyl-7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester; 6- (5-amino-1,3,4-oxadiazol-2-yl) -13-cyclohexyl-7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 6- [5- [(bromoacetyl) amino] -1,3,4-oxadiazol-2-yl] -13-cyclohexyl-7H-indole [2,1-a] [2] benzazepin-10- methyl ester carboxylic; methyl ester of 13-cyclohexyl-6- [5- [(4-morpholinyl acetyl) amino] -1,3,4-oxadiazol-2-yl] -7H-indole [2,1-a] [2] benzazepin- 10-carboxylic; 13-cyclohexyl-6- [5- [(4-morpholinyl-acetyl) amino] -1,3,4-oxadiazol-2-yl] -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; methyl ester of 13-cyclohexyl-6- [5- (3-methoxy-3-oxopropyl) -2-oxazolyl] -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-6- [5- [3- (4-morpholinyl) -3-oxopropyl] -2-oxazolyl] -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester; 13-cyclohexyl-6- [5- [3- (4-morpholinyl) -3- acid) oxopropyl] -2-oxazolyl] -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-N- [(dimethylamino) sulfonyl] -6- [5- [3- (4-morpholinyl) -3-oxopropyl] -2-oxazolyl] -7H-indole [2, 1-a] [2] benzazepin-10-carboxamide; 13-cyclohexyl-N- [(dimethylamino) sulfonyl] -6,7-dihydro-6- [5- [3- (4-morpholinyl) -3-oxopropyl] -2-oxazolyl] -5H-indole [2, 1 -a] [2] benzazepin-10-carboxamide; methyl ester of 13-cyclohexyl-6- [5- [(tetrahydro-2H-pyran-4-yl) methyl] -1,4,4-oxadiazol-2-yl] -7H-indole [2, 1-a] ] [2] benzazepin-10-carboxylic acid; methyl ester of 13-cyclohexyl-6- [5- [(tetrahydro-2H-pyran-4-yl) methyl] -1H-1, 2,4-triazol-3-yl] -7H-indole [2, 1] α] [2] benzazepin-10-carboxylic acid; methyl ester of 13-cyclohexyl-6- [l-methyl-5- [(tetrahydro-2H-pyran-4-yl) methyl] -1H-1, 2,4-triazol-3-yl] -7H-indole [2, la] [2] [benzazepin-10-carboxylic acid, 13-cyclohexyl-6- [l-methyl-5- [(tetrahydro-2H-pyran-4-yl) methyl] -1H-1, 2, 4-triazol-3-yl] -7H-indole [2,1-a] [2] benzazepin-10-carboxylic acid; 13-cyclohexyl-N- [(dimethylamino) sulfonyl] -6- [1-methyl-5- [(tetrahydro-2H-pyran-4-yl) methyl] -1H-1,2, -triazol-3-yl] -7H-indole [2, 1-a] [2] benzazepin-10-carboxamide; 13-cyclohexyl-6- [5- [(tetrahydro-2H-pyran-4-yl) methyl] -1,3,4-oxadiazol-2-yl] -7H-indole [2, 1-a] [2 ] benzazepin- 10-carboxylic; 13-cyclohexyl-6- (furan-3-yl) -7H-indole acid. { 2,1-a] [2] benzazepin-10-carboxylic acid; 13-cyclohexyl-3-methoxy-6- (5- (3-methoxy-3-oxopropyl) -1, 3-oxazol-2-yl) -7H-indole [2, 1-a] [2] benzazepin-10 -Methyl carboxylate; 3- (2- (13-Cyclohexyl-3-methoxy-10- (methoxycarbonyl) -7H-indole [2,1-a] [2] benzazepin-6-yl) -l, 3-oxazol-5-yl propanoic; 13-cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -7H-indole [2,1-a] [2 ] methyl benzazepin-10-carboxylate; 13-cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2, 1-a] [2] benzazepin-10-methyl carboxylate; 13-cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2] , 1-a] [2] benzazepin-10-carboxylic acid; 13-cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2] , 1-a] [2] benzazepin-10-carboxylic acid. (Peak 1-Chiral A-isomer); 13-cyclohexyl-3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2] , 1-a] [2] benzazepin-10-carboxylic (Pico 2-Chiral B isomer); 13-cyclohexyl-N- ((dimethylamino) sulfonyl) -3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2, 1-a] [2] benzazepin-10 -carboxamide (Isomer B); 13-cyclohexyl-N- ((dimethylamino) sulfonyl) -3-methoxy-6- (5- (3- (4-morpholinyl) -3-oxopropyl) -1,3-oxazol-2-yl) -6,7 -dihydro-5H-indole [2, 1-a] [2] benzazepin-10-carboxamide (Isomer A); 13-cyclohexyl-3-methoxy-6- (1,3-oxazol-2-yl) -7H-indol [2, 1-a] [2] benzazepin-10-carboxylic acid methyl ester; 13-cyclohexyl-3-methoxy-6- (1,3-oxazol-2-yl) -7H-indol [2, 1-a] [2] benzazepine-10-carboxylic acid methyl ester; 13-cyclohexyl-3-methoxy-6- (1, 3-oxazol-2-yl) -7H-indole [2, 1-a] [2] benzazepine-10-carboxylic acid; 13-cyclohexyl-N- ((dimethylamino) sulfonyl) -3-methoxy-6- (1,3-oxazol-2-yl) -7H-indole [2, 1-a] [2] benzazepine-10-carboxamide and 13-cyclohexyl-N- ((dimethylamino) sulfonyl) -3-methoxy-6- (1,3-oxazol-2-yl) -6,7-dihydro-5H-indole [2, 1-a] [2 ] benzazepin-10-carboxamide; or a pharmaceutically acceptable salt thereof.
7. A composition characterized in that it comprises the compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
8. 8. The composition in accordance with the claim 7, characterized in that it further comprises at least one additional compound having therapeutic benefits for HCV, wherein the compound is selected from the group consisting of interferons, cyclosporins, interleukins, HCV inhibitors, metalloproteases, HCV serine protease inhibitors, inhibitors of HCV Polymerase, HCV Helicase Inhibitors, HCV NS4B Protein Inhibitors, HCV Entry Inhibitors, HCV Assembly Inhibitors, HCV Egress Inhibitors, HCV NS5A Protein Inhibitors, HCV NS5B Protein Inhibitors, and Replicon Inhibitors of HCV.
9. 9. Use of a compound according to claim 1, for the manufacture of a medicament for treating hepatitis C infection. Use according to claim 9, wherein it further comprises administering at least one additional compound having benefits Therapeutics for HCV, of a compound is selected from the group consisting of interferons, cyclosporins, interleukins, HCV inhibitors, metalloprotease, HCV serine protease inhibitors, HCV polymerase inhibitors, HCV helicase inhibitors, HCV NS4B protein inhibitors, HCV inhibitors, HCV entry, HCV assembly inhibitors, HCV-outflow inhibitors, HCV NS5A protein inhibitors, HCV NS5B protein inhibitors, and HCV replicon inhibitors.