BINDING FUNCTION 3 (BF3) SITE COMPOUNDS AS THERAPEUTICS AND METHODS FOR THEIR USE

Abstract

This invention provides compound having a structure of Formulas:

##STR00001##

Uses of such compounds for treatment of various indications, including prostate cancer as well as methods of treatment involving such compounds are also provide.

Claims

1-20. (canceled)

21. A compound having the structure of Formula I: ##STR00885## wherein, is a double bond; A.sub.1 is H; A.sub.2 is H; A.sub.3 is H; A.sub.4 is H; D.sub.1 is E.sub.37; E.sub.37 is NH; D.sub.2 is ##STR00886## G.sub.1 is CH or CCH.sub.3; D.sub.3 is ##STR00887## ##STR00888## J.sub.2 is C; J.sub.3 is CS, CO, NH, or CH.sub.2. J.sub.4 is CH or N; J.sub.5 is CH.sub.2, NH, S or O; J.sub.6, J.sub.7, J.sub.8, J.sub.9, J.sub.10, J.sub.11, J.sub.12, and J.sub.13 are each independently H, OH, Br, Cl, F, I, or CH.sub.3; J.sub.14 is C; J.sub.15 is CS, CO, NH, or CH.sub.2; J.sub.16, J.sub.17, J.sub.18, J.sub.19, and J.sub.20 are each independently H, OH, Br, Cl, F, I, ##STR00889## NO.sub.2, or CH.sub.3; J.sub.21 is C; J.sub.22 is CH.sub.2, or NH; J.sub.23 is CH, or N; J.sub.24, J.sub.25, J.sub.26, and J.sub.27 are each independently H, OH, Br, C, F, I, or CH.sub.3; J.sub.28 is C; J.sub.31 is H, OH, Br, F, I, C(O)NH.sub.2, OCH.sub.3, or CH.sub.3; J.sub.29, J.sub.30, J.sub.32, and J.sub.33 are each independently H, OCH.sub.3, OH, Br, C, F, I, C(O)NH.sub.2, CF.sub.3, NO.sub.2, NH.sub.2, or CH.sub.3; J.sub.34 is C; J.sub.35, J.sub.36, J.sub.37, J.sub.38, and J.sub.39 are each independently H, OCH.sub.3, OH, Br, C, F, I, C(O)NH.sub.2, CF.sub.3, NO.sub.2, NH.sub.2, or CH.sub.3; J.sub.40 is C; J.sub.41 is H, OH, Br, C, F, I, NH.sub.2, or CH.sub.3, or ##STR00890## J.sub.42, J.sub.43, J.sub.44, J.sub.45, and J.sub.46 are each independently H, OH, Br, C, F, I, NH.sub.2, or CH.sub.3; J.sub.47 is C; J.sub.48 is S, CH.sub.2, CO, or NH; J.sub.49 is CH.sub.2, CO, S, O, or NH; J.sub.55 is C, or N; J.sub.50, J.sub.51, J.sub.52, J.sub.53, and J.sub.54, are each independently H, OH, NH.sub.2, Br, C, F, I, NO.sub.2, OCH.sub.3, CF.sub.3, CH.sub.3 or is absent when J.sub.50, J.sub.51, J.sub.52, J.sub.53, or J.sub.54 is N; J.sub.56 is C; J.sub.57 is N, or CH; J.sub.58, J.sub.59, J.sub.60, J.sub.61, and J.sub.62, are each independently H, OH, NH.sub.2, Br, C, F, I, NO.sub.2, OCH.sub.3, CF.sub.3, or CH.sub.3; and J.sub.63, J.sub.64, J.sub.65, J.sub.66, and J.sub.67, are each independently H, OH, NH.sub.2, Br, C, F, I, NO.sub.2, OCH.sub.3, CF.sub.3, or CH.sub.3.

22. The compound of claim 21, wherein D is ##STR00891##

23. The compound of claim 22, wherein D.sub.3 is ##STR00892## J.sub.28 is C; J.sub.31 is H, Br, OCH.sub.3, or CH.sub.3; and J.sub.29, J.sub.30, J.sub.32, and J.sub.33 are each independently H, OCH.sub.3, OH, Br, C, F, I, C(O)NH.sub.2, CF.sub.3, NO.sub.2, NH.sub.2, or CH.sub.3.

24. The compound of claim 22, wherein D.sub.3 is ##STR00893## J.sub.34 is C; and J.sub.35, J.sub.36, J.sub.37, J.sub.38, and J.sub.39 are each independently H, OCH.sub.3, OH, Br, C, F, C(O)NH.sub.2, CF.sub.3, NH.sub.2, or CH.sub.3.

25. The compound of claim 22, wherein D.sub.3 is ##STR00894## J.sub.56 is C; J.sub.57 is CH; and J.sub.58, J.sub.59, J.sub.60, J.sub.61, and J.sub.62, are each independently H, OH, NH.sub.2, Br, C, F, OCH.sub.3, CF.sub.3, or CH.sub.3.

26. The compound of claim 22, wherein D.sub.3 is ##STR00895## J.sub.40 is C; J.sub.41 is H or ##STR00896## and J.sub.42, J.sub.43, J.sub.44, J.sub.45, and J.sub.46 are each independently H, OH, Br, Cl, F, I, NH.sub.2, or CH.sub.3.

27. A compound selected from the group consisting of ##STR00897## ##STR00898## ##STR00899## or a pharmaceutically acceptable salt thereof.

28. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable excipient.

29. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 27 and a pharmaceutically acceptable excipient.

30. A method of modulating AR activity, the method comprising (a) administering a compound of claim 1 to a subject in need thereof.

31. The method of claim 30, wherein the modulating AR activity is for the treatment of at least one indication selected from the group consisting of: AR-mediated cancer, prostate cancer, breast cancer, ovarian cancer, endometrial cancer, bladder cancer, Taxene resistant triple negative breast cancer, hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty, and age-related macular degeneration.

32. The method of claim 31, wherein the modulating AR activity is for the treatment of prostate cancer.

33. The method of claim 31, wherein the modulating AR activity is for the treatment of Taxene resistant triple negative breast cancer.

34. The method of claim 31, wherein the modulating AR activity is for the treatment of ovarian cancer.

35. The method of claim 31, wherein the modulating AR activity is for the treatment of endometrial cancer.

Description

DETAILED DESCRIPTION

[0183] The BF3 site is an attractive target for direct inhibition of the AR co-activation. In silico computational drug discovery methods were used to conduct a virtual screen of 4 million purchasable lead-like compounds from the ZINC database (Irwin, J. et al. Abstracts of Papers Am. Chem. Soc. (2005) 230:U1009) to identify potential BF3 binders. The in silico methods included large-scale docking, in-site rescoring and consensus voting procedures.

[0184] It will be understood by a person of skill that COOH and NR.sub.2 may include the corresponding ions, for example carboxylate ions and ammonium ions, respectively. Alternatively, where the ions are shown, a person of skill in the art will appreciate that the counter ion may also be present.

[0185] Those skilled in the art will appreciate that the point of covalent attachment of the moiety to the compounds as described herein may be, for example, and without limitation, cleaved under specified conditions. Specified conditions may include, for example, and without limitation, in vivo enzymatic or non-enzymatic means. Cleavage of the moiety may occur, for example, and without limitation, spontaneously, or it may be catalyzed, induced by another agent, or a change in a physical parameter or environmental parameter, for example, an enzyme, light, acid, temperature or pH. The moiety may be, for example, and without limitation, a protecting group that acts to mask a functional group, a group that acts as a substrate for one or more active or passive transport mechanisms, or a group that acts to impart or enhance a property of the compound, for example, solubility, bioavailability or localization.

[0186] In some embodiments, compounds of Formula I or Formula II above may be used for systemic treatment of at least one indication selected from the group consisting of: prostate cancer, breast cancer, ovarian cancer, endometrial cancer, hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty and age-related macular degeneration. In some embodiments compounds of Formula I or Formula II may be used in the preparation of a medicament or a composition for systemic treatment of an indication described herein. In some embodiments, methods of systemically treating any of the indications described herein are also provided.

[0187] Compounds as described herein may be in the free form or in the form of a salt thereof. In some embodiment, compounds as described herein may be in the form of a pharmaceutically acceptable salt, which are known in the art (Berge S. M. et al., J. Pharm. Sci. (1977) 66(1):1-19). Pharmaceutically acceptable salt as used herein includes, for example, salts that have the desired pharmacological activity of the parent compound (salts which retain the biological effectiveness and/or properties of the parent compound and which are not biologically and/or otherwise undesirable). Compounds as described herein having one or more functional groups capable of forming a salt may be, for example, formed as a pharmaceutically acceptable salt. Compounds containing one or more basic functional groups may be capable of forming a pharmaceutically acceptable salt with, for example, a pharmaceutically acceptable organic or inorganic acid. Pharmaceutically acceptable salts may be derived from, for example, and without limitation, acetic acid, adipic acid, alginic acid, aspartic acid, ascorbic acid, benzoic acid, benzenesulfonic acid, butyric acid, cinnamic acid, citric acid, camphoric acid, camphorsulfonic acid, cyclopentanepropionic acid, diethylacetic acid, digluconic acid, dodecylsulfonic acid, ethanesulfonic acid, formic acid, fumaric acid, glucoheptanoic acid, gluconic acid, glycerophosphoric acid, glycolic acid, hemisulfonic acid, heptanoic acid, hexanoic acid, hydrochloric acid, hydrobromic acid, hydriodic acid, 2-hydroxyethanesulfonic acid, isonicotinic acid, lactic acid, malic acid, maleic acid, malonic acid, mandelic acid, methanesulfonic acid, 2-napthalenesulfonic acid, naphthalenedisulphonic acid, p-toluenesulfonic acid, nicotinic acid, nitric acid, oxalic acid, pamoic acid, pectinic acid, 3-phenylpropionic acid, phosphoric acid, picric acid, pimelic acid, pivalic acid, propionic acid, pyruvic acid, salicylic acid, succinic acid, sulfuric acid, sulfamic acid, tartaric acid, thiocyanic acid or undecanoic acid. Compounds containing one or more acidic functional groups may be capable of forming pharmaceutically acceptable salts with a pharmaceutically acceptable base, for example, and without limitation, inorganic bases based on alkaline metals or alkaline earth metals or organic bases such as primary amine compounds, secondary amine compounds, tertiary amine compounds, quaternary amine compounds, substituted amines, naturally occurring substituted amines, cyclic amines or basic ion-exchange resins. Pharmaceutically acceptable salts may be derived from, for example, and without limitation, a hydroxide, carbonate, or bicarbonate of a pharmaceutically acceptable metal cation such as ammonium, sodium, potassium, lithium, calcium, magnesium, iron, zinc, copper, manganese or aluminum, ammonia, benzathine, meglumine, methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, isopropylamine, tripropylamine, tributylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, glucamine, methylglucamine, theobromine, purines, piperazine, piperidine, procaine, N-ethylpiperidine, theobromine, tetramethylammonium compounds, tetraethylammonium compounds, pyridine, N,N-dimethylaniline, N-methylpiperidine, morpholine, N-methylmorpholine, N-ethylmorpholine, dicyclohexylamine, dibenzylamine, N,N-dibenzylphenethylamine, 1-ephenamine, N,N-dibenzylethylenediamine or polyamine resins. In some embodiments, compounds as described herein may contain both acidic and basic groups and may be in the form of inner salts or zwitterions, for example, and without limitation, betaines. Salts as described herein may be prepared by conventional processes known to a person skilled in the art, for example, and without limitation, by reacting the free form with an organic acid or inorganic acid or base, or by anion exchange or cation exchange from other salts. Those skilled in the art will appreciate that preparation of salts may occur in situ during isolation and purification of the compounds or preparation of salts may occur by separately reacting an isolated and purified compound.

[0188] In some embodiments, compounds and all different forms thereof (e.g. free forms, salts, polymorphs, isomeric forms) as described herein may be in the solvent addition form, for example, solvates. Solvates contain either stoichiometric or non-stoichiometric amounts of a solvent in physical association the compound or salt thereof. The solvent may be, for example, and without limitation, a pharmaceutically acceptable solvent. For example, hydrates are formed when the solvent is water or alcoholates are formed when the solvent is an alcohol.

[0189] In some embodiments, compounds and all different forms thereof (e.g. free forms, salts, solvates, isomeric forms) as described herein may include crystalline and amorphous forms, for example, polymorphs, pseudopolymorphs, conformational polymorphs, amorphous forms, or a combination thereof. Polymorphs include different crystal packing arrangements of the same elemental composition of a compound. Polymorphs usually have different X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability and/or solubility. Those skilled in the art will appreciate that various factors including recrystallization solvent, rate of crystallization and storage temperature may cause a single crystal form to dominate.

[0190] In some embodiments, compounds and all different forms thereof (e.g. free forms, salts, solvates, polymorphs) as described herein include isomers such as geometrical isomers, optical isomers based on asymmetric carbon, stereoisomers, tautomers, individual enantiomers, individual diastereomers, racemates, diastereomeric mixtures and combinations thereof, and are not limited by the description of the formula illustrated for the sake of convenience.

[0191] In some embodiments, pharmaceutical compositions as described herein may comprise a salt of such a compound, preferably a pharmaceutically or physiologically acceptable salt. Pharmaceutical preparations will typically comprise one or more carriers, excipients or diluents acceptable for the mode of administration of the preparation, be it by injection, inhalation, topical administration, lavage, or other modes suitable for the selected treatment. Suitable carriers, excipients or diluents (used interchangeably herein) are those known in the art for use in such modes of administration.

[0192] Suitable pharmaceutical compositions may be formulated by means known in the art and their mode of administration and dose determined by the skilled practitioner. For parenteral administration, a compound may be dissolved in sterile water or saline or a pharmaceutically acceptable vehicle used for administration of non-water soluble compounds such as those used for vitamin K. For enteral administration, the compound may be administered in a tablet, capsule or dissolved in liquid form. The tablet or capsule may be enteric coated, or in a formulation for sustained release. Many suitable formulations are known, including, polymeric or protein microparticles encapsulating a compound to be released, ointments, pastes, gels, hydrogels, or solutions which can be used topically or locally to administer a compound. A sustained release patch or implant may be employed to provide release over a prolonged period of time. Many techniques known to one of skill in the art are described in Remington: the Science & Practice of Pharmacy by Alfonso Gennaro, 20.sup.th ed., Lippencott Williams & Wilkins, (2000). Formulations for parenteral administration may, for example, contain excipients, polyalkylene glycols such as polyethylene glycol, oils of vegetable origin, or hydrogenated naphthalenes. Biocompatible, biodegradable lactide polymer, lactide/glycolide copolymer, or polyoxyethylene-polyoxypropylene copolymers may be used to control the release of the compounds. Other potentially useful parenteral delivery systems for modulatory compounds include ethylene-vinyl acetate copolymer particles, osmotic pumps, implantable infusion systems, and liposomes. Formulations for inhalation may contain excipients, for example, lactose, or may be aqueous solutions containing, for example, polyoxyethylene-9-lauryl ether, glycocholate and deoxycholate, or may be oily solutions for administration in the form of nasal drops, or as a gel.

[0193] Compounds or pharmaceutical compositions as described herein or for use as described herein may be administered by means of a medical device or appliance such as an implant, graft, prosthesis, stent, etc. Also, implants may be devised which are intended to contain and release such compounds or compositions. An example would be an implant made of a polymeric material adapted to release the compound over a period of time.

[0194] An effective amount of a pharmaceutical composition as described herein includes a therapeutically effective amount or a prophylactically effective amount. A therapeutically effective amount refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic result, such as reduced tumor size, increased life span or increased life expectancy. A therapeutically effective amount of a compound may vary according to factors such as the disease state, age, sex, and weight of the subject, and the ability of the compound to elicit a desired response in the subject. Dosage regimens may be adjusted to provide the optimum therapeutic response. A therapeutically effective amount is also one in which any toxic or detrimental effects of the compound are outweighed by the therapeutically beneficial effects. A prophylactically effective amount refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result, such as smaller tumors, increased life span, increased life expectancy or prevention of the progression of prostate cancer to an androgen-independent form. Typically, a prophylactic dose is used in subjects prior to or at an earlier stage of disease, so that a prophylactically effective amount may be less than a therapeutically effective amount.

[0195] It is to be noted that dosage values may vary with the severity of the condition to be alleviated. For any particular subject, specific dosage regimens may be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions. Dosage ranges set forth herein are exemplary only and do not limit the dosage ranges that may be selected by medical practitioners. The amount of active compound(s) in the composition may vary according to factors such as the disease state, age, sex, and weight of the subject. Dosage regimens may be adjusted to provide the optimum therapeutic response. For example, a single bolus may be administered, several divided doses may be administered over time or the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. It may be advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage.

[0196] In some embodiments, compounds and all different forms thereof as described herein may be used, for example, and without limitation, in combination with other treatment methods for at least one indication selected from the group consisting of: prostate cancer, breast cancer, ovarian cancer, endometrial cancer, hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty and age-related macular degeneration. For example, compounds and all their different forms as described herein may be used as neoadjuvant (prior), adjunctive (during), and/or adjuvant (after) therapy with surgery, radiation (brachytherapy or external beam), or other therapies (eg. HIFU).

[0197] In general, compounds as described herein should be used without causing substantial toxicity. Toxicity of the compounds as described herein can be determined using standard techniques, for example, by testing in cell cultures or experimental animals and determining the therapeutic index, i.e., the ratio between the LD50 (the dose lethal to 50% of the population) and the LD100 (the dose lethal to 100% of the population). In some circumstances however, such as in severe disease conditions, it may be appropriate to administer substantial excesses of the compositions. Some compounds as described herein may be toxic at some concentrations. Titration studies may be used to determine toxic and non-toxic concentrations. Toxicity may be evaluated by examining a particular compound's or composition's specificity across cell lines using PC3 cells as a negative control that do not express AR. Animal studies may be used to provide an indication if the compound has any effects on other tissues. Systemic therapy that targets the AR will not likely cause major problems to other tissues since anti-androgens and androgen insensitivity syndrome are not fatal.

[0198] Compounds as described herein may be administered to a subject. As used herein, a subject may be a human, non-human primate, rat, mouse, cow, horse, pig, sheep, goat, dog, cat, etc. The subject may be suspected of having or at risk for having a cancer, such as prostate cancer, breast cancer, ovarian cancer or endometrial cancer, or suspected of having or at risk for having acne, hirsutism, alopecia, benign prostatic hyperplasia, ovarian cysts, polycystic ovary disease, precocious puberty, or age-related macular degeneration. Diagnostic methods for various cancers, such as prostate cancer, breast cancer, ovarian cancer or endometrial cancer, and diagnostic methods for acne, hirsutism, alopecia, benign prostatic hyperplasia, ovarian cysts, polycystic ovary disease, precocious puberty, or age-related macular degeneration and the clinical delineation of cancer, such as prostate cancer, breast cancer, ovarian cancer or endometrial cancer, diagnoses and the clinical delineation of acne, hirsutism, alopecia, benign prostatic hyperplasia, ovarian cysts, polycystic ovary disease, precocious puberty, or age-related macular degeneration are known to those of ordinary skill in the art.

[0199] Definitions used include ligand-dependent activation of the androgen receptor (AR) by androgens such as dihydrotestosterone (DHT) or the synthetic androgen (R1881) used for research purposes. Ligand-independent activation of the AR refers to transactivation of the AR in the absence of androgen (ligand) by, for example, stimulation of the cAMP-dependent protein kinase (PKA) pathway with forskolin (FSK).

[0200] Some compounds and compositions as described herein may interfere with a mechanism specific to ligand-dependent activation (e.g., accessibility of the ligand binding domain (LBD) to androgen) or to ligand-independent activation of the AR.

[0201] Various alternative embodiments and examples of the invention are described herein. These embodiments and examples are illustrative and should not be construed as limiting the scope of the invention.

Materials and Methods

In Silico Screening

[0202] Ten million commercially available compounds from the ZINC12.0 structural libraries (Irwin, J. J. and Shoichet, B. K. ZINCa free database of commercially available compounds for virtual screening. J Chem Inf Model 2005, 45, 177-182) were imported into a molecular database using Molecular Operating Environment (MOE) version 2007.09 (MOE, Chemical Computing Group, Inc., 2008, www.chemcomp.com). These structures were energy minimized using an MMFF94x force field, exported in SD format and rigidly docked into the BF3 site of the protein structures 4HLW with Glide software (Friesner, R. A. et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004, 25, 739-49). About 2 million molecules that had a GlideScore<5.0 were then re-docked into the same BF3 binding cavity using the electronic high-throughput screening (eHiTS) docking module (Zsoldos, Z. et al. eHiTS: a new fast, exhaustive flexible ligand docking system. J Mol Graph Model 2007, 26, 198-212). From this, 500,000 structures with eHiTS docking scores <3.0 threshold were identified. They were scored by the LigX module of the MOE to account for the receptor/ligand flexibility. The pKi binding affinity was scored after energy minimization to select the ligands that showed the best binding characteristics defined mainly by the energy of hydrogen bonds and hydrophobic interactions. The virtual hits were scored using Molecular Mechanics, the Generalized Born model and Solvent Accessibility (MM-GB/SA) method with OPLS_2005 and GB/SA in MacroModel to calculate the free energies of the optimal chemical poses (Maestro, Schrodinger, LLC, New York, N.Y., 2008. www.schrodinger.com). The root mean square deviation (RMSD) was calculated between the Glide poses and the eHiTS poses to evaluate the docking consistency and thus to establish the most probable binding pose for a given ligand. Finally, very large and very small molecules were penalized based on a heavy atom count.

[0203] With this information, a cumulative scoring of five different predicted parameters (RMSD, heavy atoms count, LigX, Macromodel, pKi) was generated where each molecule receive a binary 1.0 score for every top 10% appearance. The final cumulative vote (with the maximum possible value of 5) was then used to rank the training set entries. Based on the cumulative score 5000 compounds were selected and subjected to visual inspection. After this final selection step 200 compounds were selected out of which 150 chemical substances could be readily purchased in sufficient purity and quantity.

General Synthesis and Characterization of Compounds

Exemplary Scheme 1: Synthesis of Compound 13163.

[0204] ##STR00459##

[0205] At 0 C., a solution of para-toluenesulfonic acid (13.4 g, 0.55 eq, 70.4 mmol) in acetonitrile (150 mL) was added drop-wise over 1 h to a solution of indole (15 g, 1.0 eq, 128.0 mmol) in acetonitrile (500 mL). The mixture was kept for additional 6 h at 0 C. The subsequent precipitate was filtered (at 0 C.) and washed with acetonitrile (three times). The precipitate was neutralized with saturated NaHCO.sub.3 solution and extracted with AcOEt (3100 mL). The organic extracts were combined, washed with brine, dried over Na.sub.2SO.sub.4; filtered and concentrated under reduced pressure. Any purification was needed and the crude was transformed in corresponding hydrochloride with HCl2 M solution in ether and the precipitate salt was filtered to afford 14.8 g of the white solid (54.7 mmol, 85%).

Analysis

[0206] M.p.=169-170 C.

[0207] t.sub.R (HPLC)=3.01 min

[0208] MS (ESI+) m/z=235.12 [(M+H)+]

[0209] HRMS (ESI+): calculated for C.sub.16H.sub.15N.sub.2, m/z=235.1230; found, 235.1237; calculated for C.sub.16H.sub.14N.sub.2Na, m/z=257.1049; found, 257.1058

[0210] .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm)=11.45 (s, 1H, H.sub.12), 7.77 (d, J=8.0 Hz, 1H, H.sub.18), 7.68 (d, J=2.6 Hz, 1H, H.sub.11), 7.58-7.50 (m, 1H, H.sub.6), 7.45 (d, J=8.4 Hz, 1H, H.sub.15), 7.43-7.38 (m, 4H, H.sub.1,2), 7.35-7.33 (m, 1H, H.sub.3), 7.17 (ddd, J=8.2, 7.1, 1.1 Hz, 1H, H.sub.16), 7.07 (ddd, J=8.0, 7.1, 1.0 Hz, 1H, H.sub.17), 5.58 (t, J=8.7 Hz, 1H, H.sub.18), 3.67 (d, J=8.7 Hz, 2H, H.sub.9).

[0211] .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm)=137.96 (C.sub.4-arom.), 137.00 (C.sub.13-arom.), 135.72 (C.sub.5-arom.), 128.74 (C.sub.1H-arom.), 128.50 (C.sub.2H-arom.), 126.36 (C.sub.14-arom.), 126.11 (C.sub.6H-arom.), 125.72 (C.sub.11H-arom.), 122.31 (C.sub.16H-arom.), 119.69 (C.sub.17H-arom.), 119.48 (C.sub.18H-arom.), 119.38 (C.sub.3H-arom.), 112.30 (C.sub.15H-arom.), 110.24 (C.sub.10-arom.), 56.55 (C.sub.8H), 35.37 (C.sub.9H.sub.2).

General Synthesis Methods

[0212] .sup.1H and .sup.13C NMR spectra (COSY, .sup.1H/.sup.13C 2D-correlations) were recorded with Bruker Avance III 400 MHz. Processing of the spectra was performed with MestRec software and data are reported as follows: chemical shifts (6) in parts per million, coupling constants (J) in hertz (Hz). The high-resolution mass spectra were recorded in positive ion-mode with an ESI ion source on an Agilent Time-of-Flight LC/MS mass spectrometer. HPLC analyses and purity of >95% were performed by analytical reverse-phase HPLC with a Agilent instrument with variable detector using column Agilent Zorbax 4.65 mm, Sum; flow: 2.0 mL.Math.min.sup.1, H.sub.2O (0.1% FA)/CH.sub.3CN (0.1% FA), gradient 2-98% (6 min) and 98% (0.3 min). Melting points were determined with a Fischer-Jonhs.

Analytical Methods:

[0213] .sup.1H and .sup.13C NMR spectra (COSY, .sup.1H/.sup.13C 2D-correlations) were recorded with Bruker Avance III 400 MHz. Processing of the spectra was performed with MestRec software and data are reported as follows: chemical shifts (6) in parts per million, coupling constants (J) in hertz (Hz). The high-resolution mass spectra were recorded in positive ion-mode with an ESI ion source on an Agilent Time-of-Flight LC/MS mass spectrometer. HPLC analyses and purity of >95% were performed by analytical reverse-phase HPLC with a Agilent instrument with variable detector using column Agilent Zorbax 4.65 mm, Sum; flow: 2.0 mL.Math.min.sup.1, H.sub.2O (0.1% FA)/CH.sub.3CN (0.1% FA), gradient 2-98% (6 min) and 98% (0.3 min).

Dimethyl- & Cyclohexyl-Hydroindole Moiety

General Procedure 1

[0214] Phenylhydrazine (1.0 eq) aldehyde (isobutyraldehyde or cyclohexanecarboxaldehyde) (1.0 eq) were diluted in AcOH (0.1 M). The mixture was heated at 65 C. for 2 h (until complete conversion). Reaction mixture containing imine intermediate was allowed to reach r.t. and indole (1.0 eq) was added to the mixture which was stirred additional 2 h at r.t. (until complete conversion). Acetic acid was removed under vacuo. Then, the residue was poured with H.sub.2O and neutralized at pH 7 with sat. NaHCO.sub.3 solution. The aqueous layer was extracted with AcOEt (3) and organic layers were combined, washed with brine, dried over Na.sub.2SO.sub.4 and evaporated under reduced pressure. Then, crude was purified by automated combi-flash to afford the good compound.

General Procedure 2

[0215] Benzyloxy compound (1.0 eq) was dissolved in mixture of MeOH (0.05 M) and the system was purged with vacuum/N.sub.2 (3). Then, Pd/C (20% w/w) was added to the mixture and purged again with vacuum/H.sub.2 and put under H.sub.2 atmosphere. The reaction was stirred overnight at r.t. under H.sub.2 atmosphere. The reaction mixture was filtered on a plug of Celite which was washed with MeOH. The filtrate was concentrated under reduced pressure and the residue was purified by combi-flash to afford the good compound.

General Procedure 3

[0216] Imine compound (1.0 eq) was dissolved in AcOH (0.1 M) and the system was put under argon atmosphere. Then, NaBH.sub.3CN (1.1 eq) was added quickly. Then, the reaction was stirred at r.t. After overnight, the reaction mixture was concentrated and the crude was quenched with H.sub.2O. Aqueous layer was neutralized with saturated NaHCO.sub.3 solution until pH 7 and extracted with AcOEt (2). The combined organic layers were washed with brine, dried over Na.sub.2SO.sub.4 and rotary evaporated. The crude was purified by automated combi-flash to afford the good compound.

General Procedure 4

[0217] From ester compound (1.0 eq) was diluted in mixture of MeOH/Acetone (1:3, 0.1 M). The mixture was stirred and a solution of LiOH (2.0 eq) in H.sub.2O (0.85 M) was added drop-wise over 5 min. Then, the mixture was stirred overnight at r.t. The reaction mixture was diluted in a mixture of Et.sub.2O and H.sub.2O and the aqueous phase was washed and then acidified with concentrated HCl solution until pH 3. The aqueous layer was extracted with Et.sub.2O (2). The combined organic layers were washed with brine, dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to give pure product.

General Procedure 5

[0218] A dried vessel was charged with LiAlH.sub.4 (4.0 eq), enclosed with condenser and rubber cap and put under argon atmosphere. Then, carboxylic acid (1.0 eq) was dissolved in anhydrous THE (0.28 M) and was added in system which was stirred 2 h at 70 C. The excess of LiAlH.sub.4 was destroyed by adding AcOEt drop-wise (exothermic reaction) and then by adding H.sub.2O. Aqueous saturated NH.sub.4Cl solution was added and the whole was extracted with AcOEt (2). The combined organic layers were washed with H.sub.2O and brine, dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure. The crude was purified by automated combi-flash to afford the good compound.

General Procedure 6

[0219] Phenylhydrazine (1.0 eq) and isobutyraldehyde (1.0 eq) were diluted in AcOH (0.1 M). The mixture was heated at 65 C. for 2 h (until complete conversion). Reaction mixture containing imine intermediate was allowed to reach r.t. Acetic acid was removed under vacuo. The residue was poured with H.sub.2O and neutralized at pH 7 with sat. NaHCO.sub.3 solution. The aqueous layer was extracted with AcOEt (3) and organic layers were combined, washed with brine, dried over Na.sub.2SO.sub.4 and evaporated under reduced pressure. Then, residue corresponding to imine intermediate was diluted in ACN (0.5 M). Azaindole (0.9 eq) and ZnCl.sub.2 (0.9 eq) were introduced in microwave vessel. The mixture was stirred and heated by microwave 3 h at 120 C. The resulting crystals (after avernight at r.t.) was filtered and washed with 1 N aqueous NaOH solution (50 mL) and extracted with AcOEt (2). The organic layers were combined, washed with brine, dried over Na.sub.2SO.sub.4 and concentrated under reduced pressure to provide pure compound.

[0220] Dimethyl-Hydroindole Moiety

3-(3,3-dimethylindolin-2-yl)-5-methyl-1H-indole (Procedure 1)

[0221]

TABLE-US-00003 VPC Number LabBook Code IC.sub.50 (eGFP) = 1.5 13 535 CA 2-36 F9-15 (yield = 63%) IC.sub.50 (PSA) = 1.87 [00460] t.sub.R (HPLC) = 4.07 min MS (ESI+) m/z = 277.1719 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.19H.sub.21N.sub.2O, m/z = 277.1699; found, 277.1708 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.83 (s, 1H, H.sub.14), 7.33 (d, J = 0.6 Hz, 1H, H.sub.20), 7.26 (d, J = 2.0 Hz, H.sub.13), 7.25 (d, J = 8.0 Hz, 1H, H.sub.17), 7.01 (d, J = 7.2 Hz, 1H, H.sub.6), 6.97 (td, J = 7.6, 1.3 Hz, 1H, H.sub.2), 6.88 (dd, J = 8.3, 1.5 Hz, 1H, H.sub.18), 6.60 (td, J = 7.6, 1.2 Hz, 1H, H.sub.1), 6.59 (d, J = 7.6 Hz, 1H, H.sub.3), 5.82 (d, J = 2.4 Hz, 1H, H.sub.7), 4.76 (d, J = 2.2 Hz, 1H, H.sub.8), 2.33 (s, 3H, H.sub.21), 1.39 (s, 3H, H.sub.10), 0.74 (s, 3H, H.sub.11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.99 (C.sub.4-arom.), 138.68 (C.sub.5- arom.), 135.33 (C.sub.15-arom.), 127.54 (C.sub.19-arom.), 127.29 (C.sub.2H-arom.), 127.01 (C.sub.16- arom.), 124.09 (C.sub.13H-arom.), 122.80 (C.sub.18H-arom.), 122.45 (C.sub.6H-arom.), 119.77 (C.sub.20H-arom.), 117.53 (C.sub.1H-arom.), 113.64 (C.sub.12-arom.), 111.60 (C.sub.17H-arom.), 108.85 (C.sub.3H-arom.), 68.17 (C.sub.8H), 45.20 (C.sub.9), 27.15 (C.sub.10H.sub.3), 25.01 (C.sub.11H.sub.3), 21.87 (C.sub.21H.sub.3).

3-(3,3-dimethylindolin-2-yl)-5-methoxy-1H-indole (Procedure 1)

[0222]

TABLE-US-00004 VPC Number LabBook Code IC.sub.50 (eGFP) = 2.2 13 536 CA 2-38 F10-19 (yield = 46%) IC.sub.50 (PSA) = 2.52 [00461] t.sub.R (HPLC) = 3.82 min MS (ESI+) m/z = 293.1668 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.19H.sub.21N.sub.2O, m/z = 293.1648; found, 293.1654 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.79 (s, 1H, H.sub.14), 7.27 (d, J = 2.5 Hz, 1H, H.sub.13), 7.24 (d, J = 8.8 Hz, 1H, H.sub.17), 7.02 (br d, J = 7.2 Hz, 1H, H.sub.6), 6.97 (td, J = 7.6, 1.3 Hz, 1H, H.sub.2), 6.88 (d, J = 2.4 Hz, 1H, H.sub.20), 6.70 (dd, J = 8.8, 2.4 Hz, 1H, H.sub.18), 6.61 (td, J = 7.6, 1.2 Hz, 1H, H.sub.1), 6.59 (d, J = 7.6 Hz, 1H, H.sub.3), 5.82 (d, J = 2.0 Hz, 1H, H.sub.7), 4.73 (d, J = 1.9 Hz, 1H, H.sub.8), 3.62 (s, 3H, H.sub.22), 1.38 (s, 3H, H.sub.10), 0.78 (s, 3H, H.sub.11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 153.22 (C.sub.19-arom.), 151.10 (C.sub.4- arom.), 138.59 (C.sub.5-arom.), 132.18 (C.sub.15-arom.), 127.37 (C.sub.2H-arom.), 127.36 (C.sub.16-arom.), 124.83 (C.sub.13H-arom.), 122.32 (C.sub.6H-arom.), 117.51 (C.sub.1H-arom.), 114.38 (C.sub.12-arom.), 112.44 (C.sub.17H-arom.), 111.21 (C.sub.18-arom.), 108.72 (C.sub.3H-arom.), 102.31 (C.sub.20H-arom.), 68.27 (C.sub.8H), 55.63 (C.sub.22H.sub.3), 45.21 (C.sub.9), 27.73 (C.sub.10H.sub.3) 24.58 (C.sub.11H.sub.3).

3-(3,3-dimethylindolin-2-yl)-5-amine-H-indole (Procedure 1)

[0223]

TABLE-US-00005 VPC Number LabBook Code IC.sub.50 (eGFP) = 7.7 13 538 CA 2-47 F7-17 (yield = 45%) IC.sub.50 (PSA) = No Data [00462] t.sub.R (HPLC) = 2.56 min MS (ESI+) m/z = 278.1668 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.18H.sub.20N.sub.3, m/z = 278.1652; found, 278.1657 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.53 (d, J = 1.6 Hz, 1H, H.sub.14), 7.14 (d, J = 2.4 Hz, 1H, H.sub.13), 7.08 (d, J = 8.4 Hz, 1H, H.sub.17), 7.00 (dd, J = 7.2, 0.7 Hz, 1H, H.sub.6) 6.95 (td, J = 7.6, 1.3 Hz, 1H, H.sub.2), 6.86 (d, J = 2.0 Hz, 1H, H.sub.20), 6.60 (td, J = 7.6, 0.8 Hz, 1H, H.sub.2,) 6.57 (d, J = 7.6 Hz, 1H, H.sub.3), 6.51 (dd, J = 8.5, 2.0 Hz, 1H, H.sub.18), 5.78 (s, 1H, H.sub.7), 4.86 (s 2H, H.sub.21), 4.69 (s, 1H, H.sub.8), 1.39 (s, 3H, H.sub.10), 0.75 (s, 3H, H.sub.11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.97 (C.sub.4-arom.), 138.81 (C.sub.5-arom.), 140.00 (C.sub.19-arom.), 131.08 (C.sub.15-arom.), 128.25 (C.sub.16-arom.), 127.21 (C.sub.2H-arom.), 123.86 (C.sub.13H-arom.), 122.47 (C.sub.6H-arom.), 117.47 (C.sub.1H-arom.), 112.50 (C.sub.12-arom.), 112.36 (C.sub.18H-arom.), 111.97 (C.sub.17-arom.), 108.86 (C.sub.3H-arom.), 104.09 (C.sub.20H-arom.), 68.29 (C.sub.8H), 45.21 (C.sub.9), 27.00 (C.sub.10H.sub.3, 25.15 (C.sub.11H.sub.3).

3-(3,3-dimethylindolin-2-yl)-6-(benzyloxy)-1H-indole (Procedure 1)

[0224]

TABLE-US-00006 VPC Number LabBook Code IC.sub.50 (eGFP) = 11.4 13 544 CA 2-54 Precipitate (yield = 53%) IC.sub.50 (PSA) = No Data [00463] t.sub.R (HPLC) = 4.60 min MS (ESI+) m/z = 369.1981 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.25H.sub.25N.sub.2O, m/z = 369.1961; found, 369.1979 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.77 (s, 1H, H.sub.14), 7.47 (d, J = 7.1 Hz, 2H, H.sub.24, 28), 7.42-7.38 (m, 3H, H.sub.20, 25, 27), 7.35-7.31 (m, 1H, H.sub.26) 7.18 (d, J = 2.1 Hz, 1H, H.sub.13), 6.99 (d, J = 6.8 Hz, 1H, H.sub.6), 6.98-6.94 (m, 2H, H.sub.2, .sub.17), 6.69 (dd, J = 8.7, 2.3 Hz, 1H, H.sub.19), 6.63-6.55 (m, 2H, H.sub.1, 3,), 5.83 (d, J = 2.3 Hz, 1H, H.sub.7), 5.11 (s, 2H, H.sub.22), 4.73 (d, J = 2.2 Hz, 1H, H.sub.8), 1.37 (s, 3H, H.sub.10), 0.73 (s, 3H, H.sub.11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 154.69 (C.sub.18-arom.), 150.96 (C.sub.4-arom.), 138.64 (C.sub.5-arom.), 138.14 (C.sub.23-arom.), 137.52 (C.sub.15-arom.), 128.84 (C.sub.25, 27H-arom.), 128.08 (C.sub.26H-arom.), 127.96 (C.sub.24, 28H-arom.), 127.32 (C.sub.2H-arom.), 122.77 (C.sub.13H-arom.), 122.41 (C.sub.6H-arom.), 121.88 (C.sub.16-arom.), 120.79 (C.sub.20H-arom.), 117.54 (C.sub.1H-arom.), 114.22 (C.sub.12-arom.), 109.60 (C.sub.19H-arom.), 108.83 (C.sub.3H-arom.), 96.33 (C.sub.17H-arom.), 69.92 (C.sub.22H.sub.2), 68.20 (C.sub.8H, 45.15 (C.sub.9), 27.16 (C.sub.10H.sub.3), 24.91 (C.sub.11H.sub.3).

3-(3,3-dimethylindolin-2-yl)-7-(benzyloxy)-1H-indole (Procedure 1)

[0225]

TABLE-US-00007 VPC Number LabBook Code IC.sub.50 (eGFP) = 3.7 13 543 CA 2-55 F7-10 (yield = 61%) IC.sub.50 (PSA) = 3.19 [00464] t.sub.R (HPLC) = 4.67 min MS (ESI+) m/z = 369.1976 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.25H.sub.25N.sub.2O, m/z = 369.1961; found, 369.1957 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.10 (d, J = 1.6 Hz, 1H, H.sub.14), 7.58 (d, J = 7.8 Hz, 2H, H.sub.24, 28), 7.46-7.39 (m, 2H, H.sub.25, 27), 7.38-7.31 (m, 1H, H.sub.26) 7.22 (d, J = 2.4 Hz, 1H, H.sub.13), 7.15 (d, J = 8.0 Hz, 1H, H.sub.20), 7.00 (d, J = 7.0 Hz, 1H, H.sub.6), 6.96 (td, J = 7.6, 1.3 Hz, 1H, H.sub.2), 6.85 (t, J = 7.8 Hz, 1H, H.sub.19), 6.73 (d, J = 7.6 Hz, 1H, H.sub.18, 6.62-6.56 (m, 2H, H.sub.1, 3), 5.85 (d, J = 2.4 Hz, 1H, H.sub.7), 5.26 (s, 2H, H.sub.22), 4.77 (d, J = 2.2 Hz, 1H, H.sub.8), 1.38 (s, 3H, H.sub.10), 0.74 (s, 3H, H.sub.11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.95 (C.sub.4-arom.), 145.54 (C.sub.17-arom.), 138.61 (C.sub.5-arom.), 137.89 (C.sub.23-arom.), 128.97 (C.sub.16-arom.), 128.83 (C.sub.25, 27H-arom.), 128.17 (C.sub.26H-arom.), 128.01 (C.sub.24, 28H-arom.), 127.32 (C.sub.2H-arom.), 127.15 (C.sub.15-arom.), 123.71 (C.sub.13H-arom.), 122.43 (C.sub.6H-arom.), 119.23 (C.sub.19H-arom.), 117.57 (C.sub.1H-arom.), 114.81 (C.sub.12-arom.), 113.19 (C.sub.20H-arom.), 108.83 (C.sub.3H-arom.), 103.08 (C.sub.18H-arom.), 69.56 (C.sub.22H.sub.2), 68.03 (C.sub.8H), 45.20 (C.sub.9), 27.19 (C.sub.10H.sub.3), 24.89 (C.sub.11H.sub.3).

3-(3,3-dimethylindolin-2-yl)-6-hydroxy-1H-indole (Procedure 2)

[0226]

TABLE-US-00008 VPC Number LabBook Code IC.sub.50 (eGFP) = 5.7 13 542 CA 2-61 F3-8 (yield = 62%) IC.sub.50 (PSA) = No Data [00465] t.sub.R (HPLC) = 3.25 min MS (ESI+) m/z = 279.1485 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.18H.sub.19N.sub.2O, m/z = 279.1492; found, 279.1485 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.55 (s, 1H, H.sub.14), 8.84 (s, 1H, H.sub.21), 7.28 (d, J = 8.5 Hz, 1H, H.sub.20), 7.08 (d, J = 2.0 Hz, 1H, H.sub.13), 6.99 (d, J = 6.8 Hz, 1H, H.sub.6), 6.95 (td, J = 7.6, 1.3 Hz, 1H, H.sub.2), 6.71 (d, J = 2.0 Hz, 1H,H.sub.17), 6.62-6.54 (m, 2H, H.sub.1, 3), 6.47 (dd, J = 8.6, 2.2 Hz, 1H, H.sub.19), 5.79 (d, J = 2.4 Hz, 1H, H.sub.7) 4.70 (d, J = 2,1 Hz, 1H, H.sub.8), 1.37 (s, 3H, H.sub.10), 0.73 (s, 3H, H.sub.11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 153.20 (C.sub.18-arom.), 150.98 (C.sub.4-arom.), 138.70 (C.sub.5-arom.), 138.04 (C.sub.15-arom.), 127.28 (C.sub.2H-arom.), 122.40 (C.sub.6H-arom.), 121.88 (C.sub.13H-arom.), 120.84 (C.sub.16-arom.), 120.50 (C.sub.20H-arom.), 117.48 (C.sub.1H-arom.), 114.08 (C.sub.12-arom.), 109.39 (C.sub.19H-arom.), 108.78 (C.sub.3H-arom.), 96.92 (C.sub.17H-arom.), 68.27 (C.sub.8H), 45.10 (C.sub.9), 27.17 (C.sub.10H.sub.3), 24.90 (C.sub.11H.sub.3).

3-(3,3-dimethylindolin-2-yl)-7-hydroxy-1H-indole (Procedure 2)

[0227]

TABLE-US-00009 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.5 13 541 CA 2-62 F6-11 (yield = 37%) IC.sub.50 (PSA) = 0.94 [00466] t.sub.R (HPLC) = 3.51 min MS (ESI+) m/z = 279.1525 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.18H.sub.19N.sub.2O, m/z = 279.1492; found, 279.1496 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.76 (s, 1H, H.sub.14), 9.46 (s, 1H, H.sub.21), 7.19 (d, J = 2.4 Hz, 1H, H.sub.13), 7.02-6.98 (m, 2H, H.sub.6, 20), 6.96 (td, J = 7.6, 1.3 Hz, 1H, H.sub.2), 6.73 (t, J = 7.7 Hz, 1H, H.sub.19), 6.62-6.55 (m, 2H, H.sub.1, 3), 6.48 (dd, J = 7.5, 0.6 Hz, 1H, H.sub.18), 5.82 (d, J = 2.4 Hz, 1H, H.sub.7), 4.75 (d, J = 2.2 Hz, 1H, H.sub.8), 1.38 (s, 3H, H.sub.10), 0.74 (s, 3H, H.sub.11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.98 (C.sub.4-arom.), 143.94 (C.sub.17-arom.), 138.67 (C.sub.5-arom.), 129.24 (C.sub.16-arom.), 127.29 (C.sub.2H-arom.), 126.97 (C.sub.13H-arom.), 123.40 (C.sub.13H-arom.), 122.41 (C.sub.6H-arom.), 119.42 (C.sub.19H-arom.), 117.52 (C.sub.1H-arom.), 114.60 (C.sub.12-arom.), 111.24 (C.sub.20H-arom.), 108.80 (C.sub.3H-arom.), 105.55 (C.sub.18H-arom.), 68.08 (C.sub.8H), 45.16 (C.sub.9), 27.17 (C.sub.10H.sub.3), 24.88 (C.sub.11H.sub.3).

3-(3,3-dimnethylindolin-2-yl)-7-ethyl-H-indole (Procedure 1)

[0228]

TABLE-US-00010 VPC Number LabBook Code IC.sub.50 (eGFP) = No Data 13 546 CA 2-67 F4-10 (yield = 62%) IC.sub.50 (PSA) = No Data [00467] t.sub.R (HPLC) = 4.16 min MS (ESI+) m/z = 277.1705 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.19H.sub.21N.sub.2, m/z = 277.1699; found, 277.1707 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.94 (s, 1H, H.sub.14), 7.39-7.35 (m, 1H, H.sub.20), 7.31 (d, J = 2.4 Hz, 1H, H.sub.13), 7.01 (d, J = 7.2 Hz, 1H, H.sub.6), 6.97 (td, J = 7.6, 1.3 Hz, 1H, H.sub.2), 6.87-6.83 (m, 2H, H.sub.18, 19), 6.61 (td, J = 7.2, 0.8 Hz, 1H, H.sub.1), 6.58 (d, J = 7.6 Hz, 1H, H.sub.3), 5.84 (d, J = 2.4 Hz, 1H, H.sub.7), 4.80 (d, J = 2.2 Hz, 1H, H.sub.8), 2.46 (s, 3H, H.sub.21), 1.39 (s, 3H, H.sub.10), 0.74 (s, 3H, H.sub.11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.97 (C.sub.4-arom.), 138.68 (C.sub.5-arom.), 136.42 (C.sub.15-arom.), 127.32 (C.sub.2H-arom.), 126.97 (C.sub.16-arom.), 123.73 (C.sub.13H-arom.), 122.42 (C.sub.6H-arom.), 121.72 (C.sub.19H-arom.), 120.90 (C.sub.17-arom.), 118.96 (C.sub.18H-arom.), 117.73 (C.sub.20H-arom.), 117.57 (C.sub.1H-arom.), 114.63 (C.sub.12-arom.), 108.85 (C.sub.3H-arom.), 68.11 (C.sub.8H), 45.17 (C.sub.9), 27.16 (C.sub.10H.sub.3), 24.95 (C.sub.11H.sub.3), 17.27 (C.sub.21H.sub.3).

3-(3,3-dimethylindolin-2-yl)-7-fluoro-1H-indole (Procedure 1)

[0229]

TABLE-US-00011 VPC Number LabBook Code IC.sub.50 (eGFP) = No Data 13 555 CA 2-90 F4-7 (yield = 62%) IC.sub.50 (PSA) = No Data [00468] t.sub.R (HPLC) = 4.12 min MS (ESI+) m/z = 281.1456 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.18H.sub.18FN.sub.2, m/z = 281.1449; found, 281.1454 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.49 (s, 1H, H.sub.14), 7.41-7.34 (m, 2H, H.sub.13, 20), 7.01 (d, J = 7.2 Hz, 1H, H.sub.6), 6.97 (td, J = 7.6, 1.3 Hz, 1H, H.sub.2), 6.94-6.86 (m, 2H, H.sub.18, 19), 6.65-6.57 (m, 2H, H.sub.1, 3), 5.91 (d, J = 2.5 Hz, 1H H.sub.7), 4.79 (d, J = 2.2 Hz, 1H, H.sub.8), 1.38 (s, 3H, H.sub.10), 0.74 (s, 3H, H.sub.11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.85 (C.sub.4-arom.), 148.48 (C.sub.17- arom.), 138.51 (C.sub.5-arom.), 131.28 (d, J = 5.9 Hz, C.sub.16-arom.), 127.39 (C.sub.2H- arom.), 125.19 (d, J = 0.6 Hz, C.sub.13H-arom.), 124.70 (d, J = 13.1 Hz, C.sub.15- arom.), 122.45 (C.sub.6H-arom.), 119.05 (d, J = 6.3 Hz, C.sub.19H-arom.), 117.70 (C.sub.1H- arom.), 116.45 (d, J = 3.2 Hz, C.sub.20H-arom.), 115.49 (d, J = 1.9 Hz, C.sub.12-arom.), 108.91 (C.sub.3H-arom.), 106.02 (d, J = 15.9 Hz, C.sub.18H-arom.), 67.86 (C.sub.8H), 45.25 (C.sub.9), 27.12 (C.sub.10H.sub.3), 24.90 (C.sub.11H.sub.3).

3-(3,3-dimethylindolin-2-yl)-1H-pyrrolo[2,3-b]pyridine (Procedure 3)

[0230]

TABLE-US-00012 VPC Number LabBook Code IC.sub.50 (eGFP) = 2.1 13 556 CA 2-100 F3-7 (yield = 76%) IC.sub.50 (PSA) = 2.18 [00469] t.sub.R (HPLC) = 3.52 min MS (ESI+) m/z = 264.1501 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.17H.sub.18N.sub.3, m/z = 264.1495; found, 264.1500 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.51 (s, 1H, H.sub.14), 8.18 (dd, J = 4.6, 1.5 Hz, 1H, H.sub.20), 7.86 (dd, J = 7.9, 1.1 Hz, 1H, H.sub.18), 7.44 (d, J = 2.4 Hz, 1H, H.sub.13), 7.02 (d, J = 7.2 Hz, 1H, H.sub.6), 7.00-6.96 (m, 2H, H.sub.2,19), 6.63 (td, J = 7.4, 0.9 Hz, 1H, H.sub.1), 6.60 (d, J = 7.7 Hz, 1H, H.sub.3), 5.92 (d, J = 2.3 Hz, 1H, H.sub.7), 4.74 (d, J = 2.0 Hz, 1H, H.sub.8), 1.38 (s, 3H, H.sub.10), 0.74 (s, 3H, H.sub.11). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 150.38 (C.sub.4-arom.), 148.74 (C.sub.15- arom.), 142.28 (C.sub.20H-arom.), 137.95 (C.sub.5-arom.), 127.99 (C.sub.18H-arom.), 126.96 (C.sub.2H-arom.), 123.93 (C.sub.13H-arom.), 121.97 (C.sub.6H-arom.), 118.98 (C.sub.16- arom.), 117.26 (C.sub.1H-arom.), 114.92 (C.sub.19H-arom.), 112.80 (C.sub.12-arom.), 108.47 (C.sub.3H-arom.), 67.77 (C.sub.8H), 44.77 (C.sub.9), 26.62 (C.sub.10H.sub.3), 24.34 (C.sub.11H.sub.3).

3-(3,3-dimethyindolin-2-yl)-1H-indole-7-carboxyic Acid (Procedure 4)

[0231]

TABLE-US-00013 VPC Number LabBook Code IC.sub.50 (eGFP) = No Data 13 557 CA 2-104 Ap Tmt (yield = 82%) IC.sub.50 (PSA) = No Data [00470] t.sub.R (HPLC) = 3.74 min MS (ESI+) m/z = 307.1442 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.19H.sub.19N.sub.2O.sub.2, m/z = 307.1441; found, 304.1442 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 13.01 (br s, 1H, H.sub.22), 10.98 (s, 1H, H.sub.14), 7.87 (d, J = 7.8 Hz, 1H, H.sub.20), 7.74 (d, J = 6.8 Hz, 1H, H.sub.18), 7.35 (d, J = 2.3 Hz, 1H, H.sub.13), 7.07 (t, J = 7.7 Hz, 1H, H.sub.19), 7.02 (d, J = 7.2 Hz, 1H, H.sub.6), 6.98 (td, J = 7.6, 1.1 Hz, 1H, H.sub.2), 6.65-6.58 (m, 2H, H.sub.1,3), 5.93 (br s, 1H, H.sub.7), 4.83 (s, 1H, H.sub.8), 1.39 (s, 3H, H.sub.10), 0.73 (s, 3H, H.sub.11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 168.45 (C.sub.21O), 150.89 (C.sub.4- arom.), 138.46 (C.sub.5-arom.), 135.63 (C.sub.15-arom.), 128.93 (C.sub.16-arom.), 127.41 (C.sub.2H-arom.), 125.68 (C.sub.20H-arom.), 125.66 (C.sub.13H-arom.), 124.20 (C.sub.18H- arom.), 122.48 (C.sub.6H-arom.), 118.42 (C.sub.19H-arom.), 117.69 (C.sub.1H-arom.), 114.65 (C.sub.12-arom.), 113.89 (C.sub.17-arom.), 108.90 (C.sub.3H-arom.), 67.76 (C.sub.8H), 45.25 (C.sub.9), 27.08 (C.sub.10H.sub.3), 24.91 (C.sub.11H.sub.3).

(3-(3,3-dimethylindolin-2-yl)-1H-indole-7-yl)methanol (Procedure 5)

[0232]

TABLE-US-00014 VPC Number LabBook Code IC.sub.50 (eGFP) = 1.6 13 558 CA 2-105 F6-11 (yield = 81%) IC.sub.50 (PSA) = No Data [00471] t.sub.R (HPLC) = 3.45 minMS (ESI+) m/z = 293.1651 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.19H.sub.21N.sub.2O, m/z = 293.1648; found, 293.1651 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.82 (s, 1H, H.sub.14), 7.45 (d, J = 7.8 Hz, 1H, H.sub.20), 7.29 (d, J = 2.4 Hz, 1H, H.sub.13), 7.05 (d, J = 6.8 Hz, 1H, H.sub.18), 7.01 (d, J = 7.2 Hz, 1H, H.sub.6), 6.97 (td, J = 7.6, 1.3 Hz, 1H, H.sub.2), 6.92 (dd, J = 7.8, 6.8 Hz, 1H), 6.61 (m, 2H, H.sub.1,3), 5.84 (d, J = 2.4 Hz, 1H, H.sub.7), 5.14 (t, J = 5.7 Hz, 1H, H.sub.18), 4.81 (d, J = 2.1 Hz, 1H, H.sub.8), 4.78 (d, J = 5.7 Hz, 2H, H.sub.21), 1.39 (s, 3H, H.sub.10), 0.74 (s, 3H, H.sub.11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.97 (C.sub.4-arom.), 138.66 (C.sub.5H-arom.), 134.66 (C.sub.15-arom.), 127.36 (C.sub.2H-arom.), 127.32 (C.sub.16-arom.), 125.92 (C.sub.17-arom.), 123.87 (C.sub.13H-arom.), 122.43 (C.sub.6H-arom.), 119.41 (C.sub.18H-arom.), 118.92 (C.sub.20H-arom.), 118.62 (C.sub.19H-arom.), 117.57 (C.sub.1H- arom.), 114.36 (C.sub.12-arom.), 108.85 (C.sub.3H-arom.), 68.06 (C.sub.8H), 60.82 (C.sub.21H.sub.2), 45.19 (C.sub.9), 27.15 (C.sub.10H.sub.3), 24.94 (C.sub.11H.sub.3).

(3-(3,3-dimethylindolin-2-yl)-1H-pyrrolo[2,3-c]pyridine (Procedure 6)

[0233]

TABLE-US-00015 VPC Number LabBook Code IC.sub.50 (eGFP) = 10.7 13 561 CA 2-121 Ap Tmt (yield = 35%) IC.sub.50 (PSA) = No Data [00472] t.sub.R (HPLC) = 3.07 min MS (ESI+) m/z = 264.1497 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.17H.sub.18N.sub.3, m/z = 264.1495; found, 264.1498 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.52 (s, 1H, H.sub.9), 8.73 (s, 1H, H.sub.3), 8.03 (s, 1H, H.sub.5), 7.59 (d, J = 1.7 Hz, 1H, H.sub.8), 7.49 (d, J = 4.3 Hz, 1H, H.sub.6), 7.04-6.95 (m, 2H, H.sub.11,15), 6.66-6.58 (m, 2H, H.sub.10,12), 5.94 (d, J = 1.9 Hz, 1H, H.sub.16), 4.78 (d, J = 2.3 Hz, 1H, H.sub.17), 1.38 (s, 3H, H.sub.19), 0.72 (s, 3H, H.sub.20). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 150.34 (C.sub.13-arom.), 137.94 (C.sub.14-arom.), 137.08 (C.sub.5H-arom.), 134.44 (C.sub.3H-arom.), 133.68 (C.sub.2-arom.), 130.91 (C.sub.1-arom.), 127.79 (C.sub.8H-arom.), 126.96 (C.sub.11H-arom.), 121.98 (C.sub.15H-arom.), 117.32 (C.sub.10H-arom.), 114.54 (C.sub.6H-arom.), 113.67 (C.sub.7- arom.), 108.51 (C.sub.12H-arom.), 67.25 (C.sub.17H), 44.83 (C.sub.18), 26.51 (C.sub.19H.sub.3), 24.33 (C.sub.20H.sub.3).

(3-(3,3-dimethylindolin-2-yl)-1H-pyrrolo[3,2-b]pyridine (Procedure 6)

[0234]

TABLE-US-00016 VPC Number LabBook Code IC.sub.50 (eGFP) = 2.3 13 560 CA 2-123 Ap Tmt (yield = 72%) IC.sub.50 (PSA) = No Data [00473] t.sub.R (HPLC) = 3.05 min MS (ESI+) m/z = 264.1502 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.17H.sub.18N.sub.3, m/z = 264.1495; found, 264.1502 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.16 (s, 1H, H.sub.9), 8.32 (dd, J = 4.6, 1.5 Hz, 1H, H.sub.5), 7.75 (dd, J = 8.2, 1.5 Hz, 1H, H.sub.3), 7.58 (d, J = 2.1 Hz, 1H, H.sub.8), 7.09 (dd, J = 8.2, 4.6 Hz, 1H, H.sub.4), 6.99 (d, J = 7.2 Hz, 1H, H.sub.15), 6.96 (td, J = 7.6, 1.3 Hz, 1H, H.sub.11), 6.63-6.57 (m, 2H, H.sub.10,12), 5.86 (d, J = 2.7 Hz, 1H, H.sub.16), 5.06 (dd, J = 2.8, 0.6 Hz, 1H, H.sub.17), 1.51 (s, 3H, H.sub.19), 0.72 (s, 3H, H.sub.20). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.85 (C.sub.13H-arom.), 145.29 (C.sub.1-arom.), 142.28 (C.sub.5H-arom.), 139.08 (C.sub.14-arom.), 129.27 (C.sub.2-arom.), 127.40 (C.sub.8H-arom.), 127.23 (C.sub.11H-arom.), 122.51 (C.sub.15H-arom.), 118.77 (C.sub.3H-arom.), 117.72 (C.sub.10H-arom.), 116.55 (C.sub.4H-arom.), 115.09 (C.sub.7-arom.), 108.96 (C.sub.12H-arom.), 65.98 (C.sub.17H), 45.02 (C.sub.18), 27.20 (C.sub.19H.sub.3), 25.21 (C.sub.20H.sub.3).

Cyclohexyl-Hydroindole Moiety

3-(spiro[cyclohexane-1,3-indolin]-2-yl)-1H-indole (Procedure 1)

[0235]

TABLE-US-00017 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.8 13 534 CA 2-8 F18-23 (yield = 47%) IC.sub.50 (PSA) = 1.25 [00474] (Beige Solid) t.sub.R (HPLC) = 4.39 minMS (ESI+) m/z = 303.1775 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.21H.sub.23N.sub.2, m/z = 303.1856; found, 303.1852 .sup.1H NMR (400 MHz, DMSO-d6): (ppm) = 10.92 (s, 1H, H.sub.12), 7.32 (d, J = 8.0 Hz, 1H, H.sub.18), 7.27 (d, J = 2.4 Hz, 1H, H.sub.11), 7.17 (d, J = 7.1 Hz, 1H, H.sub.6), 7.02-6.96 (m, 3H, H.sub.2,15,17), 6.78 (td, J = 7.6, 0.8 Hz, 1H, H.sub.16), 6.61 (td, J = 7.4, 1.0 Hz, 1H, H.sub.1), 6.53 (d, J = 7.4 Hz, 1H, H.sub.3), 5.71 (s, 1H, H.sub.7), 4.83 (s, 1H, H.sub.8), 1.82-1.14 (m, 2H, H.sub.19,20,21,22,23). .sup.13C NMR (101 MHz, DMSO-d6): (ppm) = 151.59 (C.sub.4-arom.), 137.65 (C.sub.5-arom.), 137.07 (C.sub.13-arom.), 127.58 (C.sub.2H-arom.), 126.78 (C.sub.14-arom.), 124.83 (C.sub.11H-arom.), 123.58 (C.sub.6H-arom.), 121.08 (C.sub.17H-arom.), 120.68 (C.sub.15H-arom.), 118.75 (C.sub.16H- arom.), 117.00 (C.sub.1H-arom.), 115.58 (C.sub.10-arom.), 111.86 (C.sub.18H-arom.), 108.32 (C.sub.3H-arom.), 65.96 (C.sub.8H), 48.29 (C9), 37.43 (C.sub.19H.sub.2), 31.94 (C.sub.23H.sub.2), 25.99 (C.sub.21H.sub.2), 22.96 (C.sub.20H.sub.2), 22.81 (C.sub.22H.sub.2).

3-(spiro[cyclohexane-1,3-indolin]-2-yl)-5-methyl-1H-indole (Procedure 1)

[0236]

TABLE-US-00018 VPC Number LabBook Code IC50 (eGFP) = 3.2 13 548 CA 2-72 F12-18 (yield = 69%) IC50 (PSA) = 4.24 [00475] (Beige Solid) tR (HPLC) = 4.57 min(MS (ESI+) m/z = 317.1950 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.22H.sub.25N.sub.2, m/z = 317.2012; found, 317.2008 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.78 (d, J = 1.4 Hz, 1H, H.sub.9), 7.22-7.19 (m, 2H, , H.sub.3,8), 7.17 (d, J = 7.6 Hz, 1H, H.sub.15), 7.00 (td, J = 7.6, 1.2 Hz, 1H, H.sub.11), 6.82 (dd, J = 8.3, 1.5 Hz, 1H, H.sub.4), 6.75 (br s, 1H, H.sub.6), 6.62 (td, J = 7.4, 1.0 Hz, 1H, H.sub.10), 6.53 (d, J = 7.6 Hz, 1H, H.sub.12), 5.65 (s, 1H, H.sub.16), 4.78 (s, 1H, H.sub.17), 2.18 (s, 3H, H.sub.24), 1.80-1.16 (m, 10H, H.sub.19,20,21,22,23). 13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 151.69 (C.sub.13-arom.), 137.72 (C.sub.14-arom.), 135.43 (C.sub.2-arom.), 127.45 (C.sub.11H-arom.), 127.03 (C.sub.5-arom.), 126.85 (C.sub.1-arom.), 124.83 (C.sub.8H-arom.), 123.64 (C.sub.15H-arom.), 122.62 (C.sub.4H-arom.), 120.51 (C.sub.6H-arom.), 116.95 (C.sub.10H-arom.), 114.98 (C.sub.7- arom.), 111.51 (C.sub.3H-arom.), 108.44 (C.sub.12H-arom.), 66.18 (C.sub.17H), 48.25 (C.sub.18), 37.22 (C.sub.19H.sub.2), 31.96 (C.sub.23H.sub.2), 26.00 (C.sub.21H.sub.2), 23.01 (C.sub.20H.sub.2), 22.75 (C.sub.22H.sub.2), 21.88 (C.sub.24H.sub.3).

3-(spiro[cyclohexane-1,3-indolin]-2-yl)-7-methyl-H-indole (Procedure 1)

[0237]

TABLE-US-00019 VPC Number LabBook Code IC.sub.50 (eGFP) = 1.7 13 549 CA 2-73 F9-15 (yield = 72%) IC.sub.50 (PSA) = 2.57 [00476] (Beige Solid) t.sub.R (HPLC) = 4.58 minMS (ESI+) m/z = 317.1932 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.22H.sub.25N.sub.2, M/Z = 317.2012; found, 317.2022 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.88 (s, 1H, H.sub.9), 7.25 (d, J = 2.5 Hz, 1H, H.sub.8), 7.16 (d, J = 7.0 Hz, 1H, H.sub.15), 6.98 (td, J = 7.6, 1.2 Hz, 1H, H.sub.11), 6.85 (d, J = 7.9 Hz, 1H, H.sub.6), 6.80 (d, J = 7.0 Hz, 1H, H.sub.4), 6.70 (t, J = 7.6 Hz, 1H, H.sub.5), 6.60 (td, J =7.4, 1.0 Hz, 1H, H.sub.10), 6.53 (dd, J = 7.6, 0.4 Hz, 1H, H.sub.12),5.67 (s, 1H, H.sub.16), 4.82 (s, 1H, H.sub.17), 2.43 (s, 3H, H.sub.24), 1.83-1.17 (m, 10H, H.sub.19,20,21,22,23). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 151.60 (C.sub.13-arom.), 137.67 (C.sub.14-arom.), 136.53 (C.sub.2-arom.), 127.56 (C.sub.11H-arom.), 126.48 (C.sub.1-arom.), 124.52 (C.sub.8H-arom.), 123.60 (C.sub.15H-arom.), 121.61 (C.sub.4H-arom.), 120.80 (C.sub.3-arom.), 118.95 (C.sub.5H-arom.), 118.30 (C.sub.6H-arom.), 116.98 (C.sub.10H- arom.), 116.02 (C.sub.7-arom.), 108.33 (C.sub.12H-arom.), 66.00 (C.sub.17H), 48.28 (C.sub.18), 37.44 (C.sub.19H.sub.2), 31.95 (C.sub.23H.sub.2), 26.00 (C.sub.21H.sub.2), 22.97 (C.sub.20H.sub.2), 22.80 (C.sub.22H.sub.2), 17.25 (C.sub.24H.sub.3).

3-(spiro[cyclohexane-1,3-indolin]-2-yl)-6-(benzyloxy)-1H-indole (Procedure 1)

[0238]

TABLE-US-00020 VPC Number LabBook Code IC.sub.50 (eGFP) = 11.8 13 550 CA 2-76 F13-24 (yield = 55%) IC.sub.50 (PSA) = No Data [00477] (Beige Solid) t.sub.R (HPLC) = 5.07 minMS (ESI+) m/z = 409.2254 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.28H.sub.29N.sub.2O, m/z = 409.2274; found, 409.2278 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.72 (d, J = 1.7 Hz, 1H, H.sub.12), 7.46- 7.42 (m, 2H, H.sub.22,26), 7.41-7.36 (m, 2H, H.sub.23,25), 7.34-7.30 (m, 1H, , H.sub.24), 7.17- 7.12 (m, 2H, , H.sub.6,11), 6.98 (td, J = 7.6, 1.2 Hz, 1H, H.sub.2), 6.89 (d, J = 2.2 Hz, 1H, H.sub.15), 6.82 (br d, J = 8.7 Hz, 1H, H.sub.18), 6.60 (td, J = 7.4, 1.0Hz, 1H, H.sub.1), 6.54-6.50 (m, 2H, , H.sub.3-17), 5.67 (s, 1H, H.sub.7), 5.07 (s, 2H, H.sub.20), 4.76 (s, 1H, H.sub.8), 1.80-1.15 (m, 10H, H.sub.19,20,21,22,23). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 154.56 (C.sub.16-arom.), 151.55 (C.sub.4-arom.), 138.16 (C.sub.21-arom.), 137.71 (C.sub.5-arom.), 137.65 (C.sub.13-arom.), 128.82 (C.sub.23,25H-arom.), 128.04 (C.sub.24H-arom.), 127.88 (C.sub.22,26H-arom.), 127.58 (C.sub.2H-arom.), 123.67 (C.sub.6H- arom.), 123.54 (C.sub.11H-arom.), 121.34 (C.sub.14-arom.), 121.31 (C.sub.18H-arom.), 116.98 (C.sub.1H-arom.), 115.58 (C.sub.10-arom.), 109.47 (C.sub.17H-arom.), 108.32 (C.sub.3H-arom.), 96.43 (C.sub.15H-arom.), 69.87 (C.sub.20H.sub.2), 66.04 (C.sub.8H), 48.22 (C.sub.9), 37.40 (C.sub.19H.sub.2), 31.91 (C.sub.23H.sub.2), 25.99 (C.sub.21H.sub.2), 22.95 (C.sub.20H.sub.2), 22.83 (C.sub.22H.sub.2).

3-(spiro[cyclohexane-1,3-indolin]-2-yl)-6-hydroxy-1H-indole (Procedure 2)

[0239]

TABLE-US-00021 VPC Number LabBook Code IC.sub.50 (eGFP) = 15.5 13 551 CA 2-83 F2-7 (yield = 38%) IC.sub.50 (PSA) = No Data [00478] (Beige Solid) t.sub.R (HPLC) = 3.57 minMS (ESI+) m/z = 319.1824 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.21H.sub.23N.sub.2O, m/z = 319.1805; found, 319.1802 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.51 (d, J = 1.5 Hz, 1H, H.sub.12), 8.79 (s, 1H, H.sub.24), 7.15 (d, J = 7.0 Hz, 1H, H.sub.6), 7.04 (d, J = 2.3 Hz, 1H, H.sub.11), 6.97 (td, J = 7.6, 1.2 Hz, 1H, H.sub.2), 6.72 (d, J = 8.5 Hz, 1H, H.sub.18), 6.67 (d, J =2.0 Hz, 1H, H.sub.15), 6.59 (td, J = 7.4, 1.0 Hz, 1H, H.sub.1), 6.51 (d, J = 7.7 Hz, 1H,H.sub.3), 6.30 (dd, J = 8.6, 2.2 Hz, 1H, H.sub.17), 5.64 (s, 1H, H.sub.7), 4.73 (s, 1H, H.sub.8), 1.81-1.16 (m, 10H, H.sub.19,20,21,22,23). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 153.10 (C.sub.16-arom.), 151.57 (C.sub.4-arom.), 138.21 (C.sub.13-arom.), 137.70 (C.sub.5-arom.), 127.52 (C.sub.2H-arom.), 123.55 (C.sub.6H- arom.), 122.74 (C.sub.11H-arom.), 121.06 (C.sub.18H-arom.), 120.26 (C.sub.14-arom.), 116.91 (C.sub.1H-arom.), 115.43 (C.sub.10- arom.), 109.35 (C.sub.17H-arom.), 108.29 (C.sub.3H-arom.), 96.85 (C.sub.15H-arom.), 66.16 (C.sub.8H), 48.18 (C.sub.9), 37.38 (C.sub.19H.sub.2), 31.91 (C.sub.23H.sub.2), 26.01 (C.sub.21H.sub.2), 22.97 (C.sub.20H.sub.2), 22.83 (C.sub.22H.sub.2).

3-(spiro[cyclohexane-1,3-indolin]-2-yl)-7-hydroxy-1H-indole (Procedure 2)

[0240]

TABLE-US-00022 VPC Number LabBook Code IC.sub.50 (eGFP) = 1.1 13 552 CA 2-84 Precipitate IC.sub.50 (PSA) = 1.14 (yield = 28%) [00479] (Brown Solid) tR (HPLC) = 3.81 minMS (ESI+) m/z = 319.1728 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.21H.sub.23N.sub.2O, m/z = 319.1805; found, 319.1814 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 10.72 (d, J = 1.8 Hz, 1H, H.sub.12), 9.42 (s, 1H, H.sub.24), 7.14 (d, J = 7.1 Hz, 1H, H.sub.6), 7.12 (d, J = 2.5 Hz, 1H, H.sub.11), 6.97 (td, J = 7.6, 1.2 Hz, 1H, H.sub.2), 6.59 (m, 2H, H.sub.1,17), 6.52 (m, 2H, H.sub.3,18), 6.42 (dd, J = 7.4, 0.8 Hz, 1H, H.sub.16), 5.65 (s, 1H, H.sub.7), 4.79 (s, 1H, H.sub.8), 1.82-1.16 (m, 10H, H.sub.19,20,21,22,23). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 151.60 (C.sub.4- arom.), 143.87 (C.sub.15-arom.), 137.66 (C.sub.5-arom.), 128.78 (C.sub.14-arom.), 127.50 (C.sub.2H-arom.), 127.06 (C.sub.13-arom.), 124.10 (C.sub.11H-arom.), 123.60 (.sub.C6H-arom.), 119.38 (C.sub.17H- arom.), 116.93 (C.sub.1H-arom.), 115.94 (C.sub.10-arom.), 111.78 (C.sub.18H-arom.), 108.29 (C.sub.3H-arom.), 105.41 (C.sub.16H-arom.), 65.88 (C.sub.8H), 48.33 (C.sub.9), 37.45 (C.sub.19H.sub.2), 31.93 (C.sub.23H.sub.2), 26.00 (C.sub.21H.sub.2), 22.98 (C.sub.20H.sub.2), 22.79 (C.sub.22H.sub.2).

Unexpected CompoundsGeneral Procedure 7

[0241] Phenylhydrazine (1.0 eq) aldehyde (isobutyraldehyde or cyclohexanecarboxaldehyde) (1.0 eq) were diluted in AcOH (0.1 M). The mixture was heated at 65 C. for 2 h (until complete conversion). Then, 7-azaindole or 1,5,6,7-Tetrahydro-4H-indol-4-one (1.0 eq) was added and the reaction mixture was stirred additional 24 h at 100 C. (until complete conversion). Acetic acid was removed under vacuo. Then, the residue was poured with H.sub.2O and neutralized at pH 7 with sat. NaHCO.sub.3 solution. The aqueous layer was extracted with AcOEt (3) and organic layers were combined, washed with brine, dried over Na.sub.2SO.sub.4 and evaporated under reduced pressure. Then, crude was purified by automated combi-flash to afford the good compound.

3-(3,3-dimethyl-3H-indol-2-yl)-1H-pyrrolo[2,3-b]pyri dine (Procedure 7)

[0242]

TABLE-US-00023 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.7 13 537 CA 2-39 F9-15 (yield = 25%) IC.sub.50 (PSA) = 0.81 [00480] (Yellow Solid) t.sub.R (HPLC) = 3.17 minMS (ESI+) m/z = 262.1345 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.17H.sub.16N.sub.3, m/z =262.1339; found, 262.1345 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 12.40 (s, 1H, H.sub.14), 8.94 (dd, J = 7.9, 1.7 Hz, IH, H.sub.18), 8.40 (s, IH, H.sub.13), 8.35 (dd, J = 4.6, 1.6 Hz, 1H, H.sub.20), 7.56 (d, J = 7.5 Hz, 1H, H.sub.3), 7.49 (d, J = 6.8 Hz, 1H, H.sub.6), 7.32 (td, J = 7.6, 1.2 Hz, 1H, H.sub.2), 7.28 (dd, J = 7.9, 4.7 Hz, 1H, H.sub.19), 7.20 (td, J = 7.4, 1.0 Hz, 1H, H.sub.1), 1.54 (s, 6H, H10,11). .sup.3C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 180.97 (C.sub.8), 154.77 (C.sub.4-arom.), 149.39 (C.sub.15-arom.), 146.90 (C.sub.5-arom.), 144.50 (C.sub.20H-arom.), 131.69 (C.sub.18H-arom.), 130.45 (C.sub.13H-arom.), 127.92 (C.sub.2H-arom.), 124.80 (C.sub.1H-arom.), 121.61 (C.sub.6H- arom.), 119.71 (C.sub.3H-arom.), 119.05 (C.sub.16-arom.), 117.73 (C.sub.19H-arom.), 108.26 (C.sub.12-arom.), 53.39 (C.sub.9), 25.82 (C.sub.10,11).

Tetrahydro-3-(3,3-dimethyl-3H-indol-2-yl)-1H-indol-4-one (Procedure 7)

[0243]

TABLE-US-00024 VPC Number LabBook Code IC.sub.50 (eGFP) = No Data 13 539 CA 2-48 F19-22 (yield = 9%) IC.sub.50 (PSA) = No Data [00481] (Yellow Solid) t.sub.R (HPLC) = 3.54 minMS (ESI+) m/z = 279.1498 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.18H.sub.19N.sub.2O, m/z = 279.1492; found, 279.1498 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 12.27 (s, 1H, H.sub.14), 7.54-7.48 (m, 2H, H.sub.3,6), 7.33 (td, J = 7.6, 1.3 Hz, 1H, H.sub.2), 7.22 (td, J = 7.4, 1.0 Hz, 1H, H.sub.1), 7.05 (d, J = 1.8 Hz, 1H, H.sub.13), 2.85 (t, J = 6.1 Hz, 2H, H.sub.17), 2.39 (t, J = 6.4 Hz, 2H, H.sub.17), 2.09-2.02 (m, 2H, H.sub.18), 1.46 (s, 6H, H.sub.10,11). .sup.3C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 193.35 (C.sub.20O), 176.21 (C.sub.8), 153.76 (C.sub.4-arom.), 148.19 (C.sub.15-arom.), 147.25 (C.sub.5-arom.), 128.13 (C.sub.2H-arom.), 126.38 (C.sub.12-arom.), 125.40 (C.sub.1H-arom.), 121.96 (C.sub.6H-arom.), 121.76 (C.sub.16-arom.), 119.76 (C.sub.3H-arom.), 109.82 (C.sub.13H-arom.), 52.57 (C.sub.9), 38.25 (C.sub.19H.sub.2), 25.49 (C.sub.10,11H.sub.3), 23.71 (C.sub.18H.sub.2), 22.70 (C.sub.17H.sub.2).

3-(spiro[cyclohexane-1,3-indolin]-2-yl)-1H-pyrrolo[2,3-b]pyridine (Procedure 7)

[0244]

TABLE-US-00025 VPC Number LabBook Code IC.sub.50 (eGFP) = 6.6 13 559 CA 2-110 F18-27 IC.sub.50 (PSA) = No Data (yield = 23%) [00482] (Brown Solid) t.sub.R (HPLC) = 3.70 minMS (ESI+) m/z = 302.1654 [(M + H).sup.+] HRMS(ESI+): calculated for C.sub.20H.sub.20N.sub.3, m/z = 302.1652; found, 302.1654 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 12.39 (s, 1H, H.sub.17), 9.00 (dd, J = 7.9, 1.7 Hz, 1H, H.sub.21), 8.45 (d, J = 2.0 Hz, 1H, H.sub.16), 8.35 (dd, J = 4.6, 1.6 Hz, 1H, H.sub.23), 7.87 (d, J = 7.3 Hz, 1H, H.sub.6), 7.62 (dd, J = 7.6, 0.6 Hz, 1H, H.sub.3), 7.38 (td, J = 7.6, 1.0 Hz, 1H,H.sub.2), 7.27 (dd, J = 7.9, 4.7 Hz, 1H, H.sub.22), 7.17 (td, J = 7.5, 1.1Hz, 1H, H.sub.1), 2.34-2.25 (m, 2H, H.sub.10), 2.07- 1.77 (m, 6H, H.sub.11,12,13), 1.32-1.26 (m, 2H, H.sub.14). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 180.61 (C.sub.8), 155.41 (C.sub.4-arom.), 149.19 (C.sub.18-arom.), 145.63 (C.sub.5-arom.), 144.45 (C.sub.23H-arom.), 132.08 (C.sub.21H-arom.), 130.23 (C.sub.16H-arom.), 127.95 (C.sub.2H-arom.), 124.74 (C.sub.6H-arom.), 123.93 (C.sub.1H-arom.), 120.36 (C.sub.3H-arom.), 119.45 (C.sub.19-arom.), 117.71 (C.sub.22H-arom.), 107.92(C.sub.15-arom.), 57.86 (C.sub.9), 33.53 (C.sub.10,14H.sub.2), 24.81 (C.sub.12H.sub.2), 21.89 (CH.sub.11,13H2).

Quinoline MoietyGeneral Procedure 9

[0245] In microwave vessel, quinoline (2.0 eq) and indole (1.0 eq) were mixed together and the system was sealed and placed under nitrogen, after a purge with vacuum/N.sub.2 (3 times). Then, HCl solution 4M in 1,4-dioxane (1.2 eq) was added with the needle immersed in the mixture (exothermic reaction). The reaction mixture was heated with microwave during 2 h at 160 C. The reaction mixture was taken up with a minimum of MeOH and when the residue was dissolved, it was transferred in mixture of AcOEt and saturated NaHCO.sub.3 solution. The resulting solution was extracted and the aqueous phase was washed with AcOEt (2). The organic layers were combined, washed with 0.01 M critic acid solution, saturated NaHCO.sub.3 solution, dried over Na.sub.2SO.sub.4 and concentrated to dryness under reduced pressure. Finally, the crude was purified by automated combi-flash to afford the good compound.

General Procedure 10

[0246] Halogenated-compound (1.0 eq), boronic acid (or boronate) (1.1 eq) and Pd(PPh.sub.3).sub.4 (10% mol) was added in microwave vessel (10-20 mL). The vial was sealed with a cap and the system was purged with vacuum and placed under N.sub.2. Then, the solids were dissolved in mixture of Toluene/EtOH (4.5:2.0, 0.11 M) and purged with vacuum/N.sub.2 one more time. Then, a solution of K.sub.2CO.sub.3 (3.0 eq) in H.sub.2O (1.8 M) was added. The reaction mixture was stirred and heated overnight at 95 C. with oil bath. The reaction mixture was filtered on plug of celite. The filtrate was was poured with water and was extracted with AcOEt (3). The organic layers were combined, washed with brine, dried over Na.sub.2SO.sub.4 and evaporated under reduced pressure. The residue was taken up in DCM/TFA (5:5) for 2 h at r.t. The solvents were evaporated under reduced pressure. The residue was then neutralized with saturated NaHCO.sub.3 solution and extracted with AcOEt (2). The organic layers were washed, dried and concentrated in vacuo. The residue was precipitate in DCM or purified by automated combi-flash to afford the good compound.

2-(1H-indol-3-yl)-4-methylquinoline

[0247]

TABLE-US-00026 VPC Number LabBook Code IC.sub.50 (eGFP) = 5.6 13 547 CA 2-69 F6-11 IC.sub.50 (PSA) = No Data (yield = 62%) [00483] (Beige Solid) t.sub.R (HPLC) = 3.20 minMS (ESI+) m/z = 259.1243 [(M + H).sup.+] Mp = 168-180 C. HRMS (ESI+): calculated for C.sub.18H.sub.15N.sub.2, m/z = 259.1230; found, 259.1237 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.63 (s, 1H, H.sub.14), 8.90-8.85 (m, 1H, H.sub.20), 8.32 (d, J = 2.8 Hz, 1H, H.sub.13), 8.04-7.98 (m, 2H, H.sub.3,6), 7.94 (d, J = 0.9 Hz, 1H, H.sub.9), 7.71 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H, H.sub.2), 7.53-7.44 (m, 2H, H.sub.1,17), 7.24-7.16 (m, 2H, H.sub.18,19), 2.71 (d, J = 0.8 Hz, 3H, H.sub.12). .sup.13C NMR (101 MHz, DMSO-d6): (ppm) = 155.74 (C.sub.8- arom.), 148.21 (C.sub.4-arom.), 143.61 (C.sub.10-arom.), 137.64 (C.sub.15-arom.), 129.51 (C.sub.2H-arom.), 129.39 (C.sub.3H-arom.), 127.98 (C.sub.13H-arom.), 126.42 (C.sub.5-arom.), 126.13 (C.sub.16- arom.), 125.18 (C.sub.1H-arom.), 124.35 (C.sub.6H-arom.), 123.12 (C.sub.20H-arom.), 122.48 (C.sub.18H-arom.), 120.68 (C.sub.19H-arom.), 119.90 (C.sub.9H-arom.), 115.97 (C.sub.11-arom.), 112.16 (C.sub.17H-arom.), 18.76 (C.sub.12H.sub.3).

2-(7-methoxy-1H-indol-3-yl)-4-methylquinoline

[0248]

TABLE-US-00027 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.6 13 554 CA 2-87 F7-10 IC.sub.50 (PSA) = 0.67 (yield = 22%) [00484] (Yellow Solid) t.sub.R (HPLC) = 3.37 minMS (ESI+) m/z = 289.1336 [(M + H).sup.+] Mp = 146-152 C. HRMS (ESI+): calculated for C.sub.19H.sub.17N.sub.2O, m/z = 289.1335; found, 289.1335 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.73 (s, 1H, H.sub.14), 8.45 (d, J = 8.0 Hz, 1H, H.sub.20), 8.21 (d, J = 2.9 Hz, 1H, H.sub.13), 8.03-7.99 (m, 2H, H.sub.3,6), 7.95 (d, J = 0.8 Hz, 1H, H.sub.9), 7.70 (ddd, J = 8.2, 6.8, 1.3 Hz, 1H, H.sub.2), 7.50 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H, H.sub.1), 7.11 (t, J = 7.9 Hz, 1H, H.sub.19), 6.79 (d, J = 7.5 Hz, 1H, H.sub.18), 3.97 (s, 3H, H.sub.22), 2.70 (d, J = 0.8 Hz, 3H, H.sub.12). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 155.23 (C.sub.8- arom.), 147.71 (C.sub.4-arom.), 146.06 (C.sub.17-arom.), 143.11 (C.sub.10-arom.), 129.00 (C.sub.2H-arom.), 128.91 (C.sub.3H-arom.), 127.23 (C.sub.15-arom.), 127.14 (C.sub.16-arom.), 126.97 (C.sub.13H- arom.), 125.95 (C.sub.5-arom.), 124.69 (C.sub.1H-arom.), 123.85 (C.sub.6H-arom.), 120.76 (C.sub.19H-arom.), 119.52 (C.sub.9H-arom.), 116.09 (C.sub.11-arom.), 115.37 (C.sub.20H-arom.), 102.58 (C.sub.18H- arom.), 55.18 (C.sub.22H.sub.3), 18.24 (C.sub.12H.sub.3).

2-(1H-indol-3-yl)quinoline

[0249]

TABLE-US-00028 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.06 13 562 CA 2-128 F8-12 IC.sub.50 (PSA) = 0.14 (yield = 46%) [00485] (Beige Solid) t.sub.R (HPLC) = 2-91 minMS (ESI+) m/z = 245.1073 [(M + H).sup.+] Mp = 184-187 C. HRMS (ESI+): calculated for C.sub.17H.sub.13N.sub.2, m/z = 245.1073; found, 245.1075 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.65 (s, 1H, H.sub.13), 8.88 (d, J = 8.5 Hz, 1H, H.sub.19), 8.35 (d, J = 2.7 Hz, 1H, H.sub.12), 8.26 (d, J = 8.6 Hz, 1H, H.sub.10), 8.06 (d, J = 8.7 Hz, 1H, H.sub.9), 8.04 (d, J = 8.3 Hz, 1H, H.sub.3), 7.89 (d, J = 7.9 Hz, 1H, H.sub.6), 7.72 (t, J = 7.6 Hz, 1H, H.sub.2), 7.51 -7.46 (m, 2H, H1,16), 7.24-7.18 (m, 2H, H.sub.17,18). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 155.56 (C.sub.8- arom.), 147.75 C.sub.4-arom.s), 137.21 (C.sub.14-arom.), 135.59 (C.sub.10H-arom.), 129.34 (C.sub.2H-arom.), 128.34 (C.sub.3H-arom.), 27.79 (C.sub.6H-arom.), 127.61 (C.sub.12H-arom.), 125.80 (C.sub.5- arom.), 125.58 (C.sub.15-arom.), 124.88 (C.sub.1H-arom.), 122.57 (C.sub.19H-arom.), 122.08 (C.sub.17H-arom.), 120.31 (C.sub.18H- arom.), 119.21 (C.sub.9H-arom.), 115.49 (C.sub.11H-arom.), 111.73 (C.sub.16H-arom.).

2-(7-fluoro-1H-indol-3-yl)quinoline (Procedure 9)

[0250]

TABLE-US-00029 VPC Number LabBook CodeIC.sub.50 (eGFP) = 1.6 13 569 CA 3-45 F13-23 Precipitate IC.sub.50 (PSA) = Not Tested (yield = 34%) [00486] (Red Solid) t.sub.R (HPLC) = 3.02 minMS (ESI+) m/z = 263.1009 [(M + H).sup.+] Mp = 152-154 C. HRMS (ESI+ ): calculated for C.sub.17H.sub.12FN.sub.2, m/z = 263.0979; found, 263.0976 .sup.1H NMR (500 MHz, DMSO-d.sub.6): (ppm) = 12.17 (s, 1H, H.sub.13), 8.71 (d,J = 8.0 Hz, 1H, H.sub.19), 8.44 (d, J = 2.8 Hz, 1H, H.sub.12), 8.29 (d, J = 8.7 Hz, 1H, H.sub.10), 8.10 (d, J = 8.7 Hz, 1H, H.sub.9), 8.05 (d, J = 8.3 Hz, 1H, H.sub.3), 7.91 (d, J = 7.5 Hz, 1H, H.sub.6), 7.73 (t, J = 7.5 Hz, 1H, H.sub.2), 7.51 (t, J = 7.5 Hz, 1H, H.sub.1), 7.21-7.15 (m, 1H, H.sub.18), 7.06 (dd, J = 11.4, 7.8 Hz, 1H, H.sub.17). .sup.13C NMR (126 MHz, DMSO-d.sub.6): (ppm) = 155.50 (C.sub.8-arom.), 149.63 (d, J = 243.4 Hz, C.sub.16-arom.), 148.13 (C.sub.4-arom.), 136.29 (C.sub.10H-arom.), 129.92 (C.sub.2H-arom.), 129.85 (d, J = 5.2 Hz, C.sub.15- arom.), 129.18 (C.sub.12H-arom.), 128.90 (C.sub.3H-arom.), 128.14 (C.sub.6H- arom.), 126.41 (C.sub.5-arom.), 125.63 (C.sub.1H-arom.), 125.52 (d, J = 13.2 Hz, C.sub.14-arom.), 121.14 (d, J = 6.2 Hz, C.sub.18H-arom.), 119.76 (C.sub.9H-arom.), 119.30 (d, J = 3.0 Hz, C.sub.19H-arom.), 116.97 (d, J = 1.3 Hz, C.sub.11-arom.), 107.43 (d, J = 15.6 Hz, C.sub.17H-arom.).

2-(7-ethyl-1H-indol-3-yl)quinoline

[0251]

TABLE-US-00030 VPC Number LabBook CodeIC.sub.50 (eGFP) = 0.2 13 567 CA 3-46 P2 F6-13 IC.sub.50 (PSA) = 0.23 (yield = 45%) [00487] (Yellow Solid) t.sub.R (HPLC) = 3.16 minMS (ESI+) m/z = 273.1719 [(M + H).sup.+]. Mp = 159-162 C. HRMS (ESI+: calculated for C.sub.19H.sub.17N.sub.2, m/z = 273.1386; found, 273.1389 .sup.1H NMR (500 MHz, DMSO-d.sub.6): (ppm) = 11.63 (s, 1H, H.sub.13), 8.73 (d, J = 7.9 Hz, 1H, H.sub.19), 8.34 (d, J = 2.9 Hz, 1H, H.sub.12), 8.25 (d, J = 8.7 Hz, 1H, H.sub.10), 8.09 (d, J = 8.7 Hz, 1H, H.sub.9), 8.03 (d, J = 8.4 Hz, 1H, H.sub.3), 7.88 (d, J = 7.2 Hz, 1H, H.sub.6), 7.71 (ddd, J = 8.3, 7.0, 1.4 Hz, 1H, H.sub.2), 7.48 (ddd, J = 7.5, 6.5, 1.0 Hz, 1H, H.sub.1), 7.15 (t, J = 7.8 Hz, 1H, H.sub.18), 7.05 (d, J = 6.9 Hz, 1H, H.sub.17), 2.93 (q, J = 7.5 Hz, 2H, H.sub.20), 1.32 (t, J = 7.5 Hz, 3H, H.sub.21). .sup.13C NMR (126 MHz, DMSO-d.sub.6): (ppm) = 156.14 (C.sub.8-arom.), 148.27 (C.sub.4-arom.), 136.38 (C.sub.14-arom.), 135.97 (C.sub.10H-arom.), 129.76 (C.sub.2H-arom.), 128.86 (C.sub.3H-arom.), 128.07 (C.sub.6H-arom.), 127.98 (C.sub.12H- arom.), 127.62 (C.sub.16-arom.), 126.28 (C.sub.5-arom.), 126.00 (C.sub.15-arom.), 125.30 (C.sub.1H-arom.), 121.28 (C.sub.17H-arom.), 121.08 (C.sub.18H-arom.), 120.74 (C.sub.19H- arom.), 119.80 (C.sub.9H-arom.), 116.39 (C.sub.11-arom.), 24.09 (C.sub.20H.sub.2), 15.01 (C.sub.21H.sub.3).

2-(2-methyl-1H-indol-3-yl)quinoline

[0252]

TABLE-US-00031 VPC Number LabBook CodeIC.sub.50 (eGFP) = 20.0 13 570 CA 3-47 F35-40 (yield = 29%) IC.sub.50 (PSA) = Not Tested [00488] (Brown Solid) t.sub.R (HPLC) = 2.91 minMS (ESI+) m/z = 259.1435 [(M + H).sup.+] Mp = 67-75 C. HRMS (ESI+): calculated for C.sub.18H.sub.15N2, m/z = 259.1230; found, 259.1230 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.48 (s, 1H, H.sub.13), 8.34 (d, J = 8.6 Hz, 1H, H.sub.10), 8.21 (dd, J = 6.5, 2.4 Hz, 1H, H.sub.19), 8.01 (d, J = 8.4 Hz, 1H, H.sub.3), 7.94 (d, J = 7.6 Hz, 1H, H.sub.6), 7.85 (d, J = 8.6 Hz, 1H, H.sub.9), 7.73 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H, H.sub.2), 7.52 (ddd, J = 8.0, 7.0, 1.1 Hz, 1H, H.sub.1), 7.40 (dd, J = 6.4, 2.2 Hz, 1H, H.sub.16), 7.15- 7.11 (m, 2H, H.sub.17,18), 2.77 (s, 3H, H.sub.20). .sup.13C NMR (126 MHz, DMSO-d.sub.6): (ppm) = 156.19 (C.sub.8-arom.), 148.41 (C.sub.4-arom.), 137.38 (C.sub.12-arom.), 136.27 (C.sub.10H-arom.), 135.74 (C.sub.14-arom.), 129.85 (C.sub.2H-arom.), 128.87 (C.sub.3H-arom.), 128.13 (C.sub.6H-arom.), 127.46 (C.sub.15-arom.), 125.97 (C.sub.5-arom.), 125.58 (C.sub.1H- arom.), 121.69 (C.sub.9H-arom.), 121.53 (C.sub.17H-arom.) 120.38 (C.sub.18H-arom.), 120.18 (C.sub.19H-arom.), 112.46 (C.sub.11-arom.), 111.34 (C.sub.16H-arom.), 14.36 (C.sub.20H.sub.3).

2-(6-bromo-1H-indol-3-yl)quinoline

[0253]

TABLE-US-00032 VPC Number LabBook Code IC.sub.50 (eGFP) = 1.3 13 568 CA 3-49 F44-63 Precipitate (yield = 46%) IC.sub.50 (PSA) = 1.56 [00489] t.sub.R (HPLC) = 3.29 minMS (ESI+) m/z = 323.0190, 325.0174 [(M + H).sup.+] Mp = 189-194 C. HRMS (ESI+): calculated for C.sub.17H.sub.12BrN.sub.2, m/z = 323.0178, 325.0159; found, 323.0183, 325.0167 .sup.1H NMR (500 MHz, DMSO-d.sub.6): (ppm) = 11.79 (s, 1H, H.sub.13), 8.84 (d, J = (Yellow Solid) 8.5 Hz, 1H, H.sub.19), 8.39 (d, J = 2.8 Hz, 1H, H.sub.12), 8.28 (d, J = 8.7 Hz, 1H, H.sub.10), 8.05 (m, 2H, H.sub.3, 9), 7.90 (d, J = 7.5 Hz, 1H, H.sub.6), 7.72 (t, J = 7.5 Hz, 1H, H.sub.2), 7.67 (d, J = 1.6 Hz, 1H, H.sub.16), 7.50 (t, J = 7.5 Hz, 1H, H.sub.1), 7.34 (dd, J = 8.5, 1.8 Hz, 1H, H.sub.18). .sup.13C NMR (126 MHz, DMSO-d.sub.6): (ppm) = 155.52 (C.sub.8-arom.), 148.15 (C.sub.4- arom.), 138.58 (C.sub.14-arom.), 136.27 (C.sub.10H-arom.), 129.91 (C.sub.2H-arom.), 129.11 (C.sub.12H-arom.), 128.88 (C.sub.3H-arom.), 128.13 (C.sub.6H-arom.), 126.37 (C.sub.5- arom.), 125.59 (C.sub.1H-arom.), 125.11 (C.sub.15-arom.), 124.82 (C.sub.19H-arom.), 123.65 (C.sub.18H-arom.), 119.57 (C.sub.9H-arom.), 116.11 (C.sub.11-arom.), 115.31 (C.sub.17- arom.), 114.82 (C.sub.16H-arom).

2-(1-methyl-1H-indol-3-yl)quinoline

[0254]

TABLE-US-00033 VPC Number LabBook Code IC.sub.50 (eGFP) = 1.1 13 571 CA 3-56 Precipitate (yield = 53%) IC.sub.50 (PSA) = Not Tested [00490] t.sub.R (HPLC) = 3.05 min MS (ESI+) m/z = 259.1355 [(M + H).sup.+] Mp = 175-179 C. HRMS (ESI+): calculated for C.sub.18H.sub.15N.sub.2, m/z = 259.1230; found, 259.1232 .sup.1H NMR (500 MHz, DMSO-d.sub.6): (ppm) = 8.88 (d, J = 8.5 Hz, 1H, H.sub.19), 8.34 (s, 1H, H.sub.12), 8.27 (d, J = 8.7 Hz, 1H, H.sub.10), 8.03 (d, J = 8.3 Hz, 1H, H.sub.3), 7.98 (d, J = 8.7 Hz, 1H, H.sub.9), 7.89 (d, J = 7.2 Hz, 1H, H.sub.6), 7.72 (t, J = 7.6 Hz, 1H, H.sub.2), (Yellow Solid) 7.54 (d, J = 7.5 Hz, 1H, H.sub.16), 7.49 (t, J = 7.6 Hz, 1H, H.sub.2), 7.29-7.26 (m, 2H, H.sub.17, 18), 3.91 (s, 3H, H.sub.20). .sup.13C NMR (126 MHz, DMSO-d.sub.6): (ppm) = 155.64 (C.sub.8-arom.), 148.28 (C.sub.4- arom.), 138.16 (C.sub.14-arom.), 136.21 (C.sub.10H-arom.), 132.24 (C.sub.12H-arom.), 129.88 (C.sub.2H-arom.), 128.84 (C.sub.3H-arom.), 128.11 (C.sub.6H-arom.), 126.43 (C.sub.15-arom.), 126.27 (C.sub.5-arom.), 125.40 (C.sub.1H-arom.), 123.16 (C.sub.19H-arom.), 122.66 (C.sub.17H- arom.), 121.07 (C.sub.18H-arom.), 119.50 (C.sub.9H-arom.), 115.00 (C.sub.11-arom.), 110.58 (C.sub.16H-arom.), 33.40 (C.sub.20H.sub.3-arom.).

2-(1H-indazol-1-yl)quinoline

[0255]

TABLE-US-00034 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.7 13 572 CA 3-59 F11 (yield = 25%) IC.sub.50 (PSA) = Not Tested [00491] t.sub.R (HPLC) = 4.44 min MS (ESI+) m/z = 246.1019 [(M + H).sup.+] Mp = 91-96 C. HRMS (ESI+): calculated for C.sub.16H.sub.12N.sub.3, m/z = 246.1026; found, 246.1028 .sup.1H NMR (500 MHz, CDCl.sub.3): (ppm) = 9.18 (d, J = 8.5 Hz, 1H, H.sub.16), 8.28 (d, J = 9.0 Hz, 1H, H.sub.9), 8.25-8.21 (m, 2H, H.sub.10, 11), 8.11 (d, J = 8.4 Hz, 1H, H.sub.3), 7.82-7.77 (m, 2H, H.sub.6, 19), 7.72 (ddd, J = 8.3, 7.0, 1.4 Hz, 1H, H.sub.2), 7.59 (ddd, J = (White Solid) 8.3, 7.0, 1.0 Hz, 1H, H.sub.17), 7.48 (ddd, J = 8.1, 7.0, 1.3 Hz, 1H, H.sub.1), 7.32 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H, H.sub.18). .sup.13C NMR (126 MHz, CDCl.sub.3): (ppm) = 152.95 (C.sub.8-arom.), 146.66 (C.sub.4- arom.), 139.00 (C.sub.4-arom.), 138.46 (C.sub.10H-arom.), 137.18 (C.sub.11H-arom.), 130.05 (C.sub.2H-arom.), 128.36 (C.sub.3H-arom.), 128.22 (C.sub.17H-arom.), 127.67 (C.sub.6H-arom.), 126.28 (C.sub.5-arom.), 126.14 (C.sub.15-arom.), 125.51 (C.sub.1H-arom.), 122.95 (C.sub.18H- arom.), 120.82 (C.sub.19H-arom.), 116.03 (C.sub.16H-arom.), 113.48 (C.sub.9H-arom.).

2-(7-methyl-1H-indol-3-yl)quinoline (Procedure 9)

[0256]

TABLE-US-00035 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.095 13 566 CA 3-67 Precipitate (yield = 48%) IC.sub.50 (PSA) = 0.056 [00492] t.sub.R (HPLC) = 3.10 min MS (ESI+) m/z = 259.1255 [(M + H).sup.+] Mp = 146-150 C. HRMS (ESI+): calculated for C.sub.18H.sub.15N.sub.2, m/z = 259.1230; found, 259.1229 .sup.1H NMR (500 MHz, DMSO-d.sub.6): (ppm) = 11.63 (s, 1H), 8.72 (d, J = 7.9 Hz, 1H), 8.35 (d, J = 2.8 Hz, 1H), 8.25 (d, J = 8.7 Hz, 1H), 8.09 (d, J = 8.7 Hz, 1H), 8.03 (d, J = 8.3 Hz, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.74-7.68 (m, 1H), (Yellow Solid) 7.48 (t, J = 7.4 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H), 7.02 (d, J = 7.0 Hz, 1H), 2.54 (s, 3H). .sup.13C NMR (126 MHz, DMSO-d.sub.6): (ppm) = 156.14, 148.27, 137.19, 135.98, 129.77, 128.86, 128.08, 128.02, 126.28, 125.82, 125.31, 123.10, 121.27, 120.98, 120.70, 119.79, 116.41, 17.27.

2-(5-methyl-1H-indol-3-yl)quinoline

[0257]

TABLE-US-00036 VPC Number LabBook Code IC.sub.50 (eGFP) = 3.2 13 577 CA 3-73 Precipitate (yield = 55%) IC.sub.50 (PSA) = 1.73 [00493] t.sub.R (HPLC) = 3.12 min MS (ESI+) m/z = 259.1248 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.18H.sub.15N.sub.2, m/z = 259.1230; found, 259.1218 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 12.64 (s, 1H, H.sub.13), 8.97 (s, 1H, H.sub.12), 8.89 (d, J = 8.1 Hz, 1H, H.sub.10), 8.58 (d, J = 8.2 Hz, 1H, H.sub.3), 8.42 (d, J = 8.9 Hz, 1H, H.sub.9), 8.22 (d, J = 8.0 Hz, 1H, H.sub.6), 8.10 (s, 1H, H.sub.19), 8.02 (t, J = 7.6 Hz, 1H, H.sub.2), 7.77 (t, J = 7.5 Hz, 1H, H.sub.1), 7.52 (d, J = 8.3 Hz, 1H, H.sub.16), 7.18 (dd, J = 8.3, 0.9 Hz, 1H, H.sub.17), 2.51 (s, 3H, H.sub.20). (Yellow Solid) .sup.13C NMR = Done but unreadable and it was the same for every compound made with this procedure

2-(6-fluoro-1H-indol-3-yl)quinoline

[0258]

TABLE-US-00037 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.144 13 576 CA 3-75 Precipitate2 (yield = 30%) IC.sub.50 (PSA) = 0.048 [00494] t.sub.R (HPLC) = 3.08 min MS (ESI+) m/z = 263.1223 [(M + H).sup.+] Mp = 259-266 C. HRMS (ESI+): calculated for C.sub.17H.sub.11FN.sub.2Na, m/z = 285.0798; found, 285.0810 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 8.71 (s, 2H, H.sub.10, 12), 8.49 (s, 1H, H.sub.19), 8.31 (s, 2H, H.sub.3, 9), 8.14 (s, 1H, H.sub.6), 7.95 (s, 1H, H.sub.2), 7.71 (s, (Yellow Solid) 1H, H.sub.1), 7.40 (d, J = 8.3 Hz, 1H, H.sub.16), 7.18 (t, J = 8.5 Hz, 1H, H.sub.18). .sup.13C NMR = Done but unreadable and it was the same for every compound made with this procedure, even proton spectra looked bad.

2-(6-(trifluoromethyl)-1H-indol-3-yl)quinoline

[0259]

TABLE-US-00038 VPC Number LabBook Code IC.sub.50 (eGFP) = 2.9 13 580 CA 3-78 Precipitate (yield = 8%) IC.sub.50 (PSA) = Not Tested [00495] t.sub.R (HPLC) = 3.50 min MS (ESI+) m/z = 313.0949 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.18H.sub.12F.sub.3N.sub.2, m/z = 313.0947; found, 313.0947 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 8.83 (s, 1H, H.sub.12), 8.75 (s, 2H, H.sub.10, 19), 8.31 (s, 2H, H.sub.3, 9), 8.11 (s, 1H, H.sub.6), 7.93 (s, 2H, H.sub.2, 16), 7.70 (s, 1H, H.sub.1), 7.58 (d, J = 7.9 Hz, 1H, H.sub.18). (Yellow Solid) .sup.13C NMR Done but unreadable and it was the same for every compound made with this procedure, even proton spectra looked bad.

2-(7-methyl-1H-indazol-1-yl)quinoline

[0260]

TABLE-US-00039 VPC Number LabBook Code IC.sub.50 (eGFP) = 3.5 13 575 CA 3-90 F4-12 Precipitate (yield = 21%) IC.sub.50 (PSA) = 1.36 [00496] t.sub.R (HPLC) = 4.54 min MS (ESI+) m/z = 260.1176 [(M + H).sup.+] Mp = 147-152 C. HRMS (ESI+): calculated for C.sub.17H.sub.14N.sub.3, m/z = 260.1182; found, 260.1172 .sup.1H NMR (500 MHz, DMSO-d.sub.6): (ppm) = 9.42 (s, 1H, H.sub.11), 8.69 (d, J = 8.8 Hz, 1H, H.sub.10), 8.49 (d, J = 8.8 Hz, 1H, H.sub.9), 8.12 (d, J = 8.0 Hz, 1H, H.sub.6), 8.09 (d, J = 8.5 Hz, 1H, H.sub.3), 7.89 (ddd, J = 8.0, 6.5, 1.0 Hz, 1H, H.sub.2), 7.71-7.65 (m, (Pale Yellow Solid) 2H, H.sub.1, 9), 7.14 (d, J = 6.6 Hz, 1H, H.sub.17), 7.05 (dd, J = 8.3, 6.7 Hz, 1H, H.sub.18), 2.62 (s, 3H, H.sub.20). .sup.13C NMR (126 MHz, DMSO-d.sub.6): (ppm) = 150.74 (C.sub.14-arom.), 150.56 (C.sub.8- arom.), 146.38 (C.sub.4-arom.), 140.60 (C.sub.10H-arom.), 131.47 (C.sub.2H-arom.), 128.69 C.sub.6H-arom.), 128.66 (C.sub.3H-arom.), 127.92 (C.sub.5-arom.), 127.89 (C.sub.16-arom.), 127.33 (C.sub.1H-arom.), 126.89 (C.sub.17H-arom.), 123.64 (C.sub.18H-arom.), 122.62 (C.sub.15- arom.), 121.65 (C.sub.11H-arom.), 119.49 (C.sub.19H-arom.), 113.50 (C.sub.9H-arom.), 17.22 (C.sub.20H.sub.3).

2-(6-(benzyloxy)-1H-indol-3-yl)quinoline

[0261]

TABLE-US-00040 VPC Number LabBook Code IC.sub.50 (eGFP) = 5.3 13 589 CA 3-94 Precipitate (yield = 20%) IC.sub.50 (PSA) = Not Tested [00497] t.sub.R (HPLC) = 3.66 min MS (ESI+) m/z = 351.1707 [(M + H).sup.+] Mp = 264-269 C. HRMS (ESI+): calculated for C.sub.24H.sub.19N.sub.2O, m/z = 351.1492; found, 351.1494 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 12.50 (s, 1H, H.sub.13), 8.85 (s, 2H, H.sub.10), 8.52 (d, J = 5.6 Hz, 1H, H.sub.3), 8.37 (d, J = 8.7 Hz, 1H, H.sub.9), 8.20 (d, J = 7.2 Hz, 2H, H.sub.6, 19), 8.00 (t, J = 7.3 Hz, 1H, H.sub.2), 7.75 (t, J = 7.3 Hz, 1H, H.sub.1), (Orange Solid) 7.51 (d, J = 7.2 Hz, 2H, H.sub.22, 26), 7.42 (t, J = 7.4 Hz, 2H, H.sub.23, 25), 7.35 (t, J = 7.3 Hz, 1H, H.sub.24), 7.19 (d, J = 1.7 Hz, 1H, H.sub.16), 7.06 (dd, J = 8.8, 2.0 Hz, 1H, H.sub.18), 5.21 (s, 2H, H.sub.27). .sup.13C NMR Done but unreadable and it was the same for every compound made with this procedure, even proton spectra looked bad.

3-(pyridin-3-yl)-1H-pyrrolo[2,3-c]pyridine (Procedure 10)

[0262]

TABLE-US-00041 VPC Number LabBook Code IC.sub.50 (eGFP) = 4.9 13 581 CA 3-105 Purified (yield = 64%) IC.sub.50 (PSA) = Not Tested [00498] t.sub.R (HPLC) = 1.45 min MS (ESI+) m/z = 196.0861 [(M + H).sup.+] Mp = 71-80 C. HRMS (ESI+): calculated for C.sub.12H.sub.10N.sub.3, m/z = 196.0869; found, 196.0862 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 12.21 (s, 1H, H.sub.13), 8.99 (s, 1H, H.sub.3), 8.90 (s, 1H, H.sub.9), 8.49 (s, 1H, H.sub.2), 8.25 (s, 1H, H.sub.7), 8.21 (s, 1H, H.sub.14), 8.16- 8.12 (m, 1H, H.sub.5), 7.94 (d, J = 4.0 Hz, 1H, H.sub.12), 7.48 (dd, J = 7.7, 4.8 Hz, 1H, (White Solid) H.sub.6). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 147.26 (C.sub.3H-arom.), 146.80 (C.sub.2H- arom.), 137.78 (C.sub.7H-arom.), 134.44 (C.sub.9H-arom.), 133.82 (C.sub.10-arom.), 133.41 (C.sub.5H-arom.), 130.47 (C.sub.4-arom.), 129.35 (C.sub.11-arom.), 128.95 (C.sub.14H-arom.), 123.95 (C.sub.6H-arom.), 113.91 (C.sub.12H-arom.), 111.96 (C.sub.15-arom.).

3-(pyridin-3-yl)-1H-indazole (Procedure 10)

[0263]

TABLE-US-00042 VPC Number LabBook Code IC.sub.50 (eGFP) = No Data 13 590 CA 3-106 Precipitate (yield = 45%) IC.sub.50 (PSA) = No Data [00499] t.sub.R (HPLC) = 2.53 min MS (ESI+) m/z = 196..0889 [(M + H).sup.+] Mp = 176-179 C. HRMS (ESI+): calculated for C.sub.12H.sub.10N.sub.3, m/z = 196.0869; found, 196.0871 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 9.21 (d, J = 1.5 Hz, 1H, H.sub.5), 8.62 (dd, J = 4.7, 1.6 Hz, 1H, H.sub.2), 8.38 (td, J = 8.4, 1.8 Hz, 1H, H.sub.3), 8.12 (d, J = 8.2 Hz, 1H, H.sub.12), 7.64 (d, J = 8.4 Hz, 1H, H.sub.9), 7.56 (ddd, J = 7.9, 4.8, 0.7 (White Solid) Hz, 1H, H.sub.1), 7.45 (ddd, J = 8.4, 7.2, 0.6 Hz, 1H, H.sub.8), 7.25 (ddd, J = 7.8, 6.6, 0.6 Hz, 1H, H.sub.8). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 148.59 (C.sub.2H-arom.), 147.42 (C.sub.5H-arom.), 141.50 (C.sub.10-arom.), 140.45 (C.sub.4-arom.), 133.90 (C.sub.3H-arom.), 129.63 (C.sub.15-arom.), 126.35 (C.sub.8H-arom.), 124.02 (C.sub.1H-arom.), 121.41 (C.sub.7H-arom.), 120.43 (C.sub.12H-arom.), 120.06 (C.sub.11-arom.), 110.72 (C.sub.9H-arom.).

2-(7-bromo-1H-indol-3-yl)quinoline

[0264]

TABLE-US-00043 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.052 13 582 CA 3-107 F9-17 Precipitate (yield = 20%) IC.sub.50 (PSA) = 0.041 [00500] t.sub.R (HPLC) = 3.25 min MS (ESI+ ) m/z = 323.0177, 325.0158 [(M + H).sup.+] Mp = 178-180 C. HRMS (ESI+): calculated for C.sub.17H.sub.12BrN.sub.2, m/z = 323.0178, 325.0159; found, 323.0172, 325.0153 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.87 (s, 1H, H.sub.13), 8.94 (d, J = 7.9 Hz, 1H, H.sub.19), 8.42 (d, J = 2.8 Hz, 1H, H.sub.12), 8.29 (d, J = 8.6 Hz, 1H, H.sub.10), (Pale Yellow Solid) 8.13 (d, J = 8.7 Hz, 1H, H.sub.9), 8.06 (d, J = 8.4 Hz, 1H, H.sub.3), 7.91 (d, J = 8.0 Hz, 1H, H.sub.6), 7.73 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H, H.sub.2), 7.51 (ddd, J = 7.8, 6.6, 0.6 Hz, 1H, H.sub.1), 7.45 (dd, J = 7.5, 0.5 Hz, 1H, H.sub.17), 7.17 (t, J = 7.8 Hz, 1H, H.sub.18). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 155.00 (C.sub.8-arom.), 147.65 (C.sub.4- arom.), 135.81 (C.sub.10H-arom.), 135.51 (C.sub.14H-arom.), 129.43 (C.sub.2H-arom.), 128.78 (C.sub.12H-arom.), 128.46 (C.sub.3H-arom.), 127.65 (C.sub.6H-arom.), 127.36 (C.sub.15- arom.), 125.96 (C.sub.5-arom.), 125.19 (C.sub.1H-arom.), 124.73 (C.sub.17H-arom.), 122.17 (C.sub.19H-arom.), 121.76 (C.sub.18H-arom.), 119.31 (C.sub.9H-arom.), 116.67 (C.sub.11-arom.), 104.34 (C.sub.16-arom.).

2-(1H-pyrrolo[2,3-c]pyridin-3-yl)quinoline (Procedure 10)

[0265]

TABLE-US-00044 VPC Number LabBook Code IC.sub.50 (eGFP) = 1.1 13 583 CA 3-109 F22-31 Precipitate (yield = 19%) IC.sub.50 (PSA) = 0.93 [00501] t.sub.R (HPLC) = 2.52 min MS (ESI+) m/z = 246.1028 [(M + H).sup.+] Mp = <270 C. HRMS (ESI+): calculated for C.sub.16H.sub.12N.sub.3, m/z = 246.1026; found, 246.1017 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 12.12 (s, 1H, H.sub.17), 8.85 (d, J = 0.8 Hz, 1H, H.sub.13), 8.72 (dd, J = 5.4, 0.9 Hz, 1H, H.sub.16), 8.58 (d, J = 2.4 Hz, 1H, H.sub.18), 8.31 (m, 2H, H.sub.10, 11), 8.09 (d, J = 8.7 Hz, 1H, H.sub.9), 8.07 (d, J = 8.3 Hz, 1H, H.sub.3), (White Solid) 7.92 (d, J = 8.0 Hz, 1H, H.sub.6), 7.74 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H, H.sub.2), 7.52 (ddd, J = 7.8, 7.2, 1.2 Hz, 1H, H.sub.1). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 154.73 (C.sub.8-arom.), 147.73 (C.sub.4- arom.), 139.35 (C.sub.11H-arom.), 136.01 (C.sub.10H-arom.), 134.88 (C.sub.13H-arom.), 134.37 (C.sub.14-arom.), 130.89 (C.sub.18H-arom.), 129.92 (C.sub.15-arom.), 129.51 (C.sub.2H-arom.), 128.46 (C.sub.3H-arom.), 127.69 (C.sub.6H-arom.), 125.97 (C.sub.5-arom.), 125.24 (C.sub.1H- arom.), 119.03 (C.sub.9H-arom.), 116.77 (C.sub.16H-arom.), 115.22 (C.sub.19-arom.).

tert-butyl 3-iodo-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

[0266]

TABLE-US-00045 Intermediate LabBook Code CA 3-111 F1-14 (yield = 86%) [00502] t.sub.R (HPLC) = 4.66 min MS (ESI+) m/z = 345.0074 [(M + H).sup.+] .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 8.44 (dd, J = 4.7, 1.5 Hz, 1H, H.sub.2), 8.03 (s, 1H, H.sub.8), 7.79 (dd, J = 7.9, 1.6 Hz, 1H, H.sub.6), 7.39 (dd, J = 7.9, 4.7 Hz, 1H, H.sub.1), 1.62 (s, 9H, H.sub.13, 14, 15). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 147.14 (C.sub.16 = O), 147.04 (C.sub.4- arom.), 146.16 (C.sub.2H-arom.), 131.54 (C.sub.8H-arom.), 130.04 (C.sub.6H-arom.), 125.25 (C.sub.5-arom.), 120.04 (C.sub.1H-arom.), 84.57 (C.sub.12-(CH.sub.3).sub.3), 63.79 (C.sub.9-arom.), 28.08 (Brown Oil) (C.sub.13, 14, 15H.sub.3).

3-(1H-pyrrolo[3,2-c]pyridin-3-yl)quinoline (Procedure 10)

[0267]

TABLE-US-00046 VPC Number LabBook Code IC.sub.50 (eGFP) = Inactive 13 637 CA 3-115 Precipitate (yield = 51%) IC.sub.50 (PSA) = Inactive [00503] t.sub.R (HPLC) = 2.22 min MS (ESI+) m/z = 246.1020 [(M + H).sup.+] Mp = 233-239 C. HRMS (ESI+): calculated for C.sub.16H.sub.12N.sub.3, m/z = 246.1026; found, 246.1016 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 12.04 (s, 1H, H.sub.13), 9.43 (s, 1H, H.sub.12), 9.37 (d, J = 2.3 Hz, 1H, H.sub.5), 8.76 (d, J = 1.9 Hz, 1H, H.sub.3), 8.31 (d, J = 5.7 Hz, 1H, H.sub.8), 8.19 (d, J = 1.7 Hz, 1H, H.sub.14), 8.13 (d, J = 7.6 Hz, 1H, H.sub.19), 8.03 (White Solid) (d, J = 8.3 Hz, 1H, H.sub.16), 7.72 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H, H.sub.17), 7.63 (ddd, J = 8.0, 7.2, 1.2 Hz, 1H, H.sub.18), 7.51 (dd, J = 5.7, 0.7 Hz, 1H, H.sub.9). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.40 (C.sub.5H-arom.), 146.38 (C.sub.2- arom.), 142.88 (C.sub.12H-arom.), 141.29 (C.sub.8H-arom.), 140.94 (C.sub.10-arom.), 131.31 (C.sub.3H-arom.), 129.08 (C.sub.17H-arom.), 129.04 (C.sub.16H-arom.), 128.62 (C.sub.1- arom.), 128.60 (C.sub.19H-arom.), 128.35 (C.sub.4-arom.), 127.31 (C.sub.18H-arom.), 126.19 (C.sub.14H-arom.), 122.63 (C.sub.11-arom.), 112.66 (C.sub.15-arom.), 107.80 (C.sub.9H- arom.).

3-(5-bromo-2-methoxyphenyl)-1H-pyrrolo[3,2-c]pyri dine (Procedure 10)

[0268]

TABLE-US-00047 VPC Number LabBook Code IC.sub.50 (eGFP) = Inactive 13 638 CA 3-116 Precipitate (yield = quant.) IC.sub.50 (PSA) = Inactive [00504] t.sub.R (HPLC) = 2.91 minMS (ESI+) m/z = 303.0118, 305.0099 [(M + H).sup.+] Mp = <270 C. HRMS (ESI+): calculated for C.sub.14H.sub.12BrN.sub.2O, m/z = 303.0128, 305.0108; found, 303.0119, 305.0100 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 12.03 (s, 1H, H.sub.13), 8.82 (d, J = 0.6 Hz, 1H, H.sub.12), 8.20 (d, J = 5.7 Hz, 1H, H.sub.8), 7.70 (d, J = 2.0 Hz, 1H, H.sub.14), 7.65 (d, J = 2.5 Hz, 1H, H.sub.2), 7.47 (dd, J = 8.8, 2.6 Hz, 1H, H.sub.6), 7.44 (dd, J = 5.7, 1.0 Hz, 1H, H.sub.9), 7.12 (d, J = 8.8 Hz, 1H, H.sub.3), 3.82 (s, 3H, H.sub.18). (White Solid) .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 155.97 (C.sub.5-arom.), 143.25 (C.sub.12H-arom.), 140.41 (C.sub.8H-arom.), 140.06 (C.sub.10-arom.), 132.27 (C.sub.3H- arom.), 130.31 (C.sub.6H-arom.), 127.00 (C.sub.14H-arom.), 126.07 (C.sub.4-arom.), 123.24 (C.sub.11-arom.), 114.24 (C.sub.2H-arom.), 112.46 (C.sub.1-arom.), 110.90 (C.sub.15- arom.), 107.57 (C.sub.9H-arom.), 56.13 (C.sub.18H.sub.3).

3-(7-bromo-1H-indol-3-yl)quinoline (Procedure 10)

[0269]

TABLE-US-00048 VPC Number LabBook Code IC.sub.50 (eGFP) = 1.13 13 653 CA 3-123 Precipitate (yield = 39%) IC.sub.50 (PSA) = 0.29 [00505] t.sub.R (HPLC) = 3.79 minMS (ESI+) m/z = 323.0176, 325.0157 [(M + H).sup.+] Mp = 217-223 C. HRMS (ESI+): calculated for C.sub.17H.sub.12BrN.sub.2, m/z = 323.0178, 325.0159; found, 323.0179, 325.0160 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.86 (s, 1H, H.sub.13), 9.33 (d, J = 2.2 Hz, 1H, H.sub.5), 8.66 (d, J = 1.9 Hz, 1H, H.sub.3), 8.12-8.06 (m, 3H, (Pale Yellow Solid) H.sub.12,14,19), 8.03 (d, J = 8.3 Hz, 1H, H.sub.16), 7.72 (t, J = 8.2 Hz, 1H, H.sub.17), 7.63 (t, J = 7.4 Hz, 1H, H.sub.18), 7.47 (d, J = 7.5 Hz, 1H, H.sub.8), 7.14 (t, J = 7.8 Hz, 1H, H.sub.7). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.63 (C.sub.5H-arom.), 146.32 (C.sub.2-arom.), 135.72 (C.sub.10-arom.), 131.21 (C.sub.3H-arom.), 129.11 (C.sub.17H-arom.), 128.99 (C.sub.1-arom.), 128.86 (C.sub.12H-arom.), 128.57 (C.sub.4-arom.), 128.48 (C.sub.19H-arom.), 127.28 (C.sub.18H-arom.), 127.19 (C.sub.11-arom.), 126.42 (C.sub.14H-arom.), 125.01 (C.sub.8H-arom.), 121.96 (C.sub.7H-arom.), 119.28 (C.sub.12H-arom.), 114.08 (C.sub.15-arom.), 105.30 (C.sub.9-arom.).

3-(7-methyl-1H-indol-3-yl)quinoline (Procedure 10)

[0270]

TABLE-US-00049 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.92 13 654 CA 3-125 Precipitate (yield = 56%) IC.sub.50 (PSA) = 0.16 [00506] t.sub.R (HPLC) = 3.43 minMS (ESI+) m/z = 259.1236 [(M + H).sup.+] Mp = 215-219 C. HRMS (ESI+): calculated for C.sub.18H.sub.15N.sub.2, m/z = 259.1230; found, 259.1234 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.59 (s, 1H, H.sub.13), 9.34 (d, J = 2.3 Hz, 1H, H.sub.5), 8.62 (d, J = 2.1 Hz, 1H, H.sub.3), 8.07 (m, 2H, H.sub.14,19), (White Solid) 8.01 (d, J = 8.4 Hz, 1H, H.sub.16), 7.92 (d, J = 7.9 Hz, 1H, H.sub.12), 7.69 (td, J = 8.4, 1.5 Hz, 1H, H.sub.17), 7.61 (td, J = 8.1, 1.2 Hz, 1H, H.sub.18), 7.12 (t, J = 7.6 Hz, 1H, H.sub.7), 7.03 (d, J = 7.0 Hz, 1H, H.sub.8), 2.54 (s, 3H, H.sub.20). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.68 (C.sub.5H-arom.), 146.10 (C.sub.2-arom.), 136.96 (C.sub.10-arom.), 130.41 (C.sub.3H-arom.), 129.74 (C.sub.17H-arom.), 129.08 (C.sub.16H-arom.), 128.72 (C.sub.1-arom.), 128.64 (C.sub.4-arom.), 128.37 (C.sub.19H-arom.), 127.19 (C.sub.18H-arom.), 125.16 (C.sub.11- arom.), 125.01 (C.sub.14H-arom.), 122.86 (C.sub.8H-arom.), 121.80 (C.sub.9-arom.), 120.77 (C.sub.7H-arom.), 117.24 (C.sub.12H-arom.), 113.06 (C.sub.15H-arom.), 17.30 (C.sub.20H.sub.3).

7-methyl-3-(pyridin-3-yl)-1H-indole (Procedure 10)

[0271]

TABLE-US-00050 VPC Number LabBook Code IC.sub.50 (eGFP) = 1.66 13 655 CA 3-127 F5 Precipitate (yield = 25%) IC.sub.50 (PSA) = 0.61 [00507] t.sub.R (HPLC) = 2.69 minMS (ESI+) m/z = 209.1076 [(M + H).sup.+] Mp = 164-166 C. HRMS (ESI+): calculated for C.sub.14H.sub.13N.sub.2, m/z = 209.1073; found, 209.1075 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.49 (s, 1H, H.sub.13), 8.94 (d, J = 1.7 Hz, 1H, H.sub.5), 8.43 (dd, J = 4.7, 1.5 Hz, 1H, H.sub.2), 8.09 (dt, J = 8.0, 1.9 Hz, 1H, H.sub.3), 7.84 (d, J = 2.7 Hz, 1H, H.sub.14), 7.70 (d, J = 7.8 Hz, 1H, (White Solid) H.sub.12), 7.44 (ddd, J = 7.9, 4.8, 0.6 Hz, 1H), 7.08-6.96 (m, 2H, H.sub.7,8), 2.51 (s, 3H, H.sub.16). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 147.81 (C.sub.5H-arom.), 146.63 (C.sub.2H-arom.), 136.86 (C.sub.10-arom.), 133.75 (C.sub.3H-arom.), 132.32 (C.sub.4-arom.), 124.99 (C.sub.11-arom.), 124.40 (C.sub.14H-arom.), 124.28 (C.sub.1H-arom.), 122.66 (C.sub.8H-arom.), 121.74 (C.sub.9-arom.), 120.62 (C.sub.7H-arom.), 116.87 (C.sub.12H- arom.), 113.02 (C.sub.15-arom.), 17.28 (C.sub.16H.sub.3).

tert-butyl 7-(benzyloxy)-3-iodo-1H-indole-1-carboxylate

[0272]

TABLE-US-00051 Intermediate LabBook Code CA 3-128 F1-4 (yield = 88%) [00508] (Pale Orange Oil) t.sub.R (HPLC) = 5.03 minMS (ESI+) m/z = 450.0575 [(M + H).sup.+] .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 7.84 (s, 1H, H.sub.8), 7.57-7.52 (m, 2H, H.sub.14,18), 7.40-7.27 (m, 4H, H.sub.1,15,16,17), 7.11 (d, J = 7.6 Hz, 1H, H.sub.2), 6.98 (dd, J = 7.8, 0.8 Hz, 1H, H.sub.6), 5.25 (s, 2H, H.sub.12), 1.50 (s, 9H, H.sub.21,22,23). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 148.11 (C.sub.24O), 147.18 (C.sub.3- arom.), 137.44 (C.sub.13-arom.), 134.78 (C.sub.5-arom.), 132.89 (C.sub.8H-arom.), 128.67 (C.sub.15,17H-arom.), 128.16 (C.sub.16H-arom.), 127.88 (C.sub.14,18H-arom.), 124.89 (C.sub.1H-arom.), 124.45 (C.sub.4-arom.), 114.11 (C.sub.6H-arom.), 109.43 (C.sub.2H-arom.), 84.39 (C.sub.20(CH.sub.3).sub.3), 70.58 (C.sub.12H.sub.2), 65.68 (C.sub.9-arom.), 27.68 (C.sub.21,22,23H.sub.3).

5,8-dibromo-2-(7-methyl-1H-indol-3-yl)quinoline (Procedure 9)

[0273]

TABLE-US-00052 VPC Number LabBook Code IC.sub.50 (eGFP) = Inactive 13 679 CA 3-137 F24-30 Precipitate (yield = 20%) IC.sub.50 (PSA) = Inactive [00509] t.sub.R (HPLC) = 5.30 minMS (ESI+) m/z = 414.9448, 416.9430, 418.9416 [(M + H).sup.+] Mp = 218-221 C. HRMS (ESI+): calculated for C.sub.18H.sub.13Br.sub.2N.sub.2, m/z = 414.9440, 416.942., 418.9402; found, 414.9448, 416.9430, 418.9415 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.84 (s, 1H, H.sub.13), 9.01 (d, J = 7.9 Hz, 1H, H.sub.19), 8.54 (d, J = 2.9 Hz, 1H, H.sub.12), 8.38 (d, J = 9.0 Hz, 1H, H.sub.10), 8.33 (d, J = 9.0 Hz, 1H, H.sub.9), 8.04 (d, J = 8.1 Hz, 1H, H.sub.2), (Yellow Solid) 7.73 (d, J = 8.1 Hz, 1H, H.sub.1), 7.16 (t, J = 7.6 Hz, 1H, H.sub.18), 7.05 (d, J = 7.1 Hz, 1H, H.sub.17), 2.55 (s, 3H, H.sub.20). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 157.55 (C.sub.8-arom.), 145.79 (C.sub.4-arom.), 137.28 (C.sub.14-arom.), 135.21 (C.sub.10H-arom.), 133.70 (C.sub.2H-arom.), 129.80 (C.sub.12H-arom.), 129.33 (C.sub.1H-arom.), 126.24 (C.sub.5-arom.), 125.67 (C.sub.15-arom.), 124.03 (C.sub.3-arom.), 123.58 (C.sub.17H-arom.), 122.06 (C.sub.9H-arom.), 121.65 (C.sub.18H-arom.), 121.42 (C.sub.16-arom.), 121.18 (C.sub.6-arom., C.sub.19H-arom.), 115.73 (C.sub.11-arom.), 17.24 (C.sub.20H.sub.3).

5-bromo-2-(7-methyl-1H-indol-3-yl)quinoline (Procedure 9)

[0274]

TABLE-US-00053 VPC Number LabBook Code IC.sub.50 (eGFP) = Inactive 13 678 CA 3-139 F15-21 Precipitate (yield = 21%) IC.sub.50 (PSA) = Inactive [00510] t.sub.R (HPLC) = 4.55 minMS (ESI+) m/z = 337.0363, 339.0354 [(M + H).sup.+] Mp = 200-204 C. HRMS (ESI+): calculated for C.sub.18H.sub.14BrN.sub.2, m/z = 337.0335, 339.0316; found, 337.0345, 339.0331 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.74 (s, 1H, H.sub.13), 8.69 (d, J = 8.0 Hz, 1H, H.sub.19), 8.42 (d, J = 3.0 Hz, 1H, H.sub.12), 8.36 (dd, J = 9.0, 0.7 Hz, 1H, H.sub.10), 8.23 (d, J = 9.0 Hz, 1H, H.sub.9), 8.06 (dt, J = 8.4, 0.9 Hz, 1H, H.sub.1), 7.81 (dd, J = 7.5, 1.0 Hz, 1H, H.sub.3), 7.64 (dd, J = 8.4, 7.6 Hz, (Pale Yellow Solid) 1H, H.sub.2), 7.13 (t, J = 7.6 Hz, 1H, H.sub.18), 7.03 (d, J = 7.0 Hz, 1H, H.sub.17), 2.54 (s, 3H, H.sub.20). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 156.97 (C.sub.8-arom.), 149.20 (C.sub.4-arom.), 137.24 (C.sub.14-arom.), 134.47 (C.sub.10H-arom.), 130.54 (C.sub.2H-arom.), 129.10 (C.sub.1H-arom.), 129.01 (C.sub.3H-arom.), 128.88 (C.sub.12H-arom.), 125.74 (C.sub.5-arom.), 125.10 (C.sub.15-arom.), 123.32 (C.sub.17H-arom.), 121.45 (C.sub.9H-arom.), 121.43 (C.sub.16-arom.), 121.37 (C.sub.6-arom.), 121.24 (C.sub.18H-arom.), 120.60 (C.sub.19H-arom.), 115.71 (C.sub.11-arom.), 17.25 (C.sub.20H.sub.3).

3-iodo-7-methyl-1-tosyl-1H-indole

[0275]

TABLE-US-00054 Intermediate LabBook Code CA 3-140 P1-3 (yield = 48%) [00511] (White Solid) t.sub.R (HPLC) = 5.50 min MS (ESI+) m/z = 411.9835 [(M + H).sup.+] .sup.1H NMR (500 MHz, DMSO-d.sub.6): (ppm) = 8.07 (s, 1H, H.sub.8), 7.68 (d, J = 8.3 Hz, 2H, H.sub.13,17), 7.41 (d, J = 8.1 Hz, 2H, H.sub.14,16), 7.29-7.21 (m, 2H, H.sub.6,1), 7.17 (d, J = 6.7 Hz, 1H, H.sub.2), 2.49 (s, 3H, H.sub.11), 2.35 (s, 3H, H.sub.18). .sup.13C NMR (126 MHz, DMSO-d.sub.6): (ppm) = 145.86 (C.sub.15-arom.), 135.85 (C.sub.12-arom.), 134.57 (C.sub.5-arom.), 134.23 (C.sub.4-arom.), 133.76 (C.sub.8H-arom.), 130.85 (C.sub.14,16H-arom.), 129.76 (C.sub.2H-arom.), 126.92 (C.sub.13,17H-arom.), 125.12 (C.sub.1H-arom.), 124.81 (C.sub.3-arom.), 120.38 (C.sub.6H-arom.), 69.54 (C.sub.9- arom.), 21.53 (C.sub.18H.sub.3), 21.47 (C.sub.11H.sub.3).

8-bromo-2-(7-methyl-1H-indol-3-yl)quinoline (Procedure 9)

[0276]

TABLE-US-00055 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.156 13 677 CA 3-141 F34-54 Precipitate (yield = 20%) IC.sub.50 (PSA) = 0.11 [00512] t.sub.R(HPLC) = 5.03 minMS (ESI+) m/z = 337.0361, 339.0345 [(M + H).sup.+] Mp = 214-217 C. HRMS (ESI+): calculated for C.sub.18H.sub.14BrN.sub.2, m/z = 337.0335, 339.0316; found, 337.0341, 339.0324 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.72 (s, 1H, H.sub.13), 9.04 (d, J = 8.0 Hz, 1H, H.sub.19), 8.47 (d, J = 3.0 Hz, 1H, H.sub.12), 8.30 (d, J = 8.8 Hz, (Yellow Solid) 1H, H.sub.10), 8.20 (d, J = 8.7 Hz, 1H, H.sub.9), 8.09 (dd, J = 7.5, 1.3 Hz, 1H, H.sub.2), 7.92 (dd, J = 8.1, 1.2 Hz, 1H, H.sub.6), 7.39 (t, J = 7.8 Hz, 1H, H.sub.1), 7.14 (t, J = 7.4 Hz, 1H, H.sub.18), 7.03 (d, J = 7.0 Hz, 1H, H.sub.17), 2.54 (s, 3H, H.sub.20). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 156.88 (C.sub.8-arom.), 144.96 (C.sub.4-arom.), 137.23 (C.sub.14-arom.), 136.61 (C.sub.10H-arom.), 133.25 (C.sub.2H- arom.), 128.92 (C.sub.12H-arom.), 128.20 (C.sub.6H-arom.), 127.68 (C.sub.5-arom.), 125.91 (C.sub.1H-arom.), 125.77 (C.sub.15-arom.), 123.97 (C.sub.3-arom.), 123.36 (C.sub.17H-arom.), 121.38 (C.sub.18H-arom.), 121.33 (C.sub.19H-arom.), 121.23 (C.sub.16- arom.), 120.45 (C.sub.9H-arom.), 116.31 (C.sub.11-arom.), 17.25 (C.sub.20H.sub.3).

3-(naphthalen-2-yl)-1H-pyrrolo[2,3-c]pyridine (Procedure 10)

[0277]

TABLE-US-00056 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.45 13 675 CA 3-144 Precipitate (yield = 83%) IC.sub.50 (PSA) = 0.468 [00513] t.sub.R (HPLC) = 3.26 minMS (ESI+) m/z = 245.1334 [(M + H).sup.+] Mp = 243-247 C. HRMS (ESI+): calculated for C.sub.17H.sub.13N.sub.2, m/z = 245.1073; found, 245.1079 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.99 (s, 1H, H.sub.13), 8.86 (s, 1H, H.sub.9), 8.27 (s, 1H, H.sub.3), 8.25 (d, J = 5.2 Hz, 1H, H.sub.7), 8.17 (s, 1H, H.sub.14), 8.05 (dd, J = 5.6, 1.0 Hz, 1H, H.sub.12), 8.02 (d, J = 8.1 Hz, 1H, H.sub.19), 8.00- (Pale Yellow Solid) 7.90 (m, 3H, H.sub.5,6,16), 7.53 (ddd, J = 8.1, 6.8, 1.4 Hz, 1H, H.sub.18), 7.47 (ddd, J = 8.0, 6.9, 1.3 Hz, 1H, H.sub.17). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 139.14 (C.sub.7H-arom.), 135.56 (C.sub.9H-arom.), 134.64 (C.sub.10-arom.), 134.14 (C.sub.1-arom.), 132.82 (C.sub.4-arom.), 131.87 (C.sub.2-arom.), 129.56 (C.sub.11-arom.), 128.76 (C.sub.6H-arom.), 128.43 (C.sub.14H-arom.), 128.18 (C.sub.19H-arom.), 127.96 (C.sub.16H-arom.), 126.72 (C.sub.18H-arom.), 126.01 (C.sub.17H-arom.), 125.73 (C.sub.5H-arom.), 124.12 (C.sub.3H- arom.), 115.47 (C.sub.15-arom.), 114.55 (C.sub.12H-arom.).

3-(naphthalen-2-yl)-1H-pyrrolo[2,3-b]pyridine (Procedure 10)

[0278]

TABLE-US-00057 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.053 13 676 CA 3-146 Precipitate (yield = 61%) IC.sub.50 (PSA) = 0.034 [00514] t.sub.R (HPLC) = 4.50 minMS (ESI+) m/z = 245.1077 [(M + H).sup.+] Mp = 207-211 C. HRMS (ESI+): calculated for C.sub.17H.sub.13N.sub.2, m/z = 245.1073; found, 245.1077 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 12.01 (s, 1H, H.sub.13), 8.50 (dd, J = 8.0, 1.1 Hz, 1H, H.sub.12), 8.32 (dd, J = 4.6, 1.5 Hz, 1H, H.sub.8), 8.27 (s, 1H, H.sub.3), 8.06 (d, J = 2.7 Hz, 1H, H.sub.14), 8.00 (d, J = 8.0 Hz, 1H, H.sub.19), 7.97- (Yellow Solid) 7.92 (m, 2H, H.sub.5,6), 7.91 (d, J = 8.0 Hz, 1H, H.sub.16), 7.52 (ddd, J = 8.2, 6.9, 1.4 Hz, 1H, H.sub.18), 7.47 (ddd, J = 8.0, 6.9, 1.3 Hz, 1H, H.sub.17), 7.22 (dd, J = 8.0, 4.6 Hz, 1H, H.sub.7). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 149.69 (C.sub.10-arom.), 143.50 (C.sub.8H-arom.), 134.16 (C.sub.1-arom.), 133.12 (C.sub.4-arom.), 131.85 (C.sub.2-arom.), 128.70 (C.sub.6H-arom.), 128.31 (C.sub.12H-arom.), 128.17 (C.sub.19H-arom.), 127.94 (C.sub.16H-arom.), 126.68 (C.sub.18H-arom.), 125.89 (C.sub.17H-arom.), 125.66 (C.sub.5H- arom.), 124.90 (C.sub.14H-arom.), 123.88 (C.sub.3H-arom.), 117.81 (C.sub.11-arom.), 116.62 (C.sub.7H-arom.), 114.55 (C.sub.15-arom.).

2-(5-bromo-1H-indol-3-yl)quinoline

[0279]

TABLE-US-00058 VPC Number LabBook Code IC.sub.50 (eGFP) = 2.6 13 683 CA 3-147 F36-46 Precipitate (yield = 39%) IC.sub.50 (PSA) = 1.906 [00515] (Yellow Solid) t.sub.R (HPLC) = 3.60 minMS (ESI+) m/z = 323.0169, 325.0153 [(M + H).sup.+] Mp = 200-203 C. HRMS (ESI+): calculated for C.sub.17H.sub.12BrN.sub.2, m/z = 323.0178, 325.0159; found, 323.0184, 325.0169 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.86 (s, 1H, H.sub.13), 9.06 (d, J = 2.0 Hz, 1H, H.sub.19), 8.42 (d, J = 2.8 Hz, 1H, H.sub.12), 8.27 (d, J = 8.5 Hz, 1H, H.sub.10), 8.05 (d, J = 8.8 Hz, 1H, H.sub.9), 8.02 (d, J = 9.0 Hz, 1H, H.sub.3), 7.89 (dd, J = 8.1, 1.2 Hz, 1H, H.sub.6), 7.72 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H, H.sub.6), 7.50 (ddd, J = 8.0, 6.9, 1.2 Hz, 1H, H.sub.1), 7.45 (dd, J = 8.4, 0.4 Hz, 1H, H.sub.17), 7.34 (dd, J = 8.6, 2.0 Hz, 1H, H.sub.17). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 155.03 (C.sub.8-arom.), 147.62 (C.sub.4-arom.), 135.92 (C.sub.10H-arom.), 135.83 (C.sub.14-arom.), 129.50 (C.sub.2H-arom.), 129.15 (C.sub.12H-arom.), 128.36 (C.sub.3H-arom.), 127.67 (C.sub.6H-arom.), 127.30 (C.sub.15-arom.), 125.88 (C.sub.5-arom.), 125.12 (C.sub.1H-arom.), 124.71 (C.sub.19H-arom.), 124.62 (C.sub.17H-arom.), 119.07 (C.sub.9H-arom.), 115.02 (C.sub.11-arom.), 113.79(C.sub.18-arom.), 113.07 (C.sub.16H-arom.).

3-(1H-indazol-3-yl)quinoline (Procedure 10)

[0280]

TABLE-US-00059 VPC Number LabBook Code IC.sub.50 (eGFP) = 1.4 13 684 CA 4-13 F3-5 (yield = 46%) IC.sub.50 (PSA) = 6.609 [00516] (White Solid) t.sub.R (HPLC) = 3.59 minMS (ESI+) m/z = 246.1322 [(M + H).sup.+] Mp = 212-215 C. HRMS (ESI+): calculated for C.sub.16H.sub.12N.sub.3, m/z = 246.1026; found, 246.1027 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 13.53 (s, 1H, H.sub.13), 9.60 (d, J = 2.2 Hz, 1H, H.sub.5), 8.98 (d, J = 2.0 Hz, 1H, H.sub.3), 8.33 (d, J = 8.2 Hz, 1H, H.sub.12), 8.21 (d, J = 7.9 Hz, 1H, H.sub.19), 8.09 (d, J = 8.3 Hz, 1H, H.sub.16), 7.8.79 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H, H.sub.17), 7.71-7.66 (m, 2H, H.sub.9,18), 7.48 (t, J = 7.4 Hz, 1H, H.sub.8), 7.31 (t, J = 7.5 Hz, 1H, H.sub.7). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 149.67 (C.sub.5H-arom.), 147.27 (C.sub.2-arom.), 142.03 (s C.sub.10-arom.), 141.01 (C.sub.1-arom.), 132.67 (C.sub.3H-arom.), 129.94 (C.sub.17H-arom.), 129.20 (C.sub.16H-arom.), 129.01 (C.sub.19H-arom.), 128.24 (C.sub.4-arom.), 127.52 (C.sub.18H-arom.), 127.29 (C.sub.15-arom.), 126.96 (C.sub.8H-arom.), 121.96 (C.sub.7H-arom.), 121.23 (C.sub.12H-arom.), 120.81 (C.sub.11-arom.), 111.26 (C.sub.9H-arom.).

3-(naphthalen-2-yl)-1H-pyrrolo[3,2-c]pyridine (Procedure 10)

[0281]

TABLE-US-00060 VPC Number LabBook Code IC.sub.50 (eGFP) = Inactive 13 685 CA 4-15 Precipitate2 (yield = 71%) IC.sub.50 (PSA) = Inactive [00517] (Pale Orange Solid) t.sub.R (HPLC) = 3.17 minMS (ESI+) m/z = 245.1082 [(M + H).sup.+] Mp = <270 C. HRMS (ESI+): calculated for C.sub.17H.sub.13N.sub.2, m/z = 245.1073; found, 245.1073 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.85 (s, 1H, H.sub.13), 9.39 (s, 1H, H.sub.12), 8.33 (s, 1H, H.sub.3), 8.28 (d, J = 5.6 Hz, 1H, H.sub.8), 8.05 (d, J = 8.0 Hz, 1H, H.sub.19), 8.02-7.94 (m, 3H, H.sub.4,6,14), 7.92 (d, J = 8.0 Hz, 1H, H.sub.16), 7.53 (ddd, J = 8.0, 7.2, 1.6 Hz, 1H, H.sub.18), 7.51-7.45 (m, 2H, H.sub.9,17). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 142.94 (C.sub.12H-arom.), 141.01 (C.sub.8H-arom.), 140.93 (C.sub.10-arom.), 134.16 (C.sub.1-arom.), 132.62 (C.sub.4-arom.), 131.97 (C.sub.2-arom.), 128.76 (C.sub.6H-arom.), 128.30 (C.sub.19H-arom.), 127.92 (C.sub.16H-arom.), 126.71 (C.sub.18H-arom.), 126.21 (C.sub.17H-arom.), 125.79 (C.sub.5H- arom.), 125.55 (C.sub.14H-arom.), 124.55 (C.sub.3H-arom.), 115.92 (C.sub.15-arom.), 107.71 (C.sub.9H-arom.).

2-phenyl-1H-benzo[d]imidazole

[0282]

TABLE-US-00061 VPC Number LabBook Code IC.sub.50 (eGFP) = Inactive 13 686 CA 4-16 F3-14 Precipitate (yield = 22%) IC.sub.50 (PSA) = Inactive [00518] t.sub.R (HPLC) = 2.39 minMS (ESI+) m/z = 195.1040 [(M + H).sup.+] Mp = <270 C. HRMS (ESI+): calculated for C.sub.13H.sub.11N.sub.2, m/z = 195.0917; found, 195.0919 .sup.1H NMR (400 MHz, DMOS-d.sub.6): (ppm) = 12.91 (s, 1H, H.sub.13), 8.22-8.17 (Pink Solid) (m, 2H, H.sub.3,5), 7.67 (br s, 1H, H.sub.9), 7.59-7.47 (m, 4H, H.sub.1,2,6,12), 7.22-7.19 (m, 2H, H.sub.7,8). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 151.19 (C.sub.14-arom.), 143.79 (C.sub.10-arom.), 134.98 (C.sub.11-arom.), 130.15 (C.sub.4-arom.), 129.81 (C.sub.2H-arom.), 128.92 (C.sub.1,6H-arom.), 126.40 (C.sub.3,5H-arom.), 122.50 (C.sub.7H-arom.), 121.64 (C.sub.8H-arom.), 118.85 (C.sub.9H-arom.), 111.30 (C.sub.12H-arom.).

2-naphthalen-3-ol-1H-benzo[d]imidazole

[0283]

TABLE-US-00062 VPC Number LabBook Code IC.sub.50 (eGFP) = Inactive 13 687 CA 4-17 Precipitate2 (yield = 14%) IC.sub.50 (PSA) = Inactive [00519] t.sub.R (HPLC) = 3.32 minMS (ESI+) m/z = 261.1080 [(M + H).sup.+] Mp = <270 C. HRMS (ESI+): calculated for C.sub.17H.sub.13N.sub.2O, m/z = 261.1022; found, 261.1022 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 13.46 (s, 1H, H.sub.20), 13.01 (s, 1H, H.sub.13), 8.72 (s, 1H, H.sub.3), 7.90 (d, J = 8.2 Hz, 1H, H.sub.19), 7.79 (d, J = 8.4 Hz, 1H, H.sub.16), 7.74 (br s, 2H, , H.sub.9,12), 7.51 (t, J = 7.5 Hz, 1H, H.sub.17), 7.43 (s, 1H, H.sub.6), 7.39 (t, J = 7.5 Hz, 1H, H.sub.18), 7.34 (br s, 2H, H.sub.7,8). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 154.60 (C.sub.5-arom.), 151.15 (C.sub.14- arom.), 141.03 (C.sub.10-arom.), 135.16 (C.sub.2-arom.), 133.41 (C.sub.11-arom.), 128.13 (C.sub.19H-arom.), 127.65 (C.sub.17H-arom.), 126.99 (C.sub.1-arom.), 126.80 (C.sub.3H-arom.), 126.05 (C.sub.16H-arom.), 123.77 (C.sub.18H-arom.), 123.60 (C.sub.7H-arom.), 122.57 (C.sub.8H-arom.), 118.21 (C.sub.9H-arom.), 115.21 (C.sub.4-arom.), 111.72 (C.sub.12H-arom.), 110.80 (C.sub.6H-arom.).

tert-butyl 3-iodo-7-nitro-1H-indole-1-carboxylate

[0284]

TABLE-US-00063 Intermediate LabBook Code CA 4-18 F4-18 (yield = 90%) [00520] t.sub.R (HPLC) = 5.24 min MS (ESI+) m/z = 410.9828 [(M + Na).sup.+] .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 8.10 (s, 1H, H.sub.8), 7.99 (dd, J = 7.9, 0.7 Hz, 1H, H.sub.2), 7.78 (dd, J = 7.9, 1.0 Hz, 1H, H.sub.6), 7.56 (t, J = 7.9 Hz, 1H, H.sub.1), 1.56 (s, 9H, H.sub.13,14,15). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 147.76 (C.sub.16O), 138.62 (C.sub.3- arom.), 135.66 (C.sub.5-arom.), 134.29 (C.sub.8H-arom.), 127.30 (C.sub.6H-arom.), 124.77 (C.sub.4-arom.), 124.25 (C.sub.1H-arom.), 121.63 (C.sub.2H-arom.), 86.64 (C.sub.12(CH.sub.3).sub.3), 66.56 (C.sub.9-arom.), 27.76 (C.sub.13,14,15H.sub.3).

3-((2H-tetrazol-5-yl)methyl)-1H-indole

[0285]

TABLE-US-00064 VPC Number LabBook Code IC.sub.50 (eGFP) = Inactive 13 700 CA 4-21 F3-4 (yield = 66%) IC.sub.50 (PSA) = Inactive [00521] t.sub.R (HPLC) = 2.80 minMS (ESI+) m/z = 200.0936 [(M + H).sup.+] Mp = 174-181 C. HRMS (ESI+): calculated for C.sub.10H.sub.10N.sub.5, m/z = 200.0931; found, 200.0929 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.03 (s, 1H, H.sub.9), 7.43 (d, J = 8.0 Hz, 1H, H.sub.6), 7.38 (d, J = 8.1 Hz, 1H, H.sub.3), 7.27 (d, J = 2.4 Hz, 1H, H.sub.8), 7.09 (ddd, J = 8.0, 7.2, 1.2 Hz, 1H, H.sub.5), 6.98 (ddd, J = 7.9, 7.1, 1.0 Hz, 1H, H.sub.4), 4.38 (d, J = 0.6 Hz, 2H, H.sub.10). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 156.20 (C.sub.11-arom.), 136.70 (C.sub.2- arom.), 126.98 (C.sub.8H-arom.), 124.34 (C.sub.1-arom.), 121.75 (C.sub.4H-arom.), 119.11 (C.sub.5H-arom.), 118.57 (C.sub.6H-arom.), 112.02 (C.sub.3H-arom.), 108.78 (C.sub.7-arom.), 19.99 (C.sub.10H.sub.2).

3-(2H-tetrazol-5-yl)-1H-indole

[0286]

TABLE-US-00065 VPC Number LabBook Code IC.sub.50 (eGFP) = Inactive 13 701 CA 4-22 F9-16 (yield = 33%) IC.sub.50 (PSA) = Inactive [00522] t.sub.R (HPLC) = 2.86 minMS (ESI+) m/z = 186.2227 [(M + H).sup.+] Mp = 220-224 C. HRMS (ESI+): calculated for C.sub.9H.sub.8N.sub.5, m/z = 186.0774; found, 186.0776 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.88 (s, 1H, H.sub.9), 8.25-8.22 (m, 1H, H.sub.6), 8.11 (d, J = 2.9 Hz, 1H, H.sub.11), 7.57-7.53 (m, 1H, H.sub.3), 7.28- 7.20 (m, 2H, H.sub.4,5). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 151.72 (C.sub.10-arom.), 136.86 (C.sub.2H-arom.), 127.53 (C.sub.8H-arom.), 124.91 (C.sub.1-arom.), 123.08 (C.sub.4H-arom.), 121.27 (C.sub.5H-arom.), 120.77 (C.sub.6H-arom.), 112.73 (C.sub.3H-arom.), 99.91 (C.sub.7- arom.).

tert-butyl 3-iodo-7-methyl-1H-indole-1-carboxylate

[0287]

TABLE-US-00066 Intermediate LabBook Code CA 4-23 P1-3 (yield = 81%) [00523] t.sub.R (HPLC) = 5.78 minMS (ESI+) m/z = .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 7.88 (s, 1H, H.sub.8), 7.30-7.19 (m, 3H, H.sub.1,2,6), 2.54 (s, 3H, H.sub.11), 1.61 (s, 9H, H.sub.14,15,16). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 148.55 (C.sub.17O), 134.13 (C.sub.4- arom.), 133.33 (C.sub.5-arom.), 132.74 (C.sub.8H-arom.), 128.83 (C.sub.2H-arom.), 125.22 (C.sub.3-arom.), 124.29 (C.sub.1H-arom.), 119.45 (C.sub.6H-arom.), 84.70 (C.sub.13(CH.sub.3).sub.3), 66.84 (C.sub.9-arom.), 27.90 (C.sub.14,15,16H.sub.3), 21.68 (C.sub.11H.sub.3).

tert-butyl 3-iodo-H-pyrrolo[3,2-b]pyridine-1-carboxylate

[0288]

TABLE-US-00067 Intermediate LabBook Code CA 4-24 F1-6 (yield = 77%) [00524] t.sub.R (HPLC) = 4.59 min MS (ESI+) m/z = 345.0111 [(M + H).sup.+] .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 8.56 (dd, J = 4.7, 1.4 Hz, 1H, H.sub.1), 8.32 (dd, J = 8.3, 1.3 Hz, 1H, H.sub.3), 8.19 (s, 1H, H.sub.8), 7.43 (dd, J = 8.3, 4.7 Hz, 1H, H.sub.2), 1.64 (s, 9H, H.sub.13,14,15). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 148.26 (C.sub.16O), 147.90 (C.sub.4- arom.), 146.39 (C.sub.1H-arom.), 133.51 (C.sub.8H-arom.), 128.04 (C.sub.5-arom.), 122.61 (C.sub.3H-arom.), 120.60 (C.sub.2H-arom.), 85.59 (C.sub.12(CH.sub.3).sub.3), 69.42 (C.sub.9-arom.), 28.05 (C.sub.13,14,15H.sub.3).

3-(naphthalen-2-yl)-7-nitro-1H-indole (Procedure 10)

[0289]

TABLE-US-00068 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.2 13 702 CA 4-27 F20-51 Precipitate3 (yield = 56%) IC.sub.50 (PSA) = 0.14 [00525] t.sub.R (HPLC) = 4.40 min MS (ESI+) m/z = 289.0915 [(M + H).sup.+] Mp = 166-171 C. HRMS (ESI+): calculated for C.sub.18H.sub.13N.sub.2O.sub.2, m/z = 289.0972; found, 289.0975 .sup.1H NMR (400 MHz, CDCl.sub.3): (ppm) = 10.13 (s, 1H, H.sub.13), 8.38 (d, J = 7.8 Hz, 1H, H.sub.12), 8.28 (d, J = 8.1 Hz, 1H, H.sub.8), 8.11 (s, 1H, H.sub.3), 7.99 (d, J = 8.4 Hz, 1H, H.sub.6), 7.95-7.90 (m, 2H, H.sub.16,19), 7.78 (dd, J = 8.5, 1.8 Hz, 1H, H.sub.5), 7.67 (d, J = 2.4 Hz, 1H, H.sub.14), 7.59-7.50 (m, 2H, H.sub.17,18), 7.35 (t, J = 8.0 Hz, 1H, H.sub.7). .sup.13C NMR (101 MHz, CDCl.sub.3): (ppm) = 133.82 (C.sub.4-arom.), 133.21 (C.sub.9- arom.), 132.41 (C.sub.2-arom.), 131.32 (C.sub.1-arom.), 130.08 (C.sub.10-arom.), 129.92 (C.sub.11-arom.), 128.67 (C.sub.6H-arom.), 128.16 (C.sub.12H-arom.), 127.83 (C.sub.19H- arom.), 127.78 (C.sub.19H-arom.), 126.48 (C.sub.5H-arom.), 126.42 (C.sub.18H-arom.), 126.14 (C.sub.3H-arom.), 125.86 (C.sub.17H-arom.), 124.23 (C.sub.14H-arom.), 119.88 (C.sub.15-arom.), 119.81 (C.sub.7H-arom.), 119.77 (C.sub.8H-arom.).

3-(naphthalen-2-yl)-1H-pyrrolo[3,2-b]pyridine (Procedure 10)

[0290]

TABLE-US-00069 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.1 13 703 CA 4-28 Precipitate (yield = 84%) IC.sub.50 (PSA) = 0.097 [00526] t.sub.R (HPLC) = 4.28 min MS (ESI+) m/z = 245.1068 [(M + H).sup.+] Mp = 221-224 C. HRMS (ESI+): calculated for C.sub.17H.sub.13N.sub.2, m/z = 245.1073; found, 245.1068 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.66 (s, 1H, H.sub.14), 8.97 (d, J = 0.8 Hz, 1H, H.sub.3), 8.53 (dd, J = 4.6, 1.5 Hz, 1H, H.sub.7), 8.35 (dd, J = 8.6, 1.7 Hz, 1H, H.sub.5), 8.33 (d, J = 2.9 Hz, 1H, H.sub.14), 7.95-7.90 (m, 2H, H.sub.6,19), 7.89-7.84 (m, 2H, H.sub.9,16), 7.50 (ddd, J = 8.2, 6.9, 1.4 Hz, 1H, H.sub.18), 7.44 (ddd, J = 8.0, 6.9, 1.3 Hz, 1H, H.sub.17), 7.22 (dd, J = 8.2, 4.6 Hz, 1H, H.sub.8). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 144.11 (C.sub.11-arom.), 143.30 (C.sub.7H-arom.), 134.01 (C.sub.1-arom.), 132.82 (C.sub.4-arom.), 131.77 (C.sub.2-arom.), 130.16 (C.sub.10-arom.), 128.07 (C.sub.6,16H-arom.), 128.06 (C.sub.19H-arom.), 127.67 (C.sub.14H-arom.), 126.53 (C.sub.18H-arom.), 125.51 (C.sub.5H-arom.), 125.34 (C.sub.17H- arom.), 123.77 (C.sub.3H-arom.), 119.47 (C.sub.9H-arom.), 117.21 (C.sub.8H-arom.), 114.52 (C.sub.15-arom.).

7-bromo-3-(naphthalen-2-yl)-1H-indole (Procedure 10)

[0291]

TABLE-US-00070 LabBook Code CA 4-29 P2 F3-7 (yield = 12%) [00527] t.sub.R (HPLC) = 5.13 min MS (ESI+) m/z = 323.0095, 325.0076 [(M + H).sup.+] .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.70 (s, 1H, H.sub.13), 8.24 (s, 1H, H.sub.3), 8.07 (d, J = 8.0 Hz, 1H, H.sub.12), 8.00 (d, J = 8.3 Hz, 1H, H.sub.19), 7.98 (d, J = 8.6 Hz, 1H, H.sub.6), 7.94-7.89 (m, 3H, H.sub.5,14,16), 7.53 (ddd, J = 8.1, 6.7, 1.4 Hz, 1H, H.sub.18), 7.48 (ddd, J = 8.1, 6.8, 1.3 Hz, 1H, H.sub.17), 7.44 (d, J = 7.4 Hz, 1H, H.sub.8), 7.12 (t, J = 7.8 Hz, 1H, H.sub.7). .sup.13C NMR .fwdarw. n.d.

3-(naphthalen-2-yl)-1H-indol-7-amine

[0292]

TABLE-US-00071 LabBook Code CA 4-34 F6-10 (yield = 28%) [00528] t.sub.R (HPLC) = 4.04 min MS (ESI+) m/z = 259.1295 [(M + H).sup.+] .sup.1H NMR (400 MHz, CDCl.sub.3) (ppm) = 8.22 (s, 1H, H.sub.13), 8.18 (s, 1H, H.sub.7), 7.96-7.88 (m, 3H, H.sub.3,6,10), 7.85 (dd, J = 8.5, 1.7 Hz, 1H, H.sub.9), 7.62 (d, J = 7.9 Hz, 1H, H.sub.19), 7.57-7.49 (m, 2H, H.sub.1,2), 7.36 (s, 1H, H.sub.12), 7.21 (t, J = 7.8 Hz, 1H, H.sub.18), 6.69 (d, J = 7.5 Hz, 1H, H.sub.17). .sup.13C NMR .fwdarw. n.d.

tert-butyl 7-methyl-3-((trimethylsilyl)ethynyl)-1H-indole-1-carboxylate

[0293]

TABLE-US-00072 Intermediate LabBook Code CA 4-35 F5-7 (yield = Quant %) [00529] t.sub.R (HPLC) = 5.48 min MS (ESI+) m/z = .sup.1H NMR (400 MHz, CDCl.sub.3): (ppm) = 7.77 (s, 1H, H.sub.8), 7.54 (d, J = 7.6 Hz, 1H, H.sub.6), 7.25 (t, J = 7.5 Hz, 1H, H.sub.1), 7.18 (d, J = 7.3 Hz, 1H, H.sub.2), 2.67 (s, 3H), 1.66 (s, 9H), 0.33 (s, 9H). .sup.13C NMR (101 MHz, CDCl.sub.3): (ppm) = 148.78 (C.sub.22O), 134.06 (C.sub.4-arom.), 131.84 (C.sub.5-arom.), 131.67 (C.sub.8H-arom.), 128.58 (C.sub.2H-arom.), 125.44 (C.sub.3- arom.), 123.61 (C.sub.1H-arom.), 117.80 (C.sub.6H-arom.), 103.32 (C.sub.9-arom.), 97.93 (C.sub.12), 96.91 (C.sub.10), 83.94 (C.sub.18(CH.sub.3).sub.3), 28.01 (C.sub.19,20,21H.sub.3), 22.09 (C.sub.11H.sub.3), 0.14 (C.sub.14,15,16H.sub.3).

3-([1,1-biphenyl]-4-yl)-7-methyl-1H-indole (Procedure 10)

[0294]

TABLE-US-00073 VPC Number LabBook Code IC.sub.50 (eGFP) = 3.815 13 733 CA 4-38 Precipitate (yield = 25 %) IC.sub.50 (PSA) = 0.919 [00530] t.sub.R (HPLC) = 4.50 min MS (ESI) m/z = 282.1207 [(M + H).sup.] Mp = 199-202 C. HRMS (ESI): calculated for C.sub.21H.sub.16N, m/z = 282.1288; found, 282.1286 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.38 (s, 1H, H.sub.13), 7.84-7.79 (m, 2H, H.sub.3,5), 7.78-7.70 (m, 6H, H.sub.1,6,12,14,18,22), 7.52-7.46 (m, 2H, H.sub.19,21), 7.40-7.34 (m, 1H, H.sub.20), 7.04 (t, J = 7.2 Hz, 1H, H.sub.7), 6.98 (d, J = 7.0 Hz, 1H, H.sub.8), 2.52 (s, 3H, H.sub.17). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 140.51 (C.sub.16-arom.), 137.29 (C.sub.2- arom.), 136.90 (C.sub.10-arom.), 135.75 (C.sub.4-arom.), 129.40 (C.sub.19,21H-arom.), 127.57 (C.sub.20H-arom.), 127.43 (C.sub.1,6H-arom.), 127.33 (C.sub.3,5H-arom.), 126.79 (C.sub.18,22H-arom.), 125.14 (C.sub.11-arom.), 123.85 (C.sub.14H-arom.), 122.44 (C.sub.8H- arom.), 121.62 (C.sub.9-arom.), 120.37 (C.sub.7H-arom.), 117.16 (C.sub.12H-arom.), 116.06 (C.sub.15-arom.), 17.31 (C.sub.17H.sub.3).

3-([1,1-biphenyl]-4-yl)-1H-pyrrolo[2,3-b]pyridine (Procedure 10)

[0295]

TABLE-US-00074 VPC Number LabBook Code IC.sub.50 (eGFP) = 4.08 13 715 CA 4-39 Precipitate3 (yield = 51%) IC.sub.50 (PSA) = 0.35 [00531] t.sub.R (HPLC) = 4.23 min MS (ESI) m/z = 271.1232 [(M + H).sup.+] Mp = <270 C. HRMS (ESI+): calculated for C.sub.19H.sub.15N.sub.2, m/z = 271.1230; found, 271.1232 .sup.1H NMR (500 MHz, DMSO-d.sub.6): (ppm) = 11.97 (s, 1H, H.sub.13), 8.35 (d, J = 7.9 Hz, 1H, H.sub.12), 8.30 (dd, J = 4.6, 1.4 Hz, 1H, H.sub.8), 7.96 (d, J = 2.6 Hz, 1H, H.sub.14), 7.84 (d, J = 8.3 Hz, 2H, H.sub.3,5), 7.79-7.71 (m, 4H, H.sub.1,6,17,21), 7.49 (t, J = 7.7 Hz, 2H, H.sub.20,18), 7.38 (t, J = 7.4 Hz, 1H, H.sub.19), 7.19 (dd, J = 7.9, 4.6 Hz, 1H, H.sub.7). .sup.13C NMR (126 MHz, DMSO-d.sub.6): (ppm) = 149.60 (C.sub.10-arom.), 143.42 (C.sub.8- arom.), 140.39 (C.sub.16-arom.), 137.73 (C.sub.2-arom.), 134.78 (C.sub.4-arom.), 129.43 (C.sub.18,20H-arom.), 128.02 (C.sub.12H-arom.), 127.68 (C.sub.19H-arom.), 127.55 (C.sub.1,6H- arom.), 127.11 (C.sub.3,5H-arom.), 126.84 (C.sub.17,21H-arom.), 124.41 (C.sub.14H-arom.), 117.74 (C.sub.11H-arom.), 116.57 (C.sub.7H-arom.), 114.24 (C.sub.15-arom.).

3-(4-bromophenyl)-1H-pyrrolo[2,3-b]pyridine (Procedure 10)

[0296]

TABLE-US-00075 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.067 13 716 CA 4-40 Precipitate (yield = 37%) IC.sub.50 (PSA) = 0.058 [00532] t.sub.R (HPLC) = 3.96 min MS (ESI) m/z = 273.0029, 275.0010 [(M + H).sup.+] Mp = 262-266 C. HRMS (ESI+): calculated for C.sub.13H.sub.10BrN.sub.2, m/z = 273.0022, 275.0002; found, 273.0024, 275.0005 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 12.00 (s, 1H, H.sub.13), 8.30-8.27 (m, 2H, H.sub.8,12), 7.95 (d, J = 2.7 Hz, 1H, H.sub.14), 7.72-7.68 (m, 2H, H.sub.1,6), 7.63- 7.59 (m, 2H, H.sub.3,5), 7.20-7.15 (m, 1H, H.sub.7). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 149.54 (C.sub.10-arom.), 143.52 (C.sub.8H-arom.), 134.83 (C.sub.4-arom.), 132.14 (C.sub.3,5H-arom.), 128.60 (C.sub.1,6H- arom.), 127.89 (C.sub.12H-arom.), 124.70 (C.sub.14H-arom.), 118.79 (C.sub.2-arom.), 117.47 (C.sub.11-arom.), 116.64 (C.sub.7H-arom.), 113.46 (C.sub.15-arom.).

3-([1,1-biphenyl]-3-yl)-1H-pyrrolo[2,3-b]pyridine (Procedure 10)

[0297]

TABLE-US-00076 VPC Number LabBook Code IC.sub.50 (eGFP) = 11.01 13 734 CA 4-48 Precipitate (yield = 39%) IC.sub.50 (PSA) = 4.129 [00533] t.sub.R (HPLC) = 4.34 min MS (ESI) m/z = 271.1226 [(M + H).sup.+] Mp = 182-185 C. HRMS (ESI+): calculated for C.sub.19H.sub.15N.sub.2, m/z = 271.1230; found, 271.1227 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.97 (s, 1H, H.sub.13), 8.34 (dd, J = 8.0, 1.5 Hz, 1H, H.sub.12), 8.30 (dd, J = 4.6, 1.5 Hz, 1H, H.sub.8), 8.01 (s, 1H, H.sub.14), 7.95 (d, J = 0.7 Hz, 1H, H.sub.3), 7.80-7.75 (m, 2H, H.sub.17,21), 7.74-7.71 (m, 1H, H.sub.5), 7.57-7.47 (m, 4H, H.sub.2,6,18,20), 7.43-7.39 (m, 1H, H.sub.19), 7.18 (dd, J = 7.9, 4.7 Hz, 1H, H.sub.7). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 149.56 (C.sub.10-arom.), 143.39 (C.sub.8H-arom.), 141.37 (C.sub.1-arom.), 140.88 (C.sub.16-arom.), 136.18 (C.sub.4-arom.), 129.97 (C.sub.6H-arom.), 129.38 (C.sub.18,20H-arom.), 127.94 (C.sub.12,19H-arom.), 127.37 (C.sub.17,21H-arom.), 125.87 (C.sub.5H-arom.), 125.07 (C.sub.3H-arom.), 124.62 (C.sub.2,14H- arom.), 117.79 (C.sub.11-arom.), 116.59 (C.sub.7H-arom.), 114.66 (C.sub.15-arom.).

4-(4-bromothiazol-2-yl)morpholine

[0298]

TABLE-US-00077 LabBook Code CA 4-50 Ap Tmt (yield = Quant Intermediate %) [00534] (Beige Solid) t.sub.R (HPLC) = 3.44 min MS (ESI+) m/z = 248.9720; 250.9700 [(M + H).sup.+] .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 6.92 (s, 1H, H.sub.2), 3.72-3.67 (m, 4H, H.sub.8,10), 3.38-3.34 (m, 4H, H.sub.7,11). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 171.17 (C.sub.4-arom.), 121.03 (C.sub.1-arom.), 105.37 (C.sub.2H-arom.), 65.72 (C.sub.8,10H.sub.2), 48.08 (C.sub.7,11H.sub.2).

3-([1,1-biphenyl]-4-yl)-1H-pyrrolo[3,2-b]pyridine (Procedure 10)

[0299]

TABLE-US-00078 VPC Number LabBook Code IC.sub.50 (eGFP) = 3.86 13 735 CA 4-55 Precipitate (yield = 79%) IC.sub.50 (PSA) = 1.433 [00535] (White Solid) t.sub.R (HPLC) = 3.55 min MS (ESI) m/z = 271.1169 [(M + H).sup.+] Mp = 254-259 C. HRMS (ESI+): calculated for C.sub.19H.sub.15N.sub.2, m/z = 271.1230; found, 271.1225 .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 11.62 (s, 1H, H.sub.13), 8.48 (dd, J = 4.6, 1.5 Hz, 1H, H.sub.7), 8.43-8.39 (m, 2H, H.sub.3,5), 8.24 (s, 1H, H.sub.14), 7.85 (dd, J = 8.2, 1.5 Hz, 1H, H.sub.9), 7.72 (m, 4H, H.sub.1,6,17,21), 7.49 (m, 2H, H.sub.18,20), 7.39-7.35 (m, 1H, H.sub.19), 7.20 (dd, J = 8.2, 4.6 Hz, 1H, H.sub.8). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 144.02 (C.sub.11-arom.), 143.19 (C.sub.7H- arom.), 140.64 (C.sub.16-arom.), 137.19 (C.sub.2-arom.), 134.48 (C.sub.4-arom.), 130.04 (C.sub.10- arom.), 129.36 (C.sub.18,20H-arom.), 127.50 (C.sub.19H-arom.), 127.16 (C.sub.14H-arom.), 126.99 (C.sub.1,6H-arom.), 126.77 (C.sub.17,21H-arom.), 126.69 (C.sub.3,5H-arom.), 119.42 (C.sub.9H-arom.), 117.09 (C.sub.8H-arom.), 114.21 (C.sub.15-arom.).

3-(4-bromophenyl)-1H-pyrrolo[3,2-b]pyridine (Procedure 10)

[0300]

TABLE-US-00079 LabBook Code VPC Number CA 4-64 Precipitate (yield = 25 IC.sub.50 (eGFP) = 0.08 13 737 %) IC.sub.50 (PSA) = 0.037 [00536] (Pale Yellow Solid) t.sub.R (HPLC) = 2.84 min MS (ESI) m/z = 273.0043, 275.0023 [(M + H).sup.+] Mp = 213-221 C. HRMS (ESI+): calculated for C.sub.13H.sub.10BrN.sub.2, m/z = 273.0022, 275.0002; found, 273.0015, 274.9995 .sup.1H NMR (400 mHz, DMSO-d.sub.6): (ppm) = 11.66 (s, 1H, H.sub.13), 8.46 (dd, J = 4.6, 1.5 Hz, 1H, H.sub.7), 8.32-8.27 (m, 2H, H.sub.1,6), 8.24 (s, 1H, H.sub.14), 7.84 (dd, J = 8.2, 1.5 Hz, 1H, H.sub.9), 7.61-7.55 (m, 2H, H.sub.3,5), 7.19 (dd, J = 8.2, 4.6 Hz, 1H, H.sub.8). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 143.76 (C.sub.11-arom.), 143.27 (C.sub.7H-arom.), 134.53 (C.sub.4-arom.), 131.61 (C.sub.3,5H-arom.), 130.02 (C.sub.10-arom.), 128.10 (C.sub.1,6H-arom.), 127.44 (C.sub.14H-arom.), 119.53 (C.sub.9H-arom.), 118.24 (C.sub.2-arom.), 117.19 (C.sub.8H-arom.), 113.32 (C.sub.15-arom.).

3-(4-bromophenyl)-7-nitro-1H-indole (Procedure 10)

[0301]

TABLE-US-00080 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.083 13 738 CA 4-65 Precipitate (yield = 12%) IC.sub.50 (PSA) = 0.062 [00537] (Orage Solid) t.sub.R (HPLC) = 4.29 min MS (ESI) m/z = 314.9732, 316.9703 [(M + H).sup.] Mp = 192-196 C. HRMS (ESI): calculated for C.sub.14H.sub.8BrN.sub.2O.sub.2, m/z = 314.9775, 316.9755; found, 314.9769, 316.9748 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 12.21 (s, 1H, H.sub.13), 8.34 (dd, J = 7.9, 0.8 Hz, 1H, H.sub.12), 8.20 (dd, J = 8.0, 0.5 Hz, 1H, H.sub.8), 7.89 (s, 1H, H.sub.14), 7.71-7.63 (m, 4H, H.sub.1,3,5,6), 7.36 (t, J = 8.0 Hz, 1H, H.sub.7). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 133.24 (C.sub.4-arom.), 132.90 (C.sub.9- arom.), 131.78 (C.sub.1,6H-arom.), 129.25 (C.sub.3,5H-arom.), 129.11 (C.sub.11-arom.), 128.95 (C.sub.10-arom.), 127.65 (C.sub.12H-arom.), 126.89 (C.sub.14H-arom.), 119.58 (C.sub.7H- arom.), 119.26 (C.sub.2-arom.), 119.13 (C.sub.8H-arom.), 116.42 (C.sub.15-arom.).

methyl 3-(4-bromophenyl)-1H-indole-7-carboxylate (Procedure 10)

[0302]

TABLE-US-00081 LabBook Code VPC Number CA 4-74 Precipitate (yield = 36 IC.sub.50 (eGFP) = 0.62 13 736 %) IC.sub.50 (PSA) = 0.68 [00538] (Grey Solid) t.sub.g (HPLC) = 4.37 min MS (ESI) m/z = 327.9978 [(M + H).sup.] Mp = 149-155 C. HRMS (ESI): calculated for C.sub.16H.sub.11BrNO.sub.2, m/z = 327.9979; found, 327.9978 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.49 (s, 1H, H.sub.13), 8.16 (d, J = 7.9 Hz, 1H, H.sub.12), 7.87 (d, J = 6.8 Hz, 1H, H.sub.8), 7.78 (d, J = 2.6 Hz, 1H, H.sub.14), 7.70-7.67 (m, 2H, H.sub.3,5), 7.65-7.61 (m, 2H, H.sub.1,6), 7.26 (t, J = 7.7 Hz, 1H, H.sub.7), 3.97 (s, 3H, H.sub.7). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 166.39 (C.sub.17O), 135.02 (C.sub.10-arom.), 134.18 (C.sub.4-arom.), 131.67 (C.sub.1,6H-arom.), 128.88 (C.sub.3,5H-arom.), 126.54 (C.sub.11-arom.), 125.42 (C.sub.14H-arom.), 124.83 (C.sub.12H-arom.), 124.30 (C.sub.8H-arom.), 119.49 (C.sub.7H-arom.), 118.57 (C.sub.2-arom.), 115.07 (C.sub.15-arom.), 113.07 (C.sub.9-arom.), 51.94 (C.sub.20H.sub.3).

3-phenyl-1H-pyrrolo[2,3-b]pyridine (Procedure 10)

[0303]

TABLE-US-00082 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.66 13 739 CA 4-75 Precipitate (yield = 54%) IC.sub.50 (PSA) = 0.67 [00539] (Beige Solid) t.sub.R (HPLC) = 3.40 min MS (ESI+) m/z = 195.0920 [(M + H).sup.+] Mp = 92-94 C. HRMS (ESI+): calculated for C.sub.13H.sub.11N.sub.2, m/z = 195.0917; found, 195.0919 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.90 (s, 1H, H.sub.13), 8.30-8.26 (m, 2H, H.sub.8,12), 7.87 (d, J = 2.6 Hz, 1H, H.sub.14), 7.73 (dd, J = 8.2, 1.1 Hz, 2H, H.sub.3.5), 7.45 (dd, J = 8.0, 7.5 Hz, 2H, H.sub.1,6), 7.26 (tdd, J = 7.2, 6.0, 1.2 Hz, 1H, H.sub.2), 7.16 (dd, J = 7.9, 4.7 Hz, 1H, H.sub.7). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 149.06 (C.sub.10-arom.), 142.87 (C.sub.8H- arom.), 135.05 (C.sub.4-arom.), 128.84 (C.sub.1,6H-arom.), 127.43 (C.sub.12H-arom.), 126.23 (C.sub.3,5H-arom.), 125.63 (C.sub.2H-arom.), 123.67 (C.sub.14H-arom.), 117.25 (C.sub.11-arom.), 116.00 (C.sub.7H-arom.), 114.25 (C.sub.15-arom.).

tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate

[0304]

TABLE-US-00083 LabBook Code Intermediate CA 4-76 F2-6 (yield = 68%) [00540] (White Solid) t.sub.R (HPLC) = 4.99 min MS (ESI+) m/z = n.d. .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 8.11-8.06 (m, 1H, H.sub.3), 7.88 (s, 1H, H.sub.8), 7.87-7.82 (m, 1H, H.sub.6), 7.37-7.32 (m, 1H, H.sub.2), 7.31-7.26 (m, 1H, H.sub.1), 1.64 (s, 9H, H.sub.21,22,23), 1.33 (s, 12H, H.sub.15,16,17,18). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 149.11 (C.sub.24O), 135.87 (C.sub.4- arom.), 135.33 (C.sub.8H-arom.), 133.22 (C.sub.5-arom.), 124.86 (C.sub.2H-arom.), 123.48 (C.sub.1H-arom.), 122.66 (C.sub.6H-arom.), 115.06 (C.sub.3H-arom.), 107.92 (C.sub.9-arom.), 84.79 (C.sub.20(CH.sub.3).sub.3), 83.74 (C.sub.12,13(CH.sub.3).sub.2), 28.07 (C.sub.21,22,23H.sub.3), 25.14 (C.sub.15,16,17,18H.sub.3).

3-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridine (Procedure 10)

[0305]

TABLE-US-00084 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.12 13 740 CA 4-85 Precipitate (yield = 50%) IC.sub.50 (PSA) = 0.12 [00541] (Beige Solid) t.sub.R (HPLC) = 3.59 min MS (ESI+) m/z = 213.0830 [(M + H).sup.+] Mp = 188-192 C. HRMS (ESI+): calculated for C.sub.13H.sub.10FN.sub.2, m/z = 213.0823; found, 213.0823 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.91 (s, 1H, H.sub.13), 8.28 (dd, J = 4.6, 1.3 Hz, 1H, H.sub.12), 8.26 (dd, J = 8.0, 1.1 Hz, 1H, H.sub.8), 7.86 (d, J = 2.6 Hz, 1H, H.sub.14), 7.77-7.73 (m, 2H, H.sub.3.5), 7.29-7.24 (m, 2H, H.sub.1,6), 7.16 (dd, J = 7.9, 4.6 Hz, 1H, H.sub.7). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 160.52 (d, J = 242.3 Hz, C.sub.2F- arom.), 148.96 (C.sub.10-arom.), 142.92 (C.sub.8H-arom.), 131.49 (d, J = 3.0 Hz, C.sub.4- arom.), 127.99 (d, J = 7.8 Hz, C.sub.3,5H-arom.), 127.27 (C.sub.12H-arom.), 123.66 (C.sub.14H-arom.), 117.15 (C.sub.11-arom.), 116.02 (C.sub.7H-arom.), 115.61 (d, J = 21.2 Hz, C.sub.1,6H-arom.), 113.28 (C.sub.15-arom.).

3-(5-(trifluoromethyl)pyridin-2-yl)-1H-indole (Procedure 10)

[0306]

TABLE-US-00085 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.29 13 741 CA 4-88 Crystals (yield = 22%) IC.sub.50 (PSA) = 0.29 [00542] (Colorless Solid) t.sub.R (HPLC) = 4.03 min MS (ESI+) m/z = 263.0793 [(M + H).sup.+] Mp = 154-157 C. HRMS (ESI+) : calculated for C.sub.14H.sub.210F.sub.3N.sub.2, m/z = 263.0791; found, 263.0789 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.77 (s, 1H, H.sub.13), 8.94-8.92 (m, 1H, H.sub.1), 8.50 (d, J = 7.7 Hz, 1H, H.sub.12), 8.32 (d, J = 2.9 Hz, 1H, H.sub.14), 8.02-8.04 (m, 2H, H.sub.5,6), 7.49 (d, J = 7.8 Hz, 1H, H.sub.9), 7.23-7.16 (m, 2H, H.sub.7,8). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 159.25 (d, J = 1.2 Hz, C.sub.4-arom.), 145.86 (q, J = 4.2 Hz, C.sub.1H-arom.), 137.12 (C.sub.10-arom.), 133.25 (q, J = 3.1 Hz, C.sub.6H-arom.), 128.17 (C.sub.14H-arom.), 125.13 (C.sub.11-arom.), 124.31 (q, J = 271.5 Hz, C.sub.16F.sub.3), 122.14 (C.sub.8H-arom.), 121.63 (C.sub.12H-arom.), 120.55 (C.sub.7H-arom.), 120.30 (q, J = 32.1 Hz, C.sub.2-arom.), 119.02 (C.sub.5-arom.), 114.24 (C.sub.15-arom.), 111.99 (C.sub.9H-arom.).

tert-butyl 7-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate

[0307]

TABLE-US-00086 LabBook Code Intermediate CA 4-89 F10-24 (yield = 68%) [00543] (White Solid) t.sub.R (HPLC) = 5.20 min MS (ESI+) m/z = n.d. .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 7.85 (s, 1H, H.sub.8), 7.71 (d, J = 7.1 Hz, 1H, H.sub.6), 7.19 (t, J = 7.5 Hz, 1H, H.sub.1), 7.11 (d, J = 7.1 Hz, 1H, H.sub.2), 2.53 (s, 3H, H.sub.19), 1.62 (s, 9H, H.sub.22,23,24), 1.33 (s, 12H, H.sub.15,16,17,18). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 148.60 (C.sub.25O), 137.15 (C.sub.8H- arom.), 134.66 (C.sub.4-arom.), 133.93 (C.sub.5-arom.), 127.27 (C.sub.2H-arom.), 124.23 (C.sub.3-arom.), 123.28 (C.sub.1H-arom.), 119.88 (C.sub.6H-arom.), 107.29 (C.sub.9-arom.), 84.18 (C.sub.20(CH.sub.3).sub.3), 83.18 (C.sub.12,13(CH.sub.3).sub.2), 27.42 (C.sub.22,23,24H.sub.3), 24.67 (C.sub.15,16,17,18H.sub.3, 21.39 (C.sub.19H.sub.3).

3-(2-(trifluoromethyl)phenyl)-1H-indole (Procedure 10)

[0308]

TABLE-US-00087 VPC Number LabBook Code IC.sub.50 (eGFP) = 1.01 13 745 CA 4-95 F4-8 (yield = 50%) IC.sub.50 (PSA) = 0.95 [00544] (Beige Solid) t.sub.R (HPLC) = 4.15 min MS (ESI+) m/z = 260.0687 [(M + H).sup.+] Mp = 62-67 C. HRMS (ESI): calculated for C.sub.15H.sub.9F.sub.3N, m/z = 260.0693; found, 260.0687 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.39 (s, 1H, H.sub.13), 7.85 (d, J = 7.9 Hz, 1H, H.sub.1), 7.72 (t, J = 7.4 Hz, 1H, H.sub.6), 7.59 (d, J = 7.5 Hz, 1H, H.sub.5), 7.55 (t, J = 7.5 Hz, 1H, H.sub.2), 7.49 (d, J = 8.1 Hz, 1H, H.sub.9), 7.40 (s, 1H, H.sub.14), 7.36 (d, J = 7.9 Hz, 1H, H.sub.12), 7.16 (t, J = 7.5 Hz, 1H, H.sub.8), 7.04 (t, J = 7.4 Hz, 1H, H.sub.7). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 135.73 (C.sub.10-arom.), 134.23 (d, J = 1.3 Hz, C.sub.4-arom.), 133.18 (C.sub.5H-arom.), 132.04 (C.sub.6H-arom.), 127.71 (q, J = 28.6 Hz, C.sub.3-arom.), 127.01 (C.sub.11-arom.), 126.89 (C.sub.2H-arom.), 126.26 (q, J = 5.4 Hz, C.sub.1H-arom.), 124.40 (d, J = 2.9 Hz, C.sub.14H-arom.), 124.39 (q, J = 273.6 Hz, C.sub.16F.sub.3), 121.46 (C.sub.8H-arom.), 119.42 (C.sub.7H-arom.), 118.32 (C.sub.12H-arom.), 112.44 (C.sub.15-arom.), 111.70 (C.sub.9H-arom.).

2,3,4-trifluoro-6-iodoaniline

[0309]

TABLE-US-00088 LabBook Code Intermediate CA 4-100 F6-11 (yield = 36%) [00545] (Dark Solid) t.sub.R (HPLC) = 3.78 min MS (ESI+) m/z = 273.9338 [(M + H).sup.+] .sup.1H NMR( 600 MHz, CDCl.sub.3): (ppm) = 7.33 (ddd, J = 9.3, 7.6, 2.5 Hz, 1H, H.sub.6), 4.07 (s, 2H, H.sub.7). .sup.13C NMR (151 MHz, CDCl.sub.3): (ppm) = 143.20 (ddd, J = 244.0, 10.8, 2.8 Hz, C.sub.3-arom.), 139.98 (ddd, J = 250.5, 161.1, 13.7 Hz, C.sub.2-arom.), 138.48 (ddd, J = 247.1, 12.6, 3.3 Hz, C.sub.1-arom.), 133-43 (dd, J = 11.2 2.4 Hz, C.sub.4-arom.), 119.96 (dd, J = 20.1, 3.9 Hz, C.sub.6H-arom.), 73.21 (ddd, J = 8.2, 4.5, 2.1 Hz, C.sub.5-arom.).

2-(5,6,7-trifluoro-1H-indol-3-yl)quinoline

[0310]

TABLE-US-00089 LabBook Code CA 4-101 F4-6 (yield = 13%) [00546] (White Solid) t.sub.R (HPLC) = 4.32 min MS (ESI+) m/z = 299.0820 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.17H.sub.10F.sub.3N.sub.2, m/z = 299.0791; found, 299.0791 .sup.1H NMR (600 MHz, CDCl.sub.3): (ppm) = 9.99 (s, 1H, H.sub.15), 8.21 (d, J = 8.4 Hz, 1H, H.sub.10), 8.12 (d, J = 8.1 Hz, 1H, H.sub.3), 7.87 (d, J = 8.4 Hz, 1H, H.sub.9), 7.84 (d, J = 8.4 Hz, 1H, H.sub.6), 7.77 (t, J = 7.5 Hz, 1H, H.sub.2), 7.57 (t, J = 7.3 Hz, 1H, H.sub.1), 7.23 (ddd, J = 9.7, 6.5, 1.6 Hz, 1H, H.sub.19), 7.12 (s, 1H, H.sub.14). .sup.13C NMR (151 MHz, CDCl.sub.3): (ppm) = 148.30 (C.sub.8-arom.), 147.32 (C.sub.4-arom.), 146.70 (dd, J = 240.3, 12.2 Hz, C.sub.16-arom.), 138.72 (C.sub.13-arom.), 137.53 (ddd, J = 249.3, 13.6, 4.5 Hz, C.sub.17-arom.), 136.93 (ddd, J = 244.8, 17.1, 11.3 Hz, C.sub.16- arom.), 136.35 (C.sub.10-arom.), 129.70 (C.sub.2H-arom.), 128.58 (C.sub.3H-arom.), 127.22 (C.sub.6H-arom.), 127.06 (C.sub.5-arom.), 126.14 (C.sub.1H-arom.), 124.01 (dd, J = 6.9, 5.5 Hz, C.sub.12-arom.), 121.44 (dd, J = 7.7, 2.9 Hz, C.sub.11-arom.), 117.52 (C.sub.9H-arom.), 101.92 (m, C.sub.14,19H-arom.).

7-(7-methyl-1H-indol-3-yl)quinoline (Procedure 10)

[0311]

TABLE-US-00090 LabBook Code VPC Number CA 4-102 Precipitate (yield = 32 IC.sub.50 (eGFP) = 0.76 13 744 %) IC.sub.50 (PSA) = 0.75 [00547] (Green Solid) t.sub.R (HPLC) = 2.94 min MS (ESI+) m/z = 259.1272 [(M + H).sup.+] Mp = 199-201 C. HRMS (ESI+): calculated for C.sub.18H.sub.15N.sub.2, m/z = 259.1230; found, 259.1228 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.54 (s, 1H, H.sub.13), 8.89 (dd, J = 4.2, 1.7 Hz, 1H, H.sub.19), 8.34 (dd, J = 8.2, 0.9 Hz, 1H, H.sub.17), 8.30 (s, 1H, H.sub.3), 8.04-8.00 (m, 2H, H.sub.5,6), 7.98 (d, J = 2.4 Hz, 1H, H.sub.14), 7.87 (d, J = 8.0 Hz, 1H, H.sub.12), 7.47 (dd, J = 8.2, 4.2 Hz, 1H, H.sub.18), 7.10 (t, J = 7.5 Hz, 1H, H.sub.8), 7.02 (d, J = 7.0 Hz, 1H, H.sub.8), 2.54 (s, 3H, H.sub.16). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 150.65 (C.sub.19H-arom.), 148.56 (C.sub.1- arom.), 137.35 (C.sub.4-arom.), 136.61 (C.sub.10-arom.), 135.55 (C.sub.17H-arom.), 128.24 (C.sub.6H-arom.), 126.41 (C.sub.5H-arom.), 125.92 (C.sub.2-arom.), 124.71 (C.sub.14H-arom.), 124.62 (C.sub.11-arom.), 124.05 (C.sub.3H-arom.), 122.23 (C.sub.8H-arom.), 121.36 (C.sub.9- arom.), 120.40 (C.sub.7H-arom.), 120.28 (C.sub.18H-arom.), 116.64 (C.sub.12H-arom.), 115.27 (C.sub.15-arom.), 16.83 (C.sub.16H.sub.3).

tert-butyl 3-iodo-1H-pyrrolo[3,2-b]pyridine-1-carboxylate

[0312]

TABLE-US-00091 LabBook Code Intermediate CA 4-104 F1-21 (yield = 83%) [00548] (White Solid) t.sub.R (HPLC) = 4.07 min MS (ESI+) m/z = 345.0106 [(M + H).sup.+] .sup.1H NMR (400 MHz, DMSO-d.sub.6): (ppm) = 8.56 (dd, J = 4.7, 1.4 Hz, 1H, H.sub.1), 8.32 (dd, J = 8.3, 1.3 Hz, 1H, H.sub.3), 8.19 (s, 1H, H.sub.8), 7.43 (dd, J = 8.3, 4.7 Hz, 1, H.sub.2), 1.64 (s, 9H, H.sub.13,14,15). .sup.13C NMR = n.d.

3-(4-(trifluoromethyl)phenyl)-1H-indole (Procedure 10)

[0313]

TABLE-US-00092 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.38 13 743 CA 4-105 F8-16 (yield = 51%) IC.sub.50 (PSA) = 0.39 [00549] t.sub.R (HPLC) = 4.34 min MS (ESI+) m/z = 262.0850 [(M + H).sup.+] Mp = 126-129 C. HRMS (ESI+): calculated for C.sub.15H.sub.11F.sub.3N, m/z = 262.0838; found, 262.0850 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.59 (s, 1H, H.sub.13), 7.94 (d, J = 8.2 Hz, 3H, H.sub.3,5,12), 7.90 (d, J = 2.6 Hz, 1H, H.sub.14), 7.76 (d, J = 8.2 Hz, 2H, H.sub.1,6), 7.50 (d, J = 8.0 Hz, 1H, H.sub.9), 7.22-7.18 (m, 1H, H.sub.8), 7.17-7.13 (m, 1H, H.sub.7). (Pale Orange Solid) .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 140.18 (d, J= 0.8 Hz, C.sub.4-arom.), 137.04 (C.sub.10-arom.), 126.48 (C.sub.3,5H-arom.), 125.58 (q, J= 3.7 Hz, C.sub.1,6H-arom.), 125.25 (d, J= 31.7 Hz, C.sub.2-arom.), 125.00 (C.sub.14H-arom.), 124.66 (C.sub.11H-arom.), 124.62 (q, J = 271.5 Hz, C.sub.16F.sub.3), 121.76 (C.sub.8H-arom.), 120.11 (C.sub.7H-arom.), 118.92 (C.sub.12H-arom.), 114.12 (C.sub.15-arom.), 112.19 (C.sub.9H-arom.).

1-methyl-5-(naphthalen-2-yl)-1H-indole (Procedure 10)

[0314]

TABLE-US-00093 VPC Number LabBook Code IC.sub.50 (eGFP) = 2.0 13 756 CA 4-108 Precipitate (yield = 45%) IC.sub.50 (PSA) = 1.49 [00550] t.sub.R (HPLC) = 4.56 min MS (ESI+) m/z = 258.1260 [(M + H).sup.+] Mp = 200-204 C. HRMS (ESI+): calculated for C.sub.19H.sub.16N, m/z = 258.1277; found, 258.1276 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 8.21 (d, J = 0.7 Hz, 1H, H.sub.7), 8.00- 7.97 (m, 3H, H.sub.6,10,16), 7.93 (d, J = 8.0 Hz, 1H, H.sub.3), 7.91 (dd, J= 8.5, 1.7 Hz, 1H, H.sub.9), 7.64 (dd, J = 8.5, 1.6 Hz, 1H, H.sub.14), 7.57 (d, J = 8.5 Hz, 1H, H.sub.13), 7.54 (t, J = 7.3 Hz, 1H, H.sub.1), 7.49 (t, J = 7.3 Hz, 1H, H.sub.2), 7.39 (d, J = 3.0 Hz, 1H, H.sub.18), 6.53 (d, J = 3.0 Hz, 1H, H.sub.19), 3.85 (s, 3H, H.sub.20). (Pale Yellow lid) .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 139.02 (C.sub.8-arom.), 136.09 (C.sub.11- arom.), 133.52 (C.sub.5-arom.), 131.70 (C.sub.4-arom.), 131.12 (C.sub.15-arom.), 130.43 (C.sub.18H-arom.), 128.68 (C.sub.12-arom.), 128.20 (C.sub.10H-arom.), 127.95 (C.sub.6H-arom.), 127.41 (C.sub.3H-arom.), 126.19 (C.sub.1H-arom.), 125.62 (C.sub.2H-arom.), 125.50 (C.sub.9H- arom.), 124.60 (C.sub.7H-arom.), 120.61 (C.sub.14H-arom.), 118.75 (C.sub.16H-arom.), 110.20 (C.sub.13H-arom.), 100.86 (C.sub.19H-arom.), 32.58 (C.sub.20H.sub.3).

3-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[3,2-b]pyridine (Procedure 10)

[0315]

TABLE-US-00094 VPC Number LabBook Code IC.sub.50 (eGFP) = 13 CA 4-109 Precipitate (yield = 69%) IC.sub.50 (PSA) = [00551] t.sub.R (HPLC) = 2.89 min MS (ESI+) m/z = 263.0792 [(M + H).sup.+] Mp = 223-226 C. HRMS (ESI+): calculated for C.sub.14H.sub.10F.sub.3N.sub.2, m/z = 263.0791; found, 263.0790 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.78 (s, 1H, H.sub.11), 8.55 (d, J = 8.2 Hz, 2H, H.sub.3,5), 8.49 (dd, J = 4.5, 1.3 Hz, 1H, H.sub.13), 8.36 (s, 1H, H.sub.7), 7.87 (dd, J = 8.2, 1.4 Hz, 1H, H.sub.15), 7.75 (d, J = 8.3 Hz, 2H, H.sub.2,6), 7.22 (dd, J = 8.2, 4.5 (Pale Yellow Solid) Hz, 1H, H.sub.14). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 143.41 (C.sub.9-arom.), 143.07 (C.sub.13H- arom.), 139.02 (d, J = 0.9 Hz, C.sub.4-arom.), 129.64 (C.sub.10-arom.), 128.07 (C.sub.7H- arom.), 125.77 (C.sub.3,5H-arom.), 125.16 (q, J = 3.7 Hz, C.sub.2,6H-arom.), 125.14 (q, J = 31.6 Hz, C.sub.1-arom.), 124.67 (q, J = 271.4 Hz, C.sub.16F.sub.3), 119.23 (C.sub.15H-arom.), 116.93 (C.sub.14H-arom.), 112.60 (C.sub.8-arom.).

3-(2-bromophenyl)-1H-pyrrolo[3,2-b]pyridine (Procedure 10)

[0316]

TABLE-US-00095 LabBook Code CA 4-110 Precipitate2 (yield = 37%) [00552] t.sub.R (HPLC) = 2.61 minMS (ESI+) m/z = 273.0018, 274.9998 [(M + H).sup.+] HRMS (ESI+): calculated for C.sub.13H.sub.10BrN.sub.2, m/z = 2273.0022, 275.0002; found, 273.0018, 274.9998 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.61 (s, 1H, H.sub.11), 8.37 (d, J = 4.4 HZ, 1H, H.sub.13), 7.99 (s, 1H, H.sub.7), 7.90 (d, J = 7.7 Hz, 1H, H.sub.5), 7.85 (d, J = 8.1 Hz, 1H, H.sub.15), 7.74 (d, J = 7.9 Hz, 1H, H.sub.2), 7.45 (t, J = 7.5 Hz, 1H, H.sub.6), 7.24 (t, J = (Beige Solid) 7.6 Hz, 1H, H.sub.1), 7.18 (dd, J = 8.1, 4.5 Hz, 1H, H.sub.14). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 143.75 (C.sub.9-arom.), 142.71 (C.sub.13H- arom.), 134.57 (C.sub.4-arom.), 132.93 (C.sub.2H-arom.), 132.70 (C.sub.5H-arom.), 128.75 (C.sub.7H-arom.), 128.29 (C.sub.10-arom.), 127.86 (C.sub.1H-arom.), 127.21 (C.sub.6H-arom.), 122.57 (C.sub.3-arom.), 118.89 (C.sub.15H-arom.), 116.70 (C.sub.14H-arom.), 113.74 (C.sub.8- arom.).

6-(7-methyl-1H-indol-3-yl)benzo[d]thiazole (Procedure 10)

[0317]

TABLE-US-00096 VPC Number LabBook Code IC.sub.50 (eGFP) = Inactive 13 757 CA 4-114 F9-15 Precipitate (yield = 27%) IC.sub.50 (PSA) = Inactive [00553] t.sub.R (HPLC) = 4.02 min MS (ESI+) m/z = 265.0787 [(M + H).sup.+] Mp = 183-185 C. HRMS (ESI+): calculated for C.sub.16H.sub.13N.sub.2S, m/z = 265.0794; found, 265.0793 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.42 (s, 1H, H.sub.14), 9.32 (s, 1H, H.sub.8), 8.48 (d, J = 0.8 Hz, 1H, H.sub.6), 8.12 (d, J = 8.5 Hz, 1H, H.sub.3), 7.90 (dd, J = 8.5, 1.6 Hz, 1H, H.sub.4), 7.84-7.80 (m, 2H, H.sub.13,18), 7.05 (t, J = 7.5 Hz, 1H, H.sub.17), 6.99 (d, (Beige Solid) J = 7.0 Hz, 1H, H.sub.16), 2.52 (s, 3H, H.sub.19). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 154.81 (C.sub.8H-arom.), 150.95 (C.sub.1- arom.), 136.43 (C.sub.10-arom.), 134.50 (C.sub.2-arom.), 133.67 (C.sub.5-arom.), 125.37 (C.sub.4H-arom.), 124.63 (C.sub.11-arom.), 123.87 (C.sub.13H-arom.), 123.01 (C.sub.3H-arom.), 122.07 (C.sub.16H-arom.), 121.15 (C.sub.15-arom.), 119.98 (C.sub.17H-arom.), 119.15 (C.sub.6H- arom.), 116.70 (C.sub.18H-arom.), 115.44 (C.sub.12-arom.), 16.81 (C.sub.19H.sub.3).

2-(quinolin-5-yl)thiazole

[0318]

TABLE-US-00097 LabBook Code CA 4-116 F14-17 (yield = 36%) [00554] t.sub.R (HPLC) = 2.95 min MS (ESI+) m/z = 213.0468 [(M + H).sup.+] .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 9.31 (d, J = 8.7 Hz, 1H, H.sub.6), 9.00 (dd, J = 4.0, 1.6 Hz, 1H, H.sub.4), 8.18 (d, J = 8.4 Hz, 1H, H.sub.10), 8.13 (d, J = 3.3 Hz, 1H, H.sub.12), 8.05 (d, J = 7.2 Hz, 1H, H.sub.8), 7.98 (d, J = 3.3 Hz, 1H, H.sub.11), 7.89 (dd, J = 8.3, 7.4 Hz, 1H, H.sub.9), 7.67 (dd, J = 8.7, 4.1 Hz, 1H, H.sub.5). .sup.13C NMR (101 MHz, DMSO-d.sub.6): (ppm) = 165.68 (C.sub.14-arom.), 150.97 (C.sub.4H- arom.), 148.04 (C.sub.2-arom.), 143.95 (C.sub.12H-arom.), 134.04 (C.sub.6H-arom.), 131.25 (C.sub.10H-arom.), 130.17 (C.sub.7-arom.), 129.09 (C.sub.9H-arom.), 128.68 (C.sub.8H-arom.), 124.92 (C.sub.1-arom.), 122.51 (C.sub.5H-arom.), 121.55 (C.sub.11H-arom.). (Pale Yellow Solid)

5-(7-methyl-1H-indol-3-yl)benzo[d]thiazole (Procedure 10)

[0319]

TABLE-US-00098 VPC Number LabBook Code IC.sub.50 (eGFP) = Inactive 13 758 CA 4-118 F18-25 (yield = 68%) IC.sub.50 (PSA) = Inactive [00555] t.sub.R (HPLC) = 3.93 min MS (ESI+) m/z = 265.0790 [(M + H).sup.+] Mp = 133-136 C. HRMS (ESI+): calculated for C.sub.16H.sub.13N.sub.2S, m/z = 265.0794; found, 265.0790 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.43 (s, 1H, H.sub.15), 9.41 (s, 1H, H.sub.8), 8.39 (d, J = 1.1 Hz, 1H, H.sub.6), 8.20 (d, J = 8.3 Hz, 1H, H.sub.3), 7.87 (dd, J = 8.4, 1.5 HZ, 1H, H.sub.4), 7.86 (d, J = 2.6 Hz, 1H, H.sub.13), 7.79 (d, J = 8.0 Hz, 1H, H.sub.18), 7.06 (Orange Solid) (t, J = 7.5 Hz, 1H, H.sub.17), 6.99 (d, J = 7.0 Hz, 1H, H.sub.16), 2.54 (s, 3H, H.sub.19). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 156.22 (C.sub.8H-arom.), 153.99 (C.sub.2- arom.), 136.44 (C.sub.10-arom.), 134.47 (C.sub.5-arom.), 130.24 (C.sub.1-arom.), 124.84 (C.sub.4H-arom.), 124.70 (C.sub.11-arom.), 123.76 (C.sub.13H-arom.), 122.52 (C.sub.3H-arom.), 122.05 (C.sub.16H-arom.), 121.21 (C.sub.15-arom.), 120.04 (C.sub.6H-arom.), 120.01 (C.sub.17H- arom.), 116.45 (C.sub.18H-arom.), 115.56 (C.sub.12-arom.), 16.83 (C.sub.19H.sub.3).

5-(7-methyl-1H-indol-3-yl)benzo[d]oxazole (Procedure 10)

[0320]

TABLE-US-00099 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.3 13 759 CA 4-119 Precipitate (yield = 26%) IC.sub.50 (PSA) = 0.27 [00556] t.sub.R (HPLC) = 3.87 min MS (ESI+) m/z = 249.1041 [(M + H).sup.+] Mp = 171-172 C. HRMS (ESI+): calculated for C.sub.16H.sub.13N.sub.2O, m/z = 249.1022; found, 249.1016 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.35 (s, 1H, H.sub.14), 8.75 (s, 1H, H.sub.8), 8.03 (d, J = 1.3 Hz, 1H, H.sub.6), 7.82 (d, J = 8.4 Hz, 1H, H.sub.3), 7.77 (dd, J = 8.4, 1.6 Hz, 1H, H.sub.4), 7.75 (d, J = 2.6 Hz, 1H, H.sub.13), 7.72 (d, J = 8.0 Hz, 1H, H.sub.18), 7.03 (Mauve Solid) (t, J = 7.5 Hz, 1H, H.sub.17), 6.98 (d, J = 7.0 Hz, 1H, H.sub.16), 2.52 (s, 3H, H.sub.19). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 154.42 (C.sub.8H-arom.), 147.60 (C.sub.1- arom.), 140.40 (C.sub.2-arom.), 136.31 (C.sub.10-arom.), 132.98 (C.sub.5-arom.), 124.75 (C.sub.4H-arom.), 124.70 (C.sub.11-arom.), 123.40 (C.sub.13H-arom.), 121.95 (C.sub.16H-arom.), 121.11 (C.sub.15-arom.), 119.88 (C.sub.17H-arom.), 117.38 (C.sub.6H-arom.), 116.32 (C.sub.18H- arom.), 115.79 (C.sub.12-arom.), 111.18 (C.sub.3H-arom.), 16.81 (C.sub.19H.sub.3).

2-(7-methyl-1H-indol-3-yl)benzo[d]thiazole (Procedure 10)

[0321]

TABLE-US-00100 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.1 13 760 CA 4-120 F12-18 Precipitate (yield = 30%) IC.sub.50 (PSA) = 0.52 [00557] t.sub.R (HPLC) = 4.02 min MS (ESI+) m/z = 265.0788 [(M + H).sup.+] Mp = 179-182 C. HRMS (ESI+): calculated for C.sub.16H.sub.13N.sub.2S, m/z = 265.0794; found, 265.0790 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.95 (s, 1H, H.sub.5), 8.25 (d, J = 2.9 Hz, 1H, H.sub.4), 8.22 (d, J = 7.9 Hz, 1H, H.sub.9), 8.06 (d, J = 7.9 Hz, 1H, H.sub.13), 7.97 (d, J = 8.1 Hz, 1H, H.sub.16), 7.49 (t, J = 7.6 Hz, 1H, H.sub.15), 7.37 (t, J = 7.6 Hz, 1H, (Grey Solid) H.sub.14), 7.17 (t, J = 7.5 Hz, 1H, H.sub.8), 7.07 (d, J = 7.1 Hz, 1H, H.sub.7), 2.54 (s, 3H, H.sub.10). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 162.90 (C.sub.18-arom.), 153.68 (C.sub.12- arom.), 136.26 (C.sub.1-arom.), 133.03 (C.sub.11-arom.), 128.52 (C.sub.4H-arom.), 126.09 (C.sub.15H-arom.), 124.32 (C.sub.2-arom.), 124.17 (C.sub.14H-arom.), 123.25 (C.sub.7H-arom.), 121.71 (C.sub.13H-arom.), 121.63 (C.sub.6-arom.), 121.53 (C.sub.16H-arom.), 121.30 (C.sub.8H- arom.), 118.22 (C.sub.9H-arom.), 110.81 (C.sub.3-arom.), 16.74 (C.sub.10H.sub.3).

3-(3-bromophenyl)-1H-pyrrolo[3,2-b]pyridine (Procedure 10)

[0322]

TABLE-US-00101 VPC Number LabBook Code 13 760 CA 4-124 Precipitate (yield = 30%) [00558] t.sub.R (HPLC) = 2.71 min MS (ESI+) m/z = 273.0006, 274.9986 [(M + H)+] HRMS (ESI+): calculated for C.sub.13H.sub.10BrN.sub.2, m/z = 273.0022, 275.0002; found, 273.0023, 275.0003 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.69 (s, 1H), 8.65 (s, 1H), 8.49 (d, J = 3.5 Hz, 1H), 8.29 (d, J = 2.8 Hz, 1H), 8.28-8.25 (m, 1H), 7.85 (dd, J = 8.2, 1.0 Hz, 1H), 7.38-7.34 (m, 2H), 7.20 (dd, J = 8.1, 4.6 Hz, 1H). (White Solid) .sup.13C NMR = n.d.

4-bromo-2-(7-methyl-1H-indol-3-yl)thiazole (Procedure 10)

[0323]

TABLE-US-00102 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.045 13766 CA 4-125 F7-11 (yield = 43%) IC.sub.50 (PSA) = 0.02 [00559] t.sub.R (HPLC) = 4.00 min MS (ESI+) m/z = 292.9743, 294.9724 [(M + H).sup.+] Mp = 127-130 C. HRMS (ESI+): calculated for C.sub.12H.sub.10BrN.sub.2S, m/z = 292.9743, 294.9722; found, 292.9743, 294.9723 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.86 (s, 1H, H.sub.5), 8.16 (s, 1H, H.sub.4), 7.93 (d, J = 7.7 Hz, 1H, H.sub.9), 7.62 (s, 1H, H.sub.14), 7.13 (t, J = 7.3 Hz, 1H, H.sub.8), 7.04 (d, J = 6.6 Hz, 1H, H.sub.7), 2.52 (s, 3H, H.sub.10). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 164.43 (C.sub.11-arom.), 136.06 (C.sub.1- (Green Solid) arom.), 126.82 (C.sub.4H-arom.), 123.71 (C.sub.13-arom.), 123.69 (C.sub.2-arom.), 123.09 (C.sub.7H-arom.), 121.67 (C.sub.6H-arom.), 121.19 (C.sub.8H-arom.), 117.45 (C.sub.9H-arom.), 113.69 (C.sub.14H-arom.), 110.13 (C.sub.3-arom.), 16.71 (C.sub.10H.sub.3).

tert-butyl 6-fluoro-3-iodo-1H-indole-1-carboxylate

[0324]

TABLE-US-00103 Intermediate LabBook Code CA 4-126 F1-6 (yield = 95%) [00560] t.sub.R (HPLC) = 4.80 minMS (ESI+) m/z = n.d. .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 7.90 (s, 1H, H.sub.8), 7.82 (dd, J = 10.2, 2.0 Hz, 1H, H.sub.3), 7.40 (dd, J = 8.7, 5.3 Hz, 1H, H.sub.6), 7.24 (td, J = 9.1, 2.4 Hz, 1H, H.sub.1), 1.64 (s, 9H, H.sub.14,15,16). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 160.69 (d, J = 239.6 Hz, C.sub.2- arom.), 147.88 (C.sub.17O), 134.17 (d, J = 13.2 Hz, C.sub.4-arom.), 130.75 (d, J = 3.8 Hz, C.sub.8H-arom.), 128.47 (C.sub.5-arom.), 122.61 (d, J = 10.3 Hz, C.sub.6H-arom.), 111.66 (d, J = 24.4 Hz, C.sub.1H-arom.), 101.61 (d, J, = 28.9 Hz, C.sub.3H-arom.), (Pale Brown Solid) 84.90 (C.sub.13), 66.05 (C.sub.9-arom.), 27.55 (s C.sub.14,15,16H.sub.3).

3-(4-methoxyphenyl)-1H-pyrrolo[3,2-b]pyridine (Procedure 10)

[0325]

TABLE-US-00104 VPC Number LabBook Code IC.sub.50 (eGFP) = 13 CA 4-127 Precipitate (yield = 89%) IC.sub.50 (PSA) = [00561] tR (HPLC) = 2.54 minMS (ESI+) m/z = 225.1037 [(M + H).sup.+] Mp = 202-206 C. HRMS (ESI+): calculated for C.sub.14H.sub.13N.sub.2O, m/z = 225.1022; found, 2251027 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.42 (s, 1H, H.sub.11), 8.43 (dd, J = 4.5, 1.5 Hz, 1H, H.sub.13), 8.22-8.18 (m, 2H, H.sub.2,6), 8.04 (d, J = 2.8 Hz, 1H, H.sub.7), 7.80 (dd, J = 8.2, 1.5 Hz, 1H, H.sub.15), 7.16 (dd, J = 8.1, 4.5 Hz, 1H, H.sub.14), 7.01- (Pale Brown Solid) 6.96 (m, 2H, H.sub.3,5), 3.79 (s, 3H, H.sub.17). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 157.12 (C.sub.1-arom.), 143.36 (C.sub.9- arom.), 142.39 (C.sub.13H-arom.), 129.37 (C.sub.10-arom.), 127.28 (C.sub.4-arom.), 127.01 (C.sub.2,6H-arom.), 125.43 (C.sub.7H-arom.), 118.69 (C.sub.15H-arom.), 116.38 (C.sub.14H- arom.), 114.10 (C.sub.8-arom.), 113.76 (C.sub.3,5H-arom.), 55.01 (C.sub.17H.sub.3).

6-(7-methyl-1H-indol-3-yl)isoquinoline (Procedure 10)

[0326]

TABLE-US-00105 VPC Number LabBook Code IC.sub.50 (eGFP) = inactive 13765 CA 4-128 Precipitate (yield = 34%) IC.sub.50 (PSA) = inactive [00562] t.sub.R (HPLC) = 3.01 min MS (ESI+) m/z = 259.1230 [(M + H).sup.+] Mp = 222-225 C. HRMS (ESI+): calculated for C.sub.18H.sub.15N.sub.2, m/z = 259.1230; found, 259.1231 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.59 (s, 1H, H5), 9.25 (s, 1H, H.sub.16), 8.47 (d, J= 5.7 Hz, 1H, H.sub.12), 8.27 (s, 1H, H.sub.17), 8.15-8.09 (m, 2H, H.sub.19,20), 8.01 (d, J = 2.7 Hz, 1H, H.sub.4), 7.95 (d, J = 8.0 Hz, 1H, H.sub.9), 7.88 (d, J = (Yellowish Solid) 5.8 Hz, 1H, H.sub.13), 7.11 (t, J = 7.5 Hz, 1H, H.sub.9), 7.03 (d, J = 7.0 Hz, 1H, H.sub.7), 2.54 (s, 3H, H.sub.10). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 151.69 (C.sub.16H-arom.), 143.10 (C.sub.12H-arom.), 138.20 (C.sub.18-arom.), 136.65 (C.sub.1-arom.), 136.13 (C.sub.14-arom.), 127.81 (C.sub.20H-arom.), 127.20 (C.sub.19H-arom.), 126.42 (C.sub.15-arom.), 125.23 (C.sub.4H-arom.), 124.55 (C.sub.2-arom.), 122.35 (C.sub.7H-arom.), 121.35 (C.sub.6-arom.), 121.17 (C.sub.17H-arom.), 120.35 (C.sub.8H-arom.), 120.20 (C.sub.13H-arom.), 116.98 (C.sub.9H-arom.), 115.17 (C.sub.3-arom.), 16.81 (C.sub.10H.sub.3).

2-(6-fluoro-1H-indol-3-yl)quinoline

[0327]

TABLE-US-00106 VPC Number LabBook Code IC.sub.50 (eGFP) = 0.1 13764 CA 4-131 F25-28 Precipitate (yield = 5%) IC.sub.50 (PSA) = 0.082 [00563] t.sub.R (HPLC) = 3.07 min MS (ESI+) m/z = 263.0968 [(M + H).sup.+] Mp = 195-198 C. HRMS (ESI+): calculated for C.sub.17H.sub.12FN.sub.2, m/z = 263.0979; found, 263.0981 .sup.1H NMR (600 MHz, DMSO-d.sub.6): (ppm) = 11.71 (s, 1H, H.sub.17), 8.90 (dd, J = 8.7, 5.9 Hz, 1H, H.sub.16), 8.36 (d, J = 2.6 Hz, 1H, H.sub.18), 8.27 (d, J = 8.7 Hz, 1H, H.sub.10), 8.06-8.02 (m, 2H, H.sub.3,9), 7.90 (d, J = 7.7 Hz, 1H, H.sub.6), 7.72 (ddd, J = (Pale Yellow Solid) 8.3, 7.2, 1.3 Hz, 1H, H.sub.6), 7.49 (ddd, J = 7.8, 6.6, 0.6 Hz, 1H, H.sub.1), 7.26 (dd, J = 9.8, 2.4 Hz, 1H, H.sub.13), 7.07 (td, J = 9.6, 2.4 Hz, 1H, H.sub.11). .sup.13C NMR (151 MHz, DMSO-d.sub.6): (ppm) = 159.13 (d, J = 235.8 Hz, C.sub.12- arom.), 155.18 (C.sub.8-arom.), 147.68 (C.sub.4-arom.), 137.16 (d, J = 12.5 Hz, C.sub.14- arom.), 135.69 (C.sub.10H-arom.), 129.38 (C.sub.2H-arom.), 128.39 (C.sub.3H-arom.), 128.32 (d, J = 2.8 Hz, C.sub.18H-arom.), 127.63 (C.sub.6H-arom.), 125.87 (C.sub.5-arom.), 125.02 (C.sub.1H-arom.), 123.78 (d, J = 9.8 Hz, C.sub.16H-arom.), 122.40 (C.sub.15-arom.), 119.08 (C.sub.9H-arom.), 115.58 (C.sub.19-arom.), 108.64 (d, J = 23.6 Hz, C.sub.11H- arom.), 97.73 (d, J = 25.4 Hz, C.sub.13H-arom.).
A person of skill in the art based on the general knowledge in the art and the information provided herein would be able to synthesize the compounds described herein or modify the compounds described herein.
eGFP Cellular Transcription Assay
AR transcriptional activity was assayed as previously described (Tavassoli, P. et al. Rapid, non-destructive, cell-based screening assays for agents that modulate growth, death, and androgen receptor activation in prostate cancer cells. Prostate 2007, 67, 416-426). Briefly, stably transfected eGFP-expressing LNCaP human prostate cancer cells (LN-ARR2PB-eGFP) containing an androgen responsive probasin-derived promoter (ARR2PB) were grown in phenol red free RPMI 1640 supplemented with 5% CSS. After 5 days, the cells were plated into a 96-well plate (35,000 cells/well) with 0.1 nM of the synthetic androgen R1881 and increasing concentrations (0-100 M) of compound. The cells were incubated for three days and the fluorescence was then measured (excitation 485 nm, emission 535 nm). The viability of these cells was assayed by MTS cell proliferation assay (CellTiter 961 Aqueous One Solution Reagent, Promega)

Structure Solution and Refinement

[0328] The ternary complex structure was solved by molecular replacement using the Phaser program (McCoy, A. J. et al. Phaser crystallographic software. J Appl Crystallogr 2007, 40, 658-674) and the coordinate of an apo-protein structure of AR-testosterone complex (Protein Data Bank entry 2AM9) as the search model. The structures were refined with iterative cycles of manual density fitting with COOT and refinement with Refmac (Murshudov, G. N. et al. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr. 1997, 53, 240-255). The extra density of testosterone was clearly observed at the initial refinement step. A characteristic electron density of the compound was observed at the BF3 binding site.

Heterologous Expression of Androgen Receptor

[0329] The AR ligand binding domain was expressed and purified as previously described (Estebanez-Perpina, E. et al. Proc. Nat. Acad. Sci. USA (2007) 104:16074-16079).
eGFP Cellular AR Transcription Assay:

[0330] AR transcriptional activity was assayed as previously described..sup.21 Briefly, stably transfected eGFP-expressing LNCaP human prostate cancer cells (LN-ARR2PBeGFP) containing an androgen-responsive probasin-derived promoter (ARR2PB) were grown in phenol-red-free RPMI 1640 supplemented with 5% CSS. After 5 days, the cells were plated into a 96-well plate (35,000 cells/well) with 0.1 nM R1881 and increasing concentrations (0-100 M) of compound. The cells were incubated for 3 days, and the fluorescence was then measured (excitation, 485 nm; emission, 535 nm). The viability of these cells has been assayed by the MTS cell proliferation assay (CellTiter 961 Aqueous One Solution Reagent, Promega) according to the instructions of the manufacturer.

Prostate Surface Antigen Assay:

[0331] The evaluation of PSA excreted into the media was performed in parallel to the eGFP assay using the same plates (see above description). After the cells were incubated for 3 days 150 l of the media was taken from each well, and added to 150p of PBS. PSA levels were then evaluated using Cobas e 411 analyzer instrument (Roche Diagnostics) according to the manufacturer's instructions.

EXAMPLES

Example 1Virtual Screen for Potential BF3 Binders

[0332] Using a previously described (Axerio-Cilies, P. et al. Inhibitors of Androgen Receptor Activation Function-2 (AF2) Site Indentified Through Virtual Screening. J Med Chem 2011 54(18):6197-205), consensus-based in silico methodology we conducted a virtual screen of 10 million purchasable chemical substances from the ZINC database to identify BF3-specific binders (also one NCI compound). The screening method used a combination of large-scale docking, ligand-based QSAR modeling, pharmacophore search, molecular field analysis, molecular-mechanic and molecular dynamic simulations (Cherkasov, A. et al. Progressive docking: a hybrid QSAR/docking approach for accelerating in silico high throughput screening. J Med Chem. 2006, 49, 7466-7478; Cherkasov, A. et al. Inductive charges on atoms in proteins: comparative docking with the extended steroid benchmark set and discovery of a novel SHBG ligand. J Chem Inf Model 2005, 45, 1842-1853; and Santos-Filho, O. A. and Cherkasov, A. Using molecular docking, 3D-QSAR, and cluster analysis for screening structurally diverse data sets of pharmacological interest. J Chem Inf Model 2008, 48, 2054-2065). The results from each stage of this multi-parametric approach were compiled and the compounds were ranked using a consensus scoring procedure. The highest ranked compounds were visualized and initial candidates, predicted to have a high potential for binding to the BF3 pocket, were selected for empirical testing.

Example 2Cell-Based Testing

[0333] All compounds were screened for their ability to inhibit AR transcriptional activity using a non-destructive, cell-based eGFP screening assay (Tavassoli, P. et al. Rapid, non-destructive, cell-based screening assays for agents that modulate growth, death, and androgen receptor activation in prostate cancer cells. Prostate 2007, 67, 416-426). In this assay, the expression of eGFP is under the control of an androgen responsive probasin-derived promoter and can quantify AR transcriptional activity. From the compounds tested, 7 showed sub-M IC50 values in the eGFP assay. Compounds that exhibited non-specific cellular toxicity were removed from further analysis. The most potent molecules had IC.sub.50's ranging in from 0.11 to 50 M range (TABLE 3). Some compounds were also tested in the PSA assay (TABLE 3).

TABLE-US-00107 TABLE 3 Structural and experimental data for the AR BF.sub.3 interactors. eGFP Internal ZINC IC.sub.50 PSA IC.sub.50 Number Number STRUCTURE (M) (M) 13555 Synthetic derivative [00564] Inactive Not tested 13557 Synthetic derivative [00565] Inactive Not tested 9039 Synthetic derivative [00566] >200 Not tested 13312 ZINC00298052 [00567] 200.0 Not tested 9040 Synthetic derivative [00568] 39.13 Not tested 13309 ZINC01234071 [00569] 27.2 Not tested 9034 Synthetic derivative [00570] 20 Not tested 13551 Synthetic derivative [00571] 15.5 Not tested 13550 Synthetic derivative [00572] 11.75 Not tested 9026 Synthetic derivative [00573] 11.67 Not tested 13544 Synthetic derivative [00574] 11.4 13561 Synthetic derivative [00575] 10.7 Not tested 13310 ZINC00297221 [00576] 10.3 Not tested 13232 ZINC02992016 [00577] 10 Not tested 9028 Synthetic derivative [00578] 10 Not tested 13050 ZINC03365783 [00579] 9.725 Not Determined 13300 ZINC00270867 [00580] 9.3 6.76 13299 ZINC00499454 [00581] 8.2 Not tested 9027 Synthetic derivative [00582] 7.721 Not tested 13538 Synthetic derivative [00583] 7.7 13304 ZINC00270887 [00584] 7.3 4.54 13258 ZINC18191564 [00585] 6.8 Not tested 13559 Synthetic derivative [00586] 6.6 Not tested 13512 Synthetic derivative [00587] 6.0 13542 Synthetic derivative [00588] 5.7 9125 ZINC30469682 [00589] 5.2 2.4 13186 ZINC00513042 [00590] 5 Not determined 13224 ZINC04106386 [00591] 5 Not determined 13524 Synthetic derivative [00592] 4.9 6.65 13508 Synthetic derivative [00593] 4.8 2.7 13250 ZINC03149578 [00594] 4.7 Not tested 13530 Synthetic derivative [00595] 4.7 1.60 13303 ZINC00270884 [00596] 4.5 Not tested 13503 Synthetic derivative [00597] 4.5 Not tested 13257 ZINC12345945 [00598] 4.2 Not tested 13502 Synthetic derivative [00599] 4.1 Not tested 9037 Synthetic derivative [00600] 4.093 Not tested 13243 ZINC00253227 [00601] 3.9 Not tested 13543 Synthetic derivative [00602] 3.7 3.19 13424 ZINC12346351 [00603] 3.7 3.58 13516 Synthetic derivative [00604] 3.6 Not tested 6054 ZINC08718421 [00605] 3.4 Not Determined 13505 Synthetic derivative [00606] 3.4 Not tested 13522 Synthetic derivative [00607] 3.4 2.19 13029 ZINC00210926 [00608] 3.221 Not Determined 13548 Synthetic derivative [00609] 3.21 4.24 9128 ZINC47424036 [00610] 3.2 3.5 13525 Synthetic derivative [00611] 3.1 7.09 13511 Synthetic derivative [00612] 3.0 1.9 13216 ZINC06025409 [00613] 2.8 Not Determined 13532 Synthetic derivative [00614] 2.8 3.10 13260 ZINC4941101 [00615] 2.7 Not tested 13416 ZINC01869964 [00616] 2.7 2.32 13509 Synthetic derivative [00617] 2.6 3.1 9043 Synthetic derivative [00618] 2.503 Not tested 13202 ZINC01768344 [00619] 2.5 Not Determined 13510 Synthetic derivative [00620] 2.5 1.54 13540 Synthetic derivative [00621] 2.5 Not tested 13411 ZINC04106386 [00622] 2.4 2.4 13560 Synthetic derivative [00623] 2.3 7.5 13214 ZINC26472877 [00624] 2.2 Not Determined 13235 ZINC01037115 [00625] 2.2 1.01 13536 Synthetic derivative [00626] 2.2 2.521 13556 Synthetic derivative [00627] 2.112 2.18 13127 ZINC00392643 [00628] 2.1 0.11 13261 ZINC48546225 [00629] 2.1 Not tested 13215 ZINC05504717 [00630] 2 Not Determined 13504 Synthetic derivative [00631] 2.0 1.69 13167 NSC105329 [00632] 1.9 1.25 13206 ZINC04962047 [00633] 1.8 Not Determined 13145 ZINC34603778 [00634] 1.7 2.46 13549 Synthetic derivative [00635] 1.7 2.57 13245 ZINC00555700 [00636] 1.7 1.69 13036 ZINC14961821 [00637] 1.602 Not Determined 13166 ZINC01723993 [00638] 1.6 2.12 13558 Synthetic derivative [00639] 1.6 2.1 13535 Synthetic derivative [00640] 1.5 1.873 13164-B ZINC02046058 [00641] 1.3 1.59 13500 Synthetic derivative [00642] 1.23 0.41 13254 ZINC18191551 [00643] 1.2 Not tested 13410 ZINC04106383 [00644] 1.2 2.03 13552 Synthetic derivative [00645] 1.125 1.14 13423 ZINC18191568 [00646] 1.1 1.2 13222 ZINC02718340 [00647] 0.95 0.74 13247 ZINC48090221 [00648] 0.9 0.43 13412 ZINC02718340 [00649] 0.9 1.23 13534 Synthetic derivative [00650] 0.8 1.251 13434 ZINC00069102 [00651] 0.8 0.73 13164-A ZINC02046058 [00652] 0.77 0.67 13220 ZINC48544111 [00653] 0.7 Not Determined 13225 ZINC18191568 [00654] 0.7 0.9 13537 Synthetic derivative [00655] 0.7 0.8057 13436 ZINC00068959 [00656] 0.6 0.4 13554 Synthetic derivative [00657] 0.59 0.67 13541 Synthetic derivative [00658] 0.5 0.94 13255 ZINC18191553 [00659] 0.5 0.46 13163-A ZINC02043019 [00660] 0.48 0.16 13163-B ZINC02043019 [00661] 0.48 0.24 13256 ZINC05848672 [00662] 0.4 0.13 13521 Synthetic derivative [00663] 0.4 0.26 13427 ZINC00588219 [00664] 0.4 0.31 13259 ZINC18191559 [00665] 0.3 0.25 13506 Synthetic derivative [00666] 0.18 0.6 13226 ZINC18191571 [00667]23 0.11 0.076 13562 Known see U.S. Pat. No. 6,207,679 [00668] 0.06 0.14 13566 Known see U.S. Pat. No. 6,207,679 [00669] 0.004 0.011 13567 Synthetic derivative [00670] 0.200 0.230 13568 Synthetic derivative [00671] 1.300 1.560 13569 Synthetic derivative [00672] 1.600 Not tested 13570 Synthetic derivative [00673] 20.000 Not tested 13571 Synthetic derivative [00674] 1.100 Not tested 13573 Synthetic derivative [00675] 0.560 Not tested 13574 Synthetic derivative [00676] 2.570 Not tested 13576 Synthetic derivative [00677] 0.144 0.048 13577 Synthetic derivative [00678] 3.200 1.730 13579 Synthetic derivative [00679] 0.101 0.043 13580 Synthetic derivative [00680] 2.900 Not tested 13582 Synthetic derivative [00681] 0.052 0.041 13585 Synthetic derivative [00682] 0.110 0.039 13587 Synthetic derivative [00683] 0.760 0.530 13589 Synthetic derivative [00684] 5.300 Not tested 13591 Synthetic derivative [00685] 0.042 0.085 13592 Synthetic derivative [00686] 1.590 1.220 13593 Synthetic derivative [00687] 0.198 0.130 13594 Synthetic derivative [00688] 0.166 0.099 13595 Synthetic derivative [00689] 0.177 Not tested 13596 Synthetic derivative [00690] Inactive Inactive 13597 Synthetic derivative [00691] 0.236 0.132 13598 Synthetic derivative [00692] Inactive Inactive 13599 Synthetic derivative [00693] Inactive Inactive 13600 Synthetic derivative [00694] 1.249 0.929 13601 Synthetic derivative [00695] 0.233 0.165 13602 Synthetic derivative [00696] 0.240 0.182 13603 Synthetic derivative [00697] 0.633 0.339 13604 Synthetic derivative [00698] Inactive Inactive 13605 Synthetic derivative [00699] Inactive Inactive 13606 Synthetic derivative [00700] 1.649 1.427 13607 Synthetic derivative [00701] 0.168 0.087 13608 Synthetic derivative [00702] Inactive Inactive 13609 Synthetic derivative [00703] Inactive Inactive 13610 Synthetic derivative [00704] 0.032 0.013 13611 Synthetic derivative [00705] 0.297 0.121 13612 Synthetic derivative [00706] 1.44 0.813 13613 Synthetic derivative [00707] 11.540 1.738 13614 Synthetic derivative [00708] 1.117 0.597 13615 Synthetic derivative [00709] Inactive Inactive 13616 Synthetic derivative [00710] Inactive Inactive 13617 Synthetic derivative [00711] Inactive Inactive 13618 Synthetic derivative [00712] 0.194 0.13 13619 Synthetic derivative [00713] 2.170 Not tested 13620 Synthetic derivative [00714] Inactive Inactive 13621 Synthetic derivative [00715] 0.02 0.008 13622 Synthetic derivative [00716] 0.1 0.075 13623 Synthetic derivative [00717] Inactive Inactive 13624 Synthetic derivative [00718] 0.100 0.042 13625 Synthetic derivative [00719] 1.900 1.230 13626 Synthetic derivative [00720] 2.700 1.650 13627 Synthetic derivative [00721] 1.500 1.160 13628 Synthetic derivative [00722] 0.800 0.610 13629 Synthetic derivative [00723] 4.900 1.780 13630 Synthetic derivative [00724] 0.600 0.430 13631 Synthetic derivative [00725] Inactive Inactive 13632 Synthetic derivative [00726] Inactive Inactive 13633 Synthetic derivative [00727] 6.000 Not tested 13634 Synthetic derivative [00728] 5.000 Not tested 13635 Synthetic derivative [00729] Inactive Inactive 13636 Synthetic derivative [00730] Inactive Inactive 13637 Synthetic derivative [00731] Inactive Inactive 13638 Synthetic derivative [00732] Inactive Inactive 13639 Synthetic derivative [00733] 0.549 0.544 13640 Synthetic derivative [00734] 12.670 Not tested 13641 Synthetic derivative [00735] 0.132 0.403 13642 Synthetic derivative [00736] 0.033 0.025 13643 Synthetic derivative [00737] 0.1638 0.156 13644 Synthetic derivative [00738] 3.000 Not tested 13645 Synthetic derivative [00739] 0.261 0.247 13646 Synthetic derivative [00740] 0.179 0.224 13647 Synthetic derivative [00741] Inactive Inactive 13648 Synthetic derivative [00742] Inactive Inactive 13649 Synthetic derivative [00743] Inactive Inactive 13650 Synthetic derivative [00744] 1.631 Not tested 13651 Synthetic derivative [00745] 0.404 Not tested 13652 Synthetic derivative [00746] 3.54 1.76 13653 Synthetic derivative [00747] 1.13 0.29 13654 Synthetic derivative [00748] 0.92 0.16 13655 Synthetic derivative [00749] 1.66 0.61 13656 Synthetic derivative [00750] 0.99 0.46 13657 Synthetic derivative [00751] Inactive Inactive 13658 Synthetic derivative [00752] 2.85 2.21 13659 Synthetic derivative [00753] Inactive Inactive 13660 Synthetic derivative [00754] 2.5 1.89 13661 Synthetic derivative [00755] Inactive Inactive 13662 Synthetic derivative [00756] Inactive Inactive 13663 Synthetic derivative [00757] Inactive Inactive 13664 Synthetic derivative [00758] Inactive Inactive 13665 Synthetic derivative [00759] 0.27 0.21 13666 Synthetic derivative [00760] Inactive Inactive 13667 Synthetic derivative [00761] Inactive Inactive 13668 Synthetic derivative [00762] Inactive Inactive 13669 Synthetic derivative [00763] Inactive Inactive 13670 Synthetic derivative [00764] Inactive Inactive 13671 Synthetic derivative [00765] Inactive Inactive 13672 Synthetic derivative [00766] Inactive Inactive 13673 Synthetic derivative [00767] Inactive Inactive 13674 Synthetic derivative [00768] 0.075 0.051 13677 Synthetic derivative [00769] 0.156 0.11 13678 Synthetic derivative [00770] Inactive Inactive 13679 Synthetic derivative [00771] Inactive Inactive 13680 Synthetic derivative [00772] 0.8 Not tested 13681 Synthetic derivative [00773] 2.5 1.7 13682 Synthetic derivative [00774] 0.89 0.99 13683 Synthetic derivative [00775] 2.6 1.906 13684 Synthetic derivative [00776] 1.4 6.609 13685 Synthetic derivative [00777] Inactive Inactive 13686 Synthetic derivative [00778] Inactive Inactive 13687 Synthetic derivative [00779] Inactive Inactive 13688 Synthetic derivative [00780] 0.069 0.068 13689 Synthetic derivative [00781] Inactive Inactive 13690 Synthetic derivative [00782] Inactive Inactive 13691 Synthetic derivative [00783] 0.4 0.48 13692 Synthetic derivative [00784] 0.1 0.082 13693 Synthetic derivative [00785] 0.11 0.12 13694 Synthetic derivative [00786] 0.07 0.067 13695 Synthetic derivative [00787] 0.069 0.087 13696 Synthetic derivative [00788] 0.042 0.042 13697 Synthetic derivative [00789] 0.029 0.029 13698 Synthetic derivative [00790] 0.041 0.041 13699 Synthetic derivative [00791] 0.073 0.073 13700 Synthetic derivative [00792] Inactive Inactive 13701 Synthetic derivative [00793] Inactive Inactive 13702 Synthetic derivative [00794] 0.21 0.14 13704 Synthetic derivative [00795] 0.35 0.169 13705 Synthetic derivative [00796] Inactive Inactive 13706 Synthetic derivative [00797] Inactive Inactive 13707 Synthetic derivative [00798] Inactive Inactive 13708 Synthetic derivative [00799] 0.29 0.29 13709 Synthetic derivative [00800] Inactive Inactive 13710 Synthetic derivative [00801] 0.23 0.25 13711 Synthetic derivative [00802] Inactive Inactive 13712 Synthetic derivative [00803] Inactive Inactive 13713 Synthetic derivative [00804] 0.037 13714 Synthetic derivative [00805] Inactive Inactive 13717 Synthetic derivative [00806] 0.49 0.33 13718 Synthetic derivative [00807] 0.37 0.11 13719 Synthetic derivative [00808] 0.11 0.13 13720 Synthetic derivative [00809] Inactive Inactive 13721 Synthetic derivative [00810] Inactive Inactive 13722 Synthetic derivative [00811] Inactive Inactive 13723 Synthetic derivative [00812] Inactive Inactive 13724 Synthetic derivative [00813] Inactive Inactive 13725 Synthetic derivative [00814] Inactive Inactive 13726 Synthetic derivative [00815] Inactive Inactive 13727 Synthetic derivative [00816] Inactive Inactive 13728 Synthetic derivative [00817] Inactive Inactive 13729 Synthetic derivative [00818] Inactive Inactive 13730 Synthetic derivative [00819] 0.149 0.198 13731 Synthetic derivative [00820] 0.304 0.255 13732 Synthetic derivative [00821] 0.42 Not tested 13733 Synthetic derivative [00822] 3.815 0.9194 13736 Synthetic derivative [00823] 0.62 0.68 13738 Synthetic derivative [00824] 0.083 0.062 13741 Synthetic derivative [00825] 0.29 0.29 13742 Synthetic derivative [00826] 0.22 0.2 13743 Synthetic derivative [00827] 0.38 0.39 13744 Synthetic derivative [00828] 0.76 0.75 13745 Synthetic derivative [00829] 1.01 0.95 13746 Synthetic derivative [00830] Inactive Inactive 13747 Synthetic derivative [00831] Inactive Inactive 13748 Synthetic derivative [00832] Inactive Inactive 13749 Synthetic derivative [00833] 0.29 0.22 13750 Synthetic derivative [00834] Inactive Inactive 13751 Synthetic derivative [00835] Inactive Inactive 13752 Synthetic derivative [00836] 0.37 0.26 13753 Synthetic derivative [00837] 0.16 0.098 13754 Synthetic derivative [00838] 0.09 0.051 13755 Synthetic derivative [00839] 0.47 0.47 13757 Synthetic derivative [00840] Inactive Inactive 13758 Synthetic derivative [00841] Inactive Inactive 13759 Synthetic derivative [00842] 0.3 0.27 13760 Synthetic derivative [00843] 0.1 0.052 13761 Synthetic derivative [00844] 0.5481 0.3829 13762 Synthetic derivative [00845] 0.4792 0.429 13764 Synthetic derivative [00846] 0.1 0.082 13765 Synthetic derivative [00847] Inactive Inactive 13766 Synthetic derivative [00848] 0.045 0.020 13769 Synthetic derivative [00849] Inactive Inactive 13770 Synthetic derivative [00850] 0.1 0.017 13771 Synthetic derivative [00851] 0.2 0.090 13772 Synthetic derivative [00852] 0.2 0.172 13773 Synthetic derivative [00853] 0.3 0.303 13774 Synthetic derivative [00854] 0.7 0.773 13775 Synthetic derivative [00855] 3.7 Not tested 13776 Synthetic derivative [00856] 0.21 0.19 13777 Synthetic derivative [00857] Not tested Not tested 13778 Synthetic derivative [00858] Not tested Not tested 13779 Synthetic derivative [00859] Not tested Not tested 13780 Synthetic derivative [00860] Not tested Not tested 13781 Synthetic derivative [00861] Not tested Not tested 13782 Synthetic derivative [00862] 0.11 Not tested 13783 Synthetic derivative [00863] Not tested Not tested 13784 Synthetic derivative [00864] Not tested Not tested 13785 Synthetic derivative [00865] 0.036 Not tested 13786 Synthetic derivative [00866] 0.013 Not tested 13787 Synthetic derivative [00867] 0.19 Not tested 13788 Synthetic derivative [00868] Not tested Not tested 13507 Synthetic derivative [00869] Not tested Not tested 13513 Synthetic derivative [00870] Not tested Not tested 13514 Synthetic derivative [00871] Not tested Not tested 13515 Synthetic derivative [00872] Not tested Not tested 13517 Synthetic derivative [00873] Not tested Not tested 13518 Synthetic derivative [00874] Not tested Not tested 13519 Synthetic derivative [00875] Not tested Not tested 13520 Synthetic derivative [00876] Not tested Not tested 13523 Synthetic derivative [00877] Not tested Not tested 13526 Synthetic derivative [00878] Not tested Not tested 13527 Synthetic derivative [00879] Not tested Not tested 13531 Synthetic derivative [00880] Not tested Not tested 13539 Synthetic derivative [00881] Not tested Not tested 13545 Synthetic derivative [00882] Not tested Not tested 13546 Synthetic derivative [00883] Not tested Not tested 13547 Synthetic derivative [00884] Not tested Not tested
Where a compound is described as inactive, no activity was detected for the compound in the assays on which it was tested.
Although various embodiments of the invention are disclosed herein, many adaptations and modifications may be made within the scope of the invention in accordance with the common general knowledge of those skilled in this art. Such modifications include the substitution of known equivalents for any aspect of the invention in order to achieve the same result in substantially the same way. Numeric ranges are inclusive of the numbers defining the range. The word comprising is used herein as an open-ended term, substantially equivalent to the phrase including, but not limited to, and the word comprises has a corresponding meaning. As used herein, the singular forms a, an and the include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to a thing includes more than one such thing. Citation of references herein is not an admission that such references are prior art to an embodiment of the present invention. The invention includes all embodiments and variations substantially as hereinbefore described and with reference to the examples and drawings.