FUSED CYCLOHEPTANE AND FUSED AZACYCLOHEPTANE COMPOUNDS AND THEIR METHODS OF USE

Abstract: The invention comprises novel compounds of formula E-B-(Alk)p-Q-(Alk)q-A-G wherein G is a radical of formula (I), (II) or (III) that are effective in the prophylaxis and treatment of diseases, such as integrin receptors mediated diseases, in particular, diseases or conditions mediated by integrin receptors, such as alpha v beta 3, alpha v beta 5, alpha v beta 6 and the like. The invention encompasses novel compounds, pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of such diseases and disorders. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Description: FUSED CYCLOHEPTANE AND FUSED AZACYCLOHEPTANE COMPOUNDS AND THEIR METHODS OF USE This application claims the benefit of U.S. Provisional Application No. 60/156,174 filed September 27, 1999, which is hereby incorporated by reference in its entirety. Background of the Invention The present invention comprises a new class of compounds useful in treating diseases, such as diseases, conditions or disorders mediated by integrin receptors, such as vitronectin and fibronectin receptors. In particular, the compounds of the invention and pharmaceutical compositions thereof are useful for the prophylaxis and treatment of diseases, conditions or disorders involving atherosclerosis, restenosis, inflammation, cancer, osteoporosis and the like. This invention also relates to intermediates and processes useful in the preparation of such compounds. Integrins are heteromeric cell surface receptors many of which have extracellular domains that bind to an Arg-Gly-Asp tripeptide (RDG) found in extracellular (plasma and matrix) proteins, such as fibronectin, vitronectin, fibrinogen and osteopontin. The fibrinogen receptor, gpIIb/IIIa integrin, is a platelet surface receptor that is thought to mediate platelet aggregation and the formation of hemostatic clot at bleeding wound sites (Blood. 71:831, 1988). Vitronectin receptors, α v β 3 and α v β 5 integrin, are expressed by a number of cells, such as endothelial, smooth muscle, osteoclast, bone resorbing, tumor and epithelial cells. Integrin α v β 3 has been reported to be involved in bone resorption (Endocrinology 137:2347-54, 1996; J. Endocrinol. 154 (Suppl . ) : S47-S56 , 1997), in cell attachment, spreading and migration (Int. J. Biochem. Cell Biol. 31:539-544, 1999; Carreitas et al . , Int. J. Cancer 80:285-294, 1999), in signal transduction, cell to cell interactions and is upregulated in response to vascular damage (Int. J. Biochem. Cell Biol. 29:721-725, 1997), in tumor cell invasion, angiogenesis, wound healing, phagocytosis of apototic cells and inflammation (J. Cell Biol. 144:767- 775, 1999; Drug News Perspect. 10:456-461, 1997; Am. J. Pathol. 148:1407-1421, 1996), in tumor growth and hypercalcemia of malignancy (Cancer Res. 58:1930-1935, 1998), in tumorigenicity of human melanoma cells (Natali et al . , Cancer Res. 57:1554-60, 1997), in melanoma metastasis (Cancer Metastasis Rev. 14:241-245, 1995; Cancer Metastasis Rev. 10:3-10, 1991), in the chondrocyte synthesis of matrix metalloproteinases (such as stromelysin, collagenase and gelatinase) which are involved in diseases such as rheumatoid arthritis and osteoarthritis (Arthritis Rheum. 38:1304-1314, 1995), in the progression of the renal injury in Fabry disease (Clin. Chim. Acta 279:55-68, 1999), and in viral infections (J. Virol. 72:3587-3594, 1998; Virology 203:357-65, 1994). Keenan et al . (J. Med. Chem. 40:2289-92, 1997) disclose examples of α v β 3 inhibitors which are selective for α v β 3 over platelet fibrinogen receptor (0S IIb β 3 ) . Integrin α v β 5 (Smith et al . , J. Biol. Chem. 265:11008-13, 1990) is thought to be involved in endocytosis and degredation of vitronectin (J. Biol. Chem. 268:11492-5, 1993), cellular locomotion of human keratinocytes (J. Biol. Chem. 269:26926-32, 1994), tumor cell metastasis (J. Clin. Invest. 99:1390-1398, 1997), differentiation of neuroblastoma metastasis (Am. J. Pathol. 150:1631-1646, 1997), and viral infections (Nat. Med. (N.Y.) 5:78-82, 1999; J. Cell Biol. 127:257- 64, 1994) . Integrin α v β 6 is an RGD, tenascin and fibronectin binding protein (J. Biol. Chem. 267:5790-6, 1992) which is expressed by a number of cells, such as carcinoma and epithelial cells, and is thought to be involved in carcinoma cell proliferation (J. Biol. Chem. 127:547- 56, 1994), in wound healing and cell attachment (J. Invest. Dermatol. 106:42-8, 1996), in epithelial inflammation, such as asthma (J. Cell Biol. 133:921- 928, 1996), in inducing gelatinase B secretion, activation of the protein kinase-C pathway, tumor cell spreading and proliferation in colon cancer cells (Biochem. Biophys. Res. Commun. 249:287-291, 1998; Int. J. Cancer 81:90-97, 1999), in regulation of pulmonary inflammation and fibrosis and binding and activating transforming growth factor βl (Munger et al . , Cell (Cambridge, Mass) 96:319-328, 1999), and in viral infections (Virology 239:71-77, 1997). Antagonists of vitronectin receptors cc v β 3 , α v β s and/or α v β 6 have been reported to be useful in the treatment and prevention of atherosclerosis, restenosis, inflammation, wound healing, cancer (e.g., tumor regression by inducing apoptosis) , metastasis, bone resorption related diseases (e.g., osteoporosis), diabetic retinopathy, macular degeneration, angiogenesis and viral disease (e.g., WO 99/30713; WO 99/30709) . WO 99/05107 discloses benzocycloheptenylacetic acid compounds useful as vitronectin receptor antagonists . WO 98/14192 discloses benzazepin-3-on-4-ylacetic acid compounds as vitronectin receptor antagonists. WO 96/26190 discloses benzodiazepine-3-one and benzazepin-3-one compounds as integrin receptor inhibitors . WO 99/11626 discloses compounds of the formula wherein m, A, E, X 1 , X 2 , R 2 , R 3 , R 4 , R 6 and R 7 are as defined therein, are useful as integrin receptor inhibitors, in particular fibrinogen (0C IIb β 3 ) or vitronectin (0C v β 3 ) receptor inhibitors. WO 97/01540 discloses compounds of the formula wherein A 1# E, X 1 , X 2 , X 3 , R 2 , R 3 , R 4 , R 6 and R 7 are as defined therein, are useful as integrin receptor inhibitors, in particular fibrinogen (α ιIb β 3 ) or vitronectin (θt v β 3 ) receptor inhibitors. US 5,565,449 discloses compounds of the formula wherein A, D, G, T, U, W and X are as defined therein, are useful as integrin inhibitors of fibrinogen GPII..III.. US 5,705,890 discloses tricyclic benzodiazepine compounds useful as platelet aggregation (fibrinogen binding) inhibitors. US 5,674,865 discloses benzodiazepinedione compounds useful as platelet aggregation (fibrinogen binding) inhibitors. WO 99/15178 and WO 99/15170 disclose benzazepineacetic acid compounds useful as vitronectin receptor antagonists. WO 99/11626 and WO 99/06049 disclose tricyclic benzazepine, benzodiazepineacetate and benzazepineacetate compounds useful as fibrinogen and vitronectin receptor antagonists. WO 99/15508 discloses dibenzo [a, d] cycloheptene-10- acetic acid compounds useful as vitronectin receptor antagonists . WO 99/15506 and WO 99/15507 disclose imino- benzazulene compounds useful as vitronectin receptor antagonists . WO 98/18461 discloses 4-10 membered mono- or polycyclic aromatic or nonaromatic ring system (containing 0-4 oxygen, sulfur and/or nitrogen heteroatoms) compounds useful as integrin receptor antagonists . WO 97/01540 discloses dibenzocycloheptene compounds useful as integrin receptor antagonists. WO 96/26190 discloses benzodiazepine-3-one and benzazepin-3-one compounds as integrin receptor inhibitors . Summary of the Invention The present invention comprises a new class of compounds useful in the prophylaxis and treatment of diseases, such as integrin receptors mediated diseases In particular, the compounds of the invention are useful for the prophylaxis and treatment of diseases or conditions mediated by integrin receptors, such as α v β 3 , α v β 5 , α v β 6 and the like. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds, methods for the prophylaxis and treatment of integrin receptors mediated diseases, such as cancer, tumor growth, metastasis, diabetic retinopathy, macular degeneration, angiogenesis, restenosis, bone resorption, atherosclerosis, inflammation, viral infection, wound healing and the like, using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of the compounds of the invention. The compounds of the invention are represented by the following general structure: E-B- (Alk) p -Q- (Alk) ,-A-G wherein E, B, Alk, Q, A, G, p and q are defined below. The foregoing merely summarizes certain aspects of the invention and is not intended, nor should it be construed, as limiting the invention in any way. All patents and other publications recited herein are hereby incorporated by reference in their entirety. Detailed Description of the Invention The present invention provides novel compounds which are useful for treating disease states involving cancer, tumor growth, metastasis, diabetic retinopathy, macular degeneration, angiogenesis, restenosis, bone resorption, atherosclerosis, inflammation, viral disease, wound healing and the like, as well as other disease states associated with the same pathways effecting the noted disease states, especially those modulated by integrin receptors and related pathways, such as the integrin receptors α v β 3 , v β 5 , α v β, and the like. In accordance with the present invention, there is provided compounds of the formula: E-B-(Alk) p -Q-(Alk) q -A-G or a pharmaceutically acceptable salt thereof, wherein p and q are each independently 0 or 1; each Alk is independently an alkyl radical; preferably, a C 1 -C 12 alkyl radical; more preferably, a C j -C j alkyl radical; and most preferably, a C 1 -C 6 alkyl radical; A and Q each independently represent a bond, -C(X)-, -S(0) t -, -S-, -0-, -N(R X )-, -C(Y)-N(R 1 )-, -N (R,) -C (Y) - , -S(0) t -N(R 1 )-, -N(R 1 )-S(0) t -, -N (R x ) -C (Y) -N (R x ) - or -N(R X ) -S(0) t -N(R 1 ) -, or a radical of cycloalkyl, aryl, heterocyclyl or heteroaryl each of which is optionally substituted by 1-3 radicals of R 2 ; preferably, A and Q each independently represent a bond, -C(X)-, -S(0) t -, -S-, -O- , -N(R -, -C (Y) -N(R X ) - , -N(R 1 )-C(Y)-, -S(0) t -N(R 1 )-, -N(R 1 )-S(0) t -, -N(R -C(Y)- N(R - or -N(R 1 )-S(0) t -N(R 1 ) -, or a radical of C 3 -C 8 cycloalkyl, aryl, heterocyclyl of 5-8 ring members or heteroaryl of 5-10 ring members each of which is optionally substituted by 1-3 radicals of R 2 ; and more preferably, A and Q each independently represent a bond, -C(0)-, -S(0) t -, -0- , -NfR,)-, -C (Y) -N(R - , -N(R 1 )-C(Y)-, -S(0) t -N(R - or -N (R -S (0) t - , or a radical of C 3 -C 6 cycloalkyl, phenyl, heterocyclyl of 5-6 ring members or heteroaryl of 5-6 ring members each of which is optionally substituted by 1-3 radicals of R 2 ; and B represents a bond, -C(Y)-, -S(0) c -, -S-, -0- , -N(R X )-, -C(Y)-N(R χ )-, -N(R 1 )-C(Y)-, -S(0) c -N(R 1 )-, -N (R χ ) -S (0) t - , -N(R 1 )-C(Y)-N(R 1 )- or -N(R l )-S(0) t -N(R 1 )-, or a radical of cycloalkyl, aryl, heterocyclyl or heteroaryl each of which is optionally substituted by 1-3 radicals of R 2 ; preferably, B represents a bond, -C(Y)-, -S(0) t -, -S-, -0-, -N(R -, -C(Y)-N(R 1 )-, -N(R 1 )-C(Y)-, -S (0) t -N (R χ ) - , -N(R x )-S(0) t -, -N(R 1 )-C(Y)-N(R 1 )- or -N (R x ) -S (0) t -N (R χ ) - , or a radical of C 3 -C 8 cycloalkyl, aryl, heterocyclyl of 5-8 ring members or heteroaryl of 5-10 ring members each of which is optionally substituted by 1-3 radicals of R 2 ; more preferably, B represents a bond, -C(Y)-, -S(0) t -, -0- or -N(R 1 )-, or a radical of phenyl, heterocyclyl of 5-6 ring members or heteroaryl of 5-6 ring members each of which is optionally substituted by 1-3 radicals of R 2 ; and most preferably, B represents a bond, -S(0) t -, -0- or -N(R X )-, or a phenyl radical which is optionally substituted by 1-3 radicals of R 2 ; provided the total number of atoms that directly connect E to G via the shortest sequence is 3-12, preferably 4-9, more preferably 4-7; each X is independently 0 or S; and preferably, 0; each Y is independently 0, S, N(R X ) or N(CN); and preferably, 0, N(R X ) or N(CN); each t is independently 1 or 2; and preferably, 2; each R χ is independently a hydrogen or alkyl radical; preferably, each R x is independently a hydrogen or C x -C 4 alkyl radical; and most preferably, each R x is independently a hydrogen or methyl radical; radicals of R 2 are each independently a halo, alkyl, alkoxy, alkylthio, haloalkyl, haloalkoxy, hydroxy, carboxy, cyano, azido, amidino, guanidino, nitro, amino, alkylamino or dialkylamino radical or two adjacent R 2 radicals represent a methylenedioxy, ethylenedioxy or propylenedioxy radical; preferably, radicals of R 2 are each independently a halo, C x -C 4 alkyl, C x -C 4 alkoxy, C x -C 4 alkylthio, C 1 -C 4 haloalkyl of 1-3 halo radicals, C 1 -C 4 haloalkoxy of 1-3 halo radicals, hydroxy, carboxy, cyano, azido, amidino, guanidino, nitro, amino, C x -C 4 alkylamino or di (C x -C 4 alkyl) amino radical or two adjacent R 2 radicals represent a methylenedioxy, ethylenedioxy or propylenedioxy radical; more preferably, radicals of R 2 are each independently a halo, C j -C, alkyl, C j -C, alkoxy, C j -C 3 alkylthio, -CF 3 , -OCF 3 , hydroxy, cyano, nitro, amino, C x -C 4 alkylamino or di(C 1 -C 4 alkyl) amino radical; and most preferably, radicals of R. are each independently a halo, methyl, methoxy, -CF 3 , -OCF 3 , hydroxy, cyano, nitro, amino, C x -C 4 alkylamino or di (C 1 -C 2 alkyl) amino radical ; E represents -R 3 , -NH-R 3 , -NH-C (Y) -R 3 , -C (Y) -NH-R 3 , -NH- S (0 ) t -R 3 , -S (0 ) c -NH-R 3 , -NH-C (Y) -NH-R 3 , -NH-C (Y) -O-R, , -NH-S (0) c -NH-R 3 , -NH-alkyl-C (Y) -R 3 , -NH-alkyl-S (0) t -R, , -NH-alkyl-C (Y) -NH-R 3 or -NH-alkyl-S ( 0 ) t -NH-R 3 radical ; preferably, E represents -R 3 , -NH-R 3 , -NH-C(Y)-R 3 , - C(Y)-NH-R 3 , -NH-S(0) t -R 3 , -S (0) C -NH-R 3 , -NH-C (Y) -NH-R 3 , - NH-C(Y) -0-R 3 , -NH-S(0) c -NH-R 3 , -NH- (C x -C 4 alkyl) -C (Y) -R 3 , -NH-(C X -C 4 alkyl) -S(0) c -R 3 , -NH- (C.-C, alkyl) -C (Y) -NH-R 3 or -NH-(C 1 -C 4 alkyl) -S (0) t -NH-R 3 radical; more preferably, E represents -R 3 , -NH-R,, -NH-C(Y)-R 3 , -C(Y)-NH-R 3 , -S(0) t -NH-R 3 , -NH-C (Y) -NH-R 3 , -NH-C (Y) -0-R 3 or -NH-(C x -C 4 alkyl) -C (Y) -NH-R 3 radical; more preferably, E represents -R 3 , -NH-R 3 , -NH-C(Y)-R 3 , -C(Y)-NH-R 3 , -NH-C(Y)-NH-R 3 or -NH-C (Y) -0-R 3 radical; and most preferably, E represents -R 3 , -NH-R 3 , -NH-C (NR x ) -R x , -C(NR X )- H-R χ/ -NH-C(NR 1 )-NH-R 1 or -NH-C ( R X ) -O-CH, radical; or alternatively preferably, E represents -NH-C (NR X ) -R 3 , -C(NR X ) -NH-R 3 , -NH-C(NR X ) -NH-R 3 or a radical of the formula : each of which formula is optionally substituted by 1-2 radicals of R 2 ; wherein n is 1-4, preferably, 1-3; more preferably, 1-2; and more preferably, E represents -NH-C (NR X ) -R 3 , -C(NR 1 )-NH- R 3 , -NH-C(NR X ) -NH-R 3 or a radical of the formula each of which formula is optionally substituted by 1-2 radicals of R, ; R 3 is a radical of hydrogen, alkyl, aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocyclyl or heterocyclyl-alkyl, wherein the aryl, heteroaryl and heterocyclyl radicals are optionally substituted by 1-3 radicals of R 2 • preferably, R 3 is hydrogen, C^C^ alkyl, aryl, aryl-C j - C 10 alkyl, heteroaryl, heteroaryl-C^C^ alkyl, heterocyclyl or heterocyclyl-C^C^ alkyl radical, wherein the heteroaryl and heterocyclyl radicals have 5-15 ring members and the aryl, heteroaryl and heterocyclyl radicals are optionally substituted by 1-3 radicals of R 2 ; more preferably, R 3 is hydrogen, C 3 -C 4 alkyl, aryl, aryl-C 1 -C 4 alkyl, heteroaryl, heteroaryl-C^C j alkyl, heterocyclyl or heterocyclyl-C 1 -C 4 alkyl radical, wherein the heteroaryl and heterocyclyl radicals have 5-15 ring members and the aryl, heteroaryl and heterocyclyl radicals are optionally substituted by 1-3 radicals of R 2 ; more preferably, R 3 is hydrogen, C 1 -C 4 alkyl, aryl, aryl-C^C j alkyl, heteroaryl or heteroaryl-C 1 -C 4 alkyl radical, wherein the heteroaryl radical has 5-15 ring members and the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of R.; more preferably, R 3 is a heteroaryl radical of 5-15 ring members and is optionally substituted by 1-3 radicals of R 2 ; most preferably, R 3 is a heteroaryl radical of 5-10 ring members and is optionally substituted by 1-3 radicals of R 2 ; G is a radical of formula preferably, G is a radical of formula more preferably, G is a radical of formula alternatively more preferably, G is a radical of formula or alternatively more preferably, G is a radical of formula W x is C-R 15 or N; W 2 is C-R 1S or N ; W 3 is C-R 17 or N; and W 4 is C-R 18 or N; or W x and W 2 , W 2 and W 3 , or W 3 and W 4 taken together represent a fused phenyl , fused C 5 -C 7 cycloalkyl , fused heteroaryl of 5 -6 ring members or fused heterocyclyl of 5-7 ring members , each of which is optionally substituted by 1-3 radicals of R 2 ; preferably, W x is C-R 15 or N; W 2 is C-R 16 or N; W 3 is C-R 17 or N; and W 4 is C-R 18 or N; and more preferably, W x is C- R 15 ; W 2 is C-R 16 ; W 3 is C-R 17 ; and W 4 is C-R 18 ; provided not more than 2 of W χ W 2 , W 3 or W 4 represent N; preferably, not more than 2 of W x , W 2 , W 3 or W 4 represent N; radicals of R 15 , R 17 and R 18 are each independently a radical of hydrogen, halo, hydroxy, carboxy, cyano, azido, amidino, nitro, amino, -R 9 , -C(Y)-R 9 , -S(0) t -R 9 , -S-R,, -0-R 9 , -N(R x )-R 9 , -C(Y)-N(R 1 )-R 9 , -N(R X ) -C (Y) -H, -N(R 1 )-C(Y)-R 9 , -0-C(Y)-N(R 1 )-R 9 , -N(R X ) -C (Y) -0-R 9 , -S(0) c -N(R 1 )-R 9 , -N(R x )-S(0) t -R 9 , -N (R χ ) -C ( Y) -N (R χ ) -R. or -N(R 1 )-S(0) c -N(R 1 )-R 9 ; preferably, radicals of R 1S , R 17 and R 18 are each independently a radical of hydrogen, halo, hydroxy, carboxy, cyano, azido, amidino, nitro, amino, -R. , - C(0)-R 9 , -S(0) t -R,, -S-R 9 , -0-R 9 , -N(R -R 9 , -C(0)-N(R 1 )- R 9 , -N(R 1 )-C(0)-H, -N(R 1 )-C(0)-R 9 , -S (0) t -N (R -R 9 or -N(R 1 )-S(0) t -R 9 ; more preferably, radicals of R 15 , R 17 and R 18 are each independently a radical of hydrogen, halo, hydroxy, cyano, C,-C 3 alkyl, C^C j alkoxy, -CF 3 or -OCF 3 ; and most preferably, R 15 , R 17 and R 18 are each independently a radical of hydrogen, fluoro, chloro, bromo, hydroxy, cyano, methyl, methoxy, -CF 3 or -OCF 3 ; and R 16 is a radical of hydrogen, halo, hydroxy, carboxy, cyano, azido, amidino, nitro, amino, -R 9 , -C(Y)-R 9 , -S(0) t -R 9 , -S-R 9 , -0-R 9 , -N(R -R 9 , -C (Y) -N (R x ) -R 9 , -N(R X )- C(Y)-H, -N(R -C(Y)-R 9 , -0-C(Y)-N(R 1 )-R 9 , -N (R x ) -C (Y) -O- R 9 , -S(0) t -N(R -R 9 , -N(R χ )-S(0) t -R 9 , -N (R -C (Y) -N (R -R 9 or -N(R 1 )-S(0) c -N(R 1 )-R 9 ; preferably, R 16 is a radical of hydrogen, halo, hydroxy, carboxy, cyano, azido, amidino, nitro, amino, -R 9 , - C(0)-R 9 , -S(0) t -R 9 , -S-R 9 , -0-R 9 , -N(R -R 9 , -C(0)-N(R x )- R 9 , -N(R 1 )-C(0)-H, -N(R -C(0)-R 9 , -S (0) t -N (R x ) -R, or -N(R x )-S(0) t -R 9 ; more preferably, R 16 is a radical of hydrogen, halo, hydroxy, carboxy, cyano, amino, -R 9 , -S(0) t -R 9 , -0-R 9 , - N(R X )-R 9 , -C(0)-N(R 1 )-R 9 , -N (R -C (0) -H, -N (R -C (0) -R 9 , -S(0) t -N(R 1 )-R 9 or -N (R 3 ) -S (0) t -R 9 ; and most preferably, R 16 is a radical of hydrogen, fluoro, chloro, bromo, hydroxy, cyano, amino, -R 9 , -S(0) t -R 9 , -0-R 9 , -N(R -R 9 , -C(0)-N(R 1 )-R 9 , -N(R X ) -C (0) -H, -N(R X )- C(0)-R 9 , -S(0) t -N(R 1 )-R, or -N (R x ) -S (0) t -R 9 ; or alternatively, R 15 and R 16 , R 16 and R 17 , or R 17 and R 18 taken together represent a methylenedioxy, ethylenedioxy or propylenedioxy radical; and provided the combined total number of aryl, cycloalkyl, heteroaryl and heterocyclyl radicals in R 15 , R 16 , R 17 and wherein each R 9 is independently a radical of alkyl, haloalkyl, arylalkyl, heteroarylalkyl , heterocyclylalkyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, wherein the aryl, cycloalkyl, heteroaryl and heterocyclyl radicals are optionally substituted by 1-3 radicals of R, 2;' preferably, each R 9 is independently a radical of C 3 -C 4 alkyl, C x -C 4 haloalkyl of 1-3 halo radicals, aryl-C x -C 4 alkyl, heteroaryl-C^C, alkyl, heterocyclyl-C^C j alkyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, wherein the aryl, cycloalkyl, heteroaryl and heterocyclyl radicals are optionally substituted by 1-3 radicals of 2 ' more preferably, each R 9 is independently a radical of C x -C 4 alkyl, -CF 3 , phenyl-C x -C 4 alkyl or phenyl, wherein each phenyl radical is optionally substituted by 1-3 radicals of R 2 ; and most preferably, each R 9 is independently a radical of C 3 -C 4 alkyl, -CF 3 , phenyl-C x -C 2 alkyl or phenyl, wherein each phenyl radical is optionally substituted by 1-3 radicals of R, 2 ;' X, , X 3 and X 6 are each independently a -C(X)-, -S(0) c -, -CHR 6 - or -CHR 7 - radical; preferably, X 2 , X 3 and X 6 are each independently a -CHR 6 - or -CHR 7 - radical; and more preferably X 2 , X 3 and X 6 are each independently a -CHR 6 - radical ; Z 1 is N or C-R 6 ; preferably, Z x is C-R 6 ; R 10 and R 12 are each independently an -R 6 , -R 7 or -OR 7 radical; preferably, R 10 and R 12 are each independently a hydrogen, hydroxy or C x -C 4 alkyl radical; more preferably, R 10 and R 12 are each independently a hydrogen, hydroxy or C j -C., alkyl radical; most preferably, R 10 and R 12 are each a hydrogen radical; provided the combined total number of aryl, heteroaryl and heterocyclyl radicals in X 2 , X 3 , X 6 , R 10 and R 12 is 0- 2; preferably, 0-1; wherein each R 6 is independently a hydrogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, halo or cyano radical; preferably, each R 6 is independently a hydrogen, hydroxy, C x -C 4 alkyl, C x -C 4 haloalkyl of 1-3 halo radicals, C x -C 4 alkoxy, C x -C 4 haloalkoxy, halo or cyano radical; more preferably, each R 6 is independently a hydrogen, hydroxy or C 1 -C 2 alkyl radical; and most preferably, each R 6 is a hydrogen radical; and each R 7 is independently a radical of aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocyclyl or heterocyclyl-alkyl , each of which is optionally substituted by 1-3 radicals of R 2 ; preferably, each R 7 is independently a radical of aryl, aryl-C x -C 4 alkyl, heteroaryl, heteroaryl-C 3 -C 4 alkyl, heterocyclyl or heterocyclyl-C 1 -C 4 alkyl, each of which is optionally substituted by 1-3 radicals of R 2 , and wherein the heteroaryl and heterocyclyl radicals have 5-10 ring members; more preferably, each R 7 is independently a radical of phenyl, phenyl-C x -C 2 alkyl, heteroaryl, heteroaryl-C 1 -C 2 alkyl, heterocyclyl or heterocyclyl-C 1 - C 2 alkyl, each of which is optionally substituted by 1- 3 radicals of R 2 , and wherein the heteroaryl and heterocyclyl radicals have 5-6 ring members; and R 4 is an alkyl radical substituted by a radical of carboxy, tetrazolyl, -C0 2 R 8 , -C (0) -NH-S (0) t -R 8 , -C(0)-NH- C(0)-R 8 or -C(0)-NH-R 8 , and optionally substituted by a radical of aryl, heteroaryl or heterocyclyl, each of which is optionally substituted by 1-3 radicals of R 2 ; preferably, R 4 is a C j -C^ alkyl radical substituted by a radical of carboxy, tetrazolyl, -C0 2 R 8 , -C (0) -NH-S (0) t - R 8 , -C(0) -NH-C(0)-R 8 or -C(0)-NH-R 8 , and optionally substituted by a radical of aryl, heteroaryl or heterocyclyl, each of which is optionally substituted by 1-3 radicals of R 2 ; more preferably, R 4 is a C x -C 4 alkyl radical substituted by a radical of carboxy, tetrazolyl, or -C0 2 R 8 , and optionally substituted by a radical of aryl, heteroaryl or heterocyclyl, each of which is optionally substituted by 1-3 radicals of R,; more preferably, R 4 is a C x -C 4 alkyl radical substituted by a radical of carboxy or -C0 2 R 8 ; and most preferably, R 4 is a C.-C., alkyl radical substituted by a radical of carboxy or -C0 2 R 8 ; wherein R 8 is an alkyl radical substituted by 1-2 radicals of hydroxy, carboxy, amino, aryl or heteroaryl, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of R 2 ; preferably, R 3 is a C 1 -C 10 alkyl radical substituted by 1-2 radicals of hydroxy, carboxy, amino, aryl or heteroaryl of 5-10 ring members, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of R 2 ; more preferably, R 8 is a C x -C 4 alkyl radical optionally substituted by a radical of aryl or heteroaryl of 5-10 ring members, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of R 2 ; more preferably, R 8 is a C x -C 4 alkyl radical optionally substituted by a phenyl radical, wherein the phenyl radical is optionally substituted by 1-3 radicals of R 2 ; and most preferably, R 8 is a C x -C 2 alkyl radical. In another aspect of the invention, there is provided a method for the therapeutic or prophylactic treatment of disease states involving tumor growth, metastasis, diabetic retinopathy, macular degeneration, angiogenesis, restenosis, bone resorption, atherosclerosis, inflammation, viral disease, wound healing or the like in a warm-blooded animal which comprises administering to a warm blooded animal in need thereof a therapeutically or prophylactically effective amount of a compound or pharmacutical composition of the invention. In a further embodiment of the invention, there is provided a method for modulation, preferably inhibition, of one or more integrin receptors which comprises administering to a warm blooded animal in need thereof an effective amount of a compound or pharmacutical composition of the invention. In a further embodiment of the invention, there is provided a method for modulation, preferably inhibition, of one or more vitronectin receptors which comprises administering to a warm blooded animal in need thereof an effective amount of a compound or pharmacutical composition of the invention. In a related embodiment, there is provided a method for modulation, preferably inhibition, of α v β 3 and/or α v β 5 and/or α v β 6 receptors which comprises administering to a warm blooded animal in need thereof an effective amount of a compound or pharmacutical composition of the invention. An additionally preferred embodiment of the invention includes a method for the therapeutic or prophylactic treatment of an integrin receptor mediated disease state in a warm-blooded animal which comprises administering to said animal a therapeutically or prophylactically effective amount of a compound or pharmacutical composition of the invention. For example, the compounds of the invention may modulate an integrin receptor mediated response, for example, by antagonizing one or more vitronectin receptors response. Especially preferred in this embodiment is the inhibition of the α v β 3 and/or α v β 5 and/or α v β 6 receptor response. The compounds and pharmacutical compositions of this invention are useful in the prophylaxis and/or treatment (comprising administering to a warm blooded animal, such as a mammal (e.g., a human, horse, sheep, pig, mouse, rat, bovine and the like) an effective amount of such compound or composition) of (1) diseases and disorders which can be effected or facilitated by modulating one or more integrin receptors, such as by antagonizing one or more integrin receptors, including but not limited to disorders induced or facilitated by one or more integrin receptors; (2) diseases and disorders which can be effected or facilitated by modulating one or more vitronectin receptors, such as by antagonizing one or more vitronectin receptors, including but not limited to disorders induced or facilitated by one or more vitronectin receptors; (3) diseases and disorders which can be effected or facilitated by modulating the α v β 3 and/or θt v β 5 and/or α v β 6 receptor response, such as by inhibition of the α v β 3 and/or α v β 5 and/or cc v β 6 receptor response, including but not limited to disorders induced or facilitated by the α v β 3 and/or α v β 5 and/or α v β 6 receptor response; or (4) disease states involving cancer, such as tumor growth; metastasis; diabetic retinopathy; macular degeneration; angiogenesis; restenosis; bone resorption, such as osteoporosis, osteoarthritis, bone formation, bone loss, hyperparathyroidism, Paget ' s disease, hypercalcemia of malignancy, osteolytic lesions, Behcet ' s disease, osteomalacia, hyperostosis or osteopetrosis; atherosclerosis; inflammation, such as rheumatoid arthritis, pain, psoriasis or allergies; viral disease; wound healing; or the like. As utilized herein, the following terms shall have the following meanings: "Alkyl", alone or in combination, means a saturated or partially unsaturated (provided there are at least two carbon atoms) straight-chain or branched-chain alkyl radical containing the designated number of carbon atoms; preferably 1-18 carbon atoms (Ci-Cis) , more preferably 1-12 carbon atoms (C 1 -C 12 ) , more preferably 1-8 carbon atoms (Ci-Cs) , more preferably 1-6 carbon atoms (Ci-Cβ) , more preferably 1-4 carbon atoms (Cι~ C4) , more preferably 1-3 carbon atoms (C 1 -C 3 ), and most preferably 1-2 carbon atoms (C 1 -C 2 ) . Examples of such radicals include methyl, ethyl, vinyl, n-propyl, allyl, isopropyl, n-butyl, 1-butenyl, 2-butenyl, 3-butenyl, sec-butyl, sec-butenyl, t-butyl, n-pentyl, 2- methylbutyl, 3-methylbutyl , 3-methylbutenyl , n-hexyl , 2-methylpentyl, 3-methylpentyl , 4-methylpentyl , 2,2- dimethylbutyl, 2 , 3-dimethylbutyl , and the like. A partially unsaturated alkyl preferably has at least one double or triple bond, more preferably 1-3 double or triple bonds, more preferably 1-2 double or triple bonds, and most preferably 1 double bond or 1 triple bond. "Alkyl" may also represent a divalent alkyl radical, such as aryl-alkyl-. "Alkoxy" , alone or in combination, means a radical of the type "R-0-" wherein "R" is an alkyl radical as defined above and "0" is an oxygen atom. Examples of such alkoxy radicals include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec- butoxy, tert-butoxy, allyloxy and the like. "Alkylthio", alone or in combination, means a radical of the type "R-S-" wherein "R" is an alkyl radical as defined above and "S" is a sulfur atom. Examples of such alkylthio radicals include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, iso- butylthio, sec-butylthio, tert-butylthio, allylthio and the like. The term "carbocyclic", alone or in combination, refers to an organic cyclic moiety in which the cyclic skeleton is comprised of only carbon atoms whereas the term "heterocyclic", alone or in combination, refers to an organic cyclic moiety in which the cyclic skeleton contains one or more, preferably , 1-4 , more preferably 1-3, most preferably 1-2, heteroatoms selected from nitrogen, oxygen, or sulfur and which may or may not include carbon atoms. The term "cycloalkyl", alone or in combination, refers to a saturated or partially unsaturated (preferably 1-2 double bonds, more preferably 1 double bond) carbocyclic moiety containing the indicated number of carbon atoms, preferably 3-12 ring members, more preferably 3-8 ring members, and most preferably, 3-6 ring members. For example, the term "C 3 -C 10 cycloalkyl" refers to an organic cyclic substituent in which three to ten carbon atoms form a three, four, five, six, seven, eight, nine or ten-membered ring, including, for example, a cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexenyl, cyclohexyl, cycloheptyl, cyclooctyl and the like ring. As used herein, "cycloalkyl" may also refer to two or more cyclic ring systems which are fused to form, for example, bicyclic, tricyclic, or other similar bridged compounds (e.g. norbornanyl , norbornenyl, adamantanyl, etc.). "Aryl" refers to an aromatic carbocyclic group having a single ring, for example, a phenyl ring, multiple rings, for example, biphenyl, or multiple condensed rings in which at least one ring is aromatic, for example, naphthyl , 1, 2 , 3 , 4, -tetrahydronaphthyl, anthryl, or phenanthryl, which can be unsubstituted or substituted with one or more (preferably 1-5, more preferably 1-4, more preferably 1-3, most preferably 1- 2) other substituents as defined above. The substituents attached to a phenyl ring portion of an aryl moiety in the compounds of this invention may be configured in the ortho-, meta- or para- orientations. Examples of typical aryl moieties included in the scope of the present invention may include, but are not limited to, the following: "Aryl-alkyl", alone or in combination, means an alkyl radical as defined above wherein a hydrogen radical is replaced with an aryl radical, such as benzyl, and for example, "aryl-C 1 -C 4 alkyl", alone or in combination, means a C x -C 4 alkyl radical as defined above wherein a hydrogen radical is replaced with an aryl radical. "Heterocycle" refers to a saturated, unsaturated or aromatic carbocyclic group having a single ring, multiple rings or multiple condensed rings, and having at least one hetero atom such as nitrogen, oxygen or sulfur within at least one of the rings. "Heteroaryl" refers to a heterocycle in which at least one ring is aromatic. Further, bi- or tri-cyclic heteroaryl moieties may comprise at least one ring which is either completely or partially saturated. Any of the heteroaryl groups can be unsubstituted or optionally substituted with one or more groups as defined above and one or more, preferably 1-2, more preferably one, "oxo" group. "Heterocyclyl" refers to a saturated or partially unsaturated, preferably one double bond, monocyclic or bicyclic, preferably monocyclic, heterocycle radical containing at least one, preferably 1 to 4, more preferably 1 to 3 , even more preferably 1- 2, nitrogen, oxygen or sulfur atom ring member and having preferably 3-8 ring members in each ring, more preferably 5-8 ring members in each ring and even more preferably 5-6 ring members in each ring. "Heterocyclyl" is intended to include sulfone and sulfoxide derivatives of sulfur ring members and N- oxides of tertiary nitrogen ring members, and carbocyclic fused, preferably 3-6 ring carbon atoms and more preferably 5-6 ring carbon atoms. Any of the heterocyclyl groups can be unsubstituted or optionally substituted with one or more groups as defined above and one or more, preferably 1-2, more preferably one, " oxo" group . As one skilled in the art will appreciate such heterocycle moieties may exist in several isomeric forms, all of which are to be encompassed by the present invention. For example, a 1 , 3 , 5-triazine moiety is isomeric to a 1 , 2 , 4-triazine group. Such positional isomers are to be considered within the scope of the present invention. Likewise, the heterocyclyl or heteroaryl groups can be bonded to other moieties in the compounds of the invention. The point (s) of attachment to these other moieties is not to be construed as limiting on the scope of the invention. Thus, by way of example, a pyridyl moiety may be bound to other groups through the 2-, 3-, or 4- position of the pyridyl group and a piperidinyl may be bound to other groups through the nitogen or carbon atoms of the piperidinyl group. All such configurations are to be construed as within the scope of the present invention. Examples of heterocyclic or heteroaryl moieties included in the scope of the present invention may include, but are not limited to, the following: heterocyclyl or heteroaryl group and a cycloalkyl or aryl group have two carbons in common, for example indole, isoquinoline, tetrahydroquinoline, methylenedioxybenzene and the like. "Benzo", alone or in combination, means the divalent radical CgH 4 = derived from benzene. "Benzo fused" forms a ring system in which benzene and a cycloalkyl or aryl group have two carbons in common, for example tetrahydronaphthylene and the like. The term "halo" or "halogen" refers to a halogen atom which may include fluoro, chloro, bromo and iodo . Preferred halo groups include chloro, bromo and fluoro with chloro and fluoro being especially preferred. "Haloalkyl", alone or in combination, means an alkyl radical as defined above in which at least one hydrogen atom, preferably 1-3, is replaced by a halogen radical, more preferably fluoro or chloro radicals. Examples of such haloalkyl radicals include 1, 1, 1-trifluoroethyl, chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, bis ( trifluoromethyl) methyl and the like. The following table defines by example certain ring structure abbreviations used herein: Certain symbols used herein are indended to have the following meanings: -CR X R Y - = -NR X R Y = -C(NR)- It should be noted that compounds of the invention may contain groups that may exist in tautomeric forms, such as cyclic and acyclic amidine and guanidine groups, heteroatom substituted heteroaryl groups (Y' = 0, S, NR) , and the like and though one form is named, described, displayed and/or claimed herein, all the tautomeric forms are intended to be inherently included in such name, description, display and/or claim. "Modulate" as used herein refers to the ability of a compound of this invention to interact with a receptor, target gene or other gene product to (a) up- regulate the activity of that receptor, target gene or other gene product or biological effect (for example, as an agonist) or (b) down-regulating the receptor, target gene or other gene product or other biological effect, particularly by acting as an antagonist for the receptor, target gene or other gene product. Additionally, encompassed by "modulate" is the ability of a compound of the invention to effect a desired biological response, even if that response occurs upstream or downstream one or more steps in a signaling pathway from the receptor, target gene or other gene product in question. Thus, by way of example, the compounds of the invention may provide the desired effect by interacting with an integrin receptor, particularly a vitronectin receptor, such as the αβ 3 and/or oc v β 5 and/or α v β 6 receptor, to act as an agonist or antagonist to that receptor or at some point, either upstream or downstream, in the signaling pathway for the receptor to effect the desired therapeutic or prophylactic response. "Pharmaceutically acceptable salt", as used herein, refers to an organic or inorganic salt which is useful in the treatment of a warm-blooded animal . Such salts can be acid or basic addition salts, depending on the nature of the compound of this invention. For examples of "pharmacologically acceptable salts," see Berge et al . , J. Pharm. Sci. 66:1 (1977). As used herein, "warm blooded animal" includes a mammal, including a member of the human, equine, porcine, bovine, murine, canine, feline and the like species. In the case of an acidic moiety in a compound of this invention, a salt may be formed by treatment of a compound of this invention with a basic compound, particularly an inorganic base. Preferred inorganic salts are those formed with alkali and alkaline earth metals such as lithium, sodium, potassium, barium and calcium. Preferred organic base salts include, for example, ammonium, dibenzylammonium, benzylammonium, 2- hydroxyethylammonium, bis (2-hydroxyethyl) ammonium, phenylethylbenzylamine, dibenzyl-ethylenediamine, and the like salts. Other salts of acidic moieties may include, for example, those salts formed with procaine, quinine and N-methylglucosamine, plus salts formed with basic amino acids such as glycine, ornithine, histidine, phenylglycine, lysine and arginine . An especially preferred salt is a sodium or potassium salt of a compound of this invention. With respect to basic moieties, a salt is formed by the treatment of a compound of this invention with an acidic compound, particularly an inorganic acid. Preferred inorganic salts of this type may include, for example, the hydrochloric, hydrobromic, hydroiodic, sulfuric, phosphoric or the like salts. Preferred organic salts of this type, may include, for example, salts formed with formic, acetic, succinic, citric, lactic, maleic, fumaric, palmitic, cholic, pamoic, mucic, d-glutamic, d-camphoric, glutaric, glycolic, phthalic, tartaric, lauric, stearic, salicyclic, methanesulfonic, benzenesulfonic, para-toluenesulfonic, sorbic, puric, benzoic, cinnamic and the like organic acids. An especially preferred salt of this type is a hydrochloride or sulfate salt of a compound of this invention. Also encompassed in the scope of the present invention are pharmaceutically acceptable esters of a carboxylic acid or hydroxyl containing group, including a metabolically labile ester or a prodrug form of a compound of this invention. A metabolically labile ester is one which may produce, for example, an increase in blood levels and prolong the efficacy of the corresponding non-esterified form of the compound. A prodrug form is one which is not in an active form of the molecule as administered but which becomes therapeutically active after some in vivo activity or biotransformation, such as metabolism, for example, enzymatic or hydrolytic cleavage. For a general discussion of prodrugs involving esters see Svensson and Tunek Drug Metabolism Reviews 165 (1988) and Bundgaard Design of Prodrugs, Elsevier (1985) . Examples of a masked carboxylate anion include a variety of esters, such as alkyl (for example, methyl, ethyl), cycloalkyl (for example, cyclohexyl), aralkyl (for example, benzyl, p-methoxybenzyl) , and alkylcarbonyloxyalkyl (for example, pivaloyloxymethyl). Amines have been masked as arylcarbonyloxymethyl substituted derivatives which are cleaved by esterases in vivo releasing the free drug and formaldehyde (Bungaard J. Med. Chem. 2503 (1989)). Also, drugs containing an acidic NH group, such as imidazole, imide, indole and the like, have been masked with N- acyloxymethyl groups (Bundgaard Design of Prodrugs, Elsevier (1985)) . Hydroxy groups have been masked as esters and ethers. EP 039,051 (Sloan and Little, 4/11/81) discloses Mannich-base hydroxamic acid prodrugs, their preparation and use. Esters of a compound of this invention, may include, for example, the methyl, ethyl, propyl, and butyl esters, as well as other suitable esters formed between an acidic moiety and a hydroxyl containing moiety. Metabolically labile esters, may include, for example, methoxymethyl , ethoxymethyl, iso-propoxymethyl, α-methoxyethyl, groups such as α- ( (C x -C 4 ) alkyloxy) ethyl ; for example, methoxyethyl , ethoxyethyl, propoxyethyl, iso- propoxyethyl, etc.; 2-oxo-l , -dioxolen-4-ylmethyl groups, such as 5-methyl-2-oxo-l , 3 , dioxolen-4-ylmethyl , etc.; C x -C 3 alkylthiomethyl groups, for example, methylthiomethyl, ethylthiomethyl , isopropylthiomethyl, etc.; acyloxymethyl groups, for example, pivaloyloxymethyl, cc-acetoxymethyl, etc.; ethoxycarbonyl-1-methyl ; or α-acyloxy-α-substituted methyl groups, for example α-acetoxyethyl . Additionally, the compounds of the invention may have one or more asymmetric carbon atoms and, therefore, may exist in stereoisomeric forms. All stereoisomers are intended to be included within the scope of the present invention. As used, "stereoisomer" or "stereoisomeric" refers to a compound which has the same molecular weight, chemical composition, and constitution as another, but with the atoms grouped such that their orientation in three- dimensional space is different. Such stereoisomers may exist as enantiomeric mixtures, diastereomers or may be resolved into individual stereoisomeric components (e.g. specific enantiomers) by methods familiar to one skilled in the art. Likewise, the compounds of this invention may exist as isomers, that is compounds of the same molecular formula but in which the atoms, relative to one another, are arranged differently. One skilled in the art will appreciate that it is possible to prepare compounds of this invention in which one or more of the substituents are reversed in orientation relative to the other atoms in the molecule. That is, the substituent to be inserted may be the same as that noted except that it is inserted into the molecule in the reverse orientation. One skilled in the art will appreciate that these isomeric forms of the compounds of this invention are to be construed as encompassed within the scope of the present invention. Further, the compounds of the invention may exist as crystalline solids which can be crystallized from common solvents such as ethanol, N, N-dimethyl- formamide, water, or the like. Thus, crystalline forms of the compounds of the invention may exist as solvates and/or hydrates of the parent compounds or their pharmaceutically acceptable salts. All of such forms likewise are to be construed as falling within the scope of the invention. While it may be possible to administer a compound of the invention alone, in the methods described, the compound administered normally will be present as an active ingredient in a pharmaceutical formulation. Thus, in one another embodiment of the invention, there is provided a formulation comprising a compound of this invention in combination with a pharmaceutically acceptable carrier, diluent or excipient therefor. The composition used in the noted therapeutic methods can be in a variety of forms. These include, for example, solid, semi-solid and liquid dosage forms, such as tablets, pills, powders, liquid solutions or suspensions, liposomes, injectable and infusible solutions . The preferred form depends on the intended mode of administration and therapeutic application. Considerations for preparing appropriate formulations will be familiar to one skilled in the art and are described, for example, in Goodman and Gilman's: "The Pharmacological Basis of Therapeutics", 8th Ed., Pergamon Press, Gilman et al . eds. (1990); and "Remington's Pharmaceutical Sciences", 18th Ed., Mack Publishing Co., A. Gennaro, ed. (1990). Methods for administration are discussed therein, e.g. for oral, topical, intravenous, intraperitoneal, or intramuscular administration. Pharmaceutically acceptable carriers, diluents, and excipients, likewise, are discussed therein. Typical carriers, diluents, and excipients may include water (for example, water for injection), buffers, lactose, starch, sucrose, and the like. As noted, a compound of the invention can be administered orally, topically or parenterally (e.g. intravenously, intraperitoneally, intramuscularly, subcutaneously, etc.), or inhaled as a dry powder, aerosol, or mist, for pulmonary delivery. Such forms of the compounds of the invention may be administered by conventional means for creating aerosols or administering dry powder medications using devices such as for example, metered dose inhalers, nasal sprayers, dry powder inhaler, jet nebulizers, or ultrasonic nebulizers. Such devices optionally may be include a mouthpiece fitted around an orifice. In certain circumstances, it may be desirable to administer the desired compound of the invention by continuous infusion, such as through a continuous infusion pump, or using a transdermal delivery device, such as a patch. The compounds of the invention may also be administered as an aerosol. The term "aerosol" includes any gas-borne suspended phase of a compound of the invention which is capable of being inhaled into the bronchioles or nasal passages. Specifically, aerosol includes a gas-borne suspension of droplets of the desired compound, as may be produced in a metered dose inhaler or nebulizer, or in a mist sprayer. Aerosol also includes a dry powder composition of a compound of the instant invention suspended in air or other carrier gas, which may be delivered by insufflation from an inhaler device, for example. For solutions used in making aerosols of the invention, the preferred range of concentration of the compounds of the invention is 0.1-100 milligrams (mg) /milliliter (mL) , more preferably 0.1-30 mg/mL, and most preferably 1-10 mg/mL. Usually the solutions are buffered with a physiologically compatible buffer such as phosphate or bicarbonate. The usual pH range is from about 5 to about 9, preferably from about 6.5 to about 7.8, and more preferably from about 7.0 to about 7.6. Typically, sodium chloride is added to adjust the osmolarity to the physiological range, preferably within 10% of isotonic. Formulation of such solutions for creating aerosol inhalants is discussed, for example, in Remington's, supra; See, also, Ganderton and Johens, "Drug Delivery to the Respiratory Tract, Ellis Horwood (1987) ; Gonda, "Critical Review in Therapeutic Drug Carrier Systems" 6 273-313 (1990); and Raeburn et al . J. Pharmacol. Toxicol. Methods. 27 143- 159 (1992). Solutions of a compound of the invention may be converted into aerosols by any of the known means routinely used for making aerosol inhalant pharmaceuticals. In general, such methods comprise pressurizing or providing a means of pressurizing a container of the solution, usually with an inert carrier gas, and passing the pressurized gas through a small orifice, thereby pulling droplets of the solution into the mouth and trachea of the animal to which the drug is to be administered. Typically, a mouthpiece is fitted to the outlet of the orifice to facilitate delivery into the mouth and trachea. In one embodiment, devices of the present invention comprise solutions of the compounds of the invention connected to or contained within any of the conventional means for creating aerosols in asthma medication, such as metered dose inhalers, jet nebulizers, or ultrasonic nebulizers. Optionally such devices may include a mouthpiece fitted around the orifice . Further, there are provided a device which may comprise a solution of a compound of the instant invention in a nasal sprayer. A dry powder comprising a compound of the invention, optionally with an excipient is another embodiment. This may be administered by a drug powder inhaler containing the described powder. Powders may be formed with the aid of any suitable powder bases, for example, talc, lactose, starch and the like. Drops may be formulated with an aqueous base or non-aqueous base also comprising one or more dispersing agents, suspending agents solubilizing agents, and the like. Any of the formulations of the invention may also include one or more preservatives or bacteriostatic agents, for example, methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate, chlorocresol , benzalkonium chlorides, and the like. Additionally, the formulations may contain other active ingredients. The pharmaceutical formulations of the invention may be administered by parenteral or oral administration for prophylactic and/or therapeutic treatment. The pharmaceutical compositions can be administered in a variety of unit dosage forms depending on the method of administration. For example, unit dosage forms suitable for oral administration may include, powders, tablets, pills, capsules and dragees . The pharmaceutical formulations can be administered intravenously. Therefore, the invention further provides formulations for intravenous administration which comprise a compound of the invention dissolved or suspended in a pharmaceutically acceptable carrier or diluent therefor. A variety of aqueous carriers can be used, for example, water, buffered water or other buffer solutions, saline, and the like. The resulting aqueous solutions can be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile aqueous solution prior to administration. The sterile aqueous solution for the lyophilized product can be packaged as a kit for use with the lyophilized formulation. The compositions can contain pharmaceutically acceptable substances to aid in administration and more closely mimic physiological conditions. Such substances, can include, for example, pH adjusting substances such as acids, bases or buffering agents, tonicity adjusting agents, wetting agents and the like. Such substances may include but are not limited to, for example, sodium hydroxide, hydrochloric acid, sulfuric acid, sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate, triethanolamine oleate, and the like or any other means familiar to one skilled in the art for maintaining pH at a desired level . For solid formulations, carriers, diluents, and excipients known to one skilled in the art may be used. Such carriers, diluents and excipients may include, for example, mannitol, lactose, starch magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, or other solid polyol sugar, magnesium carbonate, and the like. For oral administration, a pharmaceutically acceptable formulation is prepared by admixing any of the usual carrier, diluents, and excipients, such as those noted, with from about 0.1 to about 95% of a compound of the invention. The preferred dosage for use in the methods of the invention, however, is in the range of about 0.01 mg/kg to about 100 mg/kg of body weight, preferably from about 0.1 mg/kg to about 50 mg/kg, up to 4 times per day. Whatever the dosage form, one skilled in the art will recognize that the dosage administered will be adjusted to factors such as the age, weight, and condition of the patient involved. The skilled practitioner will be familiar with how to adjust the dosage to accommodate these and other factors. While the compounds of the invention can be administered as the sole active pharmaceutical agent, the compounds can also be used in combination with one or more agents such as anti-platelet agents, anti- inflammatory agents, matrix metalloproteinase inhibitors, cancer treatment agents, antiinfective agents and the like. For example, the compounds of the invention can be administered in combination with glycoprotein Ilb/IIIa receptor antagonists for the prophylaxis and/or treatment of acute coronary ischemic syndrome and the like (WO 97/35615, incorporated herein by reference in its entirety) , or in combination with IL-1 antagonists, such as, p38 inhibitors, TNF-α inhibitors, IL-1 inhibitors, IL-1 receptor antagonist (IL-lRa) and the like, for the prophylaxis and/or treatment of rheumatoid arthritis, osteoarthritis and the like (Arner et al . , Arthritis & Rheumatism 38:1304-14, 1995). When administered as a combination, the therapeutic agents can be formulated as separate compositions which are given at the same time or different times, or the therapeutic agents can be given as a single composition. Compound Synthesis Compounds of the invention can be synthesized according to one or more of the following methods. It should be noted that the general procedures are shown as it relates to preparation of compounds having unspecified stereochemistry. However, such procedures are generally applicable to those compounds of a specific stereochemistry, e.g., where the stereochemistry about a group is (S) or (R) . In addition, the compounds having one stereochemistry (e.g., (R) ) can often be utilized to produce those having opposite stereochemistry (i.e., (S) ) using well- known methods, for example, by inversion. Because compounds of the invention can possess one or more asymmetric carbon atoms, the compounds are thus capable of existing in the form of optical isomers as well as in the form of racemic or nonracemic mixtures thereof. The optical isomers can be obtained by resolution of the racemic mixtures according to conventional processes, for example by formation of diastereoisomeric salts by treatment with an optically active acid or base. Examples of appropriate acids are tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, ditoluoyltartaric acid, camphorsulfonic acid and the like. Examples of appropriate bases are brucine, ephedrine, strychnine, morphine and the like. The separation of the mixture of diastereoisomers by crystallization is followed by liberation of the optically active bases from these salts. A alternative process for separation of optical isomers involves the use of a chiral chromatography column optimally chosen to maximize the separation of the enantiomers. Another available method involves synthesis of covalent diastereoisomeric molecules by reacting compounds of the invention with an optically pure acid in an activated form or an optically pure isocyanate. The synthesized diastereoisomers can be separated by conventional means such as chromatography, distillation, crystallization or sublimation, and then hydrolyzed to deliver the enantiomerically pure compound. The optically active compounds of the invention can likewise be obtained by utilizing optically active starting materials or alternatively, by generating optically active synthetic intermediates either by chiral reactions, such as using a chiral reagent, chiral catalyst and the like, or by isolating the desired chiral synthetic intermediate isomer using the methods described above. These isomers may be in the form of a free acid, a free base, an ester or a salt. "Leaving group" (L) generally refers to groups readily displaceable by a nucleophile, such as an amine, a carbon, a thiol or an alcohol nucleophile. Such leaving groups are well known in the art. Examples of such leaving groups include, but are not limited to, N-hydroxysuccinimide, N-hydroxybenzotriazole, halides, triflates, tosylates and the like. Preferred leaving groups are indicated herein where appropriate. "Protecting group" generally refers to groups well known in the art which are used to prevent selected reactive groups, such as carboxy, amino, hydroxy, mercapto and the like, from undergoing undesired reactions, such as nucleophilic, electrophilic, oxidation, reduction and the like (see Greene, T. W. and Wuts, P. G. M. , Protective Groups in Organic Synthesis, Wiley, 1991) . Preferred protecting groups are indicated herein where appropriate. Examples of amino protecting groups include, but are not limited to, aralkyl, substituted aralkyl, cycloalkenylalkyl and substituted cycloalkenyl alkyl, allyl, substituted allyl, acyl, alkoxycarbonyl, aralkoxycarbonyl, silyl and the like. Examples of aralkyl include, but are not limited to, benzyl, ortho-methylbenzyl, trityl and benzhydryl, which can be optionally substituted with halogen, alkyl, alkoxy, hydroxy, nitro, acylamino, acyl and the like, and salts, such as phosphonium and ammonium salts. Examples of aryl groups include phenyl, naphthyl, indanyl, anthracenyl, 9- (9- phenylfluorenyl) , phenanthrenyl and the like. Examples of cycloalkenylalkyl or substituted cycloalkylenylalkyl radicals, preferably have 6-10 carbon atoms, include, but are not limited to, cyclohexenyl methyl and the like. Suitable acyl, alkoxycarbonyl and aralkoxycarbonyl groups include benzyloxycarbonyl, t- butoxycarbonyl, iso-butoxycarbonyl , benzoyl, substituted benzoyl, butyryl, acetyl, tri-fluoroacetyl , tri-chloro acetyl, phthaloyl and the like. A mixture of protecting groups can be used to protect the same amino group, such as a primary amino group can be protected by both an aralkyl group and an aralkoxycarbonyl group. Amino protecting groups can also form a heterocyclic ring with the nitrogen to which they are attached, for example, 1 , 2-bis (methylene) benzene, phthalimidyl , succinimidyl , maleimidyl and the like and where these heterocyclic groups can further include adjoining aryl and cycloalkyl rings. In addition, the heterocyclic groups can be mono-, di- or tri-substituted, such as nitrophthalimidyl . Amino groups may also be protected against undesired reactions, such as oxidation, through the formation of an addition salt, such as hydrochloride, toluenesulfonic acid, trifluoroacetic acid and the like. Many of the amino protecting groups are also suitable for protecting carboxy, hydroxy and mercapto groups. For example, aralkyl groups. Alkyl groups are also sutiable groups for protecting hydroxy and mercapto groups, such as tert-butyl. Silyl protecting groups are silicon atoms optionally substituted by one or more alkyl, aryl and aralkyl groups. Suitable silyl protecting groups include, but are not limited to, trimethylsilyl , triethylsilyl, tri-isopropylsilyl, tert- butyldimethylsilyl, dimethylphenylsilyl , 1,2- bis (dimethylsilyl) benzene, 1 , 2-bis (dimethylsilyl) ethane and diphenylmethylsilyl . Silylation of an amino groups provide mono- or di-silylamino groups. Silylation of aminoalcohol compounds can lead to a N,N, O-tri-silyl derivative. Removal of the silyl function from a silyl ether function is readily accomplished by treatment with, for example, a metal hydroxide or ammonium flouride reagent, either as a discrete reaction step or in situ during a reaction with the alcohol group. Suitable silylating agents are, for example, trimethylsilyl chloride, tert-buty-dimethylsilyl chloride, phenyldimethylsilyl chloride, diphenylmethyl silyl chloride or their combination products with imidazole or DMF. Methods for silylation of amines and removal of silyl protecting groups are well known to those skilled in the art. Methods of preparation of these amine derivatives from corresponding amino acids, amino acid amides or amino acid esters are also well known to those skilled in the art of organic chemistry including amino acid/amino acid ester or aminoalcohol chemistry. Protecting groups are removed under conditions which will not affect the remaining portion of the molecule. These methods are well known in the art and include acid hydrolysis, hydrogenolysis and the like. A preferred method involves removal of a protecting group, such as removal of a benzyloxycarbonyl group by hydrogenolysis utilizing palladium on carbon in a suitable solvent system such as an alcohol, acetic acid, and the like or mixtures thereof. A t-butoxy carbonyl protecting group can be removed utilizing an inorganic or organic acid, such as HCI or trifluoroacetic acid, in a suitable solvent system, such as dioxane or methylene chloride. The resulting amino salt can readily be neutralized to yield the free amine. Carboxy protecting group, such as methyl, ethyl, benzyl, tert-butyl, 4-methoxyphenylmethyl and the like, can be removed under hydroylsis and hydrogenolysis conditions well known to those skilled in the art. Compounds of the invention may be prepared as described in the following schemes and synthetic examples . Compounds of the invention, E-B- (Alk) p -Q- (Alk) -A- G, can be prepared by one or more of the following coupling reactions using reagents, reaction conditions and solvents typical for such coupling reactions: 1. E + L-(Alk) p -Q-(Alk) q -A-G 2. E-OH + L- (Alk) p -Q- (Alk) q -A-G 3. E-SH + L- (Alk) p -Q- (Alk) q -A-G 4. E-NHR, + L-(Alk) p -Q- (Alk) q -A-G 5. E-NHR χ + L-C(Y) - (Alk) p -Q- (Alk) q -A-G 6. E-NHR χ + -C(Y)-NR x -(Alk) p -Q-(Alk) q -A-G 7. E-NHR, + L-S(0) t - (Alk) p -Q- (Alk) q -A-G 8. E-NHR 3 + L-S(0) t -NR 1 -(Alk) p -Q- (Alk) q -A-G 9. E-L + HO-(Alk) p -Q-(Alk) q -A-G 10. E-L + HS-(Alk) p -Q- (Alk) q -A-G 11. E-L + HNR 1 -(Alk) p -Q-(Alk) q -A-G 12. E-C(Y)-L + HNR 1 -(Alk) p -Q-(Alk) g -A-G 13. E-NR 1 -C(Y)-L + HNR 3 - (Alk) p -Q- (Alk) q -A-G 14. E-S(0) t -L + HNR 1 -(Alk) p -Q-(Alk) q -A-G 15. E-NR 1 -S(0) t -L + HNR 3 -(Alk) p -Q- (Alk) q -A-G 1 166.. E E--BB--((Alk) p -OH + L-(Alk) q -A-G 17 . E-B- ( Alk) p -SH + L-(Alk) q -A-G 18 . E-B- ( Alk) p -NHR 1 + L-(Alk) q -A-G 19 . E-B- ( Alk) p -NHR X + L-C(X)- (Alk) q -A-G 20 . E-B- ( Alk) p -NHR 1 + L-C(X)-NR 1 - (Alk) q -A-G 2 211.. E E--BB-- ((Alk) p -NHR 1 + L-S (0) t - (Alk) q -A-G 22 . E-B- ( Alk) p -NHR 1 + L-S(0) c -NR 1 - (Alk) q -A-G 23 . E-B- ( Alk) p -L + H0-(Alk) q -A-G 24 . E-B- ( Alk) p -L + HS- (Alk) g -A-G 25 . E-B- ( Alk) p -L + HNR X - (Alk) q -A-G 2 266.. E E--BB--((Alk) p -C(X)-L + HNR X - (Alk) q -A-G 27 . E-B- ( Alk) p -NR x -C(X)-L + HNR 1 -(Alk) q -A-G 28 . E-B- ( Alk) p -S(0) t -L + HNR 1 -(Alk) q -A-G 29 . E-B- ( Alk) p -NR 1 -S(0) t -L + HNR 1 -(Alk) q -A-G 30 . E-B- ( Alk) p -Q-(Alk) q -L + G 3 311.. E E--BB-- ((Alk) p -Q-(Alk) q -OH + L-G 32 . E-B- ( Alk) p -Q- (Alk) q -SH + L-G 33. E-B-(Alk) p -Q- (Alk) q -NHR 1 + L-G 34. E-B- (Alk) p -Q- (Alk) q -NHR 1 + L-C(X)-G 35. E-B-(Alk) p -Q- (Alk) q -NHR χ + L-C(X)-NR 1 -G 36. E-B-(Alk) p -Q-(Alk) q -NHR x + L-S(0) t -G 37. E-B-(Alk) p -Q-(Alk) q -NHR 1 + L-S (0) t -NR x -G 38. E-B-(Alk) p -Q- (Alk) q -L + HO-G 39. E-B-(Alk) p -Q- (Alk) q -L + HS-G 40. E-B-(Alk) p -Q- (Alk) q -L + HNR.-G 41. E-B- (Alk) p -Q- (Alk) q -C(X) -L + HNR.-G 42. E-B-(Alk) p -Q- (Alk) q -NR 1 -C (X) -L + HNR χ -G 43. E-B-(Alk) p -Q- (Alk) q -S (0) t -L + HNR X -G 44. E-B-(Alk) p -Q-(Alk) q -NR χ -S(0) c -L + HNR χ -G wherein L is a leaving group, such as chloro, bromo, iodo, triflyate, N-hydroxysuccinimide, N-hydroxybenzotriazole, tosylate, mesylate, methoxy, methylthiol, phenoxy, thiophenoxy and the like. Thioethers may be oxidized to the corresponding sulfinyl groups by oxidation with an oxidizing agent, such as hydrogen peroxide, sodium periodate and the like. Thioethers and sulfinyl groups may be oxidized to the corresponding sulfonyl groups by oxidation with an oxidizing agent, such as potassium peroxymonosulfate, potassium permanganate, hydrogen peroxide and the like. The preparation of amidine groups, such as when B represents a -C(Y)-N(R X )- or -N(R X )-C(Y)- radical, is well known to those skilled in the art (see Baati et al., Synthesis 1999:927-929; Dunn, Compr . Org. funct. Group Transform. 5:741-82 and 1161-308, 1995; and Gautier et al . , Chem. Amidines Imidates, Patai (Ed.), Wiley (1975), pp. 283-348). Guanidine groups, such as when B represents -N (R x ) -C (Y) -N(R x ) - radical, can be prepared from urea groups (e.g., by reaction with P0C1 3 and a substituted amine in an organic solvent, such as toluene), from thiourea groups (e.g., by reaction with a substituted amine in the presence of CuS0 4 , Si0 2 and a base, such as triethylamine, in an organic solvent such as tetrahydrofuran (Tet. Lett. 36:2841-4, 1995) or sodium periodate in the presence of base in dimethylformaide and water (Synlett 1997:1053-4)), from substituted cyanamide groups, -N(R)-CN (e.g., by reaction with a substituted amine) , from imino ester amine groups, R'O-C (NR) -N(R) - (e.g., by reaction with a substituted amine) , or from imino thioester amine groups, R' S-C (NR) -N (R) - (by reaction with a substituted amine (Synth. Commun. 29:1757-66, 1999). Schemes 1 and 2 illustrate the preparation of compounds of the invention wherein G is a benzazepine type ring system. Compounds (21) and (22), wherein A x - represents the radical E-B- (Alk) p -Q- (Alk) q -A- or an intermediate radical (such as, M-B- (Alk) p -Q- (Alk) q -A- , M-(Alk) p -Q- (Alk) q -A-, M-Q- (Alk) q -A-, M-(Alk) q -A-, M-A- and the like wherein M is a reactive moiety such as an electrophile, nucleophile, leaving group or the like or a group that can be converted into an electrophile, nucleophile, leaving group or the like) that can be readily converted into the radical E-B- (Alk) p -Q- (Alk) q - A- , can be prepared from the corresponding amines (23) and (25) , respectively, by alkylation, acylation, sulfonylation and the like, with A x -L, wherein L is a leaving group such as halide, tosylate, mesylate, carboxylic acid activating group (such as N- hydroxysuccinimide, carbodiimide (Tetrahedron 55:6813- 6830, 1999), BOP (J. Org. Chem. 63:9678-9683, 1998) and the like) and the like. Alternatively, compounds (21) and (22) can be prepared by (a) nucleophilic displacement by A 3 -NH 2 of leaving groups (L) on compounds (24) and (26), respectively, (b) reductive amination of compounds (24) and (26) , respectively, wherein L-X 2 - and L-X 3 - represents a ketone or aldehyde, using A X -NH 2 and a reducing agent (such as sodium cyanoborohydride, PtO /H 2 and the like) , or (c) a mixture of both (a) and (b) . Reaction of A X -NH 2 with L- X 2 - and L-X 3 - can be simultaneous (one pot) or sequencial stepwise reactions. Scheme 1 Scheme 2 26 Schemes 3 and 4 illustrate the preparation of synthetic intermediates useful in the preparation of compounds (23) and (24) . Scheme 3 addresses the preparation of the X 2 portion of the compounds and Scheme 4 addresses the X 3 portion of the compounds. Compound (28a/b) can be prepared from (27a/b) , respectively, by oxidizing the hydroxy group to an aldehyde, such as by Swern oxidation or the like, and reacting the aldehyde with a nucleophile of R 4 or R , respectively, such as with organometallic agents (such Scheme 3 as (R. 2 CuLi, R 10 -Li or the like), or alternatively, oxidizing the hydroxy group to a carboxylic acid, reacting the acid with a nucleophile of R 4 or R 10 , respectively, such as R 4 -Li, R 10 -MgBr or the like, and then reducing the resulting ketone to the hydroxy group, such as with sodium cyanoborohydride . Alcohol (28a/b) can be converted into sulfonyl compound (29a/b) by converting the hydroxy group into a leaving group (such as a halide, tosylate, mesylate, triflate or the like) , nucleophilic displacement of the leaving group with a thiol salt (such as sodium sulfide or the like) and then coversion of the resulting thiol to a sulfonyl halide (such as C1 2 /H 2 0 oxidation or the like). Alcohols (27a/b) and (28a/b) can be converted into cyano compounds (30a/b) and (31a/b) , respectively, by converting the hydroxy group into a leaving group as before followed by nucleophilic displacement of the leaving group with a cyanide salt (such as sodium cyanide or the like) . Cyano compound (31a/b) can be prepared from cyano compound (30a/b) by nucleophilic displacement reaction with R 4 -L and R 10 -L, respectively, in the presence of base. Cyano compound (31a/b) can be reduced to the amine (32a/b) , such as with BH 3 -Me 2 S or the like. Cyano compounds (30a/b) and (31a/b) can be hydrolyzed to a carboxylic acid which can then be esterified (P 2 ) to form esters (33a/b) and (34a/b) respectively, or the acid of (34a/b) can be converted into an active ester (35a/b) . As in the case of the cyano compound (30a/b), the ester compound (33a/b) can undergo a nucleophilic displacement reaction with R 4 -L and R 10 -L, respectively, in the presence of base (such as sodium hydride or the like) to prepare ester (34a/b) . Esters (33a/b) and (34a/b) can undergo a condensation reaction with R 67 -C(0)-L, wherein R 67 - represents radicals R 6 - or R 7 - as defined herein, in the presence of base, such as sodium hydride or the like, followed by hydroylsis and decarboxylation to yield ketones (36a/b) and (37a/b), respectively. Ketone (36a/b) can also undergo nucleophile displacement of R 4 -L and R 10 -L, respectively, in the presence of base to yield ketone (37a/b). Ketone (37a/b) can undergo reductive amination with A 3 -NH 2 or P N -NH 2 (wherein P N - is a nitrogen protecting group, such as benzyl, BOC or the like) or alternatively, can be reduced and the corresponding alcohol can be converted into a leaving group to yield compound (38a/b). The selection of which combination of moieties for X, and X, to be used in the preparation of compound (21] is well within the skill of one skilled in the art. Scheme 4 b 38b Schemes 5, 6 and 7 illustrate the preparation of compounds (25) and (26) . Schemes 5 and 6 address the preparation of the X 2 portion of the compounds and Scheme 7 addresses the X 3 portion of the compounds. Compound (40) can be prepared from aldehyde (39) as described above for compound (28). In Scheme 5, condensation of P,0 2 CCH 2 R 12 (or alternatively, the corresponding Wittig reagent (Chem. Rev. 89:863-927, 1989) or Horner-Wadsworth-Emmons condensation (Tet. Lett. 24:4405-4408, 1983)) with compound (39) in the Scheme 5 presence of base, such as sodium hydride or the like, can yield the unsaturated ester (41) which can undergo a Michael-type nucleophilic reaction to introduce the R 4 - radical, such as with (R 4 ) 2 Cu or the like, to yield ester (42). Alternatively, condensation of P 2 0 2 CCH 2 R 12 with compound (40) in the presence of base, such as sodium hydride or the like, can yield ester (42) directly. Ester (42) can be converted into an activated ester (43) which can be reacted with A X -NH 2 or P N -NH 2 . Alternatively, ester (42) can undergo a condensation reaction with R 67 -C(0)-L followed by hydroylsis and decarboxylation to yield ketone (44). Ketone (44) can undergo reductive amination with A X -NH 2 or P H -NH 2 or alternatively, can be reduced and the corresponding alcohol can be converted into a leaving group to yield compound (45) . Scheme 6 49 48 In Scheme 6, esters (33a) and (34a) can undergo a condensation reaction with R 12 -C(0)-L in the presence of base, such as sodium hydride or the like, followed by hydroylsis and decarboxylation to yield ketones (46) and (47), respectively. Ketone (46) can also undergo nucleophile displacement of R 4 -L in the presence of base to yield ketone (47). Reduction of ketone (47) and conversion of the resulting alcohol to a leaving group (such as a halide, tosylate, mesylate, triflate or the like) as described above can yield compound (48). Nucleophilic displacement of the leaving group of compound (48) with a thiol salt (such as sodium sulfide or the like) and then coversion of the resulting thiol to a sulfonyl halide (such as C1 2 /H,0 oxidation or the like) can yield compound (49) . Scheme 7 In Scheme 7, ketone (50) can be prepared from the corresponding carboxylic acid by reacting the acid with a nucleophile of R 67 , such as R 67 -Li, R 67 -MgBr or the like, or alternatively, by acylation of the aromatic ring with R 67 -C(0)-L in the presence of a Friedel- Crafts catalyst, such as A1C1 3 or the like, or alternatively, nucleophilic reaction of R 67 -C(0)-L or R 67 -C0 2 H with the corresponding organometallic salt of the aromatic ring. Ketone (50) can undergo reductive amination with A X -NH 2 or P N -NH 2 or alternatively, can be reduced and the corresponding alcohol can be converted into a leaving group to yield compound (51) . Sulfonyl compound (53) can be prepared from the corresponding thiol (52) (such as by Cl 2 /H 2 0 oxidation or the like) which can be prepared by nucleophilic displacement of the corresponding halide with a thiol salt (such as sodium sulfide or the like) . Scheme 8 Alternatively, compounds (21) and (22) can be prepared by Heck Cyclization (Trans. Met. Org. Synth. 1:208-240, 1998) as shown in Schemes 8 and 9, respectively. Unsaturated esters (54) and (55), wherein h 1 is a leaving group, such as halide, triflate or the like, can be cyclized in the presence of Pd(PPh 3 ) 4 to yield compounds (56) and (57), respectively. The double bond of compounds (56) and (57) can be reduced (such as by hydrogenation in the presence of Pd/C catalyst, magnesium in methanol or the like) and the ester groups can be readily converted into groups represented by R 4 - radical using methods described above and standard methods well known to those skilled in the art. Unsaturated esters (54) and (55) can be prepared by nucleophilic displacement of the leaving group L of compounds (58) and (60), respectively, with amino compounds (59) and (61), respectively, which are commerically available or can be readily prepared from commerically available starting materials. In leu of the nitrogen protecting group P N -, A x - or hydrogen atom may be used. Scheme 9 Alternatively, compounds (54) and (55) can be cyclized by radical chain reaction utilizing an appropriate initiator, such as AIBN (Tet. Lett. 32:2829-2832, 1991), to esters (56) and (57), respectively, wherein the double bond is saturated. Schemes 10 and 11 illustrate the preparation of compounds of the invention wherein G is a imidazolo- fused or triazolo-fused benzazepine type ring system. In Schemes 10 and 11, imidazolo-fused or triazolo-fused benzazepine type ring system (80) and (83) can be prepared from substituted imidazoles and triazoles (which are commercially available or readily prepared from commercially available starting materials) by alkylation of the imidazole or triazole nitrogen with alkylating agents (79) and (81) . Cyclization can be effected by coversion of the hydroxy group of the alkylating agent into a leaving group which undergoes nucleophilic displacement upon metalation of the bromo (alternatively, chloro or iodo) group of the imidazole or triazole. One skilled in the art will recognize that other known processes, conditions and methods can be employed to effect the cyclization. Alkylating agents (79) and (81) can be prepared according to the processes described above. Scheme 10 Scheme 11 81 83 The reactions described above may be carried out in any number of solvents in which the reactants may be mutually soluble, including, for example, tetrahydrofuran, benzene, toluene, chloroform, dichloromethane, N, -dimethylformamide, ethyl ether, dioxane, water, acetonitrile, or the like. Generally the reaction is carried out at a temperature of between -80°C and 150°C, preferably, however, at room temperature. In certain cases, as noted in the examples provided herein, however, the temperature of the reaction may reach as high as or exceed about 360°C. The product and intermediates may be isolated or purified using one or more standard purification techniques, including, for example, one or more of simple solvent evaporation, recrystallization, distillation, sublimation, filtration, chromatography, including thin-layer chromatography, HPLC (e.g., reverse phase HPLC using, for example, dilute trifluoroacetic acid in water, acetonitrile, or methanol mixtures as eluent) , column chromatography, flash chromatography, radial chromatography, trituration, and the like. In the preparation of the compounds of the invention, one skilled in the art will understand that one may need to protect or block various reactive functionalities on the starting compounds or intermediates while a desired reaction is carried out on other portions of the molecule. After the desired reactions are complete, or at any desired time, normally such protecting groups will be removed by, for example, hydrolytic or hydrogenolytic means. Such protection and deprotection steps are conventional in organic chemistry. One skilled in the art is referred to "Protective Groups in Organic Chemistry, " McOmie, Ed., Plenum Press, New York, New York; and "Protective Groups in Organic Synthesis," Greene, Ed., John Wiley & Sons, New York, NY (1981) for the teaching of protective groups which may be useful in the preparation of compounds of the present invention. Alternate means beyond those described above for preparing the compounds of the invention will be apparent to one skilled in the art and the noted general procedures are not to be construed as limiting the invention. To more fully understand the invention, including methods of preparing compounds of the invention, the following non-limiting examples are provided. The reader will appreciate that starting materials not otherwise described herein are either available commercially or can be prepared from commercially available compounds by methods generally known in the art . Unless otherwise noted, all materials were obtained from commercial suppliers and used without further purification. Anhydrous solvents such as dimethylformamide (DMF) , tetrahydrofuran (THF) , dichloromethane (CH 2 C1 2 ) , and toluene, dioxane were obtained from Aldrich Chemical Company in Sure/Seal bottles. All reactions involving air- or moisture- sensitive compounds were performed under a N 2 atmosphere. Flash chromatography was performed using ICN Biomedicals (SiliTech 32-63D 60A) . Thin-layer chromatography (TLC) was performed with Analtech or Whatman silica gel TLC plates (250 μm) . Preparatory TLC was performed with Whatman silica gel TLC plates (2000 μm) . 1 H NMR spectra were determined with superconducting FT NMR spectrometers operating at 400 and 500 MHz. Chemical shifts are expressed in ppm downfield from internal tetramethylsilane . Significant ^ ■ H NMR data are reported in the following order: multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; quin, quintet), number of protons, and coupling constants in Hz. Elemental analyses were performed by Atlantic Microlab, Inc., Norcross, GA. Melting points were determined with a Buchi 535 capillary melting point apparatus and are uncorrected. Low resolution mass spectra (MS) were determined on a Perkin Elmer-SCIEX API 165 mass spectrometer using APCI or ES ionization modes (positive or negative) . High resolution mass spectra (HRMS) were performed by Mass Consortium, San Diego, CA using FAB ionization. Example 1 Preparation of Methyl 2 - ( 1H, 2H, 3H, 4H, 5H- benzo [el zaperhydroepin-5-yl ) acetate Hydrochloride Step A: 3- ( ( ( 2-bromophenyl ) methyl ) amino) propan-1-ol To a stirring solution of 2-bromobenzaldehyde in dichloroethane (0.4 M) at RT under nitrogen was added 3-aminopropanol (1.5 eq) , sodium triacetoxyborohydride (2 eq) , and acetic acid (4 eq) . After 5 hr the reaction was carefully quenched with 2M sodium carbonate and extracted with methylene chloride. The organic phase was extracted with IN hydrochloric acid. The aqueous phase was neutralized with IN sodium hydroxide and extracted with methylene chloride. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford the product. EI- MS m/z 245 (M+H) * Step B: (Tert-butoxy) -N- (( 2-bromophenyl ) methyl ) -N- ( 3- hydroxypropyl ) carboxamide To a stirring solution of 3- (( (2-bromophenyl) methyl) amino)propan-l-ol in methylene chloride (0.1 M) was added di-tert-butyl dicarbonate (1.1 eq) . After 1 hr, the solvent was removed by rotary evaporation, and the residue partitioned between ether and IN HCI. The ethereal portion was dried over sodium sulfate filtered and concentrated in vacuo to afford the product. EI-MS m/z 344 (M+H) + Step C: Methyl (2E) -5- (N- ( tert-butoxycarbonyl ) -N- ( (2- bromophenyl ) methyl ) amino) pent-2 -enoate To a stirring solution of dimethyl sulfoxide (3.8 eq) in methylene chloride (0.1 M) at -78°C was added oxalyl chloride (1.8 eq) . After 10 min., (tert- butoxy) -N- ( ( 2 -bromophenyl) methyl) -N- (3- hydroxypropyl) carboxamide (1 eq) was added. After stirring for 30 min., diisopropylethylamine (4 eq) was added, and the reaction was allowed to warm to RT. After 30 min, methyl ( triphenylphosphoranylidene) acetate (1.2 eq) was added, and stirring was continued for 18 hr . The mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford the product. EI-MS m/z 398 (M+H) + Step D: Methyl 2- (2- ( tert-butoxycarbonyl) -1H, 3H, H- benzo Tel azaperhydroepin-5-ylidene) acetate To a stirring solution of methyl (2E) -5- (N- ( tert- butoxycarbonyl) -N- ( ( 2 -bromophenyl) methyl) amino) pent-2- enoate in toluene (0.1 M) was added triethylamine (1.5 eq) and tetrakis (triphenylphosphine) palladium (0.05 eq) . The reaction was refluxed for 48 hr under nitrogen cooled to RT. The solvent was removed by rotary evaporation and the product was purified by flash chromatograpy (10% EtOAc/Hexane) . EI-MS m/z 326 (M-H) " Step E: Methyl 2- (2- ( tert-butoxycarbonyl) -1H.3H. H, 5H- benzo [el azaperhydroepin-5-yl) acetate To a stirring solution of methyl 2- (2- ( tert-butoxy carbonyl) -1H, 3H, 4H-benzo [e] azaperhydroepin-5- ylidene) acetate in methanol (0.1 M) was added magnesium turnings (10 eq) and the mixture was refluxed for 18hr. The mixture was filtered through celite and concentrated by rotary evaporation. The product was purified by flash chromatography (25% EtOAc/Hexane) . EI-MS m/z 318 (M+H) * Step F: Methyl 2- ( IH, 2H, 3H, 4H, 5H- benzo [el azaperhvdroepin-5-yl ) acetate Hydrochloride Methyl 2- (2- ( tert-butoxycarbonyl ) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate was dissolved in 4M HCI in dioxane (0.2 M) . After 18 hrs, removal of solvent in vacuo, followed by trituration with ether afforded the product. EI-MS m/z 220 (M+H) * Preparation of 2- (2- (N- (3- (2-pyridylamino) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid Step A: 2- (N- ( 3-aminoprop-l-yl ) amino) pyridine To a stirring solution of 2-fluoropyridine in pyridine (0.5 M) was added 1 , 3-propanediamine (5 eq) , and the solution was refluxed overnight. The solution was then concentrated in vacuo and the residue was partitioned between ethyl acetate and 10% sodium carbonate. The phases were separated, and the organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo . The residue was chromatographed (silica; 10:1:1 EtOH/NH 4 OH/H 2 0) to afford a viscous pale yellow oil. EI-MS m/z 152 (M+H) + Step B: Methyl 2- ( 2- (N- ( 3- (2-pyridylamino) prop-1-yl) carbamoyl) -IH, 3H.4H-5H-benzo [el azapin-5-yl ) acetate Methyl 2- (IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate Hydrochloride was dissolved in methylene chloride and washed with IN NaOH. The organic layer was separated, dried over sodium sulfate and concentrated by rotary evaporation. The residue was stirred under nitrogen with 20% phosgene in toluene (0.1 M) for 10 mins . After concentration by rotary evaporation, the residue was dissolved in THF (0.1 M) , followed by addition of diisopropylethylamine (1.5 eq) and 2- (N- (3-aminoprop-1-yl) amino) pyridine (1.2 eq) . The reaction was stirred for 18 hr under nitrogen, followed by concentration by rotary evaporation and the product was purified by flash chromatograpy (5% MeOH/CH 2 Cl 2 ) . EI-MS m/z 397 (M+H) * Step C: 2- (2- (N- (3- ( 2-Pyridylamino) prop-1-yl ) carbamoyl) -IH, 3H, 4H, 5H-benzo fel azapin-5-yl) acetic acid To a stirring solution of methyl-2- (2- (N- ( 3- (2- pyridylamino) propyl) carbamoyl) -IH, 3H, 4H-5H- benzo [e] azapin-5-yl) acetate in methanol (0.1 M) was added IN NaOH (3 eq) . After 18 hrs, the reaction was neutralized with 10% HCI, concentrated by rotary evaporation and purified by recrystalization from 2% MeOH/CH 2 Cl 2 . EI-MS m/z 383 (M+H) * ; X H-NMR (400 MHz, d6- DMSO) : δ 7.90 (d, J=4.4Hz, IH) , 7.31 (m, 2H) , 7.25 (m, 2H) , 7.06 (m, IH) , 6.48 (m, 4H) , 4.48 (q, J=30Hz, 2H) , 3.53 (dd, J=6Hz, 2H) , 3.39 (d, J=7Hz, IH) , 3.30 (m, IH) , 3.12 (m, 2H) , 3.00 (m, 2H) , 2.45 (d, J=5.5Hz, 2H) , 1.83 (m, IH) , 1.60 (m, 2H) , 1.49 (m, IH) . Example 3 2- (2- (N- (4- (2-pyridylamino)butyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- (2- (N- (4- (2-pyridylamino)but-l-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 2- (N- (4-aminobut-l-yl) amino) pyridine and methyl 2- (1H,2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate according to the procedure of Example 2. EI-MS m/z 397 (M+H) * ; 'H-NMR (400 MHz, d6-DMSO) : δ 7.91 (d, J=4Hz, IH) , 7.43 (m, 2H) , 7.19 (m, 3H) , 6.48 (m, 3H) , 6.32 (t, J=10Hz, IH) , 4.48 (s, 2H) , 3.52 (m, 2H) , 3.41 (m, 2H) , 3.17(d, J=5.4Hz, 2H) , 2.96 (m, 2H) , 2.68 (m, 2H) , 1.81 (m, IH) , 1.48 (m, 2H) , 1.41 (m, 2H) . Example 4 2- (2- (N- (5- (2-ρyridylamino)pent-l-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo Tel azapin-5-yl) acetic acid 2- (2- (N- (5- (2-pyridylamino)pent-l-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 2- (N- ( 5-aminopent-l-yl) amino) pyridine and methyl 2- ( IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin- 5-yl) acetate according to the procedure of Example 2. EI-MS m/z 411 (M+H) * ; 'H-NMR (400 MHz, d6-DMSO) : δ 7.89 (d, J=1.4Hz, IH) , 7.28 (m, 2H) , 7.13-7.10 (m, 4H) , 6.37 (m, 2H) , 6.25 (t, J=5.3Hz, IH) , 4.38 (s, 2H) , 3.41 (m, 2H) , 3.34 (m, 2H) , 3.25(m, 2H) , 3.09 (t, J=17Hz, 2H) , 2.61 ( , 2H) , 1.75 (m, IH) , 1.40 (m, 2H) , 1.29 (m, 2H) , 1.03 (m, 2H) . Example 5 2- (2- (N-methyl-N- (4- (2-pyridylamino) but-l-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- (2- (N-methyl-N- (4- (2-pyridylamino) butyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 2- (N- (4- (methylamino)but-l- yl) amino) pyridine and methyl 2- (IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate according to the procedure of Example 2. EI-MS m/z 411 (M+H) * ; 'H-NMR (400 MHz, d6-DMSO) : δ 8.08 (d, J=5Hz, IH) , 7.50 (m, IH) , 7.41-7.23 (m, 5H) , 6.60 (m, 2H) , 4.50 (q, J=34Hz, 2H) , 3.68 (m, 2H) , 3.35 (m, 3H) , 3.13(m, IH) , 2.87 (d, J=7Hz, 2H) , 2.69 (m, 5H) , 2.11 (m, IH) , 1.88 (m, IH) , 1.69 (m, IH) , 1.41 (m, 2H) . 2- (2- (N- (4- (2-pyridylamino) -trans-cyclohexyl) carbamoyl) -1H.3H.4H, 5H-benzo [el azapin-5-yl) acetic acid 2- (2- (N- (4- (2-pyridylamino) -trans-cyclohexyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 2- (N- ( trans-4-aminocyclohexyl) amino) pyridine and methyl 2- ( IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate according to the procedure of Example 2. EI-MS m/z 423 (M+H) * ; ^-NMR (400 MHz, d4-CD 3 OD) : δ 7.70 (d, J=4.6Hz, IH) , 7.50 (m, IH) , 7.20-6.85 (m, 6H) , 6.42 (m, 2H) , 4.45 (q, J=9Hz, 2H) , 4.38 (m, IH) , 3.52 (m, IH) , 3.41 (m, 4H) , 2.61 (m, 3H) , 1.91 (m, 3H) , 1.76 (m, 2H) , 1.50 (m, IH) , 1.39-1.11 (m, 3H) 2- (2- ( ( (4- ( 2-pyridylamino) methyl) piperid-1-yl) carbonyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- (2- ( ( (4- (2-pyridylamino) methyl) piperid-1-yl) carbonyl ) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 2- (N- (piperid-4-ylmethyl) amino) pyridine and methyl 2- ( IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate according to the procedure of Example 2. EI-MS m/z 423 (M+H) * ; "H-NMR (400 MHz, d6-DMS0) : δ 8.02 (d, J=4.5Hz, IH) , 7.43 (t, J= 16Hz, IH) , 7.29 (d, J=7Hz, IH) , 7.20-6.96 (m, 3H) , 6.74 (d, J=12Hz, IH) , 6.50 (t, J=8Hz, IH) , 4.42 (q, J=24Hz, 2H) , 4.20 (d, J=12Hz, 2H) , 3.70-3.20 (m, 4H) , 2.85 (m, 2H) , 2.62 (t, J=24Hz, 2H) , 2.31 (d, J=7Hz, 2H) , 1.79 (m, IH) , 1.59 (m, 2H) , 1.47 (m, IH) , 0.99 (q, J=llHz, 2H) . Example 8 2- (2- (N- (3- (2-pyridylamino) methylphenyl ) carbamoyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- (2- (N- (3- (2 -pyridylamino) methylphenyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 2- (N- ( (3-aminophenyl) methyl) amino) pyridine and methyl 2- ( IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate according to the procedure of Example 2. EI-MS m/z 431 (M+H) * ; *H-NMR (400 MHz, d6-DMSO) : δ 8.02 (s, IH) , 7.84 (m, IH) , 7.32 (s, IH) , 7.00 (m, 4H) , 6.83 (m, IH) , 6.78 (d, J=7.5Hz, IH) , 6.30 (m, 2H) , 4.51 (q, J=8.5Hz, 2H) , 4.26 (s, 2H) , 3.56 (s, 2H) , 3.38 (m, IH) , 2.60 (m, 2H) , 1.80 (m, IH) , 1.48 (m, IH) . 2- (2- (N- (4- ( (6-methyl-2-pyridyl) amino) but-l-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- (2- (N- (4- ( (6-methyl-2-pyridyl) amino) but-1-yl) carbamoy) 1-lH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 6-methyl-2- (N- (4-aminobut-l- yl) amino) pyridine and methyl 2- (IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate according to the procedure of Example 2. EI-MS m/z 411 (M+H) * ; l H-NMR (400 MHz, d6-DMSO) : δ 7.52 (m, IH) , 7.32 (d, J=7Hz, IH) , 7.14 (m, 4H) , 6.41 (m, 2H) , 6.32 (m, IH) , 4.48 (s, 2H) , 3.59 (s, 2H) , 3.41 (m, 2H) , 3.20 (m, 2H) , 2.99 (m, 2H) , 2.70 (q, J=17Hz, 2H) , 2.34 (s, 3H) , 1.82 (m, IH) , 1.47 (m, 4H) . 2- (2- (N- (4- (pyrimidin-2-ylamino)but-l-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- (2- (N- (4- (pyrimidin-2-ylamino)but-l-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 6-methyl-2- (N- (4-aminobut-l- yl) amino)pyrimidine and methyl 2- (IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate according to the procedure of Example 2. EI-MS m/z 398 (M+H) * ; 'H-NMR (400 MHz, d6-DMSO) : δ 8.07 (d, J= 4.4Hz , IH) , 7.25- 6.82 (m, 5H) , 6.36 (t, J=10Hz, IH) , 6.12 (m, IH) , 4.26 (s, 2H) , 3.31 (s, 2H) , 3.21 (m, 2H) , 3.00 (t, J=6Hz, 2H) , 2.78 (m, 2H) , 2.50 (q, J=48Hz, 2H) , 1.62 (m, IH) , 1.22 (m, 4H) . 2- (2- (N- (3- ( 6-amino-2-pyridyl) prop-1-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid Hydrochloride 2- (2- (N- (3- (6-amino-2-pyridyl) prop-1-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-y) acetic acid hydrochloride was prepared from 6-amino-2- ( 3- aminoprop-1-yl) pyridine and methyl 2- ( IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate according to the procedure of Example 2. EI-MS m/z 383 (M+H) * ; 'H-NMR (400 MHz, d4-CD 3 OD) : δ 7.90 (t, J=8.7Hz, IH) , 7.42 (d, J=7.1Hz, IH) , 7.30 (m, 3H) , 6.91 (d, J+8.1Hz, 3H) , 6.32 (d, J=7.2Hz, IH) , 4.69 (q, J=30Hz, 2H) , 3.80 (m, IH) , 3.69 (m, 2H) , 3.37 (t, J=12Hz, 2H) , 2.91 (m, 2H) , 2.72 (t, J=14Hz, 2H) , 2.17 (m, IH) , 1.92 (t, J=14Hz, 2H) , 1.70 (m, IH) . 2-(2-(N-(3-(6- (tert-butoxycarbonylamino) -2- pyridyl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azapin- 5-yl) acetic acid 2- (2- (N- (3- (6 ( (tert-butoxy) carbonylamino) -2- pyridyl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e]azapin- 5-yl) acetic acid was prepared from 6-(tert- butoxycarbonylamino) -2- (3-aminoprop-l-yl) pyridine and methyl 2- (IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate according to the procedure of Example 2. EI-MS m/z 483 (M+H) * ; 'H-NMR (400 MHz, d4-CD 3 OD) : δ 7.63 (m, 2H) , 7.30 (d, J=7Hz, IH) , 7.27-7.12 (m, 4H) , 6.82 (d, J=7.Hz, IH) , 4.55 (q, J=53Hz, 2H) , 3.68 (m, IH) , 3.56 (m, 2H) , 3.20 (t, J=16Hz, 2H) , 2.76 (m, 2H) , 2.63 (t, J=15Hz, 2H) , 2.04 (m, IH) , 1.86 (t, J=15Hz, 2H) , 1.59 (s, 9H) , 1.32 (m, IH) . 2-(2-(N-(3-(l,2,3, 4-tetrahvdropyridino (2 , 3-b)pyridin- 7-yl)prop-l-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azapin- 5-yl) cetic acid 2- (2- (N- (3- (1, 2, 3, 4-tetrahydropyridino (2 , 3-b)ρyridin- 7-yl) prop-1-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin- 5-yl) acetic acid was prepared from 3- (1,2, 3,4- tetrahydropyridino [2 , 3-b] pyridin-7-yl ) prop-1-ylamine and methyl 2- (IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin- 5-yl) acetate according to the procedure of Example 2. 3- ( 1 , 2 , 3 , 4-tetrahydropyridino [2 , 3-b]pyridin-7-yl)prop- 1-ylamine was prepared according to Duggan, M. E. WO 98/18460. EI-MS m/z 423 (M+H) * ; 'H-NMR (400 MHz, d6- DMSO) : δ 7.30-6.98 (m, 5H) , 6.30 (m, IH) , 6.20 (d, J=7Hz, IH) , 4.41 (q, J=36Hz, 2H) , 3.60 (m, IH) , 3.40 (m, 2H) , 3.24 (t, J=llHz, 2H) , 2.94 (m, 2H) , 2.61 (t, J=13Hz, 2H) , 2.36 (t, J=15Hz, 2H) , 2.28 (d, J=7Hz, 2H) , 1.80 (m, 3H) , 1.64 (t, J=8Hz, 2H) , 1.40 (m, IH) . Example 14 Preparation of 2- (2- ( ( (4- (2-pyridylamino)but-l-yl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid Step A: 2-Hvdroxyphenyl ( (4- (2 -pyridylamino) butyl ) amino) sulfonate To a stirring solution of N- (2 -pyridyl ) -1, 4 butanediamine and triethylamine (1.1 eq) in dimethylformamide (0.15 M) at 0°C was added catechol sulfate (1.1 eq) in methylene chloride (0.15 M) . After 3 hrs, the reaction was poured into water and extracted with diethyl ether. The ethereal extract was dried over magnesium sulfate, filtered and concentrated in vacuo to afford the product. EI-MS m/z 338 (M+H) * Step B: Methyl 2- ( ( (4- (2-pyridylamino)but-l-yl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetate 2-Hydroxyphenyl ( (4- (2-pyridylamino)but-l-yl) amino) sulfonate (1 eq) and methyl 2- ( IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate (1 eq) were dissolved in dioxane (0.1 M) and refluxed under nitrogen for 5 hr. Removal of solvent by rotary evaporation and flash chromatography (5% MeOH in CH 2 C1 2 ) afforded the product. EI-MS m/z 447 (M+H) * Step C: 2- (2- (( (4- (2-pyridylamino) but-l-yl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid Methyl 2- (2- ( ( (4- (2-pyridylamino) but-l-yl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetate was saponified according to the procedure of Example 2. EI-MS m/z 433 (M+H) * ; 'H-NMR (400 MHz, d6-DMSO) : δ 7.80 (d, J=4Hz, IH) , 7.19 (t, J=14Hz, IH) , 7.13-6.92 (m, 5H) , 6.38 (m,lH), 6.30 (m, 2H) , 4.25 (q, J=32Hz, 2H) , 3.42 (m, IH) , 3.36 (m, IH) , 3.04 (m, 2H) , 2.46 (m, 2H) , 2.28 (m, 2H) , 1.75 (m, IH) , 1.41 (m, IH) , 1.28 (m, 4H) . Example 15 2- (2- ( ( (3- (2-pyridylamino) prop-1-yl) amino) sulfonyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2-(2-( ( (3-(2-pyridylamino) propyl ) amino) sulfony1 ) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 2-hydroxyphenyl ( (3- (2-pyridylamino) prop-1-yl) amino) sulfonate and methyl 2- ( IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl ) acetate according to the procedure of Example 14. EI-MS m/z 419 (M+H) * ; 'H-NMR (400 MHz, d6-DMSO) : δ 7.95 (d, J=4.3Hz, IH) , 7.35 (t, J=14Hz, IH) , 7.26-7.06 (m, 5H) , 6.57 (m, IH) , 6.41 (t, J=13Hz, 2H) , 4.38 (q, J=41Hz, 2H) , 3.58 (m, 3H) , 3.19 (t, J=3.5Hz, 2H) , 2.70 (t, J= 3Hz, 2H) , 2.38 (d, J=7Hz, 2H) , 1.88 (m, IH) , 1.60 (m, 2H) , 1.50 (m, 2H) . Example 16 Preparation of 2- (2- (2- ( (2- (2 -pyridylamino) ethyl) amino) acetyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid Step A: Methyl 2- ( 2- (2-Bromoacetyl) -IH.3H.4H.5H- benzo [el azapin-5-yl) acetate To a stirring solution of methyl 2- (IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate hydrochloride in THF (0.1 M) was added diisopropylethylamme (1.5 eq) . The reaction was stirred for 15 min, followed by addition of bromoacetyl bromide (1.1 eq) . After 30 min, the reaction was diluted with methylene chloride and washed with 10% HCI, water and brine. The organic layer was separated, dried over sodium sulfate and concentrated by rotary evaporation. The residue was purified by flash chromatography (50% EtOAc/Hexane) . Step B: Methyl 2- (2- (2- ( (2- (2-pyridylamino) ethyl) amino) acetyl) -IH, 3H, 4H.5H-benzo [el azapin-5-yl) acetate To a stirring solution of methyl 2- (2- (2-bromoacetyl) - IH, 3H, 4H, 5H-benzo[e]azepin-5-yl) acetate in THF (0.2 M) , was added diisopropylethylamme (1.5 eq) and 2-(2- pyridylamino) -1-aminoethane (1.2 eq) . The reaction was stirred for 18 hr, followed by concentration by rotary evaporation and the product was purified by flash chromatography (10% MeOH/CH 2 Cl 2 ) . EI-MS m/z 397 (M-H) ~ Step C: 2- (2- (2- ( (2- ( 2-pyridylamino) ethyl ) amino) acetyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid Methyl 2-(2-(2-((2-(2-pyridylamino) ethyl ) amino ) acetyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetate was saponified according to the procedure of Example 2. 'H-NMR (400 MHz, d4-CD 3 OD) : δ 7.90 (m, 2H) , 7.43-7.11 (m, 5H) , 6.97 (m, IH) , 4.69 (q, J=18Hz, 2H) , 4.19 (m, IH) , 3.83 (m, 2H) , 3.65 (m, IH) , 3.55 (m, IH) , 3.38 (m, 2H) , 3.34 (s, 2H) , 2.83 (m, 2H) , 2.04 (m, IH) , 1.69 (m, IH) . 2-(2-(2-((3- (2-pyridylamino) prop-1-yl) amino) acetyl- 1H.3H.4H, 5H-benzo [el azapin-5-yl) acetic acid 2-(2-(2-((3- (2-pyridylamino) prop-1-yl) amino) acetyl- (IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 3- (2-pyridylamino) -1-aminopropane and methyl 2- (2- (2-bromoacetyl) -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl) acetate according to the procedure of Example 16. l H-NMR (400 MHz, d4-CD 3 OD) : δ 7.39-7.04 (m, 6H) , 6.44 (m, 2H) , 4.60 (m, 2H) , 3.91 (m, IH) , 3.58 (m, 2H) , 3.39 (m, 2H) , 3.29 (s, 2H) , 2.95 (m, 2H) , 2.59 (m, 2H) , 1.95 (m, IH) , 1.85 (m, 2H) , 1.60 (m, 2H) . 2-(2-(2-((4- (2 -pyridylamino) but-l-yl ) amino) acetyl- 1H, 3H, 4H, 5H-benzo [el azapin-5-yl-acetic acid 2-(2-(2-((4- (2-pyridylamino) but-l-yl) amino) acetyl- IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 4- (2-pyridylamino) -1-aminobutane and methyl 2- (2- (2-bromoacetyl) -IH, 3H, 4H, 5H-benzo[e] azepin-5-yl) acetate according to the procedure of Example 16. 'H-NMR (400 MHz, d6-DMSO) : δ 7.96(m, IH) , 7.39-7.09 (m, 6H) , 6.46 (m, IH) , 6.40 (m, 2H) , 4.61 (m, 2H) , 3.74 (s, 2H) , 3.60 (m, IH) , 3.49 (m, IH) , 3.18 (m, 3H) , 2.66 (m, 4H) , 1.89 (m, IH) , 1.52 (m, 5H) . 2- (2- ( (N- (3- (2-pyridylamino) prop-l-yl) carbamoyl) methyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- (2- ( (N- (3- (2-pyridylamino) propyl) carbamoyl) methyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl ) acetate was prepared from 3- (2-pyridylamino) -1- (2-bromoacetylamino) propane and methyl 2- ( IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin- 5-yl) acetate hydrochloride in a manner similar to the procedure of Example 16, Step B. 3- (2-pyridylamino) - 1- (2-bromoacetylamino) propane was prepared from 3- (2- pyridylamino) -1-aminopropane and bromoacetyl bromide in a manner similar to the procedure of Example 16, Step A. X H-NMR (400 MHz, d6-DMSO) : δ 7.90 (m, IH) , 7.82 (m, IH) , 7.30 (m, IH) , 7.16 (m, IH) , 7.08 (m, 3H) , 6.44 (m, IH) , 6.39 (m, 2H) , 3.86 (m, 2H) , 3.43 (m, IH) , 3.24 (m, 2H) , 3.18 (m, 2H) , 3.02 (s, 2H) , 2.86 (m, 2H) , 2.70 (m, 2H) , 1.65 (m, IH) , 1.60 (m, 3H) . Preparation of 2- (2- (4- (2-pyridylamino) but-1-oxy carbonyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid Step A: Methyl 2- ( 2- (4- (2-pyridylamino) but-1- oxycarbonyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetate To a stirring solution of methyl 2- ( IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate hydrochloride in methylene chloride (0.2 M) , was added dimethylaminopyridine (2 eq) and 4- (2- pyridylamino) butyl 4-nitrophenyl carbonate (1.1 eq) . The reaction was stirred for 18 hr under nitrogen, diluted with methylene chloride, washed with sodium carbonate, dried over sodium sulfate, filtered and concentrated in vacuo . Flash chromatograpy (4% MeOH/CH 2 Cl 2 ) afforded the product. EI-MS m/z 412 (M+H) * Step B: 2- (2- (4- (2-pyridylamino) but-1-oxycarbonyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid Methyl 2- (2- (4- (2-pyridylamino) but-1-oxycarbonyl) - IH, 3H, 4H, 5H-benzo[e]azapin-5-yl) acetate was saponified according to the procedure of Example 2. EI-MS m/z 397 (M+H) * ; 'H-NMR (400 MHz, d6-DMSO) : δ 7.90 (m, IH) , 7.30 (m, IH) , 7.22-7.01 (m, 5H) , 6.39 (m, 2H) , 4.42 (q, J=30Hz, 2H) , 3.91 (m, 2H) , 3.69 (m, IH) , 3.57 (m, IH) , 3.46 (m, 2H) , 3.28 (m, 2H) , 2.69 (m, 2H) , 1.76 (m, IH) , 1.60 (m, 5H) . Example 21 Preparation of Methyl 2- ( 8-methoxy-lH, 2H, 3H.4H.5H- benzo [el azaperhydroepin-5-yl ) acetate Step A: Methyl 2-bromo-5-methoxybenzoate Sulfuric acid (2 eq) was added to a solution of 2- bromo-5-methoxybenzoic acid (1 eq) in methanol (0.30 M) at 0°C under N 2 . The solution was allowed to warm to RT and then refluxed for 5 h. After cooling to RT, the solution was concentrated in vacuo, the residue dissolved in ethyl acetate and washed with IN NaOH solution (2X) . The combined aqueous layers were extracted with ethyl acetate and the combined organics dried over MgS0 4 . Concentration in vacuo gave methyl 2-bromo-5-methoxybenzoate as a clear oil. EI-MS m/z 245, 247 (M+H) * Step B: 2-Bromo-5-methoxybenzyl alcohol Lithium aluminum hydride (1.3 eq) was added in portions to a solution of methyl 2-bromo-5-methoxy benzoate (1 eq) in diethyl ether (0.35 M) at 0°C under N 2 and the resulting mixture allowed to warm to RT with stirring for 5 h. Quenched with H 2 0 (IX g LAH) , followed sequentially by 15% NaOH solution (3X g LAH) , and H 2 0 (3X g LAH) . The solution was filtered through a scintered glass funnel rinsing with diethyl ether and concentrated in vacuo to give 2-bromo-5- methoxybenzyl alcohol as a clear oil. EI-MS m/z 239, 241 (M+Na) * Step C: 2-Bromo-5-methoxybenzaldehvde Pyridinium Chlorochromate (1.2 eq) was added to a solution of 2 -bromo-5-methoxybenzyl alcohol (1 eq) and Celite (1.2 eq) in methylene chloride (0.30 M) at RT and the resulting mixture was stirred under nitrogen for 3 h. The mixture was filtered through a plug of silica rinsing with methylene chloride and concentrated in vacuo to give 2-bromo-5-methoxy benzaldehyde as a white solid. EI-MS m/z 232, 234 (M+NH 4 ) * Step D : 3- ( ( (2 -bromo-5-methoxyphenyl ) methyl ) amino) propan-1-ol To a stirred solution of 2-bromo-5-methoxybenzaldehyde (1 eq) in dichloroethane was added 3-aminopropanol (1.5 eq) followed by NaBH(0Ac) 3 (2 eq) and acetic acid (4 eq) and the resulting mixture was stirred at RT under nitrogen for 8 h. The reaction mixture was quenched by careful addition of 2M Na 2 C0 3 solution and stirred 1 h. The mixture was concentrated in vacuo and poured into diethyl ether. The phases were separated and the organic phase washed with IN HCI solution. The aqueous phase was then washed with diethyl ether and subsequently basified with IN NaOH solution. The aqueous phase was extracted with diethyl ether, dried over Na 2 S0 4 and concentrated in vacuo to give 3- ( ( (2-bromo-5-methoxyphenyl) methyl) amino) propan-1-ol as a clear oil. EI-MS m/z 274, 276 (M+H) * Step E: N- ( tert-butoxycarbonyl ) -N- ( ( 2-bromo-5- methoxyphenyl ) methyl ) -N- ( 3-hvdroxypropyl ) amine Di-tert-butyl dicarbonate (1.1 eq) was added to a solution of 3- ( ( (2 -bromo-5-methoxyphenyl) methyl) amino) propan-1-ol (1 eq) in methylene chloride (0.30M) at RT and the resulting mixture stirred under nitrogen 2 h. Concentration in vacuo and purification by flash chromatography (20-30% ethyl acetate/hexane) gave N- ( tert-butoxycarbonyl) -N- ( (2-bromo-5-methoxyphenyl) methyl) -N- (3-hydroxypropyl) amine as a clear oil. EI- MS m/z 374, 376 (M+H) * Step F: Methyl (2E) -5- ( (tert-butoxy) -N- ( (2-bromo-5- methoxyphenyl ) methyl ) carbonylamino) pent-2-enoate Oxalyl chloride (1.8 eq) was added to a stirred solution of dimethylsulfoxide (3.8 eq) in methylene chloride (0.25 M) at -78°C maintaining the temperature < -65°C. After 20 min, a solution of N- (tert- butoxycarbonyl) -N- ( (2-bromo-5-methoxyphenyl) methyl) -N- (3-hydroxypropyl) amine (1 eq) was added and the resulting mixture stirred 30 minutes. Hunig's base (4 eq) was added and the reaction was allowed to warm to RT. The mixture was then cooled to 15°C and methyl (triphenylphosphoranylidene) acetate was added. The resulting mixture was stirred 12 h and purified by flash chromatography on silica gel (10-20% ethyl acetate/hexane) to give methyl (2E) -5- ( (tert-butoxy) - N- ( (2-bromo-5-methoxyphenyl)methyl) carbonylamino) pent- 2-enoate as a clear oil. EI-MS m/z 428, 430 (M+H) * Step G: Methyl 2- (2- ( tert-butoxycarbonyl) -8-methoxy- IH, 3H, 4H-benzo [el azaperhvdroepin-5-ylidene) acetate Triethylamine (1.5 eq) was added to a solution of methyl (2E)-5-( ( tert-butoxy) -N- ( (2-bromo-5-methoxy phenyl) methyl) carbonylamino) pent-2 -enoate (1 eq) , palladium acetate (0.10 eq) , and tri-o-tolylphosphine (0.20 eq) in acetonitrile (0.1 M) and the resulting mixture refluxed under argon for 48 h. Concentration in vacuo and purification by flash chromatography on silica gel (10-20% ethyl acetate/hexane) gave methyl 2- (2- (tert-butoxycarbonyl) -8-methoxy-IH, 3H, 4H- benzo [e] azaperhydroepin-5-ylidene) acetate as a clear oil. EI-MS m/z 348 (M+H) * Step H: Methyl 2- (2- (tert-butoxycarbonyl ) -8-methoxy- 1H, 3H, 4H, 5H-benzo [el azaperhvdroepin-5-yl) acetate Magnesium turnings (10 eq) were added to a solution of methyl 2- (2- (tert-butoxycarbonyl) -8-methoxy-IH, 3H, 4H- benzo [e] azaperhydroepin-5-ylidene) acetate (1 eq) in methanol (0.1 M) and the mixture refluxed under nitrogen for 24 h. After cooling to RT, the mixture was poured into 1 N HCI and extracted with ethyl acetate. The organics were dried over magnesium sulfate and concentrated in vacuo to give methyl 2- (2- ( ( tert-butyl) oxycarbonyl) -8-methoxy-IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 350 (M+H) * Step I: Methyl 2- ( 8-methoxy-lH, 2H, 3H.4H, 5H- benzo Tel azaperhvdroepin-5-yl) acetate Methyl 2- (2- (tert-butoxycarbonyl) -8-methoxy- IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate (1 eq) and 4.0 M HCl/dioxane (12 eq) were stirred at RT under nitrogen for 3 h. The solvents were removed by rotary evaporation and the residue dissolved in methylene chloride and washed with IN NaOH. The organics were dried over sodium sulfate and concentrated in vacuo to give methyl 2- ( 8-methoxy- 1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate as a white solid. EI-MS m/z 250 (M+H) * Preparation of 2- ( 8-methoxy-2- (N- (4- (2- pyridylamino)but-l-yl) carbamoyl) -1H.3H.4H, 5H- benzo [el azaperhydroepin-5-yl ) acetic acid Step A: Methyl 2- (8-methoxy-2- (N- (4- (2- pyridylamino) but-l-yl) carbamoyl) -IH, 3H, 4H, 5H- benzo [el azaperhvdroepin-5-yl) acetate Methyl 2- (8-methoxy-IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate (1 eq) was stirred under nitrogen with 20% phosgene (1.1 eq) in toluene for 10 min. The excess phosgene was removed by rotary evaporation and the crude product was dissolved in THF (0.10 M) , followed by addition of diisopropylethylamme (1.5 eq) and 2- (4-aminobut-l- ylamino) pyridine (1.5 eq) . The reaction was stirred for 12 h at RT under nitrogen, concentrated in vacuo and the product was purified by flash chromatograpy (4-7% MeOH/CH 2 Cl 2 ) to give methyl 2- ( 8-methoxy-2- (N- (4- (2-pyridylamino) but-l-yl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 441 (M+H) * Step B: 2- (8-methoxy-2- (N- (4- (2-pyridylamino)but-l-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azaperhvdroepin-5-yl) acetic acid 1 N NaOH solution (2 eq) was added to a solution of methyl 2- (8-methoxy-2- (N- (4- (2-pyridylamino)but-l-yl) carbamoyl ) -IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate (1 eq) in methanol (0.05 M) and the resulting mixture stirred under nitrogen for 12 h. The mixture was neutralized to pH=7 with IN HCI solution and concentrated in vacuo. Purification by flash chromatography on silica gel (20% MeOH/80% CH,C1/1% AcOH) gave 2- ( 8-methoxy-2- (N- (4- (2- pyridylamino) but-l-yl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetic acid as a white solid. EI-MS m/z 427 (M+H) * ; X H NMR (400 MHz, D 2 0) δ 7.76 (ddd, J = 8.8, 7.2, 1.4 Hz, IH) , 7.64 (d, J = 6.3 Hz, IH) , 6.98 (d, J = 8.5 Hz, IH) , 6.81 (m, 3H) , 6.58 (dd, J = 8.4, 2.4 Hz, IH) , 4.38 (ABq, J = 16.0 Hz, 2H) , 3.67 (s, 3H) , 3.57 (m, 2H) , 3.33 (m, IH) , 3.07 (m, 4H) , 2.63 (dd, J = 14.8, 8.2 Hz, IH) , 2.53 (dd, J = 14.8, 7.6 Hz, IH) , 1.81 (m, IH) , 1.55 (m, IH) , 1.40 (m, 2H) , 1.27 (m, 2H) . Example 23 Preparation of Methyl 2- (8-fluoro-lH, 2H.3H.4H, 5H- benzo [el azaperhvdroepin-5-yl ) acetate Step A: 3- (( (2-bromo-5-fluorophenyl) methyl) amino) propan-1-ol Hunig's base (1.3 eq) and 3-aminopropan-l-ol (1.3 eq) were added to a solution of 2-bromo-5-fluoro-benzyl bromide (1 eq) in acetonitrile (0.6 M) and the resulting mixture stirred at RT under nitrogen for 12 h. Concentrated in vacuo to give 3- ( ( (2-bromo-5- fluorophenyl ) methyl) amino) propan-1-ol as a clear oil. EI-MS m/z 262, 264 (M+H) * Step B: N- (tert-butoxycarbonyl) -N- ( (2-bromo-5- fluorophenyl) methyl) -N- ( 3-hydroxypropyl ) amine Di-tert-butyl dicarbonate (1.1 eq) was added to a solution of 3- (( (2-bromo-5-fluorophenyl) methyl) amino) proρan-1-ol (1 eq) in methylene chloride (0.50M) at RT and the resulting mixture stirred under nitrogen 5 h. Concentration in vacuo and purification by flash chromatography on silica gel (20-30% ethyl acetate/hexane) gave N- ( tert-butoxycarbonyl) -N- ( (2- bromo-5-fluorophenyl) methyl) -N- (3-hydroxypropyl) amine as a clear oil. EI-MS m/z 362, 364 (M+H) * Step C: Methyl (2E) -5- (N- ( tert-butoxycarbonyl) -N- ( (2- bromo-5-fluorophenyl ) methyl ) amino) pent-2 -enoate Oxalyl chloride (1.8 eq) was added to a stirred solution of dimethylsulfoxide (3.8 eq) in methylene chloride (0.25 M) at -78°C maintaining the temperature < -65°C. After 20 min, a solution of N- (tert- butoxycarbonyl ) -N- ( ( 2-bromo-5-fluorophenyl) methyl) -N- ( 3 -hydroxypropyl ) amine (1 eq) was added and the resulting mixture stirred 30 minutes. Hunig's base (4 eq) was added and the reaction allowed to warm to RT. The mixture was then cooled to 15°C and methyl (triphenylphosphoranylidene) acetate was added. The resulting mixture was stirred 12 h and purified by flash chromatography on silica gel (10-20% ethyl acetate/hexane) to give methyl (2E) -5- (N- (tert- butoxycarbonyl ) -N- ( (2-bromo-5-fluorophenyl ) methyl ) amino) pent-2-enoate as a clear oil. EI-MS m/z 474, 476 (M-H+HOAc) " Step D: Methyl 2- (2- ( tert-butoxycarbonyl) -8-fluoro- 1H, 3H, 4H-benzo [el azaperhvdroepin-5-ylidene) acetate Triethylamine (1.5 eq) was added to a solution of methyl (2E) -5- (N- ( tert-butoxycarbonyl) -N- ( (2-bromo-5- fluorophenyl) methyl) amino) pent-2 -enoate (1 eq) , palladium acetate (0.10 eq) , and tri-o-tolylphosphine (0.20 eq) in acetonitrile (0.1 M) and the resulting mixture refluxed under argon for 48 h. Concentration in vacuo and purification by flash chromatography on silica gel (5-10% ethyl acetate/hexane) gave methyl 2- (2- (tert-butoxycarbonyl) -8-fluoro-lH, 3H, 4H- benzo [e] azaperhydroepin-5-ylidene) acetate as a clear oil. EI-MS m/z 336 (M+H) * Step E: Methyl 2- (2- (tert-butoxycarbonyl) -8-fluoro- 1H, 3H, 4H, 5H-benzo [el azaperhvdroepin-5-yl) acetate Magnesium turnings (10 eq) were added to a solution of methyl 2- (2- (tert-butoxycarbonyl) -8-flouro-lH, 3H, 4H- benzo [e] azaperhydroepin-5-ylidene) acetate (1 eq) in methanol (0.1 M) and the mixture refluxed under nitrogen for 24 h. After cooling to RT, the mixture was poured into 1 N HCI and extracted with ethyl acetate. The organics were dried over magnesium sulfate and concentrated in vacuo to give methyl 2- (2- ( tert-butoxycarbonyl) -8-fluoro-lH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 338 (M+H) * Step F: Methyl 2- ( 8-fluoro-lH, 2H, 3H.4H, 5H- benzo Tel azaperhvdroepin-5-yl ) acetate Methyl 2- (2- (tert-butoxycarbonyl) -8-fluoro- 1H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate (1 eq) and 4.0 M HCl/dioxane (12 eq) were stirred at RT under nitrogen for 3 h. The solvents were removed by rotary evaporation and the residue dissolved in methylene chloride and washed with IN NaOH. The organics were dried over sodium sulfate and concentrated in vacuo to give methyl 2-(8-fluoro- IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl ) acetate as a clear oil. EI-MS m/z 238 (M+H) * Preparation of 2- (8- ■ fluoro-2- (N- (3- (1 ,2,3, 4-tetrahvdro pvridino [2,2 S , blpvridin-7-vl) propyl) ca:rbamovl ) - IH, 3H, 4H, 5H- -benzo [el azaperhvdroepin -5- -vl) acetic acid Step A: Methvl 2- (8- •fluoro-2- (N- (3- (1 ,2,3, 4-tetrahvdro pyridino [2,2 S ,blpyridin-7-vl)propvl) ca:rbamovl ) - IH, 3H.4H, 5H- -benzo [el azaperhvdroepin -5 -vl ) acetate Methyl 2- ( 8-fluoro-lH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate (1 eq) was stirred under nitrogen with 20% phosgene (1.1 eq) in toluene for 10 min. The excess phosgene was removed by rotary evaporation and the crude product was dissolved in 1:1 THF/DMF (0.25 M) , followed by addition of diisopropylethylamme (1.1 eq) and 3- (1,2,3, 4-tetrahydropyridino [2 , 3 , b] pyridin-7-yl) propylamine (1.1 eq) . The reaction was stirred for 12 h at RT under nitrogen, concentrated in vacuo and the product was purified by flash chromatograpy (2-5% MeOH/CH 3 Cl) to give methyl 2- (8-fluoro-2- (N- (3- (1,2,3, 4-tetrahydropyridino [2,3 , b]pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 455 (M+H) * Step B: 2- ( 8-fluoro-2- (N- ( 3- ( 1 , 2 , 3 , 4-tetrahvdro pyridino [2,3, bl pyridin-7-yl) ropyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [el azaperhvdroepin-5-yl) acetic acid 1 N NaOH solution (3 eq) was added to a solution of methyl 2- ( 8-fluoro-2- (N- (3- (1, 2, 3 , 4-tetrahydropyridino [2, 3, blpyridin-7-yl) ropyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate (1 eq) in methanol (0.10 M) and the resulting mixture stirred under nitrogen for 12 h. The mixture was neutralized to pH=7 with IN HCI solution and concentrated in vacuo. Purification by flash chromatography on silica gel (4-6% MeOH/CH 2 Cl 2 ) gave 2- ( 8-fluoro-2- (N- ( 3- (1,2,3, 4-tetrahydropyridino [2,3 , b]pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetic acid as a white solid. EI-MS m/z 441 (M+H) * ; * H NMR (400 MHz, CDC1 3 ) δ 10.56 (br s, IH) , 7.22 (d, J = 7.3 Hz, IH) , 7.12 (dd, J = 8.4, 5.8 Hz, IH) , 6.93 (dd, J = 9.2, 2.2 Hz, IH) , 6.86 (t, J = 8.4 Hz, IH) , 6.27 (d, J = 7.3 Hz, IH) , 5.55 (br s, IH) , 4.90 (br s, IH) , 4.35 (d, J = 15.2 Hz, 2H) , 3.50 (m, 4H) , 3.27 (m , IH) , 3.11 (m, IH) , 2.67 (m, 6H) , 2.35 (m, IH) , 1.90 (m, 4H) , 1.74 (m, IH) , 1.42 (m, IH) . Example 25 Preparation of 2- (2- ( (N- (4- (2-pyridylamino) prop-1-yl) carbamoyl}methyl) -3-oxo-lH, 4H, 5H-benzo (e) azepin-5-yl) acetic acid Step A: trans-σlutaconic acid methyl ester To a stirring solution of glutaconic acid in DMF (0.1 M) at 0°C was added NaH (1 eq) . After 15 min, iodomethane (1.2 eq) was added, and the mixture was allowed to warm to room temperature overnight. The reaction was quenched with saturated ammonium chloride, and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo . The residue was chromatographed (silica; 10% MeOH/CHCl 3 ) to afford a colorless viscous oil. EI-MS m/z 143 (M-H) ~ Step B: Benzyl 2- (N- (2-bromophenylmethyl ) amino) acetate To a stirring solution of 2-bromobenzaldehyde in dichloromethane (0.2 M) was added glycine benzyl ester (1.2 eq) , sodium triacetoxyborohydride (2 eq) and acetic acid (4 eq) . After stirring overnight, the solution was washed with 10% sodium carbonate, dried over magnesium sulfate, filtered and concentrated in vacuo . The residue was chromatographed (silica; 30% - 40% EtOAc/Hexanes) to afford a pale yellow oil. EI-MS m/z 334, 336 (M+H) * Step C: Benzyl 2- (N- ( (3- (methoxycarbonyl) propen-1-yl) carbonyl ) -N- (2 -bromophenylmethyl ) amino) acetate Benzyl 2- (N- (2-bromophenylmethyl) amino) acetate was dissolved in dichloromethane (0.2 M) , followed by addition of trans-glutaconic acid methyl ester (1.2 eq) , triethylamine (2 eq) , EDAC (1.2 eq) , and HOAT (0.1 eq) . After stirring for 2 hrs, the solution was washed with 10% HCI, 10% sodium carbonate, water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo . Flash chromatography (50% EtOAc/Hex) afforded a viscous oil. EI-MS m/z 460,462 (M+H) * Step D: Methyl 2- (2- ( (phenylmethoxycarbonyl) methyl) -3- oxo-lH, 4H-benzo [el azaperhvdroepin-5-ylidene) acetate Benzyl 2- (N- ( (3- (methoxycarbonyl) propen-1-yl) carbonyl ) -N- (2-bromophenylmethyl ) amino) acetate was dissolved in toluene (0.1 M) , followed by addition of triethylamine (1.2 eq) and tetrakis ( triphenyl phosphine) palladium (0.05 eq) , and the solution was stirred at reflux overnight. The reaction was washed with water and brine, dried over magnesium sulfate and concentrated in vacuo . Flash chromatography (silica; 50% EtOAc/Hex) afforded a viscous oil. EI-MS m/z 380 (M+H) * Step E: Methyl 2- ( 2- (carboxymethyl ) -3-oxo-lH, 4H, 5H- benzo [el azaρerhvdroepin-5-yl) acetate The olefin was dissolved in methanol, followed by addition of 10% palladium on carbon (10%/ wt) , and subjected to hydrogenation on a parr shaker at 50 psi . After 8 hrs, the mixture was filtered through celite and concentrated in vacuo to afford a viscous oil. EI-MS m/z 292 (M+H) * Step F: Methyl 2- (2- ( (N- (4- (2-pyridylamino) prop-1-yl) carbamoyl)methyl) -3-oxo-lH, 4H, 5H-benzo (e) azepin-5-yl) acetate Methyl 2- (2- (carboxymethyl) -3-oxo-lH, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate was dissolved in dichloromethane (0.2 M) followed by addition of 2- (3- aminoprop-1-ylamino) pyridine (1.2 eq) , Hunig's base (1.5 eq) , and EDAC (1.2 eq) . After 2 hours of stirring, the reaction was washed with 10% sodium carbonate, water and brine, dried over magnesium sulfate, filtered and concentrated. Flash chromatography (silica; 10% MeOH/CHCl3) afforded a colorless solid. EI-MS m/z 425 (M+H) * Step G: 2- (2- ( (N- ( 4- (2 -pyridylamino) prop-1-yl ) carbamoyl)methyl) -3-oxo-lH, 4H, 5H-benzo (e) azepin-5-yl) acetic acid Methyl 2- (2- ( {N- (4- (2-pyridylamino) prop-1-yl) carbamoyl}methyl) -3-oxo-lH, 4H, 5H-benzo (e) azepin-5- yl) acetate was dissolved in MeOH, followed by addition of 1 N NaOH (5 eq) , and solution was stirred overnight. 1 N HCI (5eq) was added, and the reaction was concentrated in vacuo . Flash chromatography (silica; 10% MeOH/CHCl3) afforded the title compound as a colorless solid. EI-MS m/z 411 (M+H) ; 2 H NMR (400 MHz; D20) : 7.62 (IH, t, J = 8.1 Hz), 7.53 (IH, d, J = 6.0 Hz), 7.10 (4H, m) , 6.74 (IH, d, J = 9.1 Hz), 6.62 (IH, t, J = 6.8 Hz), 4.67 (IH, d, J = 16 Hz), 4.22 (IH, d, J = 16 Hz), 3.95 (2H, m) , 3.42 (IH, t, J = 6.9 Hz), 3.12 (4H, m) , 2.0-1.8 (4H, m) , 1.65 (2H, m)-. Example 26 Preparation of Methyl 2- (IH.2H, 3H, 4H, 5H-benzo [di azepin-1-yl) acetate Step A: 2- (2-Bromophenyl) -N- (phenylmethyl) acetamide To a stirring solution of 2-bromophenylacetic acid in dichloromethane (0.2 M) was added benzylamine (1.2 eq) , triethylamine (1.5 eq) , and EDAC (1.5 eq) . After 2 hrs, the solution was washed with water, 10% HCI, 10% sodium carbonate, and water, dried over magnesium sulfate, filtered and concentrated in vacuo to afford a colorless solid. EI-MS m/z 304/306 (M+H) * Step B: N- (2- ( 2 -Bromophenyl ) ethyl ) -N- (phenylmethyl ) amine 2- (2 -Bromophenyl ) -N- (phenylmethyl ) acetamide was dissolved THF (0.2 M) , followed by addition of BH 3 ■ DMS (3 eq) , and the reaction was heated to reflux with stirring. After 2 hrs, the mixture was cooled to room temerature, and quenched with excess 10% HCI. The mixture was heated to reflux for 1 hr, and then cooled to room temperature. After washing with EtOAc, the aqueous phase was made alkaline with 10% sodium carbonate, and extracted with EtOAc . The organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo . The residue was triturated with EtOAc to afford a colorless solid. EI-MS m/z 290/292 (M+H) * Step C: Methyl 4- (N- (phenylmethyl) -N- ( (2- bromophenyl ) methyl ) amino) but-2-enoate N- ( 2 - ( 2-Bromophenyl ) ethyl ) -N- (phenylmethyl ) amine was dissolved in acetonitrile (0.2 M) , followed by addition of methyl 4-bromocrotonate (1.2 eq) and triethylamine (1.5 eq) , and the reaction was refluxed overnight. After cooling to room temperature, the reaction was diluted with EtOAc, washed with 10% sodium carbonate, water, and brine, dried over magnesium sulfate, filtered and concentrated in vacuo . Flash chromatography (silica; 50% EtOAc/Hex) afforded a colorless oil. EI-MS m/z 388/390 (M+H) * Step D: Methyl 2- (3- (phenylmethyl) -2H, 4H, 5H- benzo [dl azaperhvdroepin-1-ylidene) acetate Methyl 4- (N- (phenylmethyl) -N- ( (2 -bromophenyl) methyl) amino) but-2-enoate was dissolved in toluene (0.1M) followed by addition of triethylamine (1 eq) , tetrakis (triphenylphosphine) alladium (0.05 eq) , and 2M sodium carbonate (15%/v) . The mixture was heated to reflux overnight with vigorous stirring. After cooling to room temperature, the phases were separated, and the organic phase was washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo . The residue was dissolved in EtOAc and extracted 5x with 6N HCI. The combined extracts were neutralized with 10% sodium carbonate, and extracted with EtOAc. The organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated to afford a yellow oil. EI- MS m/z 208 (M+H) * Step E: Methyl 2- (IH, 2H.3H.4H, 5H-benzo [dl azepin-1-yl ) acetate Methyl 2- (3- (phenylmethyl) -2H, 4H, 5H- benzo [d] azaperhydroepin-1-ylidene) acetate was dissolved in MeOH (0.1M), followed by addition of p- toluenesulfonic acid (1 eq) and 10% palladium on carbon (50%/wt) , and the mixture was subjected to hydrogenation on a parr shaker at 50 psi overnight. The reaction was filtered through celite and concentrated in vacuo . The residue was dissolved in EtOAc, washed with 10% sodium carbonate and brine, dried over magnesium sulfate, filtered and concentrated to afford the title compound as a colorless oil. EI-MS m/z 220 (M+H) * Example 27 Preparation of 2- ( 3- ( (N- ( 4- (2 -pyridylamino) but-l-yl ) carbamoyl Imethyl) -IH, 2H, 4H, 5H-benzo [dl azepin-1-yl) acetic acid Step A: Methyl 2- ( 3- ( (N- (4- (2-pyridylamino) but-l-yl) carbamoyl) methyl ) -IH, 2H, 4H, 5H-benzo [dl azepin-1-yl ) acetate To a stirring solution of methyl 2- ( IH, 2H, 3H, 4H, 5H- benzo [d] azepin-1-yl) acetate in acetonitrile (0.2 M) was added Hunig's base (1.5 eq) , followed by bromoacetic acid. After stirring for 2 hr, 2-((4- aminobut-1-yl) amino) pyridine (1.2 eq) was added, followed by Hunig's base (1.5 eq) and EDAC (1.5 eq) , and stirring was continued for another 2 hr . The reaction was diluted with EtOAc, and washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo . Flash chromatography (silica; 10% MeOH/EtOAc) afforded a colorless solid. EI-MS m/z 425 (M+H) * Step B: 2- ( 3- ( (N- ( 4- (2-pyridylamino) but-l-yl ) carbamoyl)methyl) -IH, 2H, 4H, 5H-benzo [dl azepin-1-yl) acetic acid Methyl 2- (3- ( {N- (4- (2-pyridylamino) but-l-yl) carbamoyl} methyl) -IH, 2H, 4H, 5H-benzo [d] azepin-1-yl) acetate was dissolved in MeOH (0.1M) followed by addition of IN NaOH (5 eq) . After stirring overnight, IN HCI (5eq) was added, and the solution was concentrated in vacuo . Flash chromatography (10% MeOH/CHCl 3 ) afforded a colorless solid. EI-MS m/z 411 (M+H) * ; X H NMR (400 MHz; D 2 0) : 7.50 (2H, m) , 6.93 (4H, m) , 6.62 (IH, d, J = 8.9 Hz), 6.51 (IH, t, J = 6.7 Hz), 3.23 (IH, m) , 3.01 (6H, m) , 2.75 (2H, br) , 2.57 (4H, m) , 2.38 (2H, m) , 1.36 (4H, br) . 2- (3-f ΓN-(3- (l,2,3,4-tetrahvdropyridino[2,3-blpyridin- 7-yl ) propyl) carbamoyl1 methyl ) -IH, 2H, 4H, 5H- benzo [dl azepinyl) acetic acid 2-(3-{[N-(3-(l,2,3, 4-tetrahydropyridino [ 2 , 3-b] pyridin- 7-yl ) propyl ) carbamoyl ] methyl } -IH, 2H, 4H, 5H-benzo [d] azepinyl) acetic acid was prepared from bromoacetic acid, 3- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3 , b] pyridin-7- yDpropylamine and methyl 2- ( IH, 2H, 3H, 4H, 5H-benzo [d] azepin-1-yl) acetate according to the procedure of Example 27. EI-MS m/z 437 (M+H) * ; * H NMR (400 MHz; CDC1 3 ) : 9.61 (IH, br) , 8.39 (IH, br) , 7.15 (5H, m) , 6.31 (IH, d, J = 7.25 Hz), 3.64 (2H, m) , 3.34 (6H, m) , 2.99 (4H, m) , 2.71 (4H, m) , 1.93 (5H, m) , 0.86 (2H, m) Example 29 2- (3- (N- (5- (2-pyridylamino) pent-1-yl) carbamoyl }- IH, 2H, 4H, 5H-benzo [dl azepinyl) acetic acid 2- (3-{N- (5- (2-pyridylamino) pent-1-yl) carbamoyl }- IH, 2H, 4H, 5H-benzo [d] azepinyl) acetic acid was prepared from methyl 2- ( IH, 2H, 3H, 4H, 5H-benzo [d] azepin-1-yl) acetate and 2- ( ( 5-aminopent-l-yl) amino) pyridine according to the procedure of Example 2. EI-MS m/z 411 (M+H) * ; X H NMR (400 MHz; D 2 0) : 7.42 (IH, d, J = 6.02 Hz), 7.33 (IH, t, J = 8.01 Hz), 6.82 (4H, m) , 6.46 (IH, d, J = 8.90 Hz) , 6.40 (IH, t, J = 6.9 Hz) , 3.18 (5H, m) , 2.90 (2H, t, J = 6.80 Hz) , 2.72 (3H, m) , 2.51 (IH, dt, J = 15.11 Hz, 4.42 Hz) , 2.18 (2H, m) , 1.23 (2H, m) , 1.06 (2H, m) , 0.94 (2H, m) . 2-(3-(N-(3-(l,2.3, 4-tetrahvdropyridino \2 , 3-blpyridin- 7-yl) propyl) carbamoyl) -IH, 2H, 4H, 5H-benzo [dl azepin-1- yljacetic acid 2- {3- (N- (3- (1,2, 3, 4-tetrahydropyridino[2,3-b]pyridin- 7-yl) propyl) carbamoyl) -IH, 2H, 4H, 5H-benzo [d] azepin-1- yl} acetic acid was prepared from methyl 2- (1H, 2H, 3H,4H,5H-benzo[d]azepin-l-yl) acetate and 3- (1,2,3, 4-tetrahydropyridino [2, 3-b]pyridin-7-yl) propylamine according to the procedure of Example 2. EI-MS m/z 423 (M+H) * ; * H NMR (400 MHz, CDC1 3 ) : 11.10 (IH, br) , 7.86 (IH, br) , 7.28-7.14 (5H, m) , 6.32 (IH, d, J = 7.18 Hz), 4.79 (IH, br) , 4.10 (IH, br) , 3.48 (5H, m) , 3.2-2.6 (10H, m) , 2.08 (IH, m) , 1.90 (4H, m) Example 31 7- ( 2-pyridylamino) heptanoic acid To a stirring solution of 7-aminoheptanoic acid in pyridine (0.5 M) was added 2-fluoropyridine (2 eq) and 2N NaOH (leq), and the reaction was refluxed overnight. The mixture was adjusted to neutral pH with 6N HCI and concentrated in vacuo. The residue was suspended in 10:1:1 EtOH/NH 4 OH/H 2 0, filtered through a plug of silica, and concentrated in vacuo to afford a colorless solid. Example 32 Preparation of 2- ( 3- (7- (2-pyridylamino) heptanoyl) - IH, 2H, 4H, 5H-benzo [dl azepin-1-yl} acetic acid Step A: Methyl 2- (3- (7- (2-pyridylamino) heptanoyl) - IH, 2H, 4H, 5H-benzo[dlazepin-l-yl}acetate To a stirring solution of methyl 2- ( IH, 2H, 3H, 4H, 5H- benzo [d] azepin-1-yl) acetate in dichloromethane (0.2 M) was added 7- (2-pyridylamino) heptanoic acid (1.2 eq) , triethylamine (1.5 eq) , and EDAC (2 eq) . After 4 hrs, the reaction was washed with water, 10% sodium carbonate, dried over magnesium sulfate, filtered and concentrated in vacuo . Flash chromatography (silica; EtOAc) afforded a colorless oil. Step B: 2- (3- (7- (2 -pyridylamino) heptanoyl) - IH, 2H, 4H, 5H-benzo [dl azepin-1-yl}acetic acid Methyl 2- (3- (7- (2-pyridylamino) heptanoyl) -1H,2H,4H, 5H- benzo [d] azepin-l-yl}acetate was dissolved in MeOH, and IN NaOH (5 eq) was added. After stirring overnight, IN HCI (5 eq) was added, and the reaction was concentrated in vacuo . Flash chromatography (silica; 10% MeOH/CHCl 3 ) afforded a colorless solid. The sodium salt was prepared by dissolving the compound in MeOH (0.1 M), adding NaOMe (1.0 eq, 0.5 M in MeOH), and concentrating in vacuo to afford a colorless solid. ESI-MS m/z 432 (M+H) * ; l H NMR (400 MHz, DMSO-d6): 7.98 (IH, m) , 7.33 (IH, m) , 7.2-7.10 (4H, m) , 6.60 (IH, d, J = 8.4 Hz), 6.43 (IH, m) , 3.71 (2H, m) , 3.49 (2H, m) , 3.24 (2H, m) , 2.90 (3H, m) , 2.40 (2H, m) , 2.24 (2H, m) , 2.07 (IH, m) , 1.53 (4H, m) , 1.20 (4H, m) . Example 33 Preparation of 2- { 6- (N- (3- ( 1 , 2 , 3 , 4-tetrahydropyridino r2 , 3-blpyridin-7-yl)propyl) carbamoyl) -5H, 7H.8H, 9H- pyridino [2 , 3-el azaperhvdroepin-9-yl) acetic acid Step A: N- ( (2-Bromo ( 3-pyridyl ) ) methyl ) -2- ( 1 , 3- dioxolan-2-yl) ethylamine To a solution of 2-bromopyridine-3-carbaldehyde (3.53 g, 19.0 mmol, 1.0 eq) (Melnyk et al . , Synthetic Commun. 23 (19 ): 2727-2730 , 1993) in 1 , 2-dichloroethane (50 mL) was added 2- ( 1, 3-dioxolan-2-yl) ethylamine (TCI-GR, 2.67 g, 22.8 mmol, 1.2 eq) , sodium triacetoxyborohydride (Aldrich, 1.61 g, 76 mmol, 4.0 eq) and glacial acetic acid (1.14 g, 19 mmol, 1.0 eq) . The reaction mixture was stirred under nitrogen at room temperature for 2 h. The reaction was quenched with 1.0 N aqueous NaOH to about pH 8 and the solution was extracted with EtOAc (200 mL x 3) . The organic extracts were washed with saturated NaCI, dried with MgS0 4 , filtered and concentrated. Flash column chromatography (silica gel, 0-10% EtOAc-Hexane) afforded the title compound as a colorless oil. MS m/z 377 (Br = 79, M + H), 379 (Br = 81, M + H). Step B: N-( (2-Bromo ( 3-pyridyl) methyl ) -N- (2- ( 1.3- dioxolan-2-yl) ethyl) (phenylmethoxy) carboxamide A biphasic mixture of N- ( (2 -bromo ( 3 -pyridyl) ) methyl ) - 2- (1, 3-dioxolan-2-yl) ethyla ine (4.15 g, 14.4 mmol, 1.0 eq) , benzyl chloroformate (Aldrich, 3.70 g, 21.7 mmol, 1.5 eq) and Na 2 C0 3 (3.05 g, 28.8 mmol, 2.0 eq) CH 2 C1 2 (20 ml) and H 2 0 (20 mL) was stirred at room temperature overnight. The reaction mixture was diluted with H 2 0 (50 mL) , and extracted with CH 2 C1 2 (60 mL x 3) . The organic extracts were washed with brine, dried with Na 2 S0 4 , filtered, and concentrated. Flash column chromatography (silica gel, ' 0-50% EtOAc-Hexane) afforded the title compound as a colorless oil. MS m/z 421 (Br = 79, M + H), 423 (Br = 81, M + H). Step C: N- ( (2-Bromo (3-pyridyl) methyl ) -N- (3-oxobutyl) (phenylmethoxy) carboxamide : A solution of N- ( (2-bromo (3 -pyridyl ) methyl ) -N- (2- (1, 3- dioxolan-2-yl) ethyl) (phenylmethoxy) carboxamide in a mixture of 5% aqueous HCI (50 mL) and acetone (50 mL) was stirred at room temperature for 24 h. Acetone was removed under reduced pressure and the aqueous reaction mixture was extracted with EtOAc (70 mL x 3 ) . The organic extracts were washed with brine, dried with Na 2 S0 4 , filtered and concentrated. Flash column chromatography (silica gel, 0-50% EtOAc-Hexane) afforded the title compound as a colorless oil. MS m/z 376 (Br = 79, M + H), 378 (Br = 81, M + H). Step D: Methyl (2E) -5- (N- ( (2-bromo ( 3-pyridyl) methyl ) - N- (phenylmethoxycarbonyl) amino}pent-2-enoate To a solution of N- ( (2-bromo ( 3 -pyridyl) methyl ) -N- ( 3- oxobutyl) (phenylmethoxy) carboxamide (4.83 g, 12.8 mmol, 1.0 eq) in CH 2 C1 2 (20 mL) at room temperature was added a solution of carbomethoxymethylene triphenylphosphorane (Avocado, 4.92 g, 14.7 mmol, 1.15 eq) in CH 2 C1 2 (50 mL) by a canular. The reaction mixture was stirred under nitrogen at room temperature for 6 h. The solvent was removed under reduced pressure. Flash column chromatography (silica gel, 0- 50% EtOAc-Hexane) afforded the title compound as a colorless oil. MS m/z 433 (Br = 79, M + H), 435 (Br = 81, M + H) . Step E: Methyl 2- ( 6- (benzyloxycarbonyl ) -5H, 7H, 8H- pyrido [2 , 3-el azaperhydroepin-9-ylidene)acetate A mixture of methyl (2E) -5- {N- ( (2-bromo (3-pyridyl) methyl) -N- (phenylmethoxycarbonyl) amino)pent-2-enoate (650 mg, 1.50 mmol, 1.0 eq) , tetrakis (triphenyl phosphine) palladium(O) (Aldrich, 581 mg, 0.50 mmol, 0.33 eq) , triethylamine (540 mg, 4.5 mmol, 3.0 eq) , aqueous sodium carbonate ( 8 mL, 2.0 M) in toluene (23.0 mL) in a sealed vessel was stirred at 120°C for 48 h. The reaction mixture was diluted with CH 2 C1 2 (40 mL) and was allowed to pass through a pad of celite. The organic layer was separated and aqueous layer was extracted with CH 2 C1 2 (40 mL x 2 ) . The combined organic layer was dried with Na 2 S0 4 , filtered and dried under reduced pressure. Reverse phase high performance liquid chromatography (0.1% TFA-H 2 0/CH 3 CN) afforded the title compound as a colorless semisolid. MS m/z 353 (M + H) . Step F: Methyl 2- ( 5H, 6H, 7H, 8H-pyridino r2 , 3-el azaperhvdroepin-9-ylidene) acetate A mixture of methyl 2-{ 6- (benzyloxycarbonyl) -5H, 7H, 8H- pyrido [2 , 3-e] azaperhydroepin-9-ylidene) acetate (127 mg, 0.36 mmol, 1.0 eq) , ammonium formate (Sigma, 192 mg, 2.72 mmol, 8.0 eq ) and 10% Pd/C (24 mg) in a mixture of solvents (10 mL of methanol and 5 mL of H 2 0) was stirred at room temperature for 3 h. Methanol was removed under reduced pressure. The remaining aqueous layer was diluted with aqueous sodium carbonate (2.0 M, 20 mL) and extracted with CH 2 C1 2 (30 mL x 3) . The organic extractants were dried with Na 2 S0 4 , filtered and concentrated. Preparative thin layer chramotography (5% Methanol + 0.5% ammonium hydroxide- CH 2 C1 2 ) afforded the title compound as a colorless semisolid. MS m/z 219 (M + H) . Step G: Methyl 2- ( 5H, 6H, 7H, 8H, 9H-pyridino \ 2 .3-el azaperhydroepin-9-yl) acetate A mixture of methyl 2- (5H, 6H, 7H, 8H-pyridino [2 , 3-e] azaperhydroepin-9-ylidene) acetate (35 mg, 0.16 mmol, 1.0 eq) and magnesium (Aldrich, powder, 42 mg, 1.73 mmol, 11 eq) in methanol (1.65 mL) was stirred for 20 h. Following the dilution of the reaction mixture with methanol, it was allowed to pass through a pad of celite and concentrated under reduced pressure. Preparative thin layer chromatography (5% Methanol + 0.5% ammonium hydroxide-CH 2 Cl 2 ) afforded the title compound as a colorless sticky solid. MS m/z 221 (M + H) . Step H: Methyl 2- ( 6- (N- (3- (1 , 2 , 3 , 4-tetrahydropyridino T2 , 3-blpyridin-7-yl)propyl) carbamoyl) -5H, 7H, 8H, 9H- pyridino [2 , 3-el azaperhvdroeρin-9-yl) acetate To a mixture of methyl 2- (5H, 6H, 7H, 8H, 9H-pyridino [2 , 3- e] azaperhydroepin-9-yl) acetate (16 mg, 0.073mmol, 1.0 eq) in THF (0.5 mL) was added a solution of phosgene (Fluka, 1.0 mL, 20% in toluene) and diisopropylethyl amine (38 mg, 0.29 mmol, 4.0 eq) . The reaction mixture was stirred at room temperature for 10 min. Solvents were removed under reduced pressure. The newly formed intermediate was dissolved in THF (1 mL) , followed by the addition of a solution of 3- (1,2, 3,4- tetrahydropyridino [2 , 3-b] yridin-7-yl)propylamine (0.212 mL, 1.1 M in THF/DMF, 0.23 mmol, 3.2 eq) and diisopropylethylamme (38 mg, 0.29 mmol, 4.0 eq) . The reaction mixture was stirred at room temperature overnight. Preparative thin layer chromatography (5% MeOH + 0.25% triethylamine-CH 2 Cl 2 ) afforded the title compound as a colorless semisolid. MS m/z 438 (M + H) . Step I: 2-(6- (N- (3- (1, 2, 3, 4-tetrahvdropyridino [2 , 3-bl Pyridin-7-yl) propyl) carbamoyl) -5H, 7H, 8H, 9H- pyridino [2 , 3-el azaperhvdroepin-9-yl}acetic acid To a solution of methyl 2- { 6- (N- (3- ( 1 , 2 , 3 , 4-tetrahydro pyridino [2 , 3-b] pyridin-7-yl) propyl) carbamoyl) - 5H,7H, 8H, 9H-pyridino[2, 3-e] azaperhydroepin-9-yl} acetate (11.1 mg, 0.254 mmol, 1.0 eq) in ethanol (0.30 mL) was added a solution of NaOH (0.028 mL, 2.0 M, 0.0556 mmol, 2.2 eq) was stirred at 55°C for 24 h. Following the neutralization of the reaction mixture with a solution of HCI (0.028 mL, 2.0 N) , all the solvents were removed under reduced pressure. The crude product was triturated 10% MeOH-CH 2 Cl 2 , filtered and concentrated under reduced pressure to afford the title compound as colorless sticky solid. X H NMR (400 MHz, CD 3 OD) : 8 8.32 (m, 1), 7.67 (d, 1, J = 7.5 Hz), 7.44 (d, 1, J = 7.3), 7.18 (m, 1), 6.49 (d, 1, J = 7.3), 4.78 (d, 1, J = 15.6), 4.53 (d, 1, J = 15.6), 3.68 (m, 1), 3.55 (m, 2), 3.45 (t, 2, J = 5.7), 3.34 (s, 1), 3.17 (m, 1), 2.97 (dd, 1, J = 5.2, 15.6), 2.77 (t, 2, J = 6.1), 2.61 (m, 3), 2.28 (m, 1), 1.80 (m, 2), 1.58 (m, 1), 1.31 (m, 1), 1.13 (m, 1). MS m/z 424 (M + H) . HRMS m/z 424.2343 (M + H, C 23 H 29 N 5 0 3 calc . 424.2349) . Example 34 Preparation of 2- (2- (N- (4- (2-pyridylamino-3-nitro-4- methyl) but-l-yl) carbamoyl) -IH.3H, 4H.5H- benzo [el azapin-5-yl) acetic acid Step A: 2- (N- ( 4-aminoproρ-l-yl ) amino-3-nitro-4- methyl ) pyridine To a stirring solution of 2-chloro-3-nitro-4- methylpyridine in pyridine (0.5 M) was added 1,4- butanediamine (5 eq) , and the solution was refluxed for 18 hrs. The solution was then concentrated in vacuo and the residue was partitioned between ethyl acetate and 10% sodium carbonate. The phases were separated, and the organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo . The residue was chromatographed (silica; 10:1:1 EtOH/NH 4 OH/H 2 0) to afford a viscous pale yellow oil. EI-MS m/z 152 (M+H) Step B: Methyl 2- (2- (N- (4- (2-pyridylamino-3-nitro-4- methyl ) but-l-yl ) carbamoyl ) -IH .3H .4H-5H- benzo [el azapin-5-yl) acetate Methyl 2- (IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate Hydrochloride was dissolved in methylene chloride and washed with IN NaOH. The organic layer was separated, dried over sodium sulfate and concentrated by rotary evaporation. The residue was stirred under nitrogen with 20% phosgene in toluene (0.1 M) for 10 mins . After stirring the reaction was concentration by rotary evaporation, the residue was dissolved in THF (0.1 M) , followed by addition of diisopropylethylamme (1.5 eq) and 2- (N- (4-aminoprop- l-yl ) amino-3-nitro-4-methyl ) pyridine (1.2 eq) . The reaction was stirred for 18 hr under nitrogen, followed by concentration by rotary evaporation and the product was purified by flash chromatograpy (5% MeOH/CH 2 Cl 2 ) . EI-MS m/z 397 (M+H) * Step C: 2- (2- (N- (4- (2-pyridylamino-3-nitro-4- methyl) but-l-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azapin- 5-yl)acetic acid To a stirring solution methyl 2- (2- (N- (4- (2- pyridylamino-3-nitro-4-methyl) but-l-yl) carbamoyl) - IH, 3H, 4H-5H-benzo [e] azapin-5-yl) acetate in methanol (0.1 M) was added IN NaOH (3 eq) . After 18 hrs, the reaction was neutralized with 10% HCI, concentrated by rotary evaporation and purified by recrystalization from 2% MeOH/CH 2 Cl 2 . EI-MS m/z 456 (M+H) * ; 'H-NMR (400 MHz, CDC1 3 ) : δ 11.0 (br s, IH) , 8.12 (d, J = 4.9 Hz, IH) , 7.52 (t, J = 4.6 Hz, IH) , 7.19 (m, 4H) , 6.46 (d, J = 4.9 Hz, IH) , 4.77 (m, IH) , 4.48 (q, J = 15.2 Hz, 2H) , 3.65 (m, IH) , 3.49 (m, 4H) , 3.23 (m, 2H) , 2.76 (m, 2H) , 2.52 (s, 3H) , 2.03 (m, IH) , 1.58 (m, 5H) . Example 35 Preparation of ethyl 2- (2- (N- (3- (2-pyridylamino) butyl- 1-yl) carbamoyl) -IH, 3H, 4H-5H-benzo [el azapin-5- yl) acetate Ethyl 2- (2- (N- (4- (2-pyridylamino) but-l-yl) carbamoyl ) - IH, 3H, 4H, 5H-benzo[e]azapin-5-yl) acetate was prepared from 2- (N- (4-aminobut-l-yl) amino) pyridine and ethyl 2- (1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl ) acetate according to the procedure of Example 34. Ethyl 2- (1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl ) cetate was prepared by transesterification of methyl 2- (1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate with HCI and ethanol. EI-MS m/z 425 (M+H) * ; 'H-NMR (400 MHz, CDC1 3 ) : δ 8.08 (d, J=4.7Hz, IH) , 7.40 (t, J=12.lHz, IH) , 7.33-7.12(m, 4H) , 6.53 (t, J=6.lHz, IH) , 6.33 (d, J=8.3Hz, IH) , 4.52 (d, J=15.3Hz, 2H) , 4.41(s, 2H) , 4.13(q, J=21.4Hz, 2H) , 3.70 (s, IH) , 3.60 (m, 2H) , 3.28 (m, 4H) , 2.81(m, IH) , 2.70 (m, IH) , 2.05 (m, IH) , 1.64 (m, IH) , 1.25 (t, J=7.10Hz, 3H) Example 36 Preparation of methyl 2- (2- (N- (3- ( 1 , 2 , 3 , 4-tetrahvdro pyridino (2 , 3-b)pyridin-7-yl) propyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) propanoate Step A: Methyl 2- (2- (tert-butoxycarbonyl ) - IH, 2H, 3H, 4H, 5H-benzo [el azaperhvdroepin-5-yl) propanoate Methyl 2- (2- (tert-butoxycarbonyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate was dissolved in in tetrahydrofuran (0.2 M) . The solution was cooled to -78°C under nitrogen and the addition of lithium diisopropylamine (1 eq.) was added. After 10 mins, methyl iodide (1 eq) was added and the temperature was warmed to 0°C and stirred for 30 mins. The reaction was then warmed to room temperature and quenched with water. The solvents were removed in vacuo, followed by dilution with ethyl acetate and extraction with saturated ammonium chloride. The solvents were removed in vacuo to give the product as a colorless oil. EI-MS m/z 334 (M+H) * Step B: Methyl 2- ( IH, 2H, 3H, 4H, 5H- benzo [el azaperhvdroepin-5-yl ) propanoate Hydrochloride Methyl 2- (2- (tert-butoxycarbonyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) propanoate was dissolved in 4M HCI in dioxane (0.2 M) . After 18 hrs, removal of solvent in vacuo, followed by trituration with ether afforded the product. EI-MS m/z 233 (M+H) * Step C: Methyl 2- (2- (N- (3- (1, 2 , 3 , 4-tetrahvdro pyridino (2 , 3 -b) yridin-7-yl) propyl) carbamoyl) - 1H.3H.4H, 5H-benzo [el azapin-5-yl) propanoate 2- (2- (N- (3- (1,2,3, 4-tetrahydropyridino (2, 3-b)pyridin- 7-y1 ) propyl ) carbamoyl ) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) propanoate was prepared from 3- (1,2, 3,4- tetrahydropyridino [2 , 3-b] pyridin-7-yl) prop-1-ylamine and methyl 2- ( IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin- 5-yl) propanoate according to the procedure of Example 34. 3- (1, 2, 3, 4-tetrahydropyridino [2, 3-b]pyridin-7- yl)prop-l-ylamine was prepared according to Duggan, M. E. WO 98/18460. EI-MS m/z 451 (M+H) * . Example 37 Preparation of 2- (2- (N- ( 3- ( 1 , 2 , 3 , 4-tetrahvdro pyridino (2 , 3-b) pyridin-7-yl ) propyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl ) propanoic acid 2-(2-(N-(3-(l,2,3, 4-tetrahydropyridino (2, 3-b)pyridin- 7 -yl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl)propanoic acid was prepared from methyl 2-(2-(N-(3- (1,2,3, 4-tetrahydropyridino (2 , 3-b) pyridin-7- yl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) propanoate according to the procedure of Example 34. EI-MS m/z 437 (M+H) * ; 'H-NMR (400 MHz, CDC1 3 ): δ 10.8 (br s, IH) , 7.25 (m, 6H) , 6.37 (m, IH) , 5.04 (d, J = 14.2 Hz, IH) , 4.36 (d, J = 14.8 Hz, IH) , 3.74 (m, 5H) , 3.46 (m, 4H) , 3.10 (m, 3H) , 2.72 (m, 5H) , 2.27 (m, IH) , 1.44 (m, IH) , 1.17 (br s, 3H) . Example 38 Preparation of 2- (2- (N- \ 2 , 2-dimethyl-3- (2- pyridylamino) ropyl 1 carbamoyl ) -IH , 3H , 4H, 5H- benzo [el azepine-5-yl) acetic acid Step A: (3-amino-2 , 2-dimethylρropyl) -2-pyridylamine A mixture of 2-fluoropyridine and 2 , 2-dimethyl-l, 3- propanediamine (2eq) in pyridine (0.3M) was refluxed for 18 hrs. and then concentrated by rotary evaporation. . The solution was then concentrated in vacuo and the residue was partitioned between ethyl acetate and 10% sodium carbonate. The phases were separated, and the organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo . The product was purified by flash chromatography using 10:1:1 EtOH/NH 4 OH/H 2 0 as eluent. EI-MS m/z 180 (M+H) * . Step B: Methyl 2- (2- (N- \ 2 .2-dimethyl-3- (2- pyridylamino) propyl 1 carbamoyl} -IH, 3H, 4H, 5H- benzo [el azepine-5-yl) acetate Methyl 2- (2-{N- [2 , 2-dimethyl-3- (2-pyridylamino) propyl] carbamoyl} -IH, 3H, 4H, 5H-benzo [e] azepine-5-yl) acetate was prepared from (3-amino-2 , 2-dimethylpropyl) -2- pyridylamine and methyl 2- ( IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) propanoate according to the procedure of Example 34. EI-MS m/s 425 (M+H) * . Step C: 2- (2- (N- [2 , 2-dimethyl-3- (2- pyridylamino) propyl 1 carbamoyl } -IH, 3H, 4H, 5H- benzo [el azepine-5-yl) acetic acid 2- (2- {N- [2 , 2-dimethyl-3- (2-pyridylamino) propyl] carbamoyl} -IH, 3H, 4H, 5H-benzo [e] azepine-5-yl) acetic acid was prepared from methyl 2- (2- {N- [2 , 2-dimethyl- 3- (2-pyridylamino) propyl] carbamoyl} -IH, 3H, 4H, 5H- benzo [e] azepine-5-yl) according to the procedure of Example 34. EI-MS m/z 411 (M+H) * ; 'H-NMR (400 MHz, MeOH-d 4 ) : δ 7.8 (d, J=5.1, IH) , 7.35 (t, J= 7.12, IH) , 7.28 (d, J= 7.03, IH) , 7.10 (m, 2H) , 7.00 (m, IH) , 6.5-6.4 (m, 2H) , 4.5 (q, J= 15.37Hz, 2H) , 3.6 (m, 2H) , 3.45 (m, IH) , 3.25 (s, 3H) , 2.9 (d, J= 8.67Hz, 4H) , 2.7-2.06 (m, 2H) , 1.95 (m, IH) , 1.55 (m, IH) , 0.7 (s, 6H) . Example 39 Preparation of 2- (2- (N- f 4- (pyrazin-2-ylamino) butyll carbamoyl} -IH, 3H, 4H, 5H-benzo [el azepin-5-yl) acetic acid Step A: ( 4-aminobutyl ) pyrazin-2-ylamine ( 4-aminobutyl)pyrazin-2-ylamine was prepared by refluxing 2-chloropyrazine and 1, 4-diaminobutane in pyridine (50mL) for 18 hrs. The solution was then concentrated in vacuo and the residue was partitioned between ethyl acetate and 10% sodium carbonate. The phases were separated, and the organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo . The desired product was isolated by flash chromatography using 10:1:1 Ethanol/Ammonium Hydroxide/water . EI-MS m/z 167 (M+H) * . Step B: Methyl 2- (2- (N- \ 2 .2-dimethyl-3- (2- pyridylamino ) propyl 1 carbamoyl } -IH, 3H , 4H , 5H- benzo [el azepine-5-yl) acetate Methyl 2- (2- {N- [2 , 2-dimethyl-3- (2-pyridylamino) propyl] carbamoyl} -IH, 3H, 4H, 5H-benzo [e] azepine-5-yl) acetate was prepared from (4-aminobutyl)pyrazin-2-ylamine and methyl 2- (IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) propanoate according to the procedure of Example 34. EI-MS m/z 412 (M+H) * . Step C: 2- (2-fN- r4- (pyrazin-2-ylamino) butyl 1 carbamoyl) -IH, 3H, 4H, 5H-benzo [el azepin-5-yl) acetic acid 2-(2-{N-[4- (pyrazin-2-ylamino)butyl] carbamoyl} - IH, 3H, 4H, 5H-benzo [e] azepin-5-yl) acetic acid was prepared from methyl 2- (2- (N- [2 , 2-dimethyl-3- (2- pyridylamino) propyl] carbamoyl} -IH, 3H, 4H, 5H- benzo [e] azepine-5-yl) acetate according to the procedure of Example 34. EI-MS m/z 398 (M+H) * . X H-NMR (400 MHz, DMS0-d 6 ) : δ 7.9 (in, IH) , 7.88 (s, IH) , 7.6 (s, IH) , 7.30 (d, 7.2, IH) , 7.18-7.08 (m, 3H) , 6.95 (t, J= 5.01,1H), 6.3 (t, J= 5.15, IH) , 4.45 (s, 2H) , 3.5 (sb, 2H) , 3.15 (m, 3H) , 2.95 (m, 2H) , 2.20-2.10 (m, 2H) , 1.8 (m, IH) , 1.4 (m, 5H) . Example 40 Preparation of 2- (2- [N- (3-imidazolo f 5 , 4-blpyridin-2- ylpropyl) carbamoyll -IH, 3H, 4H, 5H-benzo [el azepin-5- vDacetic acid Step A: N- (3-amino(2-pyridyl) ) -4- [ (phenylmethoxy) carbonylamino! butanamide 4- [ (phenylmethoxy) carbonylamino] butanoic acid (l.leq) was dissolved in methylene chloride (0.2M) followed by the addition of 1- [3- (Dimethylamino) propyl] -3- ethylcarbodiimide hydrochloride (EDCA) (1.2eq) and triethylamine (1.5eq). The mixture was stirred at room temperature under nitrogen for 30 mins, followed by addition of 2 , 3-diaminopyridine. The mixture was then stirred at room temperature for 48 hrs., quenched with saturated sodium carbonate and extracted with ether. The organic phase was concentrated in vacuo and chromatographed on silica gel. (10% MeOH/CH 2 Cl 2 ) . EI- MS m/z 329 (M+H) * . Step B: N- (3-imidazolef4, 5-bl pyridin-2- ylpropyl) (phenylmethoxy) carboxamide N- (3-amino (2-pyridyl) ) -4- [ (phenylmethoxy) carbonyl amino] butanamide was dissolved in acetic acid (0.3M) and refluxed for 18 hrs. The resulting mixture was made basic with saturated sodium carbonate, extracted with methylene chloride, dried over sodium sulfate and concentrated concentrated in vacuo . The resulting residue was purified by flash chromatography (10% MeOH/CH 2 Cl 2 ) EI-MS m/z 311 (M+H) * . Step C: 3-imidazolo [4 , 5-b1pyridin-2-ylpropylamine N- (3-imidazole [4, 5-b] pyridin-2-ylpropyl) (phenyl methoxy) carboxamide was dissolved in MeOH (60mL) and 10% Pd/C was added. Hydrogen was bubbled through the mixture and stirred under a balloon atmosphere for 18 hrs. The mixture was filtered through celite and concentrated by high vacuum to afford the desired product. EI-MS m/z 177 (M+H) * . Step D: Methyl 2- (2- rN- (3-imidazolo [5 , 4-bl Pyridin-2- yl-propyl) carbamoyll -IH, 3H, 4H, 5H-benzo [el azepin-5- yl} acetate Methyl 2- {2- [N- (3-imidazolo [5 , 4-b] pyridin-2-yl- propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl}acetate was prepared from 3-imidazolo [4 , 5- b] pyridin-2-ylpropylamine and methyl 2- (1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) propanoate according to the procedure of Example 34. EI-MS m/z 422 (M+H)\ Step E: 2- (2- [N- ( 3-imidazolo r 5 , 4-blpyridin-2- ylpropyl) carbamoyl 1 -IH, 3H, 4H, 5H-benzo [el azepin-5- vDacetic acid 2-{2- [N- (3-imidazolo [5, 4-b] pyridin-2-ylpropyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetic acid was prepared from methyl 2- (2- [N- ( 3-imidazolo [5, 4-b] pyridin-2-yl-propyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl}acetate according to the procedure of Example 34. EI-MS m/z 408 (M+H) * . Example 41 Preparation of 2- f 2- TN- (methylethyl) -N- (2- (1 , 2 , 3 , 4- tetrahydropyridino [2 , 3-blpyridin-7-yl) ethyl) carbamoyll -IH, 3H, 4H, 5H-benzo [el azepin-5-yll acetic acid Step A: Methyl-2-(2-rN- (methylethyl) -N- (2- (1,2, 3, 4- tetrahydropyridino [2 , 3-b1 yridin-7-yl) ethyl) carbamoyll -1H.3H.4H, 5H-benzo [el azepin-5-yll acetate Methyl-2-{2- [N- (methylethyl) -N- (2- (1, 2 , 3 , 4-tetrahydro pyridino [2 , 3-b]pyridin-7-yl) ethyl) carbamoyl] - IH, 3H, 4H, 5H-benzo [e] azepin-5-yl] acetate was prepared from of (methylethyl) (2- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3-b] pyridin-7-yl) ethyl) amine and methyl 2- (1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) propanoate according to the procedure of Example 34. EI-MS m/z 465 (M+H) * . Step B: 2-(2- TN- (methylethyl) -N- (2- (1, 2,3.4- tetrahvdropyridino [2 , 3-blpyridin-7- yl) ethyl) carbamoyll -IH, 3H, 4H, 5H-benzo [el azepin-5- yllacetic acid 2- {2- [N- (methylethyl) -N- (2- (1, 2 , 3 , 4-tetrahydro pyridino [2 , 3-b]pyridin-7-yl) ethyl) carbamoyl] - IH, 3H, 4H, 5H-benzo [e] azepin-5-yl] acetic acid was prepared from methyl-2- {2- [N- (methylethyl) -N- (2- (1,2,3, 4-tetrahydropyridino [2 , 3-b]pyridin-7- yl) ethyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl] acetate according to the procedure of Example 34. EI-MS m/z 451 (M+H) * . 'H-NMR (400 MHz, CDC1 3 ): δ 10.0 (bs, IH) , 7.25-7.10 (m, 6H) , 6.25 (d, J= 7.27, IH) , 4.5 (q, J= 15.30, 2H) , 3.7-3.6 (m, 2H) , 3.4 (m, 5H) , 3.23-3.15 (m, IH) , 2.78-2.65 (m, 5H) , 2.65-2.55 (m, IH) , 2.2 (m, IH) , 1.88 (m, 2H) , 1.78 (m, IH) , 1.05 (dd, J= 6.7, J= 10.23, 6H) . Preparation of 2- (2-aza-2-cvano-l ( ( 1 , 2 , 3 , 4- tetrahydropyridino [2 , 3-bl pyridin-7-yl ) propyl ) amino) vinyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid Step A: 2-aza-3-phenoxy-3- ( (3- (1 , 2 , 3 , 4-tetrahvdro pyridino [2 , 3-bl pyridin-7-yl ) propyl ) amino) ρrop-2- enenitrile 2-aza-3-phenoxy-3- ( (3- ( 1 , 2 , 3 , 4-tetrahydropyridino [2,3- b]pyridin-7-yl) propyl) amino) prop-2-enenitrile was prepared by refluxing 3- (1 , 2 , 3 , 4-tetrahydropyridino [2 , 3-b]pyridin-7-yl) prop-1-ylamine and 2-aza-3,3 diphenoxyprop-2-enenitrile in acetonitrile for 3 hrs. 3- ( 1, 2 , 3 , 4-tetrahydropyridino [2 , 3-b]pyridin-7-yl)prop- 1-ylamine was prepared according to Duggan, M. E. WO 98/18460. Step B: Methyl 2- (2-aza-2-cvano-l- ( (3- ( 1 , 2 , 3 , 4- tetrahvdropyridino [2 , 3-bl pyridin-7-yl)propyl) amino) vinyl) -IH, 3H, 4H, 5H, -benzo [el azepin-5-yl) acetate Methyl 2- (2-aza-2-cyano-l- ( (3- (1, 2,3,4- tetrahydropyridino [2 , 3-b]pyridin-7- yl) propyl) amino) vinyl) -IH, 3H, 4H, 5H, -benzo [e] azepin-5- yl) acetate was prepared by refluxing 2-aza-3-phenoxy- 3- ( (3- ( 1,2, 3, 4-tetrahydropyridino [2, 3-b] yridin-7- yl) propyl) amino) prop-2-enenitrile and and methyl 2- (1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate in isopropyl alcohol for 18 hrs. followed by flash chromatography (10% MeOH/CH 2 Cl 2 ) . Step C: 2- (2-aza-2-cvano-l ( (1, 2, 3 , 4-tetrahvdro pyridino [2 , 3-bl pyridin-7-yl) propyl) amino) vinyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- (2-aza-2-cyano-l ( (1,2,3, 4-tetrahydropyridino [2,3- b]pyridin-7-yl) propyl) amino) vinyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetic acid was prepared from methyl 2- (2-aza-2-cyano-l- ( (3- (1, 2, 3, 4-tetrahydro pyridino (2 , 3-b)pyridin-7-yl) propyl) amino) vinyl) - IH, 3H, 4H, 5H, -benzo [e] azepin-5-yl) acetate according to the procedure of Example 34. EI-MS m/z 447 (M+H) * ; 1 H- NMR (400 MHz, d6-DMSO) : δ 7.50-7.25 (m, 5H) , 7.18 (d, J=7.3Hz, IH) , 6.34 (d, J=7.2Hz, IH) , 4.81 (q, J=36Hz, 2H) , 3.82 (m, 2H) , 3.65-3.48 (m, 5H) , 3.40 (t, J=5.3Hz, 2H) , 2.76 (t, J=6.1Hz, 2H) , 2.70 (m, 2H) , 2.11 (m, IH) , 1.92 (m, 4H) , 1.70 (m, IH) . Example 43 Preparation of 2- ( 2- (N- ( (benzylamino) carbonylamino) phenyl ) carbamoyl ) -IH , 3H.4H, 5H-benzo [ e1 azapin-5- yl) acetic acid Step A: Methyl 2- (2- (N- (4-nitrophenyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [el azaρin-5-yl) acetate Methyl 2- (2- (N- (4-nitrophenyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl ) acetate was prepared by reacting 4-nitrophenyl isocyanate and and methyl 2- (IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate in dimethyl foramide at 60°C for 18hrs followed flash chromotography (10% MeOH/CH 2 Cl 2 ) . EI-MS m/z 384(M+H) * Step B: Methyl 2- (2- (N- (4-aminophenyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetate Methyl 2- (2- (N- (4-aminophenyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetate was prepared by hydrogenation of methyl 2-(2-(N-(4- nitropheny1 ) carbamoyl ) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetate with Pd/C in methanol. EI-MS m/z 354 (M+H) * Step C: Methyl 2- (2- (N- ( (benzylamino) carbonylamino) phenyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azapin-5- yl) acetate Methyl 2- (2- (N- ( (benzylamino) carbonylamino) phenyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetate was prepared by heating methyl 2- (2- (N- (4-aminophenyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetate and benzyl isocyanate in dimethyl foramide at 60°C for 18hrs followed dy flash chromotography (10% MeOH/CH 2 Cl 2 ) . EI-MS m/z 487 (M+H) * Step D: 2- (2- (N- ( (benzylamino) carbonylamino) phenyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl ) acetic acid 2- (2- (N- ( (benzylamino) carbonylamino) phenyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from methyl 2- (2- (N- ( (benzylamino) carbonylamino) phenyl ) carbamoyl ) - IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetate according to the procedure of Example 34. EI-MS m/z 473 (M+H) * ; 'H-NMR (400 MHz, d6-DMS0) : δ 8.22 (s, IH) , 8.09 (s, IH) , 7.25-6.95 (m, 13H) , 6.39 (t, J=6.0Hz, IH) , 4.52 (q, J=35Hz, 2H) , 4.12 (d, J=5.3Hz, 2H) , 3.55 (m, 2H) , 3.38 (m, IH) , 2.61 (m, 2H) , 1.81 (m, IH) , 1.47 (m, IH) . Example 44 Preparation of 2- (2- (N- (3- (2-pyridylamino) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid Step A: ( tert-butoxy) -N- ( 6-methyl (2- pyridyl) ) carboxamide To a stirring solution of 2-amino-6-methylpyridine in methylene chloride (1.0 M) was added di-tert-butyl dicarbonate (1 eq) , and the solution was stirred for 4 hrs. The solution was then concentrated in vacuo and the residue was purified by flash chromatography (50% EtOAc/Hexane) . EI-MS m/z 209 (M+H) * Step B: ( tert-butoxy) -N- ( 6-but-3-enyl (2- pyridyl) ) carboxamide To a stirring solution of ( tert-butoxy) -N- (6-methyl (2- pyridyl) ) carboxamide in tetrahydrofuran (0.1 M) was added n- butyl lithium (2.1 eq) at -78°C and the solution was warmed to 25°C and stirred for 1 hr. The solution was then cooled back down to -78°C followed by addition of allyl bromide (1.5 eq) and continued strirring for 1 hr . The reaction was quenched with saturated ammonium chloride, diluted with ethyl acetate and separated. The organic layer was washed with brine and dried with magnesium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (5% EtOAc/Hexane) . EI-MS m/z 249(M+H) * Step C: N- r 6- (3, 4-dihvdroxybutyl) (2-pyridyl) 1 (tert- butoxy) carboxamide To a stirring solution of 4-methylmorpholine N- oxide(2.1 eq) and osmium tetraoxide (2.5 eq) in tetrahydrofuran/water (5 eq/1 eq) was added (tert- butoxy) -N- (6-but-3-enyl (2-pyridyl) ) carboxamide (1.0 eq) at 25°C and stirred for 18 hr . The reaction was quenched with solution of sodium bisulfate (0.5M) and sodium sulfite (1M) and stirred for 30 mins. The reaction was poured into a brine and extracted with ethyl acetate. The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (50% EtOAc/Hexane) . EI-MS m/z 283 (M+H) * Step D: ( tert-butoxy) -N- T 6- (3 -oxopropyl) (2- pyridyl) 1 carboxamide To a stirring solution of N- [6- (3 , 4-dihydroxybutyl) (2- pyridyl)] (tert-butoxy) carboxamide in tetrahydrofuran/water (1 eq/1 eq, 0.1M) was added sodium metaperiodate (1.3 eq) at 0°C and stirred for 1 hr . The reaction was warmed to room temperature and diluted with ethyl acetate. The reaction was extracted with saturated sodium bicarbonate, dried with sodium sulfate, filtered and concentrated in vacuo to yield the product. EI-MS m/z 251 (M+H) * Step E: (tert-butoxy) -N- [6- (3- (hydroxyimino) propyl) (2- pyridyl) 1 carboxamide To a stirring solution of ( tert-butoxy) -N- [6- ( 3- oxopropyl) (2-pyridyl) ] carboxamide_in methanol (0.1M) was added sodium acetate (2.0 eq) and hydroxyamine hydrochloride. The reaction was then heated to 60°C and stirred for 18 hr . The reaction was cooled to room temperature and diluted with water. The reaction was extracted with diethyl ether. The organic layer was washed with saturated sodium bicarbonate, brine and dried with sodium sulfate, filtered and concentrated in vacuo to yield the product. EI-MS m/z 266 (M+H) * Step F : N- [6- (3-aminopropyl) (2-pyridyl) 1 (tert- butoxy) carboxamide To a solution of (tert-butoxy) -N- [6- (3- (hydroxyimino) propyl ) ( 2-pyridyl ) ] carboxamide in ethanol/acetic acid (4 eq/1 eq, 0.1M) under nitrogen was added 5% palladium on carbon. The reaction was stirred under hydrogen at 60 psi for 18 hr . The reaction was filtered thru celite and concentrated in vacuo to yield the product. EI-MS m/z 252 (M+H) * Step G: Methyl 2- (2- [N- (3- (6- r (tert- butoxy) carbonylamino! -2-pyridyl}propyl) carbamoyll - IH.3H, 4H, 5H-benzo [el azepin-5-yl)acetate Methyl 2- (IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate Hydrochloride was dissolved in methylene chloride and washed with IN NaOH. The organic layer was separated, dried over sodium sulfate and concentrated by rotary evaporation. The residue was stirred under nitrogen with 20% phosgene in toluene (0.1 M) for 10 mins. After concentration by rotary evaporation, the residue was dissolved in THF (0.1 M) , followed by addition of diisopropylethylamine (1.5 eq) and N- [6- (3-aminopropyl) (2-pyridyl)] (tert-butoxy) carboxamide (1.2 eq) . The reaction was stirred for 18 hr under nitrogen, followed by concentration by rotary evaporation and the product was purified by flash chromatography (5% MeOH/CH 2 Cl 2 ) . EI-MS m/z 497 (M+H) * Step H: Methyl 2- (2- (N- [ 3- ( 6-amino-2-Pyridyl) ropyll carbamoyl) -IH, 3H, 4H, 5H-benzo [el azepin-5-yl) acetate Methyl 2-{2-[N-(3-{6-[ (tert-butoxy) carbonylamino] -2- pyridyl}propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin- 5-yl}acetate_was dissolved in 4M HCl/dioxane and stirred for 3 hrs. at room temperature. The reaction was concentration by rotary evaporation and the product was purified by trituation with diethyl ether. EI-MS m/z 397 (M+H) * Step I: Methyl 2- (2- N- (3- ( 6- [benzylamino! -2- pyridyl)propyl) carbamoyll -1H.3H.4H.5H-benzo [el azepin- 5-yl}acetate To a stirring solution of Methyl 2- (2- {N- [3- (6-amino- 2-pyridyl ) propyl ] carbamoyl } -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl) acetate in dichloroethane (0.4 M) at RT under nitrogen was added benzaldehyde (1.2 eq) , sodium triacetoxyborohydride (2 eq) , and acetic acid (4 eq) . After 5 hr the reaction was carefully quenched with 2M sodium carbonate and extracted with methylene chloride. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (10% MeOH/ CH 2 C1 2 ) to af ford the product . EI-MS m/ z 487 (M+H) * Step J: 2-(2- [N- ( 3— ( " 6- [benzylaminol -2-pyridyl)propyl) carbamoyl 1 -IH, 3H, 4H, 5H-benzo [e! azepin-5-yl}acetic acid To a stirring solution methyl 2- {2- [N- (3- {6- [benzyl amino] -2-pyridyl}propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetate in methanol (0.1 M) was added IN NaOH (3 eq) . After 18 hrs, the reaction was neutralized with 10% HCI, concentrated concentrated in vacuo and purified by recrystalization from 2% MeOH/CH 2 Cl 2 . EI-MS m/z 473 (M+H) * ; 'H-NMR (400 MHz, d2- D 2 0) : δ 7.32-7.08 (m, 10H) , 6.48 (m, 2H) , 4.37 (s, 2H) , 4.51 (m, 2H) , 4.36 (m, 3H) , 3.99 (t, J=3.7Hz, 2H) , 2.61- 2.34 (m, 5H) , 1.75 (m, IH) , 1.63 (t, J= 3.4Hz, 2H) Example 45 Preparation of 2- (2- ( ( (2- ( 1 , 2 , 3 , 4-tetrahvdro pyridino (2 , 3-b) pyridin-7-yl) ethyl) amino) sulfonyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- (2- (N- (2- (1,2, 3, 4-tetrahydropyridino (2, 3-b) pyridin- 7-yl ) ethyl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [e] azapin- 5-yl) acetic acid was prepared from 3- (1,2, 3,4- tetrahydropyridino [2 , 3-b] pyridin-7-yl) ethylamine and methyl 2- (IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate according to the procedure of Example 14. 2- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3-b]pyridin-7- yl) ethylamine was prepared according to Duggan, M. E. WO 98/18460. EI-MS m/z 445 (M+H) * ; X H-NMR (400 MHz, d6-DMSO) : δ 7.11-687 (m, 5H) , 6.10 (m, IH) , 4.21 (q, J=48.6Hz, 2H) , 3.50-3.29 (m, 3H) , 3.11 (m, 2H) , 2.80 (m, 2H) , 2.55-2.44 (m, 4H) , 2.19 (m, 2H) , 1.80 (m, IH) , 1.68 (m, 2H) , 1.45 (m, IH) . Example 46 Preparation of methyl 3- ( IH, 2H, 3H, 4H, 5H- benzo [el azaperhvdroepin-5-yl ) propanoate Hydrochloride Step A: Tert-butyl 5- (2-hvdroxyethyl ) -IH, 3H, 4H.5H- benzo [el azaperhydroepine-2-carboxylate Tert-butyl 5- (2-hydroxyethyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepine-2-carboxylate was prepared by reacting methyl 2- (2- (tert-butoxycarbonyl ) - IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate with diisobutylaluminiumhydride ( 3eq. ) in toluene ( 0.1M) at 0°C for 1.5 hrs. The reaction was quenched with IN HCl at 0°C and extracted with ethyl acetate. The organic layer was washed with additional IN HCl, saturated sodium bicarbonate and water. Dried with sodium sulfate, filtered and concentrated in vacuo to afford the product. EI-MS m/z 292 (M+H) * Step B: Tert-butyl 5- (2 (4-methylphenyl) sulfonyloxy) - IH, 3H, 4H, 5H-benzo [el azaperhydroepine-2-carboxylate Tert-butyl 5- (2 ( (4-methylphenyl) sulfonyloxy) - IH, 3H, 4H, 5H-benzo [e] azaperhydroepine-2-carboxylate was prepared by stirring tert-butyl 5- (2-hydroxyethyl) - IH, 3H, 4H, 5H-benzo [e] azaperhydroepine-2-carboxylate with tosyl chloride (1.1 eq) and triethyl amine ( 1.5 eq) in methylene chloride at 25° C for 18 hrs. Dilute with methylene chloride and extract with water. Dried with sodium sulfate, filtered and concentrated in vacuo . Flash chromatography (25% ETOAc/ Hex) afforded the product. EI-MS m/z 446 (M+H) * Step C: Tert-butyl 5- (2-cvanoethyl ) -IH, 3H, 4H, 5H- benzo [el azaperhydroepine-2-carboxylate Tert-butyl 5- (2-cyanoethyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepine-2-carboxylate was prepared by stirring tert-butyl 5- (2 ( (4-methylphenyl ) sulfonyloxy) - IH, 3H, 4H, 5H-benzo [e] azaperhydroepine-2-carboxylate in dimethyl sulfoxide (0.1M) with sodiun cyanide (5 eq ) at 25° C for 18 hrs. Dilute with ethyl acetate and extract with water. Dried with sodium sulfate, filtered and concentrated in vacuo to afford the product. EI-MS m/z 323 (M+Na) * Step D: Methyl 3- ( IH, 2H, 3H, 4H, 5H- benzo [el azaperhvdroepin-5-yl)propanotate Hydrochloride Methyl 3- ( IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) propanoate Hydrochloride was prepared by stirring tert-butyl 5- (2-cyanoethyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepine-2-carboxylate in methanol with the addition of excess 4M HCl/dioxane for 24 hrs. Concentrated in vacuo to afford the product. EI-MS m/z 234 (M+H) * Example 47 Preparation of 3- (2- (N- (2- ( 1 , 2 , 3 , 4-tetrahvdropyridino (2.3-b) Pyridin-7-yl ) ethyl) amino) sulfonyl) -IH, 3H, 4H, 5H- benzo [el azapin-5-yl ) propanoic acid 3-(2-(N-(2-(l,2,3, 4-tetrahydropyridino (2, 3-b)pyridin- 7-yl) ethyl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [e] azapin- 5-yl) propanoic acid was prepared from 3- (1,2, 3, 4- tetrahydropyridino [2, 3-b]pyridin-7-yl ) ethylamine and methyl 3- (IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) propanoate according to the procedure of Example 14. 2- ( 1 , 2 , 3 , 4-tetrahydropyridino [2 , 3-b] pyridin-7- yl) ethylylamine was prepared according to Duggan, M. E. WO 98/18460. EI-MS m/z 459 (M+H) * ; 'H-NMR (400 MHz, d6-DMSO) : δ 7.39(m, IH) , 7.30 (m, 3H) , 7.18 (d, J=7.2Hz, IH) , 6.35 (d, J=7.3Hz, IH) , 4.50 (m, 2H) , 3.58 (m, 2H) , 3.38 (t, J=5.4Hz, 2H) , 3.08 (m, 3H) , 2.69 (m, 4H) , 2.40(m, 2H) , 2.21 (m, IH) , 2.10 (m, 2H) , 1.92 (m, 2H) , 1.80 (m, IH) . Example 48 Preparation of 5- ( 1H-1 , 2 , 3 , 4-tetraazol-5-ylmethyl) - 1H.2H.3H, 4H, 5H-benzo [e! azaperhvdroepine-2-carboxylate Step A: 3- (( (2-bromophenyl) methyl) amino) propan-1-ol To a stirring solution of 2-bromobenzaldehyde in dichloroethane (0.4 M) at RT under nitrogen was added 3-aminopropanol (1.5 eq) , sodium triacetoxyborohydride (2 eq) , and acetic acid (4 eq) . After 5 hr the reaction was carefully quenched with 2M sodium carbonate and extracted with methylene chloride. The organic phase was extracted with IN hydrochloric acid. The aqueous phase was neutralized with IN sodium hydroxide and extracted with methylene chloride. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford the product. EI- MS m/z 245 (M+H) * Step B: (Tert-butoxy) -N- ( (2 -bromophenyl) methyl ) -N- (3- hydroxypropyl ) carboxamide To a stirring solution of 3- (( ( 2 -bromophenyl ) methyl) amino) ropan-1-ol in methylene chloride (0.1 M) was added di-tert-butyl dicarbonate (1.1 eq) . After 1 hr, the solvent was removed by rotary evaporation, and the residue partitioned between ether and IN HCl. The ethereal portion was dried over sodium sulfate filtered and concentrated in vacuo to afford the product. EI-MS m/z 344 (M+H) * Step C: N- ( (3E)-4-cvanbut-3-enyl (tert-butoxy) -N- ( (2- bromophenyl ) methyl ) carboxamide To a stirring solution of dimethyl sulfoxide (3.8 eq) in methylene chloride (0.1 M) at -78°C was added oxalyl chloride (1.8 eq) . After 10 min., (tert- butoxy) -N- ( (2-bromophenyl) methyl) -N- (3-hydroxypropyl) carboxamide (1 eq) was added. After stirring for 30 min., diisopropylethylamme (4 eq) was added, and the reaction was allowed to warm to RT. After 30 min, ( triphenylphosphoranyidene) -acetonitrile (1.2 eq) was added, and stirring was continued for 18 hr. The mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford the product. EI-MS m/z 365 (M+H) * Step D: Tert-butyl-5- (cvanomethylene) -IH, 3H, 4H- benzo [el azaperhydroeρine-2-carboxlate To a stirring solution of N- ( (3E) -4-cyanbut-3-enyl (tert-butoxy) -N- ( (2-bromophenyl) methyl) carboxamide in acetonitrile (0.1 M) was added triethylamine (1.2 eq) and palladium acetate (0.05 eq) and tri-o- tolylphosphine (0.01 eq) . The reaction was refluxed for 18 hr under nitrogen cooled to RT . The solvent was removed by rotary evaporation and the product was purified by flash chromatograpy (25% EtOAc/Hexane) . EI-MS m/z 283 (M-H) " Step E: Tert-butyl-5- (cvanomethyl) -IH, 3H, 4H- benzo [el azaperhvdroepine-2 -carboxlate To a stirring solution of tert-butyl-5- (cyanomethylene) -IH, 3H, 4H-benzo [e] azaperhydroepine-2 - carboxlate in methanol (0.1 M) was added magnesium turnings (10 eq) and the mixture was refluxed for 18hr. The mixture was filtered through celite and concentrated by rotary evaporation. The product was purified by flash chromatography (25% EtOAc/Hexane) . EI-MS m/z 287 (M+H) * Step F: Tert-butyl-5- ( 1H-1 , 2 , 3 , 4-tetraazol-5- ylmethyl) -IH, 3H, 4H-benzo [el azaperhydroepine-2- carboxlate Tert-butyl-5- (lH-1,2, 3 , 4-tetraazol-5-ylmethyl) - IH, 3H, 4H-benzo [e] azaperhydroepine-2-carboxlate was prepared by reacting tert-butyl-5- (cyanomethyl) - IH, 3H, 4H-benzo [e] azaperhydroepine-2-carboxlate with sodium azide (1.8 eq) and trimethyl tin chloride in toluene at reflux for 48 hrs. Solvent was evaporated to dryness, diluted with methylene chloride ( 100ml) and extracted with IN HCl. Solvent was evaporated and the product was purified by flash chromatography (10% MeOH/CH 2 Cl 2 ) .EI-MS m/z 328 (M-H) " Step G: 5- (1H-1.2, 3 , 4-tetraazol-5-ylmethyl) - IH.2H, 3H, 4H-benzo [el azaperhydroepine-2-carboxlate Hydrochloride Tert-butyl-5- (1H-1,2, 3, 4-tetraazol-5-ylmethyl) - IH, 3H, 4H-benzo [e] azaperhydroepine-2-carboxlate was dissolved in 4M HCl in dioxane (0.2 M) . After 18 hrs, removal of solvent in vacuo, followed by trituration with ether afforded the product. EI-MS m/z 230 (M+H) Preparation of [5- ( 1H-1 , 2 , 3 , 4-tetraazol-5- ylmethyl) ) IH, 3H, 4H, 5H-benzo Tel azepin-2-yl ) 1 -N- (3- (1,2,3, 4-tetrahvdropyridino \ 2 , 3-bl pyridin-7- yl ) propyl ) carboxamide [5-(lH-l,2,3,4-tetraazol-5-ylmethyl) )1H,3H,4H, 5H- benzo [e] azepin-2-yl) ] -N- (3- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3-b] pyridin-7-yl) propyl) carboxamide was prepared from 3- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3-b]pyridin-7- yl)prop-l-ylamine and 5- (1H-1, 2 , 3 , 4-tetraazol-5- ylmethyl)- IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepine-2- carboxylate according to the procedure of Example 34. 3- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3-b] pyridin-7-yl) prop- 1-ylamine was prepared according to Duggan, M. E. WO 98/18460. EI-MS m/z 447 (M+H) * . Example 50 e Preparation of-Methyl 2- ( (5S) -IH.2H.3H.4H, 5H- benzo [el azaperhvdroepin-5-yl ) acetate Hydrochloride Step A: Methyl 2- (( 5S) -2- ( tert-butoxycarbonyl ) - IH, 3H, 4H, 5H-benzo f el azaperhydroepin-5-yl) acetate Methyl 2- (1H,2H, 3H,4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate was prepared according to the procedure of Example 34. The product was separated and purified by reverse phase high pressure liquid chromatography (2% EtOH/Hexane) on a Chiralpak AD (250 x 4.6 mm i.d.) column at room temperature at a flow rate of 1.0 ml/min. EI-MS m/z 318 (M+H) * Step B: Methyl 2- ( (5S) -IH, 2H, 3H, 4H, 5H- benzo [el azaperhydroepin-5-yl) acetate Hydrochloride (+) -Methyl 2- ( (5S) -2- (tert-butoxycarbonyl) - IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate was dissolved in 4M HCl in dioxane (0.2 M) . After 18 hrs, removal of solvent in vacuo, followed by trituration with ether afforded the product. EI-MS m/z 220 (M+H) * , Optical Rotation: +0.104 degree. Example 51 Preparation of Methyl 2- ( (5R) -IH, 2H, 3H, 4H, 5H- benzo [el azaperhvdroepin-5-yl ) acetate Hydrochloride Step A: Methyl 2- ( (5R) -2- (tert-butoxycarbonyl ) - IH, 3H, 4H, 5H-benzo [el azaperhvdroepin-5-yl) acetate Methyl 2- ( IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate was prepared according to the procedure of Example 34. The product was separated and purified by reverse phase high pressure liquid chromatography (2% EtOH/Hexane) on a Chiralpak AD (250 x 4.6 mm i.d.) column at room temperature at a flow rate of 1.0 ml/min. EI-MS m/z 318 (M+H) * Step F: Methyl 2- ( (5R) -IH.2H.3H, 4H, 5H- benzo [el azaperhvdroepin-5-yl) acetate Hydrochloride (-) -Methyl 2- ( (5R) -2- (tert-butoxycarbonyl) - IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate was dissolved in 4M HCl in dioxane (0.2 M) . After 18 hrs, removal of solvent in vacuo, followed by trituration with ether afforded the product. EI-MS m/z 220 (M+H) * , Optical Rotation: -0.113 degree. Example 52 Preparation of 2- ( (5R) -2- (N- (3- ( 1 , 2 , 3.4-tetrahvdro pyridino (2 , 3-b) yridin-7-yl)prop-l-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- ( (5R)-2- (N- (3- (1,2, 3, 4-tetrahydropyridino (2,3- b)ρyridin-7-yl)prop-l-yl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetic acid was prepared from 3- (1,2,3, 4-tetrahydropyridino [2 , 3-b]pyridin-7-yl)prop-l- ylamine and methyl 2- ( (5R) -IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate according to the procedure of Example 34. 3- (1 , 2 , 3 , 4-tetrahydro pyridino [2, 3-b] pyridin-7-yl) prop-1-ylamine was prepared according to Duggan, M. E. WO 98/18460. EI- MS m/z 423 (M+H) * ; : H-NMR (400 MHz, d6-DMSO) : δ 7.30- 6.85 (m, 5H) , 6.25 (m, IH) , 6.18 (d, J=7.3Hz, IH) , 4.41 (q, J=37.5Hz, 2H) , 3.59 (m, IH) , 3.40 (m, 2H) , 3.28 m, 2H) , 2.95 (m, 2H) , 2.60 (t, J=6.0Hz, 2H) , 2.31 (m, 4H) , 1.77 (m, 3H) , 1.61 (t, J=7.4Hz, 2H) , 1.40 (m, IH) . Example 53 pyridino (2 , 3-b)pyridin-7-yl) ethyl) carbamoyl ) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- ( (5r)-2-(N-(3- (1,2, 3 , 4-tetrahydropyridino (2 , 3- b)pyridin-7-yl) ethylyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetic acid was prepared from 3- (1,2,3, 4-tetrahydropyridino [2 , 3-b]pyridin-7- yl) ethylamine and -methyl 2- ( ( 5r) -IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate according to the procedure of Example 34. 3- (1, 2 , 3 , 4-tetrahydro pyridino [2 , 3-b] pyridin-7-yl) ethylamine was prepared according to Duggan, M. E. WO 98/18460. EI-MS m/z 409 (M+H) * ; 'H-NMR (400 MHz, d6-DMSO) : δ 7.30-6.94 (m, 5H) , 6.41 (bs, IH) , 6.30 (s, IH) , 6.20 (d, J=7.2Hz, IH) , 4.47 (q, J=38Hz, 2H) , 3.60 (m, IH) , 3.45 (m, 2H) , 3.23-3.20 (m, 5H) , , 2.60 (m, 2H) , 2.30 (m, 2H) , 1.74 (m, 3H) , 1.40 (m, 2H) . Example 54 Preparation of 2- ( ( 5S) -2- (N- ( 3- ( 1 , 2 , 3.4-tetrahvdro pyridino (2 , 3-b) pyridin-7-yl) ethyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e! azapin-5-yl ) acetic acid 2- ( (5S) -2- (N- (3- ( 1 , 2 , 3 , 4-tetrahydropyridino (2 , 3-b) pyridin-7-yl) eth-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo[e] azapin-5-yl) acetic acid was -prepared from 3-(l, 2,3,4- tetrahydropyridino [2, 3-b] pyridin-7-yl) ethyl amine and methyl 2- ( ( 5s) -IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin- 5-yl) acetate according to the procedure of example 34. 3- (1, 2, 3, 4-tetrahydropyridino [2, 3-b] pyridin-7-yl) ethyl amine was prepared according to Duggan, M. E. WO 98/18460. EI-MS m/z 409 (M+H) * ; 'H-NMR (400 MHz, d6- DMSO): δ 7.30-6.95 (m, 5H) , 6.38 (bs, IH) , 6.29 (s, IH) , 6.20 (d, J=6.8Hz, IH) , 4.48 (q, J=38.6Hz, 2H) , 3.60 (m, IH) , 3.45 (m, 2H) , 3.28-3.22 (m, 5H) , 2.61 (m, 2H) , 2.34 (m, 2H) , 1.80 (m, 3H) , 1.46 (m, 2H) . Example 55 Preparation of 2- ( (5S) -2- (4- ( 1 , 2 , 3 , 4-tetrahydro pyridino (2 , 3-b)pyridin-7-yl) butanoyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e! azapin-5-yl) acetic acid 2-Methyl- ( (5S)-2- (4- (1,2,3, 4-tetrahydropyridino (2 , 3- b)pyridin-7-yl) butanoyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared from 3- (1,2,3, 4-tetrahydropyridino [2 , 3-b] pyridin-7-yl) butyic acid and methyl 2- ( (5s) -IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate by stirring the two compounds in acetonitrile (0.1M) with triethylamine (l.leq) and 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide hydrochloride (l.leq) for 18 hrs at room temperture. The reaction was concentrated concentrated in vacuo and purified by flash chromatography to gave 2 -methyl- ( (5S) -2- (N- (3- (1,2,3, 4-tetrahydropyridino (2 , 3-b) pyridin-7-yl) prop-1- yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin- 5-yl ) acetate . 2- ((5s) -2- (4- (1,2, 3, 4-tetrahydropyridino (2, 3- b)pyridin-7-yl) butanoyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetic acid was prepared according to example 34. 3- (1 , 2 , 3 , 4-tetrahydropyridino [2 , 3- b]pyridin-7-yl)butyic acid was prepared according to Duggan, M. E. WO 98/18460. EI-MS m/z 406 (M-H) " ; X H- NMR (400 MHz, d6-DMSO) : δ 7.27-6.97 (m, 5H) , 6.21 (bs, IH) , 6.17 (m, IH) , 4.52 (q, J=33.6Hz, 2H) , 3.80 (m, IH) , 3.56-3.45(m, 2H) , 3.30 (s, 2H) , 2.94 (m, 2H) , 2.60 (m, 4H) , 2.36 (m, 2H) , 2.25( m, 3H) , 1.65 (m, 4H) , 1.50 (m, 2H) . Preparation of 2- [2- (4- (1 , 2 , 3 , 4-tetrahvdro pyridino [2, 3 -blpyridin-7-yl) butanoyl) -IH, 3H, 4H, 5H- benzo [el azepin-5-yl! acetic acid Step A: Methyl-2- \ 2 - (4- { 1- f ( tert-butyl ) oxycarbonyl 1 1,2,3, 4-tetrahvdropyridino [2 , 3-bl yridin-7- yl)butanoyl) -IH, 3H, 4H, 5H-benzo [el azepin-5-yll acetate Methyl-2- [2- (4-{l- [ (tert-butyl) oxycarbonyl] -1,2,3,4- tetrahydropyridino [2 , 3-b] pyridin-7-yl}butanoyl) - IH, 3H, 4H, 5H-benzo [e] azepin-5-yl] acetate according to the procedure of Example 55. EI-MS m/z 422 (M+H) * . Step B: 2- f 2- ( 4- ( 1 , 2 , 3 , 4-tetrahvdropyridino r 2.3- blpyridin-7-yl) butanoyl) -IH, 3H.4H, 5H-benzo [el azepin-5- yllacetic acid To methyl-2- [2- (4-{l- [ ( tert-butyl) oxycarbonyl] - 1,2,3, 4-tetrahydropyridino [2 , 3-b] pyridin-7- yl}butanoyl) -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl] acetate was added 4. OM HCl/dioxane (4mL) and the resulting mixture was stirred for 18 hrs at room temperature, concentrated by rotary evaporation, diluted in MeOH followed by the addition of IN NaOH (5eq) . The mixture was stirred at room temperature for 48 hrs., acidified with IN HCl, concentrated by rotary evaporation and extracted with dichloromethane. The organic solvent was concentrated concentrated in vacuo to afford the desired product. EI-MS m/z 408 (M+H) * . 'H-NMR (400MHz, CDC1 3 ) : δ 7.3-7.1 (m, 4H) , 6.35 (m, 2H) , 4.75 (d, J= 15.1, IH) , 4.55 (m, 2H) , 3.8 (m, IH) , 3.5 (m, 5H) , 2.4 (m, 3H) , 2.15 (m, 2H) , 2.0 (m, 3H) , 1.9 (m, 3H) , 1.7 (m, lH) . Example 57 Preparation of 2- (2- ( (5- ( (4 , 5-dichloroimidazolyl) methyl-2-furyl) carbonyl) -IH, 3H, 4H, 5H-benzo [el azapin-5- vD acetic acid 2- (2- ( (5- ( (4, 5-Dichloroimidazolyl)methyl-2- furyl) carbonyl) -IH, 3H, 4H, 5H-benzo[e] azapin-5-yl ) acetic acid was prepared from 5- ( (4 , 5-dichloroimidazolyl) methyl-2-furyl) carboxylic acid and methyl 2- IH, 2H, 3H, 4H, 5H-benzo[e]azaperhydroepin-5-yl) acetate by stirring the two compounds in acetonitrile (O.IM) with triethylamine (1. leq) and 1- (3-dimethylaminopropyl ) -3- ethylcarbodiimide hydrochloride (l.leq) for 18 hrs at room temperture. The reaction was concentrated concentrated in vacuo and purified by flash chromatography to gave methyl-2- (2- ( ( 5- ( (4 , 5- dichloroimidazolyl)methyl-2-furyl) carbonyl) - IH, 3H, 4H, 5H-benzo[e]azapin-5-yl) acetate. 2- (2- ( (5- ( (4, 5-dichloroimidazolyl ) methyl-2-furyl ) carbonyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid was prepared according to example 34. EI-MS m/z 449 (M+H) * ; 'H-NMR (500 MHz, CDCl 3 ): δ 10.8 (br s, IH) , 7.56 (m, IH) , 7.23 (m, 4H) , 6.93 (m, IH) , 6.43 (m, IH) , 5.07 (m, 2H) , 4.64 (m, 2H) , 3.82 (m, IH) , 3.58 (m, IH) , 2.72 (m, IH) , 2.18 (m, IH) , 1.58 (m, IH) . Example 58 Preparation of Methyl 2- (2- (( 5- ( (benzylamino) carbonyl amino)phenyl) -2-furyl) carbonyl) -1H.3H.4H.5H- benzo [el azaρin-5-yl) acetate Methyl 2- (2- ( (5- ( (benzylamino) carbonylamino) phenyl) -2- furyl) carbonyl) -IH, 3H, 4H, 5H-benzo [e]azapin-5- yl) acetate as prepared from 5- ( (benzylamino) carbonyl amino) phenyl) -2-furyl) carboxylic acid and methyl 2- 1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl ) acetate by stirring the two compounds in acetonitrile (0.1M) with triethylamine (1. leq) and 1- (3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (l.leq) for 18 hrs at room temperture. The reaction was concentrated concentrated in vacuo and purified by flash chromatography to gave methyl 2- (2- ( (5- ( (benzylamino) carbonylamino) phenyl) -2-furyl) carbonyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetate. EI-MS m/z 538 (M+H) * . Preparation of 2- (2- ((5- ( (benzylamino) carbonylamino) phenyl) -2-furyl) carbonyl) - IH, 3H, 4H, 5H-benzo [el azapin-5-yl) acetic acid 2- (2- ( ( 5- ( (benzylamino) carbonylamino) phenyl ) -2- furyl) carbonyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid_was prepared according to example 34. EI-MS m/z 524 (M+H) * ; X H-NMR (400 MHz, CDC1 3 ) : δ 11.2 (br s, IH) , 8.00 (br s, IH) , 7.49 (m, IH) , 7.24 (m, 12H) , 6.48 (d, J = 3.3 Hz, IH) , 5.86 (m, IH) , 4.77 (m, 2H) , 4.42 (m, 2H) , 3.73 (m, IH) , 3.65 (m, IH) , 3.32 (m, IH) , 2.97 (m, IH) , 2.75 (m, IH) , 2.59 (m, IH) , 1.50 (m, IH) . Example 60 Preparation of 2- [3- (3- (N- [2- (2-pyridylamino) ethyl 1 carbamoyl }phenyl ) -IH , 2H , 4H , 5H- benzo [dl azaperhydroepinyll acetic acid Step A: 2- ( 2-bromophenyl ) -N- f 3- (hydroxymethyl ) henyl 1 acetamide To a stirring solution of 2- (2-bromophenyl) acetic acid in dichloromethane (0.2 M) was added (3-aminophenyl ) methan-1-ol (1.2 eq) , triethylamine (1.5 eq) , and EDAC (1.5 eq) . After 2 hrs, the solution was washed with water, 10% HCl, 10% sodium carbonate, and water, dried over magnesium sulfate, filtered and concentrated in vacuo to afford a colorless solid. EI-MS m/z 320/322 (M+H) * Step B: ( 3- ( \ 2 - (2-bromophenyl ) ethyll amino}phenyl ) methan-1-ol 2- (2-bromophenyl) -N- [3- (hydroxymethyl ) phenyl ] acetamide was dissolved THF (0.2 M) , followed by addition of BH 3 -DMS (3 eq) , and the reaction was heated to reflux with stirring. After 2 hrs, the mixture was cooled to room temerature, and quenched with excess 10% HCl. The mixture was heated to reflux for 1 hr, and then cooled to room temperature. After washing with EtOAc, the aqueous phase was made alkaline with 10% sodium carbonate, and extracted with EtOAc. The organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo . The residue was triturated with EtOAc to afford a colorless solid. EI-MS m/z 307/309 (M+H) * Step C: Methyl (2E) -4- ( \ 2- (2-bromophenyl ) ethyll \ > - (hydroxymethyl) phenyl! amino)but-2-enoate (3- { [2- (2-bromophenyl) ethyl] amino}phenyl)methan-l-ol was dissolved in acetonitrile (0.2 M) , followed by addition of methyl 4-bromocrotonate (1.2 eq) and triethylamine (1.5 eq) , and the reaction was refluxed for 18 hrs. After cooling to room temperature, the reaction was diluted with EtOAc, washed with 10% sodium carbonate, water, and brine, dried over magnesium sulfate, filtered and concentrated in vacuo . Flash chromatography (silica; 50% EtOAc/Hex) afforded a colorless oil. EI-MS m/z 403/405 (M+H) * Step D: Methyl 2- { 3- [3- (hydroxymethyl ) phenyl 1 - 2H, 4H, 5H-benzo[dl azaperhvdroepinylidene} acetate Methyl (2E)-4-( [2- (2-bromophenyl) ethyl] [3- (hydroxymethyl) phenyl] amino}but-2-enoate was dissolved in toluene (O.IM) followed by addition of triethylamine (1 eq) , tetrakis (triphenylphosphine) palladium (0.05 eq) , and 2M sodium carbonate (15%/v). The mixture was heated to reflux ofor 18 hrs. with vigorous stirring. After cooling to room temperature, the phases were separated, and the organic phase was washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo . The residue was dissolved in EtOAc and extracted 5x with 6N HCl. The combined extracts were neutralized with 10% sodium carbonate, and extracted with EtOAc. The organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated to afford a yellow oil. EI-MS m/z 323 (M+H) * Step E: Methyl 2- (3- [3- (hydroxymethyl) phenyl! - IH , 2H, 4H, 5H-benzo fd! azaperhvdroepinyl }acetate Methyl 2- (3- [3- (hydroxymethyl) phenyl] -2H, 4H, 5H- benzo [d] azaperhydroepinylidene} acetate was dissolved in MeOH (0.1M) followed by addition of magnesium turnings (10 eq) and the mixture was refluxed for 18hr. The mixture was filtered through celite and concentrated by rotary evaporation. The product was purified by flash chromatography (25% EtOAc/Hexane) . EI-MS m/z 325 (M+H) * Step F: Methyl 2- [3- (3-formylphenyl) -IH, 2H, 4H, 5H- benzo [dl azaperhvdroepinyll acetate Methyl 2- {3- [3- (hydroxymethyl) phenyl] -IH, 2H,4H, 5H- benzo [d] azaperhydroepinyl } acetate was dissolved in methylene chloride (O.IM) followed by addition of triethylamine (1 eq) , dimethyl sulfoxide (2 eq) and sulfur trioxide-pyridine (1 eq) and stirred for 5 hrs The mixture was filtered through celite and concentrated by rotary evaporation. The product was purified by flash chromatography (20% EtOAc/Hexane) . EI-MS m/z 323 (M+H) * Step G: Methyl 2- [3- ( 3- (N- \ 2 - (2 -pyridylamino) ethyll carbamoyl)phenyl) -IH, 2H, 4H, 5H- benzo [dl azaperhydroepinyl 1 acetate Methyl 2 - [ 3- ( 3-formylpheny1 ) -IH, 2H, 4H, 5H- benzo [d] azaperhydroepinyl] acetate was dissolved in methylene chloride (0.4M) at RT under nitrogen followed by addition of and 2- (N- (2-aminoethyl) amino) pyridine (1.5 eq) , sodium triacetoxyborohydride (2 eq) , and acetic acid (4 eq) . After 5 hrs., the reaction was carefully quenched with 2M sodium carbonate and extracted with methylene chloride. The organic phase was extracted with IN hydrochloric acid. The aqueous phase was neutralized with IN sodium hydroxide and extracted with methylene chloride. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford the product. EI- MS m/z 445 (M+H) * Step H: 2- \ 3 - (3- IN- [2- (2-ρyridylamino) ethyl! carbamoyl} phenyl) -IH, 2H, 4H, 5H-benzo [dl azaperhydroepinyl! acetic acid To a stirring solution of methyl 2- [3- (3- {N- [2- (2- pyridylamino) ethyl] carbamoyl}phenyl) -IH, 2H, 4H, 5H- benzo [d] azaperhydroepinyl] acetate in methanol (0.1 M) was added IN NaOH (3 eq) . After 18 hrs, the reaction was neutralized with 10% HCl, concentrated by rotary evaporation and purified by recrystalization from 2% MeOH/CH 2 Cl 2 . EI-MS m/z 431 (M+H) * ; 'H-NMR (400 MHz, d6- DMSO) : δ 7.908(d, J=4.8Hz, IH) , 7.33 (m, 2H) , 7.21-7.04 (m, 3H) , 6.83 (m, IH) , 6.61 (d, J= 7.3 Hz, IH) , 6.49 (m, 2H) , 3.86 (m, 2H) , 3.75 (m, 2H) , 3.35 (t, J= 3.5Hz), 3.05 (m, IH) , 2.93 (m, 3H) , 2.40 (m, 2H) , 2.25 (m, IH) , 2.09 (t, J= 3.5Hz, IH) . Example 61 Preparation of 2- [3- ( (4- f (amidinoamino) methyl! phenyl) methyl) -IH, 2H, 4H, 5H-benzo [d! azepinyl! acetic acid Step A: Tert-butyl (2Z) -2-aza-3- \ ( tert- butoxy) carbonylamino! -3 -methyl hioprop-2 -enoate To a stirring solution of methylthiocarboxamidine in methylene chloride (0.2 M) was added di-tert-butyl dicarbonate (4 eq) , followed by saturated sodium carbonate. After stirring for 18 hr the reaction was diluted with methylene chloride and separated, dried over magnesium sulfate, filtered and concentrated in vacuo . Flash chromatography (silica; 10% CHC1 3 ) afforded a colorless solid. EI-MS m/z 291 (M+H) * Step B: Tert-butyl (2E) -3-amino-2-aza-3- [( tert- butoxy) carbonylamino! prop-2-enoate Tert-butyl (2Z) -2-aza-3- [ (tert-butoxy) carbonylamino] - 3-methylthioprop-2-enoate was dissolved in MeOH (0.1M) followed by addition of IN NH 4 OH (5 eq) . After stirring overnight the solution was concentrated in vacuo to afford a colorless solid. EI-MS m/z 411 (M+H) * . Step C: (Tert-butoxy) -N- ([( tert-butoxy) carbonylamino! iminomethyl} -N- ( [4- (bromomethyl ) phenyl! methyl} carboxamide Tert-butyl (2E) -3-amino-2-aza-3- [( tert-butoxy) carbonyl amino] rop-2-enoate was dissolved in dimethyl foramide (O.IM) followed by addition of NaH (1 eq) . After stirring for 5 mins . the addition of α, α' -dibromo-p- xylene in dimethyl foramide was added. The solution was stirred for 18 hrs. and then quenched with saturated ammonium chloride. Diluted with ethyl acetate and washed with water, brine and dried with magnesium sulfate. The solution was concentrated in vacuo to afford a colorless foam. EI-MS m/z 444 (M+H) * . Step D: Methyl 2- [3- ( (4- [( (tert-butoxy) -N- I \ (tert- butoxy) carbonylamino! iminomethyl) carbonylamino) methyl 1 phenyl }methyl ) -IH, 2H, 4H , 5H- benzo [dl azepinyl! acetate Methyl 2- (3- (phenylmethyl) -2H, 4H, 5H- benzo [d] azaperhydroepin-1-ylidene) acetate and (tert- butoxy) -N- { [ (tert-butoxy) carbonylamino] iminomethyl} -N- { [ 4- (bromomethy1 ) phenyl ] methyl } carboxamide were dissolved in acetonitrile (O.IM) followed by addition of triethylamine (1 eq) . After stirring for 18 hrs. at 60°C the reaction was cooled to room temperature and diluted with ethyl acetate The solution was extracted with 10% sodium bicarbonate, water and brine. The organic layer was dried with magnesium sulfate and concentrated in vacuo to afford a colorless foam. Flash chromatography (silica; 100% EtOAc) afforded a colorless solid. EI-MS m/z 444 (M+H) * . Step E: 2- r3- (14- r ( (tert-butoxy) -N- ( [carbonylamino1 iminomethyl) carbonylamino) methyl! phenyl}methyl) -1H.2H.4H, 5H- benzo [dl azepinyl! acetic acid To a stirring solution Methyl 2- [3- ( (4- [(( tert- butoxy) -N-{ [ (tert-butoxy) carbonylamino] iminomethyl} carbonylamino) methyl] phenyl}methyl) -IH, 2H, 4H, 5H- benzo [d] azepinyl] acetate in methanol (0.1 M) was added IN NaOH (3 eq) . After 18 hrs, the reaction was neutralized with 10% HCl, concentrated by rotary evaporation and purified by recrystalization from 2% MeOH/CH 2 Cl 2 . EI-MS m/z 466. Step F: 2- [3- ( (4- [ (amidinoamino) methyl! phenyl }methyl ) - 1H.2H.4H.5H-benzo [dl azepinyl! acetic acid 2- [3- ( {4- [ ( (tert-butoxy) -N- { [carbonylamino] iminomethyl } carbonylamino) methyl ] phenyl }methyl ) - IH, 2H, 4H, 5H-benzo [d.] azepinyl] acetic acid was dissolved in 4M HCl/dioxane and stirred for 3 hrs. at room temperature. The reaction was concentration by rotary evaporation and the product was purified by trituation with diethyl ether. EI-MS m/z 366 (M+H) * ; (M+H) * ; * H- NMR (400 MHz, d2-D 2 0) : δ 7.40 (d, J=8.0Hz, IH) , 7.3 (d, J= 8.0Hz, 2H) , 7.24-7.09 (m, 4H) , 4.39(s, 2H) , 4.22 (q, J=6.5Hz, 2H) , 3.70-3.60 (m, 2H) , 3.48 (m, IH) , 3.24 (m, 2H) , 3.01-2.78 (m, 2H) , 2.71 (m, IH) . Preparation of 2- (3- (N- [4- (amidinoamino) butyl 1 carbamoyl }-lH, 2H, 4H, 5H-benzo [d! azepinyl) acetic acid Step A: tert-butyl (2E) -3- [ (4-aminobutyl) amino! -2-aza- 3- [ ( tert-butoxy) carbonylamino! prop-2-enoate Tert-butyl (2Z) -2-aza-3- [ ( tert-butoxy) carbonylamino) - 3-methylthioprop-2-enoate was dissolved in MeOH (O.IM) followed by the addition of 1 , 4-diaminobutane (5eq) . After stirring for 18 hrs., the solution was concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was separated and extracted with 10% HCl. The aqueous layer was neutralized with sodium bicarbonate and extracted with ethyl acetate. The organic layers were combined, dried over magnesium sulfate and concentrated in vacuo. Flash chromatography (10% MeOH/CH 2 Cl 2 ) afforded the product. EI-MS 331 (M+H) . Step B: tert-butyl (2E) -2-aza-3- r (tert- butoxy) carbonylamino1 -3-([4-((l- [ (methoxycarbonyl) methyl! (IH, 2H, 4H, 5H-benzo Tdl azepin- 3-yl) ) carbonylamino) butyl! amino}prop-2-enoate Methyl-2-(lH,2H,3H,4H, 5H- benzo [d] azaperhydroepinyl) acetate Hydrocloride was dissolved in methylene chloride and washed with IN NaOH. The organic layer was separated, dried over sodium sulfate and concentrated by rotary evaporation. Excess of phosgene (20% in toluene) was added and stirred for 5 min. The excess of phosgene was evaporated and the residue was diluted with DMF (2.5mL) ander nitrogen. Tert-butyl (2E)-3-[(4- aminobutyDamino] -2 -aza-3- [ (tert-butoxy) carbonylamino] prop-2-enoate and triethylamine, previously dissolved in DMF (2mL) , were added to the mixture. The resulting mixture was stirred for 18 hrs. at room temperature, concentrated in high vacuum and chromatographed on silica gel using 10% MeOH/CH 2 Cl 2 as eluent . EI-MS m/z 576 (M+H) * . Step C: 2- (3- (N- [4- (amidinoamino) butyl 1 carbamoyl} - IH, 2H, 4H, 5H-benzo [dl azepinyl ) acetic acid Tert-butyl (2E) -2-aza-3- [ ( tert-butoxy) carbonylamino] -3- { [4- ( {1- [ (methoxycarbonyl) methyl] (IH, 2H, 4H, 5H- benzo [d] azepin-3-yl) } carbonylamino) butyl] amino}prop-2- enoate was dissolved in ethanol (40mL) followed by the addition of IN NaOH (7mL) . The mixture was stirred overnight at room temperature, acidified with IN HCl and extracted with dichloromethane. The organic layer was washed with water, dried over sodium sulfate, concentrated by high vacuum and chromatographed on silica gel using 5% MeOH/CH 2 Cl 2 as eluent . The resulting product was dissolved in 4. OM HCl/dioxane, stirred for 18 hrs., concentrated by rotary evaporation and the residue obtained was re-dissolved in acetonitrile to remove excess of HCl and afforded the desired product. EI-MS m/z 396 (M-H) " . 'H-NMR (400 MHz, MeOH- d 4 ) : δ 7.80 (s, IH) , 7.00 (m, 4H) , 3.82-3.6 (m, 2H) , 3.5 (s, IH) , 3.45-3.31 (m, 2H) , 3.10 (m, 5H) , 2.80-2.5 (m, 3H) , 1.5-1.35 (m, 5H) . Example 63 Preparation 2- (2- [N- (2- (1,2,3, 4-tetrahvdropyridino \ 2 .3 -blPyridin-7-yl) ethyl) carbamoyl 1-4H.5H, 10H- benzo [dl imidazolo [1, 2-a! azepin-5-yl) acetic acid Step A: 2- (4-bromophenyl) ethanenitrile To a stirring solution of 2-bromo benzylbromide in dimethyl sulfoxide (1.0 M) was added sodium cyanide (2 eq) , and the solution was stirred for 18 hrs. The reaction was then diluted with water and extracted with ethyl acetate. The organic phase was washed with 10% HCl, brine and dried with magnesium sulfate. The solution was concentrated in vacuo to afford the product. EI-MS m/z 196, 198 (M+H) * Step B: 2- ( 4-bromophenyl ) -1- (hydroxyimino) ethylamine To a stirring solution of 2- (4-bromophenyl) ethanenitrile in methanol/ water (leq /leq, O.I M) was added hydroxyamine hydrochloride (2.1 eq) and sodium carbonate (2.0 eq) . The reaction was strirred at 60°C for 5 hrs. The reaction was diluted with ethyl acetate and separated. The organic layer was washed with 10% hydochloric acid and separated. The aqueous layer was neutrized with 10% sodium carbonate and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered and concentrated in vacuo to afford the product. EI-MS rrf/z 229, 231 (M+H) * Step C: Phenylmethyl (3E) -4- r (1Z) -2-amino-l-aza-3- (4- bromophenyl ) prop-1-enyloxyl but-3-enoate To a stirring solution of 2- (4-bromophenyl) -1- (hydroxyimino) ethylamine (1.0 eq) in ethanol (0.1M) was added phenylmethyl prop-2-ynoate (2.0 eq) at 25°C and stirred for 36 hrs. The reaction concentrated in vacuo . and the residue was purified by flash chromatography (40% EtOAc/Hexane) . EI-MS m/z 389, 39KM+H) * Step D: Phenylmethyl 2- [ (2-bromophenyl) methyl! imidazole-4-carboxylate Phenylmethyl (3E) -4- [ (1Z) -2-amino-l-aza-3- (4- bromophenyl)prop-l-enyloxy]but-3-enoate in diphenyl ether at 200°C for 2 hrs. The reaction was cooled to room temperature and diluted with ethyl acetate. The reaction was extracted with 10% hydrochloric acid. The aqueous layer was neutralized with saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was extracted with brine, and the organic layer was dried with magnesium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (20% EtOAc/Hexane) . EI-MS m/z 369/371(M+H) * Step E: Methyl (2E) -4- (2- r (2-bromophenyl) methyl] -4- [benzyloxycarbonyl 1 imidazolyl)but-2-enoate To a stirring solution of phenylmethyl 2-[(2- bromophenyl ) methyl ] imidazole-4-carboxylate in dimethyl foramide (O.IM) was added sodium hydride (1.2 eq) The reaction was allowed to stir for 10 mins. followed by addition of methyl 4-bromocrotonate continued stirring for 18 hr. The reaction was diluted with water and extracted with ethyl acetate. The organic layer was extracted with 10% hydrochloric acid and the aqueous layer was neutralized with saturated sodium carbonate. The aqueous layer eas extracted with ethyl acetate and dried with magnesium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (50% EtOAc/Hexane). EI-MS m/z 406/408(M+H) * Step F: Methyl 2- {2- [benzyloxycarbonyl! -4H, 5H, 10H- benzo [dl imidazolo [1 , 2-al azepin-5-yl) acetate To a solution of methyl (2E) -4- (2- [ (2- bromophenyl) methyl] -4- [benzyloxycarbonyl] imidazolyl}but-2-enoate in benzene was added tributyl tin hydride (2 eq) and 2,2"- azobisisobutyronitrile (20%/ wt) under nitrogen. The reaction was stirred under nitrogen at reflux for 2 hrs. The reaction was cooled to room temperature and concentrated in vacuo . The residue was purified by flash chromatography (50% EtOAc/Hexane) . EI-MS m/z 39KM+H) * Step G: 5- [ (methoxycarbonyl) methyl! -4H, 5H, 10H- benzo [dl imidazolo [ 1 , 2-al azeρine-2-carboxylic acid Methyl 2- {2- [benzyloxycarbonyl] -4H, 5H, 10H- benzo [d] imidazolo [1 , 2-a] azepin-5-yl} acetate was dissolved in ethanol followed by addition of 10% palladium on carbon (10%/ wt) , and subjected to hydrogenation at ballon pressure. After 3 hrs, the mixture was filtered through celite and concentrated in vacuo to afford a viscous oil. Step H: Methyl 2- (2- rN- (2- (1.2.3 , 4-tetrahvdropyridino [2 , 3-blpyridin-7-yl) ethyl) carbamoyll -4H, 5H, 10H- benzo [dl imidazolo [1 , 2-a! azepin-5-yl) acetate 5- [ (Methoxycarbonyl) methyl] -4H, 5H, 10H- benzo [d] imidazolo [1 , 2-a] azepine-2-carboxylic acid and 2- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3-b]pyridin-7- yl ) ethylamine were dissolved in methylene chloride (0.1M) with triethylamine (l.leq) and l-(3- dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (l.leq) and stirred for 18 hrs at room temperture. The reaction was diluted with methylene chloride and washed with water, dried with magnesium sulfate andconcentrated under vacuum. The residue was purified by flash chromatography (10% MeOH/ CH 2 C1 2 ) . EI-MS m/z 459(M+H) * Step I: 2-(2- fN- (2- (1, 2, 3 , 4-tetrahvdropyridino [2 , 3- bl pyridin-7 -yl ) ethyl ) carbamoyl 1 -4H, 5H , 10H- benzo [dl imidazolo [1, 2-a! azepin-5-yl}acetic acid To a stirring solution of methyl 2- {2- [N- (2- ( 1 , 2 , 3 , 4- tetrahydropyridino [2, 3-b] pyridin-7-yl) ethyl) carbamoyl] -4H, 5H, lOH-benzo [d] imidazolo [1, 2-a] azepin-5- yl) acetate in methanol (0.1 M) was added IN NaOH (3 eq) . After 18 hrs, the reaction was neutralized with 10% HCl, concentrated by rotary evaporation and purified by recrystalization from 2% MeOH/CH 2 Cl 2 . EI- MS m/z 431 (M+H) * . Preparation 2- (2- fN- (methylethyl) -N- (2- (1,2, 3, 4- tetrahydropyridino r2 , 3-b!ρyridin-7- yl) ethyl) carbamoyll -4H, 5H, lOH-benzord! imidazolo [1, 2- al azepin-5-yl)acetic acid Step A: Methyl 2- f 2- fN- (methylethyl) -N- (2- (1.2 , 3 , 4- tetrahvdropyridino r2 , 3-blρyridin-7-yl) ethyl) carbamoyll -4H, 5H, lOH-benzo fdl imidazolo f 1 , 2-al azepin-5- vDacetate 5- [ (methoxycarbonyl ) methyl ] -4H, 5H, 10H- benzo [d] imidazolo [1 , 2-a] azepine-2-carboxylic acid and 2-N-methylethy1-(1,2,3,4-tetrahydropyridino [2,3- b]pyridin-7-yl) ethylamine were dissolved in methylene chloride (0.1M) with triethylamine ( 1. leq) and l-(3- dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (l.leq) and stirred for 18 hrs at room temperture. The reaction was diluted with methylene chloride and washed with water, dried over magnesium sulfate and concentrated concentrated in vacuo . The residue was purified by flash chromatography (10% MeOH/ CH 2 C1 2 ) . EI-MS m/z 501 (M+H) * Step B: 2- (2- [N- (methylethyl) -N- (2- (1,2, 3, 4-tetrahvdro pyridino [2 , 3-bl pyridin-7-yl ) ethyl) carbamoyl 1 -4H, 5H, lOH-benzo [dl imidazolo [1 , 2-a! azepin-5-yl}acetic acid To a stirring solution of methyl 2-{2-[N- (methyethyl) -N- (2- (1, 2, 3, 4-tetrahydropyridino [2 , 3- b]pyridin-7-yl) ethyl) carbamoyl] -4H, 5H, 10H- benzo [d] imidazolo [1, 2-a] azepin-5-yl}acetate in methanol (0.1 M) was added IN NaOH (3 eq) . After 18 hrs, the reaction was neutralized with 10% HCl, concentrated by rotary evaporation and purified by recrystalization from 2% MeOH/CH 2 Cl 2 . EI-MS m/z 487 (M+H) * ; : H-NMR (400 MHz, d-CDCl 3 ) : δ 7.50 (s, IH) , 7.34- 7.09 (m, 4H) , 6.20 (d, J= 6.3Hz, IH) , 5.50 (m, IH) , 4.37-4.00 (m, 2H) , 3.46-3.17 (m, 3H) , 2.88 (m, IH) , 2.69 (m, 4H) , 2.25 (d, J=13.0 Hz, 2H) , 1.86 (m, 3H) , 1.60 (m, 7H) . Example 65 Preparation of 2- (2- [N- (methylethyl) -N- (1,2,3, 4tetrahvdropyridino [2 , 3-bl pyridine-6- ylmethyl) carbamoyll -4H, 5H, 10H-benzo[d! imidazolo [1, 2- al zepin-5-yl}acetic acid Step A: (methylethyl ) ( 1 , 2 , 3 , 4-tetrahvdropyridino [2 , 3- blpyridin-7-ylmethyl) amine To a solution of 1, 2 , 3 , 4-tetrahydropyridino [2 , 3- b]pyridine-7-carbaldehyde in dry dichloromethane (32mL) were added 4°A seives, sodium sulfate and isopropyl amine. The mixture was cooled to 0°C followed by the addition of acetic acid (300μL) . The resulting mixture was stirred at room temperature under nitrogen for 18 hrs. The mixture was filtered through celite, diluted with ethyl acetate, washed with saturated sodium bicarbonate and brine, dried over sodium sulfate, evaporated concentrated in vacuo and purified by flash chromatography ( 10% MeOH/CH 2 Cl 2 ) . EI-MS m/z 206 (M+H) * . Step B: Methyl-2- ( 2- [N- (methylethyl) -N- ( 1 , 2 , 3 , 4- tetrahvdropyridino [2 , 3-b! yridine-6- ylmethyl) carbamoyll -4H, 5H, 10H-benzo[d! imidazolo [1,2- a! azepin-5-yl) acetate [ (Methoxycarbonyl) methyl] -4H, 5H, lOH-benzo [d] imidazole [3 , 2-f ] azepine-2-carboxylic acid was dissolved in methylene chloride (lmL) followed by the addition of diisopropyl ethylamine (1.2eq) and EDC (1.2eq). Methylethyl (1,2,3, 4-tetrahydropyridino [2 , 3-b] pyridin- 7-ylmethyl) amine was dissolved in methylene chloride (lmL), and added to the resulting mixture. The reaction was stirred at room temperature for 18 hrs., concentrated by rotary evaporation and purified by flash chromatography (5% MeOH/CH 2 Cl 2 ) . EI-MS m/z 488 (M+H) * . Step C: 2- (2- [N- (methylethyl) -N- (1,2,3, 4tetrahydropyridino [2 , 3-bl yridine-6- ylmethyl ) carbamoyl 1 -4H, 5H, lOH-benzo [dl imidazolo [1,2- al azepin-5-yl}acetic acid Methyl-2-{2- [N- (methylethyl) -N- (1,2,3,4- tetrahydropyridino [2 , 3-b]pyridine-6-ylmethyl) carbamoyl] -4H, 5H, lOH-benzo [d] imidazolo [ 1, 2-a] azepin-5- yl} acetate was dissolved in methanol (0.2M) followed by the addition of IN NaOH (5eq) . The mixture was stirred at room temperature for 18 hrs., acidified with IN NaOH, concentrated by rotary evaporation and the product was purified by flash chromatography (5% MeOH/CH 2 Cl 2 ) . EI-MS m/z 474 (M+H) * ; X H-NMR (400 MHz, MeOH-d 4 ) : δ 7.43-7.10 (m, 6H) , 6.5 (s, IH) , 5.45 (s, 2H) , 4.53-4.40 (m.3H), 4.12- 3.83 (m,3H), 3.40 (m,2H), 2.70 (m,3H), 2.55 (m, IH) , 1.85(m, 2H) , 1.15(d, J=6.33 Hz , 6H ) . Example 66 Preparation of 2- (2- [N- ( 1 , 2 , 3 , 4-tetrahydropyridino f2 , 3-bl pyridin-6-ylmethyl) carbamoyl! -4H, 5H, 10H- benzo [dl imidazolo [ 1 , 2-a! azepin-5-yl) acetic acid Step A: Dimethoxypyridino [ 3 , 2-el pyridin-2-ylmethane A mixture of 2-aminopyridine-3-carbaldehyde, prepared according to Duggan, M. E. WO 98/18460, pyruvic aldehyde dimethylacetal (4eq) and L-proline (0.3eq) in MeOH (0.2M) were refluxed under nitrogen for 20hr. The mixture cooled to room temperature, concentrated by rotary evaporation and the residue was diluted with methylene chloride (32mL) and washed with water and brine, dried over sodium sulfate, filtered, concentrated concentrated in vacuo . The residue was purified by flash chromatography (10% MeOH/CH 2 Cl 2 ) . X H-NMR (400 MHz, CDC1 3 ): 9.15 (dd, J=1.95, J= 4.20, IH) , 8.25 (d, J=8.42, IH) , 8.20 (dd, J= 1.95, 8.14, IH) , 7.8 (d, J= 8.36, IH) , 7.52 (q, J= 4.24, IH) , 5.5 (s, IH) , 3.5 (s, 6H) . Step B: Dimethoxy-1, 2 , 3 , 4-tetrahydropyridino [2 , 3- blpyridin-7-ylmethane Dimethoxypyridino [3 , 2-e]pyridin-2-ylmethane was dissolved in methanol (0.5M) followed by addition of 10% Pd/C) , and subjected to hydrogenation at ballon pressure. The mixture was filtered through celite and concentrated by rotary evaporation. EI-MS m/z 209 (M+H) * . Step C: 1, 2, 3 , 4-tetrahvdropyridino [2 , 3-b!pyridine-7- carbaldehvde Dimethoxy-1, 2,3, 4-tetrahydropyridino [2 , 3-b] pyridin-7- ylmethane was dissolved in trifluoroacetic acid (14mL) and stirred under nitrogen for 16hrs. The mixture was quenched with saturated sodium bicarbonate, extracted with methylene chloride, dried over sodium sulfate, filtered, in vacuo and purified by flash chromatography (5% MeOH/CH 2 Cl 2 ). EI-MS m/z 163 (M+H) * . Step D: 1 , 2 , 3 , 4- etrahvdropyridino [ 2 , 3-bl pyridin-7- ylmethylamine Hydroxyamine hydrochloride (2eq), sodium acetatetrihydrate (2eq) and water (0.4M) were heated at 60°C. 1, 2, 3, 4-tetrahydropyridino [2 , 3-b]pyridine-7- carbaldehyde was dissolved in methanol (2.5mL) and added to the resulting solution. Additional methanol was added until the solution became clear, the reaction was stirred at 60°C for 18 hrs. The mixture was cooled to room temperature, diluted with water (25mL) and extracted with ether. The organic layer was extracted with saturated sodium bicarbonate and brine, dried over sodium sulfate, filtered and concentrated by in vacuo . To a solution of the oxime in trifluoroacetic acid (5mL) was added zinc dust (5.6eq) in several portions, while keeping the temperature between 15-25°C. After stirring for 15 mins., the mixture was added to a solution of an aqueous 2N NaOH (39mL) solution and methylene chloride (21mL) at 0°C and stirred for an additional 15 mins. The reaction was filtered and the organic layer was separated, washed with water and brine, dried over sodium sulfate and concentrated in vacuo to yield the product. EI-MS m/z 163 (M+H) * . Step E: Methyl-2- (2- rN- ( 1 , 2 , 3 , 4-tetrahvdropyridino r2,3-blpyridin-6-ylmethyl) carbamoyl! -4H, 5H, 10H- benzo rdl imidazolo ri , 2-a! azepin-5-yl) acetate 5- [ (methoxycarbonyl ) methyl ] -4H, 5H, 10H- benzo [d] imidazole [3 , 2-f ] azepine-2-carboxylic acid was dissolved in methylene chloride (0.5mL), followed by addition of diisopropyl ethylamine (1.2eq) and EDC (1.2eq) . 1, 2 , 3, 4-tetrahydropyridino [2 , 3-b] pyridin-7- ylmethylamine was dissolved methylene chloride ( 0.5mL) and added to the resulting solution. The reaction was stirred at room temperature for 48 hrs., concentrated in vacuo and purified by flash chromatography ( 5% MeOH/CH 2 Cl 2 ) . EI-MS m/ z 446 (M+H ) * . Step F: 2- { 2- [N- ( 1 , 2 , 3 , 4-tetrahvdropyridino r2 , 3- blpyridin-6-ylmethyl) carbamoyll -4H, 5H, 10H- benzo [dl imidazolo TI , 2-al azepin-5-yl} acetic acid Methyl-2 -2- [N- ( 1, 2 , 3 , 4-tetrahydropyridino [2 , 3- b]pyridin-6-ylmethyl) carbamoyl] -4H, 5H, 10H- benzo [d] imidazolo [ 1, 2-a] azepin-5-yl}acetate was dissolved in MeOH (6mL) and IN NaOH (5eq) was added. The mixture was stirred at room temperature for 18 hrs., acidified with IN HCl, concentrated in vacuo and the product was purified by flash chromatography (5% MeOH/CH 2 Cl 2 ) . EI-MS m/z 432 (M+H) * . "H-NMR (400 MHz, MeOH-d 4 ) : δ 7.55 (s, IH) , 7.38-7.10 (m, 6H) , 6.5 (d, J= 5.77, IH) , 4.54-4.46 (m, 2H) , 4.37 (s, 2H) , 4.10 (d, J- 15.6, 2H) , 3.95 (t, J= 11.79, 2H) , 3.30 (m, 2H) , 2.7 (m, 2H) , 2.5 (m, IH) , 1.85 (m, 2H) . Preparation of 2- (2- (N-methyl-N- r 3- (2- pyridylamino) propyl 1 carbamoyl} -4H, 5H, 10H- benzo [dl imidazolo [1, 2-al azepin-5-yl) acetic acid Step A: Methyl-2- (2- (N-methyl-N- [3- (2- pyridylamino) propyl! carbamoyl} -4H, 5H, 10H- benzo [dl imidazolo [1, 2-al azepin-5-yl) acetate [ (Methoxycarbonyl) methyl] -4H, 5H, 10H- benzo [d] imidazole [3 , 2-f ] azepine-2-carboxylic acid was dissolved in methylene chloride (0.5mL), followed by addition of diisopropyl ethylamine (1.2eq) and EDC (1.2eq) . 1, 2 , 3 , 4-tetrahydropyridino [2 , 3-b] pyridin-7- ylmethylamine was dissolved methylene chloride (0.5mL) and added to the resulting solution. The reaction was stirred at room temperature for 48 hrs., concentrated in vacuo and purified by flash chromatography (5% MeOH/CH 2 Cl 2 ). EI-MS m/z 448 (M+H) * Step B: 2- ( 2- (N-methyl-N- f 3- (2- pyridylamino) propyl 1 carbamoyl) -4H, 5H, 10H- benzo [dl imidazolo [ 1 , 2-a! azepin-5-yl) acetic acid Methyl-2- (2- {N-methyl-N- [3- (2-pyridylamino) propyl] carbamoyl }-4H, 5H, lOH-benzo [d] imidazolo [1, 2-a] azepin-5- yl) acetate was dissolved in MeOH (6mL) and IN NaOH (5eq) was added. The mixture was stirred at room temperature for 18 hrs., acidified with IN HCl, concentrated in vacuo and the product was purified by flash chromatography (5% MeOH/CH 2 Cl 2 ) . EI-MS m/z 434 (M+H) * . 'H-NMR (400 MHz, CDC1 3 ): δ 8.0 (d, J= 5.4, IH) , 7.4 (m, 2H) , 7.3 (m, 4H) , 6.55 (m, 3H) , 4.20-4.05 (m, 4H) , 3.9 (m, IH) , 3.3 (t, J= 6.8, 2H) , 3.15 (s, 3H) , 2.7 (dd, J= 16.5, J= 6.3, 2H) , 1.9 (m, 2H) . Example 68 Preparation of 2- (2- (N-methyl-N- [2- (2- pyridylamino) ethyll carbamoyl} -4H, 5H, 10H- benzo [dl imidazolo [ 1 , 2-a! azepin-5-yl) acetic acid Step A: Methyl-2- (2- (N-methyl-N- [2- (2- pyridylamino) ethyll carbamoyl) -4H, 5H, 10H- benzo [dl imidazolo f 1 , 2-al azepin-5-yl) acetate [ (Methoxycarbonyl) methyl] -4H, 5H, 10H- benzo [d] imidazole [3 , 2-f ] azepine-2-carboxylic acid was dissolved in methylene chloride (0.5mL), followed by addition of diisopropyl ethylamine (1.2eq) and EDC (1.2eq) . 1, 2 , 3 , 4-tetrahydropyridino [2 , 3-b] pyridin-7- ylmethylamine was dissolved methylene chloride (0.5mL) and added to the resulting solution. The reaction was stirred at room temperature for 48 hrs., concentrated in vacuo and purified by flash chromatography (5% MeOH/CH 2 Cl 2 ). EI-MS m/z 434 (M+H) * . Step B: 2- (2- (N-methyl-N- r2- (2- pyridylamino) ethyll carbamoyl) -4H, 5H, 10H- benzo fdl imidazolo [ 1 , 2-al azepin-5-yl ) acetic acid Methyl-2- (2- (N-methyl-N- [2- (2-pyridylamino) ethyl] carbamoyl }-4H, 5H, lOH-benzo [d] imidazolo [1, 2-a] azepin-5- yl) acetate was dissolved in MeOH (6mL) and IN NaOH (5eq) was added. The mixture was stirred at room temperature for 18 hrs., acidified with IN HCl, concentrated in vacuo and the product was purified by flash chromatography (5% MeOH/CH 2 Cl 2 ) . EI-MS m/z 420 (M+H) * . 'H-NMR (400 MHz, d 6 -DMSO) : δ 12.35 (s, IH) , 7.5 (s, IH) , 7.33-7.16 (m, 8H) , 6.5 (bs, IH) , 4.4 (m, IH) , 4.10-3.8 (m, 4H) , 3.15 (s, 3H) , 2.9 (m, 2H) , 2.8-2.6 (m, 2H) , 1.75 (s, 2H) . Example 69 Preparation of 2- (2- [N- (benzimidazol-2-ylmethyl) -N- methylcarbamoyl! -4H, 5H, lOH-benzo [dl imidazolo [1,2- a! azepin-5-yl)acetic acid Step A: Methyl-2-(2- [N- (benzimidazol-2-ylmethyl) -N- methy1carbamoyll -4H, 5H, lOH-benzo [dl imidazolo fl , 2- al azepin-5-yl) acetate [ (Methoxycarbonyl) methyl] -4H, 5H, 10H- benzo [d] imidazole [3 , 2-f] azepine-2 -carboxylic acid was dissolved in methylene chloride (0.5mL), followed by addition of diisopropyl ethylamine (1.2eq) and EDC (1.2eq) . 1, 2 , 3 , 4-tetrahydropyridino [2 , 3-b] pyridin-7- ylmethylamine was dissolved methylene chloride (0.5mL) and added to the resulting solution. The reaction was stirred at room temperature for 48 hrs., concentrated in vacuo and purified by flash chromatography (5% MeOH/CH 2 Cl 2 ) . EI-MS m/z 444 (M+H) * . Step B: 2- ( 2- fN- (benzimidazol-2 -ylmethyl ) -N- methylcarbamoyl! -4H, 5H, lOH-benzo [dl imidazolo [1,2- al azepin-5-yl}acetic acid Methyl-2-(2- [N- (benzimidazol-2-ylmethyl) -N- methylcarbamoyl] -4H, 5H, lOH-benzo [d] imidazolo [1,2- a] azepin-5-yl}acetate was dissolved in MeOH (6mL) and IN NaOH (5eq) was added. The mixture was stirred at room temperature for 18 hrs., acidified with IN HCl , concentrated in vacuo and the product was purified by flash chromatography (5% MeOH/CH 2 Cl 2 ) . EI-MS m/z 430 (M+H) * . 'H-NMR (400 MHz, MeOH-d 4 ): δ 7.42 (s, IH) , 7.17 (m, 8H) , 4.4 (m, 2H) , 4.10-3.90 (m, 4H) , 3.3 (m, 2H) , 3.0 (m, 2H) , 2.10 (m, 2H) . Example 70 Preparation of Methyl 2- (8-methoxy-2- (N- (3- ( 1 , 2 , 3 , 4- tetrahydropyridino [2 , 3 ,bl pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azaperhvdroepin-5-yl) acetate Methyl 2- ( 8-methoxy-IH, 2H, 3H, 4H, 5H-benzo[e] azaperhydroepin-5-yl) acetate (1 eq, prepared according to Example 56) was stirred under nitrogen with 20% phosgene (1.1 eq) in toluene for 10 min. The excess phosgene was removed by rotary evaporation and the crude product was dissolved in 1:1 THF/DMF (0.25 M) , followed by addition of diisopropylethylamme (1.1 eq) and 3- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3 , b]pyridin-7-yl) propylamine (1.1 eq, prepared according to Duggan, M. E. WO 98/18460) . The reaction was stirred for 12 h at RT under nitrogen, concentrated in vacuo and the product was purified by flash chromatograpy (2-5% MeOH/CH 3 Cl) to give methyl 2- (8-methoxy-2- (N- ( 3- (1,2,3, 4-tetrahydropyridino [2,3, b] pyridin-7 -yl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 467 (M+H) * . Example 71 Preparation of 2- ( 8-methoxy-2- (N- (3- ( 1 , 2 , 3 , 4- tetrahvdropyridino [2,3 , bl pyridin-7-yl ) propyl) carbamoyl) -1H.3H.4H, 5H-benzo [el azaperhydroepin-5-yl 1 acetic acid 1 N NaOH solution (3 eq) was added to a solution of methyl 2- (8-methoxy-2- (N- (3- ( 1 , 2 , 3 , 4-tetrahydro pyridino [2,3, b]pyridin-7-yl) propyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate ( 1 eq) in methanol (0.10 M) and the resulting mixture stirred under nitrogen for 12 h. The mixture was neutralized to pH=7 with IN HCl solution and concentrated in vacuo . Purification by flash chromatography on silica gel (4-6% MeOH/CH 2 Cl 2 ) gave 2- (8-methoxy-2- (N- (3- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3,b] pyridin-7 -yl) propyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetic acid as a white solid. EI-MS m/z 453 (M+H) * ; 'H-NMR (400 MHz, CDC1 3 ) : . 11.0 (br s, IH) , 7.22 (d, J = 7.3 Hz, IH) , 7.08 (d, J = 8.5 Hz, IH) , 6.84 (d, J = 2.5 Hz, IH) , 6.70 (dd, J = 8.4, 2.5 Hz, IH) , 6.27 (d, J = 7.3 Hz, IH) , 5.74 (m, IH) , 4.65 (d, J = 15.1 Hz, IH) , 4.41 (d, J = 15.1 Hz, IH) , 3.72 (s, 3H) , 3.66 (m, IH) , 3.45 (m, 4H) , 3.30 (m, IH) , 3.16 (m, IH) , 2.69 (m, 6H) , 2.12 (m, IH) , 1.87 (m, 2H) , 1.80 (m, 2H) , 1.52 (m, IH) . Example 72 Preparation of 2- ( 8-benzyloχy-2- (N- (3- ( 1 , 2 , 3.4- tetrahydropyridino [2 , 3 , bl pyridin-7-yl ) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azaperhydroepin-5-yl) acetic acid Step A: Methyl 2- (8-hydroxy-IH, 2H, 3H, 4H, 5H- benzo [el azaperhydroepin-5-yl) acetic acid Boron tribromide (2 eq) was added to a solution of methyl 2- (8-methoxy-IH, 2H, 3H, 4H, 5H-benzo[e] azaperhydroepin-5-yl) cetate (1 eq, prepared according to Example 56) in methylene chloride (0.1 M) at -78 °C and the resulting mixture allowed to warm to RT with stirring under nitrogen. Quenched with 10% HCl solution and washed with IN HCl solution followed by brine. Collected aqueous layer and concentrated in vacuo to give 2- (8-hydroxy-IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetic acid as a white solid. EI-MS m/z 222 (M+H) * . Step B: Methyl 2- ( 8-hvdroxy-lH, 2H, 3H, 4H, 5H- benzo [el azaperhydroeρin-5-yl ) acetate Thionyl chloride (1.2 eq) was added to a solution of 2- (8-hydroxy-IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetic acid (1 eq) in methanol (0.1 M) at 0 °C and the resulting mixture was allowed to warm to RT with stirring under nitrogen. Concentrated in vacuo, dissolved residue in methylene chloride, and washed with saturated NaHC0 3 solution. Dried organics over sodium sulfate and concentrated in vacuo to give methyl 2- (8-hydroxy-IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate as a white solid. EI-MS m/z 236 (M+H) * . Step C: Methyl 2- (2- ( tert-butoxycarbonyl) -8-hvdroxy- IH, 2H, 3H, 4H, 5H-benzo [el azaperhydroepin-5-yl) acetate Di-tert-butyl dicarbonate (1.1 eq) was added to a solution of methyl 2- (8-hydroxy-IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin- 5-yl ) acetate in methylene chloride (0.50 M) at RT and the resulting mixture stirred under nitrogen 5 hrs. Concentrated in vacuo and purified by flash chromatography on silica gel (10-20% EtOAc/Hexane) to give methyl 2- (2- (tert- butoxycarbonyl) -8- hydroxy-IH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 336 (M+H) * . Step D: Methyl 2- (2- ( tert-butoxycarbonyl) -8- benzyloxy-lH, 2H, 3H, 4H, 5H-benzo [el azaperhydroepin-5- yl) acetate NaH (1.2 eq) was added to a solution of methyl 2- (2- ( tert-butoxycarbonyl) -8- hydroxy-lH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate (1 eq) in THF (0.10M) at 0°C under nitrogen. After 10 min, benzyl bromide (1.2 eq) was added and the resulting mixture allowed to warm to RT with stirring. The reaction was quenched with saturated NaHC0 3 solution and concentrated in vacuo . The residue was dissolved in ethyl acetate and washed with water. The organics were dried over Na 2 S0 4 , concentrated in vacuo, and purified by flash chromatography on silica gel (10-20% EtOAc/Hexane) to give methyl 2- (2- ( tert- butoxycarbonyl ) -8- benzyloxy-lH,2H, 3H,4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 426 (M+H) * . Step E: Methyl 2- (8-benzyloxy-lH.2H.3H, 4H, 5H- benzo [el azaperhydroepin-5-yl ) acetate Methyl 2- (2- ( tert-butoxycarbonyl) -8-benzyloxy- 1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate (1 eq) and 4.0 M HCl /dioxane (5 eq) were stirred at RT under nitrogen for 3 h. The solvents were removed by rotary evaporation and the residue dissolved in methylene chloride and washed with IN NaOH. The organics were dried over sodium sulfate and concentrated in vacuo to give methyl 2- ( 8-benzyloxy- IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin- 5-yl) acetate as a white solid. EI-MS m/z 326 (M+H) * . Step F: 2-(8-benzyloxy-2- (N- (3-(l, 2, 3, 4- tetrahydropyridino [2, 3, bl pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azaperhydroepin-5- yl) acetate Methyl 2- (8-benzyloxy-lH, 2H, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate (1 eq) was stirred under nitrogen with 20% phosgene (1.1 eq) in toluene for 10 min. The excess phosgene was removed by rotary evaporation and the crude product was dissolved in 1:1 THF/DMF (0.25 M) , followed by addition of diisopropylethylamme (1.1 eq) and 3- (1,2,3, 4-tetrahydropyridino [2 , 3 , b] pyridin-7-yl) propylamine (1.1 eq, prepared according to Duggan, M. E. WO 98/18460) . The reaction was stirred for 12 h at RT under nitrogen, concentrated in vacuo and the product was purified by flash chromatograpy (2-5% MeOH/CH 3 Cl) to give methyl 2- (8-benzyloxy-2- (N- (3- (1,2,3, 4-tetrahydropyridino [2,3 , b] pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 543 (M+H) * . Step G: Preparation of 2- (8-benzyloxy-2- (N- ( 3- (1,2,3.4-tetrahvdropyridino f2 , 3 , bl pyridin-7-yl ) propyl ) carbamoyl ) -IH, 3H, 4H, 5H-benzo [e1 azaperhydroepin- 5-yl) acetic acid 1 N NaOH solution (3 eq) was added to a solution of methyl 2- ( 8-benzyloxy-2- (N- (3- (1,2,3, 4-tetrahydro pyridino [2,3, b]pyridin-7-yl) propyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl ) acetate ( 1 eq) in methanol (0.10 M) and the resulting mixture stirred under nitrogen for 12 h. The mixture was neutralized to pH=7 with IN HCl solution and concentrated in vacuo . Purification by flash chromatography on silica gel (4-6% MeOH/CH 2 Cl 2 ) gave 2- (8-benzyloxy-2- (N- (3- (1, 2, 3 , 4-tetrahydropyridino [2,3 ,b]pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetic acid as a white solid. EI-MS m/z 529 (M+H) * ; X H-NMR (400 MHz, CDC1 3 ): δ 10.7 (br s, IH) , 7.39 (m, 6H) , 7.04 (d, J = 8.4 Hz, IH) , 6.91 (m, IH) , 6.83 ( , IH) , 6.31 (d, J = 7.2 Hz, IH) , 5.30 (s, 2H) , 5.03 (br s, 2H) , 4.32 (m, IH) , 4.21 (m, IH) , 3.67 (m, IH) , 3.47 (m, 4H) , 3.22 (m, IH) , 3.11 ( , IH) , 2.70 (m, 6H) , 1.90 (m, 3H) , 1.74 (m, 2H) , 1.63 (m, IH) . Preparation of 2- (8-phenyl-2- (N- (3- ( 1 , 2 , 3 , 4- tetrahvdropyridino [2,3 , bl pyridin-7-yl) propyl ) carbamoyl) -IH, 3H, 4H, 5H-benzo [e! azaperhydroepin-5-yl) acetic acid Step A: Methyl 2- (2- ( tert-butoxycarbonyl) -8- trifluoromethanesulfonyl-lH, 2H, 3H, 4H, 5H- benzo [el azaperhydroepin-5-yl ) acetate Triflie anhydride (1.1 eq) was added to a solution of methyl 2- (2- (tert-butoxycarbonyl) -8-hydroxy- 1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate (1 eq, prepared according to Example 72, Step C) and 2,6- lutidine (1.3.eq) in methylene chloride (0.1 M) at 0°C and the resulting mixture stirrred under nitrogen for 1 h. Water was added, the organic layer collected, washed with IN HCl solution, and dried over magnesium sulfate. Concentration in vacuo gave methyl 2- (2- (tert-butoxycarbonyl) -8-trifluoromethanesulfonyl- 1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 468 (M+H) * . Step B: Methyl 2- (2- ( (tert-butyl) oxycarbonyl) -8- phenyl-lH, 3H, 4H, 5H-benzo Tel azaperhydroepin-5- yl) acetate Toluene (0.1 M) was added to a degassed mixture of methyl 2- (2- ( (tert-butyl) oxycarbonyl) -8-trifluoro methanesulfonyl-lH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate (1 eq) phenylboronic acid (2 eq) , tetrakis (triphenylphosphine) palladium(O) (0.1 eq) , and potassium carbonate (2 eq) and the resulting mixture heated at 90°C for 12 h. Concentrated in vacuo and purified by flash chromatography on silica gel (20% EtOAc/Hexane) to give methyl 2- (2- ((tert- butyl) oxycarbonyl) -8-phenyl-IH, 3H,4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 396 (M+H) * . Step C: Methyl 2- ( 8-phenyl-lH, 2H, 3H, 4H, 5H- benzo [el azaperhydroepin-5-yl ) acetate Methyl 2- (2- (tert-butoxycarbonyl) -8-phenyl- 1H, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate (1 eq) and 4.0 M HCl/dioxane (5 eq) were stirred at RT under nitrogen for 3 h. The solvents were removed by rotary evaporation and the residue dissolved in methylene chloride and washed with IN NaOH. The organics were dried over sodium sulfate and concentrated in vacuo to give methyl 2-(8-phenyl- IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 296 (M+H) * . Step D: 2- ( 8-phenyl-2- (N- (3- (1,2, 3.4-tetrahvdro pyridino [2 , 3 , bl pyridin-7-yl) propyl ) carbamoyl) - IH, 3H, 4H, 5H-benzo [el azaperhydroepin-5-yl ) acetate Methyl 2- (8-phenyl-lH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl ) acetate (1 eq) was stirred under nitrogen with 20% phosgene (1.1 eq) in toluene for 10 min. The excess phosgene was removed by rotary evaporation and the crude product was dissolved in 1:1 THF/DMF (0.25 M) , followed by addition of diisopropylethylamme (1.1 eq) and 3- (1,2, 3,4- tetrahydropyridino [2 , 3 , b] pyridin-7-yl ) propylamine (1.1 eq, prepared according to Duggan, M. E. WO 98/18460) . The reaction was stirred for 12 h at RT under nitrogen, concentrated in vacuo and the product was purified by flash chromatograpy (2-5% MeOH/CH 3 Cl) to give methyl 2- ( 8-phenyl-2- (N- (3- ( 1, 2 , 3 , 4- tetrahydropyridino [2,3, b] pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetate as a clear oil. EI-MS m/z 513 (M+H) * . Step E: Preparation of 2- ( 8-phenyl-2- (N- (3- ( 1 , 2 , 3 , 4- tetrahydropyridino [2,3, bl pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [el azaperhydroepin-5- yl) acetic acid 1 N NaOH solution (3 eq) was added to a solution of methyl 2- (8-phenyl-2- (N- (3- (1, 2, 3, 4-tetrahydropyridino [2, 3, b]pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetate (1 eq) in methanol (0.10 M) and the resulting mixture stirred under nitrogen for 12 h. The mixture was neutralized to pH=7 with IN HCl solution and concentrated in vacuo . Purification by flash chromatography on silica gel (4-6% MeOH/CH 2 Cl 2 ) gave 2- ( 8-phenyl-2- (N- (3- (1,2,3, 4-tetrahydropyridino [2, 3 , b] pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5-yl) acetic acid as a white solid. EI-MS m/z 499 (M+H) * ; 'H-NMR (400 MHz, CDC1 3 ) : δ 10.9 (br s, IH) , 7.41 (m, 6H) , 7.09 (d, J = 8.4 Hz, IH) , 6.93 (m, IH) , 6.85 (m, IH) , 6.29 (d, J = 7.2 Hz, IH) , 5.57 (br s, IH) , 4.91 (br s, IH) , 4.32 (m, 2H) , 3.50 (m, 4H) , 3.27 (m, IH) , 3.11 (m, IH) , 2.68 (m, 6H) , 2.34 (m, IH) , 1.90 (m, 4H) , 1.74 (m, IH) , 1.42 (m, IH) . Preparation of 2- (2- N- 3 - (2-amino-5H-l , 3-thiazol-4- yl) propyl 1 carbamoyl) -IH, 3H, 4H, 5H-benzo [el azepin-5- yl) acetic acid Step A: Preparation of methyl 6-bromo-5-oxohexanoate Ethyl 4-acetylbutyrate was dissolved in MeOH (0.5M) and cooled to 0°C . Bromine (l.Oeq) was added dropwise and the mixture was stirred at room temperature for 18 hrs . The solvent was removed in vacuo and the residue was dissolved in ether, washed with water, saturated sodium bicarbonate, brine, dried over sodium sulfate. The solvent was removed in vacuo and the residue was purified by flash chromatograpy (7% EtOAc/Hexanes) . EI-MS m/z 224 (M+H) * . Step B: Preparation of Methyl 4- (2-amino-3H-l , 3- thiazol-4-yl ) butanoate Methyl 6-bromo-5-oxohexanoate and thiourea (1.2 eq) in ethanol (0.2M solution) were refluxed for 18 hrs. The reaction was cooled to room temperature, diluted with ethyl acetate, washed with water and brine. The organic layer was dried over sodium sulfate, concentrated in vacuo and the residue was purified by flash chromatography (100% ethyl acetate) . EI-MS m/z 201 (M+H) * . Step C: Preparation of 4-((2-tert- butoxy) carbonylamino) -1 , 3-thiazol-4-yl) butanoic acid Methyl 4- (2-amino-3H-l, 3-thiazol-4-yl) butanoate was dissolved in methylene chloride followed by the addition of di-ter-butyl dicarbonate (l.leq) and a catalytic amount of 4- (dimethylamino) pyridine (DMAP) . The resulting mixture was refluxed until the starting material was consumed, concentrated in vacuo and the residue was purified by flash chromatography (60% Hexanes/EtOAc) . EI-MS m/z 401 (M+H) * . The ester was dissolved in ethanol and IN NaOH was added. The reaction was stirred for 18 hrs. Followed by addition of IN HCl. The mixture was concentrated in vacuo . EI-MS m/z 285 (M-H) " . Step D: Methyl 2- (2- (N- ( 3- (2-pyridylamino) prop-1-yl) carbamoyl ) -IH, 3H, 4H-5H-benzo [el azapin-5-yl ) acetate Methyl 2- (IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate Hydrochloride was dissolved in methylene chloride and washed with IN NaOH. The organic layer was separated, dried over sodium sulfate and concentrated by rotary evaporation. A solution of 4- ( (2-tert-butoxy) carbonylamino) -1, 3-thiazol-4-yl) butanoic acid, triethylamine (2eq) in toluene (0.2M solution) and DPPA (1.5eq) was refluxed for 2h, then methyl 2- (IH, 2H, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate was added. The reaction mixture was refluxed overnight, brought to room temperature, concentrated and extracted with dichloromethane and water (1:1). The organic layers were combined, dried over magnesium sulfate and concentrated by high vacuum. The resulting residue was purified by flash chromatography ( 10%MeOH/CH 2 Cl 2 ) . EI-MS m/z 503 (M+H) * . Step E: 2- (2-(N- [3- (2-amino-5H-l , 3-thiazol- 4yl) propyl! carbamoyl} -IH, 3H, 4H, 5H-benzo fe! azepin-5- vD acetic acid 2 - ( 2 - {N- [ 3 - ( 2 -amino- 5H- l , 3 - thiazol-4- yl) propyl] carbamoyl} -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl) acetic acid was prepared from the saponification of methyl 2- (2- (N- (3- (2-pyridylamino) prop-1-yl) carbamoyl) -IH, 3H, 4H-5H-benzo [e] azapin-5-yl) acetate in ethanol (60mL) and IN NaOH (20mL) . The mixture was stirred overnight at room temperature, acidified with IN HCl, concentrated and the residue was extracted with dichloromethane (CH 2 C1 2 ) . The organic solvent was concentrated and the residue was dissolved in 4. OM HCl/dioxane and stirred at room temperature overnight. The mixture was concentrated by high vacuum and the residue was redissolved in acetonitrile to afford the desired product. EI-MS m/z 389 (M+H) * . Example 75 Preparation of 2- (2- (N- (4- (4 , 5-dihvdroimidazo-2- yl)aminobut-l-yl) carbamoyl) -IH, 3H.4H-5H- benzo [el azapin-5-yl) acetic acid Step A: Methyl 2- ( 2- (N- ( 4-tertbutoxycarbonylaminobut- 1-yl) carbamoyl) -IH, 3H, 4H-5H-benzo [el azapin-5- yl) acetate Methyl 2- (1H,2H, 3H,4H, 5H-benzo [e] azaperhydroepin-5- yl) acetate Hydrochloride was dissolved in methylene chloride and washed with IN sodium hydroxide. The organic layer was separated, dried over sodium sulfate and concentrated by rotary evaporation. The residue stirred under nitrogen with 20% phosgene in toluene (O.IM) for lOmins. After stirring, the reaction was concentrated in vacuo and the residue was dissolved in tetrahydrofuran (O.IM), followed by addition of diisopropylethylamme (1.5 eq) and 4- tertbutoxycarbamoyl but-l-yl amine(1.2 eq) . The reaction was stirred at 60°C for 1 h under nitrogen, cooled to room temperature and diluted with ethyl acetate. The mixture was washed with saturated sodium bicarbonate and the organic phase was dried over sodium sulfate and concentrated in vacuo . The product was purified by flash chromatograpy (EtOAc/Hexane 1:1 to 1:0). EI-MS m/z 434 (M+H) * Step B: Methyl 2- (2- (N- (4-aminobut-l-yl) carbamoyl) - IH, 3H, 4H-5H-benzo [el azapin-5-yl) acetate Methyl 2- (2- (N- (4-tertbutoxycarbonylaminobut-l-yl) carbamoyl ) -IH, 3H, 4H-5H-benzo [e] azapin-5-yl ) acetate was stirred in HCl in ethyl acetate (1.17M, 20 mL) at room temperature for 12h. The solvent was removed under vacuum and the residue was trituated with ether. The product was diluted with methylene chloride and extracted with sodium hydroxide (0.5M). The organic phase was concentrated in vacuo and azeotroped with toluene to yield the product as a white solid. EI-MS m/z 334 (M+H) * Step C: 2- (2- (N- (4- (4, 5-dihvdroimidazo-2-yl) aminobut- 1-yl) carbamoyl) -IH, 3H, 4H-5H-benzo Tel azapin-5-yl) acetic acid A solution of methyl 2- (2- (N- (4-aminobut-l-yl ) carbamoyl) -IH, 3H, 4H-5H-benzo [e] azapin-5-yl) acetate, 4, 5-hihydroimidazo-2-yl methyl sulfide hydrogen iodide (2eq), and sodium bicarbonate (200 mg) in dioxane/water (3ml/2ml) was heated at 100°C for 24 h. The mixture was cooled to room temperature and the product was purified by preparative HPLC (18 mg) . EI- MS m/z 388 (M+H) * ; 'H-NMR (400 MHz, MeOH-d4): δ 7.34 (d, J=7.0 Hz, IH) , 7.28-7.20 (m, 3H) , 4.60 (q, J=15.0 Hz, 2H) , 3.7-3.55 (m, 6H) , 3.36 (m, IH) , 3.22-3.17 (m, 4H) , 3.02 (t, J= Hz, IH) , 2.89-2.74 (m, 2H) , 2.10- 2.04 (m, IH) , 1.68-1.66 (m, IH) , 1.55-1.52 (m, 4H) . Example 76 Preparation of 2- (2- (N- (4- (2-propylcarbamoyl) aminobut- 1-yl) carbamoyl) -IH, 3H, 4H-5H-benzo [el azapin-5-yl) acetic acid Step A: Methyl 2- (2- (N- (4-aminobut-l-yl) carbamoyl) - IH, 3H, 4H-5H-benzo [el azapin-5-yl) acetate Methyl 2- (2- (N- (4-aminobut-l-yl) carbamoyl) -IH, 3H, 4H- 5H-benzo [e] azapin-5-yl) acetate was prepared according to the procedure of example 75. Step B: 2- ( 2- (N- ( 4- ( 2-propylcarbamoyl ) aminobut-1-yl) carbamoyl) -IH, 3H, 4H-5H-benzo [el azapin-5-yl) acetic acid A solution of methyl 2- (2- (N- (4-aminobut-l-yl) carbamoyl) -IH, 3H, 4H-5H-benzo [e] azapin-5-yl) acetate and 2 -propyl isocyanate (leq) in ethyl acetate (2 mL) was heated at 60°C for 48 hrs. The solvent was removed in vacuo and the residue was dissolved in methanol (O.IM) and IN sodium hydroxide (3eq). The mixture was heated at 60°C for 24 hrs. The product was purified by preparative HPLC as a white solid (TFA salt, 55.5 mg, 59%): EI-MS m/z 405 (M+H); 'H-NMR (400 MHz, MeOH-d4): 7.29-7.14 (m, 4H) , 4.54 (q, J=15.0 Hz, 2H) , 3.79 (m, IH) , 3.66 (m, IH) , 3.54 (m, 2H) , 3.15-3.06 (m, 4H) , 2.84-2.79 (m, IH) , 2.74-2.68 (m, IH) , 2.05-2.00 (m, IH) , 1.62-1.58 (m, IH) , 1.40-1.38 (m, 4H) , 1.1 (d, J=6.8 Hz, 6H) . Example 77 Preparation of Methyl 2- (8-amino-2- [ ( tert- butyl) oxycarbonyl! -IH, 3H, 4H, 5H-benzo [el azepin-5- vDacetate Step A: (2-Bromo-5-nitrophenyl)methan-l-ol To a stirring solution of 2-bromo-5-nitrobenzoic acid (1 eq) in tetrahydrofuran (0.4 M) at 0°C under nitrogen was added BH 3 /THF (1 M) (1.5 eq) . The reaction mixture was stirred at 70 °C for 1 hr and quenched with methanol. The reaction mixture was concentrated in vacuo to afford the product. EI-MS m/z 232 (M+H) * . Step B: 2-Bromo-5-nitrobenzaldehyde To a stirring solution of (2-bromo-5-nitrophenyl) methan-1-ol (1 eq) in methylene chloride (0.1 M) at room temperature was added pyridinium chlorochromate (2 eq) . After 2 hr the reaction mixture was filtered through celite and the product was purified by flash chromatography (15% EtOAc/Hexane) . EI-MS m/z 230 (M+H) * . Step C: 3-f [ (2-bromo-5-nitrophenyl) methyl 1 amino) propan-1-ol To a stirring solution of 2-bromo-5-nitrobenzaldehyde (1 eq) in methylene chloride (O.I M) at room temperature was added 3-amino-l-propanol (2 eq) . After stirring for 4 hr, sodium triacetoxyborohydride (2 eq) and acetic acid (5 eq) was added. The reaction mixture was stirred for 3 hr and carefully quenched with methanol. The organic phase was washed with saturated sodium bicarbonate and brine. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated in vacuo and purified by flash chromatography (10%EtOAc/Hexane) . EI-MS m/z 289 (M+H) * . Step D: ( tert-Butoxy) -N- [ ( 2-bromo-5- nitrophenyl ) methyl 1 -N- ( 3 -hydroxypropyl ) carboxamide To a stirring solution of 3- ( [ (2-bromo-5-nitrophenyl) methyl] amino}propan-l-ol (1 eq) in tetrahydrofuran (0.07 M) and saturated sodium bicarbonate (20 eq) at room temperature was added di-tert-butyl dicarbonate (2 eq) . After stirring for 4 hr, the solvent was removed by rotary evaporation and the residue was extracted with ethyl acetate. The organic phase was separated, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (10%EtOAc/Hexane) . EI-MS m/z 389 (M+H) * . Step E: ( tert-Butoxy) -N- f (2-bromo-5- nitrophenyl) ethyl! -N- (3-oxopropyl) carboxamide To a stirring solution of (tert-butoxy) -N- [ (2-bromo-5- nitrophenyl) methyl] -N- (3-hydroxypropyl) carboxamide (1 eq) in methylene chloride (0.1 M) at room temperature was added Dess-Martin reagent (1.2 eq) . After stirring for 1.5 hr, the reaction mixture was quenched with ether, saturated sodium bicarbonate, and followed by the addition of solid sodium thiosulfate. The organic phase was separated, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford product. EI-MS m/z 387 (M+H) * . Step F: Methyl (2E) -5- (( ert-butoxy) -N- [ (2-bromo-5- nitrophenyl) methyl! carbonylamino)pent-2-enoate To a stirring solution of ( tert-butoxy) -N- [( 2-bromo-5- nitrophenyl) methyl] -N- (3-oxopropyl) carboxamide (1 eq) in 200 ml of tetrahydrofuran (0.06 M) at room temperature was added methyl ( triphenylphosphoranylidene) acetate (1.5 eq) . The reaction mixture was stirred at 80 °C for 2 hr and the reaction solvent was removed by rotary evaporation. The residue was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic phase was separated, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (20%EtOAc/Hexane) . EI-MS m/z : 443 (M+H) * . Step G: Methyl (2E) -5- (N- f (3-amino-6-bromophenyl) methyl! ( tert-butoxy) carbonylamino) ent-2-enoate To a stirring solution of methyl (2E) -5-{ (tert- butoxy) -N- [ ( 2 -bromo-5-nitrophenyl) methyl] carbonyl amino}pent-2-enoate (1 eq) in 20 ml of N,N- dimethylformamide (0.1 M) at room temperature was added tin (II) chloride dihydrate (10 eq) . After stirring for 3 hr, the solvent was removed by rotary evaporation. The residue was partitioned between ethyl acetate and saturated sodium bicarbonate. The mixture was filtered through celite. The organic phase was separated, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (20% EtOAc/Hexane). EI-MS m/z 413 (M+H) * . Step H: Methyl 2- { 8-amino-2- [( tert-butyl) oxycarbonyl! - IH, 3H, 4H-benzo [el azepin-5-ylidene}acetate To a stirring solution of methyl (2E) -5- (N- [ ( 3-amino- 6-bromophenyl ) methyl] ( tert-butoxy) carbonylamino}pent- 2-enoate (1 eq) in toluene (0.08 M) at room temperature was added tetrakis ( triphenylphosphine) palladium(0.03 eq) and triethylamine (3 eq) . The reaction mixture was stirred at 100 °C for 18 hr and filtered through celite. The reaction solvent was removed by rotary evaporation. The residue was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic phase was separated, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (30% EtOAc/Hexane) . EI-MS m/z 333 (M+H) * . Step I: Methyl 2- ( 8-amino-2- f ( tert-butyl) oxycarbonyl! - IH, 3H, 4H, 5H-benzo [el azepin-5-yl} acetate To a stirring solution of methyl 2- (8-amino-2- [ (tert- butyl) oxycarbonyl] -IH, 3H, 4H-benzo [e] azepin-5- ylidene}acetate in 25 ml of ethanol at room temperature was added 10% Pd/C (0.01M) . The reaction was stirred under hydrogenation conditions at ballon pressure. After stirring for 4 hr, the reaction mixture was filtered through celite. The reaction solvent was removed by rotary evaporation. The residue was purified by flash chromatography (50%EtOAc/Hexane) . EI-MS m/z 335 (M+H) * . Example 78 Preparation of 2- ( 8-Chloro-2- [N- (3- ( 1 , 2 , 3 , 4- tetrahydropyridino [2 , 3 -b] pyridin-7 -yl) ropyl) carbamoyll -IH, 3H, 4H, 5H-benzo [el azepin-5-yl) acetic acid Step A: Methyl 2- (2- [ (tert-butyl) oxycarbonyl! -8- chloro-lH, 3H, 4H, 5H-benzo [el azepin-5-yl}acetate To a stirring solution of copper (II) chloride (1.2 eq) in dry acetonitrile (0.3 M) was added tert-butyl nitrite (1.5 eq) through syringe at room temperature under nitrogen. The resulting dark green suspension was then heated at 65°C for 15 min. Methyl 2-{8-amino- 2- [ (tert-butyl) oxycarbonyl] -IH, 3H,4H, 5H- benzo [e] azepin-5-yl}acetate (1 eq) in acetonitrile (0.13 M) was added slowly for 5 min. The resulting black solution was heated at 65°C for 1 hr . The reaction mixture was diluted with methylene chloride and aqueous ammonium hydroxide. The organic phase was separated, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (30% EtOAc/Hexane) . EI-MS m/z 353 (M+H) * .- Step B: Methyl 2- ( 8-chloro-2- fN- (3- ( 1 , 2 , 3 , 4- tetrahvdropyridino [2 , 3-blpyridin-7-yl)propyl) carbamoyl! -IH.3H, 4H, 5H-benzo [el azepin-5-yl}acetate A solution of methyl 2- {2- [ (tert-butyl) oxycarbonyl] -8- chloro-lH, 3H, 4H, 5H-benzo[e]azepin-5-yl}acetate (1 eq) in 1.17M of HCl/ethyl acetate (30 eq) was stirred at room temperature for 18 hr . The reaction mixture was concentrated and dried under vacuum oven. The resulting residue was dissolved in methylene chloride (0.15 M) and followed by the addition of phosgene/toluene (20 %) (10 eq) under nitrogen. After stirring for 1 hr, the solvent was removed by rotary evaporation. The residue was dissolved in 1 ml of N,N- dimethylformamide (0.07 M) , followed by the addition of 3- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3-b] pyridin-7- yDpropylamine (2 eq) and N, N-diisopropylethylamine (10 eq) . The reaction mixture was heated at 50 °C for 2 hr . The reaction solvent was removed by rotary evaporation and the residue was purified by flash chromatography ( 5%methanol /methylene chloride. EI-MS m/z 471 (M+H) * . Step C: 2-(8-Chloro-2- TN- (3- (1,2, 3, 4-tetrahvdro pyridino [2 , 3-bl pyridin-7-yl) propyl) carbamoyll - IH, 3H, 4H, 5H-benzo [el azepin-5-yl) acetic acid To a stirring solution of methyl 2- {8-chloro-2- [N- ( 3- (1,2,3, 4-tetrahydropyridino [2, 3-b]pyridin-7- yl) ropyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl}acetate (1 eq) in tetrahydrofuran (0.05 M) and water (0.05 M) was added lithium hydroxide monohydrate (1.5 eq) . The reaction mixture was stirred at room temperature for 10 h. 1 M of hydrogen chloride (1.5 eq) was added and the reaction solvent was evaporated in vacuo . The residue was diluted with (5%MeOH/CH 2 Cl 2 ) and the precipitate was filtered. The filtrate was concentrated and dried under vacuum oven for 24 h to afford product. El- MS m/z 457 (M+H) * ; 1 H NMR (CD 3 OD; 400 MHz): δ 7.53 (d, J=7.3Hz, IH) , 7.39 (s, IH) , 7.18 (s, 2H) , 6.51 (d, 7.3Hz, IH) , 4.56 (s, 2H) , 3.80-3.45 (m, 5H) , 3.21 (m, 2H) , 2.80 (m, 4H) , 2.75 (m, 2H) , 2.00-1.50 (m, 6H) . Preparation of 2- { 8-Bromo-2- [N- ( 3- ( 1 , 2 , 3 , 4-tetrahydro pyridino [2 , 3-b! pyridin-7-yl) propyl ) carbamoyll - IH, 3H, 4H, 5H-benzo [el azepin-5-yl)acetic acid Step A: Methyl 2- (2- [ (tert-butyl) oxycarbonyl! -8-bromo- 1H, 3H, 4H, 5H-benzo [el azepin-5-yl} acetate To a stirring solution of copper (II) bromide (1.3) in dry acetonitrile (0.22 M) was added tert-butyl nitrite (1.8 eq) through syringe at room temperature under nitrogen. The resulting dark green suspension was then heated at 65 °C for 15 min. Methyl 2- (8-amino-2- [ (tert-butyl) oxycarbonyl] -IH, 3H, 4H, 5H-benzo [e] azepin- 5-yl}acetate (1 eq) in acetonitrile (0.1 M) was added slowly for 5 min. The resulting black solution was heated at 65 °C for 2 hr . The reaction mixture was diluted with methylene chloride and aqueous ammonium hydroxide. The organic phase was separated, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (30%EtOAc/Hexane) . EI-MS m/z 398 (M+H) * . Step B: Methyl 2- ( 8-bromo-2- [N- (3- (1 , 2 , 3 , 4-tetrahvdro pyridino [2 , 3-b!ρyridin-7-yl)propyl) carbamoyl! - IH, 3H, 4H, 5H-benzo [el azepin-5-yl} acetate Methyl 2-{8-bromo-2- [N- (3- (1, 2, 3, 4-tetrahydropyridino [2, 3-b]pyridin-7-yl) propyl) carbamoyl ]-lH,3H,4H, 5H- benzo [e] azepin-5-yl}acetate was prepared from methyl 2- {2- [ (tert-butyl) oxycarbonyl] -8-bromo-lH, 3H, 4H, 5H- benzo [e] azepin-5-yl}acetate according to the procedure of Example 34. EI-MS m/z 515 (M+H) * . Step C: 2- 8-Bromo-2- [N-(3- ( 1 , 2 , 3 , 4-tetrahvdropyridino [2 , 3 -blpyridin-7-yl) propyl) carbamoyll -IH, 3H, 4H, 5H- benzo [el azepin-5-yl)acetic acid 2- { 8-Bromo-2- [N-(3-(l,2,3,4-tetrahydropyridino [2,3- b]pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl}acetic acid was prepared from methyl 2- {8-bromo-2- [N- (3- ( 1 , 2 , 3 , 4-tetrahydropyridino [2 , 3-b] pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl}acetate according to the precedure of Example 34. EI-MS m/z 501 (M+H) * ; !H NMR (CD 3 OD; 400 MHz): δ 7.55 (m, 2H) , 7.34 (d, IH) , 7.14 (d, J=8.3Hz, IH) , 6.51 (d, J=7.3HzlH), 4.57 (s, 2H) , 3.80- 3.45 (m, 5H) , 3.21 (m, 2H) , 2.76 (m, 4H) , 2.52 (m, 2H) , 2.00-1.50 (m, 6H) . Example 80 Preparation of 2- (7.8-Dibromo-2- rN- (3- (1 , 2 , 3 , 4- tetrahvdropyridino r2 , 3-blpyridin-7-yl) propyl) carbamoyll -IH, 3H, 4H, 5H-benzo re! azepin-5-yl}acetic acid Step A: Methyl 2- (7.8-dibromo-2- rN- (3- ( 1 , 2 , 3 , 4- tetrahvdropyridino [2 , 3-b! ρyridin-7-yl) propyl) carbamoyll -IH, 3H, 4H, 5H-benzo [el azepin-5-yl}acetate During the column chromatography of methyl 2-{8-bromo- 2- [N- (3- (1, 2, 3, 4-tetrahydropyridino [2, 3-b]pyridin-7- yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl}acetate, methyl 2- (7 , 8-dibromo-2- [N- (3- (1 , 2 , 3 , 4- tetrahydropyridino [2, 3-b] pyridin-7- yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo[e] azepin-5- yDacetate was obtained. EI-MS m/z 594 (M+H) * . Step B: 2- ( 7 , 8-Dibromo-2- TN- ( 3- ( 1 , 2 , 3.4-tetrahvdro pyridino [2 , 3-bl pyridin-7-yl ) propyl ) carbamoyll - IH, 3H, 4H, 5H-benzo Tel azepin-5-yl} acetic acid 2-{7, 8-Dibromo-2- [N- (3- ( 1, 2 , 3 , 4-tetrahydropyridino [2 , 3 -b] pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl}acetic acid was prepared from methyl 2- (7, 8-dibromo-2- [N- (3- ( 1 , 2 , 3 , 4-tetrahydro pyridino [2 , 3-b] pyridin-7-yl) propyl) carbamoyl] - IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetate according to the procedure of Example 34. EI-MS m/z 580 (M+H) * ; !H NMR (CD 3 OD; 400 MHz): δ 7.67(s, IH) , 7.53(d, J=7.4Hz, 7.49(s, IH) , 6.50 (d, J=7.4Hz, IH) , 4.88 (s, 2H) , 3.45-3.80 (m, 5H) , 3.21 (m, 2H) , 2.76 (m, 4H) , 2.50 (m, 2H) , 2.00-1.50 (m, 6H) . Example 81 Preparation of 2- (8- [ (Methylsulfonyl) amino! -2- [N- (3- (1,2,3, 4-tetrahydropyridino [2 , 3-bl pyridin-7- yl) propyl) carbamoyll -IH, 3H, 4H, 5H-benzo [el azepin-5- vPacetic acid Step A: Methyl 2- (2- [ (tert-butyl) oxycarbonyl! -8- [ (methylsulfonyl) amino! -IH, 3H, 4H, 5H-benzo [el azepin-5- yllacetate To a stirring solution of methyl 2- (8-amino-2- [ (tert- butyl) oxycarbonyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl} acetate (1 eq) in methylene chloride (0.1 M) was added methanesulfonyl chloride (1.1 eq) and triethylamine (5 eq) at room temperature. After stirring for 5 hr, the reaction mixture was diluted with methylene chloride. The organic phase was washed with saturated sodium bicarbonate, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (20% EtOAc/Hexane) . EI-MS m/z 413 (M+H) * . Step B: Methyl 2- { 8- [ (methylsulfonyl) amino] -2- rN- (3- (1,2,3, 4-tetrahvdropyridino [2 , 3-bl pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [el azepin-5-yl)acetate Methyl 2- {8- [ (methylsulfonyl) amino] -2- [N- (3- (1 , 2 , 3 , 4- tetrahydropyridino [2 , 3-b] pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetate was prepared from methyl 2- (2- [ (tert-butyl) oxycarbonyl] -8- [ (methylsulfonyl) amino] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl}acetate according to the procedure of Example 34. EI-MS m/z 530 (M+H) * . Step C: 2-(8-r (Methylsulfonyl ) aminol -2- [N- ( 3- ( 1.2,3,4- tetrahydropyridino [2 , 3-bl pyridin-7-yl) ropyl) carbamoyl! -IH, 3H, 4H, 5H-benzo [el azepin-5-yl}acetic acid 2- (8- [ (Methylsulfonyl)amino]-2- [N- ( 3- (1 , 2 , 3 , 4- tetrahydropyridino [2 , 3-b] pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl)acetic acid was prepared from methyl 2- (8- [ (methylsulfonyl) amino] - 2-[N-(3-(l,2,3, 4-tetrahydropyridino [2 , 3-b]pyridin-7- yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl} acetate according to the procedure of Example 34. EI-MS m/z 516 (M+H) * ; 1-H NMR (CD 3 OD; 400 MHz): δ 7.52 (d, J=7.3Hz, IH) , 7.28 (s, IH) , 7.19 (d, J=8.2Hz, IH) , 7.05 (d, J=6.6Hz, IH) , 6.51 (d, J=14.7Hz, IH) , 4.55 (s, 2H) , 3.70-3.50 (m, 5H) , 3.21 (m, 2H) , 2.92 (s, 3H) , 2.75 (m, 4H) , 2.55 (m, 2H) , 2.00-1.60 (m, 6H) Preparation of 2- • {8- - [ (Phenylsulfonvl) amino! -2- [N- (3- (1,2,3,4-tetrahvdropyridino f2 , .3-blpvridin-7-vl)propvl) carbamoyll -IH, 3H, 4H. 5H-benzo [el azepin-5-vl}acetic acid Step A: Methvl 2- ■ (2- - [ (tert- -butvl ) oxvcarbonvl 1 -8- [ (phenvlsulfonvl) aminol -IH, ,3H, .4H, 5H-benzo fel azepin-5- vDacetate To a stirring solution of methyl 2- { 8-amino-2- [( tert- butyl) oxycarbonyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl} acetate (1 eq) in methylene chloride (0.1 M) was added benzenesulfonyl chloride (1.1 eq) and triethylamine (5 eq) at room temperature. After stirring for 5 hr, the reaction mixture was diluted with methylene chloride. The organic phase was washed with saturated sodium bicarbonate, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (20% EtOAc/Hexane) . EI-MS m/z 475 (M+H) * . Step B: Methyl 2- ( 8- \ (phenylsulfonyl) amino! -2- [N- ( 3- (1,2,3, 4-tetrahvdropyridino [2 , 3-b! pyridin-7- yl) propyl) carbamoyll -1H.3H.4H, 5H-benzo [e! azepin-5- yllacetate Methyl 2- { 8- [ (phenylsulfonyl) amino] -2- [N- (3- (1 , 2 , 3 , 4- tetrahydropyridino [2 , 3 -b]pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo[e] azepin-5-yl } acetate was prepared from methyl 2- (2- [( tert-butyl) oxycarbonyl] -8- [ (phenylsulfonyl) amino] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yljacetate according to the procedure of Example 34. EI-MS m/z 592 (M+H) * . Step C: 2-(8- [ (Phenylsulfonyl) amino! -2- fN- (3- (1,2, 3,4- tetrahvdropyridino [2 , 3-blpyridin-7-yl ) propyl) carbamoyl! -IH, 3H, 4H, 5H-benzo [el azepin-5-yl)acetic acid 2-(8-[ (Phenylsulfonyl)amino]-2- [N- (3- (1 , 2 , 3 , 4- tetrahydropyridino [2 , 3-b] pyridin-7-yl) propyl ) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetic acid was prepared from methyl 2- {8- [ (phenylsulfonyl) amino] - 2- [N- (3- (1, 2, 3, 4-tetrahydropyridino [2, 3-b] pyridin-7- yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl}acetate according to the procedure of Example 34. EI-MS m/z 578 (M+H) * ; ^-H NMR (CD 3 OD; 400 MHz): δ 7.71 (d, J=7.2Hz, 2H) , 7.51 (m, 2H) , 7.44(d, 2H) , 7.22 (s, IH) , 7.03 (d, J=8.lHz, IH) , 6.82 (d, J=6.4Hz, IH) , 6.51 (d, J=7.2Hz, IH) , 4.51 (s, 2H) , 3.50-3.65 (m, 5H) , 3.21 (m, 2H) , 2.80-2.60 (m, 4H) , 2.52 (m, 2H) , 2.00-1.50 (m, 6H) . Example 83 Preparation of 2- ( 8-Carbonylamino-2- ΪN- (3- ( 1 , 2 , 3 , 4- tetrahydropyridino [2 , 3-b! pyridin-7-yl) ropyl) carbamoyl! -IH, 3H, 4H, 5H-benzo [el azeρin-5-yl}acetic acid Ste p A: Methyl 2- (2- [ (tert-butyl ) oxycarbonyl! -8- {[ (4- nitrophenyl ) methoxy! carbonylamino) -IH, 3H, 4H, 5H- benzo [el azepin-5-yl) acetate To a stirring solution of methyl 2- (8-amino-2- [ ( tert- butyl) oxycarbonyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl) acetate (1 eq) in methylene chloride (0.1 M) was added 4-nitrobenzyl chloroformate (1.1 eq) and triethylamine (5 eq) at room temperature. After stirring for 5 hr, the reaction mixture was diluted with methylene chloride. The organic phase was washed with saturated sodium bicarbonate, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo . The residue was purified by flash chromatography (20% EtOAc/Hexane) . EI-MS m/z 514 (M+H) * . Step B: Methyl 2- ( 8- ([ (4-nitrophenyl) methoxy! carbonyl amino) -2-[N-(3-(l,2,3, 4-tetrahydropyridino [2,3- b!pyridin-7-yl) propyl) carbamoyll -IH, 3H, 4H, 5H- benzo Te! azepin-5-yl) acetate Methyl 2-(8-( [ ( 4-nitrophenyl) ethoxy] carbonylamino} -2- [N- (3- (1, 2, 3, 4-tetrahydropyridino [2, 3-b]pyridin-7- yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl) acetate was prepared from methyl 2-(2-[(tert- butyl) oxycarbonyl] -8- { [ (4-nitrophenyl) methoxy] carbonyl amino} -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl) acetate according to the procedure of Example 34. EI-MS m/z 631 (M+H) * . Step C: Methyl 2- I 8-carbonylamino-2- rN- ( 3- (1.2 , 3 , 4- tetrahvdropyridino \ 2 , 3-b1pyridin-7-yl) propyl) carbamoyll -IH, 3H, 4H, 5H-benzo fel azepin-5-yl)acetate To a stirring solution of methyl 2- (8- { [ (4-nitro phenyl) methoxy] carbonylamino} -2- [N- (3- (1 , 2 , 3 , 4- tetrahydropyridino [2 , 3-b] pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl) acetate in ethanol (0.05 M) at room temperature was added 10% Pd/C (0.10M). After stirring 4 hr, under hydrogen, at balloon pressure, the reaction mixture was filtered through celite. The reaction solvent was removed by rotary evaporation. The residue was purified by flash chromatography (50% EtOAc/Hexane) . EI-MS m/z 480 (M+H) * . Step D: 2- ( 8-Carbonylamino-2- [N- ( 3- ( 1 , 2 , 3 , 4- tetrahvdropyridino [2 , 3-blpyridin-7-yl ) propyl) carbamoyll -IH, 3H, 4H, 5H-benzo [el azepin-5-yl)acetic acid 2-{8-Carbonylamino-2- [N-(3-(l,2,3, 4-tetrahydropyridino [2, 3-b]pyridin-7-yl)propyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl}acetic acid was prepared from methyl 2- { 8-carbonylamino-2- [N- (3- ( 1 , 2 , 3 , 4- tetrahydropyridino [2 , 3-b]pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetate according to the procedure of Example 34. EI-MS m/z 466 (M+H) * ; 1 H NMR (CD 3 OD; 400 MHz): δ 7.98 (s, IH) , 7.60-7.20 (m, 4H) , 6.56 (d, J=7.3Hz, IH) , 4.60 (s, 2H) , 3.70-3.40 (m, 2H) , 3.30 (m, 2H) , 2.80-2.70 (m, 4H) , 2.63 (m, 2H) , 2.00-1.50 (m, 6H) . Example 84 Preparation of 2-f 8- (Dimethylamino) -2- TN- (3- (1.2.3.4- tetrahvdropyridino [2 , 3-bl pyridin-7-yl) propyl) carbamoyll -IH, 3H, 4H, 5H-benzo [el azepin-5-yl}acetic acid Step A: Methyl 2- ( 8- (dimethylamino) -2- [ (tert- butyl) oxycarbonyll -IH, 3H, 4H, 5H-benzo [el azepin-5- yl jacetate To a stirring solution of methyl 2- (8-amino-2- [ ( tert- butyl ) oxycarbonyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl)acetate (1 eq) in benzene (0.02 M) at room temperature was added Pd/C (10 %) (20 % weight) and HCHO (37 %) (20 eq) . After stirring for 4 hr under hydrogen, at balloon pressure , the reaction mixture was filtered through celite. The reaction solvent was removed by rotary evaporation. The residue was purified by flash chromatography (50% EtOAc/Hexane). EI-MS m/z 363 (M+H) * . Step B: Methyl 2- ( 8- (dimethylamino) -2- [N- ( 3- ( 1 , 2 , 3 , 4- tetrahydropyridino [2 , 3-bl pyridin-7-yl) propyl ) carbamoyll -IH, 3H, 4H, 5H-benzo [el azepin-5-yl} acetate Methyl 2-{8- (dimethylamino) -2- [N- (3- (1, 2, 3, 4- tetrahydropyridino [2 , 3-b] pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetate was prepared from methyl 2- { 8- (dimethylamino) -2- [ (tert- butyl) oxycarbonyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl}acetate according to the procedure of Example 34. EI-MS m/z 480 (M+H) * . Step C: 2- (8- (Dimethylamino) -2- \N- (3- (1,2.3,4- tetrahydropyridino [2 , 3-bl pyridin-7-yl) propyl) carbamoyll -IH, 3H, 4H, 5H-benzo [el azepin-5-yl}acetic acid 2-{8- (Dimethylamino) -2- [N- (3- (1, 2, 3 , 4-tetrahydro pyridino [2 , 3 -b] pyridin-7-yl) propyl) carbamoyl] - IH, 3H, 4H, 5H-benzo[e]azepin-5-yl}acetic acid was prepared from methyl 2- (8- (dimethylamino) -2- [N- ( 3- (1,2,3, 4-tetrahydropyridino [2 , 3-b] pyridin-7- yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5- yl} acetate according to the procedure of Example 34. EI-MS m/z 466 (M+H) * ; ^- NMR (CD 3 OD; 400 MHz) : δ 7.51 (d, J=7.4Hz, IH) , 7.08 (d, J=4.8Hz, IH) , 6.91 (s, IH) , 6.71 (m, IH) , 6.46 (d, J=7.4Hz, IH) , 4.51 (m, 2H) , 3.70-3.40 (m, 5H) , 3.21 (m, 2H) , 2.92 (s, 6H) , 2.80- 2.70 (m, 4H) , 2.69 (m, 2H) , 2.00-1.50 (m, 6H) . Example 85 Using the procedures of the above general description and the above examples, the following compounds were prepared. Example 86 Using the procedures of the above general description and the above examples, the compounds of Tables 1-4 (wherein OBn represents benzyloxy) can be prepared. Table 1 4- ( 2 -pyridylaminobuty1 ) C-H C-H C-Cl C-H carbamoyl 3- (1, 2, 3, 4-tetrahydro C-H C-H C-Cl C-H pyridino (2 , 3-b) pyridin-7- yl ) -propyl ) carbamoyl - (4-methyl) -2-pyridyl ; C-H C-H C-Cl C-H amino) butyl ) carbamyl Table 2 Table 3 Table 4 Example 87 Using the procedures of the above general description and the above examples, the following compounds of Table 5 can be prepared. The groups B[2]A, B[3]A, IBA(I), IBA(II), TBA(I) and TBA(III) represent the ring systems as defined above. Table 5 Example 88 Biological Studies The following assays can be used to characterize the biological activity properties of compounds of the invention. Purified integrin αyβ 3 may be obtained using the methods of Marcinkiewicz et al . (Protein Expression Purif. 8:68-74, 1996) and Pytela et al . (Meth. Enzymol. 144:475-489, 1987). Purified integrin Oyβ. may be obtained using the methods of Smith et al . (J. Biol. Chem. 265:11008-13, 1990). Purified integrin cc^ 6 may be obtained using the methods of Busk et al . (J. Biol. Chem. 267:5790-6, 1992). Primary human umbilical cord endothelial cells (HUVEC) can be used to show that the compounds of the invention inhibit cellular proliferation and/or cellular adhesion. HUVEC Proliferation Assay 1. Coat 3 NUNC polystyrene 96 well plate (VWR, 62409- 120; lids 62409-118) with vitronectin (purified internally) , fibronectin (Collaborative Biomed 40008A) or fibrinogen (Calbiochem 341578) 50 ng/well in 50 ul PBS, 1 hr @ RT. 2. Trypsinize HUVEC's: a. rinse with 5 mis PBS (no Ca, Mg) b. 2 ml trypsin, remove c. 10 ml growth medium 3. Rinse vitronectin plates lx in 200 μl PBS -/- and add 3000 cells per well in 100 ul growth medium (EBM2 (Clonetics, CC-3156) + EGM2 bullet kit (CC- 4176) ) . 4. Incubate 24 hours at 37°C to allow attachment. 5. Remove growth medium and add 100 μl growth medium + drugs (25 μM and down by five fold steps in DMSO— 0.25 % final DMSO concentration). 6. Incubate for 3 days changing media (+drugs) . 7. Remove non-adherent cells on Friday with Raindance 12 well plate washer. 8. Wash twice with 200 μl PBS (+ Mg & Ca) . 9. Tap out excess liquid. 10. Freeze @ -70°C for 30 minutes. 11. Thaw plate and add 150 μl CyQuant fluorescent dye (Molecular Probes C-7026) . 12. Read after 4 minutes @ 485λ (excitation), 530λ (emission) . HUVEC Adhesion Assay 1. Coat 2 NUNC polystyrene 96 well plates (VWR, 62409- 120; lids 62409-118) with 50 μl vitronectin (purified internally) at 50 ng/well in PBS (-Mg & Ca) , for 1 hour @ 37°C. 2. Rinse with PBS & block with 150 μl PBS/1% BSA (Sigma A8918) , 1 hour at @ 37°C. 3. Prepare drug dilutions: a. 400 fold concentrate in 100% DMSO b. 0.25% DMSO [assay] fιMl c. 10 mM & down (25 μM £ιnal & down) d. dilute 1 μl of 400 fold cone into 200 μl adhesion media e. use 50 μl/well 4. Trypsinize HUVEC ' s : a. rinse with 5 ml PBS (no Ca, Mg) b. 2 ml trypsin, remove c. 10 ml growth medium 5. Spin @ 1200 rpm for 10 minutes. 6. Rinse blocking buffer from assay plate and add 50 μl of drug dilutions. 7. Resuspend cells in adhesion media, count and add 2e4 cells/well in 50 μl (4e5/ml) . 8. Incubate 60 minutes @ 37°C. 9. Remove non-adherent cells with Raindance 12 well plate washer. 10. Wash twice with 200 μl PBS (+ Mg & Ca) 11. Tap out excess liquid. 12. Freeze @ -70°C for 30 minutes to overnite. 13. Thaw plate and add 150 μl CyQuant fluorescent dye (Molecular Probes C-7026) . 14. Read after 2-5 minutes @ 485λ (excitation), 530λ (emission) . Adhesion medium: Media 199 (which contains 36 mM CaCl 2 and 0.8 mM MgS0 4 ) , 0.5% BSA, 10 mM HEPES, 1 mM MgCl 2 , and 1 mM MnCl 2 Integrin Binding Assay Purification of Vitronectin Vitronectin was prepared from out-dated human plasma as described by Yatohgo et al . (Cell Struct. Funct. 13:281-292, 1988) with modifications. Normal human blood collected in citrate tubes was centrifuged and clotted overnight with the addition of CaCl . The clot 2 was centrifuged, filtered at 0.45 μm, and applied to a Heparin Sepharose column that was equilibrated with 10 mM NaPO 4 , 5 mM EDTA, 0.13 M NaCI pH 7.7. The column flow through was collected as a single pool, urea was added to a final concentration of 8M, and mixed overnight. The sample was then incubated with Heparin Sepharose which had been equilibrated with 10 mM NaPO 4 , 5 mM EDTA, 8 M urea pH 7.7 (buffer A) overnight. The Heparin Sepharose was separated from the liquid by centrifugation and washed once with buffer A, buffer A + 0.13 M NaCI, and buffer A + 0.13 NaCI and 10 mM BME . The vitronectin was eluted from the column with buffer A + 0.5 M NaCI. The fractions containing Vitronectin were buffer exchanged into PBS and stored at -70°C. Ruthenylation of Vitronectin and Fibrinogen Purified human vitronectin or purified human fibrinogen (Calbiochem) was dialyzed into 50 mM borate, 100 mM NaCI pH 8.0. A stock solution of ruthenium (II) tris bipyridine N-hydroxysuccinimide ester (Origen TAG * Ester, Igen Inc. Gaithersburg, MD) was freshly prepared by adding 50 μL DMSO to 150 μg of the Origen TAG-NHS ester. Fifty microliters of the Origen TAG-NHS ester was added to one fifth molar ratio of the matrix protein. After one hour incubation at 25°C, the reaction was quench by the addition of 50 μL of 2 M glycine. Unincorporated ruthenium and excess glycine were removed by dialysis into PBS, 0.05% NaN3. Protein concentrations were determined using Micro-BCA (Pierce, Rockford, IL) . Origen TAG incorporation was assessed at 455 nm (e=13,700 M _1 cm _1 ) . Vitronectin-Ru and Fibrinogen-Ru were stored at -70°C until needed. Purification of Platelet Fibrinogen Receptor ilbβ3 Twelve units of outdated platelets were washed with PBS and centrifuged at low speed to remove RBCs . The washed platelets were lysed in, 20 mM Tris-HCl pH 7.4, 140 mM NaCI, 2 mM CaCl , 1 mM pefabloc, 3% octylglucoside with gentle stirring for two hours at 4°C. The lysate was centrifuged at 100,000xg for 1 hour to pellet insoluble cellular debris. The resulting supernatant was applied to a lentil lectin (EY labs) column and washed with lysis buffer containing 1% octylglucoside (binding buffer) until a stable UV baseline was reached. Purified αllbβ3 was eluted from the column with binding buffer containing 10% dextrose. Purified αllbβ3 was stored at -70°C until needed. Purification of αvβ3 and αvβ5 Frozen placentas were thawed overnight at 4°C, cut into 1 cm sections, and washed with 50 mM Tris-HCl, 100 mM NaCI, 1 mM PMSF pH 7.5 (buffer A) . The placentas were then incubated overnight in buffer A with the addition of 3% (w/v) octyglucoside. Extracted protein was separated from whole tissue by centrifugation. The extract was then 0.45 μm filtered and NaN3 was added to a final concentration of 0.02%. The sample was then loaded on to an anti-ccvβ3 or anti-αvβ5 affinity column, washed with buffer A plus 1% (w/v) octyglucoside, and eluted with Gentle Elution Buffer * (Pierce) . The fractions containing αvβ3 or αvβ5 were exchanged into buffer A plus 1% octylglucoside and stored at -70°C. Purified αvβ3 and αvβ5 were also purchased from Chemicon International Inc. Incorporation of αvβ3 , αvβ5 , or αllbβ3 on paramagnetic beads αvβ3 , αvβ5, or αilbβ3 paramagnetic beads were prepared from 4.5μ uncoated Dynabeads * (Dynal ® , Lake Success, NY) . Uncoated Dynabeads * were washed three times in phosphate buffered saline pH 7.4 (PBS) and resuspended in 50 mM Tris-HCl, 100 mM NaCI, 1 mM MgCl , 1 mM CaCl2, and 1 mM MnCl2 pH 7.5 (Buffer A) . Purified receptor αvβ3, αvβ5 (Chemicon) , or αllbβ3 were quickly diluted in buffer A and added to the uncoated Dynabeads* at a ratio of 50 μg protein to 10 7 beads. The bead suspension was incubated with agitation overnight at 4°C . The beads were washed three times in buffer A, 0.1% bovine serum albumin (BSA) and resuspended buffer A + 3% BSA. After three hours at 4°C the beads were wash three times in Buffer A, 1% BSA, 0.05% azide and stored at -70°C until needed. Solid Phase Binding Assay All compounds were dissolved and serially diluted in 100% DMSO prior to a final dilution in assay buffer (50 mM Tris-HCl pH 7.5, 100 mM NaCI, 1 mM CaCl 2 , ImM Mg Cl 2 , lmM MnCl 2 , 1% BSA, 0.05% Tween-20) containing Vitronectin-Ru or Fibrinogen-Ru and appropriate integrin coated paramagnetic beads. The assay mixture was incubated at 25°C for two hours with agitation and subsequently read on an Origen Analyzer * (Igen Inc. Gaithersburg, MD. ) Non-specific binding was determined using 1 μM Vitronectin, 1 μM Fibrinogen or 5 mM EDTA. The data was prepared using a four-parameter fit by the Levenburg Marquardt algorithm (XLfit * ID Business Solutions.) Ki values were calculated using the equation of Cheng and Prusoff (Biochem. Pharmacology 22 :3099-3108, 1973) . The following compounds exhibit activities in the HUVEC proliferation assay and/or HUVEC adhesion assay with IC 50 values of 30 μM or less: 2- (2- (N- (3- (2-pyridylamino) propyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (4- (2 -pyridylamino) butyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (5- (2-pyridylamino) pent-1-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N-methyl-N- (4- (2-pyridylamino) but-l-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl ) acetic acid; 2- (2- (N- (4- (2-pyridylamino) -trans-cyclohexyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- ( ( (4- (2-pyridylamino) methyl )piperid-1-yl) carbonyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl ) acetic acid; 2- ( 2- (N- ( 3- (2-pyridylamino) methylphenyl ) carbamoyl ) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (4- ( (6-methyl-2 -pyridyl) amino) but-1-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (4- (pyrimidin-2-ylamino) but-1-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (3- (6-amino-2-pyridyl) prop-1-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (3- (6- ( tert-butoxycarbonylamino) -2- pyridyl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetic acid; 2-(2-(N-(3-(l,2,3, 4-tetrahydropyridino (2 , 3-b) pyridin-7- yl)prop-l-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetic acid; 2- (2- ( ( (4- (2-pyridylamino) but-1-yl) amino) sulfonyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- ( ( (3- (2-pyridylamino) prop-1-yl) amino) sulfonyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2-(2-(2-((2- (2-pyridylamino) ethyl) amino) acetyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2-(2-(2-((3- (2-pyridylamino) prop-1-yl) amino) acetyl- IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (2- ( (4- (2-pyridylamino)but-l-yl) amino) acetyl- 1H, 3H, 4H, 5H-benzo [e] azapin-5-yl-acetic acid; 2- (2- ( (N- (3- ( 2-pyridylamino) prop-1-yl) carbamoyl) methyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl ) acetic acid; 2- (2- (4- (2-pyridylamino) but-1-oxy carbonyl) - IH, 3H, 4H, 5H-benzo [e]azapin-5-yl) acetic acid; 2- (8-methoxy-2- (N- (4- (2-pyridylamino) but-l- yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetic acid; 2-(8-fluoro-2-(N-(3- ( 1 , 2 , 3 , 4-tetrahydropyridino [2 , 3,b] pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetic acid; 2- (2- ( {N- (4- (2 -pyridylamino) prop-1-yl) carbamoyl} methyl) -3-oxo-lH, 4H, 5H-benzo (e) azepin-5-yl) acetic acid; 2- (3- ( {N- (4- (2 -pyridylamino) but-1-yl) carbamoyl} methyl) -IH, 2H, 4H, 5H-benzo [d] azepin-1-yl) acetic acid; 2-(3-{ [N-(3- (1,2, 3 , 4-tetrahydropyridino [2 , 3-b] pyridin- 7-y1 ) propyl ) carbamoyl ] methyl } -IH, 2H, 4H, 5H- benzo [d] azepinyl) acetic acid; 2- (3-{N- (5- (2-pyridylamino) pent-1-yl) carbamoyl} - IH, 2H, 4H, 5H-benzo [d] azepinyl) acetic acid; 2-{3-(N-(3-(l,2,3, 4-tetrahydropyridino [2 , 3-b] pyridin-7- yl)propyl) carbamoyl) -IH, 2H, 4H, 5H-benzo [d] azepin-1- yl}acetic acid; 2- {3- (7- (2-pyridylamino) heptanoyl) -IH, 2H, 4H, 5H- benzo [d] azepin-l-yl}acetic acid; 2-(2-(N-(3-(l,2,3, 4-tetrahydropyridino (2 , 3-b) pyridin-7- yl ) propyl ) carbamoyl ) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) ropanoic acid; 2-{2- [N- (methylethyl) -N- (2- (1,2, 3 , 4-tetrahydropyridino [2, 3-b]pyridin-7-yl) ethyl) carbamoyl] -1H,3H,4H, 5H- benzo [e] azepin-5-yl] acetic acid; 2- (2-aza-2-cyano-l ( (1,2,3, 4-tetrahydropyridino [2 , 3- b] pyridin-7-yl) propyl) amino) vinyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetic acid; 2-(2-(((2-(l,2, 3, 4-tetrahydropyridino (2, 3-b) pyridin-7- yl) ethyl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetic acid; 3-(2-(N-(2-(l,2,3, 4-tetrahydropyridino (2, 3-b) pyridin-7- yl) ethyl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) propanoic acid; 2- (2- (N- (3- (2-pyridylamino) propyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- ( (5R) -2- (N- (3- (1, 2, 3, 4-tetrahydropyridino (2, 3- b)pyridin-7-yl)prop-l-yl) carbamoyl) -1H,3H,4H, 5H- benzo [e] azapin-5-yl) acetic acid; 2- ( (5R) -2- (N- (3- ( 1 , 2 , 3 , 4-tetrahydropyridino (2 , 3- b)ρyridin-7-yl) ethyl ) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetic acid; 2-((5S)-2-(N-(3-(l,2,3,4-tetrahydropyridino (2,3- b)pyridin-7-yl) ethyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetic acid; 2-((5S)-2-(4-(l,2,3, 4-tetrahydropyridino (2 , 3-b) pyridin- 7-yl) butanoyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetic acid; 2- [2- (4- ( 1,2, 3, 4-tetrahydropyridino [2, 3-b] pyridin-7- yl) butanoyl) -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl] acetic acid; 2-{2- [N- (2- (1, 2, 3, 4-tetrahydropyridino [2, 3-b] pyridin-7- yl) ethyl) carbamoyl] -4H, 5H, 10H-benzo[d] imidazolo [1, 2- a] azepin-5-yl}acetic acid; 2-{2- [N- (methylethyl) -N- (2- ( 1 , 2 , 3 , 4-tetrahydropyridino [2, 3-b] pyridin-7-yl) ethyl) carbamoyl] -4H, 5H, 10H- benzo [d] imidazolo [1, 2-a] azepin-5-yl}acetic acid; 2-{2- [N- (methylethyl) -N- (1,2,3, 4tetrahydropyridino [2 , 3- b] pyridine-6-ylmethyl) carbamoyl] -4H, 5H, 10H- benzo [d] imidazolo [1, 2-a] azepin-5-yl} acetic acid; 2-{2- [N- (1, 2, 3, 4-tetrahydropyridino [2, 3-b] pyridin-6- ylmethyl) carbamoyl] -4H, 5H, lOH-benzo [d] imidazolo [1,2- a] azepin-5-yl)acetic acid; 2- (2- {N-methyl-N- [3- (2-pyridylamino) propyl] carbamoyl) - 4H, 5H, lOH-benzo [d] imidazolo [1, 2-a] azepin-5-yl) acetic acid; 2- (8-methoxy-2- (N-(3-(l,2,3, 4-tetrahydropyridino [2, 3, b] pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetic acid; 2- ( 8-benzyloxy-2- (N- ( 3- ( 1 , 2 , 3 , 4-tetrahydropyridino [2, 3, b] pyridin-7-yl) propyl) carbamoyl) -IH, 3H,4H, 5H- benzo [e] azaperhydroepin-5-yl) acetic acid; 2- (8-phenyl-2- (N- ( 3- ( 1 , 2 , 3 , 4-tetrahydropyridino [2, 3, b] pyridin-7-yl) propyl) carbamoyl) -1H,3H,4H, 5H- benzo [e] azaperhydroepin-5-yl) acetic acid; 2- (2- (N- (4- (4, 5-dihydroimidazo-2-yl) aminobut-1-yl) carbamoyl) -IH, 3H, 4H-5H-benzo [e] azapin-5-yl) acetic acid; 2-{8-Chloro-2- [N- (3- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3- b] pyridin-7-yl) propyl) carbamoyl] -1H,3H,4H,5H- benzo [e] azepin-5-yl}acetic acid; 2-{8-Bromo-2- [N- (3- (1, 2 , 3 , 4-tetrahydropyridino [2 , 3- b]pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl}acetic acid; 2-{7, 8-Dibromo-2- [N- (3- (1,2, 3 , 4-tetrahydropyridino [2 , 3- b]pyridin-7-yl)propyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl} acetic acid; 2-{8- [ (Methylsulfonyl) amino] -2- [N- (3- (1,2, 3,4- tetrahydropyridino [2 , 3 -b] pyridin-7 -yl ) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetic acid; 2-{8-[ (Phenylsulfonyl)amino]-2-[N- (3- (1,2, 3, 4- tetrahydropyridino [2 , 3-b] pyridin-7-yl) propyl ) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetic acid; 2-{8-Carbonylamino-2- [N-(3-(l,2,3, 4-tetrahydropyridino [2 , 3-b] pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl} acetic acid; 2- (8- (Dimethylamino) -2- [N-(3- ( 1 , 2 , 3 , 4-tetrahydro pyridino [2 , 3 -b] pyridin-7-yl) propyl) carbamoyl] - IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetic acid; 2- (2- (N- (3- (6- (methylamino) -2-pyridyl) propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2-(2-(N-(2-(l,2,3, 4-tetrahydropyridino (2, 3-b) pyridin-7- yl) ethyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e]azapin-5- yl) acetic acid; 2- (3-(N- (2- ( 1,2, 3, 4-tetrahydropyridino (2, 3-b) pyridin-7- yl) propyl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetic acid; 3-(2-(N-(2-(l,2,3, 4-tetrahydropyridino (2, 3-b) pyridin-7- yl) ethyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) propanoic acid; 3- (2- (N- (3- (1,2,3, 4-tetrahydropyridino (2, 3-b)pyridin-7- yl) propyl) carbamoyl-IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) propanoic acid; 3-(2-(N-(3-(l,2,3, 4-tetrahydropyridino (2 , 3-b) pyridin-7- yl ) propyl ) amino) sulfonyl ) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) propanoic acid; 2- [3- ( {N- [5- (2-pyridylamino) pentyl] carbamoyl}methyl) - IH, 2H, 4H, 5H-benzo [d] azepinyl] acetic acid; 2-[3-(2-{[4-(2 -pyridylamino) butyl ] amino} acetyl ) - IH, 2H, 4H, 5H-benzo [d] azepinyl] acetic acid; 2- (2-{N- [3- (5-methyl-l, 2, 3, 4-tetrahydropyridino [2, 3- b] pyridin-7-yl) propyl] carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl) acetic acid; 2- (3-{N- (2- (2-pyridylamino) ethyl) carbamoyl} - IH, 2H, 4H, 5H-benzo [d] azepinyl) acetic acid; 2-{3-(N-(2-(l,2, 3, 4-tetrahydropyridino [2, 3-b] pyridin-7- yl) ethyl) carbamoyl) -IH, 2H, 4H, 5H-benzo [d] azepin-1- yl}acetic acid; 2- (8-fluoro-2- (N- (2- (1,2, 3 , 4-tetrahydropyridino (2 , 3- b)pyridin-7-yl) ethyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azapin- 5-yl) acetic acid; 2- [2- (N-{4-[ (4-methyl-2-pyridyl) amino] butyl} carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azepin-5-yl] acetic acid; and 2- {2- [N- (4- { [benzylamino] carbonylamino}butyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl} acetic acid. Compounds of the invention may be shown to inhibit vitronectin a^ 3 binding in vitronectin a^ 3 binding assays and to inhibit osteoclasts mediated bone resorption in bone resorption pit assays as described in Woo et al . (Eur. J. Pharm. 300:131-5, 1996), EP 528587, WO 97/01540, WO 98/18461 and WO 99/30713 (each of which is incorporated herein by reference in its entirety) . Compounds of the invention may be shown to inhibit smooth muscle cell migration in human aortic smooth muscle cell migration assay described in WO 97/01540 and Liaw et al . , J. Clin. Invest. 95:713-724, 1995 (each of which is incorporated herein by reference in its entirety) . Compounds of the invention may be shown to inhibit vitronectin α v β 5 and/or θt v β 6 binding in vitronectin θt v β 5 and GCyβ j binding assays as described in WO 99/30709 and WO 99/30713 (each of which are incorporated herein by reference in its entirety) . Compounds of the invention may be shown to inhibit α^ integrin binding in aβ 1 integrin binding assays as described in WO 99/58139 (incorporated herein by reference in its entirety) . Compounds of the invention may be shown to have anti-bone resorption properties in a rat animal models described in WO 97/01540 and Wronski et al . , Cells and Mat. 1991:69-74 (each of which is incorporated herein by reference in its entirety) . Compounds of the invention may be shown to have anti-angiogenic properties in an animal model described in Passaniti et al., Lab. Invest. 67:519-528, 1992 (incorporated herein by reference in its entirety) . Compounds of the invention may be shown to inhibit restenosis in a pig restenosis model described in Schwartz et al . , J. Am. College of Cardiology 19:267-274, 1992 (incorporated herein by reference in its entirety) . Compounds of the invention may be shown to inhibit retinopathy in a mouse retinopathy model described in Smith et al . , Invest. Ophthal. & Vis. Sci. 35:101-111, 1994 (incorporated herein by reference in its entirety) . The foregoing is merely illustrative of the invention and is not intended to limit the invention to the disclosed compounds. Variations and changes which are obvious to one skilled in the art are intended to be within the scope and nature of the invention which are defined in the appended claims. From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.

Claims: WHAT IS CLAIMED IS: 1. A compound of the formula E-B- (Alk) p -Q- (Alk) q -A-G or a pharmaceutically acceptable salt thereof, wherein p and q are each independently 0 or 1; each Alk is independently an alkyl radical; A and Q each independently represent a bond, -C(X)-, -S(0) c -, -S-, -0-, -N(R -, -C(Y)-N(R 1 )-, -N (R x ) -C (Y) - , -S(0) t -N(R 1 )-, -N(R 1 )-S(0) t -, -N(R 1 )-C(Y)-N(R 1 )- or -N(R -S(0) c -N(R 1 ) -, or a radical of cycloalkyl, aryl, heterocyclyl or heteroaryl each of which is optionally substituted by 1-3 radicals of R 2 ; and B represents a bond, -C(Y)-, -S(0) t -, -S-, -0-, -N(R -, -C(Y)-N(R 1 )-, -N(R 1 )-C(Y)-, -S(0) t -N(R 1 )-, -N (R -S (0) t - , -N(R 3 ) -C(Y) -N(R 1 )- or -N(R -S (0) t -N(R 1 ) - , or a radical of cycloalkyl, aryl, heterocyclyl or heteroaryl each of which is optionally substituted by 1-3 radicals of R 2 ; provided the total number of atoms that directly connect E to G via the shortest sequence is 3-12; each X is independently 0 or S; and each Y is independently 0, S, N(R or N(CN) ; and each t is independently 1 or 2; each R : is independently a hydrogen or alkyl radical; radicals of R 2 are each independently a halo, alkyl, alkoxy, alkylthio, haloalkyl, haloalkoxy, hydroxy, carboxy, cyano, azido, amidino, guanidino, nitro, amino, alkylamino or dialkylamino radical or two adjacent R 2 radicals represent a methylenedioxy, ethylenedioxy or propylenedioxy radical; E represents -R 3 , -NH-R 3 , -NH-C(Y)-R 3 , -C(Y)-NH-R 3 , -NH- S(0) t -R 3 , -S(0) c -NH-R 3 , -NH-C(Y)-NH-R 3 , -NH-C (Y) -0-R 3 , -NH-S(0) t -NH-R 3 , -NH-alkyl-C(Y)-R 3 , -NH-alkyl-S (0) C -R 3 , -NH-alkyl-C(Y) -NH-R 3 or -NH-alkyl-S (0) t -NH-R, radical; R 3 is a radical of hydrogen, alkyl, aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocyclyl or heterocyclyl-alkyl , wherein the aryl, heteroaryl and heterocyclyl radicals are optionally substituted by 1-3 radicals of R 2 ; G is a radical of formula W x is C-R 15 or N ; W 2 is C-R 16 or N; W 3 is C-R 17 or N; and W 4 is C-R 18 or N; or W x and W 2 , W 2 and W 3 , or W 3 and W 4 taken together represent a fused phenyl , fused C 5 -C 7 cycloalkyl , fused heteroaryl of 5-6 ring members or fused heterocyclyl of 5-7 ring members , each of which is optionally substituted by 1-3 radicals of R 2 ; provided not more than 2 of W 3 , W 2 , W 3 or W 4 represent N; radicals of R 15 , R , R 17 and R 18 are each independently a radical of hydrogen, halo, hydroxy, carboxy, cyano, azido, amidino, nitro, amino, -R 9 , -C(Y)-R 9 , -S(0) t -R 9 , -S-R 9 , -0-R 9 , -N(R -R 9 , -C(Y)-N(R 1 )-R 9 , -N (R -C (Y) -H, -N(R 3 )-C(Y)-R 9 , -0-C(Y)-N(R 1 )-R 9 , -N (R -C (Y) -0-R, , -S(0) c -N(R 1 )-R 9 , -N(R 1 )-S(0) c -R 9 , -N (R -C (Y) -N (R -R. or -N(R -S(0) t -N(R 1 ) -R 9 , or R 15 and R 16 , R 16 and R 17 , or R 17 and R 18 taken together represent a methylenedioxy, ethylenedioxy or propylenedioxy radical; provided the combined total number of aryl, cycloalkyl, heteroaryl and heterocyclyl radicals in R 15 , R 16 , R 17 and R 18 is 0-1; wherein each R 9 is independently a radical of alkyl, haloalkyl, arylalkyl, heteroarylalkyl, heterocyclylalkyl , aryl, cycloalkyl, heteroaryl or heterocyclyl, wherein the aryl, cycloalkyl, heteroaryl and heterocyclyl radicals are optionally substituted by 1-3 radicals of R 2 ; X 2 , X 3 and X 6 are each independently a -C(X)-, -S(0) t -, -CHR 6 - or -CHR 7 - radical; Z 1 is N or C-R 6 ; R 10 and R 12 are each independently an -R 6 , -R 7 or -0R 7 radical ; wherein each R 6 is independently a hydrogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, halo or cyano radical; and each R 7 is independently a radical of aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocyclyl or heterocyclyl-alkyl, each of which is optionally substituted by 1-3 radicals of R 2 ; provided the combined total number of aryl, heteroaryl and heterocyclyl radicals in X 2 , X 3 , X 6 , R 10 and R 12 is 0-2; and R 4 is an alkyl radical substituted by a radical of carboxy, tetrazolyl, -C0 2 R 8 , - -C (0) -NH-S (0) t -R 8 , -C(0)-NH- C(0)-R B or -C(0)-NH-R 8 , and optionally substituted by a radical of aryl, heteroaryl or heterocyclyl, each of which is optionally substituted by 1-3 radicals of R 2 ; wherein R 8 is an alkyl radical optionally substituted by 1-2 radicals of hydroxy, carboxy, amino, aryl or heteroaryl, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of R 2 . 2. The compound of Claim 1 or a pharmaceutically acceptable salt thereof, wherein each Alk is independently a C j -C^ alkyl radical; A and Q each independently represent a bond, -C(X)-, -S(0) c -, -S-, -0-, -N R -, -C(Y)-N(R 1 )-, -N (R 3 ) -C (Y) - , -S(0) t -N(R 1 )-, -N(R 1 )-S(0) t -, -N (R -C (Y) -N (R - or - tR,) -S(0) t -N(R 1 ) -, or a radical of C 3 -C 8 cycloalkyl, aryl, heterocyclyl of 5-8 ring members or heteroaryl of 5-10 ring members each of which is optionally substituted by 1-3 radicals of R 2 ; and B represents a bond, -C(Y)-, -S(0) t -, -S-, -0- , -N(R 1 )-, -C(Y)-N(R 1 )-, -N(R -C(Y)-, -S(0) t -N(R -, -N (R -S (0) t - , -N(R -C(Y)-N(R 1 ) - or -NtR -S (O) t -N (R - , or a radical of C 3 -C 8 cycloalkyl, aryl, heterocyclyl of 5-8 ring members or heteroaryl of 5-10 ring members each of which is optionally substituted by 1-3 radicals of R 2 ; provided the total number of atoms that directly connect E to G via the shortest sequence is 3-12; each X is independently 0 or S; and each Y is independently 0, S, N(R or N(CN); and each t is independently 1 or 2 ; each R x is independently a hydrogen or C 3 -C 4 alkyl radical ; radicals of R 2 are each independently a halo, C j -C 4 alkyl, C x -C 4 alkoxy, C^C, alkylthio, C 1 -C 4 haloalkyl of 1-3 halo radicals, C 1 -C 4 haloalkoxy of 1-3 halo radicals, hydroxy, carboxy, cyano, azido, amidino, guanidino, nitro, amino, C x -C 4 alkylamino or di (C 1 -C 4 alkyl) amino radical or two adjacent R 2 radicals represent a methylenedioxy, ethylenedioxy or propylenedioxy radical; E represents -R 3 , -NH-R 3 , -NH-C(Y)-R 3 , -C(Y)-NH-R 3 , -NH- S(0) t -R 3 , -S(0) t -NH-R 3 , -NH-C(Y) -NH-R 3 , -NH-C (Y) -0-R 3 , -NH-S(0) t -NH-R 3 , -NH-(C X -C 4 alkyl) -C(Y)-R 3 , -NH- (C x -C 4 alkyl) -S(0) t -R 3 , -NH-(C 1 -C 4 alkyl) -C (Y) -NH-R 3 or -NH- (C,- C 4 alkyl) -S(0) t -NH-R 3 radical; R 3 is hydrogen, C^C^ alkyl, aryl, aryl-C^C^ alkyl, heteroaryl, heteroaryl-C j -C^ alkyl, heterocyclyl or heterocyclyl-C j -C^ alkyl radical, wherein the heteroaryl and heterocyclyl radicals have 5-15 ring members and the aryl, heteroaryl and heterocyclyl radicals are optionally substituted by 1-3 radicals of 2 ■ G is a radical of formula W 3 is C-R 15 or N; W 2 is C-R 16 or N; W 3 is C-R 17 or N; and W 4 is C-R 18 or N; or W x and W 2 , W 2 and W 3 , or W 3 and W 4 taken together represent a fused phenyl, fused C 5 -C 7 cycloalkyl, fused heteroaryl of 5-6 ring members or fused heterocyclyl of 5-7 ring members, each of which is optionally substituted by 1-3 radicals of R 2 ; provided not more than 2 of W 1# W 2 , W 3 or W 4 represent N; radicals of R 15 , R l6 , R l7 and R 18 are each independently a radical of hydrogen, halo, hydroxy, carboxy, cyano, azido, amidino, nitro, amino, -R 9 , -C(Y)-R 9 , -S(0) t -R 9 , -S-R 9f -0-R 9 , -N(R X )-R 9 , -C (Y) -N (R -R 9 , -N (R -C (Y) -H, -N(R 1 )-C(Y)-R 9 , -0-C(Y)-N(R 3 )-R 9 , -N (R -C (Y) -0-R 9 , -S(0) t -N(R 1 )-R 9 , -N(R 1 )-S(0) t -R 9 , -N (R -C (Y) -N (R x ) -R. or -N(R -S(O) t -N(R 1 ) -R 9 , or R 15 and R 16 , R 16 and R 17 , or R 17 and R 18 taken together represent a methylenedioxy, ethylenedioxy or propylenedioxy radical; provided the combined total number of aryl, cycloalkyl, heteroaryl and heterocyclyl radicals in R 15 , R 16 , R 17 and R 18 is 0-1; wherein each R 9 is independently a radical of C J -C J alkyl, C x -C 4 haloalkyl of 1-3 halo radicals, aryl-C x -C 4 alkyl, heteroaryl-C.-C, alkyl, heterocyclyl-C^C, alkyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, wherein the aryl, cycloalkyl, heteroaryl and heterocyclyl radicals are optionally substituted by 1-3 radicals of R 2 ; X 2 , X 3 and X 6 are each independently a -C(X)-, -S(0) t -, -CHR 6 - or -CHR 7 - radical; Z x is N or C-R 6 ; R 10 and R 12 are each independently an -R 6 , -R 7 or -0R 7 radical ; wherein each R 6 is independently a hydrogen, hydroxy, C.-C, alkyl, C.-C, haloalkyl of 1-3 halo radicals, C^C, alkoxy, C x -C 4 haloalkoxy, halo or cyano radical; and each R 7 is independently a radical of aryl, aryl-C 3 -C 4 alkyl, heteroaryl, heteroaryl-C j -C j alkyl, heterocyclyl or heterocyclyl-C 1 -C 4 alkyl, each of which is optionally substituted by 1-3 radicals of R 2 , and wherein the heteroaryl and heterocyclyl radicals have 5-10 ring members; provided the combined total number of aryl, heteroaryl and heterocyclyl radicals in X 2 , X 3 , X 6 , R 10 and R 12 is 0-2; and R 4 is a C^C^ alkyl radical substituted by a radical of carboxy, tetrazolyl, -C0 2 R 8 , -C (0) -NH-S (0) t -R 8 , -C(0)-NH- C(0)-R 8 or -C(0)-NH-R 8 , and optionally substituted by a radical of aryl, heteroaryl or heterocyclyl, each of which is optionally substituted by 1-3 radicals of R 2 ; wherein R 8 is a C^C^ alkyl radical optionally substituted by 1-2 radicals of hydroxy, carboxy, amino, aryl or heteroaryl of 5-10 ring members, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of R 2 . 3. The compound of Claim 2 or a pharmaceutically acceptable salt thereof, wherein each Alk is independently a C j -C 8 alkyl radical; each X is 0; and each Y is independently 0, N(R or N(CN); and each t is 2; E represents -R 3 , -NH-R 3 , -NH-C(Y)-R 3 , -C(Y)-NH-R 3 , -S(0) t -NH-R 3 , -NH-C(Y) -NH-R 3 , -NH-C (Y) -0-R 3 or -NH- (C 3 -C 4 alkyl) -C(Y)-NH-R 3 radical; R 3 is hydrogen, C 1 -C 4 alkyl, aryl, aryl-C 1 -C 4 alkyl, heteroaryl, heteroaryl-C 1 -C 4 alkyl, heterocyclyl or heterocyclyl-C j^ -C j alkyl radical, wherein the heteroaryl and heterocyclyl radicals have 5-15 ring members and the aryl, heteroaryl and heterocyclyl radicals are optionally substituted by 1-3 radicals of R 2 ; W x is C-R 15 or N; W 2 is C-R 16 or N; W 3 is C-R 17 or N; and W 4 is C-R 18 or N; provided not more than 2 of W x , W 2 , W 3 or W 4 represent N; radicals of R 15 , R 16 , R 17 and R 18 are each independently a radical of hydrogen, halo, hydroxy, carboxy, cyano, azido, amidino, nitro, amino, -R 9 , -C(0)-R 9 , -S(0) t -R 9 , -S-R 9 , -0-R 9 , -NΪR -R,, -C(0)-N(R -R 9 , -N (R 3 ) -C (0) -H, -N(R 1 )-C(0)-R 9 , -S(0) t -N(R 1 )-R 9 or -N(R) -S (0) C -R 9 , or R 15 and R 16 , R 16 and R 17 , or R 17 and R 18 taken together represent a methylenedioxy, ethylenedioxy or propylenedioxy radical; provided the combined total number of aryl, cycloalkyl, heteroaryl and heterocyclyl radicals in R 15 , R 16 , R 17 and R 13 is 0-1; X 2 , X 3 and X 6 are each independently a -CHR 6 - or -CHR 7 - radical ; R 10 and R l2 are each independently a hydrogen, hydroxy or C x -C t alkyl radical; and R 4 is a C 1 -C 4 alkyl radical substituted by a radical of carboxy, tetrazolyl, or -C0 2 R 8 , and optionally substituted by a radical of aryl, heteroaryl or heterocyclyl, each of which is optionally substituted by 1-3 radicals of R 2 ; wherein R 8 is a C 1 -C 4 alkyl radical optionally substituted by a radical of aryl or heteroaryl of 5-10 ring members, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of R 2 . 4. The compound of Claim 3 or a pharmaceutically acceptable salt thereof, wherein each Alk is independently a C^C g alkyl radical; A and Q each independently represent a bond, -C(0)-, -S(0) t -, -0-, -N(R -, -C(Y)-N(R 1 )-, -NfR -Cm-, -S(0) t -N(R 1 ) - or -N(R -S (0) t - , or a radical of C 3 -C 6 cycloalkyl, phenyl, heterocyclyl of 5-6 ring members or heteroaryl of 5-6 ring members each of which is optionally substituted by 1-3 radicals of R 2 ; and B represents a bond, -C(Y)-, -S(0) t -, -0- or -N(R 1 )-, or a radical of phenyl, heterocyclyl of 5-6 ring members or heteroaryl of 5-6 ring members each of which is optionally substituted by 1-3 radicals of R 2 ; provided the total number of atoms that directly connect E to G via the shortest sequence is 4-9; radicals of R 2 are each independently a halo, C j -C 3 alkyl, C x -C 3 alkoxy, C.-C, alkylthio, -CF 3 , -OCF 3 , hydroxy, cyano, nitro, amino, C x -C 4 alkylamino or di(C 1 - C 4 alkyl) amino radical; E represents -R 3 , -NH-R 3 , -NH-C(Y)-R 3 , -C(Y)-NH-R 3 , -NH- C(Y)-NH-R 3 or -NH-C (Y) -0-R 3 radical; R 3 is hydrogen, C 1 -C 4 alkyl, aryl, aryl-C 1 -C 4 alkyl, heteroaryl or heteroaryl-C 1 -C 4 alkyl radical, wherein the heteroaryl radical has 5-15 ring members and the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of R 2 ; W x is C-R 15 ; W 2 is C-R 16 ; W 3 is C-R 17 ; and W 4 is C-R 18 ; radicals of R 15 , R 17 and R 18 are each independently a radical of hydrogen, halo, hydroxy, cyano, C x -C 3 alkyl, C 3 -C 3 alkoxy, -CF 3 or -OCF 3 ; R 16 is a radical of hydrogen, halo, hydroxy, carboxy, cyano, amino, -R 9 , -S(0) t -R 9 , -0-R 9 , -N(R -R 9 , -C(O)- N(R 1 )-R 9 , -N(R 1 )-C(0)-H, -N (R -C (0) -R 9 , -S (0) t -N (R -R 9 or -N(R 1 )-S(0) c -R 9 ; wherein each R 9 is independently a radical of C^C j alkyl, -CF 3 , phenyl-C 1 -C 4 alkyl or phenyl, wherein each phenyl radical is optionally substituted by 1-3 radicals of R 2 ; X 2 , X 3 and X 6 are each independently a -CHR 6 - radical; Z, is C-R 6 ; R 10 and R 12 are each independently a hydrogen, hydroxy or C 3 -C 2 alkyl radical; wherein each R 6 is independently a hydrogen, hydroxy or C x -C 2 alkyl radical; and R 4 is a C j -C 4 alkyl radical substituted by a radical of carboxy or -C0 2 R 8 ; wherein R 8 is a C x -C 4 alkyl radical optionally substituted by a phenyl radical, wherein the phenyl radical is optionally substituted by 1-3 radicals of R, . 5. The compound of Claim 4 or a pharmaceutically acceptable salt thereof, wherein G is a radical of formula 6. The compound of Claim 5 or a pharmaceutically acceptable salt thereof, wherein B represents a bond, -S(0) t -, -0- or -N(R 1 )-, or a phenyl radical which is optionally substituted by 1-3 radicals of R 2 ; provided the total number of atoms that directly connect E to G via the shortest sequence is 4- 7; each R L is independently a hydrogen or methyl radical; radicals of R 2 are each independently a halo, methyl, methoxy, -CF 3 , -0CF 3 , hydroxy, cyano, nitro, amino, C 1 -C 4 alkylamino or di (C 1 -C 2 alkyl) amino radical; E represents -R 3 , -NH-R 3 , -NH-C (NR -R lf -C (NR -NH-R 1# -NH-C(NR 1 )-NH-R 1 or -NH-C (NR -O-CH, radical; R 3 is a heteroaryl radical of 5-15 ring members and is optionally substituted by 1-3 radicals of R j ,- R 15 , R 17 and R 18 are each independently a radical of hydrogen, fluoro, chloro, bromo, hydroxy, cyano, methyl, methoxy, -CF 3 or -OCF 3 ; R 16 is a radical of hydrogen, fluoro, chloro, bromo, hydroxy, cyano, amino, -R 9 , -S(0) c -R 9 , -0-R 9 , -N(R 3 )-R 9 , -C(0)-N(R 1 )-R 9 , -N(R -C(0)-H, -N (R 3 ) -C (0) -R 9 , -S(0) t - N(R -R 9 or -N(R 1 )-S(0) t -R 9 ; wherein each R 9 is independently a radical of C l -C 4 alkyl, -CF 3 , phenyl-C 3 -C 2 alkyl or phenyl, wherein each phenyl radical is optionally substituted by 1-3 radicals of R 2 ; each R 6 is a hydrogen radical; and R 4 is a C J -C J alkyl radical substituted by a radical of carboxy or -C0 2 R 8 ; wherein R 8 is a C^C j alkyl radical. 7. The compound of Claim 6 which is 2- (2- (N- (3- (2-pyridylamino) propyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (4- (2 -pyridylamino) butyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (5- (2-pyridylamino) pent-1-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N-methyl-N- (4- (2-pyridylamino) but-l-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (4- (2-pyridylamino) -trans-cyclohexyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- ( ( (4- (2-pyridylamino)methyl)piperid-l-yl) carbonyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (3- (2 -pyridylamino) methylphenyl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (4- ( (6-methyl-2-pyridyl) amino) but-l-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (4- (pyrimidin-2-ylamino)but-l-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (3- (6-amino-2-pyridyl) prop-1-yl) carbamoyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- ( 3- ( 6- ( tert-butoxycarbonylamino) -2- pyridy1 ) propyl ) carbamoyl ) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetic acid; 2- (2- (N- (3- (1,2, 3, 4-tetrahydropyridino (2, 3-b)pyridin-7- yl) prop-1-yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetic acid; 2- (2- ( ( (4- (2-pyridylamino) but-1-yl) amino) sulfonyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- ( ( (3- (2 -pyridylamino) prop-1-yl) amino) sulfonyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- ( 2- (2- ( (2-(2-pyridylamino) ethyl ) amino) acetyl ) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (2- ( (3- (2-pyridylamino) prop-1-yl) amino) acetyl- 1H, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2-(2-(2-((4- (2 -pyridylamino) but-1-yl) amino)acetyl- 1H, 3H, 4H, 5H-benzo [e] azapin-5-yl-acetic acid; 2- (2- ( (N- (3- (2-pyridylamino) prop-1-yl) carbamoyl) methyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (4- (2-pyridylamino)but-l-oxy carbonyl) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (8-methoxy-2- (N- (4- (2-pyridylamino) but-l- yl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azaperhydroepin-5- yl) acetic acid; 2- (8-fluoro-2- (N- (3- ( 1 , 2 , 3 , 4-tetrahydropyridino [2 , 3,b] pyridin-7-yl) propyl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl ) acetic acid; 2- (2- ( {N- (4- (2-pyridylamino ' ) prop-1-yl) carbamoyl} methyl) -3-oxo-lH, 4H, 5H-benzo (e) azepin-5-yl ) acetic acid; 2- (3- ( {N- (4- (2-pyridylamino)but-l-yl) carbamoyl} methyl) -IH, 2H, 4H, 5H-benzo [d] azepin-1-yl) acetic acid; 2- (3-{ [N- (3- (1, 2, 3, 4-tetrahydropyridino [2, 3-b]pyridin- 7-y1 ) propyl ) carbamoyl ] methyl} -IH, 2H, 4H, 5H- benzo [d] azepinyl ) acetic acid; 2- (3- (N- (5- ( 2-pyridylamino) pent-1-yl) carbamoyl} - IH, 2H, 4H, 5H-benzo [d] azepinyl ) acetic acid; 2-{3- (N- ( 3- (1,2, 3, 4-tetrahydropyridino [2, 3-b] pyridin-7- yl) propyl) carbamoyl) -IH, 2H, 4H, 5H-benzo [d] azepin-1- yl}acetic acid; 2- { 3- ( 7- ( 2-pyridylamino) heptanoy1 ) -IH, 2H, 4H, 5H- benzo [d] azepin-l-yl}acetic acid; 2-(2-(N-(3-(l,2,3, 4-tetrahydropyridino (2 , 3-b) pyridin-7- yl)propyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) propanoic acid; 2-{2- [N- (methylethyl) -N- (2- (1,2, 3 , 4-tetrahydropyridino [2 , 3-b] pyridin-7-yl) ethyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl] acetic acid; 2- (2-aza-2-cyano-l ( (1,2,3, 4-tetrahydropyridino [2, 3- b]pyridin-7-yl) propyl) amino) vinyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetic acid; 2-(2-( ( (2-(l,2,3, 4-tetrahydropyridino (2, 3-b) pyridin-7- yl) ethyl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetic acid; 3-(2-(N-(2-(l,2, 3 , 4-tetrahydropyridino (2 , 3-b) pyridin-7- yl) ethyl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) propanoic acid; 2- ( 2- (N- ( 3- ( 2-pyridylamino) propyl ) carbamoyl ) - IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2-( (5R)-2-(N- (3- ( 1 , 2 , 3 , 4-tetrahydropyridino (2 , 3- b)pyridin-7-yl)prop-l-yl) carbamoyl) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetic acid; 2-( (5R)-2-(N- (3- ( 1,2, 3, 4-tetrahydropyridino (2,3- b)pyridin-7-yl) ethyl) carbamoyl) -1H,3H,4H, 5H- benzo [e] azapin-5-yl) acetic acid; 2-( (5S) -2-(N- (3- (1, 2, 3, 4-tetrahydropyridino (2,3- b) pyridin-7-yl ) ethyl ) carbamoyl ) -IH, 3H, 4H, 5H- benzo [e] azapin-5-yl) acetic acid; 2-((5S)-2-(4-(l,2, 3, 4-tetrahydropyridino (2, 3-b) pyridin- 7 -yl) butanoyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetic acid; 2- [2- (4- (1, 2, 3, 4-tetrahydropyridino [2, 3-b] pyridin-7- yl) butanoyl) -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl] acetic acid; 2-{2- [N- (2- (1, 2, 3 , 4-tetrahydropyridino [2, 3-b]pyridin-7- yl) ethyl) carbamoyl] -4H, 5H, 10H-benzo[d] imidazolo [1, 2- a] azepin-5-yl}acetic acid; 2-{2- [N- (methylethyl) -N- (2- (1 , 2 , 3 , 4-tetrahydropyridino [2, 3-b] pyridin-7-yl) ethyl) carbamoyl] -4H, 5H, 10H- benzo [d] imidazolo [ 1, 2-a] azepin-5-yl} acetic acid; 2- { 2- [N- (methylethyl ) -N- (1,2,3, 4tetrahydropyridino [2,3- b] pyridine-6-ylmethyl) carbamoyl] -4H, 5H, 10H- benzo [d] imidazolo [1, 2-a] azepin-5-yl}acetic acid; 2- {2- [N- (1,2,3, 4-tetrahydropyridino [2, 3-b] pyridin-6- ylmethyl) carbamoyl] -4H, 5H, lOH-benzo [d] imidazolo [1,2- a] azepin-5-yl)acetic acid; 2- (2- {N-methyl-N- [3- (2-pyridylamino) propyl] carbamoyl }- 4H, 5H, lOH-benzo [d] imidazolo [1, 2-a] azepin-5-yl) acetic acid; 2- (8-methoxy-2- (N-(3-(l,2,3, 4-tetrahydropyridino [2, 3, b] pyridin-7-yl) propyl) carbamoyl) -IH, 3H,4H, 5H- benzo [e] azaperhydroepin-5-yl) acetic acid; 2- (8-benzyloxy-2- (N-(3-(l,2,3, 4-tetrahydropyridino [2,3, b] pyridin-7-yl ) propyl ) carbamoyl ) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetic acid; 2- (8-phenyl-2- (N- (3- (1,2, 3, 4-tetrahydropyridino [ 2 , 3 , b] pyridin-7-yl ) propyl ) carbamoyl ) -IH, 3H, 4H, 5H- benzo [e] azaperhydroepin-5-yl) acetic acid; 2- (2- (N- (4- (4, 5-dihydroimidazo-2-yl)aminobut-l-yl) carbamoyl) -IH, 3H, 4H-5H-benzo [e] azapin-5-yl) acetic acid; 2-{8-Chloro-2-[N- (3- ( 1, 2 , 3 , 4-tetrahydropyridino [2 , 3- b] pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl}acetic acid; 2-{8-Bromo-2- [N- (3- ( 1, 2 , 3 , 4-tetrahydropyridino [2 , 3- b] pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl}acetic acid; 2- {7, 8-Dibromo-2- [N- (3- (1,2, 3 , 4-tetrahydropyridino [2 , 3- b]pyridin-7-yl) propyl) carbamoyl ]-lH,3H,4H, 5H- benzo [e] azepin-5-yl}acetic acid; 2-{8-[ (Methylsulfonyl)amino]-2-[N-(3-(l,2,3,4- tetrahydropyridino [2, 3-b] pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetic acid; 2-{8-[ (Phenylsulfonyl) amino] -2- [N- (3- ( 1 , 2 , 3 , 4- tetrahydropyridino [2 , 3-b]pyridin-7-yl) propyl) carbamoyl] -IH, 3H, 4H, 5H-benzo [e] azepin-5-yl}acetic acid; 2-{8-Carbonylamino-2- [N-(3-(l,2,3, 4-tetrahydropyridino [2 , 3-b]pyridin-7-yl)propyl) carbamoyl] -IH, 3H, 4H, 5H- benzo [e] azepin-5-yl} acetic acid; 2-{8- (Dimethylamino) -2- [N- (3- (1,2, 3 , 4-tetrahydro pyridino [2 , 3-b] pyridin-7-yl) propyl) carbamoyl] - IH, 3H, 4H, 5H-benzo [e] azepin-5-yl} acetic acid; 2- (2- (N- (3- (6- (methylamino) -2-pyridyl) propyl ) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5-yl) acetic acid; 2- (2- (N- (2- (1, 2 , 3 , 4-tetrahydropyridino (2 , 3-b) ρyridin-7- yl) ethyl) carbamoyl ) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetic acid; 2- (3- (N- (2- (1, 2, 3 , 4-tetrahydropyridino (2 , 3-b) pyridin-7- yl)propyl) amino) sulfonyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) acetic acid; 3-(2-(N-(2-(l,2,3,4-tetrahydropyridino ( 2 , 3-b) pyridin-7- yl) ethyl) carbamoyl) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) propanoic acid; 3- (2- (N- (3- (1, 2, 3, 4-tetrahydropyridino (2, 3-b)pyridin-7- yl)propyl) carbamoyl-lH, 3H, 4H, 5H-benzo [e] azapin-5- yl) propanoic acid; 3-(2-(N-(3-(l,2,3, 4-tetrahydropyridino (2 , 3-b) pyridin-7- yl ) propyl ) amino ) sulfony1 ) -IH, 3H, 4H, 5H-benzo [e] azapin-5- yl) propanoic acid; 2- [3- ( {N- [5- (2-pyridylamino) pentyl] carbamoyl}methyl) - IH, 2H, 4H, 5H-benzo [d] azepinyl] acetic acid; 2- [3- (2-{ [4- (2-pyridylamino) butyl] amino} acetyl) - IH, 2H, 4H, 5H-benzo [d] azepinyl] acetic acid; 2- (2-{N-[3- (5-methyl-1,2, 3, 4-tetrahydropyridino [2 , 3- b] pyridin-7-yl) propyl] carbamoyl}-lH, 3H, 4H, 5H- benzo [e] azepin-5-yl) acetic acid; 2- (3- {N- (2- (2-pyridylamino) ethyl) carbamoyl }- IH, 2H, 4H, 5H-benzo [d] azepinyl) acetic acid; 2-{3-(N-(2-(l,2,3, 4-tetrahydropyridino [2, 3 -b] pyridin-7- yl) ethyl) carbamoyl) -IH, 2H, 4H, 5H-benzo [d] azepin-1- yl}acetic acid; 2- (8-fluoro-2- (N-(2- (1 , 2 , 3 , 4-tetrahydropyridino (2 , 3- b)pyridin-7-yl) ethyl) carbamoyl) -1H,3H,4H, 5H- benzo [e] azapin-5-yl) acetic acid; 2- [2- (N-{4- [ ( 4-methyl-2-pyridyl) amino] butyl} carbamoyl) - IH, 3H, 4H, 5H-benzo[e] azepin-5-yl] acetic acid; or 2- {2- [N- (4- { [benzylamino] carbonylamino}butyl) carbamoyl] -IH, 3H, 4H, 5H-benzo[e]azepin-5-yl}acetic acid; or a pharmaceutically acceptable salt thereof. 8. A pharmaceutical composition comprising a compound according to any one of Claims 1-7 and a pharmaceutically acceptable carrier. 9. A method of treatment of a disease or disorder modulated by an integrin receptor comprising administering an effective amount of a compound according to any one of Claims 1-7. 10. The method of Claim 9 wherein the integrin receptor is vitronectin receptor α v β 3 , α v β 5 or oc v β 6 . 11. A method of treatment of a disease or disorder modulated by an integrin receptor comprising administering an effective amount of a composition of Claim 8. 12. The method of Claim 11 wherein the an integrin receptor is vitronectin receptor cc v β 3 , α v β 5 or cc v β 6 . 13. A method of antagonizing an integrin receptor comprising administering an effective amount of a compound according to any one of Claims 1-7. 14. The method of Claim 13 wherein the an integrin receptor is vitronectin receptor α v β 3 , α v β 5 or oc v β 6 . 15. A method of antagonizing an integrin receptor comprising administering an effective amount of a composition of Claim 8. 16. The method of Claim 15 wherein the an integrin receptor is vitronectin receptor α v β 3 , c v β 5 or α v β 6 . 17. A method of treatment of atherosclerosis, restenosis, inflammation, wound healing, cancer, metastasis, bone resorption related diseases, diabetic retinopathy, macular degeneration, angiogenesis or viral infections comprising administering an effective amount of a compound according to any one of Claims 1- 7. 18. A method of prophylaxis or treatment of atherosclerosis, restenosis, inflammation, wound healing, cancer, metastasis, bone resorption related diseases, diabetic retinopathy, macular degeneration, angiogenesis or viral infections comprising administering an effective amount of a composition of Claim 8.

Inventors: CHEN ZHIDONG, DOMINGUEZ CELIA, GRENZER-LABER ELLEN, HAN NIANHE, LIU LONGBIN, MORENO OFIR A, RUTLEDGE MELVIN C, TASKER ANDREW, CHEN, ZHIDONG, DOMINGUEZ, CELIA, GRENZER-LABER, ELLEN, HAN, NIANHE, LIU, LONGBIN, MORENO, OFIR, A., RUTLEDGE, MELVIN, C., TASKER, ANDREW
Applicants: AMGEN INC, AMGEN INC.
Application year: 2000
Main classification: C07D223
IPC codes: A61P7, A61P35, C07D213, C07D223, C07D401, C07D403, C07D405, C07D417, C07D471, C07D487, C07D519