CYCLICSULFONATE PYRROLE INDOLINONES AS KINASE INHIBITORS This application claims the benefit of U.S. Provisional Application Serial No. 60/573,127, filed May 20, 2004, the disclosure of which is incorporated herein by reference in its entirety. Field of Invention The invention relates to certain indolinone compounds and their methods of synthesis. The invention also relates to methods of modulating the function of protein kinases, in particular CDK2. protein kinase, using compounds of the invention and methods of treating diseases by modulating the function of protein kinases, in particular CDK2 protein kinase, and related signal transduction â–  pathways. Background Cellular signal transduction is a fundamental mechanism whereby extracellular stimuli are relayed to the interior of cells and subsequently regulate diverse cellular processes. One of the key biochemical mechanisms of signal transduction involves the reversible phosphorylation of proteins. Phosphorylation of polypeptides regulates the activity of mature proteins by altering their structure and function. Phosphate most often resides on the hydroxyl moiety (--OH) of serine, threonine, or tyrosine amino acids in proteins. Enzymes that mediate phosphorylation of cellular effectors generally fall into two classes. The first class consists of protein kinases which transfer a phosphate moiety from adenosine triphosphate to protein substrates. The second class consists of protein phosphatases which hydrolyze phosphate moieties from phosphoryl protein substrates. The converse functions of protein kinases and protein phosphatases balance and regulate the flow of signals in signal transduction processes. Protein kinases , and protein phosphatases are generally divided into two groups-receptor and non-receptor type proteins. Most-receptor-type protein phosphatases contain two conserved catalytic domains, each of which encompasses a segment of 240 amino acid residues. Saito, et al., 1991 , Cell Growth and Diff. 2:59-65. Receptor protein phosphatases can be subclassified further based upon the amino acid sequence diversity of their extracellular domains. Saito, et al., supra; Krueger, et al., 1992, Proc. Natl. Acad. Sci. USA 89:7417-7421. Protein kinases and protein phosphatases are also typically divided into three classes based upon the amino acids they act upon. Some catalyze the addition or hydrolysis of phosphate on serine or threonine only, some catalyze the addition or hydrolysis of phosphate on tyrosine only, and some catalyze the addition or hydrolysis of phosphate on serine, threonine, and tyrosine. Kinases can regulate the catalytic activity of other protein kinases involved in cell proliferation. Protein kinases with inappropriate activity are also involved in some types of cancer. Abnormally elevated levels of cell proliferation are associated with receptor and non-receptor protein kinases with unregulated activity. In addition to their role in cellular proliferation, protein kinases are thought to be involved in cellular differentiation processes. Cell differentiation occurs in some cells upon nerve growth factor (NGF) or epidermal growth factor (EGF) stimulation. Cellular differentiation is characterized by rapid membrane ruffling, cell flattening, and increases in cell adhesion. Chao, 1992, Cell 68:995-997. There remains a need in the art to identify the particular structures and substitution patterns that form the compounds capable of modulating the function of particular protein kinases. Summary of the Invention The present invention is directed to certain indolinone compounds and methods of treating diseases mediated by protein kinases, in particular CDK2 protein kinase, using these compounds. Thus, in one embodiment, the invention provides a compound of Formula (I):

wherein: Z is oxygen or sulfur; R5 is hydrogen or alkyl; R8 is hydrogen, alkyl or -C(R1')2NR3' R4', wherein R1' is hydrogen or alkyl; and R R33'' ε and R4' are independently alkyl or combine to form a heteroaiicyclic ring or a heteroaryl ring; X is NR9 or O, and R9 is (i) hydrogen; (ii) saturated or unsaturated alkyl optionally substituted with one, two or three substituents selected from the group consisting of halogen, trihalomethyl, alkoxy, carboxylate, amino, nitro, ester, and a five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; or (iii) an aromatic ring or heteroaromatic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, amino, nitro, ester, an aliphatic ring or a heteroaliphatic ring; and Y is a aromatic ring or heteroaromatic ring, which can be optionally fused with a four, five or six membered aliphatic or aromatic ring, and wherein Y is optionally substituted with one, two, or three substituents independently selected from the group consisting of (i) hydrogen or hydroxy; (ii) saturated or unsaturated alkyl optionally substituted with one, two or three substituents selected from the group consisting of halogen, trihalomethyl, alkoxy, carboxylate, amino, nitro, ester, and a five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (iii) an aromatic or heteroaromatic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, amino, nitro, ester, an aliphatic ring or a heteroaliphatic ring; (iv) an aliphatic or heteroaliphatic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, amino, nitro, ester, and an aromatic or heteroaromatic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (v) an alcohol of formula -(X1)ni -OH or an alkoxyalkyl of formula ~[X2)n2 --0-X3, where X1, X2, and X3 are independently selected from the group consisting of saturated or unsaturated alkyl, amide, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl, and each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, aryl, heteroaryl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; and n1 and n2 are independently O or 1 ; (vi) a halogen, trihalomethyl or trihalomethanesulfonyl; (vii) a carboxylic acid of formula ~(X4)n4 --COOH or ester of formula ~(X5)n5 -COO--X6, where X4, X5, and X6 are independently selected from the group consisting of alkyl and five- membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring; and n4 and n5 are independently O or 1 ; (viii) an amide or thioamide of formula -(X7W --NHCOX8, -(X7W --NHCSX8, ~(X9)n9~ CONX10X11, or of formula ~(X9)n9 --CSNX10X11, where X7 and X9 are each independently selected from the group consisting of alkyl and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where each of the ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; n7 and n9 are independently O or 1 ; and X8, X10, and X11, are each independently selected from the group consisting of hydrogen, alkyl, hydroxyl, alkoxy, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, alkoxy, thioalkyl, aryl, heteroaryl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; or where X10 and X11 taken together form a five-membered or six- membered aliphatic or heteroaliphatic ring or a fused bicyclic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (ix) a sulfonamide of formula ~(X12)n12 --SO2NX13X14 or of formula ~(X12)ni2 -NX18-SO2-X14, where X12 is selected from the group consisting of alkyl, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, hydroxy, trihalomethyl, carboxylate, amino, nitro, and ester; n12 is 0, 1, or 2; and X13, and X14 are independently selected from the group consisting of hydrogen, alkyl, and three-, four-, five-, or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, alkoxy, aryl, heteroaryl, halogen, trihalomethyl, aldehyde, carboxylate, amino, nitro, and ester; or where X13 and X14 taken together form a five-membered or six-membered aliphatic or heteroaliphatic ring or a fused bicyclic ring optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (x) a sulfo of formula -(X15)n15--SO3H, where X15 is selected from the group consisting of alkyl, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; n15 is 0, 1 , or 2; (xi) an amine of formula ~(X16)n16-NX17X18, where X16 is selected from the group consisting of saturated or unsaturated alkyl, and five-membered or six-membered aromatic, heteroaromatic, or aliphatic ring; n16 is 0 or 1 ; and X17 and X18, are independently selected from the group consisting of hydrogen, saturated or unsaturated alkyl, and five-membered or six-membered aromatic, heteroaromatic, or aliphatic ring where each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (xii) a ketone of formula -(X19)n19-CO-X20, where X19 and X20 are independently selected from the group consisting of alkyl and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; and n19 is 0 or 1 ; (xiii) a nitro group of the formula -NO2; (xiv) a cyano group of the formula -CN; (xv) a sulfonyl of the formula -(X21 )n21 -SO2-X22 or a sulfinyl of the -(X21)n21-SO-X22, where X21 and X22 are independently selected from the group consisting of alkyl and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; and n21 is 0 or 1 ; with the proviso that Y does not include a lactone or lactam moiety, or a pharmaceutically acceptable salt, solvate or hydrate thereof. In a preferred aspect of this embodiment, X is oxygen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, Z is oxygen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, Y is a pyrrole group, optionally substituted as described above. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, Y is a phenyl group, optionally substituted as described above. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, R5 is hydrogen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, R8 is hydrogen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, Z is oxygen, Y is a pyrrole group optionally substituted as described above, R5 is hydrogen and R8 is hydrogen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, Z is oxygen, Y is a phenyl group optionally substituted as described above, R5 is hydrogen and R8 is hydrogen. In another embodiment, the invention providesa compound of Formula (II):

(H) wherein: Z is oxygen or sulfur; R5 is hydrogen or alkyl; R8 is hydrogen, alkyl or -C(R1')2NR3' R4', wherein R1> is hydrogen or alkyl; and R3' and R4' are independently alkyl or combine to form a heteroalicyclic ring or a heteroaryl ring; A is selected from the group consisting of carbon, nitrogen, oxygen and sulfur and it is understood that when A is oxygen or sulfur, R4 does not exist and there is no bond; R1, R2, R3, and R4 are independently selected from the group consisting of (i) hydrogen or hydroxy; (ii) saturated or unsaturated alkyl optionally substituted with one, two or three substituents selected from the group consisting of halogen, trihalomethyl, alkoxy, carboxylate, amino, nitro, ester, and a five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (iii) an aromatic or heteroaromatic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, amino, nitro, ester, an aliphatic ring or a heteroaliphatic ring; (iv) an aliphatic or heteroaliphatic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, amino, nitro, ester, and an aromatic or heteroaromatic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (v) an alcohol of formula ~(X1)ni -OH or an alkoxyalkyl of formula -(X2W --0--X3, where X1, X2, and X3 are independently selected from the group consisting of saturated or unsaturated alkyl, amide, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl, and each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, aryl, heteroaryl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; and n1 and n2 are independently O or 1 ; (vi) a halogen, trihalomethyl or trihalomethanesulfonyl; (vii) a carboxylic acid of formula -(X4)n4 --COOH or ester of formula ~(X5)Ï€5 --COO--X6, where X4, X5, and X6 are independently selected from the group consisting of alkyl and five- membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring; and n4 and n5 are independently 0 or 1 ; * (viii) an amide or thioamide of formula ~(X7)n7 --NHCOX8, ~(X7)n7 --NHCSX8, --(X9)Ï€9- CONX10X11, or of formula -(X9)n9 -CSNX10X11, where X7 and X9 are each independently selected from the group consisting of alkyl and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where each of the ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; n7 and n9 are independently 0 or 1 ; and X8, X10, and X11, are each independently selected from the group consisting of hydrogen, alkyl, hydroxyl, alkoxy, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, alkoxy, thioalkyl, aryl, heteroaryl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; or where X10 and X11 taken together form a five-membered or six- membered aliphatic or heteroaliphatic ring or a fused bicyclic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (ix) a sulfonamide of formula ~(X12)m2 -SO2NX13X14 or of formula ~(X12)n12 ~NX13-SO2-X14, where X12 is selected from the group consisting of alkyl, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, hydroxy, trihalomethyl, carboxylate, amino, nitro, and ester; n12 is 0, 1 , or 2; and X13, and X14 are independently selected from the group consisting of hydrogen, alkyl, and three-, four-, five-, or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, alkoxy, aryl, heteroaryl, halogen, trihalomethyl, aldehyde, carboxylate, amino, nitro, and ester; or where X13 and X14 taken together form a five-membered or six-membered aliphatic or heteroaliphatic ring or a fused bicyclic ring optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (x) a sulfo of formula ~(X15)n15~SO3H, where X15 is selected from the group consisting of alkyl, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; n15 is 0, 1 , or 2; (xi) an amine of formula ~(X16)ni6~NX17X18, where X16 is selected from the group consisting of saturated or unsaturated alkyl, and five-membered or six-membered aromatic, heteroaromatic, or aliphatic ring; n16 is 0 or 1 ; and X17 and X18, are independently selected from the group consisting of hydrogen, saturated or unsaturated alkyl, and five-membered or six-membered aromatic, heteroaromatic, or aliphatic ring where each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (xii) a ketone of formula -(X19)n19-CO-X20, where X19 and X20 are independently selected from the group consisting of alkyl and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; and n19 is 0 or 1 ; (xiii) a nitro group of the formula -NO2; (xiv) a cyano group of the formula -CN; (xv) a sulfonyl of the formula -(X21)n21-SO2-X22 or a sulfinyl of the -(X21)n21-SO-X22, where X21 and X22 are independently selected from the group consisting of alkyl and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; and n21 is 0 or 1 ; or (xvi) two adjacent R1, R2, R3 or R4 groups form an optionally substituted five-membered, six- membered or seven-membered aliphatic, heteroaliphatic, aromatic or heteroaromatic ring, with the proviso that the heteroaliphatic ring formed by the two adjacent R1, R2, R3 or R4 groups does not include a lactone or a lactam, or a pharmaceutically acceptable salt, solvate or hydrate thereof. In a preferred aspect of this embodiment, R1 and R2 do not form a heteroaliphatic ring. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, R1 and R2 do not form a ring. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, A is nitrogen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, Z is oxygen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, R5 is hydrogen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, R8 is hydrogen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, A is nitrogen and R4 is hydrogen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, A is nitrogen, Z is oxygen, and each of R4, R5 and R8 is hydrogen. In another embodiment, the invention provides a compound of Formula (III):

wherein: Z is oxygen or sulfur; R6 is hydrogen or alky]; R7 is hydrogen, alkyl or -C(R1')2NR3' R4', wherein R1' is hydrogen or alkyl; and R3' and R4' are independently alkyl or combine to form a heteroalicyclic ring or a heteroaryl ring; R1, R2, R3, R4 and R5 are independently selected from the group consisting of (i) hydrogen or hydroxy (ii) saturated or unsaturated alkyl optionally substituted with one, two or three substituents selected from the group consisting of halogen, trihalomethyl, alkoxy, carboxylate, amino, nitro, ester, and a five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (iii) an aromatic or heteroaromatic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, amino, nitro, ester, an aliphatic ring or a heteroaliphatic ring; (iv) an aliphatic or heteroaliphatic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, amino, nitro, ester, and an aromatic or heteroaromatic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (v) an alcohol of formula ~(X1)n1--OH or an alkoxyalkyl of formula -(X2)Ï€2--O~X3, where X1, X2, and X3 are independently selected from the group consisting of saturated or unsaturated alkyl, amide, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl, and each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, aryl, heteroaryl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; and n1 and n2 are independently 0 or 1 ; (vi) a halogen, trihalomethyl or trihalomethanesulfonyl, (vii) a carboxylic acid of formula --(X4)n4--COOH or ester of formula ~(X5)n5--COO--X6, where X4, X5, and X6 are independently selected from the group consisting of alkyl and five- membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring; and n4 and n5 are independently 0 or 1 ; (viii) an amide or thioamide of formula ~(X7)n7 -NHCOX8, ~(X7)n7 -NHCSX8, ~(X9)n9 - CONX10X11, or of formula ~(X9)n9-CSNX10X11, where X7 and X9 are each independently selected from the group consisting of alkyl and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where each of the ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; n7 and n9 are independently 0 or 1 ; and X8, X10, and X11, are each independently selected from the group consisting of hydrogen, alkyl, hydroxyl, alkoxy, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, alkoxy, thioalkyl, aryl, heteroaryl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; or where X10 and X11 taken together form a five-membered or six- membered aliphatic or heteroaliphatic ring or a fused bicyclic ring optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (ix) a sulfonamide of formula ~(X12)n12 --SO2NX13X14 or of formula --(X12)ni2 ~NX13~SO2~X14, where X12 is selected from the group consisting of alkyl, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, hydroxy, trihalomethyl, carboxylate, amino, nitro, and ester; n12 is 0, 1 , or 2; and X13, and 1X14 are independently selected from the group consisting of hydrogen, alkyl, and three-, four-, five-, or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, alkoxy, aryl, heteroaryl, halogen, trihalomethyl, aldehyde, carboxylate, amino, nitro, and ester; or where X13 and X14 taken together form a five-membered or six-membered aliphatic or heteroaliphatic ring or a fused bicyclic ring optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (x) a sulfo of formula ~(X15)ni5-SO3H, where X15 is selected from the group consisting of alkyl, and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; n15 is 0, 1 , or 2; and (xi) an amine of formula --(X16)ni6~NX17X18, where X16 is selected from the group consisting of saturated or unsaturated alkyl, and five-membered or six-membered aromatic, heteroaromatic, or aliphatic ring; n16 is 0 or 1 ; and X17 and X18, are independently selected from the group consisting of hydrogen, saturated or unsaturated alkyl, and five-membered or six-membered aromatic, heteroaromatic, or aliphatic ring where each ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; (xii) a ketone of formula -(X19)n19-CO-X20, where X19 and X20 are independently selected from the group consisting of alkyl and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, five-membered qr six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; and n19 is 0 or 1 ; (xiii) a nitro group of the formula -NO2 ; (ix) a cyano group of the formula -CN; (x) a sulfonyl of the formula -(X21 )n21 -SO2-X22 or a sulfinyl of the -(X21)n21-SO-X22, where X21 and X22 are independently selected from the group consisting of alkyl and five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring where the alkyl and each ring is optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, five-membered or six-membered aromatic, heteroaromatic, aliphatic, or heteroaliphatic ring, halogen, trihalomethyl, carboxylate, amino, nitro, and ester; and n21 is O or 1 ; or (xvi) two adjacent R1, R2, R3, R4 or R5 groups form an optionally substituted five-membered, six-membered or seven-membered aliphatic, heteroaliphatic, aromatic or heteroaromatic ring, with the proviso that the heteroaliphatic ring formed by the two adjacent R1, R2, R3, R4 or R5 groups does not include a lactone or a lactam; R6, is independently selected from the group consisting of hydrogen, alkyl according to (ii) above, an aromatic or heteroaromatic ring according to (iii) above, an aliphatic or heteroaliphatic ring according to (iv) above, an alcohol or an alkoxyalkyl according to (v) above, a halogen, trihalomethyl, or trihalomethanesulfonyl, according to (vi) above, a carboxylic or ester according to (vii) above, a sulfonamide according to (ix) above, a sulfo according to (x) above, an amine according to (xi) above, a ketone according to (xii) above, a nitro according to (xiii) above, a cyano according to (xiv) above, or a sulfonyl or sulfinyl according to (xv) above; and R7 is selected from the group consisting of hydrogen, and alkyl according to (ii) above, or a pharmaceutically acceptable salt, solvate or hydrate thereof. In a preferred aspect of this embodiment, R1 and R2 do not form a heteroaliphatic ring. In a preferred aspect of this embodiment, Z is oxygen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, R6 is hydrogen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, R7 is hydrogen. In another preferred aspect of this embodiment, and in combination with any other preferred aspects, Z is oxygen, and each of R6 and R7 is hydrogen. In another embodiment, the invention provides a pharmaceutical composition comprising any of the inventive compounds described herein, and a pharmaceutically acceptable excipient. In another embodiment, the invention provides a method of treating a disease mediated by a protein kinase, in particular CDK2 protein kinase, in a mammal, including a human, by administering to the mammal a pharmaceutical composition comprising any of the inventive compounds described herein and a pharmaceutically acceptable excipient. In a particular aspect of this embodiment, the disease is cancer. Types of cancer treatable with the present invention include squamous cell carcinoma, astrocytoma, Kaposi's sarcoma, glioblastoma, lung cancer, bladder cancer, head and neck cancer, melanoma, ovarian cancer, prostate cancer, breast cancer, small-cell lung cancer, glioma, colorectal cancer, genitourinary cancer and gastrointestinal cancer. Other diseases treatable with the present invention include diabetic retinopathy, a hyperproliferation disorder, von Hippel- Lindau disease, restenosis, fibrosis, psoriasis, inflammatory disorders such as rheumatoid arthritis, osteoarthritis, immunological disorders such as autoimmune diseases, cardiovasular disorders such as atherosclerosis and angiogenesis related disorders. The diseases treated with the compounds of the present invention are preferably CDK2 related diseases. In another embodiment, the invention is directed to the use of any of the inventive compounds described herein, in the preparation of a medicament which is most preferably useful in the treatment of a disease mediated by abnormal protein kinase activity, preferably CDK2 kinase activity. Detailed Description Definitions Unless otherwise stated the following terms used in the specification and claims have the meanings discussed below: As used herein, the term "alkyl" refers to an aliphatic hydrocarbon group. The alkyl moiety may be a "saturated alkyl" group, which means that it does not contain any alkene or alkyne moieties. The alkyl moiety may also be an "unsaturated alkyl" moiety, which means that it contains at least one alkene or alkyne moiety. An "alkene" moiety refers to a group consisting of at least two carbon atoms and at least one carbon-carbon double bond, and an "alkyne" moiety refers to a group consisting of at least two carbon atoms and at least one carbon-carbon triple bond. The alkyl moiety, whether saturated or unsaturated, may be branched, non-branched, or cyclic. The alkyl group has 1 to 20 carbon atoms (whenever it appears herein, a numerical range such as "1 to 20" refers to each integer in the given range; e.g., "1 to 20 carbon atoms" means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms, although the present definition also covers the occurrence of the term "alkyl" where no numerical range is designated). More preferably, it is a "medium" size alkyl having 1 to 10 carbon atoms. Most preferably, it is a "lower" alkyl having 1 to 4 carbon atoms e.g., methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, iso-butyl. The alkyl group may be substituted or unsubstituted. When substituted, the substituent group(s) is(are) preferably one or more group(s) individually and independently selected from hydroxy, alkoxy, mercapto, alkylthio, cyano, halo, carbonyl, nitro, and amino. The term "aromatic" refers to a mono or bicyclic aromatic group of 6 to 12 carbon atoms which has at least one ring having a conjugated pi electron system e.g., phenyl, naphthyl or anthracene groups. The term "heteroaromatic" refers to a mono or bicyclic aromatic group of 5 to 10 ring atoms wherein one, two or three rings atoms are selected from a group consisting of nitrogen, oxygen or sulfur, the remaining ring atoms being carbon e.g., pyridine, pyrrole, thiophene, indole, imidazole, quinoline, isoquinoline, pyrazine, furan, pyrimidine, oxazole, triazole, pyrazole and the like. The term "aliphatic ring" refers to a saturated cyclic group of 3 to 10 carbon atoms e.g., cyclcopropane, cyclobutane, cyclopentane, cyclohexane and the like. The term "heteroaliphatic ring" refers to a saturated cyclic group of 5 to 10 ring atoms wherein one, two or three ring atoms are selected from the group consisting of nitrogen, sulfur, sulfoxide, sulfone, -SO2O-- group or oxygen the remaining ring atoms being carbon e.g., tetrahydropyran, piperidine, pyrrolidine, piperazine, morpholine and the like. The term "amine" refers to a chemical moiety of formula -NR3Rb where R3 and Rb are independently selected from the group consisting of hydrogen, saturated or unsaturated alkyl, and five-membered or six-membered aromatic or heteroaromatic ring, where the ring is optionally substituted with one, two or three substituents independently selected from the group consisting of alkyl, halogen, trihalomethyl, carboxylate, nitro, and ester moieties. The term "halogen" refers to an atom selected from the group consisting of fluorine, chlorine, bromine, and iodine. ' The term "trihalomethyl" refers to the -CX3 group, where X is a halogen, e.g., trifluoromethyl. The term "carboxylic acid" or "carboxylate" refers to a chemical moiety with formula -(R)n-- COOH, where R is selected from the group consisting of saturated or unsaturated alkyl and five- membered or six-membered aromatic or heteroaromatic ring and where n is O or 1. The term "ester" refers to a chemical moiety with formula -(R)n-COOR', where R and R' are independently selected from the group consisting of saturated or unsaturated alkyl and five- membered or six-membered aromatic or heteroaromatic ring and where n is O or 1. The term "aldehyde" refers to a chemical moiety with formula -(R)n -CHO, where R is selected from the group consisting of saturated or unsaturated alkyl and five-membered or six- membered aromatic or heteroaromatic ring and where n is O or 1. The term "alkoxy" refers to a group -OR0 where R0 is unsubstituted lower alkyl e.g., methoxy, ethoxy, propoxy, butoxy, and the like. The term "fused bicyclic ring" refers to a five- or six-membered heteroaliphatic ring fused with an aromatic or heteroaromatic ring. "Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. For example, "alkyl group optionally substituted with halogen" means that the halogen may, but need not be present, and the description includes situations where the alkyl group is substituted with a halogen group and situations where the alkyl group is not substituted with the halogen group. The compounds of Formulas (I), (II) or (III) may exhibit the phenomena of tautomerism and structural isomerism. For example, the compounds described herein may adopt an E or a Z configuration about the double bond connecting the 2-indolinone moiety to the pyrrole moiety or they may be a mixture of E and Z. This invention encompasses any tautomeric or structural isomeric form and mixtures thereof which possess the ability to modulate RTK1 CTK and/or STK activity and is not .limited to any one tautomeric or structural isomeric form. A "pharmaceutical composition" refers to a mixture of one or more of the compounds described herein, or physiologically/pharmaceutically acceptable salts or prodrugs thereof, with other chemical components, such as physiologically/pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration of a compound to an organism. The compound of Formula (I) may also act as a prodrug. A "prodrug" refers to an agent which is converted into the parent drug in vivo. Prodrugs are often useful because, in some situations, they may be easier to administer than the parent drug. They may, for instance, be bioavailable by oral administration whereas the parent drug is not. The prodrug may also have improved solubility in pharmaceutical compositions over the parent drug. An example, without limitation, of a prodrug would be a compound of the present invention which is administered as an ester (the "prodrug") to facilitate transmittal across a cell membrane where water solubility is detrimental to mobility but then is metabolically hydrolyzed to the carboxylic acid, the active entity, once inside the cell where water solubility is beneficial. As used herein, a "pharmaceutically acceptable carrier" refers to a carrier or diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered compound. A "pharmaceutically acceptable excipient" refers to an inert substance added to a pharmaceutical composition to further facilitate administration of a compound. Examples, without limitation, of excipients include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils and polyethylene glycols. As used herein, the term "pharmaceutically acceptable salts, solvates or hydrates" refers to those salts, solvates or hydrates which retain the biological effectiveness and properties of the parent compound. Further, it should be understood that the term "compound" as used herein includes the pharmaceutically acceptable salts, solvates and hydrates of the compound, even if not explicitly recited. "PK" refers to receptor protein tyrosine kinase (RTKs), non-receptor or "cellular" tyrosine kinase (CTKs) and serine-threonine kinases (STKs). "Modulation" or "modulating" refers to the alteration of the catalytic activity of protein kinases, in particular CDK2 kinase. In particular, modulating refers to the activation of the catalytic activity, preferably the activation or inhibition of the catalytic activity of, protein kinases, in particular CDK2 kinase, depending on the concentration of the compound or salt to which the protein kinases, in particular CDK2 kinase, is exposed or, more preferably, the inhibition of the catalytic activity of protein kinases, in particular CDK2 kinase. "Therapeutically effective amount" refers to that amount of the compound being administered which will relieve to some extent one or more of the symptoms of the disorder being treated. In reference to the treatment of cancer, a therapeutically effective amount refers to that amount which has the effect of: (1) reducing the size of the tumor; (2) inhibiting (that is, slowing to some extent, preferably stopping) tumor metastasis; (3) inhibiting to some extent (that is, slowing to some extent, preferably stopping) tumor growth, and/or, (4) relieving to some extent (or, preferably, eliminating) one or more symptoms associated with the cancer. The term "function" refers to the cellular role of a protein kinase. The protein kinase family includes members that regulate many steps in signaling cascades, including cascades controlling cell growth, migration, differentiation, gene expression, muscle contraction, glucose metabolism, cellular protein synthesis, and regulation of the cell cycle. The term "catalytic activity," in the context of the invention, defines the rate at which a protein kinase phosphorylates a substrate. Catalytic activity can be measured, for example, by determining the amount of a substrate converted to a product as a function of time. Phosphorylation of a substrate occurs at the active-site of a protein kinase. The active-site is normally a cavity in which the substrate binds to the protein kinase and is phosphorylated. The term "substrate" as used herein refers to a molecule phosphorylated by a protein kinase. The substrate is preferably a peptide and more preferably a protein. The term "activates" refers to increasing the cellular function of a protein kinase. The protein kinase function is preferably the interaction with a natural binding partner and most preferably catalytic activity. The term "inhibit" refers to decreasing the cellular function of a protein kinase. The protein kinase function is preferably the interaction with a natural binding partner and most preferably catalytic activity. The term "modulates" refers to altering the function of a protein kinase by increasing or decreasing the probability that a complex forms between a protein kinase and a binding partner. A modulator preferably increases the probability that such a complex forms between the protein kinase and the binding partner, more preferably increases or decreases the probability that a complex forms between the protein kinase and the binding partner depending on the concentration of the compound exposed to the protein kinase, and most preferably decreases the probability that a complex forms between the protein kinase and the binding partner. A modulator preferably activates the catalytic activity of a protein kinase, more preferably activates or inhibits the catalytic activity of a protein kinase depending on the concentration of the compound exposed to the protein kinase, or most preferably inhibits the catalytic activity of a protein kinase. The term "complex" refers to an assembly of at least two molecules bound to one another. Signal transduction complexes often contain at least two protein molecules bound to one another. The term "binding partner" refers to a compound that binds to a protein kinase in cells. Binding partners can play a role in propagating a signal in a protein kinase signal transduction process. A change in the interaction between a protein kinase and a binding partner can manifest itself as an increased or decreased probability that the interaction forms, or an increased or decreased concentration of the protein kinase/binding partner complex. A binding partner may be a natural binding partners, in which case the binding partner is one which binds to the protein kinase during a cell's normal function. However, other molecules which bind to the protein kinase are also the protein kinase's binding partners. A protein kinase binding partner can bind to a protein kinase's intracellular region with high affinity. High affinity represents an equilibrium binding constant on the order of 10'6 M or less. In addition, a natural binding partner can also transiently interact with a protein kinase intracellular region and chemically modify it. Protein kinase natural binding partners are chosen from a group that includes, but is not limited to, SRC homology 2 (SH2) or 3 (SH3) domains, other phosphoryl tyrosine binding (PTB) domains, guanine nucleotide exchange factors, protein phosphatases, and other protein kinases. Methods of determining changes in interactions between protein kinases and their natural binding partners are readily available in the art. The term "contacting" as used herein refers to mixing a solution comprising a compound of the invention with a liquid medium bathing the cells of the methods. The solution comprising the compound may also comprise another component, such as dimethylsulfoxide (DMSO), which facilitates the uptake of the compound or compounds into the cells of the methods. The solution comprising the compound of the invention may be added to the medium bathing the cells by utilizing a delivery apparatus, such as a pipet-based device or syringe-based device. The compounds of the invention preferably modulate the activity of the protein kinase in vitro. These compounds preferably show positive results in one or more in vitro assays for an activity corresponding to treatment of the disease or disorder in question (such as the assays described in the Examples below). The invention also features a method of identifying compounds that modulate the function of protein kinase, comprising the following steps: (a) contacting cells expressing the protein kinase with the compound; and (b) monitoring an effect upon the cells. The effect upon the ceils is preferably a change or an absence of a change in cell phenotype, more preferably it is a change or an absence of a change in cell proliferation, even more preferably it is a change or absence of a change in the catalytic activity of the protein kinase, and most preferably it is a change or absence of a change in the interaction between the protein kinase with a natural binding partner, as described herein. The term "monitoring" refers to observing the effect of adding the compound to the cells of the method. The effect can be manifested in a change in cell phenotype, cell proliferation, protein kinase catalytic activity, or in the interaction between a protein kinase and a natural binding partner. The term "effect" describes a change or an absence of a change in cell phenotype or cell proliferation. "Effect" can also describe a change or an absence of a change in the catalytic activity of the protein kinase. "Effect" can also describe a change or an absence of a change in an interaction between the protein kinase and a natural binding partner. The term "cell phenotype" refers to the outward appearance of a cell or tissue or the function of the cell or tissue. Examples of cell phenotype are cell size (reduction or enlargement), cell proliferation (increased or decreased numbers of cells), cell differentiation (a change or absence of a change in cell shape), cell survival, apoptosis (cell death), or the utilization of a metabolic nutrient (e.g., glucose uptake). Changes or the absence of changes in cell phenotype are readily measured by techniques known in the art. In a preferred embodiment, the invention features a method for identifying the compounds of the invention, comprising the following steps: (a) lysing the cells to render a lysate comprising protein kinase; (b) adsorbing the protein kinase to an antibody; (c) incubating the adsorbed protein kinase with a substrate or substrates; and (d) adsorbing the substrate or substrates to a solid support or antibody. In other preferred embodiments, the step of monitoring the effect on the cells comprises measuring the phosphate concentration of the substrate or substrates. The invention also features a method of regulating kinase signal transduction comprising administering to a subject a therapeutically effective amount of a compound of the invention as described herein. Furthermore, the invention features a method of preventing or treating an abnormal condition in an organism, where the abnormal condition is associated with an aberration in a signal transduction pathway characterized by an interaction between a protein kinase and a natural binding partner, where the method comprises the following steps: (a) administering a compound of the invention as described herein; and (b) promoting or disrupting the abnormal interaction. The organism is preferably a mammal and the abnormal condition is preferably cancer. In other preferred embodiments, the abnormal condition is an angiogenesis-related disorder or a dermatologic, ophthalmic, neurologic, cardiovascular, or immune disorder. Some specific abnormal conditions include hypertension, depression, generalized anxiety disorder, phobias, post-traumatic stress syndrome, avoidant personality disorder, sexual dysfunction, eating disorders, obesity, chemical dependencies, cluster headache, migraine, pain, Alzheimer's disease, obsessive-compulsive disorder, panic disorder, memory disorders, Parkinson's disease, endocrine disorders, vasospasm, cerebellar ataxia, and gastrointestinal tract disorders. The term "aberration," in conjunction with a signal transduction process, refers to a protein kinase that is over- or under-expressed in an organism, mutated such that its catalytic activity is lower or higher than wild-type protein kinase activity, mutated such that it can no longer interact with a natural binding partner, is no longer modified by another protein kinase or protein phosphatase, or no longer interacts with a natural binding partner. The term "promoting or disrupting the abnormal interaction" refers to a method that can be accomplished by administering a compound of the invention to cells or tissues in an organism. A compound can promote an interaction between a protein kinase and natural binding partners by forming favorable interactions with multiple atoms at the complex interface. Alternatively, a compound can inhibit an interaction between a protein kinase and natural binding partners by compromising favorable interactions formed between atoms at the complex interface. The term "indolinone" is used as that term is commonly understood in the art and includes a large subclass of substituted or unsubstituted compounds that are capable of being synthesized from an aldehyde moiety and an oxindole moiety. Particular examples of compounds of the invention include the compounds shown in Table 1 : Table 1

H-

H-

/7-

H-

Biological activity of certain compounds of the invention, determined as described in the Examples herein, is shown in Table 2. , Table 2

Another aspect of the invention provides for a method for synthesizing compounds of the invention by reacting a compound of formula A with a compound of formula B or C

(A) (B) (C) wherein R1 - R5 in Formula (B) are as defined herein for Formula (II) and R1 - R6 in Formula (Vl) are as defined herein for Formula (III). To synthesize the compounds of the invention a base may be used. The base is preferably a nitrogen base or an inorganic base. "Nitrogen bases" are commonly used in the art and are selected from acyclic and cyclic amines. Examples of nitrogen bases include, but are not limited to, ammonia, methylamine, trimethylamine, triethylamine, aniline, 1 ,8-diazabicyclo[5.4.0]undec-7-ene, diisopropylethylamine, pyrrolidine, piperidine, and pyridine or substituted pyridine (e.g., 2,6-di- tertbutylpyridine). "Inorganic bases" are bases that do not contain any carbon atoms. Examples of inorganic bases include, but are not limited to, hydroxide, phosphate, bisulfate, hydrosulfide (SH'), and amide anions. Those skilled in the art know which nitrogen base or inorganic base would match the requirements of the reaction conditions. In certain embodiments of the invention, the base used may be pyrrolidine or piperidine. In other embodiments the base may be the hydroxide anion, preferably used as its sodium or potassium salt. The synthesis of the compounds of the invention generally takes place in a solvent. The solvent of the reaction is preferably a protic solvent or an aprotic solvent. "Protic solvents" are those that are capable of donating a proton to a solute. Examples of protic solvents include, but are not limited to, alcohols and water. "Aprotic solvents" are those solvents that, under normal reaction conditions, do not donate a proton to a solute. Typical organic solvents, such as hexane, toluene, benzene, methylene chloride, dimethylformamide, chloroform, tetrahydrofuran, are some of the examples of aprotic solvents. Other aprotic solvents are also within the scope of the present invention. In some preferred embodiments, the solvent of the reaction is an alcohol, which may preferably be isopropanol or most preferably ethanol. Water is another preferred protic solvent. Dimethylformamide, known in the chemistry art as DMF, is a preferred aprotic solvent. The synthetic method of the invention preferably takes place at a temperature greater than room temperature. More preferably, the elevated temperature is preferably about 30-150cC, more preferably is about 80-1000C, and most preferably is about 80-900C, which is about the temperature at which ethanol boils (i.e., the boiling point of ethanol). By "about" a certain temperature it is meant that the temperature range is preferably within 100C of the listed temperature, more preferably within 5 °C of the listed temperature, and most preferably within 2°C of the listed temperature. Therefore, by way of example, by "about 800C" it is meant that the temperature range is preferably 80±10 0C, more preferably 80±5 0C, and most preferably 80±2°C. The synthetic method of the invention may be accompanied by the step of screening a library for a compound of the desired activity and structure, thus, providing a method of synthesis of a compound by first screening for a compound having the desired properties and then chemically synthesizing that compound. Methods of Modulating Kinases The invention also features a method of identifying compounds that modulate the function of protein kinase, comprising the following steps: (a) contacting cells expressing the protein kinase with the compound; and (b) monitoring an effect upon the cells. The effect upon the cells is preferably a change or an absence of a change in cell phenotype, more preferably it is a change or an absence of a change in cell proliferation, even more preferably it is a change or absence of a change in the catalytic activity of the protein kinase, and most preferably it is a change or absence of a change in the interaction between the protein kinase with a natural binding partner, as described herein. In yet another aspect, the invention features a method for treating a disease related to unregulated kinase signal transduction, where the method includes the step of administering to a subject in need thereof a therapeutically effective amount of a compound of the invention as described herein. The invention also features a method of regulating kinase signal transduction comprising administering to a subject a therapeutically effective amount of a compound of the invention as described herein. Furthermore, the invention features a method of preventing or treating an abnormal condition in an organism, where the abnormal condition is associated with an aberration in a signal transduction pathway characterized by an interaction between a protein kinase and a natural binding partner, where the method comprises the following steps: (a) administering a compound of the W

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invention as described herein; and (b) promoting or disrupting the abnormal interaction. The organism is preferably a mammal and the abnormal condition is preferably cancer. In other preferred embodiments, the abnormal condition is an angiogenesis-related disorder or a dermatologic, ophthalmic, neurologic, cardiovascular, or immune disorder. Some specific abnormal conditions include hypertension, depression, generalized anxiety disorder, phobias, post-traumatic stress syndrome, avoidant personality disorder, sexual dysfunction, eating disorders, obesity, chemical dependencies, cluster headache, migraine, pain, Alzheimer's disease, obsessive-compulsive disorder, panic disorder, memory disorders, Parkinson's disease, endocrine disorders, vasospasm, cerebellar ataxia, and gastrointestinal tract disorders. The present invention relates to compounds capable of regulating and/or modulating cellular signal transduction and, in preferred embodiments, receptor and non-receptor tyrosine kinase signal transduction. ■ Receptor kinase mediated signal transduction is initiated by extracellular interaction with a specific growth factor (ligand), followed by receptor dimerization, transient stimulation of the intrinsic protein kinase activity and phosphorylation. Binding sites are thereby created for intracellular signal transduction molecules and lead to the formation of complexes with a spectrum of cytoplasmic signaling molecules that facilitate the appropriate cellular response (e.g., cell division, metabolic effects to the extracellular microenvironment). See, Schlessinger and Ullrich, 1992, Neuron 9:303- 391. It has been shown that tyrosine phosphorylation sites in growth factor receptors function as high-affinity binding sites for SH2 (src homology) domains of signaling molecules. Fantl et ai, 1992, Cell 69:413-423; Songyang et ai, 1994, MoI. Cell. Biol. 74:2777-2785); Songyang et al., 1993, Cell 72:767-778; and Koch et ai, 1991 , Science 252:668-678. Several intracellular substrate proteins that associate with receptor kinases have been identified. They may be divided into two principal groups: (1) substrates which have a catalytic domain; and (2) substrates which lack such domain but serve as adapters and associate with catalytically active molecules. Songyang et ai, 1993, Cell 72:767-778. The specificity of the interactions between receptors and SH2 domains of their substrates is determined by the amino acid residues immediately surrounding the phosphorylated tyrosine residue. Differences in the binding affinities between SH2 domains and the amino acid sequences surrounding the phosphotyrosine residues on particular receptors are consistent with the observed differences in their substrate phosphorylation profiles. Songyang et ai, 1993, Cell 72:767-778. These observations suggest that the function of each receptor kinase is determined not only by its pattern of expression and ligand availability but also by the array of downstream signal transduction pathways that are activated by a particular receptor. Thus, phosphorylation provides an important regulatory step which determines the selectivity of signaling pathways recruited by specific growth factor receptors, as well as differentiation factor receptors. Kinase signal transduction results in, among other responses, cell proliferation, differentiation and metabolism. Abnormal cell proliferation may result in a wide array of disorders and diseases, including the development of neoplasia such as carcinoma, sarcoma, leukemia, glioblastoma, hemangioma, psoriasis, arteriosclerosis, arthritis and diabetic retinopathy (or other disorders related to uncontrolled angiogenesis and/or vasculogenesis). This invention is therefore directed to compounds which regulate, modulate and/or inhibit kinase signal transduction by affecting the enzymatic activity of the RKs and/or the non-receptor kinases and interfering with the signal transduced by such proteins. More particularly, the present invention is directed to compounds which regulate, modulate and/or inhibit the receptor tyrosine kinase (RTK) and/or non-receptor kinase mediated signal transduction pathways as a therapeutic approach to cure many kinds of tumors, including but not limited to carcinoma, sarcoma, erythroblastoma, glioblastoma, meningioma, astrocytoma, melanoma and myoblastoma. Indications may include, but are not limited to brain cancers, bladder cancers, ovarian cancers, gastric cancers, pancreas cancers, colon cancers, blood cancers, lung cancers and bone cancers. In particular, this invention is related to treated of disorders mediated by CDK2 protein kinases. A group of STKs that comprise a particularly attractive therapeutic target for cell proliferative disorders are the cyclin dependent kinases or CDKs. CDKs play a prominent role in control of cellular proliferation. That is, the proliferation of all eukaryotic cells occurs through a continuum of events called the "cell cycle." While in fact a continuum, for purposes of discussion, the cell cycle is conveniently broken down into four phases, G1 , S, G2 and M. There is another phase, known as G0, which is not part of the cell cycle per se but rather is a quiescent state in which a cell resides prior to entering the cell cycle at G1. In G1 , cellular activity is heavily dependent on the stimulating influence of external growth factors. It is during G1 that the machinery necessary for DNA replication is assembled. Between G1 and S is a critical point called the "restriction" point. At the restriction point a cell must decide whether it is prepared to continue with the cell cycle. If so, the cell commits to entry into S phase at which time it no longer requires the stimulation of external growth factors. Progress through the cell cycle is entirely intracellular from this point. It is in the S phase that DNA is replicated. At the end of S phase and entry into G2, a cell has 4N DNA content. In G2, a cell begins preparation for M phase and cytokinesis. Progression through the cell cycle is regulated by CDKs. As the name suggests, in order to perform their functions, the CDKs require association with cyclin regulatory subunits. Presently, about nine CDKs and about 12 families of cyclins with which the CDKs can interact are known. Two or these, cyclin D/CDK4 and cyclin E/CDK2 are responsible for controlling entry of a cell into G1 from G0, passage of the cell through the restriction point and commitment to S phase. Progress through S phase is driven by cyclin E/CDK2 and cyclin A/CDK2, the latter of which promotes completion of S phase and entry into G2. Finally, progression through G2, DNA segregation and eventual separation of the parent cell into two daughter cells during M phase and subsequent cytokinesis is controlled by cyclins A and B in conjunction with CDK1. Throughout the cell cycle there are checkpoints at which a cell monitors both its external and internal environments to assure that continued progress through the cycle is appropriate. Two important, well-studied check points occur in G1 and G2/mitosis. At the G1 checkpoint, the cell checks to see that it has adequate nutrition, that it is properly interacting with other cells or their substratum and that its DNA is intact. At the G2 checkpoint, the cell assures that DNA replication is complete and correct and that the mitotic spindle has properly formed. A negative response at any of these checkpoints results in arrest of the cell cycle which can be temporary, if repairs can be made, or permanent, that is, death of the cell, if repairs cannot be made. These checkpoints are important because inappropriate cell cycle progress is a hallmark of cell proliferation disorders such as malignant tumor growth. Since CDKs are primarily responsible for driving cells through the cell cycle, including the checkpoints, their proper functioning is critical to proper cell proliferation. It is for this reason that CDKs have attracted much interest as therapeutic targets. While therapeutic potential exists in all the CDKs, CDK2 has come under particular scrutiny due to the apparently critical role that it play in the cell cycle. For example, it has been demonstrated that CDK2 dominant negative constructs can halt cell cycle progression completely (S. Van den Heuval, et al., Science, 1993, 262:2050-2054). Furthermore, anchorage- independent growth, a key feature of tumor cells, is mediated by CDK2 complexes (G. Orend, et al., Oncogene, 1998, 16:2575-2583). In another study, a peptide inhibitor of CDK2 function was shown to selectively kill tumor cells over normal cells (Y. N. Chen, et al., Proc. Natl. Acad. Sci. USA, 1999, 96:4221 -4223). Target Diseases The compounds described herein are useful for treating disorders related to unregulated kinase signal transduction, including cell proliferative disorders, fibrotic disorders and metabolic disorders. Cell proliferative disorders which can be treated or further studied by the present invention include cancers, blood vessel proliferative disorders and mesangial cell proliferative disorders. Blood vessel proliferative disorders refer to angiogenic and vasculogenic disorders generally resulting in abnormal proliferation of blood vessels. The formation and spreading of blood vessels, or vasculogenesis and angiogenesis, respectively, play important roles in a variety of physiological processes such as embryonic development, corpus luteum formation, wound healing and organ regeneration. They also play a pivotal role in cancer development. Other examples of blood vessel proliferation disorders include arthritis, where new capillary blood vessels invade the joint and destroy cartilage, and ocular diseases, like diabetic retinopathy, where new capillaries in the retina invade the vitreous, bleed and cause blindness. Conversely, disorders related to the shrinkage, contraction or closing of blood vessels, such as restenosis, are also implicated. Fibrotic disorders refer to the abnormal formation of extracellular matrix. Examples of fibrotic disorders include hepatic cirrhosis and mesangial cell proliferative disorders. Hepatic cirrhosis is characterized by the increase in extracellular matrix constituents resulting in the formation of a hepatic scar. Hepatic cirrhosis can cause diseases such as cirrhosis of the liver. An increased extracellular matrix resulting in a hepatic scar can also be caused by viral infection such as hepatitis. Lipocytes appear to play a major role in hepatic cirrhosis. Other fibrotic disorders implicated include atherosclerosis (see, below). Mesangial cell proliferative disorders refer to disorders brought about by abnormal proliferation of mesangial cells. Mesangial proliferative disorders include various human renal diseases, such as glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombotic microangiopathy syndromes, transplant rejection, and glomerulopathies PTKs have been associated with such cell proliferative disorders. For example, some members of the RTK family have been associated with the development of cancer. Some of these receptors, like the EGFR (Tuzi et al., 1991 , Br, J. Cancer 63:227-233; Torp et al., 1992, APMIS 700:713-719) HER2/neu (Slamon et al., 1989, Science 244:707-712) and the PDGF-R (Kumabe et al., 1992, Oncogene 7:627-633) are overexpressed in many tumors and/or persistently activated by autocrine loops. In fact, in the most common and severe cancers these receptor overexpressions (Akbasak and Suner-Akbasak et al., 1992, J. Neurol. ScI. 177:119-133; Dickson et al., 1992, Cancer Treatment Res. 67:249-273; Korc et al., 1992, J. Clin. Invest. 00:1352-1360) and autocrine loops (Lee and Donoghue, 1992, J. Cell. Biol. 775:1057-1070; Korc etal., supra; Akbasak and Suner-Akbasak et al., supra) have been demonstrated. For example, the EGFR receptor has been associated with squamous cell carcinoma, astrocytoma, glioblastoma, head and neck cancer, lung cancer and bladder cancer. HER2 has been associated with breast, ovarian, gastric, lung, pancreas and bladder cancer. The PDGF-R has been associated with glioblastoma, lung, ovarian, melanoma and prostate cancer. The RTK c-met has been generally associated with hepatocarcinogenesis and thus hepatocellular carcinoma. Additionally, c-met has been linked to malignant tumor formation. More specifically, the RTK c-met has been associated with, among other cancers, colorectal, thyroid, pancreatic and gastric carcinoma, leukemia and lymphoma. Additionally, over-expression of the c- met gene has been detected in patients with Hodgkin's disease, Burkitt's disease, and the lymphoma cell line. The association between abnormalities in RTKs and disease are not restricted to cancer, however. For example, RTKs have been associated with metabolic diseases like psoriasis, diabetes meilitus, wound healing, inflammation, and neurodegenerative diseases. These diseases include, but are not limited to hypertension, depression, generalized anxiety disorder, phobias, post-traumatic stress syndrome, avoidant personality disorder, sexual dysfunction, eating disorders, obesity, chemical dependencies, cluster headache, migraine, pain, Alzheimer's disease, obsessive- compulsive disorder, panic disorder, memory disorders, Parkinson's disease, endocrine disorders, vasospasm, cerebellar ataxia, and gastrointestinal tract disorders. For example, the EGF-R is indicated in corneal and dermal wound healing. Defects in the Insulin-R and the IGF-1 R are indicated in type-ll diabetes meilitus. A more complete correlation between specific RTKs and their therapeutic indications is set forth in Plowman etal., 1994, DN&P 7:334-339. Not only receptor type kinases, but also many cellular kinases (CKs) including src, abl, fps, yes, fyn, lyn, lck, blk, hck, fgr, yrk (reviewed by Bolen et al., 1992, FASEB J. 6:3403-3409) are involved in the proliferative and metabolic signal transduction pathway and thus in indications of the present invention. For example, mutated src (v-src) has been demonstrated as an oncoprotein (pp60v"src) in chicken. Moreover, its cellular homologue, the proto-oncogene ppδO0"^0 transmits oncogenic signals of many receptors. For example, overexpression of EGF-R or HER2/neu in tumors leads to the constitutive activation of pp60°~~src, which is characteristic for the malignant cell but absent from the normal cell. On the other hand, mice deficient for the expression of c-src exhibit an osteopetrotic phenotype, indicating a key participation of c-src in osteoclast function and a possible involvement in related disorders. Similarly, Zap 70 is implicated in T-cell signaling. Furthermore, the identification of CTK modulating compounds to augment or even synergize with RTK aimed blockers is an aspect of the present invention. Finally, both RTKs and non-receptor type kinases have been connected to hyperimmune disorders. The compounds of the present invention are also effective in treating diseases that are related to the PYK-2 protein. This protein, its cellular function, and diseases related to them are set forth in detail in U.S. Patent Number 5,837,524, issued November 17, 1998, and entitled "PYK2 RELATED PRODUCTS AND METHODS," and U.S. Patent Number 5,837,815, issued November 17, 1998, and entitled "PYK2 RELATED PRODUCTS AND METHODS," both of which are hereby incorporated by reference herein in their entirety, including any drawings. Pharmaceutical Formulations And Routes Of Administration The compounds described herein can be administered to a human patient per se, or in pharmaceutical compositions where they are mixed with other active ingredients, as in combination therapy, or suitable carriers or excipient(s). Techniques for formulation and administration of the compounds of the instant application may be found in "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA1 latest edition. (a) Routes Of Administration Suitable routes of administration may, for example, include oral, rectal, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intravenous, intramedullary injections, as well as intrathecal, direct intraventricular, intraperitoneal, intranasal, or intraocular injections. Alternately, one may administer the compound in a local rather than systemic manner, for example, via injection of the compound directly into a solid tumor, often in a depot or sustained release formulation. Furthermore, one may administer the drug in a targeted drug delivery system, for example, in a liposome coated with tumor-specific antibody. The liposomes will be targeted to and taken up selectively by the tumor. (b) Composition/Formulation The pharmaceutical compositions of the present invention may be manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes. Pharmaceutical compositions for use in accordance with the present invention thus may be formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. Types of administration includes, injection, oral administration, buccal administration, inhalation, parenteral administration by injection, e.g., by bolus injection or continuous infusion, rectal administration, depot preparation by such as implantation (for example subcutaneously or intramuscularly) or by intramuscular injection For injection, the agents of the invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art. For oral administration, the compounds can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art. Such carriers enable the compounds of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated. Pharmaceutical preparations for oral use can be obtained by mixing one or more solid excipient with one or more compound of the invention, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate. Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses. Pharmaceutical preparations which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. All formulations for oral administration should be in dosages suitable for such administration. For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner. For administration by inhalation, the compounds for use according to the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebuliser, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, e.g., gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch. The compounds may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form. Additionally, suspensions of the active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides. In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. Alternatively, other delivery systems for hydrophobic pharmaceutical compounds may be employed. Liposomes and emulsions are well known examples of delivery vehicles or carriers for hydrophobic drugs. Certain organic solvents such as dimethylsulfoxide also may be employed, although usually at the cost of greater toxicity. Additionally, the compounds may be delivered using a sustained-release system, such as semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent. Various sustained-release materials have been established and are well known by those skilled in the art. Sustained-release capsules may, depending on their chemical nature, release the compounds for a few weeks up to over 100 days. Depending on the chemical nature and the biological stability of the therapeutic reagent, additional strategies for protein stabilization may be employed. Many of the PTK modulating compounds of the invention may be provided as salts with pharmaceutically compatible counterions. Pharmaceutically compatible salts may be formed with many acids, including but not limited to hydrochloric, sulfuric, acetic, lactic, tartaric, maleic, succinic, etc. Salts tend to be more soluble in aqueous or other protic solvents than are the corresponding free base forms. (c) Effective Dosage. Pharmaceutical compositions suitable for use in the present invention include compositions where the active ingredients are contained in an amount effective to achieve its intended purpose. More specifically, a therapeutically effective amount means an amount of compound effective to prevent, alleviate or ameliorate symptoms of disease or prolong the survival of the subject being treated. Determination of a therapeutically effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein. For any compound used in the methods of the invention, the therapeutically effective dose can be estimated initially from cell culture assays. For example, a dose can be formulated in animal models to achieve a circulating concentration range that includes the IC50 as determined in cell culture (i.e., the concentration of the test compound which achieves a half-maximal inhibition of the PTK activity). Such information can be used to more accurately determine useful doses in humans. Toxicity and therapeutic efficacy of the compounds described herein can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio between LD50 and ED50. Compounds which exhibit high therapeutic indices are preferred. The data obtained from these cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. (See e.g., Fingl et al., 1975, in "The Pharmacological Basis of Therapeutics", Ch. 1 p.1). Dosage amount and interval may be adjusted individually to provide plasma levels of the active moiety which are sufficient to maintain the kinase modulating effects, or minimal effective concentration (MEC). The MEC will vary for each compound but can be estimated from in vitro data; e.g., the concentration necessary to achieve 50-90% inhibition of the kinase using the assays described herein. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. However, HPLC assays or bioassays can be used to determine plasma concentrations. Dosage intervals can also be determined using MEC value. Compounds should be administered using a regimen which maintains plasma levels above the MEC for 10-90% of the time, preferably between 30-90% and most preferably between 50-90%. In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to plasma concentration. Examples The examples below are non-limiting and are merely representative of various aspects and features of the present invention. The examples describe methods for synthesizing compounds of the invention and methods for measuring an effect of a compound on the function of protein kinases. Synthetic Examples General reaction scheme

1. chlorasulfonio acid 2. water

Example 1 : 6,6-Dioxo-3,6,8,9-tetrahvdro-1 /-/-7-oxa-6λ -thia-S-aza-cvclopentalalnaphthalen^-one 4-Hydroxyethyl oxindole (5 g, 28.2 mmol) was dissolved in 20 ml_ of chlorosulfonic acid with stirring at room temperature. After 30 minutes, the reaction mixture was slowly added to 300 ml_ of ice water with stirring. The solids were filtered and dried to afford 1.9 g (28 % yield) of 6,6-dioxo- 3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one as a white powder. Rf = 0.62 (10% methanol in dichloromethane). 1H-NMR (300 MHz, dimethylsulfoxide-d6) 10.79 (s, 1 H, NH), 7.65 (d, J = 8.2 Hz, 1 H, aromatic), 6.90 (d, J = 8.2 Hz, 1 H, aromatic), 4.87 (t, J = 5.7 Hz, 2H, CH2OSO2), 3.51 (s, 2H, CH2CO), 3.04 (t, J= 5.9 Hz, 2H, CH2). MS (m/z) 239 M+. Example 2 General method for condensation of an oxindole with a pyrrole aldehyde: 6,6-Dioxo-3,6,8,9- tetrahydro-1 /-/-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one (1.0 eq) and 1.05 - 1.20 eq of the pyrrole aldehyde were suspended in reagent ethanol at a concentration of 0.25 - 1.0 M. Piperidine (0.05 -2.0 eq) was added and the mixture refluxed for 1 - 4 hours. Thin layer chromatography was used to determine when most or all of the starting materials were consumed. If the pyrrole aldehyde contained a carboxylic acid group, 1.0 - 2.0 eq of acetic acid was added and the refluxing continued for 10 minutes. The reaction mixture was cooled to room temperature and the solids collected by vacuum filtration and washed with ethanol. The solids were slurry-washed by heating and stirring in ethanol for 5 - 20 minutes. The mixture was cooled to room temperature. The solids were collected by vacuum filtration, washed with ethanol and dried under vacuum to give the condensed indolinone. Example 3: 4-methyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6λ6-th ia-3-aza-cyclopenta[a]naphthalen- (1Z)-ylidenemethyl]-1H-pyrrole-3-carboxylic acid, was prepared using the general method of Example 2. 6,6-Dioxo-3,6,8,9-tetrahydro-1H-7-oxa-6λ6-thia-3-aza-cyclop enta[a]naphthalen-2-one (239 mg, 1 mmol), 168 mg (1.1 mmol) of 5-formyl-4-methyl-1λ/-pyrrole-3-carboxylic acid and 102 mg (1.2 mmol) of piperidine were refluxed in 3 ml. of ethanol for 2 hours. Thin layer chromatography (10 % methanol in dichloromethane) showed that all of the starting oxindole was consumed. Acetic acid (144 mg, 2.4 mmol) was added and the refluxing continued for 10 minutes. The reaction mixture was cooled to room temperature and the solids collected by vacuum filtration and washed with ethanol. The solids were slurry-washed by refluxing and stirring in ethanol for 10 minutes. The mixture was cooled to room temperature. The solids were collected by vacuum filtration, washed with ethanol and dried under vacuum to give 187 mg (50 % yield) of Example 3, 4-methyl-5-[2,6,6-trioxo-3,6,8,9- tetrahydro-2H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen- (1Z)-ylidenemethyl]-1H-pyrrole-3- carboxylic acid as a red-orange solid. Example 4: ({4-methyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2W-7-oxa-6λ6- thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1W-pyrrole-3-car bonyl}-amino)-acetic acid ethyl ester, was prepared using the general method of Example 2. 6,6-Dioxo-3,6,8,9-tetrahydro-1 f/-7-oxa-6λ6- thia-3-aza-cyclopenta[a]naphthalen-2-one (84 mg, 0.35 mmol), 100 mg (0.42 mmol) of [(5-formyl-4- methyl-1H-pyrrole-3-carbonyl)-amino]-acetic acid ethyl ester and 18 mg (0.21 mmol) of piperidine were refluxed in 1 ml_ of ethanol for 2 hours. Thin layer chromatography (10% methanol in dichloromethane) showed that all of the starting oxindole was consumed. Acetic acid (25.2 mg, 0.42 mmol) was added and the refluxing continued for 10 minutes. The reaction mixture was cooled to room temperature and the solids collected by vacuum filtration and washed with ethanol. The solids were slurry-washed by refluxing and stirring in ethanol for 10 minutes. The mixture was cooled to room temperature. The solids were collected by vacuum filtration, washed with ethanol and dried under vacuum to give 60 mg (37% yield) of Example 4, ({4-methyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro- 2H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-(1Z)-yliden emethyl]-1 H-pyrrole-3-carbonyl}-amino)- acetic acid ethyl ester as a red-orange solid. 1H-NMR (300 MHz, dimethylsulfoxide-d6) 13.60 (s, 1H, NH), 11.45 (br s, 1H, CONH), 8.40 (t, 1H1 CONH), 7.80 (m, 1H, aromatic), 7.65 (d, 1H, aromatic), 7.05 (d, 1H, pyrrole CH), 4.95 (t, 2H, CH2OSO2), 4.15 (q, 2H, CH2O), 3.90 (d, 2H, CH2CO)1 3.60 (t, 2H, CH2), 3.30 (s, 3H, CH3), 1.20 (t, 3H, CH3). MS (m/z) 459 (M+). Example 5: 1-[1-f3-methyl-4-(morpholine-4-carbonyl)-1H-pyrrol-2-yl]-met h-(Z)-ylidene]-6,6-dioxo-3,6,8,9- tetrahydro-1 /7-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one, was prepared using the general method of Example 2. 6,6-Dioxo-3,6,8,9-tetrahydro-1H-7-oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-2-one (96 mg, 0.40 mmol), 111 mg (0.50 mmol) of [(5-formyl-4-methyl-1 H- pyrrole-3-carbonyl)-amino]acetic acid ethyl ester and 18 mg (0.20 mmol) of piperidine were refluxed in 1 mL of ethanol for 2 hours. Thin layer chromatography (10 % methanol in dichloromethane) showed that all of the starting oxindole was consumed. Acetic acid (24 mg, 0.40 mmol) was added and the refluxing continued for 10 minutes. The reaction mixture was cooled to room temperature and the solids collected by vacuum filtration and washed with ethanol. The solids were slurry-washed by refluxing and stirring in ethanol for 10 minutes. The mixture was cooled to room temperature. The solids were collected by vacuum filtration, washed with ethanol and dried under vacuum to give 73 mg (41% yield) of Example 5, 1-[1 -[3-methyl-4-(morpholine-4-carbonyl)-1W-pyrrol-2-yl]-meth-(Z )- ylidene]-6,6-dioxo-3,6,8,9-tetrahydro-1H-7-oxa-6λ6-thia-3-a za-cyclopenta[a]naphthalen-2-one as a red-orange solid. Example 6: 1 -[1 -[3-(3-Dimethylamino-propyl)-1 H-indol-2-yl]-meth-(Z)-ylidene]-6,6-dioxo-3,6,8,9- tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one (70 mg, 45 % yield), was prepared by condensing 3-(3-dimethylamino-propyl)-1 W-indole-2-carbaldehyde with 6,6-dioxo-3,6,8,9- tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. Example 7: 4-Methyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6λ6-th ia-3-aza-cyclopenta[a]naphthalen- (1Z)-ylidenemethyl]-1 W-pyrrole-2-carboxylic acid (3-pyrrolidin-1-yl-propyl)-amide. was prepared by condensing 5-formyl-4-methyl-1W-pyrrole-2-carboxylic acid (3-pyrrolidin-1-yl-propyl)-amide with 6,6- dioxo-3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. Example 8: 4-methyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6λ6-th ia-3-aza-cyclopenta[a]naphthalen- (1Z)-ylidenemethyl]-1 /V-pyrrole-3-carboxylic acid ethyl ester (79 mg, 47 % yield), was prepared by condensing 5-formyl-4-methyl-1 H-pyrrole-3-carboxylic acid ethyl ester with 6,6-dioxo-3,6,8,9- tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. Example 9: 1 -[1 -[3-methyl-4-(piperidine-1 -carbonyl)-1 W-pyrrol-2-yl]-meth-(Z)-ylidene]-6,6-dioxo-3,6,8,9- tetra-hydro-1 W-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one (77 mg, 44 % yield), was prepared by condensing 3-methyl-4-(piperidine-1-carbonyl)-1/-/-pyrrole-2-carbaldehy de with 6,6- dioxo-3,6,8,9-tetra-hydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. Example 10: 6,6-Dioxo-1 -[1 -[3-phenyl-4-(piperidine-1 -carbonyl)-1 H-pyrrol-2-yl]meth-(Z)-ylidene]-3,6,8,9- tetra-hydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one (98 mg, 62 % yield), was prepared by condensing 3-phenyl-4-(piperidine-1-carbonyl)-1 W-pyrrole-2-carbaldehyde with 6,6- dioxo-3,6,8,9-tetra-hydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. Example 11 : ^[^(S.S-Dimethyl-IH-pyrrol^-yO-meth-CZJ-ylideneJ-e.e-dioxo-S .e.δ.θ-tetrahydro-I H-T-oxa- 6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one was prepared by condensing 3,5-dimethyl-1 /V-pyrrole- 2-carbaldehyde with 6,6-dioxo-3,6,8,9-tetrahydro-1W-7-oxa-6λ6-thia-3-aza-cyclop enta[a]naphthalen-2- one using the general method of Example 2. MS (m/z) 345 (M+1). Example 12: 6,6-Dioxo-1 -[1 -(4,5,6,7-tetrahydro-1 H-indol-2-yl)-meth-(Z)-ylidene]-3,6,8,9-tetrahydro-1 H-I- oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one was prepared by condensing 4,5,6,7-tetrahydro- 1 H-indole-2-carbaldehyde with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 371 (M+1). Example 13: 3-{2-[2,6,6-Trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6λ6-thia-3-a za-cyclopentata]naphthalen-(1Z)- ylidenemethyl]-4,5,6,7-tetrahydro-1H-indol-3-yl}-propionic acid was prepared by condensing 3-(2- formyl-4,5,6,7-tetrahydro-1 H-indol-3-yl)-propionic acid with 6,6-dioxo-3,6,8,9-tetrahydro-1 AY-7-oxa- 6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 443 (M+1). Example 14: 1 -[1 -(1 H-lndol-2-yl)-meth-(Z)-ylidene]-6,6-dioxo-3,6,8,9-tetrahydro -1 H-7-oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-2-one was prepared by condensing 1 H-indole-2-carbaldehyde with 6,6- dioxo-3,6,8,9-tetrahydro-1 W-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 367 (M+1). Example 15: 1 -[1 -(4-Morpholin-4-yl-phenyl)-meth-(Z)-ylidene]-6,6-dioxo-3,6,8 ,9-tetrahydro-1 W-7-oxa-6λ6- thia-3-aza-cyclopenta[a]naphthalen-2-one was prepared by condensing 4-morpholin-4-yl- benzaldehyde with 6,6-dioxo-3,6,8,9-tetrahydro-1 W-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2- one usihg the general method of Example 2. MS (m/z) 413 (M+1). Example 16: 3-{5-Methyl-2-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6λ6 -thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1/-/-pyrrol-3-yl }-propionic acid was prepared by condensing 3-(2-formyl-5-methyl-1 f/-pyrrol-3-yl)-propionic acid with 6,6-dioxo-3,6,8,9-tetrahydro-1 H- 7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 403 (M+1). Example 17: 3-{2,4-Dimethyl-5-[2,6,6-trioxo-3,6(8,9-tetrahydro-2W-7-oxa- 6λ6-thia-3-aza- cyclopentatalnaphthalen^iZJ-ylidenemethylJ-IH-pyrrol-S-ylJ-p ropionic acid was prepared by condensing 3-(5-formyl-2,4-dimethyl-1 H-pyrrol-3-yl)-propionic acid with 6,6-dioxo-3,6,8,9-tetrahydro- 1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 416 (M+1). Example 18: 2,4-Dimethyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6λ 6-thia-3-aza- cyclopenta[a]naphthalen-(1 Z)-ylidenemethyl]-1 H-pyrrole-3-carboxylic acid (2-diethylamino-ethyl)- amide was prepared by condensing 5-formyl-2,4-dimethyl-1 H-pyrrole-3-carboxylic acid (2- diethylamino-ethyl)-amide with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 487 (M+1). Example 19: 2,4-Dimethyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6λ 6-thia-3-aza- cyclopenta[a]naphthalen-(1 Z)-ylidenemethyl]-1 H-pyrrole-3-carboxylic acid (2-pyrrolidin-1 -yl-ethyl)- amide was prepared by condensing 5-formyl-2,4-dimethyl-1 H-pyrrole-3-carboxylic acid (2-pyrrolidin- 1 -yl-ethyl)-amide with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen- 2-one using the general method of Example 2. MS (m/z) 485 (M+1 ). Example 20: 4-Methyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6λ6-th ia-3-aza-cyclopenta[a]naphthalen- (1Z)-ylidenemethyl]-1 H-pyrrole-2-carboxylic acid was prepared by condensing 5-formyl-4-methyl-1 H- pyrrale-2-carboxylic acid with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 375 (M+1 ). Example 21 : S-Methyl^-p^^-trioxo-S.e^.θ-tetrahydro^H^-oxa-eλ^thia-S-az a-cyclopentafaJnaphthalen- (1Z)-ylidenemethyÏŠ]-1 H-pyrrole-3-carboxylic acid was prepared by condensing 2-formyl-5-methyl-1 H- pyrrole-3-carboxylic acid with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 375 (M+1 ). Example 22: 2,4-Dimethyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6λ 6-thia-3-aza- cyclopenta[a]naphtha!en-(1Z)-ylidenemethyl]-1 H-pyrrole-3-carboxylic acid was prepared by condensing 5-formyl-2,4-dimethyl-1 H-pyrrole-3-carboxylic acid with 6,6-dioxo-3,6,8,9-tetrahydro-1 H- 7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 389 (M+1 ). Example 23: 4-(2-Carboxy-ethyl)-2-methyl-5-[2,6,6-trioxo-3,6,8,9-tetrahy dro-2H-7-oxa-6λ6:thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1 H-pyrrole-3-carboxylic acid ethyl ester was prepared by condensing 4-(2-carboxy-ethyl)-5-formy!-2-methyl-1 H-pyrrole-3-carboxylic acid ethyl ester with 6,6- dioxo-3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 448 (M+1). Example 24: {2,4-Dimethyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2W-7-oxa-6Î »a6-thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1H-pyfrol-3-yl}- acetic acid was prepared by condensing (5-formyl-2,4-dimethyl- 7H-pyrrol-3-yl)-acetic acid with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia- 3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 403 (M+1). Example 25: 6,6-Dioxo-1 -[1 -(2,4,5,6-tetrahydro-cyclopenta[c]pyrrol-1 -yl)-meth-(Z)-ylidene]-3,6,8,9- tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one was prepared by condensing 2,4,5,6-tetrahydro-cyclopenta[clpyrrol-1 -carbaldehyde with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-7-oxa- 6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 357 (M+1). Example 26: 4-(2-Hydroxy-ethyl)-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7- oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1f/-pyrrole-3-ca rboxylic acid was prepared by condensing 5-formyl-4-(2-hydroxy-ethyl)-1H-pyrrole-3-carboxylic acid with "6,6-dioxo-3,6,8,9- tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 405 (M+1). Example 27: 4-(2-Carbamoyl-ethyl)-3-methyl-5-[2,6,6-trioxo-3,6,8,9-tetra hydro-2H-7-oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1H-pyrrole-2-car boxylic acid ethyl ester was prepared by condensing 4-(2-carbamoyl-ethyl)-5-formyl-3-methyl-1 /-/-pyrrole-2-carboxylic acid ethyl ester with 6,6-dioxo-3,6,8,9-tetrahydro-1 /7-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 474 (M+1). Example 28: 1 -[1 -(5-Methyl-3-phenyl-1 W-pyrrol-2-yl)-meth-(Z)-ylidene]-6,6-dioxo-3,6,8,9-tetrahydr o-1 H-I- oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one was prepared by condensing 5-methyl-3-phenyl- 1 W-pyrrole-2-carbaldehyde with 6,6-dioxo-3,6,8,9-tetrahydro-1 W-7-oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 407 (M+1). Example 29: 2-Methyl-4-phenyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2f/-7-o xa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1 H-pyrrole-3-carboxylic acid ethyl ester was prepared by condensing 5-formyl-2-methyl-4-phenyl-1 W-pyrrole-3-carboxylic acid ethyl ester with 6,6-dioxo- 3,6,8, 9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 479 (M+1). Example 30: 3-{2-[2,6,6-Trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6λ6-thia-3-a za-cyclopenta[a]naphthalen-(1Z)- ylidenemethyl]-1 ^.δ.δJ.S-hexahydro-cycloheptarøpyrrol-S-ylJ-propionic acid was prepared by condensing 5-formyl-4-(2-hydroxy-ethyl)-1H-pyrrole-3-carboxylic acid with 6,6-dioxo-3,6,8,9- tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 457 (M+1). Example 31 : 3-{4-Benzenesulfonyl-5-methyl-2-[2,6,6-trioxo-3,6,8(9-tetrah ydro-2W-7-oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1 AV-pyrrol-3-yl}-propionic acid was prepared by condensing 3-(4-benzenesulfonyl-2-formyl-5-methyl-1 H-pyrrol-3-yl)-propionic acid with 6,6-dioxo- 3,6,8, 9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 543 (M+1). Example 32: 4-{2,4-Dimethyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2W-7-oxa- 6λ6-thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1 H-pyrrol-3-yl}-benzoic acid was prepared by condensing 4-(5-formyl-2,4-dimethyl-1 H-pyrrol-3-yl)-benzoic acid with 6,6-dioxo-3,6,8,9-tetrahydro- 1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 465 (M+1). Example 33: 3-{5-[2,6,6-Trioxo-3,6,8,9-tetrahydro-2W-7-oxa-6λ6-thia-3-a za-cyclopenta[a]naphthalen-(1Z)- ylidenemethyl]-1 H-pyrrol-2-yl}-propionic acid was prepared by condensing 3-(5-formyl-1 H-pyrrol-2-yl)- propionic acid with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2- one using the general method of Example 2. MS (m/z) 389 (M+1). Example 34: 2,4-Dimethyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6λ 6-thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1 W-pyrrole-3-carboxylic acid ethyl ester was prepared by condensing 5-formyl-2,4-dimethyl-1 /-/-pyrrole-3-carboxylic acid ethyl ester with 6,6-dioxo-3,6,8,9- tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 417 (M+1). Example 35: {2,4-Dimethyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7-oxa-6Î »6-thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1 H-pyrrol-3-yl}-acetic acid ethyl ester was prepared by condensing (5-formyl-2,4-dimethyl-1 /+pyrrol-3-yl)-acetic acid ethyl ester with 6,6-dioxo-3,6,8,9- tetrahydro-1 AV-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 431 (M+1). Example 36: 1 -[1 -(5-Ethyl-3-phenyl-1 H-pyrrol-2-yl)-meth-(Z)-ylidene]-6,6-dioxo-3,6,8,9-tetrahydr o-1 H-7- oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one was prepared by condensing 5-ethyl-3-phenyl-1 H- pyrrole-2-carbaldehyde with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 421 (M+1 ). Example 37: 1 -[1 -[3-(4-Bromo-phenyl)-5-methyl-1 H-pyrrol-2-yl]-meth-(Z)-ylidene]-6,6-dioxo-3,6,8,9- tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one was prepared by condensing 3- (4-bromo-phenyl)-5-methyl-1 H-pyrrole-2-carbaldehyde with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-7-oxa- 6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 485, 487 (M+1). Example 38: 2-Methyl-4-phenyl-5-[2,6,6-trioxo-3,6,8,9-tetrahydro-2H-7-ox a-6λ6-thia-3-aza- cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]-1 AY-pyrrole-3-carboxylic acid was prepared by condensing δ-formyl^-methyM-phenyl-IH-pyrrole-S-carboxylic acid with 6,6-dioxo-3,6,8,9- tetrahydro-1 H-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 451 (M+1). Example 39: 3-{4-(2-Diethylamino-ethyicarbamoyl)-5-methyl-2-[2,6,6-triox o-3,6,8,9-tetrahydro-2H-7-oxa- 6λ6-thia-3-aza-cyclopenta[a]naphthalen-(1Z)-ylidenemethyl]- 1 H-pyrrol-3-yl}-propionic acid ethyl ester was prepared by condensing 3-[4-(2-diethylamino-ethylcarbamoyl)-2-formyl-5-methyl-1 H-pyrrol-3-yl]- propionic acid ethyl ester with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-7-oxa-6λ6-thia-3-aza- cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 573 (M+1). Example 40: 1-[1-(3,5-Dimethyl-4-morpholin-4-ylmethyl-1 H-pyrrol-2-yl)-meth-(Z)-ylidene]-6,6-dioxo-3,6,8,9- tetrahydro-1 /7-7-oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one was prepared by condensing 3,5- dimethyl-4-morpholin-4-ylmethyl-1 H-pyrrole-2-carbaldehyde with 6,6-dioxo-3,6,8,9-tetrahydro-1 H-I- oxa-6λ6-thia-3-aza-cyclopenta[a]naphthalen-2-one using the general method of Example 2. MS (m/z) 444 (M+1). Assay Procedures CDK2/CYCLIN A ASSAY The following protocol describes the procedures used to analyze protein serine/threonine kinase activity of cdk2/cyclin A in an SPA. The procedure also describes the protocol for the initial screening of drugs for inhibition or activation of the kinase activity. Materials and Reagents: 1. Wallac 96-well polyethylene terephthalate (flexi) plates (Wallac Catalog # 1450-401 ). 2. Amersham Redivue [Y33P] ATP (Amersham catalog #AH 9968). 3. Amersham streptavidin coated polyvinyltoluene SPA beads (Amersham catalog #RPNQ0007). Reconstitute beads in PBS without magnesium or calcium, at 20 mg/mL Store reconstituted beads at 4 0C. 4. Activated cdk2/cyclin A enzyme complex purified from Sf9 cells, -80 0C, 200 μl_ aliquots 5. Biotinylated peptide substrate (deb-tide). Peptide biotin-X-PKTPKKAKKL dissolved in dH2O at a concentration of 5 mg/mL. Stored at -80 0C in 100 μL aliquots. 6. Peptide/ATP Mixture:

7.

8. 1O mM ATP (Sigma Catalog # A-5394). 9. 1 M Tris, pH 7.4 10. 1 M MgCI2 11. 1 M DTT 12. PBS (Dulbecco's Phosphate-Buffered Saline) without magnesium or calcium (Gibco Catalog # 14190-144) 13. EDTA (14.12 g per 10O mL). 14. Stop solution:

Procedure: 1. Prepare solutions of inhibitors at 5x the desired final concentration in 5% DMSO. Add 10 μL to each well. For negative controls, add 10 μL 5% DMSO. 2. Dilute 5 μl_ of cdk2/cyclin A solution into 2.1 ml_ 2x kinase buffer (per plate). 3. Add 20 μL enzyme per well. This can be added using a hand pipette or by using the Titertek Multidrop. 4. Add 10 μL of 0.5 M EDTA to the neagtive control wells. 5. To start kinase reaction, add 20 μL of peptide/ATP mixture using either a hand pipette or the Titertek Multidrop. Let sit on benchtop behind reactive shield for 1 hr. 6. Add 200 μL stop solution per well using either the Titertek Multidrop or hand pipette. 7. Let stand at least 10 min. 8. Spin plate approx. 2300 rpm 3-5 min. 9. Count plate on Trilux reader using protocol #28 (Brian's SPA assay). All patents and publications are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference. In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group. For example, if X is described as selected from the group consisting of bromine, chlorine, and iodine, claims for X being bromine and claims for X being bromine and chlorine are fully described. The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.