This invention relates to substituted cyanopyridines as protein kinase inhibitors Field The present teachings relate to substituted 3-cyanopyridines (also known as mcotinonirriles) that are capable of inhibiting protein kinases. The present teachings also relate to methods for the preparation of the substituted cyanopyridines and methods of their use. For example, the compounds of the present teachings can be useful for the treatment of autoimmune and inflammatory diseases such as asthma and arthritis. Introduction Protein kinases are enzymes that catalyze the transfer of a phosphate group from adenosine triphosphate (ATP) to an amino acid residue (e.g., tyrosine, serine, threonine or histidine) on a protein. Regulation of these protein kinases is essential for the control of a wide variety of cellular events including proliferation and migration. A large number of diseases including various inflammatory diseases and autoimmune diseases such as asthma, colitis, multiple sclerosis, psoriasis, arthritis, rheumatoid arthritis, osteoarthritis, and joint inflammation, are associated with abnormal cellular events that are mediated by these kinases. See, e.g., Salek-Ardakami, S. et al. (2004), J. Immunology, 173(10): 6440-47; Marsland, B. et al. (2004), /. Exp. Med., 200(2): 181-89; Tan, S, et al. (2006), J. Immunology, 176: 2872-79; Salek-Ardakami, S. etal. (2005), J. Immunology, 175(11): 7635-41; Anderson, K. et al. (2006), Autoimmunity, 39(6): 469-78; Healy, A. et al. (2006), J. Immunology, 177(3): 1886-93; Sun, Z. et al. (2000), Nature, 404: 402-7; and Pfeifhofer, C. et al. (2003), J. Exp. Med., 197(11): 1525-35. One class of serine/threonine kinases is the protein kinase C (PKC) family. This group of kinases consists of 10 members that share sequence and structural homology. The PKCs are divided into 3 groups and include the classic, the novel, and the atypical isoforms. The theta isoform (PKCθ) is a member of the novel calcium-independent class of PKCs (Baier, G. et al. (1993), J. Biol. Chem., 268: 4997-5004). PKCO is highly expressed in T cells (Mischak, H. et al. (1993), FEES Lett., 326: 51-5), with some expression reported in mast cells (Liu, Y. et al. (2001), J. Leukoc. Biol., 69: 831-40), endothelial cells (Mattila, P. et al. (1994), Life Sci., 55: 1253-60), and skeletal muscles (Baier, G. et al. (1994), Eur. J. Biochem., 225: 195-203). It has been shown that PKCθ plays an essential role in T cell receptor (TCR)-mediated signaling (Tan, S.L. et al. (2003), Biochem. J., 376: 545-52). Specifically, it has been observed that inhibiting PKCθ signal transduction, as demonstrated with two independent PKCθ knockout mouse lines, will result in defects in T cell activation and interleukin-2 (IL-2) production (Sun, Z. et al. (2000), Nature, 404: 402-7; Pfeifhofer, C. et al. (2003), J. Exp. Med., 197: 1525-35). It also has been shown that PKCG-deficient mice show impaired pulmonary inflammation and airway hyperresponsiveness (AHR) in a Th2-dependent murine asthma model, with no defects in viral clearance and Thl-dependent cytotoxic T cell function (Berg-Brown, N.N. et al. (2004), J. Exp. Med., 199: 743-52; Marsland, B.J. et al. (2004), J, Exp. Med., 200: 181-9). The impaired Th2 cell responses result in reduced levels of interleukin-4 (IL-4) and immunoglobulin E (IgE), contributing to the AHR and inflammatory pathophysiology. Evidence also exists that PKCθ participates in the IgE receptor (FceRI)-mediated response of mast cells (Liu, Y. et al. (2001), J. Leukoc. Biol., 69: 831-840). In human-cultured mast cells (HCMC), it has been demonstrated that PKC kinase activity rapidly localizes (in less than five minutes) to the membrane following FceRI cross-linking (Kimata, M. et al. (1999), Biochem. Biophys. Res. Commun., 257(3): 895-900). A recent study examining in vitro activation of bone marrow mast cells (BMMCs) derived from wild-type and PKCθ-deficient mice shows that upon FceRI cross-linking, BMMCs from PKCθ-deficient mice produced reduced levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), and interleukin-13 (IL-13) in comparison with BMMCs from wild-type mice, suggesting a potential role for PKC9 in mast cell cytokine production in addition to T cell activation (Ciarletta, A.B. et al. (2005), poster presentation at the 2005 American Thorasic Society International Conference). Other serine/threonine kinases include those of the mitogen-activated protein kinase (MAPK) pathway which consists of the MAP kinases (MAPK) (e.g., erk) and the MAPK kinases (MAPKK) (e.g., mek and their substrates). Members of the raf family of kinases phosphorylate residues on mek. The cyclin-dependent kinases (cdks), including cdc2/cyclin B, cdk2/cyclin A, cdk2/cyclin E and cdk4/cyclin D, and others, are serine/threonine kinases that regulate mammalian cell division. Additional serine/threonine kinases include the protein kinases A and B. These kinases, known as PKA or cyclic AMP-dependent protein kinase and PKB (Akt), play key roles in signal transduction pathways. Tyrosine kinases (TKs) are divided into two classes: the non- transmembrane TKs and transmembrane growth factor receptor TKs (RTKs). Growth factors, such as epidermal growth factor (EOF), bind to the extracellular domain of their partner RTK on the cell surface which activates the RTK, initiating a signal transduction cascade that controls a wide variety of cellular responses. In addition to EGF, there are several other RTKs including FGFR (the receptor for fibroblast growth factor (FGF)); flk-1 (also known as KDR), and flt-1 (the receptors for vascular endothelial growth factor (VEGF)); and PDGFR (the receptor for platelet derived growth factor (PDGF)). Other RTKs include tie-1 and tie-2, colony stimulating factor receptor, the nerve growth factor receptor, and the insulin-like growth factor receptor. In addition to the RTKs there is another family of TKs termed the cytoplasmic protein or non-receptor TKs. The cytoplasmic protein TKs have intrinsic kinase activity, are present in the cytoplasm and nucleus, and participate in diverse signaling pathways. There are a large number of non-receptor TKs including Abl, Jak, Fak, Syk, Zap-70 and Csk, and the Src family of kinases (SFKs) which include Src, Lck, Lyn, Fyn and others. Certain pyridine and pyrimidine derivatives have been noted as kinase inhibitors. These compounds differ both in nature and placement of substituents at various positions when compared to the compounds of the present teachings. Summary The present teachings relate to substituted 3-cyanopyridines of formula I: (Formula Removed) and their pharmaceutically acceptable salts, hydrates, and esters, wherein R1, R2, and X are defined as described herein. The present teachings also relate to pharmaceutical compositions that include a pharmaceutically effective amount of one or more compounds of formula I (including their pharmaceutically acceptable salts, hydrates, and esters) and a pharmaceutically acceptable carrier or excipient. Another aspect of the present teachings relates to methods of preparing the compounds of formula I and their pharmaceutically acceptable salts, hydrates, and esters. The present teachings also provide methods of using the compounds of formula I and their pharmaceutically acceptable salts, hydrates, and esters. In some embodiments, the present teachings provide methods of treating autoimmune and inflammatory diseases, such as asthma, colitis, multiple sclerosis, psoriasis, arthritis, rheumatoid arthritis, osteoarthritis, and joint inflammation, which include administering a therapeutically effective amount of one or more compounds of formula I (or their pharmaceutically acceptable salts, hydrates, or esters) to a mammal including a human. Detailed Description The present teachings provide compounds of formula I: (Formula Removed) and their pharmaceutically acceptable salts, hydrates, and esters, wherein: X is selected from a) NR3-Y , b) -O-Y-, c) -S(O)m-Y-, d) -S(O)mNR3- Y-, e) -NR3S(0)m-Y-, f) -C(0)NR3-Y- g) ~C(S)NR3-Y-, h) -NR3C(O)-Y , i) -NR3C(S)-Y-, j) -C(0)0-Y-, k) -OC(O)-Y-, and 1) a covalent bond; Y, at each occurrence, independently is selected from a) a divalent C1-10 alkyl group, b) a divalent C2-10 alkenyl group, c) a divalent C2-10 alkynyl group, d) a divalent C1-10 haloalkyl group, and e) a covalent bond; R1 is a phenyl group optionally substituted with 1-4 -Y-R4 groups; R2 is a C6-14 aryl group or a 5-14 membered heteroaryl group, wherein each group optionally is substituted with 1-4 groups independently selected from —Y-R4 and -O-Y-R4; R3 is selected from a) H, b) a C1-10 alkyl group, c) a C1-10 alkeny] group, d) a C2-10 alkynyl group, and e) a C1-10 haloalkyl group; R4, at each occurrence, independently is selected from a) halogen, b) -CN, c) -NO2, d) oxo, e) -O-Y-R5, i) -NR6-Y-R7, g) -N(O)R6-Y-R7, h) - S(0)m-Y-R5, i) -S(O)mO-Y-R5, j) -S(O)mNR6-Y-R7, k) -C(O)-Y-R5,1) -C(O)O-Y- R5, m) -C(O)NR6-Y-R7, n) -C(S)NR6 Y-R7, o) a C1-10 alkyl group, p) a C2-10 alkenyl group, q) a C2-10 alkynyl group, r) a C1-10 haloalkyl group, s) a C3. 14 cycloalkyl group, t) a C6-14 aryl group, u) a 3-14 membered cycloheteroalkyl group, and v) a 5-14 membered heteroaryl group, wherein each of o) - v) optionally is substituted with 1-4 -Y-R8 groups; R5, at each occurrence, independently is selected from a) H, b) -C(O)R9, c) -C(O)OR9, d) a C1-10 alkyl group, e) a C1-10 alkenyl group, f) a C2-10 alkynyl group, g) a C1-10 haloalkyl group, h) a C3-14 cycloalkyl group, i) a C6-14 aryl group, j) a 3-14 membered cycloheteroalkyl group, and k) a 5-14 membered heteroaryl group, wherein each of d) - k) optionally is Q substituted with 1 -4 -Y-R groups; R6 and R7, at each occurrence, independently are selected from a) H., b) -O-Y-R9, c) -S(0)m-Y-R9, d) -S(0)mO-Y R9, e) -C(O)-Y-R9, f) -C(O)O-Y R9, g) -C(O)NR'°-Y-Rn, h) -C(S)NR'°-Y-Rn, i) a C1-10 alkyl group, j) a C2_ 10 alkenyl group, k) a C2-10 alkynyl group, 1) a C1-10 haloalkyl group, m) a C3-14 cycloalkyl group, n) a C6-14 aryl group, o) a 3-14 membered cycloheteroalkyl group, and p) a 5-14 membered heteroaryl group, wherein each of i) - p) optionally is substituted with 1-4 -Y-R8 groups; R , at each occurrence, independently is selected from a) halogen, b) -CN, c) -NO2, d) oxo, e) -Y-R9, f) -NR10-Y-Rn, g) -N(O)R10-Y-R'', h) S(0)m-Y-R9, i) -S(0)mO-Y-R9, j) S(0)mNR10-Y-R11, k) -C(O)-Y-R9,1) -C(O)O-Y- R9, m) -C(O)NR'°-Y-Rn, n) -C(S)NR10-Y-Rn, o) a C1-10 alkyl group, p) a C2-10 alkenyl group, q) a C2-10 alkynyl group, r) a C1-10 haloalkyl group, s) a C3-14 cycloalkyl group, t) a C6-14 aryl group, u) a 3-14 membered cycloheteroalkyl group, and v) a 5-14 membered heteroaryl group, wherein each of o) v) optionally is substituted with 1-4 -Y-R12 groups; R9, at each occurrence, independently is selected from a) H, b) -C(O)-C1- 10 alkyl, c) -C(O)OH, d) -C(O)O-C1-10 alkyl, e) a C1-10 alkyl group, f) a C2-10 alkenyl group, g) a C2-10 alkynyl group, h) a C1-10 haloalkyl group, i) a C3- H cycloalkyl group, j) a C6-14 aryl group, k) a 3-14 membered cycloheteroalkyl group, and 1) a 5-14 membered heteroaryl group, wherein each of the C1-10 alkyl group, the C2- 10 alkenyl group, the C1-10 alkynyl group, the C1-10 haloalkyl group, the C1- 14 cycloalkyl group, the C6-14aryl group, the 3-14 membered cycloheteroalkyl group, and the 5-14 membered heteroaryl group optionally is substituted with 1-4 -Y-R12 groups; R10 and R11, at each occurrence, independently are selected from a) H, b) - OH, c) -SH, d) -NH2, e) -NH-C1-10 alkyl, f) -N(C1-10 alkyl)2, g) -S(O)m-C1-10 alkyl, h) -S(0)2OH, i) -S(0)m-OC1-10 alkyl, j) -C(O)-C1-10 alkyl, k) -C(O)OH, 1) -C(0)-OC1-10 alkyl, m) -C(O)NH2, n) -C(O)NH-C1-10 alkyl, o) -C(0)N(C1-10 alkyl)2, p) -C(S)NH2, q) -C(S)NH-C1-10 alkyl, r) - C(S)N(C1-10 alkyl)2, s) a C1-10 alkyl group, t) a C2-10 alkenyl group, u) a C2_ 10 alkynyl group, v) a C1-10 alkoxy group, w) a C1-10 haloalkyl group, x) a C3-14 cycloalkyl group, y) a C6-14 aryl group, z) a 3-14 membered cycloheteroalkyl group, and aa) a 5-14 membered heteroaryl group, wherein each of the C1-10 alkyl group, the C2-10 alkenyl group, the C2-10 alkynyl group, the C1-10 alkoxy group, the C1-10 haloalkyl group, the C3-14 cycloalkyl group, the C6-14 aryl group, the 3-14 membered cycloheteroalkyl group, and the 5-14 membered heteroaryl group optionally is substituted with 1-4 -Y-R12 groups; R12, at each occurrence, independently is selected from a) halogen, b) - CN, c) -N02, d) oxo, e) -OH, f) -NH2, g) -NH(C1-10alkyl), h) -N( C1-10 alkyl)2, i) -SH, j) -S(0)m-C1-10 alkyl, k) -S(0)2OH, 1) -S(O)m-OC1-10 alkyl, m) -C(O)-Ci. 10 alkyl, n) -C(0)OH, o) -C(0)-OC1-10 alkyl, p) -C(O)NH2, q) -C(O)NH-C1-10 alkyl, r) -C(O)N(C1-10 alkyl)2, s) -C(S)NH2, t) -C(S)NH-C1-10 alkyl, u) - C(S)N(C1-10 alkyl)2, v) a C1-10 alkyl group, w) a C2-10 alkenyl group, x) a C2-10 alkynyl group, y) a C1-10 alkoxy group, z) a C1-10 haloalkyl group, aa) a C3-14 cycloalkyl group, ab) a C6-14 aryl group, ac) a 3-14 membered cycloheteroalkyl group, and ad) a 5-14 membered heteroaryl group; and mis 0, 1, or2. In some embodiments, the pyridine ring can be oxidized on the nitrogen atom to provide the corresponding N-oxide having the formula I': (Formula Removed) wherein R1, R2, and X are as defined herein. In some embodiments, X can be selected from —NR3-Y~, -O—Y-, arid a covalent bond. For example, X can be selected from -NH-, -N(CH3)-, -NH-CH2-, NH-CH2CH2-, -NH-CH2CH2CH2-, -O-, and a covalent bond, hi particular embodiments, X can be -NH-. In certain embodiments, R1 can be selected from: (Formula Removed) wherein R is as defined herein. In particular embodiments, R4, at each occurrence, can be independently selected from -F, Cl, -Br, -CN, -NO2, -O-Y-R5, -C(O) Y-R5,-C(O)O-Y-R5, -NR6-Y-R7, and a C1-6 alkyl group. For example, R4, at each occurrence, can be independently selected from -F, -Cl, -Br, -O-C1-3 alkyl, -O-phenyl, and a C1-3 alkyl group. In some embodiments, R" can be selected from a phenyl group, a C8-14 aryl group, and a 5-14 membered heteroaryl group, wherein each of these groups can be optionally substituted with 1-4 groups independently selected from -Y-R4 and ~O-Y-R , wherein Y and R4 are as defined herein. For example, R2 can be selected from a phenyl group, a pyridyl group, a pyrimidyl group, a pyrazinyl group, a furyl group, a thienyl group, a thiazolyl group, an oxazolyl group, a benzofuranyl group, a benzothienyl group, an indolyl group, a benzodioxinyl group, a benzodioxolyl group, a benzodioxanyl group, a dibenzofuranyl group, a dibenzothienyl group, a benzoindolyl group, an indanyl group, an indenyl group, an isothiazolyl group, a pyridazinyl group, a pyrazolyl group, a tetrahydronaphthyl group, an isoxazolyl group, a quinolinyl group, a naphthyl group, an imidazolyl group, and a pyrrolyl group, wherein each of these groups can be optionally substituted with 1-4 groups independently selected from -Y-R4 or -O-Y-R4, wherein Y and R4 are as defined herein. In certain embodiments, R~ can be (Formula Removed) wherein D1, D2, and D3 independently can be H, a -Y-R4 group, or an -O-Y-R4 group, wherein Y and R4 are as defined herein. For example, at least one of D1, D", and D3 can be a -Y-R4 group or an O-Y-R4 group, wherein Y, at each occurrence, can be independently a divalent C1-4 alkyl group or a covalent bond, and R4, at each occurrence, can be independently selected from a halogen, -CN -NO2, O-Y-R5, -NR6-Y-R7, -S(O)2-Y-R5, -S(0)2NR6-Y-R7, -C(O)-Y-R5, -C(O)O- Y-R5,-C(O)NR6-Y-R7, a C1-10 alkyl group, a CMC haloalkyl group, a C3-14 cycloalkyl group, a C6-14 aryl group, a 3-14 membered cycloheteroalkyl group, and a 5-14 membered heteroaryl group, wherein each of the C1-10 alkyl group, the C1-10 haloalkyl group, the C3-14 cycloalkyl group, the CVi4 aryl group, the 3-14 membered cycloheteroalkyl group, and the 5-14 membered heteroaryl group can be optionally substituted with 1-4 -Y-R8 groups, wherein Y, R5, R6, R7, and R are as defined herein. In certain embodiments, at least one of D1, D2, and D3 can be an -O-(CH2)n-R group, wherein n, at each occurrence, independently can be 0, 1, 2, 3, or 4, and R4, at each occurrence, can be independently selected from F, Cl, Br, -NO2, -O-Y-R5, -NR6-Y-R7, S(0)2-Y-R5, -S(O)2NR6-Y-R7, -C(O)NR6-Y-R7, a C1-10 alkyl group, a CJ-H cycloalkyl group, a C6_14 aryl group, a 3-14 membered cycloheteroalkyl group, and a 5-14 membered heteroaryl group, wherein each of the C1-10 alkyl group, the C3-14 cycloalkyl group, the C6-14 aryl group, the 3-14 membered cycloheteroalkyl group, and the 5-14 membered heteroaryl group can be optionally substituted with 1-4 -Y-R8 groups, wherein Y, R , R6, R7, and R are as defined herein. In particular embodiments, at least one of D1, D2, and D3 can be -O-(CH2)nNR6-Y-R7 or an -O-(CH2)n-3-14 membered cycloheteroalkyl group, wherein the 3-14 membered cycloheteroalkyl group can be optionally substituted with 1-4 -Y-R groups, wherein Y, R6, R7, and R8 are as defined herein, and n, at each occurrence, independently can beO, 1,2, 3, or 4. In some embodiments, at least one of D1, D2, and D3 can be -(CH2)nNR6-Y-R7 or a-(CH2)n-3-14 membered cycloheteroalkyl group, wherein the 3-14 membered cycloheteroalkyl group can be optionally substituted with 1 -4 -Y-R8 groups, Y, R6, R7, and R8 are as defined herein, and n, at each occurrence, independently can be 0, 1, 2, 3, or 4. In embodiments where at least one of D1, D2, and D3 can be an -O-(CH2)nNR6-Y-R7 group or a -245°C. A mixture of 4-hydroxy-5-iodonicotinonitrile (57.5 g, 234 mmol) and POCls (200 mL) was heated at 100°C for 2 hours, cooled to room temperature and evaporated to remove excess POCl3. The residue was cooled in an iC6-14ater bath, adjusted to pH 8-9 with aqueous ION NaOH and extracted with EtOAc. The combined organics were washed with water and brine, dried over MgSO4, filtered and concentrated. The resulting solid residue was washed with a minimum amount of MeOH and CH2Cl2 to give 46.5 g (75%) of 4-chloro-5-iodonicotinonitrile as a tan solid, mp 120-122°C. A mixture of 4-chloro-5-iodonicotinonitrile (2.0 g, 7.6 mmol) and 2-chloro-5-hydroxyaniline (1.09 g, 7.6 mmol) in EtOH (20 mL) was heated at 90°C in a sealed vial overnight, poured into aqueous NaHCOs and filtered. The crude solid was washed with water and dried to afford 3.0 g (quantitative yield) of 4-[(2-chloro-5-hydroxyphenyl)amino]-5-iodonicotmonitrile as a brown solid, which was used for the next step without further purification. MS (M+H): 372.1. A mixture of 4-[(2-chloro-5-hydroxyphenyl)amino]-5-iodonicotinonitrile (500 mg, 1.35 mmol), 2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzo[b]thiophene-5-carbaldehyde (389 mg, 1.35 mmol) and Pd(PPh3)4 (78 mg, 0.070 mmol) in DME (10 mL) and NaHCO3 (aq, 2M, 1.4 mL) was heated at 80°C overnight, cooled to room temperature and concentrated to a reduced volume. The residue was partitioned between EtOAc and water. The combined organics were dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography to give 160 mg (30%) of 4-[(2-chloro-5-hydroxyphenyl)amino]-5-(5-formyl-l-benzothien-2-yl)nicotinonitrile 162 as a yellow solid, MS (M+H): 406.2; HPLC retention timetc): 11.7 min.. Example 17: Preparation of 4-[(2-chloro-5-hydroxyphenyl)ammo]-5-[5-(piperidin-l-ylmethyl)-l-benzothien-2-yl]nicotinonitrile 163 To a mixture of 4-[(2-chloro-5-hydroxyphenyl)amino]-5-(5-formyl-l-benzothien-2-yl)nicotinonitrile 162 (130 mg, 0.32 mmol) and piperidine (82 mg, 0.96 mmol) in THF (5.0 mL) was added AcOH (106 mg, 1.76 mmol). The resulting mixture was stirred at room temperature for one hour and sodium triacetoxyborohydride (203 mg, 0.96 mmol) was added. After stirring at room temperature overnight, the reaction mixture was concentrated and purified by silica gel column chromatography to give 105 mg (69%) of the title compound as a pale yellow solid. HPLC retention time (c): 7.8 min.; MS: 475.1 m/e (M+H). Compound 164 in Table 6 was prepared following procedures analogous to those described for the preparation of compound 160 in Example 14. Compounds 165 and 166 were prepared by coupling intermediate 66 with the appropriate anilines then treating with 2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzo[b]thiophene-5-carbaldehyde following procedures analogous to those described for the preparation of compound 162 described in Example 16, followed by reductive amination following the procedures of compound 163, Example 17. Table 6 (Table Removed) Example 18: Preparation of 4-chloro-5-iodo-l-oxy-nicotinonitrile To a solution of 4-chloro-5-iodo-nicotinonitrile (529 mg, 2.0 mmol) in TFA (5 mL) was added H2O2 (30wt% in FbO, 5 mL). The reaction mixture was stirred at room temperature overnight, heated to 50°C for 8h, and concentrated. To the residue was added saturated aqueous NaHCOs (10 mL) followed by extraction with EtOAc/THF. The organic extracts were washed with water, dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (CH2C12-THF = 10:1) to give 202 mg (36%) of 4-chloro-5-iodo-l-oxy-nicotinomtrile as a pale-yellow solid. Example 19: Preparation of 4-fluoro-5-[3-methoxy-4-(2-methoxyethoxy)phenyl]nicotinonitrile 4-Chloro-5-(3,4-dimethoxyphenyl)nicotinonitrile (7.3 mmol, 2.0g) was dissolved in 70 mL DMF and treated with CsF (14.6 mmol, 2.2g). After heating for 2 h at 80°C, additional 7 mmol (Ig) of CsF was added and the heating was continued overnight. The suspension was evaporated onto silica gel and the product was purified by chromatography (EtOAc/Hex) to give 300 mg of 4-fluoro-5-[3-methoxy-4-(2-methoxyethoxy)phenyl]nicotinonitrile. Example 20: Preparation of l-benzofuran-5-carbaldehyde To a solution of 1-benzofuran-5-carbonitrile (5.0 g, 34.9 mmol) in CH2Cl2 under nitrogen at -15 to -20°C was added DIBAL-H (41.9 mL, 41.9 mmol, IM/heptane) and the temperature was maintained below -15°C. After addition was complete, the reaction mixture was stirred at -15 to -20°C for an additional 10 min. The reaction mixture was quenched via dropwise addition of aqueous 2N HC1. The organic layer was separated and washed with water, dried over sodium sulfate, and concentrated to give 4.0 g (78%) of l-benzofuran-5-carbaldehyde as a yellow oil. Example 21: Preparation of dimethyl 5-(piperidin-l-ylmethyl)benzofuran-2-ylboronate l-Benzofuran-5-carbaldehyde was treated with piperidine and sodium triacetoxyborohydride under standard reductive amination procedures to provide l-(5-benzofuranylmethyl)piperidine. Treatment of l-(5-benzofuranylmethyl)piperidine with butyl lithium and trimethylborate at low temperature provided dimethyl 5-(piperidin-l-ylmethyl)benzofuran-2-ylboronate. Compounds 167-169,171, and 172 in Table 7 were provided following procedures analogous to those described in Scheme 10 by coupling with dimethyl 5-(piperidin-l-ylmethyi)benzofuran-2-ylboronate. Table 7 (Table Removed) Example 22: Preparation of 4-{[3-(aminomethyl)benzyl]amino}-5-(3,4-dimethoxyphenyl)nicotinonitrile 170 A mixture of 4-chloro-5-(3,4-dimethoxvphenyl)nicotinonitrile (74 mg, 0.27 mmol), 1,3-phenylenedimethanamine (54 mg, 0.40 mmol) and triethylamine (40 mg, 0.40 mmol) in 3 mL of DMF was heated to 60° C overnight. After cooled to the room temperature, the reaction was concentrated to dryness and the residue was dissolved in 3 mL DMSO, filtered, and purified by a preparative HPLC to give 4-{[3-(aminomethyl)benzyl]amino}-5-(3,4-dimethoxyphenyl)nicotinonitrile. HPLC retention time(d): 1.33 min.; MS: 375.2 m/e (M+H). Example 23: Pharmacological testing Evaluation of representative compounds of the present teachings in several standard pharmacological test procedures indicated that the compounds of the present teachings are inhibitors of PKC9. Based on the activity shown in the standard pharmacological test procedures, the compounds of the present teachings are therefore useful as anti-inflammatory agents. A radioactive kinase assay for inhibition of the active kinase domain (KD) ofPKCθ This assay is based on the phosphorylation of a biotinylated substrate by a kinase utilizing radiolabeled ATP (ATP y P33). The substrate was a biotinylated peptide with a sequence of biotin-FARKGSLRQ-C(O)NH2. The enzyme was purified recombinant active kinase domain of full length PKC theta (amino acids 362-706). The assay buffer was composed of lOOmM Hepes, pH7.5, 2mM MgC^, 20mM p-glycerophosphate and 0.008% TritonX 100. A reaction mixture of ATP, ATP y P33 (PerkinElmer), DTT, and the enzyme was prepared in the assay buffer and added to a 96-well polypropylene plate. The compound (diluted in DMSO in a separate 96-well polypropylene plate) was added to the reaction mixture and incubated at room temperature. Following the incubation, the peptide substrate was added to the reaction mixture to initiate the enzymatic reaction. The reaction was terminated with the addition of a stop solution (lOOmM EDTA, 0.2% TritonXlOO, and 20mM NaHPCU) and transferred from the assay plate to a washed streptavidin-coated 96-well scintiplate (PerkinElmer). The scintiplate was incubated at room temperature, washed in PBS with 0.1% TritonX 100, and counted in the 1450 Microbeta Trilux (Wallac, Version 2.60). Counts were recorded for each well as corrected counts per minute (CCPM). The counts were considered corrected because they were adjusted according to a P33 normalization protocol, which corrects for efficiency and background differences between the instrument detectors (software version 4.40,01). A radioactive kinase assay for inhibition of full length (FL) PKCθ inhibitors This assay differs from what was described above in that the enzyme used was purified recombinant full length PKC theta (Panvera, P2996). PKCθIMAP Assay The materials used include the following: human PKC9 foil length enzyme (Panvera Cat# P2996); substrate peptide: 5FAM-RFARKGSLRQKNV-OH (Molecular Devices, RP7032); ATP (Sigma Cat # A2383); DTT (Pierce, 20291); 5x kinase reaction buffer (Molecular Devices, R7209); 5x binding buffer A (Molecular Devices, R7282), 5x binding buffer B (Molecular Devices, R7209); IMAP Beads (Molecular Devices, R7284); and 384-well plates (Corning Costar, 3710). The reaction buffer was prepared by diluting the 5x stock reaction buffer and adding DTT to obtain a concentration of 3.0 mM. The binding buffer was prepared by diluting the 5x binding buffer A. A master mix solution was prepared using a 90% dilution of the reaction buffer containing 2x ATP (12 uM) and 2x peptide (200 nm). Compounds were diluted in DMSO to 20x of the maximum concentration for the IC50 measurement. 27 µl of the master mix solution for each IC50 curve was added to the first column in a 384-well plate and 3 µl of 20x compound in DMSO was added to each well. The final concentration of compound was 2x and 10% DMSO. DMSO was added to the rest of the master mix to increase the concentration to 10%. 10 µl of the master mix containing 10% DMSO was added to the rest of the wells on the plate except the 2nd column. 20 µl was transferred from the first column to the 2nd column. The compounds were serially diluted in 2:1 ratio starting from the 2nd column. A 2x (2 nM) PKCθ solution was made in the reaction buffer. 10 µl of the PKC9 solution was added to every well to achieve these final concentrations: PKCθ -1 nM; ATP - 6 uM; peptide - 100 nM; DMSO - 5%. Samples were incubated for 25 minutes at room temperature. The binding reagent was prepared by diluting the beads in Ix binding buffer to 800:1. 50 µl of the binding reagent was added to every well and incubated for 20 minutes. FP was measured using Envision2100 (PerkinElrner Life Sciences). Wells with no ATPs and wells with no enzymes were used as controls. The results obtained are summarized in Table 8 below. Data presented represent the average value when one or more samples were tested. Table 8 (Table Removed) Variations, modifications, and other implementations of what is described herein will occur to those of ordinary skill in the art without departing from the spirit and the essential characteristics of the present teachings. Accordingly, the scope of the present teachings is to be defined not by the preceding illustrative description but instead by the following claims, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein. WE CLAIM: 1. A compound of formula I or formula I': (Formula Removed) or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein: X is selected from a) -NR3-Y- b) -O-Y-, c) -S(O)m-Y-, d) -S(O)mNR3-Y-, e) -NR3S(O)m-Y-, f) C(O)NR3-Y~, g) -C(S)NR3-Y- h) -NR3C(O)-Y-, i) -NR3C(S)-Y-, j) ~C(O)O-Y- k) - OC(O}-Y-, and 1) a covalent bond; Y, at each occurrence, independently is selected from a) a divalent C1-10 alkyl group, b) a divalent C2-10 alkenyl group, c) a divalent C1-10 alkynyl group, d) a divalent C1-10 haloalkyl group, and e) a covalent bond; R1 is a phenyl group optionally substituted with 1-4 -Y-R4 groups; R2 is a C3-14 aryl group or a 5-14 membered heteroaryl group, wherein each group optionally is substituted with 1-4 groups independently selected from Y-R4or-O-Y-R4; R3 is selected from a) H, b) a C1-10 alkyl group, c) a C1-10 alkenyl group, d) a C2-10 alkynyl group, and e) a C1-10 haloalkyl group; R4, at each occurrence, independently is selected from a) halogen, b) -CN, c) -N02, d) oxo, e) -0-Y-R5, f) NR6-Y-R7, g) -N(O)R6-Y-R7, h) -S(O)m-Y R5, i) -S(0)mO-Y~R5, j) -S(0)mNR6-Y-R7, k) -C(O)-Y-R5,1) -C(O)O-Y-R5, m) -C(O)NR6-Y-R7, n) -C(S)NR6-Y-R7, o) a C1-10 alkyl group, p) a C2-10 alkenyl group, q) a C2-10 alkynyl group, r) a C1-10 haloalkyl group, s) a C3-14 cycloalkyl group, t) a C6-14 aryl group, u) a 3-14 membered cycloheteroalkyl group, and v) a 5-14 membered heteroaryl group, wherein each of o) - v) optionally is substituted with 1 -4 --Y-R groups; R5, at each occurrence, independently is selected from a) H, b) -C(O)R9, c) C(O)OR9, d) a C1-10 alkyl group, e) a C1-10 alkenyl group, f) a C1-10 alkynyl group, g) a C1-10 haloalkyl group, h) a C3.14 cycloalkyl group, i) a C6-14 aryl group, j) a 3-14 membered cycloheteroalkyl group, and k) a 5-14 membered heteroaryl group, wherein each of d) - k) optionally is substituted with 1-4 -Y-R8 groups; R6 and R7, at each occurrence, independently are selected from a) H, b) -O-Y-R9, c) -S(0)m-Y-R9, d) -S(0)mO-Y-R9, e) -C(O)-Y-R9, f) -C(O)O-Y-R9, g) -C(O)NR10-Y-R'', h) -C(S)NR10-Y-R11, i) a C1-10 alkyl group, j) a C2_ 10 alkenyl group, k) a C2-10 alkynyl group, 1) a C1-10 haloalkyl group, m) a C3-14 cycloalkyl group, n) a C6-14 aryl group, o) a 3-14 membered cycloheteroalkyl group, and p) a 5-14 membered heteroaryl group, wherein each of i) - p) optionally is substituted with 1 -4-Y-R groups; R , at each occurrence, independently is selected from a) halogen, b) -CN, c) -NO2, d) oxo, e) -O-Y-R9, f) -NR10-Y-R11, g) -N(O)R10-Y-R11, h) -S(O)m-Y-R9, i) -S(O)mO-Y-R9, j) -S(O)mNR10-Y-R", k) -C(O)-Y-R9,1) -C(O)O~ Y-R9, m) -C(0)NR10-Y-R'', n) -C(S)NR10-Y-Rn, o) a C1-10 alkyl group, p) a C2-10 alkenyl group, q) a C2-10 alkynyl group, r) a C1-10 haloalkyl group, s) a C3-14 cycloalkyl group, t) a C6-14 aryl group, u) a 3-14 membered cycloheteroalkyl group, and v) a 5-14 membered heteroaryl group, wherein each of o) - v) optionally is substituted with 1-4 —Y-R12 groups; R9, at each occurrence, independently is selected from a) H, b) -C(O)-C1-10 alkyl, c) -C(O)OH, d) -C(O)O-C1-10 alkyl, e) a C1-10 alkyl group, f) a C2-10 alkenyl group, g) a C2-10 alkynyl group, h) a C1-10 haloalkyl group, i) a C3-14 cycloalkyl group, j) a C6-14 aryl group, k) a 3-14 membered cycloheteroalkyl group, and 1) a 5-14 membered heteroaryl group, wherein each of the C1-10 alkyl group, the C2-10 alkenyl group, the C2-10 alkynyl group, the C1-10 haloalkyl group, the C3-14 cycloalkyl group, the C6-14 aryl group, the 3-14 membered cycloheteroalkyl group, and the 5-14 membered heteroaryl group optionally is substituted with 1 -4 -Y-R groups; R10 and R1', at each occurrence, independently are selected from a) H, b) -OH, c) -SH, d) -NH2, e) -NH-C1-10 alkyl, f) -N(C1-10 alkyl)2, g) -S(O)m-C1-10 alkyl, h) -S(0)2OH, i) -S(O)m-OC1-10 alkyl, j) -C(O)-C1-10 alkyl, k) -C(O)OH, 1) -C(O)-OC1-10 alkyl, m) -C(O)NH2, n) -C(O)NH- C1-10 alkyl, o) - C(0)N(C1-10 alkyl)2, p) -C(S)NH2, q) -C(S)NH-C1-10 alkyl, r) -C(S)N( C1-10 alkyl)2, s) a C1-10 alkyl group, t) a C2-10 alkenyl group, u) a C2-10 alkynyl group, v) a C1-10 alkoxy group, w) a C1-10 haloalkyl group, x) a C3-14 cycloalkyl group, y) a C6-14 aryl group, z) a 3-14 membered cycloheteroalkyl group, and aa) a 5-14 membered heteroaryl group, wherein each of the C1-10 alkyl group, the C2-10 alkenyl group, the C2-10 alkynyl group, the C1-10 alkoxy group, the C1-10 haloalkyl group, the C^ .\4 cycloalkyl group, the C6-14 aryl group, the 3-14 membered cycloheteroalkyl group, and the 5-14 membered heteroaryl group optionally is substituted with 1-4 -Y-R12 groups; R , at each occurrence, independently is selected from a) halogen, b) -CN, c) -N02, d) oxo, e) -OH, f) -NH2, g) -NH(C,.,o alkyl), h) -N(C1-10 alkyl)2, i) -SH, j) -S(0)m-C1-10 alkyl, k) S(O)2OH, 1) -S(O)m-OC1-10 alkyl, m) -C(O)- C1-10 alkyl, n) -C(O)OH, o) C(O)-OC1-10 alkyl, p) ~C(O)NH2, q) -C(O)NH C1-10 alkyl, r) -C(O)N(C1-10 alkyl)2, s) -C(S)NH2, t) -C(S)NH-C1-10 alkyl, u) -C(S)N(C1-10 alkyl)2, v) a C1-10 alkyl group, w) a C2-10 alkenyl group, x) a C2-10 alkynyl group, y) a C1-10 alkoxy group, z) a C1-10 haloalkyl group, aa) a C3-14 cycloalkyl group, ab) a C6-14 aryl group, ac) a 3-14 membered cycloheteroalkyl group, and ad) a 5-14 membered heteroaryl group; and m is 0, 1, or 2; provided that when R1 is a 3-chloro-4-fluorophenyl group, R2 is not a 2-[(lH-imidazol-5-ylmethyl)amino]phenyl group. 2. The compound of claim 1 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein X is selected from -NH-, -N(CH3)-, -NH-CH2-, - NH-CH2CH2-, -NH-CH2CH2CH2 , -O-, and a covalent bond. 3. The compound of claim 1 or 2 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein R1 is selected from: (Formula Removed) 4. The compound of any one of claims 1-3 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein R , at each occurrence, is independently selected from -F, -Cl, -Br, -CN, -NO2, -O-Y-R5, -C(O)-Y-R5, -C(O)O-Y- R5, -NR6-Y-R7, and a C1-6 alkyl group. 5. The compound of any one of claims 1-4 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein R2 is selected from a phenyl group, a C8-14 aryl group and a 5-14 membered heteroaryl group, wherein each group optionally is substituted with 1-4 groups independently selected from -Y—R4 and -O-Y-R4. 6. The compound of any one of claims 1-5 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein R2 is: (Formula Removed) wherein D1, D2, and D3 independently are H, a -Y-R4 group, or an -O-Y-R4 group. 7. The compound claim 6 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein at least one of D1, D2, and D3 is a -Y-R4 group or an -O-Y— R4 group, wherein Y, at each occurrence, independently is a divalent C1-4 alkyl group or a covalent bond, and R4, at each occurrence, independently is selected from a halogen, -CN, NO2, -O-Y-R5, -NR6-Y-R7, -S(O)2-Y-R5, -S(O)2NR6-Y-R7, -C(O)-Y-R5, -C(O)O-Y-R5, -C(O)NR6-Y-R7, a C1-10 alkyl group, a C1-10 haloalkyl group, a C3-14 cycloalkyl group, a C6-14 aryl group, a 3-14 membered cycloheteroalkyl group, and a 5-14 membered heteroaryl group, wherein each of the C1-10 alkyl group, the C1-10 haloalkyl group, the C3-14 cycloalkyl group, the 05-14 aryl group, the 3-14 membered cycloheteroalkyl group, and the 5-14 membered heteroaryl group is optionally substituted with 1-4 -Y-R8 groups. 8. The compound of claim 7 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein the -Y-R4 group and the -O-Y-R4 group are selected from -O-(CH2)nNR6-Y-R7, -(CH2)nNR6-Y-R7, an -O-(CH2)n-3-14 membered cycloheteroalkyl group, and a -(CH2)n-3-14 membered cycloheteroalkyl group, wherein each of the 3-14 membered cycloheteroalkyl group optionally is substituted with 1-4 -Y-R8 groups, and n, at each occurrence, independently is 0, 1, 2, 3, or 4. 9. The compound of claim 8 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein the 3-14 membered cycloheteroalkyl group of the ~O- (CH2)n-3-14 membered cycloheteroalkyl group and the -(CH2)n—3-14 membered cycloheteroalkyl group is selected from a pyrrolidinyl group, a morpholinyl group, a piperazinyl group, a piperidinyl group, an azepanyl group, a diazepanyl group, and a thiomorpholinyl group. 10. The compound of claim 7 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein the -Y-R4 group and the -O-Y-R4 group are (Formula Removed) wherein R8, at each occurrence, independently is selected from -O-Y-R9, -NR10-Y-Rn, a C6-14 aryl group, and a 5-14 membered heteroaryl group, wherein the C6-14 aryl group and the 5-14 membered heteroaryl group optionally are substituted with 1-4 -Y-R12 groups, and n, at each occurrence, independently is 0, 1, 2, 3, or 4. 11. The compound of any one of claims 7-10 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein at least one of D1, D2, and D3 is selected from a halogen, -CN, -NO2, -S(O)2-Y-R5, -S(O)2NR6-Y-R7, -C(O)O--Y- R5, -C(O)NR6-Y-R7, a Ci_10 alkyl group, and a C1-10 haloalkyl group. 12. The compound of any one of claims 7-11 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein at least one of D1, D2, and D3 is a CVn aryl group or a 5-14 membered heteroaryl group, wherein each group optionally is substituted with 1 -4 -Y-R8 groups. 13. The compound of claim 12 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein at least one of D1, D2, and D3 is selected from a benzothienyl group, a benzofuryl group, a furyl group, a pyridyl group, a pyrimidinyl group, a pyrrolyl group, and a thienyl group, wherein each group optionally is substituted with 1-4 -Y-R8 groups, Y, at each occurrence, is o independently a CM alkyl group or a covalent bond, and R , at each occurrence, is independently selected from halogen, -CN, -NO2, -O-Y-R9, -NR10-Y-R11, -C(O)-Y-R9, C(O)NR10-Y-R11, -S(O)2-Y-R9, -S(O)2NR10-Y-R11, and a 3-14 membered cycloheteroalkyl group optionally substituted with a CM alkyl group. 14. The compound of any one of claims 1-5 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein R2 is a C8-14 bicyclic aryl group or a 5-14 membered heteroaryl group, wherein each of the C8-14 bicyclic aryl group and the 5-14 membered heteroaryl group is optionally substituted with 1-4 groups independently selected from -Y-R4 and -O-Y-R4. 15. The compound of claim 14 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein R2 is selected from a pyridyl group, a pyrimidyl group, a pyrazinyl group, a furyl group, a thienyl group, a thiazolyl group, an oxazolyl group, a benzofiiranyl group, a benzothienyl group, an indolyl group, a benzodioxinyl group, a benzodioxolyl group, a benzodioxanyl group, a dibenzofuranyl group, a dibenzothienyl group, a benzoindolyl group, an indanyl group, an indenyl group, an isothiazolyl group, a pyridazinyl group, a pyrazolyl group, a tetrahydronaphthyl group, an isoxazolyl group, a quinolinyl group, a naphthyl group, an imidazolyl group, and a pyrrolyl group, wherein each group optionally is substituted with 1-4 groups independently selected from -(CH2)n-R4 and -O-(CH2)n-R4, wherein n, at each occurrence, independently is 0, 1, 2, 3, or 4, and R4, at each occurrence, independently is -NR6-Y-R7 or a 3-14 membered cycloheteroalkyl group optionally substituted with a -Y-R8 group. 16. A compound of claim 1 selected from the following compounds: 4-[(3-chlorophenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 5-(3,4-dimethoxyphenyl)-4-[(3-fluoro phenyl)amino]nicotinonitrile, 4-anilino-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-[(2,5-difluorophenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 5-(3,4-dimethoxyphenyl)-4-[(3,4-dimethoxyphenyl)amino]nicotinonitrile, 4-[(4-chloro-2-fluorophenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-[(3-chloro-4-fluorophenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitiile, 4-[(4-chlorophenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 5-(3,4-dimethoxyphenyl)-4-[(2,4-dimethylphenyl)amino]nicotinonitrile, 5-(3,4-dimethoxyphenyl)-4-[(4-methoxyphenyl)amino]nicotinonitrile, 4-[(3-chloro-4-methoxyphenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 5-(3,4-dimethoxyphenyl)-4-[(4-phenoxy phenyl)amino]nicotinonitrile, 4-[(2,5-dichlorophenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 5-(3,4-dimethoxyphenyl)-4-[(4-methoxy-2-methylphenyl)amino]nicotinonitrile, 4-[(3,4-dichlorophenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-[(5-chloro-2-methoxyphenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-{[3-(benzyloxy)phenyl]amino}-5-(3,4-dimethoxyphenyl)nicotinonitrile, 5-(3,4-dimethoxyphenyl)-4-[(4-methyl phenyl)amino]nicotinonitrile, 5-(3,4-dimethoxyphenyl)-4-[(3,4,5-trimethoxyphenyl)amino]nicotinonitrile, 5-(3,4-dimethoxyphenyl)-4-[(3-phenoxy phenyl)amino]nicotinonitrile, 4-[(2-chloro-5-methoxyphenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-({3-chloro-4-[(3-cyanobenzyl)oxy]phenyl}amino)-5-(3,4-dimethoxy phenyl) nicotinonitrile, 4-( { 3 -chloro-4- [(3 -methylbenzyl)oxy]phenyl} amino)-5 -(3,4-dimethoxyphenyl) nicotinonitrile, 4-[(3-chloro-4-{[3-(dimethylamino)benzyl]oxy}phenyl)amino]-5-(3,4-dimethoxy phenyl)nicotinonitrile, 4-[(2,4-dichlorophenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, N-(3 - {[3-cyano-5-(3,4-dimethoxyphenyl)pyridin-4-yl] amino} phenyl)acetamide, N-(3-{[3-cyano-5-(3,4-dimethoxyphenyl)pyridin-4-yl]amino}phenyl)-N-methylacetamide, N-(3 - {[3-cyano-5-(3,4-dimethoxyphenyl)pyridin-4-yl]amino}phenyl)methanesulfonamide, 5-[4-(dimethylamino)phenyl]-4-[(3-methoxyphenyl)amino]nicotinonitrile, 5-[4-(dimethylamino)phenyl]-4-[(3-fluorophenyl)amino]nicotinonitrile, 4-( {3-cyano-5-[4-(dimethylamino)phenyl]pyridin-4-yl}amino)benzoic acid, 4-[(4-cyanophenyl)amino]-5-[4-(dimethylamino)phenyl]nicotinonitrile, 4-[(3,4-difluorophenyl)amino]-5-[4-(dimethylamino)phenyl]nicotinonitrile, 4-[(3 -bromophenyl)amino] -5 -(3,4-dimethoxyphenyl)nicotinonitrile, 4-{[3-(benzyloxy)-4-chloro phenyl]amino}-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-[(2,4-dichloro-5-methoxyphenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-[(2,4-dichloro-5-ethoxyphenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-[(2,4-dichloro-5-propoxyphenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-[(5-butoxy-2,4-dichlorophenyl)amino]-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-{[2,4-dichloro-5-(2-hydroxy ethoxy)phenyl]amino}-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-{[4-(benzyloxy)-3-chlorophenyl]amino}-5-(3-nitro phenyl)nicotinonitrile, 4-{[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}-5-(3-nitrophenyl)nicotinonitrile, 4-[(3-chloro-4-fluorophenyl) amino]-5-(3-nitrophenyl)nicotinonitrile, 5-(3-aminophenyl)-4-{[4-(benzyloxy)-3-chlorophenyl]amino}nicotinonitrile, 4-[(3-chloro-4-fluorophenyl) amino]-5-(2-nitrophenyl)nicotinonitrile, 5-(2-aminophenyl)-4-[(3-chloro-4-fluorophenyl)amino]nicotinonitrile, 4-[(2,4-dichloro-5-methoxy phenyl)amino]-5-[4-methoxy-3-(2-methoxy ethoxy)phenyl]nicotinonitrile, 4-[(2,4-dichloro-5-methoxy phenyl)amino]-5-[3-methoxy-4-(2-methoxyethoxy)phenyl]nicotinonitrile, 5-[3-(2-chloroethoxy)phenyl]-4-[(2,4-dichloro-5-methoxyphenyl)amino]nicotinonitrile, 4-[(2,4-dichloro-5-methoxyphenyl)amino]-5-[3-(2-pyrrolidin-l-ylethoxy)phenyl]nicotinonitrile, 5-[4-(dimethylamino)phenyl]-4-[(3-nitrophenyl)amino]nicotinonitrile, 5-(3-methoxyphenyl)-4-[(3-nitrophenyl)amino]nicotinonitrile, 5-(3-methoxyphenyl)-4-[(3-methoxy phenyl)amino]nicotinonitrile, 4-[(3-fluorophenyl)amino]-5-(3-methoxyphenyl)nicotinonitrile, 4- {[3-cyano-5-(3-methoxyphenyl)pyridin-4-y 1]amino} benzoic acid, 4-[(4-cyanophenyl)amino]-5-(3-methoxyphenyl)nicotinonitrile, 4-[(3,4-difluorophenyl)amino]-5-(3-methoxyphenyl)nicotmonitrile, 5-(3,4-dimethoxyphenyl)-4-[(3-hydroxy phenyl)amino]nicotinonitrile, 5-(3,4-dimethoxyphenyl)-4-{[3-(2-hydroxyethoxy)phenyl] amino} nicotinonitrile, 4-[(3-{[(2S)-2-amino-3-phenyl propyl]-oxy}-phenyl)amino]-5-(3,4-dimethoxy phenyl)nicotinonitrile, 4-[(2-chloro-5-hydroxyphenyl) amino]-5-(5-formyl-l-benzo thien-2-yl)nicotinonitrile, 4-[(2-chloro-5-hydroxy phenyl)amino]-5-[5-(piperidin-1 -ylmethyl)-1 -benzothien-2-yl]nicotinonitrile, 4-{[2-chloro-5-(2-hydroxyethoxy)phenyl]amino}-5-[5-(piperidin-l-yl methyl)-1 -benzothien-2-yl]nicotinonitrile, 4-[(4-amino-2,3-dimethylphenyl)amino]-5-[5-(piperidin-l-ylmethyl)-1-benzothien-2-yl]nicotinonitrile, 4-[(4-amino-3-methylphenyl) amino]-5-[5-(piperidin-l-yl methyl)-! -benzothien-2-yl]nicotinonitrile, 4-[(2-chloro-5-methoxyphenyl)amino]-5-[5-(piperidin-l-ylmethyl)-1-benzofiiran-2-yl]nicotinonitrile, 4-[(2-chloro-5-methylphenyl)amino]-5-[5-(piperidin-l-ylmethyl)-l-benzofuran-2-yl]nicotinonitrile, 4-[(5-hydroxy-2-phenoxyphenyl)amino]-5-[5-(piperidin-1 -ylmethyl)-1 -benzofuran-2-yl]nicotinonitrile, 4-{[3-(aminomethyl)benzyl]amino}-5-(3,4-dimethoxyphenyl)nicotinonitrile, 4-[(2,4-dichloro-5-hydroxyphenyl)amino]-5-[5-(piperidin-1 -ylmethyl)-1 -benzofuran-2-yl]nicotinonitrile, and 4-[(4-methoxy-2-methylphenyl)amino]-5-[5-(piperidin-l-ylmethyl)-l-benzofuran-2-yl]nicotinonitrile. 17. The compound of any one of claims 1 -16 or a pharmaceutically acceptable salt, hydrate, or ester thereof, wherein the compound is in the form of an enantiomer. 18. A pharmaceutical composition comprising the compound of any one of claims 1-17 and a pharmaceutically acceptable carrier or excipient. 19. A method of treating or inhibiting a pathological condition or disorder mediated by a protein kinase in a mammal, the method comprising providing to the mammal an effective amount of the compound of any one of claims 1 - 17 or a pharmaceutically acceptable salt, hydrate, or ester thereof. 20. The method of claim 19, wherein the protein kinase is protein kinase C. 21. The method of claim 19 or 20, wherein the pathological condition or disorder is an inflammatory disease or an autoimmune disease selected from asthma, colitis, multiple sclerosis, psoriasis, arthritis, rheumatoid arthritis, osteoarthritis, and joint inflammation. 22. A compound as claimed in any one of claims 1-17 or a pharmaceutically acceptable salt, hydrate, or ester thereof for use as a medicament. 23. Use of a compound as claimed in any one of claims 1-17 or a pharmaceutically acceptable salt, hydrate, or ester thereof in the preparation of a medicament for the treatment or inhibition of a pathological condition or disorder mediated by a protein kinase in a mammal. 24. Substituted cyanopyridines as protein kinase inhibitors and its application substantially such as herein described.