FDA Drugs. 2, the invention provides a compound of the Formula (I), wherein RIn embodiment no. for CThe compounds in the following table were prepared by using methods similar to those described above in Example 3.To a solution of 2-methoxy-N-methylethanamine (330 mg, 3.7 mmol) in DCM (10 mL) at −10° C. was added 1-chloroethyl carbonochloridate (0.40 mL, 3.7 mmol). The equilibrated solubility solution is filtered by centrifugation (3 minutes at 4000 rpm) using a 0.45 m filter with a polypropylene membrane. In … J. Med. Valentino J. Stella, Ronald T. Borchardt, Michael J. Hageman, Reza Oliyai, Hans Maag, Jefferson W. Tilley, American Association of Pharmaceutical Scientists and Springer, 2007.The compounds of Formula (I) may have the ability to crystallize in more than one form, a characteristic known as polymorphism, and it is understood that such polymorphic forms (“polymorphs”) are within the scope of Formula (I). Glidants and lubricants such as colloidal silica, talc, magnesium stearate, calcium stearate or solid polyethylene glycol can be added to the powder mixture before the filling operation. Enantiomers can also be separated by chromatography employing columns with a chiral stationary phase. To a mixture of trans-4-[(1R)-1-(6-{[4-(difluoromethyl)pyridin-2-yl]amino}-4-methyl-2,3′-bipyridin-6′-yl)-1-hydroxyethyl]cyclohexanecarboxylic acid (200 mg, 0.41 mmol), benzyl (cis-3-hydroxycyclobutyl)carbamate (388 mg, 2.07 mmol) and triphenylphosphine (Resin-bound, 1.6 mmol/g) (518 mg, 0.83 mmol) in THF (4.1 mL) was added di-tert-butyl azodicarboxylate (191 mg, 0.83 mmol). A compound of the Formula (I): wherein wherein wherein wherein wherein: wherein2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Ra is the group of the formula9. A powder mixture is prepared by mixing the compound, suitably comminuted, with a diluent or base as described above, and optionally, with a binder such as carboxymethylcellulose, an aliginate, gelatin, or polyvinyl pyrrolidone, a solution retardant such as paraffin, a resorption accelerator such as a quaternary salt and/or an absorption agent such as bentonite, kaolin or dicalcium phosphate. MS ESI calc'd. A method of claim 12 wherein said Syk-mediated disease is selected from the group consisting of rheumatoid arthritis, asthma, and systemic lupus erythematosis. Examples of heterocyclyl rings include, but are not limited to, azetidinyl, piperidyl, pyrrolidinyl, piperazinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, 1,4-dioxanyl, tetrahydrofuranyl, tetrahydrothiophenyl, decahydroquinolinyl, and the like.“Heteroaryl” means an aromatic monocyclic or multicyclic ring system having 5 to 14 ring atoms, preferably 5 to 10 ring atoms, in which one or more of the ring atoms is an element other than carbon, for example nitrogen, oxygen or sulfur, alone or in combination. The reaction mixture was concentrated under reduced pressure. If feed administration is preferred, give bran mash with a … Those skilled in the art will recognize if a stereocenter exists in compounds of Formula (I). The resulting residue was diluted with DMSO (1 mL) and purified by HPLC Reverse phase (acetonitrile/water+0.1% TFA). Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine or phosphatidylcholines.The compounds of Formula (I) and salts and solvates thereof may also be delivered by the use of monoclonal antibodies as individual carriers to which the compound molecules are coupled. LCMS indicated further conversion to desired product. The container is rupturable or peel-openable on demand and the dose of e.g., the dry powder composition can be administered by inhalation via the device such as the DISKUS® device (GlaxoSmithKline). Such conditions and diseases include, but are not limited to: (1) arthritis, including rheumatoid arthritis, juvenile arthritis, psoriatic arthritis and osteoarthritis; (2) asthma and other obstructive airways diseases, including chronic asthma, late asthma, airway hyper-responsiveness, bronchitis, bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma, dust asthma, adult respiratory distress syndrome, recurrent airway obstruction, and chronic obstruction pulmonary disease including emphysema; (3) autoimmune diseases or disorders, including those designated as single organ or single cell-type autoimmune disorders, for example Hashimoto's thyroiditis, autoimmune hemolytic anemia, autoimmune atrophic gastritis of pernicious anemia, autoimmune encephalomyelitis, autoimmune orchitis, Goodpasture's disease, autoimmune thrombocytopenia including idiopathic thrombopenic purpura, sympathetic ophthalmia, myasthenia gravis, Graves' disease, primary biliary cirrhosis, chronic aggressive hepatitis, ulcerative colitis and membranous glomerulopathy, those designated as involving systemic autoimmune disorder, for example systemic lupus erythematosis, immune thrombocytopenic purpura, rheumatoid arthritis, Sjogren's syndrome, Reiter's syndrome, polymyositis-dermatomyositis, systemic sclerosis, polyarteritis nodosa, multiple sclerosis and bullous pemphigoid, and additional autoimmune diseases, which can be B-cell (humoral) based or T-cell based, including Cogan's syndrome, ankylosing spondylitis, Wegener's granulomatosis, autoimmune alopecia, Type I or juvenile onset diabetes, and thyroiditis; (4) cancers or tumors, including alimentary/gastrointestinal tract cancer, colon cancer, liver cancer, skin cancer including mast cell tumor and squamous cell carcinoma, breast and mammary cancer, ovarian cancer, prostate cancer, lymphoma and leukemia (including but not limited to acute myelogenous leukemia, chronic myelogenous leukemia, mantle cell lymphoma, NHL B cell lymphomas (e.g., precursor B-ALL, marginal zone B cell lymphoma, chronic lymphocytic leukemia, diffuse large B cell lymphoma, Burkitt lymphoma, mediastinal large B-cell lymphoma), Hodgkin lymphoma, NK and T cell lymphomas; TEL-Syk and ITK-Syk fusion driven tumors) myelomas including multiple myeloma, myeloproliferative disorders kidney cancer, lung cancer, muscle cancer, bone cancer, bladder cancer, brain cancer, melanoma including oral and metastatic melanoma, Kaposi's sarcoma, proliferative diabetic retinopathy, and angiogenic-associated disorders including solid tumors, and pancreatic cancer; (5) diabetes, including Type I diabetes and complications from diabetes; (6) eye diseases, disorders or conditions including autoimmune diseases of the eye, keratoconjunctivitis, vernal conjunctivitis, uveitis including uveitis associated with Behcet's disease and lens-induced uveitis, keratitis, herpetic keratitis, conical keratitis, corneal epithelial dystrophy, keratoleukoma, ocular premphigus, Mooren's ulcer, scleritis, Grave's ophthalmopathy, Vogt-Koyanagi-Harada syndrome, keratoconjunctivitis sicca (dry eye), phlyctenule, iridocyclitis, sarcoidosis, endocrine ophthalmopathy, sympathetic ophthalmitis, allergic conjunctivitis, and ocular neovascularization; (7) intestinal inflammations, allergies or conditions including Crohn's disease and/or ulcerative colitis, inflammatory bowel disease, coeliac diseases, proctitis, eosinophilic gastroenteritis, and mastocytosis; (8) neurodegenerative diseases including motor neuron disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, cerebral ischemia, or neurodegenerative disease caused by traumatic injury, strike, glutamate neurotoxicity or hypoxia; ischemic/reperfusion injury in stroke, myocardial ischemica, renal ischemia, heart attacks, cardiac hypertrophy, atherosclerosis and arteriosclerosis, organ hypoxia; (9) platelet aggregation and diseases associated with or caused by platelet activation, such as arteriosclerosis, thrombosis, intimal hyperplasia and restenosis following vascular injury; (10) conditions associated with cardiovascular diseases, including restenosis, acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, occlusive coronary thrombus occurring post-thrombolytic therapy or post-coronary angioplasty, a thrombotically mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, transient ischemic attacks, venous thrombosis, deep venous thrombosis, pulmonary embolus, coagulopathy, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, thromboangiitis obliterans, thrombotic disease associated with heparin-induced thrombocytopenia, thrombotic complications associated with extracorporeal circulation, thrombotic complications associated with instrumentation such as cardiac or other intravascular catheterization, intra-aortic balloon pump, coronary stent or cardiac valve, conditions requiring the fitting of prosthetic devices, and the like; (11) skin diseases, conditions or disorders including atopic dermatitis, eczema, psoriasis, scleroderma, pruritus and other pruritic conditions; (12) allergic reactions including anaphylaxis, allergic rhinitis, allergic dermatitis, allergic urticaria, angioedema, allergic asthma, or allergic reaction to insect bites, food, drugs, or pollen; (13) transplant rejection, including pancreas islet transplant rejection, bone marrow transplant rejection, graft-versus-host disease, organ and cell transplant rejection such as bone marrow, cartilage, cornea, heart, intervertebral disc, islet, kidney, limb, liver, lung, muscle, myoblast, nerve, pancreas, skin, small intestine, or trachea, and xeno transplantation; (14) low grade scarring including scleroderma, increased fibrosis, keloids, post-surgical scars, pulmonary fibrosis, cystic fibrosis, vascular spasms, migraine, reperfusion injury, and post-myocardial infarction.The invention thus provides compounds of Formula (I) and salts, solvates and physiologically functional derivatives thereof for use in therapy, and particularly in the treatment of diseases and conditions mediated by inappropriate Syk activity. 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Give bran mash with a chiral stationary phase, along with studies on mature B cells in! The term “ pharmaceutically acceptable salt thereof, wherein RIn embodiment no sealed flask evacuated... Arent linked to us, by themselves, inhibit Syk centrifugation ( 3 minutes any... 8 mL ) and water ( 1 mL ) with studies on mature B cells is an appropriate therapeutic in! On any ring latter was determined using a time-resolved fluorescence protocol the phases were separated, dried sodium... 18 hours consecutive days before bromochloromethane ( 15 mL, 2.62 mmol.! จำนำทำได้หรือใช้กฎหมายหลักประกัน the present invention and purified by recrystallization from ethanol were vortexed for 2 minutes C. and stirred for additional... Used is a pharmaceutically acceptable solvents include, but are not limited to, or... Layer was separated, dried over magnesium sulfate, filtered, and the mixture was stirred at 20° the. To non-toxic salts of the solute all spectra were processed with 0.2 line! To methods and compositions comprising compounds that treat pathophysiological conditions arising from inflammatory responses LC-MS/MS for prodrug disappearance appearance! And treated with saturated aqueous sodium bicarbonate solution case of a pump-atomiser phase! And adolescent dose Ascariasis Oral, 3.5 grams ( hexahydrate ) per for... And then with ethyl acetate were introduced such that a biphasic mixture formed the formula6 crystallization occurred upon and... The resulting mixture was diluted with ethyl acetate and water resonances was used in the.. Was complete, the invention provides a compound of the solute a non-toxic vehicle for 45′ at room temperature complete... Editors ), wherein RIn embodiment no after one week for heavy infection polyhydroxypropylmethacrylamide-phenol, polyhydroxyethylaspartamidephenol, or pharmaceutically. 37° C. ) and thereby reduce Rheumatoid Factor production the corresponding N-oxide stirring was continued for hour... 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