The present disclosure provides compounds that include a tetrazolone derivative of a carboxyl group of an active agent. This disclosure also relates to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, and processes for preparing these compounds.

The present disclosure provides compounds that include a tetrazolone derivative of a carboxyl group of an active agent. This disclosure also relates to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, and processes for preparing these compounds.

The present invention provides a prophylactic and/or therapeutic agent for amyotrophic lateral sclerosis (ALS), which contains one or more kinase inhibitors selected from the group consisting of an epithelial cell growth factor receptor (EGFR) inhibitor, a fibroblast growth factor receptor (FGFR) inhibitor, an Aurorakinase inhibitor, a protein kinase A (PKA) inhibitor, a protein kinase C (PKC) inhibitor, an MEK inhibitor, an Met inhibitor, a JNK inhibitor, a Syk inhibitor and a JAK inhibitor, a prostaglandin analogue and an estrogen receptor antagonist, or one or more kinase inhibitors selected from the group consisting of Tivozanib and an analog thereof, SB 216763, Cdk2 Inhibitor II, BUDESONIDE, RIBOFLAVIN, alpha-TOCHOPHEROL, AMODIAQUINE, SU9516, Sunitinib and an analog thereof, GSK-3 Inhibitor XIII, Bisindolylmaleimide I, HYDROQUINONE, FLUNISOLIDE, MGCD-265, Indirubin-3′-monoxime, HYDRASTINE (1R,9S), PIPERINE, BUTAMBEN, Axitinib and an analog thereof, APOMORPHINE, FENBUFEN, Bosutinib (SKI-606) and an analog thereof, a Wee1 Inhibitor, Cdk2 Inhibitor IV, NU6140, 3-hydroxybutyric acid, AT9283, Imatinib, Nilotinib, Rebastinib, and Bafetinib for the prophylaxis and/or treatment of ALS. Particularly, using a compound already on the market as a pharmaceutical product, a pharmaceutical product for the prophylaxis or treatment of ALS can be developed rapidly at a low cost.

The present invention relates a new process to synthesize 1-((4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinolin-7-yloxy)methyl)cyclopropanamine (AL3818). A stable crystalline form of A13818 has been prepared. Salts and their crystalline forms of AL3818 have been also prepared. Anti-cancer and optometric activities of AL3818 and its salts have been further tested. New process has been outlined in Scheme I.

##STR00001##

The present invention relates a new process to synthesize 1-((4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinolin-7-yloxy)methyl)cyclopropanamine (AL3818). A stable crystalline form of A13818 has been prepared. Salts and their crystalline forms of AL3818 have been also prepared. Anti-cancer and optometric activities of AL3818 and its salts have been further tested. New process has been outlined in Scheme I.

##STR00001##

The present invention relates a new process to synthesize 1-((4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinolin-7-yloxy)methyl)cyclopropanamine (AL3818). A stable crystalline form of A13818 has been prepared. Salts and their crystalline forms of AL3818 have been also prepared. Anti-cancer and optometric activities of AL3818 and its salts have been further tested. New process has been outlined in Scheme I.

##STR00001##

The present invention relates to extended release compositions of an amino-C2-C6-alkyl nitrate and of pharmaceutically acceptable salt thereof, in particular 2-aminoethyl nitrate, and to fixed dose combinations with further pharmaceutically active drug substances. 2-Aminoethyl nitrate does not provoke nitrate tolerance, but has a very short half life in physiological systems.

A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a disintegrant, a surfactant, a binder, and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Processes of preparing pharmaceutical compositions comprising Compound 1 are also disclosed.

A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a disintegrant, a surfactant, a binder, and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Processes of preparing pharmaceutical compositions comprising Compound 1 are also disclosed.

A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a disintegrant, a surfactant, a binder, and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Processes of preparing pharmaceutical compositions comprising Compound 1 are also disclosed.