The present invention relates to a compound having general formula (I) for use in the activation of AMPK. A composition comprising said compound for use in the activation of AMPK is also provided.

The present invention relates to a process for the preparation of angiotensin receptor blockers or its pharmaceutically acceptable salts thereof containing less than 10 ppm of the azido impurities. More particularly, the present invention relates to process for the preparation of Losartan, Losartan potassium of Formula I or its other pharmaceutically acceptable salts thereof containing less than 10 ppm of each of the azido impurities, wherein the azido impurity is selected from the group comprising of 5-(4′-(azidomethyl)-[1,1′-biphenyl]-2-yl)-1H-tetrazole, 4′-(azidomethyl)-[1,1′-biphenyl]-2-carbonitrile, 4′-((5-(azidomethyl)-2-butyl-4-chloro-1H-imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-carbonitrile, 5-(4′-((5-(azidomethyl)-2-butyl-4-chloro-1H-imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-yl)-1H-tetrazole, 5-(azidomethyl)-2-butyl-4-chloro-1H-imidazole, 4′-((4-(azidomethyl)-2-butyl-5-chloro-1H-imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-carbonitrile, 5-(4′-((4-(azidomethyl)-2-butyl-5-chloro-1H-imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-yl)-1H-tetrazole and 1-((1-((2′-(1H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-butyl-4-chloro-1H-imidazol-5-yl)methyl)-5-(4′-((5-(azidomethyl)-2-butyl-4-chloro-1H-imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-yl)-1H-tetrazole. More particularly, the present invention relates to a simple, economical and industrially efficient process for the preparation of Losartan potassium of Formula I. The present invention also relates to solid oral pharmaceutical compositions and process for preparing solid oral pharmaceutical compositions comprising losartan or its pharmaceutically acceptable salts thereof and method of detecting azido impurities in these solid oral pharmaceutical compositions.

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The present disclosure provides peptides, or variants or analogs thereof, with between 8 and 30 amino acids, having growth factor receptor-binding capability, wherein the RMSD value of the structure coordinates of said peptide, variant or analog thereof with respect to PEPREF is 2.45 Å (Angstroms) or less.

The present invention is directed to co-therapy and methods for the treatment and prevention of glucose-related disorders such as Type 2 diabetes mellitus and Syndrome X. The present invention is further directed to pharmaceutical compositions for the co-therapy and methods described herein.

There is a method of treating or preventing pulmonary arterial hypertension (PAH) or associated pulmonary arterial hypertension (APAH) in a patient. The method has the step of systemically administering to the patient a therapeutically effective amount of one or more compounds: (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof, or (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroeth-oxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof, or a combination of the foregoing. There is also a method of treating or preventing PAH or APAH in a patient by systemically administering a therapeutically effective amount of a THP1 inhibitor from about 1 mg/kg/day to about 50 mg/kg/day. There is a method for treating PAH or APAH in a patient with a single daily dose.

There is a method of treating or preventing pulmonary arterial hypertension (PAH) or associated pulmonary arterial hypertension (APAH) in a patient. The method has the step of systemically administering to the patient a therapeutically effective amount of one or more compounds: (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof, or (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroeth-oxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof, or a combination of the foregoing. There is also a method of treating or preventing PAH or APAH in a patient by systemically administering a therapeutically effective amount of a THP1 inhibitor from about 1 mg/kg/day to about 50 mg/kg/day. There is a method for treating PAH or APAH in a patient with a single daily dose.

The present disclosure relates to methods of treating gastrointestinal stromal tumors to a subject in need thereof, comprising administering to the subject a therapeutically effective amount of ripretinib or a pharmaceutically acceptable salt thereof.

The present disclosure relates to methods of treating gastrointestinal stromal tumors to a subject in need thereof, comprising administering to the subject a therapeutically effective amount of ripretinib or a pharmaceutically acceptable salt thereof.

The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF, and low immunogenicity. The antibodies are designed for the diagnosis and/or treatment of TNF-mediated disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of the antibodies in medicine are also described.

The present invention relates to a transdermal therapeutic system for the transdermal administration of guanfacine comprising a guanfacine-containing layer structure, said guanfacine-containing layer structure comprising: A) a backing layer; and B) a guanfacine-containing layer; wherein the transdermal therapeutic system comprises at least one silicone polymer.