Abstract: A composition comprising BL-8040 (SEQ ID NO: 1) is disclosed herein, which may be for use in treating a condition treatable by BL-8040. The composition further comprises at least one compound characterized by a relative retention time of from 0.86 to 0.88 and/or a relative retention time of from 0.71 to 0.73 (wherein a relative retention time of BL-8040 is 1) under conditions described herein.

Abstract: A composition comprising BL-8040 (SEQ ID NO: 1) is disclosed herein, which may be for use in treating a condition treatable by BL-8040. The composition further comprises at least one compound characterized by a relative retention time of from 0.86 to 0.88 and/or a relative retention time of from 0.71 to 0.73 (wherein a relative retention time of BL-8040 is 1) under conditions described herein.

Abstract: A large-scale process is described herein for preparing a cyclic peptide as described, comprising solid phase peptide synthesis of a linear peptide and cleaving it from the resin; oxidizing cysteine residues to form an intramolecular disulfide bond; and isolating the cyclic peptide, wherein: (i) coupling uses diisopropylcarbodiimide and ethyl cyanohydroxyiminoacetate and/or N-hydroxybenzotriazole; (ii) cleaving comprises contacting the peptide with a solution comprising TFA and dithioerythritol and/or dithiothreitol; (iii) the peptide is precipitated after cleaving without prior concentration of the peptide by evaporation; (iv) oxidizing comprises contacting an aqueous solution comprising at least 5 mg/mL peptide with hydrogen peroxide; (v) isolating comprises loading the peptide on a reverse phase chromatography at up to 40 grams/kg column, and elution from the column; (vi) isolating comprises lyophilization, followed by grinding the peptide; and/or (vii) substitution of the resin is at least 0.

Abstract: A composition comprising BL-8040 (SEQ ID NO: 1) is disclosed herein, which may be for use in treating a condition treatable by BL-8040. The composition further comprises at least one compound characterized by a relative retention time of from 0.86 to 0.88 and/or a relative retention time of from 0.71 to 0.73 (wherein a relative retention time of BL-8040 is 1) under conditions described herein.

Abstract: A large-scale process is described herein for preparing a cyclic peptide as described, comprising solid phase peptide synthesis of a linear peptide and cleaving it from the resin; oxidizing cysteine residues to form an intramolecular disulfide bond; and isolating the cyclic peptide, wherein: (i) coupling uses diisopropylcarbodiimide and ethyl cyanohydroxyiminoacetate and/or N-hydroxybenzotriazole; (ii) cleaving comprises contacting the peptide with a solution comprising TFA and dithioerythritol and/or dithiothreitol; (iii) the peptide is precipitated after cleaving without prior concentration of the peptide by evaporation; (iv) oxidizing comprises contacting an aqueous solution comprising at least 5 mg/mL peptide with hydrogen peroxide; (v) isolating comprises loading the peptide on a reverse phase chromatography at up to 40 grams/kg column, and elution from the column; (vi) isolating comprises lyophilization, followed by grinding the peptide; and/or (vii) substitution of the resin is at least 0.

Abstract: A composition comprising BL-8040 (SEQ ID NO: 1) is disclosed herein, which may be for use in treating a condition treatable by BL-8040. The composition further comprises at least one compound characterized by a relative retention time of from 0.86 to 0.88 and/or a relative retention time of from 0.71 to 0.73 (wherein a relative retention time of BL-8040 is 1) under conditions described herein.

Abstract: An acid addition salt of a nortriptyline-GABA conjugate, a novel crystalline form of a fumaric acid addition salt of a nortriptyline-GABA conjugate, and processes of preparing the forgoing are disclosed. Uses of the above-indicated forms of a nortriptyline-GABA conjugate in the treatment of CNS disorders, and in the treatment of pain in particular, are also disclosed. Further disclosed in a large-scale process of preparing a nortriptyline-GABA conjugate.

Abstract: Novel crystalline form of perphenazine 4-aminobutyrate trimesylate and a process of producing the same are disclosed. The novel crystalline form is characterized by a unique XRPD pattern and a DSC that exhibits an endothermic peak at a relatively high temperature (e.g., higher than 209° C.). Also disclosed are a process of preparing perphenazine 4-aminobutyrate trimesylate by in situ deprotection and salification, in a single-step synthesis, and a highly pure perphenazine 4-aminobutyrate trimesylate obtained thereby. Uses of any of the described perphenazine 4-aminobutyrate trimesylate are also disclosed.

Abstract: Novel crystalline form of perphenazine 4-aminobutyrate trimesylate and a process of producing the same are disclosed. The novel crystalline form is characterized by a unique XRPD pattern and a DSC that exhibits an endothermic peak at a relatively high temperature (e.g., higher than 209° C.). Also disclosed are a process of preparing perphenazine 4-aminobutyrate trimesylate by in situ deprotection and salification, in a single-step synthesis, and a highly pure perphenazine 4-aminobutyrate trimesylate obtained thereby. Uses of any of the described perphenazine 4-aminobutyrate trimesylate are also disclosed.

Abstract: Ectonucleoside triphosphate diphosphohydrolases [NTPDases; EC 3.6.1.5] constitute a family of enzymes which are involved in the metabolism of extracellular nucleotides, catalysing the hydrolysis of the gamma and beta phosphate bonds of triphospho- and diphosphonucleosides (whereas 5′nucleotidases [EC 3.1.3.5] catalyse the hydrolysis of alpha phosphate bond of monophosphonucleosides). These extracellular nucleotides interact with endothelial, epithelial and smooth muscle cells, as well as blood cells and lymphoid cells, to influence the different physiological systems of vertebrates.

Abstract: C8-substituted purine nucleotide analogs, such as ATP analogs, and their use is described, including their use as inhibitors of NTPDases and thereby as tools to modulate the conversion of nucleotides into nucleoside derivatives, and thus modulate the levels of these compounds. Such modulation further provides for the modulation of the activity and function of many processes which are affected by these compounds.