C07H5/10

NONIONIC, REDOX-CLEAVABLE SURFACTANT FOR MASS SPECTROMETRY-BASED PROTEOMICS AND STRUCTURAL BIOLOGICAL APPLICATIONS
20240076553 · 2024-03-07 ·

The present invention provides nonionic cleavable surfactants (NCS), specifically n-Decyl-disulfide--D-maltoside (DSSM), suitable for MS-based proteomics and analysis. These surfactants are designed to mimic the properties of a commonly used surfactant in structural biology, n-dodecyl--d-maltoside (DDM), but contain a disulfide bond that allows for facile cleavage and surfactant removal before analysis. DSSM and other NCS are compatible with native mass spectrometry, top-down and bottom-up proteomics, ESI-MS and other analytical techniques, and reduce signal suppression typically observed with other surfactants. DSSM and other NCS provide versatile surfactants that can facilitate protein sample preparation under non-denaturing conditions for a myriad of proteomic and structural biology applications and act as a general replacement for DDM.

Treatment of metabolic disorders in feline animals

The present invention relates to one or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof for use in the treatment and/or prevention of a metabolic disorder in a feline animal, preferably wherein the metabolic disorder is one or more selected from the group consisting of: ketoacidosis, pre-diabetes, diabetes mellitus type 1 or type 2, insulin resistance, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, atherosclerosis, inflammation of the pancreas, neuropathy and/or Syndrome X (metabolic syndrome) and/or loss of pancreatic beta cell function and/or wherein the remission of the metabolic disorder, preferably diabetic remission, is achieved and/or maintained.

Treatment of metabolic disorders in feline animals

The present invention relates to one or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof for use in the treatment and/or prevention of a metabolic disorder in a feline animal, preferably wherein the metabolic disorder is one or more selected from the group consisting of: ketoacidosis, pre-diabetes, diabetes mellitus type 1 or type 2, insulin resistance, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, atherosclerosis, inflammation of the pancreas, neuropathy and/or Syndrome X (metabolic syndrome) and/or loss of pancreatic beta cell function and/or wherein the remission of the metabolic disorder, preferably diabetic remission, is achieved and/or maintained.

NON-ANTICOAGULANT SULFATED OR SULFONATED POLYSACCHARIDES

The present invention provides non-anticoagulant sulfated or sulfonated polysaccharides (NASPs), which accelerate the blood clotting process. Also provided are pharmaceutical formulations comprising a NASP of the invention in conjunction with a pharmaceutically acceptable excipient and, in various embodiments, these formulations are unit dosage formulations. The invention provides a NASP formulation, which is orally bioavailable. Also provided are methods for utilizing the compounds and formulations of the invention to promote blood clotting in vivo as therapeutic and prophylactic agents and in vitro as an aid to studies of the blood clotting process.

IDIOPATHIC PULMONARY FIBROSIS-DETECTION, MONITORING, PREDICTION METHODS

Provided is a compound of the general formula (I):

##STR00001##

The compound of formula (I) is suitable for treating pulmonary fibrosis, such as Idiopathic pulmonary fibrosis in a mammal. Also provided is a method for treatment of pulmonary fibrosis, such as Idiopathic pulmonary fibrosis in a human subject having a galectin-3 level indicative of pulmonary fibrosis or exacerbation of symptoms as well as a method for making said compound.

IDIOPATHIC PULMONARY FIBROSIS-DETECTION, MONITORING, PREDICTION METHODS

Provided is a compound of the general formula (I):

##STR00001##

The compound of formula (I) is suitable for treating pulmonary fibrosis, such as Idiopathic pulmonary fibrosis in a mammal. Also provided is a method for treatment of pulmonary fibrosis, such as Idiopathic pulmonary fibrosis in a human subject having a galectin-3 level indicative of pulmonary fibrosis or exacerbation of symptoms as well as a method for making said compound.

Alpha-selective sialyl donor and its uses for preparation of sialosides
10435425 · 2019-10-08 · ·

Disclosed herein a sialyl donor and its use for the synthesis of gangliosides. The sialyl donor has the structure of, ##STR00001##
wherein, R.sub.1 and R.sub.2 are independently benzoyl, toluenesulfonyl, pivaloyl or acetyl optionally substituted with a halogen; and R.sub.3 is acetyl or (O)CCH.sub.2OH. In one preferred embodiment, in the sialyl donor of formula (I), R is acetyl. Also disclosed herein is a method of synthesizing a sialoside. The method comprises steps of: coupling the sialyl donor of formula (I) with a glycosyl acceptor having a primary hydroxyl group in the presence of N-iodosuccinimide (NIS) and trifluoromethanesulfonic acid (TfOH) under suitable conditions; and isolating the sialoside, which has an -glycosidic linkage. According to preferred embodiments, the coupling is conducted in a solvent selected from the group consisting of, CH.sub.3CN, CH.sub.3Cl, and CH.sub.2Cl.sub.2 at a temperature between 20 C. to 60 C. Additionally or optionally, the coupling is conducted in CH.sub.2Cl.sub.2 with the presence of a powdered molecular sieve at 40 C.

Alpha-selective sialyl donor and its uses for preparation of sialosides
10435425 · 2019-10-08 · ·

Disclosed herein a sialyl donor and its use for the synthesis of gangliosides. The sialyl donor has the structure of, ##STR00001##
wherein, R.sub.1 and R.sub.2 are independently benzoyl, toluenesulfonyl, pivaloyl or acetyl optionally substituted with a halogen; and R.sub.3 is acetyl or (O)CCH.sub.2OH. In one preferred embodiment, in the sialyl donor of formula (I), R is acetyl. Also disclosed herein is a method of synthesizing a sialoside. The method comprises steps of: coupling the sialyl donor of formula (I) with a glycosyl acceptor having a primary hydroxyl group in the presence of N-iodosuccinimide (NIS) and trifluoromethanesulfonic acid (TfOH) under suitable conditions; and isolating the sialoside, which has an -glycosidic linkage. According to preferred embodiments, the coupling is conducted in a solvent selected from the group consisting of, CH.sub.3CN, CH.sub.3Cl, and CH.sub.2Cl.sub.2 at a temperature between 20 C. to 60 C. Additionally or optionally, the coupling is conducted in CH.sub.2Cl.sub.2 with the presence of a powdered molecular sieve at 40 C.

5`S-LNA nucleotides and oligonucleotides

The invention relates to a compound of formula (I) wherein R2 and R4 are joined and together form a group, such a CH2O. The compound of formula (I) can be used in the manufacture of 5S-LNA oligonucleotides as antisense drugs.

##STR00001##

NON-ANTICOAGULANT SULFATED OR SULFONATED POLYSACCHARIDES

The present invention provides non-anticoagulant sulfated or sulfonated polysaccharides (NASPs), which accelerate the blood clotting process. Also provided are pharmaceutical formulations comprising a NASP of the invention in conjunction with a pharmaceutically acceptable excipient and, in various embodiments, these formulations are unit dosage formulations. The invention provides a NASP formulation, which is orally bioavailable. Also provided are methods for utilizing the compounds and formulations of the invention to promote blood clotting in vivo as therapeutic and prophylactic agents and in vitro as an aid to studies of the blood clotting process.