Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

In one aspect, the disclosure relates to a method for the direct synthesis of complex N,N,O-trisubstituted hydroxylamines by NO bond formation. In another aspect, the method can successfully be employed using a wide variety of commercially available alcohols and secondary amines and enables the construction of large fragment-based libraries of trisubstituted hydroxylamines for drug discovery purposes. Also disclosed are N,N,O-trisubstituted hydroxylamines having low basicity, high stability at ambient temperatures, and an inherent lack of reactivity towards acetylating and sulfonylating enzymes that confer mutagenicity on less-substituted hydroxylamines.

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.

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.

Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): ##STR00001##
including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q.sub.1, Q.sub.2, Q.sub.3, R.sub.11 and R.sub.12 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Compositions including derivatives of spinosyns and methods for the production of derivatives of spinosyns are provided. The spinosyn derivatives described herein include spinosyn derivatives functionalized on the C5-C6 double bond of spinosyn A to provide an additional ring system. The method produces spinosyn derivatives that exhibit activity towards insects, arachnids, and/or nematodes and are useful in the agricultural and animal health markets.

Compositions including derivatives of spinosyns and methods for the production of derivatives of spinosyns are provided. The spinosyn derivatives described herein include spinosyn derivatives functionalized on the C5-C6 double bond of spinosyn A to provide an additional ring system. The method produces spinosyn derivatives that exhibit activity towards insects, arachnids, and/or nematodes and are useful in the agricultural and animal health markets.

A method and an intermediate for preparing a tulathromycin. The method includes the following step: in an organic solvent, subjecting a compound represented by formula (II) and an n-propylamine to a ring-opening addition shown below to obtain a tulathromycin represented by formula (I), wherein the organic solvent is a 1,2-propandiol. Tulathromycin obtained using the method has a high purity, with an HPLC purity being 95% and above, and up to 99% and above, satisfying a required purity for preparing a tulathromycin as a pharmaceutical formulation. The method has a high yield, is simple to operate, and is more suitable for industrial production. ##STR00001##

A method and an intermediate for preparing a tulathromycin. The method includes the following step: in an organic solvent, subjecting a compound represented by formula (II) and an n-propylamine to a ring-opening addition shown below to obtain a tulathromycin represented by formula (I), wherein the organic solvent is a 1,2-propandiol. Tulathromycin obtained using the method has a high purity, with an HPLC purity being 95% and above, and up to 99% and above, satisfying a required purity for preparing a tulathromycin as a pharmaceutical formulation. The method has a high yield, is simple to operate, and is more suitable for industrial production. ##STR00001##

It is an object of the present invention to provide a fluorescence imaging probe capable of selectively visualizing target cells such as cells expressing -galactosidase (lacZ expressing cells) at a single-cell level in a red fluorescence region, and of performing co-staining together with GFP.

An intracellularly-retainable red fluorescent probe comprising a compound represented by the following formula (I) or a salt thereof:

##STR00001## wherein: A represents a monovalent group cleaved by an enzyme; R.sup.1 represents a hydrogen atom, or one to four of the same or different substituents bonded to a benzene ring; R.sup.3, R.sup.4, R.sup.5, and R.sup.6 each independently represent CFR.sup.10R.sup.11, CF.sub.2R.sup.12, a hydrogen atom, a hydroxyl group, an alkyl group, or a halogen atom, wherein at least one of R.sup.3, R.sup.4, R.sup.5, and R.sup.6 is CFR.sup.10R.sup.11 or CF.sub.2R.sup.12; R.sup.2 and R.sup.7 each independently represent a hydrogen atom, a hydroxyl group, an alkyl group, or a halogen atom; R.sup.8 and R.sup.9 each independently represent a hydrogen atom or an alkyl group; R.sup.10, R.sup.11, and R.sup.12 each independently represent a hydrogen atom, an alkyl group, or an alkenyl group; X represents Si(R.sup.a) (R.sup.b), wherein R.sup.a and R.sup.b each independently represent a hydrogen atom or an alkyl group; and Y is C(O) or R.sup.cC(O), wherein R.sup.c is an alkylene group having 1-3 carbon atoms.