The present disclosure relates to 2-alkynylmannose Derivative and Application Thereof. The mannose derivatives, and a pharmaceutically acceptable salt, an isotope, and an isomer thereof have a structure shown as formula I:

##STR00001##

and are used for treating or preventing bacterial infections. The present disclosure also provides pharmaceutically acceptable compositions comprising the above compounds and their use in the treatment or prevention of bacterial infections.

One or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof are provided for use in the treatment and/or prevention of a metabolic disorder in a feline animal, preferably where 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 where the remission of the metabolic disorder, preferably diabetic remission, is achieved and/or maintained.

One or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof are provided for use in the treatment and/or prevention of a metabolic disorder in a feline animal, preferably where 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 where the remission of the metabolic disorder, preferably diabetic remission, is achieved and/or maintained.

The invention relates to a process to prepare a compound of the following formula (I):

##STR00001## in which P represents a protective group of a hydroxyl function which is a —COR.sup.1 group with R.sup.1 representing an aryl or a (C.sub.1-C.sub.6)alkyl, R represents a hydrogen atom or a protective group of a terminal alkyne, from mannose, comprising the following steps: (a) protecting the 5 hydroxyl groups of the mannose by a protective group P; (b) coupling the protected mannose obtained at step (a) with a compound of the following formula (II)

##STR00002##

The present invention also relates to a compound of formula (IIIa):

##STR00003## wherein R.sup.10 represents a hydrogen, a (C.sub.1-C.sub.6)alkyl, —SO.sub.2R.sup.6, —C(O)R.sup.6 or —C(O)OR.sup.6, with R.sup.6 being a hydrogen or a radical selected from a (C.sub.1-C.sub.6)alkyl, an aryl, a heteroaryl, a 3-8 membered ring cycloalkyl and a 3-8 membered ring heterocycloalkyl, said radical being optionally substituted by a (C.sub.1-C.sub.6) alkyl, an aryl, a heteroaryl, a 3-8 membered ring cycloalkyl or a 3-8 membered ring heterocycloalkyl, a halogen, —NR.sup.8R.sup.9, —CN, —C(O)OR.sup.8, —C(O)NR.sup.8R.sup.9 or —OR.sup.8, with R.sup.8 and R.sup.9 being independently a hydrogen atom or a (C.sub.1-C.sub.6) alkyl, or R.sup.8 and R.sup.9 form together with the nitrogen to which they are bound a 3-8 membered ring heterocycloalkyl, and R″ represents —COR.sup.1 group with R.sup.1 being an aryl or a (C.sub.1-C.sub.6)alkyl.

The present invention relates to a method for the stereoselective preparation of apiose derivatives from allylic alcohol compounds and allene compounds using catalytic asymmetric synthesis. The method for the stereoselective preparation of apiose derivatives of the present invention is based on the catalytic asymmetric synthesis from allylic alcohol compounds and allene compounds in the presence of a metal catalyst, so that apiose derivatives can be produced stereoselectively, with high yield, with high optical purity regardless of the types of substituents of the compounds. The method of the invention can also be used for the preparation of oligosaccharides including monosaccharides, disaccharides, and polysaccharides or various compounds including apiose derivatives because the method can minimize the production of by-products without using an activating group, unlike the conventional method for the preparation of adipose derivatives.

The present invention relates to a method for the stereoselective preparation of apiose derivatives from allylic alcohol compounds and allene compounds using catalytic asymmetric synthesis. The method for the stereoselective preparation of apiose derivatives of the present invention is based on the catalytic asymmetric synthesis from allylic alcohol compounds and allene compounds in the presence of a metal catalyst, so that apiose derivatives can be produced stereoselectively, with high yield, with high optical purity regardless of the types of substituents of the compounds. The method of the invention can also be used for the preparation of oligosaccharides including monosaccharides, disaccharides, and polysaccharides or various compounds including apiose derivatives because the method can minimize the production of by-products without using an activating group, unlike the conventional method for the preparation of adipose derivatives.

A process for the production of dihydronepetalactone including hydrogenating nepetalactone in the presence of a catalytic metal is provided. The catalytic metal may include nickel. The process may be performed in an aqueous medium.

A process for the production of dihydronepetalactone including hydrogenating nepetalactone in the presence of a catalytic metal is provided. The catalytic metal may include nickel. The process may be performed in an aqueous medium.

One or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof are provided for use in the treatment and/or prevention of a metabolic disorder in a canine animal, preferably where the metabolic disorder is one or more selected from ketoacidosis, pre-diabetes, insulin dependent diabetes mellitus, insulin resistance diabetes, insulin resistance, obesity, hyperglycemia, hyperglycemia induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, inflammation of the pancreas, metabolic disorder consequences, such as hypertension, renal dysfunction and/or musculoskeletal disorders, and/or Syndrome X (metabolic syndrome), wherein preferably the development of hyperglycemia induced cataract formation is prevented or remission is achieved and/or wherein preferably the development of metabolic disorder consequences, such as hypertension, renal dysfunction and/or musculoskeletal disorders, is prevented or progression is slowed or remission is achieved.

One or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof are provided for use in the treatment and/or prevention of a metabolic disorder in a canine animal, preferably where the metabolic disorder is one or more selected from ketoacidosis, pre-diabetes, insulin dependent diabetes mellitus, insulin resistance diabetes, insulin resistance, obesity, hyperglycemia, hyperglycemia induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, inflammation of the pancreas, metabolic disorder consequences, such as hypertension, renal dysfunction and/or musculoskeletal disorders, and/or Syndrome X (metabolic syndrome), wherein preferably the development of hyperglycemia induced cataract formation is prevented or remission is achieved and/or wherein preferably the development of metabolic disorder consequences, such as hypertension, renal dysfunction and/or musculoskeletal disorders, is prevented or progression is slowed or remission is achieved.