C07F9/59

SOLUBLE C5aR ANTAGONISTS

Compounds are provided to modulate the C5a receptor. The compounds have the following Formula (I):

##STR00001## including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2 and R.sup.3 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Kinase inhibitors

There are provided compounds of formula IIb, ##STR00001##
wherein: LG.sup.1 represents imidazolyl, chloro, or aryloxy; and Z.sup.1 represents a structural fragment of formula V: ##STR00002##
wherein R.sup.2 to R.sup.4, R.sup.5a, L and X.sup.1 to X.sup.3 have meanings given in the description, or a salt or protected derivative thereof, wherein said protected derivative is a compound in which the carboxyl moiety of R.sup.4 is protected as a C.sub.1-8 alkyl ester. The compounds have antiinflammatory activity, for example through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

Kinase inhibitors

There are provided compounds of formula IIb, ##STR00001##
wherein: LG.sup.1 represents imidazolyl, chloro, or aryloxy; and Z.sup.1 represents a structural fragment of formula V: ##STR00002##
wherein R.sup.2 to R.sup.4, R.sup.5a, L and X.sup.1 to X.sup.3 have meanings given in the description, or a salt or protected derivative thereof, wherein said protected derivative is a compound in which the carboxyl moiety of R.sup.4 is protected as a C.sub.1-8 alkyl ester. The compounds have antiinflammatory activity, for example through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

Alkylated imino sugars exhibiting glucosidase inhibition and their method of use

Pharmaceutical compositions of the invention comprise alkylated imino sugars derivatives having a disease-modifying action in the treatment of diseases associated with glucosidase activity that include Viral hemorrhagic fevers, and any other diseases involving glucosidase activity.

Alkylated imino sugars exhibiting glucosidase inhibition and their method of use

Pharmaceutical compositions of the invention comprise alkylated imino sugars derivatives having a disease-modifying action in the treatment of diseases associated with glucosidase activity that include Viral hemorrhagic fevers, and any other diseases involving glucosidase activity.

Aryl dihydropyridinones and piperidinone MGAT2 inhibitors

The present invention provides compounds of Formula (I): ##STR00001##
or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.

Aryl dihydropyridinones and piperidinone MGAT2 inhibitors

The present invention provides compounds of Formula (I): ##STR00001##
or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.

Enolase inhibitors and methods of treatment therewith

Provided herein are compounds of the formula (I) wherein the variables R.sub.1, R.sub.2, R.sub.3, R.sub.4, X.sub.1, X.sub.2, Y.sub.1, and A.sub.1 are as defined herein. Such compounds may be used, for example, for the inhibition of enolase enzymes, including preferential inhibition of one isoenzyme of over one or more of the other isoenzymes. Methods of treatment using these compounds, as well as pharmaceutical compositions thereof, are also provided. ##STR00001##

Enolase inhibitors and methods of treatment therewith

Provided herein are compounds of the formula (I) wherein the variables R.sub.1, R.sub.2, R.sub.3, R.sub.4, X.sub.1, X.sub.2, Y.sub.1, and A.sub.1 are as defined herein. Such compounds may be used, for example, for the inhibition of enolase enzymes, including preferential inhibition of one isoenzyme of over one or more of the other isoenzymes. Methods of treatment using these compounds, as well as pharmaceutical compositions thereof, are also provided. ##STR00001##

OLIGONUCLEOTIDE ANALOGUES HAVING MODIFIED INTERSUBUNIT LINKAGES AND/OR TERMINAL GROUPS

Oligonucleotide analogues comprising modified intersubunit linkages and/or modified 3 and/or 5-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.