The present invention relates to a novel process for the preparation of dolutegravir and pharmaceutically acceptable salts thereof using novel intermediates.

The present invention relates to a novel process for the preparation of dolutegravir and pharmaceutically acceptable salts thereof using novel intermediates.

A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity.

A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity.

In one aspect, the invention relates to compounds having the formula: ##STR00001##
where R.sup.1-R.sup.5 and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

In one aspect, the invention relates to compounds having the formula: ##STR00001##
where R.sup.1-R.sup.5 and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

Non-lactone carbocyclic and heterocyclic antagonists and agonists of bacterial quorum sensing. Pharmaceutical composition containing antagonists. Methods employing antagonists and agonists for modulation of quorum sensing. Compounds are exemplified by those of formula:

A-[Z].sub.n-L1-[Y].sub.q-W-[V].sub.m-L2-HG,

where A is an acyclic aliphatic group, and HG is an optionally substituted phenyl group. Compounds include those where m and n are both 0, W is NH, Y is present and is COCH.sub.2CO, and L1 and L2 independently are [CH.sub.2].sub.p1 and [CH.sub.2].sub.p2, where p1 and p2, independently, are 0 or integers ranging from 1-10.

Non-lactone carbocyclic and heterocyclic antagonists and agonists of bacterial quorum sensing. Pharmaceutical composition containing antagonists. Methods employing antagonists and agonists for modulation of quorum sensing. Compounds are exemplified by those of formula:

A-[Z].sub.n-L1-[Y].sub.q-W-[V].sub.m-L2-HG,

where A is an acyclic aliphatic group, and HG is an optionally substituted phenyl group. Compounds include those where m and n are both 0, W is NH, Y is present and is COCH.sub.2CO, and L1 and L2 independently are [CH.sub.2].sub.p1 and [CH.sub.2].sub.p2, where p1 and p2, independently, are 0 or integers ranging from 1-10.

In one aspect, the invention relates to compounds having the formula:

##STR00001##

where R.sup.1-R.sup.5 and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

In one aspect, the invention relates to compounds having the formula:

##STR00001##

where R.sup.1-R.sup.5 and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.