Compounds of formula (I) can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX). ##STR00001##

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, Formula (I), wherein, the group XY is NHSO.sub.2; Z is a monocyclic or polycyclic cycloalkyl group or a monocyclic or polycyclic heterocycloalkyl group, each of which is optionally substituted by one or more groups selected from haloalkyl, alkyl, alkenyl, alkynyl and (CR.sub.16R.sub.17).sub.mR.sub.18, where m is 0 to 6; L is a direct bond or a group (CR.sub.14R.sub.15).sub.n, where n is 1 or 2; R.sub.1 is H, CN, Cl or F or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, halo, alkoxy and alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, SO.sub.2NR.sub.12R.sub.13, heteroaryl, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.9 is selected from H, alkyl and halo; Rio, R.sub.1, R.sub.12 and R.sub.13 are each independently H or alkyl; R.sub.14 and R.sub.15 are each independently H, halo or alkyl; R.sub.16 and R.sub.17 are each independently H, halo, haloalkyl or alkyl; and each R.sub.18 is independently selected from OH, CN, alkoxy and halo. Further aspects of the invention relate to such compounds for use in the field of immune-oncology and related applications.

##STR00001##

Compounds of formula (I) can modulate the activity of one or more S1P receptors and/or the activity of autotaxin (ATX).

##STR00001##

A method of preparing a cyclopropane ring-bearing compound of the formula I ##STR00001##
in which R.sup.1 and R.sup.2 are independently selected from C.sub.1-C.sub.10 alkyl, optionally substituted, or R.sup.1 and R.sup.2, together with the bonds linking them to the cyclopropane ring, form a monocyclic or bicyclic ring system, which may comprise at least one hetero-atom, comprising the reaction of a compound of formula II
R.sup.1CHCHR.sup.2II
in which R.sup.1 and R.sup.2 have the significances hereinabove defined, with a compound of formula III
XCH.sub.2YIII
in which X is a nucleofuge selected from halides and pseudohalides and Y is an electrofuge selected from boranes and borates, in the presence of a metal catalyst complex selected from those useful for catalytic cyclopropanation and those useful for catalyzing Heck coupling. The method provides a particularly easy and non-hazardous method of cyclopropanation.

Described are improved linking agents that are useful for facilitating the attachment of targeting groups, pharmacokinetic (PK) enhancers or modifiers, or other delivery agents to oligonucleotides. The described linking agents may exhibit improved reaction yields, stability, and biological activity, particularly when used in connection with oligonucleotide-based compounds, such as RNA interference (RNAi) agents.

Compounds of formula (I) can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX). ##STR00001##

A method for producing a bicyclic hydrocarbon molecule includes oxidizing a terpene molecule to provide a first intermediate compound, wherein the first intermediate compound includes an aldehyde functional group, reacting the first intermediate compound with a 1,3-diene molecule to form a second intermediate compound including the aldehyde functional group, and reducing the second intermediate compound to yield a first bicyclic hydrocarbon molecule, wherein reducing the second intermediate compound includes removing the aldehyde functional group.

A method for producing a bicyclic hydrocarbon molecule includes oxidizing a terpene molecule to provide a first intermediate compound, wherein the first intermediate compound includes an aldehyde functional group, reacting the first intermediate compound with a 1,3-diene molecule to form a second intermediate compound including the aldehyde functional group, and reducing the second intermediate compound to yield a first bicyclic hydrocarbon molecule, wherein reducing the second intermediate compound includes removing the aldehyde functional group.

The present disclosure details various lipids, compositions, and/or methods of optimized systems and delivery vehicles for the delivery of nucleic acid sequences, polypeptides or peptides for use in vaccinating against infectious agents.