Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.

Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.

A compound, or a pharmaceutically acceptable salt thereof, having a formula I of: ##STR00001## wherein Ar is an arylene or heteroarylene;
R.sup.1 has a structure of: ##STR00002## wherein W is an alkanediyl, alkenediyl, a carbonyl, or a combination thereof; X is —NR.sup.5—, wherein R.sup.5 is H or an alkyl, or —O—; and Y is optionally-substituted cycloalkyl, optionally-substituted cycloalkyl-substituted alkyl, optionally-substituted heterocycloalkyl, or optionally-substituted heterocycloalkyl-substituted alkyl;
each R.sup.2 is the same or different and has a structure of: ##STR00003## wherein Z is —NR.sup.6—, wherein R.sup.6 is H or an alkyl, —O—, —S—, or —CH.sub.2—; Z.sup.1 is (—CH.sub.2-).sub.m wherein m is 0 to 5, or an alkenediyl having 2 to 6 carbon atoms; Cy is a 3-8-membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring; and each R.sup.4 is the same or different and is selected from hydroxy, halogen, substituted or unsubstituted alkoxy, substituted or unsubstituted alkyl, or amino; and c is 0 to 5; and each R.sup.3 is the same or different and is selected from hydroxy, halogen, substituted or unsubstituted alkoxy, substituted or unsubstituted alkyl, amino, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or a nitro, wherein a is 2 to 5, and b is 0 to 3.

A compound, or a pharmaceutically acceptable salt thereof, having a formula I of: ##STR00001## wherein Ar is an arylene or heteroarylene;
R.sup.1 has a structure of: ##STR00002## wherein W is an alkanediyl, alkenediyl, a carbonyl, or a combination thereof; X is —NR.sup.5—, wherein R.sup.5 is H or an alkyl, or —O—; and Y is optionally-substituted cycloalkyl, optionally-substituted cycloalkyl-substituted alkyl, optionally-substituted heterocycloalkyl, or optionally-substituted heterocycloalkyl-substituted alkyl;
each R.sup.2 is the same or different and has a structure of: ##STR00003## wherein Z is —NR.sup.6—, wherein R.sup.6 is H or an alkyl, —O—, —S—, or —CH.sub.2—; Z.sup.1 is (—CH.sub.2-).sub.m wherein m is 0 to 5, or an alkenediyl having 2 to 6 carbon atoms; Cy is a 3-8-membered cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring; and each R.sup.4 is the same or different and is selected from hydroxy, halogen, substituted or unsubstituted alkoxy, substituted or unsubstituted alkyl, or amino; and c is 0 to 5; and each R.sup.3 is the same or different and is selected from hydroxy, halogen, substituted or unsubstituted alkoxy, substituted or unsubstituted alkyl, amino, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or a nitro, wherein a is 2 to 5, and b is 0 to 3.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Provided herein are compounds of formula I: ##STR00001##
wherein the variables are defined herein, processes of making them, and methods of treating cancer comprising administering such compounds.

Provided herein are compounds of formula I: ##STR00001##
wherein the variables are defined herein, processes of making them, and methods of treating cancer comprising administering such compounds.

The compounds of Formula I is described herein along with their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof. The compounds described herein, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof are bicyclic compounds that are inhibitors of PD-1/PD-L1 interaction/activation. ##STR00001##

This disclosure relates bis-amine compounds disclosed herein and uses related to CXCR4 inhibition. In certain embodiments, the compounds have formula I, ##STR00001## salts, derivatives, and prodrugs thereof wherein, A is an bridging aryl or heterocyclyl and R.sup.1 and R.sup.2 are further disclosed herein. In certain embodiments, the disclosure contemplates pharmaceutical compositions comprising compounds disclosed herein. In certain embodiments, the disclosure relates to methods of treating or preventing CXCR4 related diseases or conditions by administering an effective amount of a compound disclosed herein to a subject in need thereof.