SOLUBILITY FOR TARGET COMPOUNDS

摘要

The present disclosure relates to compounds having an improved solubility thereby increasing their bioavailability, lower dosages, etc. The target compounds, may include but are not limited to, macrophage migration inhibitory factor (MIF) inhibitors, epidermal growth factor receptor (EGRF) inhibitors, kinase inhibitors and prodrugs of alpha4 beta1 and alpha4 beta7 integrin antagonists. An illustrative compound is shown below:;

主权项

1. A compound according to Formula I wherein: R1 is -aryl, -heteroaryl, or C(O)R3, wherein
i) each of said aryl or heteroaryl may additionally be fused with an independently selected aryl or heteroaryl; andii) each of said aryl, heteroaryl, and alkyl is either unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents which can be the same or different and are independently selected from the group consisting of halo, hydroxyl, cyano, oxo, amino, aminoalkyl-, (amino)alkoxy-, -alkyl, -alkenyl, -alkynyl, alkoxy-, hydroxy, -alkylhydroxy, aryloxy-, -alkyl(aryl), (alkoxyalkyl)amino-, -aryl, -aryl(halo), -heteroaryl, C(O)OCn, —NRaRb; deuterium, hydroxyl-alkyl-, hydroxyl-aryl-, amino, aminoalkyl, (amino)alkoxy-, —CONH2, —C(O)NH(alkyl), —C(O)N(alkyl)2, —C(O)NH(aryl), —C(O)N(aryl)2, —CHzF3-z, —OCHzF3-z, (alkoxyalkyl)amino-, —O(alkyl), —O(aryl), O(heteroaryl), —NH(SO2)alkyl, —NH(SO2)aryl, —NH(SO2)heteroaryl, (aryl)alkyl-, —S(O)2-alkyl, —S(O)2-aryl, —C(O)alkyl, —NHC(O)-alkyl, NH—, —NH—C(O)—Rc—(O)alkyl, —NH—C(O)-aryl, —NH—C(O)—NH-alkyl, NH—C(O)—NH—C(O)—NH-aryl, —NH—C(O)—O-alkyl, —NH(Rc)—C(O)-alkyl, —NH(Rc)—C(O)-aryl, —S(O2)NH2, —S(O2)NH(alkyl), —S(O2)N(alkyl)2, —C(O)N(H)(alkyl), —CHzF3-z, —OCHzF3-z; R2 is hydrogen, hydroxyl, OC(O)CH3, -oxy(aryl), or a group selected from -oxy(alkyl), -oxy(alkene), alkyl, -alkenyl, -oxy(alkyl)-aryl, -oxyalkynyl, OC(O)(alkyl), OC(O)(haloalkyl), and OC(O)(aryl) which is either substituted or non-substituted and straight or branched, where the substituents can be the same or different and are from the group consisting of oxo or halo; R3 is an alkyl, alkyl(benzyl), alkoxy(alkyl) all of which may be substituted or unsubstituted, or substituted or unsubstituted monocyclic or bicyclic aryl or heteroaryl, or alkyl(aryl), the substituted or unsubstituted monocyclic or bicyclic heteroaryl having 0, 1, 2 or 3 heteroatoms independently selected from N, O, or S; Ra is an alkyl, alkyl(benzyl), alkoxy(alkyl) all of which may be substituted or unsubstituted, or substituted or unsubstituted monocyclic or bicyclic aryl or heteroaryl, or alkyl(aryl), the substituted or unsubstituted monocyclic or bicyclic heteroaryl having 0, 1, 2 or 3 heteroatoms independently selected from N, O, or S; Rb is hydrogen or halo; Rc is hydrogen, halo, or alkyl; -------- is an optional bond that is present only when R2 is hydrogen; n is 0, 1, 2, or 3; and z is 0, 1, or 2.