Analogs of fexaramine and methods of making and using

A compound having a formula

• or a pharmaceutically acceptable salt thereof, wherein:
• Y is CRg, N or N—O (N-oxide);
• R is selected from
• Ra is selected from aryl, heteroaryl, alkyl, alkenyl, cycloalkyl, heterocyclic, or polycyclic;
• Rb is selected from alkyl, alkenyl, or cycloalkyl;
• Rc, Rd, Re and Rg are each independently selected from hydrogen, deuterium, halide, alkyl, alkenyl, alkoxy, alkylthio, amino, sulfonyl, aminosulfonyl, aminocarbonyl, cycloalkyl, heterocyclic, acyl, hydroxyl or nitro;
• Rfa and Rfb are each independently selected from hydrogen, deuterium, halide or alkyl;
• X is aryl, heterocyclic or heteroaryl;
• La and Lb are each independently selected from hydrogen, deuterium, alkyl or cycloalkyl, or together form a pi-bond;
• Lc and Ld are each independently selected from hydrogen, deuterium, alkyl or cycloalkyl;
• W is selected from O or —(C(Lc)(Ld))s-;
• s is 1, 2, 3, 4, 5 or 6;
• n is 0 or 1;
• and
• wherein X is not substituted with —Rx-Lx-Rx2, where
• Rx is selected from O, NRx3, sulfonyl or S;
• Rx3 is selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, or aryl;
• Lx is selected from a bond, alkylene, alkenylene, alkynylene, cycloalkyl, cycloalkenyl, heterocyclic, aryl, heteroaryl or CRx4Rx5;
• Rx4 and Rx5 are each independently selected from H, D, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —C(O)ORx6, or —C(O)NRx6Rx7;
• Rx6 and Rx7 are each independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl;
• Rx2 is selected from —C(O)Lx2Rx8 or a carboxyl bioisostere;
• Lx2 is a bond or NRx3;
• Rx8 is H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —ORx9, N(Rx9)2, —C(O)Rx9, —S(O)2Rx9, —C(O)ORx9, —S(O)2N(Rx9)2 or —C(O)N(Rx9)2;
• and
• each Rx9 is independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl.

A compound having a formula

• or a pharmaceutically acceptable salt thereof, wherein:
• R is selected from
• La and Lb are each independently selected from hydrogen, deuterium, alkyl or cycloalkyl, or together form a pi-bond;
• Lc and Ld are each independently selected from hydrogen, deuterium, alkyl or cycloalkyl;
• W is selected from O or —(C(Lc)(Ld))s-;
• s is 1, 2, 3, 4, 5 or 6;
• n is 0 or 1;
• Rb is selected from alkyl, alkenyl, or cycloalkyl;
• Y is CRg, N or N—O (N-oxide);
• Rc, Re and Rg are each independently selected from hydrogen, deuterium, halide, alkyl, alkenyl, alkoxy, alkylthio, amino, sulfonyl, aminosulfonyl, aminocarbonyl, cycloalkyl, heterocyclic, acyl, hydroxyl or nitro;
• Rfa and Rfb are each independently selected from hydrogen, deuterium, halide or alkyl;
• Rh and Rj are each independently selected from hydrogen, deuterium, halide, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, aryl or heteroaryl;
• X is aryl, heterocyclic or heteroaryl;
• and
• X is not substituted with —Rx-Lx-Rx2, where
• Rx is selected from O, NRx3, sulfonyl or S;
• Rx3 is selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, or aryl;
• Lx is selected from a bond, alkylene, alkenylene, alkynylene, cycloalkyl, cycloalkenyl, heterocyclic, aryl, heteroaryl or CRx4Rx5;
• Rx4 and Rx5 are each independently selected from H, D, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —C(O)ORx6, or —C(O)NRx6Rx7;
• Rx6 and Rx7 are each independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl;
• Rx2 is selected from —C(O)Lx2Rx8 or a carboxyl bioisostere;
• Lx2 is a bond or NRx3;
• Rx8 is H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —ORx9, N(Rx9)2, —C(O)Rx9, —S(O)2Rx9, —C(O)ORx9, —S(O)2N(Rx9)2 or —C(O)N(Rx9)2;
• and
• each Rx9 is independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl.