Biaryl spiroaminooxazoline analogues as Alpha2C adrenergic receptor modulators

A compound represented by Formula I

• or a pharmaceutically acceptable salt thereof
• wherein:
• wherein is a single bond when R15 is present or double bond when R15 is absent;
• R1 is a ring selected from the group consisting of cycloalkyl, cycloalkenyl, aryl, heterocyclyl, heterocyclenyl, and heteroaryl, each of which is optionally substituted with at least one R12;
• R3 is independently selected from the group consisting of H, —OH, halo, —CN, —NO2, —S(O)pR7, —NR7R7′, —S(O)pNR7R7′, and (═O), and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R5, provided that when w is 3, no more than 2 of the R3 groups may be (═O);
• R4 is independently selected from the group consisting of H, D, —OH, halo, —CN, —S(O)pR7, —NR7R7′ and —S(O)pNR7R7′, and alkyl, deuterated alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R5;
• R4′ is independently selected from the group consisting of H, D, halo, —OH, and alkyl, deuterated alkyl and alkoxy;
• or
• R4 and R4′ may be taken together to form (═O);
• R5 is independently selected from the group consisting of H, halo, —OH, —CN, —NO2, —NR7R7′, and —S(O)pR7, and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO2, —NR7R7′, and —S(O)pR7 substituents and/or 1 or 2 (═O) groups,
• R7 is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloclenyl, cyclocyclenylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, hetrocyclenyl, hetrocyclenylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted one or more times by R12;
• R7′ is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloclenyl, cyclocyclenylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, hetrocyclenyl, hetrocyclenylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted one or more times by R12;
• or
• a) when a variable is —NR7R7′, —C(O)NR7R7′ or —SO2NR7R7′, R7 and R7′ together with the nitrogen atom to which they are attached independently form a 3- to 8-membered heterocyclyl, heterocyclenyl or heteroaryl ring having, in addition to the N atom, 1 or 2 additional hetero atoms independently selected from the group consisting of O, N, —N(R9)— and S, wherein said rings are optionally substituted by 1 to 5 independently selected R12 moieties and/or 1 or 2 (═O) groups, or
• b) when a variable is —(CH2)qON═CR7R7′, R7 and R7 together with the carbon atom to which they are attached independently form a 3- to 8-membered cycloalkyl, cycloalkenyl, aryl, heterocyclyl, heterocyclenyl or heteroaryl ring, wherein said heterocyclyl, heterocyclenyl or heteroaryl rings have 1-3 heteroatoms which are independently selected from the group consisting of O, N, —N(R9)— and S, wherein said rings are optionally substituted by 1 to 5 independently selected R12 moieties and/or 1 or 2 (═O) groups,
• R9 is independently selected from the group consisting of H, —C(O)—R19, —C(O)—OR10, and —S(O)p—R10 and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO2, —N(R11)2, and —S(O)pR11 substituents and/or 1 or 2 (═O) groups;
• and
• R10 is independently selected from the group consisting of H, and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO2, —N(R11)2, and —S(O)pR11 substituents and/or 1 or 2 (═O);
• R11 is a moiety independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl, each of which is optionally substituted by at least one substituent independently selected from the group consisting of halo, —OH, —CN, —NO2, —N(R11)2, and —S(O)pR11′ and/or 1 or 2 (═O) groups;
• R11′ is independently selected from the group consisting of H, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
• R12 is independently selected from the group consisting of H, halo, —OH, —CN, —NO2, —N(R11)2, C(O)—OR14, —N(R14)—C(O)—R14, —N(R14)—C(O)2—R14, —C(O)—N(R11)2, —N(R14)—S(O)2—R11, —S(O)2—N(R11)2 and —S(O)pR11 and/or 1 or 2 (═O) groups, and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkenyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroaryloxy, heteroarylalkyl, heterocyclyl, heterocyclenyl, heterocyclenyloxy, heterocyclylalkyl, heterocyclenylalkyl, arylalkoxy, heteroarylalkoxy, heterocyclylalkoxy, and heterocyclenylalkoxy groups, each of which in turn is optionally substituted by at least once by a substituent selected from the group consisting of H, alkyl, haloalkyl, halo, —OH, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted cycloalkoxy, optionally substituted heteroaryloxy, optionally substituted heterocyclenyloxy, —CN, —NO2, —N(R11)2, and —S(O)pR11 and/or 1 or 2 (═O) groups, wherein said optionally substituted alkoxy, aryloxy, optionally substituted cycloalkoxy, optionally substituted heteroaryloxy, and heterocyclenyloxy when substituted are substituted one or more times by R11;
• R14 is independently H, alkyl, or aryl;
• R15 is absent or is independently selected from the group consisting of H, —C(O)—R10, —C(O)—OR10, —C(O)—N(R7)(R7′), and —S(O)p—R10, SO2—NR7R7′ and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO2, —NR7R7′, and —S(O)pR7 and/or 1 or 2 (═O) groups substituents, and —C(═O)R7, —C(═O)OR7, —C(═O)NR7R7′, —SO2R10 and —SO2NR7R7′;
• q is independently an integer from 0-10;
• p is independently an integer from 0-2;
• and
• w is an integer from 0-3.