Compounds that participate in cooperative binding and uses thereof

A compound of formula I:

• a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein:
• Q is a bicyclic arylene, a bicyclic heteroarylene, or a bicyclic heterocyclylene, wherein a first ring in Q is bonded to X, and a second ring in Q is bonded to Z, and wherein Q is optionally substituted;
• X is a bond;
• a straight chain C1-C3 alkylene optionally substituted with 1 to 3 substituents independently selected from fluoro, —CN, —C1-C3 alkyl, and —O—C1-C3 alkyl;
• —O—;
• —S(O)0-2—;
• *—CH2—O—;
• *—CH2—S(O)0-2—;
• *—O—CH2—;
• or *—CH2—S(O)0-2—, wherein “*” represents a portion of X bound to —C(R4)(R5)—;
• Y is —O—, —NH— or —N(C1-C3 alkyl)-;
• ring Z is phenyl or a 6-membered heteroaryl;
• R1 is optionally substituted C1-C6 alkyl, —(CH2)0-1—(C3-C6 optionally substituted cycloalkyl), —(CH2)0-1-(optionally substituted aryl), or optionally substituted heterocyclyl;
• R2 is:
• wherein:
• ring A is a 4-8 membered cycloalkyl or a 4-8 membered heterocyclyl;
• W is —N(R12)—, —O—, or —C(R12a)(R12b)—;
• each RA is each independently fluoro;
• chloro;
• —CN;
• —OH;
• —NH2;
• —C1-C3 alkyl optionally substituted with CN, OH, NH2 or —O—C1-C3 alkyl;
• —O—C1-C3 alkyl;
• or —NH—C1-C3 alkyl;
• R9, if present, is —N(C0-C5 alkylene-H)—, —N(C(O)—(C0-C5 alkylene-H)—, —C(C0-C3 alkylene-H)(C0-C5 alkylene-H)—, or —C(C0-C3 alkylene-H)(C(O)—C0-C5 alkylene-H)—, wherein each alkylene portion of R9 is optionally substituted with one or more substituent, wherein each substituent is, independently, selected from halo, —CN, —OH, —C1-C3 alkyl, and —O—C1-C3 alkyl;
• R10, if present, is C1-C4 alkylene optionally substituted with one or more substituent, wherein each substituent is, independently, selected from halo, —CN, —OH, —C1-C3 alkyl, and —O—C1-C3 alkyl;
• R11 is —N(C0-C5 alkylene-H)—, —N(C(O)—(C0-C5 alkylene-H)—, —C(C0-C3 alkylene-H)(C0-C5 alkylene-H)—, —C(C0-C3 alkylene-H)(C(O)—C0-C5 alkylene-H)—, or a saturated, nitrogen-containing heterocyclyl, where each alkylene portion of R11 is optionally substituted with one or more substituent, wherein each substituent is, independently, selected from halo, —CN, —OH, —C1-C3 alkyl, and —O—C1-C3 alkyl;
• R12 is hydrogen, or —C1-C3 alkyl, or
• R12 is taken together with one RA, the atoms to which they are respectively attached and any intervening atoms to form an optionally substituted, 5-8 membered heterocyclyl that is fused or spiro-fused to ring A, or
• R12 is taken together with any methylene unit in R10, or any methylene unit in R11, the atoms to which they are respectively attached and any intervening atoms to form an optionally substituted, 5-8 membered heterocyclyl;
• each of R12a and R12b are independently hydrogen, or —C1-C3 alkyl, or R12a and R12b are taken together with the carbon atom to which they are bound to form a 3-6 membered cycloalkyl ring;
• R13 is O, S, N—CN, or N—O—C1-C3 alkyl;
• and
• WH is
• each R14 is independently hydrogen, —CN, or —C1-C3 alkyl optionally substituted with one or more substituents independently selected from —OH, —O—C1-C3 alkyl, —NH2, —NH(C1-C3 alkyl), —N(C1-C3 alkyl)2, or an optionally substituted 4-7 membered saturated heterocyclyl;
• R15 is —C1-C3 alkyl optionally substituted with one or more substituents independently selected from —OH, —O—C1-C3 alkyl, —NH2, —NH(C1-C3 alkyl), —N(C1-C3 alkyl)2, or an optionally substituted 4-7 membered saturated heterocyclyl;
• R16 is hydrogen, —C1-C3 alkyl optionally substituted with one or more substituents independently selected from —OH, —O—C1-C3 alkyl, —NH2, —NH(C1-C3 alkyl), —N(C1-C3 alkyl)2, or an optionally substituted 4-7 membered saturated heterocyclyl;
• or
• R14 is taken together with either of R9 or R11, the atoms to which they are attached and any intervening atoms to form an optionally substituted 5-8 membered ring system;
• or
• R16 is taken together with either of R9 or R11, the atoms to which they are attached and any intervening atoms to form an optionally substituted 5-8 membered ring system;
• R3 is hydrogen, halogen, C1-C3 alkyl, or C1-C3 hydroxyalkyl;
• R4 is hydrogen, halogen, or optionally substituted C1-C3 alkyl;
• R5 is hydrogen, halogen, —OH, —CN, —O-(optionally substituted C1-C3 alkyl), optionally substituted C1-C3 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, —(CH2)0-1-aryl, —(CH2)0-1-heteroaryl, —(CH2)0-1-cycloalkyl, or —(CH2)0-1-heterocyclyl;
• or
• R4 and R5 are taken together to form ═CH2, an optionally substituted C3-C6 cycloalkyl, or a 3-7 membered saturated heterocyclyl;
• or
• R5 is taken together with a ring atom in Q, the carbon atom to which R4 is bound and X to form a 4-9 membered saturated or unsaturated heterocyclyl that is fused to Q;
• R6 is hydrogen or —CH3;
• each R7 is independently halo, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 hydroxyalkyl, —OH, —O—C1-C3 alkyl, —O—C1-C3 haloalkyl, —NRn1Rn2, —NRn1ORn2, —ONRn1Rn2, or —NRn1NRn2Rn3;
• Rn1 is H, C1-C3 alkyl, C1-C3 heteroalkyl, C1-C3 haloalkyl, —C1-C3 hydroxyalkyl, or C1-C3 aminoalkyl, wherein one methylene unit of Rn1 is optionally substituted with
• Rn2 is H, C1-C3 alkyl, C1-C3 heteroalkyl, C1-C3 haloalkyl, C1-C3 hydroxyalkyl, or C1-C3 aminoalkyl, wherein one methylene unit of Rn2 is optionally substituted with
• Rn3 is H, C1-C3 alkyl, C1-C3 heteroalkyl, C1-C3 haloalkyl, C1-C3 hydroxyalkyl, or C1-C3 aminoalkyl, wherein one methylene unit of Rn3 is optionally substituted with
• each R8 is independently halo, C1-C3 alkyl, or C1-C3 haloalkyl;
• n is 0, 1, 2, 3, 4, 5, or 6;
• p is 0, 1, 2, or 3;
• and
• r is 0, 1, 2, 3, or 4.