COMPOUNDS THAT PARTICIPATE IN COOPERATIVE BINDING AND USES THEREOF

1 . 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 C 1 -C 3 alkylene optionally substituted with 1 to 3 substituents independently selected from fluoro, —CN, —C 1 -C 3 alkyl, and —O—C 1 -C 3 alkyl; —O—; —S(O) 0-2 —; *—CH 2 O—; *—CH 2 —S(O) 0-2 —; *—O—CH 2 —; or *—CH 2 —S(O) 0-2 —, wherein “*” represents a portion of X bound to —C(R 4 )(R 5 )—;

Y is —O—, —NH— or —N(C 1 -C 3 alkyl)-;

ring Z is phenyl or a 6-membered heteroaryl;

R 1 is optionally substituted C 1 -C 6 alkyl, —(CH 2 ) 0-1 —(C 3 -C 6 optionally substituted cycloalkyl), —(CH 2 ) 0-1 -(optionally substituted aryl), or optionally substituted heterocyclyl;

R 2 is:

wherein:

ring A is a 4-8 membered cycloalkyl or a 4-8 membered heterocyclyl;

W is —N(R 12 )—, —O—, or —C(R 12a )(R 12b )—;

each R A is each independently fluoro; chloro; —CN; —OH; —NH 2 ; —C 1 -C 3 alkyl optionally substituted with CN, OH, NH 2 or —O—C 1 -C 3 alkyl; —O—C 1 -C 3 alkyl; or —NH—C 1 -C 3 alkyl;

R 9 , if present, is —N(C 0 -C 5 alkylene-H)—, —N(C(O)—(C 0 -C 5 alkylene-H)—, —C(C 0 -C 3 alkylene-H)(C 0 -C 5 alkylene-H)—, or —C(C 0 -C 3 alkylene-H)(C(O)—C 0 -C 5 alkylene-H)—, wherein each alkylene portion of R 9 is optionally substituted with one or more substituent, wherein each substituent is, independently, selected from halo, —CN, —OH, —C 1 -C 3 alkyl, and —O—C 1 -C 3 alkyl;

R 10 , if present, is C 1 -C 4 alkylene optionally substituted with one or more substituent, wherein each substituent is, independently, selected from halo, —CN, —OH, —C 1 -C 3 alkyl, and —O—C 1 -C 3 alkyl;

R 11 is —N(C 0 -C 5 alkylene-H)—, —N(C(O)—(C 0 -C 5 alkylene-H)—, —C(C 0 -C 3 alkylene-H)(C 0 -C 5 alkylene-H)—, —C(C 0 -C 3 alkylene-H)(C(O)—C 0 -C 5 alkylene-H)—, or a saturated, nitrogen-containing heterocyclyl, where each alkylene portion of R 11 is optionally substituted with one or more substituent, wherein each substituent is, independently, selected from halo, —CN, —OH, —C 1 -C 3 alkyl, and —O—C 1 -C 3 alkyl;

R 12 is hydrogen, or —C 1 -C 3 alkyl, or

R 12 is taken together with one R A , 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

R 12 is taken together with any methylene unit in R 10 , or any methylene unit in R 11 , the atoms to which they are respectively attached and any intervening atoms to form an optionally substituted, 5-8 membered heterocyclyl;

each of R 12a and R 12b are independently hydrogen, or —C 1 -C 3 alkyl, or R 12a and R 12b are taken together with the carbon atom to which they are bound to form a 3-6 membered cycloalkyl ring;

R 13 is O, S, N—CN, or N—O—C 1 -C 3 alkyl; and

WH is

each R 14 is independently hydrogen, —CN, or —C 1 -C 3 alkyl optionally substituted with one or more substituents independently selected from —OH, —O—C 1 -C 3 alkyl, —NH 2 , —NH(C 1 -C 3 alkyl), —N(C 1 -C 3 alkyl) 2 , or an optionally substituted 4-7 membered saturated heterocyclyl;

R 15 is —C 1 -C 3 alkyl optionally substituted with one or more substituents independently selected from —OH, —O—C 1 -C 3 alkyl, —NH 2 , —NH(C 1 -C 3 alkyl), —N(C 1 -C 3 alkyl) 2 , or an optionally substituted 4-7 membered saturated heterocyclyl;

R 16 is hydrogen, —C 1 -C 3 alkyl optionally substituted with one or more substituents independently selected from —OH, —O—C 1 -C 3 alkyl, —NH 2 , —NH(C 1 -C 3 alkyl), —N(C 1 -C 3 alkyl) 2 , or an optionally substituted 4-7 membered saturated heterocyclyl; or

R 14 is taken together with either of R 9 or R 11 , the atoms to which they are attached and any intervening atoms to form an optionally substituted 5-8 membered ring system; or

R 11 is taken together with either of R 9 or R 11 , the atoms to which they are attached and any intervening atoms to form an optionally substituted 5-8 membered ring system;

R 3 is hydrogen, halogen, C 1 -C 3 alkyl, or C 1 -C 3 hydroxyalkyl;

R 4 is hydrogen, halogen, or optionally substituted C 1 -C 3 alkyl;

R 5 is hydrogen, halogen, —OH, —CN, —O-(optionally substituted C 1 -C 3 alkyl), optionally substituted C 1 -C 3 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, —(CH 2 ) 0-1 -aryl, —(CH 2 ) 0-1 -heteroaryl, —(CH 2 ) 0-1 -cycloalkyl, or —(CH 2 ) 0-1 -heterocyclyl; or

R 4 and R 5 are taken together to form ═CH 2 , an optionally substituted C 3 -C 6 cycloalkyl, or a 3-7 membered saturated heterocyclyl; or

R 5 is taken together with a ring atom in Q, the carbon atom to which R 4 is bound and X to form a 4-9 membered saturated or unsaturated heterocyclyl that is fused to Q;

R 6 is hydrogen or —CH 3 ;

each R 7 is independently halo, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 hydroxyalkyl, —OH, —O—C 1 -C 3 alkyl, —O—C 1 -C 3 haloalkyl, —NR n1 R n2 , —NR n1 OR n2 , —ONR n1 R n2 , or —NR n1 NR n2 R n3 ;

R n1 is H, C 1 -C 3 alkyl, C 1 -C 3 heteroalkyl, C 1 -C 3 haloalkyl, —C 1 -C 3 hydroxyalkyl, or C 1 -C 3 aminoalkyl, wherein one methylene unit of R n1 is optionally substituted with

R n2 is H, C 1 -C 3 alkyl, C 1 -C 3 heteroalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 hydroxyalkyl, or C 1 -C 3 aminoalkyl, wherein one methylene unit of R n2 is optionally substituted with

R n3 is H, C 1 -C 3 alkyl, C 1 -C 3 heteroalkyl, C 1 -C 3 haloalkyl, C 1 -C 3 hydroxyalkyl, or C 1 -C 3 aminoalkyl, wherein one methylene unit of R n3 is optionally substituted with

each R 6 is independently halo, C 1 -C 3 alkyl, or C 1 -C 3 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.

2 . The compound of claim 1 , wherein said compound has the structure of formula (Ia):

or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof,

wherein:

X is a bond, —O—, —CH 2 —, —CH(CH 3 )—, *—CH 2 —O—, or —CH 2 —CH 2 —, wherein “*” represents a portion of X bound to C(R 4 )(R 5 );

Y is —O— or —NH—;

R 1 is —C 1 -C 4 alkyl, —(CH 2 ) 0-1 —(C 3 -C 6 cycloalkyl), or —C 4 -C 6 cycloalkyl;

R 2 is:

wherein:

ring A is a 4-8 membered cycloalkyl or a 4-8 membered saturated heterocyclyl;

each R A is each independently fluoro; chloro; —CN; —OH; —NH 2 ; —C 1 -C 3 alkyl optionally substituted with CN, OH, NH 2 or —O—C 1 -C 3 alkyl; —O—C 1 -C 3 alkyl; or —NH—C 1 -C 3 alkyl;

n is 0, 1, 2, 3, 4, 5, or 6;

R 9 , if present, is —N(C 0 -C 5 alkylene-H)—, —N(C(O)—(C 0 -C 5 alkylene-H)—, —C(C 0 -C 3 alkylene-H)(C 0 -C 5 alkylene-H)—, or —C(C 0 -C 3 alkylene-H)(C(O)—C 0 -C 5 alkylene-H)—, wherein each alkylene portion of R 9 is optionally substituted with one or more substituent independently selected from halo, —CN, —OH, —C 1 -C 3 alkyl, and —O—C 1 -C 3 alkyl;

R 10 , if present, is C 1 -C 4 alkylene optionally substituted with one or more substituent independently selected from halo, —CN, —OH, —C 1 -C 3 alkyl, and —O—C 1 -C 3 alkyl;

R 11 is —N(C 0 -C 5 alkylene-H)—, —N(C(O)—(C 0 -C 5 alkylene-H)—, —C(C 0 -C 3 alkylene-H)(C 0 -C 5 alkylene-H)—, or —C(C 0 -C 3 alkylene-H)(C(O)—C 0 -C 5 alkylene-H)—, wherein each alkylene portion of R 11 is optionally substituted with one or more substituent independently selected from halo, —CN, —OH, —C 1 -C 3 alkyl, and —O—C 1 -C 3 alkyl;

R 12 is hydrogen, or —C 1 -C 3 alkyl, or

R 12 is taken together with one R A , the atoms to which they are respectively attached and any intervening atoms to form an optionally substituted, 5-8 membered heterocyclyl that is fused to ring A, or

R 12 is taken together with any methylene unit in R 10 , or any methylene unit in R 11 , the atoms to which they are respectively attached and any intervening atoms to form an optionally substituted, 5-8 membered heterocyclyl;

WH is

each R 14 is independently hydrogen, —CN, —C 1 -C 3 alkyl, —C 1 -C 3 hydroxyalkyl, —O—C 1 -C 3 alkyl;

R 15 is —C 1 -C 3 alkyl, —C 1 -C 3 hydroxyalkyl, or —C 1 -C 3 alkylene-O—C 1 -C 3 alkyl;

R 16 is hydrogen, —C 1 -C 3 alkyl, —C 1 -C 3 hydroxyalkyl, or C 1 -C 3 alkylene-O—C 1 -C 3 alkyl; or

R 14 is taken together with either of R 9 or R 11 , the atoms to which they are attached and any intervening atoms to form an optionally substituted 5-8 membered ring system, or

R 16 is taken together with either of R 9 or R 11 , the atoms to which they are attached and any intervening atoms to form an optionally substituted 5-8 membered ring system;

R 4 is hydrogen, halo, or C 1 -C 3 alkyl;

R 5 is hydrogen, halo, —OH, C 1 -C 3 alkyl, C 1 -C 3 hydroxyalkyl, C 1 -C 3 alkylene-O—C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —(CH 2 ) 0-1 —C 3 -C 6 cycloalkyl, C 1 -C 3 cyanoalkyl, or —(CH 2 ) 0-1 -aryl (benzyl), or

R 4 and R 5 are taken together to form ═CH 2 , or a C 3 -C 6 cycloalkyl, or

R 5 is taken together with a ring atom of Q, the carbon atom to which it is bound and X to form a 5-7 membered saturated heterocyclyl;

R 7 is —OH, —NH 2 , or C 1 -C 3 haloalkyl;

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 Z; and

Q is optionally substituted with one or more independently selected substituents selected from ═O; —CN; —C 1 -C 5 alkyl optionally substituted with one or more independently selected halo, CN, OH, —O—(C 1 -C 3 alkyl), —C(O)—(C 1 -C 3 alkyl), —O—(C 2 -C 3 alkynyl), —(C 3 -C 6 cycloalkyl), or a 4-7 membered saturated heterocyclyl; —O—(C 1 -C 3 alkyl) optionally substituted with one or more independently selected halo; C 2 -C 5 alkenyl optionally substituted with one or more independently selected —CN, or —OH; C 2 -C 3 alkynyl; —S(O) 2 —C 1 -C 3 alkyl; —(CH 2 ) 0-1 —C 3 -C 6 cycloalkyl optionally substituted with one or more independently selected halo, ═O, —CN, C 1 -C 3 alkyl optionally substituted with —CN or —O—C 1 -C 3 alkyl, —C(O)-saturated heterocyclyl, —O-saturated heterocyclyl, O-cycloalkyl, or —O-aryl; —(CH 2 ) 0-1 -heteroaryl optionally substituted with one or more independently selected halo, —CN, C 1 -C 3 alkyl optionally substituted with —CN or —O—C 1 -C 3 alkyl, —C(O)-saturated heterocyclyl, —O-saturated heterocyclyl, O-cycloalkyl, or —O-aryl; —(CH 2 ) 0-1 -heterocyclyl optionally substituted with one or more independently selected halo, ═O, —CN, C 1 -C 3 alkyl optionally substituted with —CN or —O—C 1 -C 3 alkyl, —C(O)-saturated heterocyclyl, —O-saturated heterocyclyl, O-cycloalkyl, or —O-aryl; —(CH 2 ) 0-1 -aryl optionally substituted with one or more independently selected halo, —CN, —C 1 -C 3 alkyl optionally substituted with —CN or —O—C 1 -C 3 alkyl, —C(O)-saturated heterocyclyl, —O-saturated heterocyclyl, O-cycloalkyl, or —O-aryl; —C(O)—NH—(C 1 -C 3 alkyl); —C(O)—N(C 1 -C 3 alkyl) 2 ; C 2 -C 3 alkenylene ═N—O—(C 1 -C 3 alkyl) optionally substituted with C 3 -C 6 cycloalkyl; or

two substituents on the same or adjacent ring atoms of Q are taken together to form a 5-7 membered monocyclic ring or a 6-12 membered bicyclic ring optionally substituted with one or more independently selected halo, ═O, —CN, C 1 -C 3 alkyl, or —O—C 1 -C 3 alkyl; and fused to Q.

3 . The compound of claim 2 , wherein said compound has the structure of formula (Ib):

or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof or

said compound has the structure of formula (Ic):

or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof.

4 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein Q is a 5,6 bicyclic heteroarylene, a 5,6 bicyclic heterocyclylene, a 6,6 bicyclic heteroarylene, or a 6,6 bicyclic heterocyclylene; and wherein Q is optionally substituted.

5 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein Q is selected from the group consisting of:

wherein:

each of V 1 , V 2 , V 3 and V 4 is independently C, CH, or N;

R Q1 is —S(O) 2 —R Q11 , —C(O)—R Q11 , —S(O) 2 —N(R Q11 )R Q12 , —C(O)—N(R Q11 )R Q12 , C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, a 4-14 membered heterocyclyl, aryl, or heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl are optionally substituted; or

R Q1 is taken together with the nitrogen atom to which it is attached and an adjacent ring atom to form an optionally substituted 4-8 membered ring, which is optionally further fused to a 5-6 membered ring;

each of R Q11 and R Q12 is independently C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, a 4-14 membered heterocyclyl, aryl, or heteroaryl, wherein each of R Q11 and R Q12 is optionally substituted; or

R Q11 and R Q12 are taken together with the nitrogen atom to which they are both attached to form an optionally substituted 4-8 membered ring, wherein the ring formed by taking R Q11 and R Q12 together is optionally fused to another 5-6 membered ring.

6 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein Q is selected from the group consisting of:

wherein:

each of V 1 , V 2 , V 3 and V 4 is independently C, CH, N, C(F), C(CH 3 ), C(OH), C(OCH 3 ), or C(CN);

each of V 5 , V 6 , and V 7 is independently, C(R 17a )(R 17b ), or C(═O), wherein each of R 17a and R 17b is independently selected from hydrogen, halo, —C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —O—C 1 -C 3 alkyl, —O—C 1 -C 3 haloalkyl, and no more than two of V 5 , V 6 , and V 7 is C(═O);

R NQ1 is hydrogen, optionally

substituted —S(O) 2 —R Q11 , —C(O)—R Q11 , —S(O) 2 —N(R Q11 )R Q12 , —C(O)—N(R Q11 )R Q12 , C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, a 4-14 membered heterocyclyl, aryl, or heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl are optionally substituted;

each R Q2 is independently hydrogen, CN, optionally

substituted —S(O) 2 —R Q11 , —C(O)—R Q11 , —S(O) 2 —N(R Q11 )R Q12 , —C(O)—N(R Q11 )R Q12 , C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, a 4-14 membered heterocyclyl, aryl, or heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl are optionally substituted; or

R NQ1 and one R Q2 are taken together with the atoms to which they are bound to form an optionally

substituted 4-8 membered ring, wherein the ring formed by taking R NQ1 and one R Q2 together is optionally further fused to a 5-6 membered ring;

each R Q3 is independently hydrogen, CN, optionally

substituted —S(O) 2 —R Q11 , —C(O)—R Q11 , —S(O) 2 —N(R Q11 )R Q12 , —C(O)—N(R Q11 )R Q12 , C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, a 4-14 membered heterocyclyl, aryl, or heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl are optionally substituted, or

two R Q3 bound to the same atom are taken together to form ═CH, ═O, ═S, or ═NR V4 ; or

two R Q3 bound to the same atom are taken together with the atom to which they are bound to form an optionally substituted 4-8 membered ring, wherein the ring formed by taking each R Q3 together is optionally further fused to a 5-6 membered ring; or

R NQ1 and one R Q3 are taken together with the atoms to which they are bound to form an optionally substituted 4-8 membered ring, wherein the ring formed by taking R NQ1 and R Q3 together is optionally further fused to a 5-6 membered ring;

each of R Q11 and R Q12 is independently C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, a 4-14 membered heterocyclyl, aryl, or heteroaryl, wherein each of R Q11 and R Q12 is optionally substituted; or

R Q11 and R Q12 are taken together with the atoms to which they are attached to form an optionally substituted 4-8 membered ring, wherein the ring formed by taking R Q11 and R Q12 together is optionally fused to another 5-6 membered ring; and

“*” represents a portion of Q that is bound to ring Z.

7 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein Q is selected from the group consisting of:

8 . The compound of claim 7 , wherein said compound has the structure of formula (Id):

or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof or

said compound has the structure of formula (Ij):

a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof.

9 . The compound of claim 1 , wherein said compound has the structure of formula (IL):

or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein R 18 is Br or Cl or

said compound has the structure of formula (Im):

or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein each R 14 is H.

10 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein Q is selected from the group consisting of:

wherein:

“1” indicates a portion of Q bound to X; and

Q is further optionally substituted.

11 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein Q is selected from the group consisting of:

wherein:

R is —CH 2 CH 3 ,

—CH 2 CH 2 —OCH 3 , —CH 2 CHF 2 , —CH 2 —CN, —C(CH 3 ) 2 —CN, —C(CH 3 ) 2 —CH 2 CN, —CH 2 CH 2 —CN, cyclohexyl, cyclobutyl, cyclopropyl, pyridin-4-yl, tetrahydropyran-4-yl, tetrahydropyran-4-ylmethyl, oxetan-3-ylmethyl, 2-cyano-5-methoxyphenyl, 2-cyano-5-methoxymethylphenyl, 2-cyano-6-(methoxymethyl)phenyl, 2-cyano-6-bromophenyl, 2-methoxyethan-1-yl, 2-cyanopropan-2-yl, 2-tetrahydropyran-4-ylethan-1-yl, 3-cyanopentan-3-yl, or 2-cyano-4-methoxybut an-2-yl, or

R is

R 23 is hydrogen or fluoro;

R 24 is hydrogen,

chloro, —CN, —CH 3 , —CH 2 CH 3 , —CHF 2 , —CF 3 , —CH 2 —CN, —CH(CN)—CH 3 , —C(CH 3 ) 2 —CN, —C(CH 2 CH 3 ) 2 —CN, —CH 2 —CH 2 —CN, —C(CH 3 )═N—O—CH(CH 3 ) 2 , —C(CH 3 )═N—O—CH 3 , —C(O)—N(CH 3 ) 2 , —C(O)—NH—CH 3 , —OCH 3 , —CH 2 —O—CH 3 , —C≡CH, —C≡C—CH 3 , —S(O) 2 CH 3 , 1-(cyclopentyl)-1-cyanoethan-1-yl, 1-(tetrahydropyran-4-yl)-1-cyanoethan-1-yl, 1-(tetrahydrofuran-3-yl)-1-cyanoethan-1-yl, 1,3-dimethoxy-2-cyanopropan-2-yl, 1,4-dimethylpyrazol-5-yl, 1-cyanocyclobutyl, 1-cyanocyclopropyl, 1-cyanocylopentyl, 1-methyl-1,2,3,6-tetrahydropyridin-4-yl, 1-methylpyrazol-3-yl, 1-methylpyrazol-4-ylcyanomethyl, 1-methylpiperidin-4-yl, 1-methylpyrazol-5-yl, 1-oxoindolin-5-yl, 1-oxoisoindolin-4-yl, 1-oxoisoindolin-6-yl, 2-(2-methoxyethan-1-yl)phenyl, 2-(methoxymethyl)phenyl, 2-(tetrahydropyran-4-yloxy)phenyl, 2,2-difluoro-benzo[d][1,3]dioxol-4-yl, 2,3-dicyanopropan-2-yl, 2-chiorophenyl, 2-cyano-3-(tetrahydropyran-4-yl)propan-2-yl, 2-cyano-3-chlorophenyl, 2-cyano-3-fluorophenyl, 2-cyano-3-methoxyphenyl, 2-cyano-4-fluorophenyl, 2-cyano-4-chlorophenyl, 2-cyano-5-chlorophenyl, 2-cyano-5-fluorophenyl, 2-cyano-5-methoxyphenyl, 2-cyano-6-chlorophenyl, 2-cyano-6-fluorophenyl, 2-cyano-6-(tetrahydropyran-4-yloxy)phenyl, 2-cyanomethylphenyl, 2-cyanophenyl, 2-cyanopropan-2-yl, 2-cyclopentylphenyl, 2-difluoromethoxyphenyl, 2-fluorophenyl, 2-methoxy-6-cyanophenyl, 2-methoxyphenyl, 2-methoxycarbonylphenyl, 2-nitrophenyl, 2-oxopyrrolidin-1-yl, 2-phenoxyphenyl, 3-(1,1-dioxothiomorpholin-4-ylmethyl)phenyl, 3-(2-methoxyethan-1-yl)phenyl, 3,5-difluoro-4-(pyrrolidin-1-ylcarbonyl)phenyl, 3-cyano-2-methylpropan-2-yl, 3-cyanomethylphenyl, 3-cyanopentan-3-yl, 3-cyanophenyl, 3-hydroxy-2-methylbutan-2-yl, 3-hydroxy-3-methyl-but-1-yne-1-yl, 3-methoxy-2-methylbutan-2-yl, 3-methoxymethyl-5-methylisoxazol-4-yl, 3-methoxyphenyl, 3-methoxycarbonylphenyl, 3-oxo-2-methylbutan-2-yl, 4-cyanophenyl, 4-cyanotetrahydropyran-4-yl, 4-methoxyphenyl, benzo[d][1,3]dioxol-4-yl, benzo[d]oxazol-7-yl, benzo[d]thiazol-2-yl, benzo[d]thiazol-4-yl, benzo[d]thiazol-5-yl, benzo[d]thiazol-6-yl, benzo[d]thiazol-7-yl, cyclobutyl, cyclopropyl, cyclopropylcyanomethyl, N-methoxycyclopropanecarbimidoyl, phenyl, pyridin-2-ylmethyl, pyridin-3-yl, pyridin-3-ylmethyl, pyridin-4-ylmethyl, tetrahydrofuran-3-ylmethyl, tetrahydrofuran-3-ylcyanomethyl, tetrahydropyran-4-yl, or tetrahydropyran-4-ylcyanomethyl;

R 27 is hydrogen, —CH 3 , —CHF 2 , —CH 2 CH 3 , —CH 2 —O—CH 3 ,

CH 2 CN, —CN, —CH 2 —O—CH 2 —CN, —C(O)—N(CH 3 ) 2 , —C(O)—NH—CH 3 , —CH 2 —O—CH 2 —C≡CH, 2-methoxyphenyl, 3-methoxyphenyl, 2,2-difluorobenzo[d][1,3]dioxol-4-yl, 2-cyanophenyl, 3-cyanophenyl, phenyl, 2-benzyl methyl ether, 2-(2-methoxyethyl) benzene, 2-(2-difluoromethoxymethyl)benzene, 2-(2-dimethylmethoxyethyl)benzene, pyridin-3-yl, pyridin-2-yl, pyridin-3-ylmethyl, or tetrahydropyridin-4-yl, or

R 24 and R 27 are taken together to form 4-cyanobenzene-1,2-diyl, 3-cyanobenzene-1,2-diyl, 5-methyl-5-cyanotetrahydropyran-3,4-diyl, 3-cyanocyclohexan-1,2-diyl, 3-methoxybenzene-1,2-diyl, benzene-1,2-diyl, 3-oxocyclohexyl-1,2-diyl, 3-cyanocyclopentan-1,2-diyl, or pyridin-3,4-diyl;

R 28 is hydrogen, —CH 3 , or —CH 2 —O—CH 3 ; and

R 29 is hydrogen, acetyl,

CN, —CH 2 —CN, —CH 2 —CH 2 —CN, —CH 2 —O—CH 3 , —CH═CH—CN, —CH 2 —O—C(O)—N(CH 3 ) 2 , morpholin-4-ylmethyl, pyrazol-1-ylmethyl, pyridin-3-yl, pyridin-3-ylethynyl, pyridin-2-yloxymethyl, or 2-cyanopropan-2-yl, or

R 28 and R 29 are taken together to form 2,3-dihydrobenzofuran-3,3-diyl, 2,3-dihydrofuro[2,3-b]pyridin-3,3-diyl, tetrahydropyran-3,3-diyl, 6,7-dihydro-5H-cyclopenta[c]pyridin-6-yl, tetrahydropyran-4,4-diyl, or 4-methoxycyclohexane.

12 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein R 1

is —CH 3 , —CH 2 CH 3 , —(CH 2 ) 2 CH 3 , —CH(CH 3 ) 2 , —CH(CH 3 )CH 2 CH 3 , cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 4-methoxybenzyl, or tetrahydropyran-4-yl.

13 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein R 9 is absent and ring A is a saturated, nitrogen-containing heterocyclyl.

14 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein the portion of R 2 represented by:

is selected from the group consisting of:

wherein each ring system in R 2 is optionally substituted with up to 4 substituents independently selected from fluoro;

chloro; —CN; —OH; —NH 2 ; —C 1 -C 3 alkyl optionally substituted with CN, OH, NH 2 or —O—C 1 -C 3 alkyl; —O—C 1 -C 3 alkyl; and —NH—C 1 -C 3 alkyl.

15 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein:

the portion of R 2 represented by WH is —C(O)—C≡C—CH 3 , —C(O)—CH═CH 2 , —S(O) 2 —CH═CH 2 , —C(O)—CH 2 Cl, —C(O)—CH(CH 3 )Cl, or —C(O)—CH(Cl)—CH 2 —O—CH 3 , or

the portion of R 2 represented by —R 11 —WH, when R 11 is taken together with one R 14 is

16 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein R 2 is selected from the group consisting of: 1-(2-chloro-3-methoxypropanoyl)azetidin-3-yl-N-methylcarboxamido, 1-(2-chloroacetyl)azetidin-3-ylcarboxamido, 1-(2-chloroacetyl)azetidin-3-yl-N-ethylcarboxamido, 1-(2-chloroacetyl)azetidin-3-yl-N-methylcarboxamido, 1-(2-chloroacetyl) piperidin-3-yl-N-methylcarboxamido, 1-(2-chloroacetyl)piperidin-4-yl-N-methylcarboxamido, 1-(2-chloroacetyl) pyrrolidin-3-yl-N-methylcarboxamido, 1-(2-chloropropanoyl)-piperidin-4-yl-N-methylcarboxamido 1-(2-chloropropanoyl)-3-fluoroazetidin-3-yl-N-methylcarboxamido 1-(2-chloropropanoyl)azetidin-3-yl-N-methylcarboxamido, 1-(2-chloropropanoyl)pyrolidin-3-yl-N-methylcarboxamido, 1-(but-2-ynoyl)-4-fluoropiperidin-4-ylcarbonylmethylamino, 1-(but-2-ynoyl))azetidin-2-yl-N-methylcarboxamido, 1-(but-2-ynoyl)azetidin-3-yl-N-methylcarboxamido, 1-(but-2-ynoyl)-piperidin-3-ylcarbonylmethylamino, 1-(but-2-ynoyl-piperidin-4-ylcarbonylmethylamino, 1-(but-2-ynoyl)pyrrolidin-2-ylcarbonyl-N-methylamino 1-(but-2-ynoyl)pyrrolidin-3-ylcarbonyl-N-methylamino 1-acryloyl-2-oxo-imidazolidin-3-yl, 1-acryloyl-3-fluoroazetidin-3-yl-N-methylcarboxamido, 1-acryloyl-3-fluoropyrrolidin-3-yl-N-methylcarboxamido, 1-acryloyl-4-fluoropiperidin-4-ylcarbonylmethylamino 1-acryloylazetidin-2-yl-N-methylcarboxamido, 1-acryloylazetidin-3-yl-N-methylcarboxamido, 1-acryloyl-piperidin-3-ylcarbonylmethylamino, 1-acryloyl-piperidin-4-ylcarbonylmethylamino, 1-acryloylpyrrolidin-2-yl-N-methylcarboxamido, 1-acryloylpyrrolidin-3-yl-N-methylcarboxamido, 1-oxo-7-(2-chloroacetyl)-2,7-diazaspiro[4.3]octan-2-yl, 1-oxo-7-(2-chloroacetyl)-2,7-diazaspiro[4.4]nonan-2-yl, 1-oxo-2-(2-chloroacetyl)-2,7-diazaspiro[4.5]decan-7-yl, 1-oxo-7-(2-chloroacetyl)-2,7-diazaspiro[4.5]decan-2-yl, 1-oxo-7-(2-chloropropanoyl)-2,7-diazaspiro[4.3]octan-2-yl, 1-oxo-7-(but-2-ynoyl)-2,7-diazaspiro[4.4]nonan-2-yl, 1-oxo-7-acryloyl-2,7-diazaspiro[4.3]octan-2-yl, 1-oxo-7-acryloyl-2,7-diazaspiro[4.4]nonan-2-yl, 1-oxo-7-acryloyl-2,7-diazaspiro[4.5]decan-2-yl, 1-oxo-8-(2-chloroacetyl)-2,8-diazaspiro[4.5]decan-2-yl, 1-oxo-8-(but-2-ynoyl)-2,8-diazaspiro[4.5]decan-2-yl, 1-oxo-8-acryloyl-2,8-diazaspiro[4.5]decan-2-yl, 1-vinylsulfonyl-2-oxoimidazolidin-3-yl, 1-vinylsulfonylazetidin-3-N-methylcarboxamido, 2-(1-acryloylpiperidin-4-yl)-N-methylacetamido, 2-(but-2-ynoyl)-5-oxo-2,6-diazaspiro[3.4]octan-1-yl, 2,5-dioxo-3,4-dimethyl-2,5-dihydropyrrol-1-yl-N-methylacetamido, 2-acryloyl-2-azabicyclo[2.1.1]hexan-4-yl-N-methylcarboxamido, 2-chloroacetamidomethyl-N-methylcarboxamido, 2-oxo-2,5-dihydro-1H-pyrrol-1-yl-N-methylacetamido, 2-oxo-3-(2-chloroacetamido)pyrrolidin-1-yl, 2-oxo-3-(N-methyl-2-chloroacetamido)pyrrolidin-1-yl, 2-oxo-3-(N-methylacrylamido)pyrrolidin-1-yl, 2-oxo-3-acrylamidopyrrolidin-1-yl, 2-oxo-4-(2-chloroacetyl)piperazin-1-yl, 2-oxo-4-acryloylpiperazin-1-yl, 2-oxo-4-vinylsulfonylpiperazin-1-yl, 2-oxocyclopent-3-en-1-yl-N-methylacetamido, 3-(4-(dimethylamino)but-2-enamido)phenyl-N-methylcarboxamido, 4-(but-2-ynoyl)-piperazin-1-yl-N-methylcarboxamido, 4-acryloylpiperazin-1-yl-N-methylcarboxamido, 6-oxo-2-(2-chloroacetyl)-2,7-diazaspiro[4.5]decan-7-yl, and 6-oxo-2-acryloyl-2,7-diazaspiro[4.5]decan-7-y.

17 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein:

R 4 is hydrogen, fluoro, or —CH 3 ; and

R 5 is hydrogen, fluoro,

chloro, —OH, —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 OH, —CH 2 OCH 3 , —CH 2 F, —CHF 2 , CH 2 CN, —CH 2 -cyclopropyl, cyclopropyl, pyridyl, phenyl, or —CH 2 -phenyl, wherein any phenyl portion of R 5 is optionally substituted with up to 4 substituents independently selected from halo, —CN, and —O—C 1 -C 3 alkyl: or

R 4 and R 5 are taken together to form ═CH 2 or cyclopropyl, or cyclobutyl, or cyclopentyl, or cyclohexyl; or

R 5 is taken together with the carbon atom to which it is bound, a ring atom of Q, and X to form oxazepane.

18 . The compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, wherein R 7 is —OH, —NH 2 , or —CHF 2 .

19 . A compound, or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, selected from FIG. 1 .

20 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, and a pharmaceutically acceptable carrier.

21 . A complex comprising a presenter protein, a RAS protein, and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

22 . A method of producing a complex, the method comprising contacting a presenter protein and a KRAS G12C protein with a compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof, under conditions suitable to permit complex formation.

23 . A method of treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof.

24 . A method of inhibiting a KRAS G12C protein in a cell, the method comprising contacting the cell with an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof.

25 . A method of treating a KRAS G12C protein-related disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof.

26 . A method of inhibiting RAF-RAS binding in a cell, the method comprising contacting the cell with an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, an enantiomer, a stereoisomer, or a tautomer thereof.

27 . The method of claim 23 , wherein the method or use further comprises administering an additional therapeutic agent.

28 . The method of claim 27 , wherein the additional therapeutic agent is a HER2 inhibitor, an EGFR inhibitor, a second Ras inhibitor, a SHP2 inhibitor, a SOS1 inhibitor, a Raf inhibitor, a MEK inhibitor, an ERK inhibitor, a PI3K inhibitor, a PTEN inhibitor, an AKT inhibitor, an mTORC1 inhibitor, a BRAF inhibitor, a PD-L1 inhibitor, a PD-1 inhibitor, a CDK 4/6 inhibitor, or a combination thereof.