HETEROCYCLIC COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH

1 . A compound having Formula (I):

or a pharmaceutically acceptable salt, tautomer, isotopologue, stereoisomer, enantiomer, atropisomer, or prodrug thereof,

wherein

ring A is unsubstituted or substituted aryl, or unsubstituted or substituted heteroaryl;

ring B is unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heterocyclyl;

X is N, or C—R 8 ;

each of R 0 is, independently, H, halogen, amino, —CN, —OH, unsubstituted or substituted C 1-4 alkyl, unsubstituted or substituted C 1-4 alkenyl, unsubstituted or substituted C 1-4 alkynyl, unsubstituted or substituted C 1-4 alkoxy, unsubstituted or substituted C 3-5 cycloalkyl, unsubstituted or substituted 3-member to 5-member heterocyclyl, unsubstituted or substituted C 1-4 alkylamino, carboxy, nitro, thiol, or thioether; or one or more pairs of the R 0 groups, together with the atom to which they are attached to, form unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, or unsubstituted or substituted heteroaryl;

each of R 3a , R 3b , R 4a , R 4b , R 5 , R 6a , R 6b , R 7a , and R 7b , is, independently, H, halogen, unsubstituted or substituted amino, —CN, —OH, unsubstituted or substituted C 1-4 alkyl, unsubstituted or substituted C 1-4 alkoxy, unsubstituted or substituted C 3-5 cycloalkyl, unsubstituted or substituted 3-member to 5-member heterocyclyl, unsubstituted or substituted C 1-4 alkylamino, carboxy, nitro, thiol, or thioether; optionally, R 3a , and R 3b , together with the atom to which they are attached to, form unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heterocyclyl; or R 4a , and R 4b , together with the atom to which they are attached to, form unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heterocyclyl; or R 6a , and R 6b , together with the atom to which they are attached to, form unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heterocyclyl; or R a , and R 7b , together with the atom to which they are attached to, form unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heterocyclyl; or optionally, R 3a , and R 4a , together with the atoms to which they are attached to, form unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heterocyclyl; or R 4a , and R 5 , together with the atoms to which they are attached to, form unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heterocyclyl; or R 5 , and R 6a , together with the atoms to which they are attached to, form unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heterocyclyl; or R 6a , and R a , together with the atoms to which they are attached to, form unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heterocyclyl;

R 8 is H, halogen, unsubstituted or substituted C 1-4 alkyl, unsubstituted or substituted C 1-4 alkenyl, unsubstituted or substituted C 3-5 cycloalkyl, unsubstituted or substituted C 1-4 alkoxyl, unsubstituted or substituted C 1-4 halogenated alkyl, unsubstituted or substituted C 3-5 halogenated cycloalkyl, unsubstituted or substituted C 1-4 halogenated alkoxyl, CN, OH, or amino;

t is 0, or 1;

u is 1, 2, 3, or 4; and

each of m, and q is, independently, an integer between 0 and the maximum number of the substituent groups allowed on rings A, and B, respectively.

2 . The compound of claim 1 , wherein X is N, C—H, C—Cl, or C—CF 3 .

3 . The compound of claim 2 , wherein ring A is substituted or unsubstituted phenyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted naphthyl, substituted or unsubstituted benzo[b]thiophenyl, or substituted or unsubstituted benzo[d]thiazolyl; and

ring B is substituted or unsubstituted hexahydro-1H-pyrrolizinyl, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted aminomethylcyclopropyl, substituted or unsubstituted oxetanyl, substituted or unsubstituted tetrahydrofuranyl, substituted or unsubstituted oxabicyclo[2.1.1]hexanyl, substituted or unsubstituted oxabicyclo[2.2.1]heptanyl.

4 . The compound of claim 0 , wherein ring A is

5 . The compound of claim 4 , wherein ring B is

wherein each of R a and R b is, independently, substituted or unsubstituted C 1-4 alkyl; substituted or unsubstituted C 3-5 cycloalkyl; or R a and R b together with the N they are attached to form a substituted or unsubstituted heterocycle containing N, O or S; and

R c is H, halogen, CN, substituted or unsubstituted C 1-4 alkyl, substituted or unsubstituted C 3-5 cycloalkyl, substituted or unsubstituted C 1-4 alkoxyl.

6 . The compound of claim 5 , wherein the compound is a compound having formula (II):

7 - 9 . (canceled)

10 . The compound of claim 5 , wherein the compound is a compound having formula (III):

11 .- 18 . (canceled)

19 . The compound of claim 5 , wherein the compound is a compound having formula (IV):

20 .- 24 . (canceled)

25 . The compound of claim 5 , wherein the compound is a compound having formula (V):

26 . (canceled)

27 . The compound of claim 5 , wherein the compound is a compound having formula (VI):

28 . (canceled)

29 . The compound of claim 0 , wherein the compound is a compound having formula (VII):

30 .- 37 . (canceled)

38 . The compound of claim 5 , wherein the compound is a compound having formula (VIII):

39 .- 40 . (canceled)

41 . The compound of claim 5 , wherein the compound is a compound having formula (IX):

42 . (canceled)

43 . The compound of claim 5 , wherein the compound is a compound having formula (Ia):

or a pharmaceutically acceptable salt, tautomer, stereoisomer, enantiomer, atropisomer, isotopologue, or prodrugs thereof,

wherein:

ring C is unsubstituted or substituted C 3-6 cycloalkyl, or unsubstituted or substituted 3-membered to 6-membered heterocyclyl;

each of u and v is, independently, an integer; and

the sum of u and v is 1, 2, 3, or 4.

44 . The compound of claim 1 , wherein the compound is selected from

or a pharmaceutically acceptable salt thereof.

45 . A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, isotopologue, stereoisomer, enantiomer, atropisomer, or prodrug thereof, and a pharmaceutically acceptable carrier, excipient or vehicle.

46 . A method for inhibiting the activity of KRAS mutant protein or KRAS amplification in a cell, comprising contacting said cell with an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, isotopologue, stereoisomer, enantiomer, atropisomer, or prodrug thereof, optionally wherein the KRAS mutant protein is KRAS G12D and/or G12V mutant protein.

47 . A method for treatment or prevention of cancer, the method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, tautomer, isotopologue, stereoisomer, enantiomer, atropisomer, or prodrug thereof, optionally wherein the cancer is mediated by KRAS mutation; preferably KRAS G12D and/or G12V mutation.