HETEROCYCLIC COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH

1 - 38 . (canceled)

39 . A compound having Formula (II):

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;

moiety B is unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted C 2-5 alkyl;

X is N, or C—R 8 ;

W is O, NH, N—R 9 , N—C(═O)—R 10 , or O═S═O;

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 , R 7b , R 8a , and R 8b , is, independently, H, halogen, 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 7a , and R 7b , together with the atom to which they are attached to, form unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heterocyclyl; or

R 8a , and R 8b , 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 7a , together with the atom to which they are attached to, form an unsubstituted or substituted bridge; or

R 6a , and R 8a , together with the atom to which they are attached to, form an unsubstituted or substituted bridge; or

R 5 , and R 7a , together with the atom to which they are attached to, form an unsubstituted or substituted bridge; or

R 5 , and R 8a , together with the atom to which they are attached to, form an unsubstituted or substituted bridge;

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;

R 9 is substituted or unsubstituted C 1-4 alkyl, or unsubstituted or substituted C 3-5 cycloalkyl;

R 10 is substituted or unsubstituted C 1-4 alkyl, unsubstituted or substituted C 1-4 alkoxy, unsubstituted or substituted C 3-5 cycloalkyl, or unsubstituted or substituted 3-member to 5-member heterocyclyl;

t is 0, or 1;

each of s and r, is independently, is 1, or 2; 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.

40 . The compound of claim 39 , wherein the compound has formula (IIf):

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

wherein X is N, or CH; W is O, or NH;

ring A is

moiety B is

 and

each of R 3a , R 3b , R 4a , R 4b , R 5 , R 6a , R 6b , R 7a , R 7b , R 8a1 , R 8b1 , R 8a2 , and R 8b2 , independently, is H, OH, CN, unsubstituted or substituted amino, or unsubstituted or substituted C 1-4 alkyl.

41 . The compound of claim 39 , wherein the compound has formula (IIg):

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

wherein X is N, or CH; W is O, or NH;

ring A is

moiety B is

 and

each of R 3a , R 3b , R 4a , R 4b , R 5 , R 6a1 , R 6b1 , R 6a2 , R 6b2 , R 7a , R 7b , R 8a , and R 8b , independently, is H, OH, CN, unsubstituted or substituted amino, or unsubstituted or substituted C 1-4 alkyl.

42 . The compound of claim 39 , wherein the compound has formula (IIh):

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

wherein R 11 is deuterium, or substituted or unsubstituted C 1-3 alkyl; and

u is 0, 1, 2, 3, 4, or 5.

43 . (canceled)

44 . The compound of claim 39 , wherein ring A is

wherein R 12 is H, halogen, substituted or unsubstituted C 1-3 alkyl or cyclopropyl optionally substituted with F; and R 12a is H, deuterium, F or Me.

45 . The compound of claim 39 , wherein ring A is

46 . (canceled)

47 . The compound of claim 39 , wherein moiety 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, or C 1-4 alkoxyl-C(O)—.

48 . The compound of claim 39 , wherein moiety B is

49 . The compound of claim 39 , wherein moiety B is oxabicyclo[2.1.1]hexanyl, optionally substituted with halogen, cyano, hydroxy, C 1-3 alkoxy, or C 1-3 alkyl optionally substituted with halogen, cyano, hydroxy, or C 1-3 alkoxy.

50 . The compound of claim 39 , wherein moiety B is

or 2-oxabicyclo[2.1.1]hexan-4-yl.

51 . The compound of claim 39 , wherein moiety B is

52 . The compound of claim 39 , wherein the compound is selected from:

or a pharmaceutically acceptable salt thereof.

53 . A pharmaceutical composition comprising an effective amount of a compound of claim 39 , or a pharmaceutically acceptable salt, tautomer, isotopologue, stereoisomer, enantiomer, atropisomer, or prodrug thereof, and a pharmaceutically acceptable carrier, excipient or vehicle.

54 . (canceled)

55 . 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 39 , 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.

56 . The compound of claim 39 , wherein the compound has one of the following formulas:

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

wherein:

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

57 . The compound of claim 56 , wherein ring C is cyclopropyl, cyclobutyl, or oxetanyl.

58 . The compound of claim 39 , wherein

R 6a , and R 7a , together with the atom to which they are attached to, form an unsubstituted or substituted bridge; or R 6a , and R 8a , together with the atom to which they are attached to, form an unsubstituted or substituted bridge; or R 5 , and R 7a , together with the atom to which they are attached to, form an unsubstituted or substituted bridge; or R 5 , and R 8a , together with the atom to which they are attached to, form an unsubstituted or substituted bridge; and the bridge is —(CH 2 ) 2 —, —(CH 2 ) 3 —, or —CH 2 —O—CH 2 —.

59 . The compound of claim 39 , wherein X is N, C—H, C—Cl, or C—CF 3 .

60 . The compound of claim 39 , wherein W is O, or NH.