KAT6 Inhibitors

1 . A compound of formula (I):

or a pharmaceutically acceptable salt, deuterated analog, N-oxide, or tautomer thereof,

Y 1 is CR 1 or N, Y 2 is CR 2 or N, Y 3 is CR 3 or N, Y 4 is CR 4 or N, Y 5 is CR 5 or N, provided that at most two of Y 1 , Y 2 , Y 3 , Y 4 and Y 5 are N;

is selected from the group consisting of:

(a)

wherein Y 9 is CR 9 or N, Y 10 is CR 10 or N, Y 11 is CR 11 or N, Y 12 is CR 12 ;

(b)

wherein Y 9 is CR 9 or N, Y 10 is CR 10 or N, Y 12 is CR 12A R 12B or NR 12A ;

(c)

wherein Y 9 is CR 9A R 9B , NR 9A , O or S, Y 10 is CR 10 or N, Y 12 is CR 12 ; and

(d)

wherein Y 9 is CR 9 or N, Y 10 is CR 10 or N, Y 12 is CR 12 ;

Y 6 is CR 6 or N, Y 7 is CR 7 or N, Y 8 is CR 8 or N, provided that at most two of Y 6 , Y 7 and Y 8 are N;

R 1 , R 2 , R 3 , R 4 and R 5 are each independently hydrogen, halogen, —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclyl, aryl, heteroaryl, —CN, —NO 2 , —OR 1a , —SO 2 R 1a , —COR 1a , —CO 2 R 1a , —CONR 1a R 1b , —C(═NR 1a )NR 1b R 1c , —NR 1a R 1b , —NR 1a COR 1b , —NR 1a CONR 1b R 1c , —NR 1a CO 2 R 1b , —NR 1a SONR 1b R 1c , —NR 1a SO 2 NR 1b R 1c , —P(═O)R 1a R 1b , —NR 1a SO 2 R 1b or —SOR 1a (═NR 1b ), wherein each of said —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclyl, aryl or heteroaryl is optionally substituted with at least one substituent R 1d ;

or (R 1 and R 2 ), (R 2 and R 3 ), (R 3 and R 4 ), or (R 4 and R 5 ), together with the atoms to which they are attached, form a (i) C 3-10 cycloalkyl, (ii) C 3-10 cycloalkenyl, (iii) 4- to 12-membered heterocyclyl ring containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, (iv) 6- to 12-membered aryl, or (v) 4- to 12-membered heteroaryl ring containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, and wherein (i), (ii), (iii), (iv), or (v) is optionally substituted with 1, 2 or 3 R 1d ;

R 1a , R 1b , and R 1c are each independently hydrogen, —C 1-10 alkyl, deuterated-C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclyl, aryl, or heteroaryl, wherein each of said —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with at least one substituent R 1j ;

each R 1d and R 1j is independently halogen, —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclyl, aryl, heteroaryl, —CN, —NO 2 , —OR 1e , —SO 2 R 1e , —COR 1e , —CO 2 R 1e , —CONR 1e R 1f , —C(═NR 1e )NR 1f R 1g , —NR 1e R 1f , —NR 1e COR 1f , —NR 1e CONR 1f R 1g , —NR 1e CO 2 R 1f , —NR 1e SONR 1f R 1g , —NR 1e SO 2 NR 1f R 1g , —P(═O)R 1e R 1f , —NR 1e SO 2 R 1f , or —SOR 1e (═NR 1f ), wherein each of said —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with at least one substituent selected from halogen, —CN, —C 1-10 alkyl, —OR 1h , —NR 1h R 1j , cycloalkyl, heterocyclyl, aryl, or heteroaryl; or

two of R 1d , together with the atom(s) to which they are attached and any intervening atoms, form an oxo, C 3-10 cycloalkyl, 4- to 12-membered heterocyclyl ring containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, 6- to 12-membered aryl, or 4- to 12-membered heteroaryl ring containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur; wherein said C 3-10 cycloalkyl, 4- to 12-membered heterocyclyl ring, 6- to 12-membered aryl, or 5- to 12-membered heteroaryl ring is optionally substituted with 1, 2, or 3 R 1k ,

each R 1k is independently halogen, —C 1-10 alkyl, -haloC 1-10 alkyl, or —C 1-10 alkoxy;

R 1e , R 1f , R 1g , R 1h and R 1i are each independently hydrogen, —C 1-10 alkyl, -haloC 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;

R 6 , R 7 and R 8 are each independently hydrogen, halogen, C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, CN, NO 2 , —NR 2a R 2b , —OR 2a , or —C(O)R 2a ; wherein said C 1-10 alkyl, —C 2-10 alkenyl, or —C 2-10 alkynyl is optionally substituted with 1, 2, or 3 R 2c ;

R 2a and R 2b are each independently hydrogen, C 1-10 alkyl, -haloC 1-10 alkyl, —C 2-10 alkenyl, or —C 2-10 alkynyl;

each R 2c is independently halogen, —C 1-5 alkyl, —CN, —NH 2 , —NO 2 , —OH, -haloC 1-5 alkyl, —C 1-8 alkoxyl, or -haloC 1-8 alkoxyl; or

two R 2c , attached to the same atom, form an oxo;

R 9 , R 10 , R 11 , R 12 , R 9A and R 12A are each independently hydrogen, halogen, —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclyl, aryl, heteroaryl, —CN, —NO 2 , —OR 3a , —SO 2 R 3a , —COR 3a , —CO 2 R 3a , —CONR 3a R 3b , —C(═NR 3a )NR 3b R 3c , —NR 3a R 3b , —NR 3a COR 3b , —NR 3a CONR 3b R 3c , —NR 3a CO 2 R 3b , —NR 3a SONR 3b R 3c , —NR 3a SO 2 NR 3b R 3c , —P(═O)R 3a R 3b , —NR 3a SO 2 R 3b and —SOR 3a (═NR 3b ), wherein each of said —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with at least one substituent R 3d ;

R 3a , R 3b , and R 3c are each independently hydrogen, —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclyl, aryl, or heteroaryl; wherein each of said —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with R 3j ;

each R 3d and R 3j ais independently halogen, —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclyl, aryl, heteroaryl, —CN, —NO 2 , —OR 3e , —SO 2 R 3e , —COR 3e , —CO 2 R 3e , —CONR 3e R 3f , —C(═NR 3e )NR 3f R 3g , —NR 3e R 3f , —NR 3e COR 3f , —NR 3e CONR 3f R 3g , —NR 3e CO 2 R 3f , —NR 3e SONR 3f R 3g , —NR 3e SO 2 NR 3f R 3g , —P(═O)R 3e R 3f , —NR 3e SO 2 R 3f , or —SOR 3e (═NR 3f ), wherein each of said —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with at least one substituent selected from halogen, —C 1-10 alkyl, —OR 3h , —NR 3h R 3i , cycloalkyl, heterocyclyl, aryl, heteroaryl, -haloC 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, —CN, or —NO 2 ; or

two R 3d or two R 3j , attached to the same atom, form an oxo;

R 3e , R 3f , R 3g , R 3h and R 3i are each independently hydrogen, —C 1-10 alkyl, -haloC 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, cycloalkyl, heterocyclyl, alkoxy-substituted benzyl, aryl, or heteroaryl;

R 9B and R 12B are each independently hydrogen, —C 1-10 alkyl, or -haloC 1-10 alkyl.

2 . The compound of claim 1 , wherein Y 1 is CR 1 , Y 2 is CR 2 , Y 3 is CR 3 , and Y 4 is CR 4 ;

R 1 is hydrogen, halogen, —C 1-8 alkyl, -haloC 1-8 alkyl, —C 1-8 alkoxyl, -haloC 1-8 alkoxyl, deuterated-C 1-8 alkoxyl, —CN, —NH 2 , —NO 2 , —OH, or —O-heteroaryl of 4- to 12-members containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur;

R 2 , R 3 , and R 5 are each independently hydrogen, halogen, —C 1-8 alkyl, -haloC 1-8 alkyl, or —C 1-8 alkoxyl;

R 4 is hydrogen, halogen, —C 1-8 alkyl, —C 2-10 alkenyl, —C 1-8 alkoxyl, C 3-8 cycloalkyl, 4- to 12-membered heterocyclyl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, 6- to 12-membered aryl, or 4- to 12-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur; wherein each of said —C 1-8 alkyl, —C 2-10 alkenyl, C 3-8 cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with 1, 2, 3, or 4 R 1d ; or

(R 1 and R 2 ), (R 2 and R 3 ), (R 3 and R 4 ), or (R 4 and R 5 ), together with the atoms to which they are attached, form a (i) C 3-10 cycloalkyl, (ii) C 3-10 cycloalkenyl, (iii) 4- to 12-membered heterocyclyl ring containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, (iv) 6- to 12-membered aryl, or (v) 4- to 12-membered heteroaryl ring containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, and wherein (i), (ii), (iii), (iv), or (v) is optionally substituted with 1, 2 or 3 R 1d ;

each R 1d is independently halogen, —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, —C 1-8 alkoxyl, —O-haloC 1-10 alkyl, —CN, —OH, —NH 2 , —NO 2 , —CO 2 C 1-10 alkyl, 4- to 12-membered heterocyclyl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, or 4- to 12-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur; wherein said —C 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, heterocyclyl, or heteroaryl is optionally substituted with halogen, —C 1-8 alkyl, —CN, —NH 2 , —OH, or —C 1-8 alkoxyl; or

two R 1d , together with the atom(s) to which they are attached and any intervening atoms, form an oxo, C 3-10 cycloalkyl, 4- to 12-membered heterocyclyl ring containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, 6- to 12-membered aryl, or 4- to 12-membered heteroaryl ring containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur; wherein said C 3-10 cycloalkyl, 4- to 12-membered heterocyclyl ring, 6- to 12-membered aryl, or 5- to 12-membered heteroaryl ring is optionally substituted with 1, 2, or 3 R 1k .

3 . The compound of claim 2 , wherein R 1 is —C 1-5 alkoxyl, or deuterated —C 1-5 alkoxyl;

R 2 , R 3 , and R 5 are hydrogen;

R 4 is tert-butyl, cyclopropanyl, cyclobutanyl, cyclopentanyl, oxetanyl, tetrahydrofuranyl, tetrahydro-pyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyrazolyl, 2-oxabicyclo[2.1.1]hexanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, 5-azaspiro[2.4]heptanyl, morpholinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, or 2-oxa-7-azaspiro[4.4]nonanyl; wherein each of said tert-butyl, cyclopropanyl, cyclobutanyl, cyclopentanyl, oxetanyl, tetrahydrofuranyl, tetrahydro-pyranyl, oxepanyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, pyrazolyl, 2-oxabicyclo[2.1.1]hexanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, 5-azaspiro[2.4]heptanyl, morpholinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, 2-oxa-7-azaspiro[4.4]nonanyl, or 3-oxa-8-azabicyclo[3.2.1]octany is optionally substituted with 1, 2, 3, or 4 R 1d ; or

(R 1 and R 2 ), (R 2 and R 3 ), (R 3 and R 4 ), or (R 4 and R 5 ), together with the atoms to which they are attached and any intervening atoms, form dihydrofuranyl, cyclopentenyl, cyclohexenyl, furanyl, benzenyl, dihydro-pyranyl, dihydro-pyrrolyl, isoxazolyl, 2-oxabicyclo[3.1.1]hept-3-enyl, 4-oxaspiro[2.4]hept-5-enyl, 5-oxaspiro[2.4]hept-6-enyl, or 2,8-dioxaspiro[4.5]dec-3-enyl; wherein each of said dihydrofuranyl, cyclopentenyl, cyclohexenyl, furanyl, benzenyl, dihydro-pyranyl, dihydro-pyrrolyl, isoxazolyl, 2-oxabicyclo[3.1.1]hept-3-enyl, 4-oxaspiro[2.4]hept-5-enyl, 5-oxaspiro[2.4]hept-6-enyl, or 2,8-dioxaspiro[4.5]dec-3-enyl is optionally substituted with 1, 2, or 3 R 1d ;

each R 1d is independently halogen, —C 1-5 alkyl, —C 1-5 alkoxyl, —CN, —OH, —NH 2 , —CO 2 C 1-5 alkyl, morpholinyl, oxetanyl, or triazolyl; wherein said halogen, —C 1-5 alkyl, —C 1-5 alkoxyl, oxo, —CN, —OH, —NH 2 , —COOC 1-5 alkyl, morpholinyl, oxetanyl, or triazolyl is optionally substituted with halogen, —C 1-5 alkyl, —CN, —NH 2 , —OH, or —C 1-5 alkoxyl; or

two R 1d , together with the atom(s) to which they are attached and any intervening atoms, form an oxo, cyclopropanyl, cyclobutanyl, tetrahydrofuranyl, morpholinyl, tetrahydrofuranyl, or piperidinyl; wherein said cyclopropanyl, cyclobutanyl, tetrahydrofuranyl, morpholinyl, tetrahydrofuranyl, or piperidinyl is optionally substituted with 1, 2, or 3 R 1k ;

each R 1k is independently hydrogen, halogen, —C 1-5 alkyl, -haloC 1-5 alkyl, or —C 1-5 alkoxy.

4 . The compound of claim 2 , wherein

R 1 is methoxy or -OCD 3 ;

R 2 , R 3 , and R 5 , if present, are hydrogen;

R 4 is tert-butyl,

5 - 9 . (canceled)

10 . The compound of claim 1 , wherein

is selected from the group consisting of:

11 . The compound of claim 10 , wherein

R 6 , R 7 and R 8 are each independently hydrogen, halogen, —C 1-5 alkyl, -haloC 1-8 alkyl, —C 1-8 alkoxyl, -haloC 1-8 alkoxyl, —CN, —OH, —NH 2 or —NO 2 ;

R 9 is hydrogen, halogen, C 1-8 alkyl, -haloC 1-8 alkyl, —C 1-8 alkoxyl, -haloC 1-8 alkoxyl, CN, NO 2 , —C 3-8 cycloalkyl, 4- to 9-membered heterocyclyl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, —OR 3a , or -NR 3a R 3b , wherein each of said —C 3-8 cycloalkyl or heterocyclyl is optionally substituted with halogen, —C 1-10 alkyl, -haloC 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, —C 1-10 alkoxyl, -haloC 1-10 alkoxyl, oxo, —CN, —OH, —NH 2 or —NO 2 ;

R 3a and R 3b are each independently hydrogen, —C 1-8 alkyl, —C 3-8 cycloalkyl, —C 1-8 alkyl-heterocyclyl of 4- to 9-members containing 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, or —C 1-8 alkyl-aryl of 6- to 12-members;

wherein said —C 1-8 alkyl-C 3-8 cycloalkyl, —C 1-8 alkyl-heterocyclyl, or —C 1-8 alkyl-aryl is optionally substituted with halogen, —C 1-10 alkyl, -haloC 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, —C 1-10 alkoxyl, -haloC 1-10 alkoxyl, oxo, —CN, —OH, —NH 2 or —NO 2 ;

R 10 and R 11 are each independently hydrogen, halogen, —C 1-8 alkyl, -haloC 1-8 alkyl, —C 1-8 alkoxyl, -haloC 1-8 alkoxyl, —OH, —CN, —NO 2 , or —NH 2 ;

R 9A is hydrogen, —C 1-10 alkyl, or -haloC 1-10 alkyl; and

R 12 and R 12A are each independently-C 3-8 cycloalkyl, 4- to 9-membered heterocyclyl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, 6- to 12-membered aryl, 4- to 12-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, or —C 1-8 alkyl-heteroaryl ring of 4- to 12-members containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, wherein each of said —C 3-8 cycloalkyl, heterocyclyl, aryl, heteroaryl, or —C 1-8 alkyl-heteroaryl is optionally substituted with halogen, —C 1-10 alkyl, -haloC 1-10 alkyl, —C 2-10 alkenyl, —C 2-10 alkynyl, —C 1-10 alkoxyl, -haloC 1-10 alkoxyl, —(C 1-10 alkyl)-O—(C 1-10 alkyl), oxo, —CN, —OH, —NH 2 or —NO 2 .

12 - 15 . (canceled)

16 . The compound of claim 10 , wherein the compound has a formula (IV-1)-formula (IV-5):

or a pharmaceutically acceptable salt, deuterated analog, N-oxide, or tautomer thereof, wherein

is

n is 0, 1, 2, 3 or 4.

17 . The compound of claim 10 , wherein the compound has formula (V-5-1)-(V-5-5):

or a pharmaceutically acceptable salt, deuterated analog, N-oxide, or tautomer thereof, wherein

m is 0, 1 or 2.

18 . (canceled)

19 . The compound of claim 10 , wherein the compound has formula (VI-6):

R 1 is —C 1-5 alkoxyl or deuterated-C 1-5 alkoxyl;

if present, R 6 is hydrogen or —C 1-5 alkyl;

R 2 , R 3 , and, if present, R 5 are each independently hydrogen, halogen, —C 1-8 alkyl, -haloC 1-8 alkyl, or —C 1-8 alkoxyl;

R 4 is —C 1-8 alkyl, C 3-8 cycloalkyl, 4- to 12-membered heterocyclyl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, 6- to 12-membered aryl, or 4- to 12-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur; wherein each of said —C 1-8 alkyl, —C 2-10 alkenyl, C 3 -cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with 1, 2, 3, or 4 R 1d , or (R 3 and R 4 ) or (R 4 and R 5 ), together with the atoms to which they are attached, form a 4- to 12-membered heterocyclyl ring containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, 6- to 12-membered aryl, or 4- to 12-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, and are optionally substituted with 1, 2 or 3 R 1d ;

each R 1d is independently halogen, —C 1-10 alkyl, —C 1-8 alkoxyl, —O-haloC 1-10 alkyl, —CN, —OH, —NH 2 , —NO 2 , —CO 2 C 1-10 alkyl, 4- to 12-membered heterocyclyl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur, or 4- to 12-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and optionally oxidized sulfur; wherein said —C 1-10 alkyl, heterocyclyl, or heteroaryl is optionally substituted with halogen, —C 1-8 alkyl, —CN, —NH 2 , —OH, or —C 1-8 alkoxyl; or

two R 1d , together with the atom(s) to which they are attached and any intervening atoms, form oxo or cyclopropanyl, cyclobutanyl, tetrahydrofuranyl, morpholinyl, tetrahydrofuranyl, or piperidinyl; wherein said cyclopropanyl, cyclobutanyl, tetrahydrofuranyl, morpholinyl, tetrahydrofuranyl, or piperidinyl, each of which is optionally substituted with 1, 2, or 3 R 1k ;

each R 1k is independently halogen, —C 1-5 alkyl, -haloC 1-5 alkyl, or —C 1-5 alkoxy;

R 7 , R 8 , R 10 and R 11 are each hydrogen;

R 9 is hydrogen or —C 1-5 alkyl;

is

each R 3d is independently halogen, —NH 2 , or —C 1-5 alkyl; and

n is 0, 1, or 2.

20 - 21 . (canceled)

22 . The compound of claim 17 , wherein the compound has formula (VI-2):

or a pharmaceutically acceptable salt, deuterated analog, N-oxide, or tautomer thereof, wherein:

is dihydrofuranyl, cyclopentenyl, cyclohexenyl, furanyl, benzenyl, dihydro-pyranyl, dihydro-pyrrolyl, isoxazolyl, 2-oxabicyclo[3.1.1]hept-3-enyl, 4-oxaspiro[2.4]hept-5-enyl, 5-oxaspiro[2.4]hept-6-enyl, or 2,8-dioxaspiro[4.5]dec-3-enyl;

each R 1d is independently halogen, —C 1-5 alkyl, -haloC 1-5 alkyl, —C 1-5 alkoxyl, —CN, —OH, —NH 2 , or —CO 2 C 1-5 alkyl; or

two R 1d , together with the atom(s) to which they are attached and any intervening atoms, form oxo, cyclopropanyl, cyclobutanyl, tetrahydrofuranyl, morpholinyl, tetrahydrofuranyl, or piperidinyl; wherein said cyclopropanyl, cyclobutanyl, tetrahydrofuranyl, morpholinyl, tetrahydrofuranyl, or piperidinyl is optionally substituted with 1, 2, or 3 R 1k ;

R 2 and R 3 are hydrogen;

if present, R 6 is hydrogen; and

each R 3d is independently F, Cl, —NH 2 , or —C 1-5 alkyl.

23 . The compound of claim 22 , wherein the compound has formula (VI-3) or (VI-4):

or a pharmaceutically acceptable salt, deuterated analog, N-oxide, or tautomer thereof, wherein:

each R 1d is independently halogen, —C 1-5 alkyl, -haloC 1-5 alkyl, —C 1-5 alkoxyl, —CN, —OH, —NH 2 , or —CO 2 C 1-5 alkyl; or

two R 1d , together with the atom(s) to which they are attached and any intervening atoms, form oxo or cyclopropanyl, cyclobutanyl, tetrahydrofuranyl, morpholinyl, tetrahydrofuranyl, or piperidinyl; wherein said cyclopropanyl, cyclobutanyl, tetrahydrofuranyl, morpholinyl, tetrahydrofuranyl, or piperidinyl, which is optionally substituted with 1, 2, or 3 R 1k ;

R 2 and R 3 are hydrogen;

if present, R 6 is hydrogen; and

each R 3d is independently hydrogen, F, Cl, —NH 2 , or —C 1-5 alkyl.

24 . (canceled)

25 . The compound of claim 23 , wherein Y 6 is N.

26 . The compound of claim 23 , wherein n is 0.

27 . The compound of claim 23 , wherein

each R 1d is independently fluoro, methyl, trifluoromethyl, methoxy, —CN, —OH, —NH 2 , or -CO 2 C 1 alkyl.

28 . The compound of claim 23 ,

wherein

R 1 is hydrogen, —OCH 3 , or -OCD 3 ;

R 9 is hydrogen or methyl;

R 2 , R 3 , R 7 , R 8 , R 10 , and R 11 are hydrogen;

R 1d is methyl, or two R 1d attached to the same atom form cyclopropyl or tetrahydropyranyl;

R 3d is —NH 2 ; and

n is 0 or 1.

29 . A compound selected from:

C1

C2

C3

C4

C5

C6

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C254

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C261

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C279

or a pharmaceutically acceptable salt, deuterated analog, N-oxide, or tautomer thereof.

30 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, deuterated analog, N-oxide, or tautomer thereof, and at least one pharmaceutically acceptable carrier or excipient.

31 . A method of treating a disease responsive to inhibition of KAT6, comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, deuterated analog, N-oxide, or tautomer thereof.

32 . (canceled)

33 . A method of treating cancer, comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, deuterated analog, N-oxide, or tautomer thereof.

34 . (canceled)

35 . The compound of claim 29 with the structure:

or a pharmaceutically acceptable salt, deuterated analog, N-oxide, or tautomer thereof.