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CN-122003411-A - MYST inhibitors

CN122003411ACN 122003411 ACN122003411 ACN 122003411ACN-122003411-A

Abstract

Provided herein are compounds and pharmaceutically acceptable derivatives thereof that are MYST inhibitors. Pharmaceutical compositions containing the compounds and methods of using the compounds to treat subjects having hyperproliferative diseases, including cancer, are also provided.

Inventors

  • RAI ROOPA
  • A. Pandy
  • L. J. Hallsinger

Assignees

  • 爱索斯特里克斯公司

Dates

Publication Date
20260508
Application Date
20240926
Priority Date
20240227

Claims (20)

  1. 1. A compound of formula I: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 and R 2 together form an alkylene group; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 、Z 5 and Z 6 are selected from (i), (ii), (iii) or (iv): (i) Z 4 is N, Z 5 is CR 5 , and Z 6 is CH, (Ii) Z 4 is CR 16 ,Z 5 is N, and Z 6 is CH, (Iii) Z 4 is CR 16 ,Z 5 is CR 5 and Z 6 is N, or (Iv) Z 4 is CR 16 ,Z 5 is CR 5 , and Z 6 is CH; r 5 and R 16 are selected from (i) or (ii): (i) R 5 and R 16 are each independently H, cyano, halogen, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or (Ii) R 5 and R 16 together form alkylene or heteroalkylene; X is O, S (O) x or CH 2 , wherein X is 0 to 2; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 、-S(O)R 18 or-SO 2 R 18 ; R 17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylaynyl, aminomethylalkynyl, methylaminomethyl alkynyl, dimethylaminomethyl alkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, -NH- (CH 2 ) 2 -R 19 、-O-(CH 2 ) 2 -R 19 , OR-NR 20 R 21 , wherein R 19 is-OR 9 OR-NR 9 R 10 , and R 20 and R 21 are each independently H, alkyl, cycloalkyl, OR haloalkyl, and R 18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylaynyl, alkoxymethylaynyl, aminomethylalkynyl or-NR 20 R 21 .
  2. 2. A compound of formula I: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 and R 2 are selected from (i) or (ii): (i) R 1 is H, alkyl, haloalkyl or halogen, and R 2 is alkyl, cycloalkyl or haloalkyl, or (Ii) R 1 and R 2 together form an alkylene group; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 is CR 16 ; Z 5 is CR 5 ; Z 6 is N or CH; R 5 and R 16 together form alkylene or heteroalkylene; X is O, S (O) x or CH 2 , wherein X is 0 to 2; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 、-S(O)R 18 or-SO 2 R 18 ; R 17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylaynyl, aminomethylalkynyl, methylaminomethyl alkynyl, dimethylaminomethyl alkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, -NH- (CH 2 ) 2 -R 19 、-O-(CH 2 ) 2 -R 19 , OR-NR 20 R 21 , wherein R 19 is-OR 9 OR-NR 9 R 10 , and R 20 and R 21 are each independently H, alkyl, cycloalkyl, OR haloalkyl, and R 18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylaynyl, alkoxymethylaynyl, aminomethylalkynyl or-NR 9 R 10 .
  3. 3. A compound of formula I: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 and R 2 are selected from (i) or (ii): (i) R 1 is H, alkyl, haloalkyl or halogen, and R 2 is alkyl, cycloalkyl or haloalkyl, or (Ii) R 1 and R 2 together form an alkylene group; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 、Z 5 and Z 6 are selected from (i), (ii), (iii) or (iv): (i) Z 4 is N, Z 5 is CR 5 , and Z 6 is CH, (Ii) Z 4 is CR 16 ,Z 5 is N, and Z 6 is CH, (Iii) Z 4 is CR 16 ,Z 5 is CR 5 and Z 6 is N, or (Iv) Z 4 is CR 16 ,Z 5 is CR 5 , and Z 6 is CH; r 5 and R 16 are selected from (i) or (ii): (i) R 5 and R 16 are each independently H, cyano, halogen, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or (Ii) R 5 and R 16 together form alkylene or heteroalkylene; X is O or S (O) x , wherein X is 0 to 2; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 、-S(O)R 18 or-SO 2 R 18 ; R 17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylaynyl, aminomethylalkynyl, methylaminomethyl alkynyl, dimethylaminomethyl alkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, -NH- (CH 2 ) 2 -R 19 、-O-(CH 2 ) 2 -R 19 , OR-NR 20 R 21 , wherein R 19 is-OR 9 OR-NR 9 R 10 , and R 20 and R 21 are each independently H, alkyl, cycloalkyl, OR haloalkyl, and R 18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylaynyl, alkoxymethylaynyl, aminomethylalkynyl or-NR 9 R 10 .
  4. 4. A compound of formula I: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; r 1 is H, alkyl, haloalkyl, alkoxy, cycloalkoxy, haloalkoxy or halogen; r 2 and R 4 together form an alkylene group; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 、Z 5 and Z 6 are selected from (i), (ii), (iii) or (iv): (i) Z 4 is N, Z 5 is CR 5 , and Z 6 is CH, (Ii) Z 4 is CR 16 ,Z 5 is N, and Z 6 is CH, (Iii) Z 4 is CR 16 ,Z 5 is CR 5 and Z 6 is N, or (Iv) Z 4 is CR 16 ,Z 5 is CR 5 , and Z 6 is CH; r 5 and R 16 are selected from (i) or (ii): (i) R 5 and R 16 are each independently H, cyano, halogen, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or (Ii) R 5 and R 16 together form alkylene or heteroalkylene; X is O, S (O) x or CH 2 , wherein X is 0 to 2; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 、-S(O)R 18 or-SO 2 R 18 ; R 17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylaynyl, aminomethylalkynyl, methylaminomethyl alkynyl, dimethylaminomethyl alkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, -NH- (CH 2 ) 2 -R 19 、-O-(CH 2 ) 2 -R 19 , OR-NR 20 R 21 , wherein R 19 is-OR 9 OR-NR 9 R 10 , and R 20 and R 21 are each independently H, alkyl, cycloalkyl, OR haloalkyl, and R 18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylaynyl, alkoxymethylaynyl, aminomethylalkynyl or-NR 9 R 10 .
  5. 5. A compound of formula I: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 is H, alkyl, haloalkyl or halogen; R 2 is alkyl, cycloalkyl or haloalkyl; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 、Z 5 and Z 6 are selected from (i), (ii), (iii) or (iv): (i) Z 4 is N, Z 5 is CR 5 , and Z 6 is CH, (Ii) Z 4 is CR 16 ,Z 5 is N, and Z 6 is CH, (Iii) Z 4 is CR 16 ,Z 5 is CR 5 and Z 6 is N, or (Iv) Z 4 is CR 16 ,Z 5 is CR 5 , and Z 6 is CH; r 5 and R 16 are selected from (i) or (ii): (i) R 5 and R 16 are each independently H, cyano, halogen, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or (Ii) R 5 and R 16 together form alkylene or heteroalkylene; X is CR 22 R 23 , wherein R 22 and R 23 are each independently H or alkyl; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 , and R 17 is alkoxy, alkenyloxy, alkynyloxy OR-O- (CH 2 ) 2 -R 19 ), wherein R 19 is-OR 9 OR-NR 9 R 10 .
  6. 6. The compound according to any one of claims 1 to 5, having formula Ia: or a pharmaceutically acceptable derivative thereof.
  7. 7. A compound according to any one of claims 1 to 6, wherein: r 1 is H; R 2 is alkyl, cycloalkyl or haloalkyl; R 8 is H, CN, OH, aryl, heteroaryl, NR 9 R 10 , or C (O) R 11 ; R 9 and R 10 are each independently H or C (O) R 13 , wherein R 13 is alkyl or alkoxy; r 11 is alkyl or alkoxy; X is CH 2 , and R 17 is alkoxy.
  8. 8. The compound according to any one of claims 1 to 7, wherein: r 1 is H; R 2 is alkyl or haloalkyl; R 8 is H, CN, OH, aryl, NR 9 R 10 or C (O) R 11 ; R 9 and R 10 are each independently H or C (O) R 13 , wherein R 13 is alkyl; r 11 is alkoxy; X is CH 2 , and R 17 is alkoxy.
  9. 9. A compound of formula II: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 and R 2 together form an alkylene group; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 、Z 5 and Z 6 are selected from (i), (ii), (iii) or (iv): (i) Z 4 is N, Z 5 is CR 5 , and Z 6 is CH, (Ii) Z 4 is CR 16 ,Z 5 is N, and Z 6 is CH, (Iii) Z 4 is CR 16 ,Z 5 is CR 5 and Z 6 is N, or (Iv) Z 4 is CR 16 ,Z 5 is CR 5 , and Z 6 is CH; r 5 and R 16 are selected from (i) or (ii): (i) R 5 and R 16 are each independently H, cyano, halogen, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or (Ii) R 5 and R 16 together form alkylene or heteroalkylene; X is O, S (O) x or CH 2 , wherein X is 0 to 2; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 、-S(O)R 18 or-SO 2 R 18 ; R 17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylaynyl, aminomethylalkynyl, methylaminomethyl alkynyl, dimethylaminomethyl alkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, -NH- (CH 2 ) 2 -R 19 、-O-(CH 2 ) 2 -R 19 , OR-NR 20 R 21 , wherein R 19 is-OR 9 OR-NR 9 R 10 , and R 20 and R 21 are each independently H, alkyl, cycloalkyl, OR haloalkyl, and R 18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylaynyl, alkoxymethylaynyl, aminomethylalkynyl or-NR 20 R 21 .
  10. 10. A compound of formula II: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 and R 2 are selected from (i) or (ii); (i) R 1 is alkyl, cycloalkyl or haloalkyl, and R 2 is H, alkyl, haloalkyl, alkoxy, cycloalkoxy, haloalkoxy or halogen, or (Ii) R 1 and R 2 together form an alkylene group; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 is CR 16 ; Z 5 is CR 5 ; Z 6 is N or CH; R 5 and R 16 together form alkylene or heteroalkylene; X is O, S (O) x or CH 2 , wherein X is 0 to 2; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 、-S(O)R 18 or-SO 2 R 18 ; R 17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylaynyl, aminomethylalkynyl, methylaminomethyl alkynyl, dimethylaminomethyl alkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, -NH- (CH 2 ) 2 -R 19 、-O-(CH 2 ) 2 -R 19 , OR-NR 20 R 21 , wherein R 19 is-OR 9 OR-NR 9 R 10 , and R 20 and R 21 are each independently H, alkyl, cycloalkyl, OR haloalkyl, and R 18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylaynyl, alkoxymethylaynyl, aminomethylalkynyl or-NR 9 R 10 .
  11. 11. A compound of formula II: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 and R 2 are selected from (i) or (ii): (i) R 1 is alkyl, cycloalkyl or haloalkyl, and R 2 is H, alkyl, haloalkyl, alkoxy, cycloalkoxy, haloalkoxy or halogen, or (Ii) R 1 and R 2 together form an alkylene group; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 、Z 5 and Z 6 are selected from (i), (ii), (iii) or (iv): (i) Z 4 is N, Z 5 is CR 5 , and Z 6 is CH, (Ii) Z 4 is CR 16 ,Z 5 is N, and Z 6 is CH, (Iii) Z 4 is CR 16 ,Z 5 is CR 5 and Z 6 is N, or (Iv) Z 4 is CR 16 ,Z 5 is CR 5 , and Z 6 is CH; r 5 and R 16 are selected from (i) or (ii): (i) R 5 and R 16 are each independently H, cyano, halogen, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or (Ii) R 5 and R 16 together form alkylene or heteroalkylene; X is O or S (O) x , wherein X is 0 to 2; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 、-S(O)R 18 or-SO 2 R 18 ; R 17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylaynyl, aminomethylalkynyl, methylaminomethyl alkynyl, dimethylaminomethyl alkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, -NH- (CH 2 ) 2 -R 19 、-O-(CH 2 ) 2 -R 19 , OR-NR 20 R 21 , wherein R 19 is-OR 9 OR-NR 9 R 10 , and R 20 and R 21 are each independently H, alkyl, cycloalkyl, OR haloalkyl, and R 18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylaynyl, alkoxymethylaynyl, aminomethylalkynyl or-NR 9 R 10 .
  12. 12. A compound of formula II: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 is alkyl, cycloalkyl or haloalkyl; r 2 is H, alkyl, haloalkyl, alkoxy, cycloalkoxy, haloalkoxy or halogen; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 、Z 5 and Z 6 are selected from (i), (ii), (iii) or (iv): (i) Z 4 is N, Z 5 is CR 5 , and Z 6 is CH, (Ii) Z 4 is CR 16 ,Z 5 is N, and Z 6 is CH, (Iii) Z 4 is CR 16 ,Z 5 is CR 5 and Z 6 is N, or (Iv) Z 4 is CR 16 ,Z 5 is CR 5 , and Z 6 is CH; r 5 and R 16 are selected from (i) or (ii): (i) R 5 and R 16 are each independently H, cyano, halogen, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or (Ii) R 5 and R 16 together form alkylene or heteroalkylene; X is CR 22 R 23 , wherein R 22 and R 23 are each independently H or alkyl; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 , and R 17 is alkoxy, alkenyloxy, alkynyloxy OR-O- (CH 2 ) 2 -R 19 ), wherein R 19 is-OR 9 OR-NR 9 R 10 .
  13. 13. The compound according to any one of claims 9 to 12, wherein the compound has formula IIa: or a pharmaceutically acceptable derivative thereof.
  14. 14. The compound according to any one of claims 9 to 13, wherein: R 1 is alkyl, cycloalkyl or haloalkyl; R 2 is H; R 8 is H, CN, OH, aryl, heteroaryl, NR 9 R 10 , or C (O) R 11 ; R 9 and R 10 are each independently H or C (O) R 13 , wherein R 13 is alkyl or alkoxy; r 11 is alkyl or alkoxy; X is CH 2 , and R 17 is alkoxy.
  15. 15. The compound according to any one of claims 9 to 13, wherein: r 1 is alkyl or haloalkyl; R 2 is H; R 8 is H, CN, OH, aryl, NR 9 R 10 or C (O) R 11 ; R 9 and R 10 are each independently H or C (O) R 13 , wherein R 13 is alkyl; r 11 is alkoxy; X is CH 2 , and R 17 is alkoxy.
  16. 16. A compound of formula III: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 and R 2 together form an alkylene group; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 、Z 5 and Z 6 are selected from (i), (ii), (iii) or (iv): (i) Z 4 is N, Z 5 is CR 5 , and Z 6 is CH, (Ii) Z 4 is CR 16 ,Z 5 is N, and Z 6 is CH, (Iii) Z 4 is CR 16 ,Z 5 is CR 5 and Z 6 is N, or (Iv) Z 4 is CR 16 ,Z 5 is CR 5 , and Z 6 is CH; r 5 and R 16 are selected from (i) or (ii): (i) R 5 and R 16 are each independently H, cyano, halogen, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or (Ii) R 5 and R 16 together form alkylene or heteroalkylene; X is O, S (O) x or CH 2 , wherein X is 0 to 2; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 、-S(O)R 18 or-SO 2 R 18 ; R 17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylaynyl, aminomethylalkynyl, methylaminomethyl alkynyl, dimethylaminomethyl alkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, -NH- (CH 2 ) 2 -R 19 、-O-(CH 2 ) 2 -R 19 , OR-NR 20 R 21 , wherein R 19 is-OR 9 OR-NR 9 R 10 , and R 20 and R 21 are each independently H, alkyl, cycloalkyl, OR haloalkyl, and R 18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylaynyl, alkoxymethylaynyl, aminomethylalkynyl or-NR 20 R 21 .
  17. 17. A compound of formula III: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 and R 2 are selected from (i) or (ii): (i) R 1 and R 2 are each independently alkyl, cycloalkyl or haloalkyl, or (Ii) R 1 and R 2 together form an alkylene group; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 is CR 16 ; Z 5 is CR 5 ; Z 6 is N or CH; R 5 and R 16 together form alkylene or heteroalkylene; X is O, S (O) x or CH 2 , wherein X is 0 to 2; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 、-S(O)R 18 or-SO 2 R 18 ; R 17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylaynyl, aminomethylalkynyl, methylaminomethyl alkynyl, dimethylaminomethyl alkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, -NH- (CH 2 ) 2 -R 19 、-O-(CH 2 ) 2 -R 19 , OR-NR 20 R 21 , wherein R 19 is-OR 9 OR-NR 9 R 10 , and R 20 and R 21 are each independently H, alkyl, cycloalkyl, OR haloalkyl, and R 18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylaynyl, alkoxymethylaynyl, aminomethylalkynyl or-NR 9 R 10 .
  18. 18. A compound of formula III: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 and R 2 are selected from (i) or (ii): (i) R 1 and R 2 are each independently alkyl, cycloalkyl or haloalkyl, or (Ii) R 1 and R 2 together form an alkylene group; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 、Z 5 and Z 6 are selected from (i), (ii), (iii) or (iv): (i) Z 4 is N, Z 5 is CR 5 , and Z 6 is CH, (Ii) Z 4 is CR 16 ,Z 5 is N, and Z 6 is CH, (Iii) Z 4 is CR 16 ,Z 5 is CR 5 and Z 6 is N, or (Iv) Z 4 is CR 16 ,Z 5 is CR 5 , and Z 6 is CH; r 5 and R 16 are selected from (i) or (ii): (i) R 5 and R 16 are each independently H, cyano, halogen, alkoxy, amino, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl or haloalkyl, or (Ii) R 5 and R 16 together form alkylene or heteroalkylene; X is O or S (O) x , wherein X is 0 to 2; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 、-S(O)R 18 or-SO 2 R 18 ; R 17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylaynyl, aminomethylalkynyl, methylaminomethyl alkynyl, dimethylaminomethyl alkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, -NH- (CH 2 ) 2 -R 19 、-O-(CH 2 ) 2 -R 19 , OR-NR 20 R 21 , wherein R 19 is-OR 9 OR-NR 9 R 10 , and R 20 and R 21 are each independently H, alkyl, cycloalkyl, OR haloalkyl, and R 18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylaynyl, alkoxymethylaynyl, aminomethylalkynyl or-NR 9 R 10 .
  19. 19. The compound according to any one of claims 16 to 18, wherein the compound has formula IIIa: 。
  20. 20. A compound of formula IIIa: or a pharmaceutically acceptable derivative thereof, wherein: a is 0 to 2; R 1 and R 2 are selected from (i) or (ii): (i) R 1 and R 2 are each independently alkyl, cycloalkyl or haloalkyl, or (Ii) R 1 and R 2 together form an alkylene group; R 3 is-O- (CH 2 ) b -R 8 ); b is 1 to 4; r 8 is H, CN, OH, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, NR 9 R 10 、C(O)R 11 、C(=NH)(R 12 ) or C (=n-O-R 9 )(R 12 ); R 9 and R 10 are each independently H, alkyl or C (O) R 13 , wherein R 13 is alkyl, alkoxy or NR 14 R 15 ; R 11 is hydroxy, alkyl, alkoxy or NR 14 R 15 ; R 12 is alkyl or NR 14 R 15 ; R 14 and R 15 are each independently H, OH, alkoxy or alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic group; r 4 is H or alkoxy; Z 1 、Z 2 and Z 3 are selected from (i), (ii) or (iii): (i) Z 1 is N, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N, (Ii) Z 1 is NH or O, and Z 2 and Z 3 are C, or (Iii) Z 1 is CH, one of Z 2 and Z 3 is C, and the other of Z 2 and Z 3 is N; Z 4 is N or CR 16 wherein R 16 is H, alkyl, haloalkyl, alkoxy, halogen, alkenyl or alkynyl; R 5 is H, alkyl, haloalkyl, alkoxy, halogen, alkenyl, or alkynyl; X is O, S (O) x or CH 2 , wherein X is 0 to 2; Het and R 6 are selected from (i) or (ii): (i) Het is a 5-or 6-membered heteroaryl group and R 6 is H, alkyl or haloalkyl, or (Ii) Het is a 5-or 6-membered heteroaryl, R 6 is- (CH 2 ) 1-2 -, and R 6 and Het together with the atoms to which they are attached form a 5,5-, 5,6-, 5,7-, 6,5-, 6-or 6, 7-bicyclic ring system; R 7 is-C (O) R 17 or-SO 2 R 18 ; R 17 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, dimethylaminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylalkynyl, alkoxymethylaynyl, aminomethylalkynyl, methylaminomethyl alkynyl, dimethylaminomethyl alkynyl, alkoxy, haloalkoxy, alkenyloxy, alkynyloxy, -NH- (CH 2 ) 2 -R 19 、-O-(CH 2 ) 2 -R 19 , OR-NR 20 R 21 , wherein R 19 is-OR 9 OR-NR 9 R 10 , and R 20 and R 21 are each independently H, alkyl, cycloalkyl, OR haloalkyl, and R 18 is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkenyl, haloalkenyl, cyanoalkenyl, hydroxymethylalkenyl, alkoxymethylalkenyl, aminomethylalkenyl, alkynyl, haloalkynyl, cyanoalkynyl, hydroxymethylaynyl, alkoxymethylaynyl, aminomethylalkynyl or-NR 9 R 10 .

Description

MYST inhibitors RELATED APPLICATIONS The present application claims priority from U.S. provisional patent application Ser. No. 63/585,817, U.S. provisional patent application Ser. No. 63/558,419, U.S. provisional patent application Ser. No. 63/655,961, U.S. provisional patent application Ser. No. 63/558,419, and U.S. provisional patent application Ser. No. 4, U.S. 6/4, 2024, filed on 27, both of 9/2023, the disclosures of which are incorporated herein by reference in their entireties. Sequence listing The present application contains a sequence listing filed as an XML file of size 5406 bytes, named "ISTX104 X104wo_sl.xml", created at 2024, 9, 11, which is incorporated herein by reference in its entirety. Technical Field Provided herein are compounds and compositions of the MYST family for inhibiting lysine acetyltransferase (KAT). In one embodiment, methods of treating diseases, including hyperproliferative diseases, with the compounds and compositions provided herein are provided. In another embodiment, the hyperproliferative disease is cancer. Background The MYST family of enzymes is KAT and includes KAT6A (also known as MOZ or MYST), KAT6B (also known as MORF or MYST), KAT5 (also known as Tip 60), KAT7 (also known as HBO1 or MYST 2) and KAT8 (also known as MOF or MYST 1) (see, e.g., wiesel-Motiuk et al, drug Resistance Updates 2020, 53, 100729; wapenaar et al, CLINICAL EPIGENETICS 2016, 8 (59), 1 (DOI 10.1186/s 13148-016-0225-2)). The MYST family of KATs is particularly important in regulating the cell cycle (Carrozza et al TRENDS IN GENETICS 2003, 19, 321-329). Deregulation of KAT6 protein expression supports tumor progression (see, e.g., trisciuoglio et al, STEM CELLS int.2018, ARTICLE ID 8908751 (https:// doi.org/10.1155/2018/8908751)). Deregulation of gene amplification, overexpression or mutation via KAT6A has been described in a variety of cancer types, including breast, lung, ovarian, colon and rectal adenocarcinomas, cervical cancer (see, e.g., huang et al, molecular and Cellular Biology 2016, 63, 1900-1907; zack et al, nature Genetics 2013, 45, 1134-1140). The locus containing the gene for KAT6A (8 p11-p12 amplicon) is reported to be the 12 th most amplified region of the genome in all cancer types (see, e.g., zack et al, 2013, supra). In Acute Myelogenous Leukemia (AML), recurrent oncogenic fusions of KAT6A have been described to drive the transformation to a malignant state (see, e.g., sheikh et al, blood 2015, 125, 1910-1921). Translocation and fusion of KAT6A with partners such as CBP, p300, TIF2 and NCOA3 are known to lead to invasive forms of AML (see, e.g., sheikh et al, 2015, supra). In addition to the role KAT plays in epigenetic regulation, KAT also acetylates non-histone proteins. KAT involves modulating protein function and stability, protein-protein and protein-DNA interactions, and regulating enzymatic activity by modifying the acetylation status of non-histone proteins (see, e.g., glozak et al, gene 2005, 363, 15-23; das et al, IUBMB Life 2005, 57, 137-148). Accordingly, MYST inhibitors for the treatment of hyperproliferative diseases, including cancer, are needed. Disclosure of Invention Provided herein is a compound of formula I: Or a pharmaceutically acceptable derivative thereof, wherein R 1-R4、R6、R7, a, het, X and Z 1-Z6 are as defined elsewhere herein. Also provided herein is a compound of formula II: Or a pharmaceutically acceptable derivative thereof, wherein R 1-R4、R6、R7, a, het, X and Z 1-Z6 are as defined elsewhere herein. Also provided herein is a compound of formula III: Or a pharmaceutically acceptable derivative thereof, wherein R 1-R4、R6、R7, a, het, X and Z 1-Z6 are as defined elsewhere herein. Also provided are pharmaceutical compositions containing a compound of formula I, II or III and a pharmaceutically acceptable excipient. In one embodiment, a compound of formula I, II or III provided herein inhibits one or more of the MYST family of lysine acetyltransferases. In another embodiment, a compound provided herein inhibits KAT6A. In another embodiment, the compounds provided herein are covalent inhibitors of KAT6A. Without being bound by any theory, in one embodiment, the compounds provided herein inhibit KAT6A by covalent modification of a cysteine residue at or near the Ac-CoA binding site. In another embodiment, the compounds provided herein are non-covalent inhibitors of KAT6A. In other embodiments, methods of treating hyperproliferative diseases by administering a compound or composition provided herein are provided. In one embodiment, the hyperproliferative disease is cancer. In another embodiment, the cancer is breast cancer, lung cancer, ovarian cancer, colon cancer, prostate cancer, uterine/cervical cancer, or leukemia. In another embodiment of the methods provided herein, the compounds of formula I are used as a single agent or in combination with standard-of-care treatment for a particular cancer. In another embodiment, methods of inhibiting MYST enzyme