Submission Details

Molecule(s):
O=C(O)Cc1ccc(O)c(NC(=O)c2conc2CCl)c1

MAR-TRE-a78003aa-1

O=C(O)Cc1ccc(O)c(NC(=O)c2conc2CCl)c1

CC(=O)c1cc(Cl)sc1NC(=O)c1conc1CCl

MAR-TRE-a78003aa-2

CC(=O)c1cc(Cl)sc1NC(=O)c1conc1CCl

COC(=O)C(CBr)CNC(=O)c1conc1CCl

MAR-TRE-a78003aa-3

COC(=O)C(CBr)CNC(=O)c1conc1CCl

COc1ccc(O)c(NC(=O)c2conc2CCl)c1

MAR-TRE-a78003aa-5

COc1ccc(O)c(NC(=O)c2conc2CCl)c1

COc1ccc(NC(=O)c2conc2CCl)c(C(=O)O)c1

MAR-TRE-a78003aa-7

COc1ccc(NC(=O)c2conc2CCl)c(C(=O)O)c1

COc1ccc(OC)c(NC(=O)c2conc2CCl)c1

MAR-TRE-a78003aa-9

COc1ccc(OC)c(NC(=O)c2conc2CCl)c1

O=C(O)CC(NC(=O)c1conc1CCl)C(=O)O

MAR-TRE-a78003aa-12

O=C(O)CC(NC(=O)c1conc1CCl)C(=O)O

CCOC(=O)CNC(=O)CNC(=O)c1conc1CCl

MAR-TRE-a78003aa-14

CCOC(=O)CNC(=O)CNC(=O)c1conc1CCl

O=C(Nc1cc(F)c(F)cc1O)c1conc1CCl

MAR-TRE-a78003aa-21

O=C(Nc1cc(F)c(F)cc1O)c1conc1CCl

O=C(Nc1cc(F)cc(F)c1O)c1conc1CCl

MAR-TRE-a78003aa-25

O=C(Nc1cc(F)cc(F)c1O)c1conc1CCl

O=C(O)c1cc(F)ccc1NC(=O)c1conc1CCl

MAR-TRE-a78003aa-26

O=C(O)c1cc(F)ccc1NC(=O)c1conc1CCl

O=C(CCNC(=O)c1conc1CCl)c1ccccc1

MAR-TRE-a78003aa-29

O=C(CCNC(=O)c1conc1CCl)c1ccccc1

O=C(Nc1cc(F)cc(Cl)c1O)c1conc1CCl

MAR-TRE-a78003aa-31

O=C(Nc1cc(F)cc(Cl)c1O)c1conc1CCl

COC(=O)C(NC(=O)c1conc1CCl)C(=O)OC

MAR-TRE-a78003aa-33

COC(=O)C(NC(=O)c1conc1CCl)C(=O)OC

Nc1ccc(NC(=O)c2conc2CCl)c(C(=O)O)c1

MAR-TRE-a78003aa-35

Nc1ccc(NC(=O)c2conc2CCl)c(C(=O)O)c1

O=C(Nc1cc(F)cc(Br)c1O)c1conc1CCl

MAR-TRE-a78003aa-38

O=C(Nc1cc(F)cc(Br)c1O)c1conc1CCl

Cc1ccc(NC(=O)c2conc2CCl)c(C(=O)O)c1

MAR-TRE-a78003aa-42

Cc1ccc(NC(=O)c2conc2CCl)c(C(=O)O)c1

COc1ccc(NC(=O)c2conc2CCl)c(OC)c1

MAR-TRE-a78003aa-45

COc1ccc(NC(=O)c2conc2CCl)c(OC)c1

O=C(Nc1cccc(F)c1C(=O)O)c1conc1CCl

MAR-TRE-a78003aa-50

O=C(Nc1cccc(F)c1C(=O)O)c1conc1CCl

CCOC(=O)CC(=O)CNC(=O)c1conc1CCl

MAR-TRE-a78003aa-52

CCOC(=O)CC(=O)CNC(=O)c1conc1CCl

CSc1ccc(NC(=O)c2conc2CCl)c(C(=O)O)c1

MAR-TRE-a78003aa-53

CSc1ccc(NC(=O)c2conc2CCl)c(C(=O)O)c1

Nc1cccc(NC(=O)c2conc2CCl)c1C(=O)O

MAR-TRE-a78003aa-57

Nc1cccc(NC(=O)c2conc2CCl)c1C(=O)O

C=CCOC(=O)C(C)(C)NC(=O)c1conc1CCl

MAR-TRE-a78003aa-61

C=CCOC(=O)C(C)(C)NC(=O)c1conc1CCl

CCOC(=O)C(NC(=O)c1conc1CCl)C(C)=O

MAR-TRE-a78003aa-63

CCOC(=O)C(NC(=O)c1conc1CCl)C(C)=O

O=C(CCCNC(=O)c1conc1CCl)c1ccc(O)cc1

MAR-TRE-a78003aa-70

O=C(CCCNC(=O)c1conc1CCl)c1ccc(O)cc1

CC(=O)C(NC(=O)c1conc1CCl)C(=O)N(C)C

MAR-TRE-a78003aa-71

CC(=O)C(NC(=O)c1conc1CCl)C(=O)N(C)C

Nc1cc(Cl)c(O)c(NC(=O)c2conc2CCl)c1

MAR-TRE-a78003aa-74

Nc1cc(Cl)c(O)c(NC(=O)c2conc2CCl)c1

O=C(Nc1cccc(C(=O)O)c1O)c1conc1CCl

MAR-TRE-a78003aa-75

O=C(Nc1cccc(C(=O)O)c1O)c1conc1CCl

N=C(N)SCc1ccc(NC(=O)c2conc2CCl)cc1

MAR-TRE-a78003aa-77

N=C(N)SCc1ccc(NC(=O)c2conc2CCl)cc1

O=C(NCS(=O)(=O)c1ccccc1)c1conc1CCl

MAR-TRE-a78003aa-78

O=C(NCS(=O)(=O)c1ccccc1)c1conc1CCl

O=C(O)c1cc(Cl)ccc1NC(=O)c1conc1CCl

MAR-TRE-a78003aa-79

O=C(O)c1cc(Cl)ccc1NC(=O)c1conc1CCl

COC(=O)C(NC(=O)c1conc1CCl)C(C)=O

MAR-TRE-a78003aa-80

COC(=O)C(NC(=O)c1conc1CCl)C(C)=O

COC(=O)c1cc(Cl)ccc1NC(=O)c1conc1CCl

MAR-TRE-a78003aa-81

COC(=O)c1cc(Cl)ccc1NC(=O)c1conc1CCl

CC(=O)C(NC(=O)c1conc1CCl)C(C)=O

MAR-TRE-a78003aa-83

CC(=O)C(NC(=O)c1conc1CCl)C(C)=O

Nc1cc(Br)c(O)c(NC(=O)c2conc2CCl)c1

MAR-TRE-a78003aa-86

Nc1cc(Br)c(O)c(NC(=O)c2conc2CCl)c1

CCOC(=O)C(C)(C)NC(=O)c1conc1CCl

MAR-TRE-a78003aa-89

CCOC(=O)C(C)(C)NC(=O)c1conc1CCl

CC(=O)c1cc(Cl)ccc1NC(=O)c1conc1CCl

MAR-TRE-a78003aa-93

CC(=O)c1cc(Cl)ccc1NC(=O)c1conc1CCl


Design Rationale:

Chloroacetamides are well known inhibitors of cysteine proteases. This is set 3 of 6 novel ChloroMethyl- Heteroaromatics with commercially available R-group substituents which are predicted to bind to 6WNP using the THINK software (https://treweren.com). No detailed reactivity calculations have been completed at this time but it is expected that some of these series will show greater reactivity and more reversibility than chloroacetamides.

Other Notes:

SD files of the docked molecules are available. More series have been docked.

Discussion: