Submission Details

EDJ-MED-827e7cb4
Molecule(s):
CS(=O)(=O)c1ccc2cncc(NC(=O)C3CNC(=O)c4ccc(Cl)cc43)c2c1

EDJ-MED-827e7cb4-1

CS(=O)(=O)c1ccc2cncc(NC(=O)C3CNC(=O)c4ccc(Cl)cc43)c2c1

3-aminopyridine-like Assayed Check Availability on Manifold View
CNS(=O)(=O)N1CC(C(=O)Nc2cncc3ccc(S(C)(=O)=O)cc23)c2cc(Cl)ccc2C1=O

EDJ-MED-827e7cb4-2

CNS(=O)(=O)N1CC(C(=O)Nc2cncc3ccc(S(C)(=O)=O)cc23)c2cc(Cl)ccc2C1=O

3-aminopyridine-like Ordered Check Availability on Manifold View
CNC(=O)CN1CC(C(=O)Nc2cncc3ccc(S(C)(=O)=O)cc23)c2cc(Cl)ccc2C1=O

EDJ-MED-827e7cb4-3
Duplicate of:
EDJ-MED-ce467fd5-1

CNC(=O)CN1CC(C(=O)Nc2cncc3ccc(S(C)(=O)=O)cc23)c2cc(Cl)ccc2C1=O

Duplicate Ugi Assayed Check Availability on Manifold View
CS(=O)(=O)c1ccc2cncc(NC(=O)C3CNC(=O)c4c(F)cc(F)cc43)c2c1

EDJ-MED-827e7cb4-4

CS(=O)(=O)c1ccc2cncc(NC(=O)C3CNC(=O)c4c(F)cc(F)cc43)c2c1

3-aminopyridine-like Assayed Check Availability on Manifold View
C[C@H]1NC(=O)c2ccc(Cl)cc2[C]1C(=O)Nc1cncc2ccc(S(C)(=O)=O)cc12

EDJ-MED-827e7cb4-5

C[C@H]1NC(=O)c2ccc(Cl)cc2[C]1C(=O)Nc1cncc2ccc(S(C)(=O)=O)cc12

3-aminopyridine-like Check Availability on Manifold View
CCC1(C(=O)Nc2cncc3ccc(S(C)(=O)=O)cc23)CNC(=O)c2ccc(Cl)cc21

EDJ-MED-827e7cb4-6

CCC1(C(=O)Nc2cncc3ccc(S(C)(=O)=O)cc23)CNC(=O)c2ccc(Cl)cc21

3-aminopyridine-like Assayed Check Availability on Manifold View
O=C1NCC(C(=O)Nc2cnc3ccccn23)c2cc(Cl)ccc21

EDJ-MED-827e7cb4-7

O=C1NCC(C(=O)Nc2cnc3ccccn23)c2cc(Cl)ccc21

3-aminopyridine-like Assayed Check Availability on Manifold View
COc1ccc2ncc(NC(=O)C3CNC(=O)c4ccc(Cl)cc43)n2c1

EDJ-MED-827e7cb4-8

COc1ccc2ncc(NC(=O)C3CNC(=O)c4ccc(Cl)cc43)n2c1

3-aminopyridine-like Check Availability on Manifold View
CS(=O)(=O)c1ccc2cncc(NC(=O)C3CN(S(=O)(=O)CC4(C#N)CCC4)C(=O)c4ccc(Cl)cc43)c2c1

EDJ-MED-827e7cb4-9

CS(=O)(=O)c1ccc2cncc(NC(=O)C3CN(S(=O)(=O)CC4(C#N)CCC4)C(=O)c4ccc(Cl)cc43)c2c1

Design Rationale:

Teaching from MIC-UNK-91acba05-1 and ALP-UNI-8d415491-5 is that the S2 isoquinolone and S1 isoquinoline improve metabolic stability, therefore combine and add in groups precedented to increase potency. Difluoro S2 substitution good for cell activity, S2 3-Me to test Castagnoli reaction (see https://pubs.acs.org/doi/abs/10.1021/cr8002714). Imidazopyridine and OMe imidazopyridine to see if stability is additive and if OMe increases potency of imidazopyridine in line with pKa.

Inspired By:
Discussion:

Contributor: Ed J Griffen, MedChemica Ltd - Fri, 28 May 2021 15:15:10 +0000