Submission Details

VLA-UNK-5d8210f0
Molecule(s):
CNC(=O)CN1Cc2c(F)cc(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)C1

VLA-UNK-5d8210f0-1

CNC(=O)CN1Cc2c(F)cc(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)C1

3-aminopyridine-like Check Availability on Manifold View
CNC(=O)CN1Cc2cc(F)c(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)C1

VLA-UNK-5d8210f0-2

CNC(=O)CN1Cc2cc(F)c(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)C1

3-aminopyridine-like Check Availability on Manifold View
CNC(=O)CN1Cc2c(F)cc(F)cc2C2(CCN(c3cncc4ccccc34)C2=O)C1

VLA-UNK-5d8210f0-3

CNC(=O)CN1Cc2c(F)cc(F)cc2C2(CCN(c3cncc4ccccc34)C2=O)C1

3-aminopyridine-like Check Availability on Manifold View
CNC(=O)CN1Cc2ccc(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)C1C(F)(F)F

VLA-UNK-5d8210f0-4

CNC(=O)CN1Cc2ccc(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)C1C(F)(F)F

3-aminopyridine-like Check Availability on Manifold View
CNC(=O)CN1Cc2ccc(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)C1C(F)F

VLA-UNK-5d8210f0-5

CNC(=O)CN1Cc2ccc(Cl)cc2C2(CCN(c3cncc4ccccc34)C2=O)C1C(F)F

3-aminopyridine-like Check Availability on Manifold View
Design Rationale:

Transformations to increase the half-life based on published MMPs in "Strategy for Extending Half-life in Drug Design and Its Significance" (DOI: 10.1021/acsmedchemlett.8b00018) and "Why Decreasing Lipophilicity Alone Is Often Not a Reliable Strategy for Extending IV Half-life (DOI:10.1021/acsmedchemlett.8b00047). Add non-metabolically liable lipophilicity to net improve half-life (by improving vol. of distribution by a bigger margin than clearance).

Inspired By:
Discussion:

Contributor: Vladas Oleinikovas - Fri, 07 Jan 2022 17:58:03 +0000