(R)-2-(4'-((4-(4-fluorobenzoyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid

ID: ALA468722

PubChem CID: 11613810

Max Phase: Preclinical

Molecular Formula: C31H28FNO6S

Molecular Weight: 561.63

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC(C)[C@@H](NS(=O)(=O)c1ccc(-c2ccc(COc3ccc(C(=O)c4ccc(F)cc4)cc3)cc2)cc1)C(=O)O

Standard InChI:  InChI=1S/C31H28FNO6S/c1-20(2)29(31(35)36)33-40(37,38)28-17-11-23(12-18-28)22-5-3-21(4-6-22)19-39-27-15-9-25(10-16-27)30(34)24-7-13-26(32)14-8-24/h3-18,20,29,33H,19H2,1-2H3,(H,35,36)/t29-/m1/s1

Standard InChI Key:  ZHXMXRVBOZWQPF-GDLZYMKVSA-N

Molfile:  

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M  END

Alternative Forms

1. Parent:

   

   ALA468722

   (R)-2-(4''-((4-(4-fluorobenzoyl)phenoxy)methyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 561.63

Molecular Weight (Monoisotopic): 561.1621

AlogP: 5.69

#Rotatable Bonds: 11

Polar Surface Area: 109.77

Molecular Species: ACID

HBA: 5

HBD: 2

#RO5 Violations: 2

HBA (Lipinski): 7

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.34

CX Basic pKa: ┄

CX LogP: 6.55

CX LogD: 3.13

Aromatic Rings: 4

Heavy Atoms: 40

QED Weighted: 0.23

Np Likeness Score: -0.86

References

1. Hopper DW, Vera MD, How D, Sabatini J, Xiang JS, Ipek M, Thomason J, Hu Y, Feyfant E, Wang Q, Georgiadis KE, Reifenberg E, Sheldon RT, Keohan CC, Majumdar MK, Morris EA, Skotnicki J, Sum PE..  (2009)  Synthesis and biological evaluation of ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides: a class of potent aggrecanase-1 inhibitors.,  19  (9): [PMID:19329309] [10.1016/j.bmcl.2009.03.056]

2. Xiang, Jason S JS and 12 more authors.  2006-01-15  Synthesis and biological evaluation of biphenylsulfonamide carboxylate aggrecanase-1 inhibitors.  [PMID:16275085]

3. Hopper, Darrin W DW and 17 more authors.  2009-05-01  Synthesis and biological evaluation of ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides: a class of potent aggrecanase-1 inhibitors.  [PMID:19329309]

4. De Savi, Chris C and 13 more authors.  2011-03-01  The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis.  [PMID:21300546]

5. Shiozaki, Makoto M and 24 more authors.  2011-04-28  Discovery of (1S,2R,3R)-2,3-dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates: novel and highly selective aggrecanase inhibitors.  [PMID:21417219]

6. De Savi, Chris C and 11 more authors.  2011-06-01  Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis.  [PMID:21536437]

7. Deng, Hongfeng H and 24 more authors.  2012-08-23  Discovery of highly potent and selective small molecule ADAMTS-5 inhibitors that inhibit human cartilage degradation via encoded library technology (ELT).  [PMID:22891645]

8. Nuti, Elisa E and 14 more authors.  2013-04  Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: synthesis and biological evaluation.  [PMID:23376997]

9. Maingot, Lucie L and 12 more authors.  2013-11  Aggrecanase-2 inhibitors based on the acylthiosemicarbazide zinc-binding group.  [PMID:24044937]

10. Durham, Timothy B TB and 13 more authors.  2014-12-26  Identification of potent and selective hydantoin inhibitors of aggrecanase-1 and aggrecanase-2 that are efficacious in both chemical and surgical models of osteoarthritis.  [PMID:25415648]

11. Ding, Yun Y and 13 more authors.  2015-08-13  Discovery of Potent and Selective Inhibitors for ADAMTS-4 through DNA-Encoded Library Technology (ELT).  [PMID:26288689]

12. Durham, Timothy B TB and 10 more authors.  2017-07-13  A Highly Selective Hydantoin Inhibitor of Aggrecanase-1 and Aggrecanase-2 with a Low Projected Human Dose.  [PMID:28613895]

Source

Source(1):

• Scientific Literature