(2R,5R)-1-[4-(3-Fluoro-2-methyl-benzyloxy)-benzenesulfonyl]-5-hydroxy-3,3-dimethyl-piperidine-2-carboxylic acid hydroxyamide

ID: ALA189216

PubChem CID: 44399712

Max Phase: Preclinical

Molecular Formula: C22H27FN2O6S

Molecular Weight: 466.53

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1c(F)cccc1COc1ccc(S(=O)(=O)N2C[C@H](O)CC(C)(C)[C@@H]2C(=O)NO)cc1

Standard InChI:  InChI=1S/C22H27FN2O6S/c1-14-15(5-4-6-19(14)23)13-31-17-7-9-18(10-8-17)32(29,30)25-12-16(26)11-22(2,3)20(25)21(27)24-28/h4-10,16,20,26,28H,11-13H2,1-3H3,(H,24,27)/t16-,20+/m1/s1

Standard InChI Key:  QEWCDBOSGBDOOY-UZLBHIALSA-N

Molfile:  

     RDKit          2D

 32 34  0  0  1  0  0  0  0  0999 V2000
    2.9542   -2.3500    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    2.9542   -3.1792    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.2417   -3.5917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2375   -4.4167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5250   -3.1792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6792   -3.5917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9625   -1.5250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7792   -2.3417    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.1292   -2.3417    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.1292    1.3500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9542   -4.8292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5292   -2.3542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.6750   -4.4167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4125    0.9458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8375    0.9333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8125   -3.5875    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.7042    1.3583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2542   -1.1042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6792   -1.1167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9792    0.9583    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.9792    0.1333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5542    1.3458    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    2.2292   -5.2417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4125   -4.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6875   -0.2917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2542   -0.2792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0917   -3.1750    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.3875   -4.8375    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.1125   -0.3000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1292    2.1750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4042    0.1208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8292    0.1083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  3  2  1  0
  4  3  1  0
  3  5  1  6
  6  2  1  0
  7  1  1  0
  8  1  2  0
  9  1  2  0
 10 14  1  0
 11 13  1  0
 12  5  2  0
 13  6  1  0
 14 17  1  0
 15 10  2  0
 16  5  1  0
 17 20  1  0
 18  7  2  0
 19  7  1  0
 20 21  1  0
 21 25  1  0
 22 15  1  0
 23  4  1  0
 24  4  1  0
 25 19  2  0
 26 18  1  0
 27 16  1  0
 13 28  1  6
 29 31  1  0
 30 10  1  0
 31 14  2  0
 32 29  2  0
 26 21  2  0
 11  4  1  0
 32 15  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA189216

   (2R,5R)-1-[4-(3-Fluoro-2-methyl-benzyloxy)-benzenesulfonyl]-5-hydroxy-3,3-dimethyl-piperidine-2-carboxylic acid hydroxyamide

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: 466.53

Molecular Weight (Monoisotopic): 466.1574

AlogP: 2.37

#Rotatable Bonds: 6

Polar Surface Area: 116.17

Molecular Species: NEUTRAL

HBA: 6

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 8.71

CX Basic pKa: ┄

CX LogP: 2.65

CX LogD: 2.63

Aromatic Rings: 2

Heavy Atoms: 32

QED Weighted: 0.44

Np Likeness Score: -0.72

References

1. Noe MC, Natarajan V, Snow SL, Mitchell PG, Lopresti-Morrow L, Reeves LM, Yocum SA, Carty TJ, Barberia JA, Sweeney FJ, Liras JL, Vaughn M, Hardink JR, Hawkins JM, Tokar C..  (2005)  Discovery of 3,3-dimethyl-5-hydroxypipecolic hydroxamate-based inhibitors of aggrecanase and MMP-13.,  15  (11): [PMID:15911259] [10.1016/j.bmcl.2005.03.105]

2.  (2001)  Selective inhibitors of aggrecanase in osteoarthritis treatment, 

Source

Source(2):

• Scientific Literature
• Patent Bioactivity Data