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

ID: ALA190415

PubChem CID: 44399341

Max Phase: Preclinical

Molecular Formula: C22H27FN2O6S

Molecular Weight: 466.53

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1cc(F)ccc1COc1ccc(S(=O)(=O)N2C[C@H](O)CC(C)(C)[C@@H]2C(=O)NO)cc1

Standard InChI:  InChI=1S/C22H27FN2O6S/c1-14-10-16(23)5-4-15(14)13-31-18-6-8-19(9-7-18)32(29,30)25-12-17(26)11-22(2,3)20(25)21(27)24-28/h4-10,17,20,26,28H,11-13H2,1-3H3,(H,24,27)/t17-,20+/m1/s1

Standard InChI Key:  LOMOBWUKCBVLNJ-XLIONFOSSA-N

Molfile:  

     RDKit          2D

 32 34  0  0  1  0  0  0  0  0999 V2000
    3.0292   -2.0292    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    3.0292   -2.8542    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.3167   -3.2667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3125   -4.0917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6000   -2.8542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7542   -3.2667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0375   -1.2042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8542   -2.0250    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.2042   -2.0250    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.0292   -4.5042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2042    1.6708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4875    1.2625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6042   -2.0292    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.7500   -4.1000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9125    1.2583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8875   -3.2667    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.7792    1.6833    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3292   -0.7875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7542   -0.7917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4792    0.4375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0542    1.2750    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.9042    0.4250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0542    0.4500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4875   -4.0917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3042   -4.9167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1875    0.0208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7625    0.0333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3292    0.0458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6167    0.0083    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    0.1667   -2.8542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.4625   -4.5167    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.2042    2.4958    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 12  1  0
 12 17  1  0
 13  5  2  0
 14  6  1  0
 15 11  2  0
 16  5  1  0
 17 21  1  0
 18  7  2  0
 19  7  1  0
 20 12  2  0
 21 23  1  0
 22 26  2  0
 23 27  1  0
 24  4  1  0
 25  4  1  0
 26 20  1  0
 27 19  2  0
 28 18  1  0
 29 22  1  0
 30 16  1  0
 14 31  1  6
 32 11  1  0
 28 23  2  0
 10  4  1  0
 22 15  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA190415

   (2R,5R)-1-[4-(4-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: -0.80

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