2-[1-(Hydroxycarbamoylmethyl-carbamoyl)-2-methyl-propylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester

ID: ALA2369423

PubChem CID: 73349980

Max Phase: Preclinical

Molecular Formula: C20H28N4O6

Molecular Weight: 420.47

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC(C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)OCc1ccccc1)C(=O)NCC(=O)NO

Standard InChI:  InChI=1S/C20H28N4O6/c1-13(2)17(19(27)21-11-16(25)23-29)22-18(26)15-9-6-10-24(15)20(28)30-12-14-7-4-3-5-8-14/h3-5,7-8,13,15,17,29H,6,9-12H2,1-2H3,(H,21,27)(H,22,26)(H,23,25)/t15-,17-/m0/s1

Standard InChI Key:  QXJNOQBVVDSYDO-RDJZCZTQSA-N

Molfile:  

     RDKit          2D

 30 31  0  0  0  0  0  0  0  0999 V2000
    0.0802   -0.4954    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.5484   -0.5724    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0913   -1.3024    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2628   -0.1599    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.8339   -0.1599    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9773   -0.5724    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6918   -0.1599    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8352   -0.5724    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4062   -0.5724    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8759   -1.5574    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.5484   -1.3974    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.5218   -1.8545    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.6918    0.6651    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.8352   -1.3974    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.1207   -0.1599    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5497   -0.1599    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.9773   -1.3974    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4718    0.1176    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0475   -2.3643    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2641   -0.5724    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.7477    0.6606    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8321   -2.6193    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0593    0.8321    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6918   -1.8099    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2628   -1.8099    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4452   -2.0672    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0036   -3.4262    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7882   -3.6812    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2298   -2.3222    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4013   -3.1291    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  5  2  1  1
  3  1  1  0
  4  2  1  0
  5  1  1  0
  6  4  1  0
  7  6  1  0
  8 15  1  0
  9  7  1  0
 10  3  1  0
 11  2  2  0
 12  3  2  0
 13  7  2  0
 14  8  2  0
 15  9  1  0
 16  8  1  0
  6 17  1  6
 18  1  1  0
 19 10  1  0
 20 16  1  0
 21  5  1  0
 22 19  1  0
 23 18  1  0
 24 17  1  0
 25 17  1  0
 26 22  2  0
 27 22  1  0
 28 27  2  0
 29 26  1  0
 30 28  1  0
 21 23  1  0
 30 29  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA2369423

   2-[1-(Hydroxycarbamoylmethyl-carbamoyl)-2-methyl-propylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester

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: 420.47

Molecular Weight (Monoisotopic): 420.2009

AlogP: 0.55

#Rotatable Bonds: 8

Polar Surface Area: 137.07

Molecular Species: NEUTRAL

HBA: 6

HBD: 4

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 8.75

CX Basic pKa: ┄

CX LogP: 0.29

CX LogD: 0.27

Aromatic Rings: 1

Heavy Atoms: 30

QED Weighted: 0.36

Np Likeness Score: -0.82

References

1. Bihovsky R, Levinson BL, Loewi RC, Erhardt PW, Polokoff MA..  (1995)  Hydroxamic acids as potent inhibitors of endothelin-converting enzyme from human bronchiolar smooth muscle.,  38  (12): [PMID:7783143] [10.1021/jm00012a011]

2. Umekawa, K K and 5 more authors.  2000-09  Pharmacological characterization of a novel sulfonylureid-pyrazole derivative, SM-19712, a potent nonpeptidic inhibitor of endothelin converting enzyme.  [PMID:11043447]

3. Inguimbert, Nicolas N and 6 more authors.  2002-03-28  Toward an optimal joint recognition of the S1' subsites of endothelin converting enzyme-1 (ECE-1), angiotensin converting enzyme (ACE), and neutral endopeptidase (NEP).  [PMID:11906289]

4. Berger, Yann Y and 6 more authors.  2005-01-27  Endothelin-converting enzyme-1 inhibition and growth of human glioblastoma cells.  [PMID:15658862]

5. Seed, Alison A and 8 more authors.  2012-10-15  The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans.  [PMID:22480515]

6. McKinnell, R Murray RM and 13 more authors.  2019-01-10  Discovery of TD-0212, an Orally Active Dual Pharmacology AT1 Antagonist and Neprilysin Inhibitor (ARNI).  [PMID:30655952]

Source

Source(1):

• Scientific Literature