2-(2-Chlorophenyl)-10-(pyridin-3-ylmethyl)-2,3,8,9,10,11-hexahydro-1H-pyrazolo[4',3':3,4]pyrido[1,2-a][1,4]diazepine-1,5(7H)-dione hydrochloride

ID: ALA1927156

PubChem CID: 57390546

Max Phase: Preclinical

Molecular Formula: C22H21Cl2N5O2

Molecular Weight: 421.89

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cl.O=c1c2c3n(c(=O)cc2[nH]n1-c1ccccc1Cl)CCCN(Cc1cccnc1)C3

Standard InChI:  InChI=1S/C22H20ClN5O2.ClH/c23-16-6-1-2-7-18(16)28-22(30)21-17(25-28)11-20(29)27-10-4-9-26(14-19(21)27)13-15-5-3-8-24-12-15;/h1-3,5-8,11-12,25H,4,9-10,13-14H2;1H

Standard InChI Key:  ZZBWPWGBVSWJIP-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 31 34  0  0  0  0  0  0  0  0999 V2000
    2.4125   -1.7813    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -5.3172   -0.8530    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.7072   -1.5851    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.2683   -2.2868    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4396   -2.2575    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0517   -1.5206    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4929   -0.8221    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9997   -2.9578    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -3.2252   -1.4881    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7155   -2.1401    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7683   -0.8029    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9722   -1.0272    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9426   -1.8549    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2151   -2.2409    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5125   -1.8037    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3925    0.1175    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1163    0.7669    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8973    0.7629    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.1914   -0.6625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5408   -0.9779    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2743   -0.5857    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4112    0.1679    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0550   -0.0272    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.2173   -2.1930    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2925    1.4368    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9064    2.1160    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1259    2.1186    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2601    2.7969    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1351    3.4718    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9203    3.4640    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3028    2.7851    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 14 15  1  0
 15 20  1  0
  5  8  1  0
  4  5  2  0
  6  9  1  0
  9 10  1  0
  5  6  1  0
 10 13  1  0
 16 17  1  0
 17 18  1  0
 16 19  1  0
 20 21  1  0
 21 22  1  0
 22 18  1  0
 19 20  1  0
 12 11  1  0
 11 23  2  0
 11  9  1  0
 15 24  2  0
 12 13  1  0
 18 25  1  0
  3  4  1  0
 25 26  1  0
  6  7  2  0
 26 27  2  0
  7  2  1  0
 27 28  1  0
  2  3  2  0
 28 29  2  0
 12 21  2  0
 29 30  1  0
 13 14  2  0
 30 31  2  0
 31 26  1  0
M  END

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: 421.89

Molecular Weight (Monoisotopic): 421.1306

AlogP: 2.93

#Rotatable Bonds: 3

Polar Surface Area: 75.92

Molecular Species: ACID

HBA: 6

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 5.43

CX Basic pKa: 6.87

CX LogP: -0.10

CX LogD: -0.07

Aromatic Rings: 4

Heavy Atoms: 30

QED Weighted: 0.55

Np Likeness Score: -1.41

References

1. Gaggini F, Laleu B, Orchard M, Fioraso-Cartier L, Cagnon L, Houngninou-Molango S, Gradia A, Duboux G, Merlot C, Heitz F, Szyndralewiez C, Page P..  (2011)  Design, synthesis and biological activity of original pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives as novel dual Nox4/Nox1 inhibitors.,  19  (23): [PMID:22041175] [10.1016/j.bmc.2011.10.016]

2. Laleu, Benoît B and 11 more authors.  2010-11-11  First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis.  [PMID:20942471]

3. Gaggini, Francesca F and 11 more authors.  2011-12-01  Design, synthesis and biological activity of original pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives as novel dual Nox4/Nox1 inhibitors.  [PMID:22041175]

4. Aoyama, Tomonori and 11 more authors.  2012-12  Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent.  [PMID:22806357]

5. Lu, Jiamo and 16 more authors.  2017-11-01  Characterization of potent and selective iodonium-class inhibitors of NADPH oxidases.  [PMID:28709950]

Source

Source(1):

• Scientific Literature