2-[4-(2,3-Dioxo-2,3-dihydroindol-1-ylmethyl)benzyl]isothiourea hydrobromide

ID: ALA4778505

PubChem CID: 155235371

Max Phase: Preclinical

Molecular Formula: C17H16BrN3O2S

Molecular Weight: 325.39

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Br.N=C(N)SCc1ccc(CN2C(=O)C(=O)c3ccccc32)cc1

Standard InChI:  InChI=1S/C17H15N3O2S.BrH/c18-17(19)23-10-12-7-5-11(6-8-12)9-20-14-4-2-1-3-13(14)15(21)16(20)22;/h1-8H,9-10H2,(H3,18,19);1H

Standard InChI Key:  IUSQIVICVSUMRQ-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 24 25  0  0  0  0  0  0  0  0999 V2000
    8.8447   -2.8478    0.0000 Br  0  0  0  0  0  0  0  0  0  0  0  0
    2.4708   -2.0760    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4696   -2.8955    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1777   -3.3045    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1759   -1.6671    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8845   -2.0724    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8848   -2.8955    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6677   -3.1497    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.1515   -2.4836    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6673   -1.8178    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9196   -1.0405    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.9687   -2.4833    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.9205   -3.9268    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.7199   -4.0965    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9700   -4.8732    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.7686   -5.0430    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3162   -4.4353    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0596   -3.6549    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2617   -3.4887    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1158   -4.6039    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3695   -5.3807    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    9.1691   -5.5493    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.4229   -6.3261    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.7150   -4.9411    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  2  3  2  0
  3  4  1  0
  4  7  2  0
  6  5  2  0
  5  2  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  1  0
 10  6  1  0
 10 11  2  0
  9 12  2  0
  8 13  1  0
 13 14  1  0
 14 15  2  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 14  1  0
 17 20  1  0
 20 21  1  0
 21 22  1  0
 22 23  1  0
 22 24  2  0
M  END

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 325.39

Molecular Weight (Monoisotopic): 325.0885

AlogP: 2.54

#Rotatable Bonds: 4

Polar Surface Area: 87.25

Molecular Species: BASE

HBA: 4

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 5

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 10.54

CX LogP: 2.60

CX LogD: 0.26

Aromatic Rings: 2

Heavy Atoms: 23

QED Weighted: 0.51

Np Likeness Score: -0.92

References

1. Dinavahi,SS.; Gowda,R.; Bazewicz,CG.; Battu,MB.; Lin,JM.; Chitren,RJ.; Pandey,MK.; Amin,S.; Robertson,GP.; Gowda,K..  (2020)  Design, synthesis characterization and biological evaluation of novel multi-isoform ALDH inhibitors as potential anticancer agents.,  187  [PMID:31887569] [10.1016/j.ejmech.2019.111962]

2. Duveau, Damien Y DY and 9 more authors.  2014-01-15  Structure-activity relationship studies and biological characterization of human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase inhibitors.  [PMID:24360556]

3. Kimble-Hill, Ann C AC, Parajuli, Bibek B, Chen, Che-Hong CH, Mochly-Rosen, Daria D and Hurley, Thomas D TD.  2014-02-13  Development of selective inhibitors for aldehyde dehydrogenases based on substituted indole-2,3-diones.  [PMID:24444054]

4. Morgan, Cynthia A CA and Hurley, Thomas D TD.  2015-02-26  Characterization of two distinct structural classes of selective aldehyde dehydrogenase 1A1 inhibitors.  [PMID:25634381]

5. Buchman, Cameron D and Hurley, Thomas D.  2017-03-23  Inhibition of the Aldehyde Dehydrogenase 1/2 Family by Psoralen and Coumarin Derivatives.  [PMID:28219011]

6. Yang, Shyh-Ming SM and 19 more authors.  2018-06-14  Discovery of Orally Bioavailable, Quinoline-Based Aldehyde Dehydrogenase 1A1 (ALDH1A1) Inhibitors with Potent Cellular Activity.  [PMID:29767973]

7. Huddle, Brandt C BC and 15 more authors.  2018-10-11  Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy.  [PMID:30221940]

8. Liang, Dailin and 6 more authors.  2020-02-01  Discovery of coumarin-based selective aldehyde dehydrogenase 1A1 inhibitors with glucose metabolism improving activity.  [PMID:31816557]

9. Dinavahi, Saketh S and 9 more authors.  2020-02-01  Design, synthesis characterization and biological evaluation of novel multi-isoform ALDH inhibitors as potential anticancer agents.  [PMID:31887569]

10. Huddle, Brandt C and 16 more authors.  2021-02-05  Development of 2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of aldehyde dehydrogenase 1A (ALDH1A) as potential adjuncts to ovarian cancer chemotherapy.  [PMID:33341649]

Source

Source(1):

• Scientific Literature