trans-benzyl (2-(4-(2-aminocyclopropyl)phenyl)amino)-2-oxoethyl)carbamate hydrochloride

ID: ALA3735379

PubChem CID: 127037635

Max Phase: Preclinical

Molecular Formula: C19H22ClN3O3

Molecular Weight: 339.40

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cl.N[C@@H]1C[C@H]1c1ccc(NC(=O)CNC(=O)OCc2ccccc2)cc1

Standard InChI:  InChI=1S/C19H21N3O3.ClH/c20-17-10-16(17)14-6-8-15(9-7-14)22-18(23)11-21-19(24)25-12-13-4-2-1-3-5-13;/h1-9,16-17H,10-12,20H2,(H,21,24)(H,22,23);1H/t16-,17+;/m0./s1

Standard InChI Key:  HQIILNNHFUOFMZ-MCJVGQIASA-N

Molfile:  

     RDKit          2D

 26 27  0  0  0  0  0  0  0  0999 V2000
   11.0195   -7.3569    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    3.8912   -5.2578    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.1894   -6.0109    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1873   -7.5117    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1470   -8.1099    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.4855   -8.2648    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.8933   -3.7570    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5951   -3.0039    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.9336   -3.1588    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.5973   -1.5031    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2990    0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990    0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4833   -9.7656    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7798  -10.5202    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7746  -12.0202    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4729  -12.7657    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1765  -12.0112    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1817  -10.5112    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4678  -14.2664    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.7117  -15.4703    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2117  -15.4779    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2574  -16.0664    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  2  3  1  0
  3  4  1  0
  4  5  2  0
  4  6  1  0
  2  7  1  0
  7  8  1  0
  7  9  2  0
  8 10  1  0
 10 11  1  0
 11 12  2  0
 12 13  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 16 11  1  0
  6 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 21 22  2  0
 22 17  1  0
 24 23  1  0
 25 24  1  0
 23 25  1  0
 23 20  1  1
 25 26  1  6
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: 339.40

Molecular Weight (Monoisotopic): 339.1583

AlogP: 2.37

#Rotatable Bonds: 6

Polar Surface Area: 93.45

Molecular Species: BASE

HBA: 4

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 13.26

CX Basic pKa: 9.62

CX LogP: 1.82

CX LogD: -0.35

Aromatic Rings: 2

Heavy Atoms: 25

QED Weighted: 0.75

Np Likeness Score: -0.79

References

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2. Liang, Yu Y and 5 more authors.  2013-02-05  A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency.  [PMID:23386436]

3. Zheng, Yi-Chao YC and 15 more authors.  2013-11-14  Triazole-dithiocarbamate based selective lysine specific demethylase 1 (LSD1) inactivators inhibit gastric cancer cell growth, invasion, and migration.  [PMID:24131029]

4. Sorna, Venkataswamy V and 6 more authors.  2013-12-12  High-throughput virtual screening identifies novel N'-(1-phenylethylidene)-benzohydrazides as potent, specific, and reversible LSD1 inhibitors.  [PMID:24237195]

5. Rotili, Dante D and 18 more authors.  2014-01-09  Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities.  [PMID:24325601]

6. Kumarasinghe, Isuru R IR and Woster, Patrick M PM.  2014-01-09  Synthesis and evaluation of novel cyclic Peptide inhibitors of lysine-specific demethylase 1.  [PMID:24883177]

7. Ma, Li-Ying LY and 17 more authors.  2015-02-26  Design, synthesis, and structure-activity relationship of novel LSD1 inhibitors based on pyrimidine-thiourea hybrids as potent, orally active antitumor agents.  [PMID:25610955]

8. Maes, Tamara T and 6 more authors.  2015  KDM1 histone lysine demethylases as targets for treatments of oncological and neurodegenerative disease.  [PMID:26111032]

9. Wu, Fangrui F and 6 more authors.  2016-01-14  3-(Piperidin-4-ylmethoxy)pyridine Containing Compounds Are Potent Inhibitors of Lysine Specific Demethylase 1.  [PMID:26652247]

10. Amano, Yuichi Y and 6 more authors.  2017-05-01  Development and crystallographic evaluation of histone H3 peptide with N-terminal serine substitution as a potent inhibitor of lysine-specific demethylase 1.  [PMID:28336409]

11. Li, Zhong-Hua ZH and 10 more authors.  2017-04-13  Discovery of [1,2,3]Triazolo[4,5-d]pyrimidine Derivatives as Novel LSD1 Inhibitors.  [PMID:28435523]

12. Mould, Daniel P DP and 11 more authors.  2017-10-12  Development of (4-Cyanophenyl)glycine Derivatives as Reversible Inhibitors of Lysine Specific Demethylase 1.  [PMID:28892629]

13. Mould, Daniel P and 7 more authors.  2017-10-15  Development and evaluation of 4-(pyrrolidin-3-yl)benzonitrile derivatives as inhibitors of lysine specific demethylase 1.  [PMID:28927796]

14. Sun, Kai K and 6 more authors.  2017-11-15  Discovery of tranylcypromine analogs with an acylhydrazone substituent as LSD1 inactivators: Design, synthesis and their biological evaluation.  [PMID:29037950]

15. and Abdel-Magid, Ahmed F AF.  2017-11-09  Lysine-Specific Demethylase 1 (LSD1) Inhibitors as Potential Treatment for Different Types of Cancers.  [PMID:29152043]

16. Schulz-Fincke, Johannes J and 15 more authors.  2018-01-20  Structure-activity studies on N-Substituted tranylcypromine derivatives lead to selective inhibitors of lysine specific demethylase 1 (LSD1) and potent inducers of leukemic cell differentiation.  [PMID:29247860]

17. Xu, Siyuan S and 6 more authors.  2018-09-15  Optimization of 5-arylidene barbiturates as potent, selective, reversible LSD1 inhibitors for the treatment of acute promyelocytic leukemia.  [PMID:30153955]

18. Nie, Zhe Z and 11 more authors.  2019-01-01  Structure-based design and discovery of potent and selective lysine-specific demethylase 1 (LSD1) inhibitors.  [PMID:30409536]

19. Duan, Yingchao Y and 7 more authors.  2018-12-15  Design, synthesis and in vitro evaluation of stilbene derivatives as novel LSD1 inhibitors for AML therapy.  [PMID:30448189]

20. Ma, Qi-Sheng QS and 6 more authors.  2019-01-15  Ligand-based design, synthesis and biological evaluation of xanthine derivatives as LSD1/KDM1A inhibitors.  [PMID:30472603]

21. Liu, Hong-Min HM and 10 more authors.  2019-08-01  Discovery and synthesis of novel indole derivatives-containing 3-methylenedihydrofuran-2(3H)-one as irreversible LSD1 inhibitors.  [PMID:31096156]

22. Holshouser, Steven S and 8 more authors.  2019-05-01  Dual inhibitors of LSD1 and spermine oxidase.  [PMID:31191868]

23. Romussi, Alessia and 19 more authors.  2020-05-14  Discovery of Reversible Inhibitors of KDM1A Efficacious in Acute Myeloid Leukemia Models.  [PMID:32435381]

24. Dai, Xing-Jie and 5 more authors.  2020-12-10  Tranylcypromine Based Lysine-Specific Demethylase 1 Inhibitor: Summary and Perspective.  [PMID:32931269]

25. Kanouni, Toufike and 18 more authors.  2020-12-10  Discovery of CC-90011: A Potent and Selective Reversible Inhibitor of Lysine Specific Demethylase 1 (LSD1).  [PMID:33034194]

26. Naveen Sadhu, M and 10 more authors.  2021-02-15  Novel dual LSD1/HDAC6 inhibitors for the treatment of multiple myeloma.  [PMID:33359604]

27. Mehndiratta, Samir and Liou, Jing-Ping.  2020-09-01  Histone lysine specific demethylase 1 inhibitors.  [PMID:33479691]

Source

Source(1):

• Scientific Literature