3-(3-(4-(4-(2H-Tetrazole-5-yl)phenoxy)butoxy)-4-methoxyphenyl)-1-cycloheptyl-4,4-dimethyl-1H-pyrazol-5(4H)-one

ID: ALA2171452

Chembl Id: CHEMBL2171452

Cas Number: 1403598-56-0

PubChem CID: 71460703

Max Phase: Preclinical

Molecular Formula: C30H38N6O4

Molecular Weight: 546.67

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  COc1ccc(C2=NN(C3CCCCCC3)C(=O)C2(C)C)cc1OCCCCOc1ccc(-c2nn[nH]n2)cc1

Standard InChI:  InChI=1S/C30H38N6O4/c1-30(2)27(33-36(29(30)37)23-10-6-4-5-7-11-23)22-14-17-25(38-3)26(20-22)40-19-9-8-18-39-24-15-12-21(13-16-24)28-31-34-35-32-28/h12-17,20,23H,4-11,18-19H2,1-3H3,(H,31,32,34,35)

Standard InChI Key:  JPXAIORZGBCHIB-UHFFFAOYSA-N

Alternative Forms

1. Parent:

   

   ALA2171452

   Dnmt3A-IN-1

Molecule Features

Natural Product: Yes

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: 546.67

Molecular Weight (Monoisotopic): 546.2955

AlogP: 5.41

#Rotatable Bonds: 11

Polar Surface Area: 114.82

Molecular Species: ACID

HBA: 8

HBD: 1

#RO5 Violations: 2

HBA (Lipinski): 10

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 5.97

CX Basic pKa: 1.13

CX LogP: 6.35

CX LogD: 5.15

Aromatic Rings: 3

Heavy Atoms: 40

QED Weighted: 0.25

Np Likeness Score: -0.55

References

1. Orrling KM, Jansen C, Vu XL, Balmer V, Bregy P, Shanmugham A, England P, Bailey D, Cos P, Maes L, Adams E, van den Bogaart E, Chatelain E, Ioset JR, van de Stolpe A, Zorg S, Veerman J, Seebeck T, Sterk GJ, de Esch IJ, Leurs R..  (2012)  Catechol pyrazolinones as trypanocidals: fragment-based design, synthesis, and pharmacological evaluation of nanomolar inhibitors of trypanosomal phosphodiesterase B1.,  55  (20): [PMID:22963052] [10.1021/jm301059b]

2. MMV Pathogen Box,  [10.6019/CHEMBL3637841]

3. Nathan group, Weill Cornell Medical College; Barry Lab, NIAID NIH; Winzeler lab, UCSD; Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Univ. of Antwerp; London School of Hygiene and Tropical Medicine; Parasite Chemotherapy Unit at Swiss Tropical and Public Health Institute; Huston group at the University of Vermont; Castellanos group at UTMB, Galveston, Texas; Sakanari Lab, Univ. of Calif. San Francisco; Townson (Simon) Lab, Imperial College London; Fidelis Cho-Ngwa Lab, University of Buea, Buea, Cameroon; Laboratory of Molecular Parasitology at the New York Blood Center; Bickle Lab, London School of Hygiene and Tropical Medicine; Keiser Lab, Swiss Tropical and Public Health Institute; Caffrey group at the Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego; University of Cape Town; Shanmugam group at CSIR-National Chemical Laboratory, Pune (India); Novartis Institute for Tropical Disease-Singapore; Abbvie. MMV Pathogen Box Bioactivity Data,  [10.6019/CHEMBL3832761]

4. Anna Ehmann. The Australian National University Dept Of Immunology Pathogen Box Compounds Screened,  [10.6019/CHEMBL3987221]

5. Veale CGL, Hoppe HC..  (2018)  Screening of the Pathogen Box reveals new starting points for anti-trypanosomal drug discovery.,  9  (12): [PMID:30647879] [10.1039/C8MD00319J]

6. Sarink, M; Mykytyn, A; Tielens, A; van Hellemond, J. Naegleria gruberi Pathogen Box compounds screening,  [10.6019/CHEMBL4513101]

7. Johannes Zuegg, Alysha Elliott, Maite Amado, Emma Cowie, Ali Hinton, Geraldine Kaeslin, Angela Kavanagh, Anne Kunert, Gabriell Lowe, Soumya Ramu, Janet Reid, Robin Trauer, Mathilde Desselle, Ruth Neale, Karl Hansford, Mark Blascovich, Matthew Cooper. CO-ADD screening of MMV (CH) - MMV compounds,  [10.6019/CHEMBL4513149]

8. Huang S, Stillson NJ, Sandoval JE, Yung C, Reich NO..  (2021)  A novel class of selective non-nucleoside inhibitors of human DNA methyltransferase 3A.,  40  [PMID:33705897] [10.1016/j.bmcl.2021.127908]

9. Sandoval JE, Ramabadran R, Stillson N, Sarah L, Fujimori DG, Goodell MA, Reich N..  (2022)  First-in-Class Allosteric Inhibitors of DNMT3A Disrupt Protein-Protein Interactions and Induce Acute Myeloid Leukemia Cell Differentiation.,  65  (15.0): [PMID:35866897] [10.1021/acs.jmedchem.2c00725]

Source

Source(3):

• Scientific Literature
• MMV Pathogen Box
• CO-ADD antimicrobial screening data