ID: ALA595134

Max Phase: Preclinical

Molecular Formula: C19H13N3OS

Molecular Weight: 331.40

Molecule Type: Small molecule

Representations

Canonical SMILES:  N#CC1=C2C(=NC1=O)c1cccc3c(N4CCSCC4)ccc2c13

Standard InChI:  InChI=1S/C19H13N3OS/c20-10-14-17-12-4-5-15(22-6-8-24-9-7-22)11-2-1-3-13(16(11)12)18(17)21-19(14)23/h1-5H,6-9H2

Standard InChI Key:  BRPRPURMGRJSHP-UHFFFAOYSA-N

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

Properties

Molecular Weight: 331.40

Molecular Weight (Monoisotopic): 331.0779

AlogP: 3.01

#Rotatable Bonds: 1

Polar Surface Area: 56.46

Molecular Species: NEUTRAL

HBA: 4

HBD: 0

#RO5 Violations: 0

HBA (Lipinski): 4

HBD (Lipinski): 0

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 3.05

CX LogP: 2.45

CX LogD: 2.45

Aromatic Rings: 2

Heavy Atoms: 24

QED Weighted: 0.81

Np Likeness Score: -1.07

References

1. Xie L, Xiao Y, Wang F, Xu Y, Qian X, Zhang R, Cui J, Liu J..  (2009)  Novel acenaphtho[1,2-b]pyrrole-carboxylic acid family: synthesis, cytotoxicity, DNA-binding and cell cycle evaluation.,  17  (21): [PMID:19815418] [10.1016/j.bmc.2009.02.031]

2. Zhang Z, Wu G, Xie F, Song T, Chang X..  (2011)  3-Thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (S1) based molecules as potent, dual inhibitors of B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1): structure-based design and structure-activity relationship studies.,  54  (4): [PMID:21235240] [10.1021/jm101181u]

3. Zhang Z, Yang H, Wu G, Li Z, Song T, Li XQ..  (2011)  Probing the difference between BH3 groove of Mcl-1 and Bcl-2 protein: Implications for dual inhibitors design.,  46  (9): [PMID:21684048] [10.1016/j.ejmech.2011.05.062]

4. Song T, Li X, Chang X, Liang X, Zhao Y, Wu G, Xie S, Su P, Wu Z, Feng Y, Zhang Z..  (2013)  3-Thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-xL and Mcl-1.,  21  (1): [PMID:23206987] [10.1016/j.bmc.2012.11.008]

5. Zhang Z, Liu C, Li X, Song T, Wu Z, Liang X, Zhao Y, Shen X, Chen H..  (2013)  Fragment-based design, synthesis, and biological evaluation of N-substituted-5-(4-isopropylthiophenol)-2-hydroxynicotinamide derivatives as novel Mcl-1 inhibitors.,  60  [PMID:23314054] [10.1016/j.ejmech.2012.12.016]

6. Zhang Z, Song T, Li X, Wu Z, Feng Y, Xie F, Liu C, Qin J, Chen H..  (2013)  Novel soluble myeloid cell leukemia sequence 1 (Mcl-1) inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g) developed using a fragment-based approach.,  59  [PMID:23220642] [10.1016/j.ejmech.2012.10.050]

7. Mark Wenlock and Nicholas Tomkinson. Experimental in vitro DMPK and physicochemical data on a set of publicly disclosed compounds,  [10.6019/CHEMBL3301361]

8. Yap JL, Chen L, Lanning ME, Fletcher S..  (2017)  Expanding the Cancer Arsenal with Targeted Therapies: Disarmament of the Antiapoptotic Bcl-2 Proteins by Small Molecules.,  60  (3): [PMID:27749061] [10.1021/acs.jmedchem.5b01888]

Source

Source(2):

• Scientific Literature
• AstraZeneca Deposited Data