ID: ALA1614712

Max Phase: Preclinical

Molecular Formula: C27H29N5O

Molecular Weight: 439.56

Molecule Type: Small molecule

Representations

Canonical SMILES:  Nc1ncnc2c1c(-c1cccc(OCc3ccccc3)c1)cn2[C@H]1C[C@@H](CN2CCC2)C1

Standard InChI:  InChI=1S/C27H29N5O/c28-26-25-24(21-8-4-9-23(14-21)33-17-19-6-2-1-3-7-19)16-32(27(25)30-18-29-26)22-12-20(13-22)15-31-10-5-11-31/h1-4,6-9,14,16,18,20,22H,5,10-13,15,17H2,(H2,28,29,30)/t20-,22+

Standard InChI Key:  AECDBHGVIIRMOI-GRGXKFILSA-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: 439.56

Molecular Weight (Monoisotopic): 439.2372

AlogP: 4.92

#Rotatable Bonds: 7

Polar Surface Area: 69.20

Molecular Species: BASE

HBA: 6

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 9.31

CX LogP: 4.15

CX LogD: 2.22

Aromatic Rings: 4

Heavy Atoms: 33

QED Weighted: 0.44

Np Likeness Score: -0.69

References

1. Stauffer F, Cowan-Jacob SW, Scheufler C, Furet P..  (2016)  Identification of a 5-[3-phenyl-(2-cyclic-ether)-methylether]-4-aminopyrrolo[2,3-d]pyrimidine series of IGF-1R inhibitors.,  26  (8): [PMID:26951750] [10.1016/j.bmcl.2016.02.074]

2. Fairhurst RA, Marsilje TH, Stutz S, Boos A, Niklaus M, Chen B, Jiang S, Lu W, Furet P, McCarthy C, Stauffer F, Guagnano V, Vaupel A, Michellys PY, Schnell C, Jeay S..  (2016)  Optimisation of a 5-[3-phenyl-(2-cyclic-ether)-methyl-ether]-4-aminopyrrolopyrimidine series of IGF-1R inhibitors.,  26  (8): [PMID:26951753] [10.1016/j.bmcl.2016.02.075]

3. Doris A.Schuetz, Wilhelmus Egbertus Arnout de Witte, Yin Cheong Wong, Bernhard Knasmueller, Lars Richter, Daria B. Kokh, S. Kashif Sadiq, Reggie Bosma, Indira Nederpelt, Laura H. Heitman, Elena Segala, Marta Amaral, Dong Guo, Dorothee Andres, Victoria Georgi, Leigh A. Stoddart, Steve Hill, Robert M. Cooke, Chris De Graaf, Rob Leurs, Matthias Frech, Rebecca C. Wade, Elizabeth Cunera Mariade Lange, Adriaan P. IJzerman, Anke Müller-Fahrnow, Gerhard F. Ecker. K4DD drug target binding kinetics data,  [10.6019/CHEMBL3885741]

4. Talele TT..  (2018)  Natural-Products-Inspired Use of the gem-Dimethyl Group in Medicinal Chemistry.,  61  (6): [PMID:28850227] [10.1021/acs.jmedchem.7b00315]

5. Gao Y, Ye DY, Zhou WC, Chu Y..  (2017)  The discovery of novel benzothiazinones as highly selective non-ATP competitive glycogen synthase kinase 3β inhibitors for the treatment of ovarian cancer.,  135  [PMID:28460311] [10.1016/j.ejmech.2017.04.039]

6. Zhang Q, Shen Q, Gao L, Tong L, Li J, Chen Y, Lu W..  (2018)  Pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR.,  158  [PMID:30241010] [10.1016/j.ejmech.2018.09.032]

7. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]

8. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]

9. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]

10. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

11. Gao D, Jin N, Fu Y, Zhu Y, Wang Y, Wang T, Chen Y, Zhang M, Xiao Q, Huang M, Li Y..  (2021)  Rational drug design of benzothiazole-based derivatives as potent signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitors.,  216  [PMID:33689932] [10.1016/j.ejmech.2021.113333]

12. Turvey SJ, McPhillie MJ, Kearney MT, Muench SP, Simmons KJ, Fishwick CWG..  (2022)  Recent developments in the structural characterisation of the IR and IGF1R: implications for the design of IR-IGF1R hybrid receptor modulators.,  13  (4.0): [PMID:35647546] [10.1039/d1md00300c]

13. Wu RZ, Zhou HY, Song JF, Xia QH, Hu W, Mou XD, Li X..  (2021)  Chemotherapeutics for Toxoplasma gondii: Molecular Biotargets, Binding Modes, and Structure-Activity Relationship Investigations.,  64  (24.0): [PMID:34894691] [10.1021/acs.jmedchem.1c01569]

14. Chen X, Huang Y, Xu W, Cai Y, Yang Y..  (2022)  4-Aminopyrazolopyrimidine scaffold and its deformation in the design of tyrosine and serine/threonine kinase inhibitors in medicinal chemistry.,  13  (9.0): [PMID:36324498] [10.1039/d2md00139j]

Source

Source(4):

• Scientific Literature
• K4DD Project
• SARS-CoV-2 Screening Data 2020-21
• Fraunhofer HDAC6