(R)-1-(2-(2-(4-(4-fluorobenzyl)-2-methylpiperazin-1-yl)-2-oxoethoxy)-5-chlorophenyl)urea

ID: ALA232656

Chembl Id: CHEMBL232656

Max Phase: Phase

Molecular Formula: C21H24ClFN4O3

Molecular Weight: 434.90

Molecule Type: Small molecule

Names and Identifiers

Synonyms: BX-471 | BX-741

Synonyms from Alternative Forms(7): Bx 471 | Bx-471 | Zk-811752 | BAY-86-5047 | BAY-865047 | BAY86-5047 | ZK811752

Canonical SMILES:  C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1NC(N)=O

Standard InChI:  InChI=1S/C21H24ClFN4O3/c1-14-11-26(12-15-2-5-17(23)6-3-15)8-9-27(14)20(28)13-30-19-7-4-16(22)10-18(19)25-21(24)29/h2-7,10,14H,8-9,11-13H2,1H3,(H3,24,25,29)/t14-/m1/s1

Standard InChI Key:  XQYASZNUFDVMFH-CQSZACIVSA-N

Alternative Forms

1. Parent:

   

   ALA232656

   BX 471 FREE BASE

2. Alternative Forms:

   

   ALA232656

   BX471 hydrochloride

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: 434.90

Molecular Weight (Monoisotopic): 434.1521

AlogP: 3.08

#Rotatable Bonds: 6

Polar Surface Area: 87.90

Molecular Species: NEUTRAL

HBA: 4

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.92

CX Basic pKa: 6.46

CX LogP: 2.57

CX LogD: 2.53

Aromatic Rings: 2

Heavy Atoms: 30

QED Weighted: 0.73

Np Likeness Score: -2.03

References

1. Brown MF, Bahnck KB, Blumberg LC, Brissette WH, Burrell SA, Driscoll JP, Fedeles F, Fisher MB, Foti RS, Gladue RP, Guzman-Martinez A, Hayward MM, Lira PD, Lillie BM, Lu Y, Lundquist GD, McElroy EB, McGlynn MA, Paradis TJ, Poss CS, Roache JH, Shavnya A, Shepard RM, Trevena KA, Tylaska LA..  (2007)  Piperazinyl CCR1 antagonists--optimization of human liver microsome stability.,  17  (11): [PMID:17383873] [10.1016/j.bmcl.2007.03.037]

2. Xie YF, Lake K, Ligsay K, Komandla M, Sircar I, Nagarajan G, Li J, Xu K, Parise J, Schneider L, Huang D, Liu J, Dines K, Sakurai N, Barbosa M, Jack R..  (2007)  Structure-activity relationships of novel, highly potent, selective, and orally active CCR1 antagonists.,  17  (12): [PMID:17446072] [10.1016/j.bmcl.2007.03.104]

3. Merritt JR, Liu J, Quadros E, Morris ML, Liu R, Zhang R, Jacob B, Postelnek J, Hicks CM, Chen W, Kimble EF, Rogers WL, O'Brien L, White N, Desai H, Bansal S, King G, Ohlmeyer MJ, Appell KC, Webb ML..  (2009)  Novel pyrrolidine ureas as C-C chemokine receptor 1 (CCR1) antagonists.,  52  (5): [PMID:19183043] [10.1021/jm801416q]

4. Pease J, Horuk R..  (2012)  Chemokine receptor antagonists.,  55  (22): [PMID:22931505] [10.1021/jm300682j]

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

6. 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]

7. Ortiz Zacarías NV, van Veldhoven JPD, Portner L, van Spronsen E, Ullo S, Veenhuizen M, van der Velden WJC, Zweemer AJM, Kreekel RM, Oenema K, Lenselink EB, Heitman LH, IJzerman AP..  (2018)  Pyrrolone Derivatives as Intracellular Allosteric Modulators for Chemokine Receptors: Selective and Dual-Targeting Inhibitors of CC Chemokine Receptors 1 and 2.,  61  (20): [PMID:30256641] [10.1021/acs.jmedchem.8b00605]

8. Harcken C, Sarko C, Mao C, Lord J, Raudenbush B, Razavi H, Liu P, Swinamer A, Disalvo D, Lee T, Lin S, Kukulka A, Grbic H, Patel M, Patel M, Fletcher K, Joseph D, White D, Amodeo L, Berg K, Brown M, Thomson DS..  (2019)  Discovery and optimization of pyrazole amides as antagonists of CCR1.,  29  (3): [PMID:30455146] [10.1016/j.bmcl.2018.11.015]

9. 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]

10. 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]

11. 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]

12. 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]

13. Ellen Van Damme.  (2021)  Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity,  [10.6019/CHEMBL4651402]

14. 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]

15.  (2022)  Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte),  [10.6019/CHEMBL5058564]

16.  (2022)  Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Multiplex),  [10.6019/CHEMBL5058577]

17. EUbOPEN.  (2022)  EUbOPEN Chemogenomics Library wave 2 - DSF,  [10.6019/CHEMBL5060014]

18. EUbOPEN.  (2023)  GPCR results for EUbOPEN Chemogenomics Library 3,  [10.6019/CHEMBL5209801]

19. Arimont M, Sun SL, Leurs R, Smit M, de Esch IJP, de Graaf C..  (2017)  Structural Analysis of Chemokine Receptor-Ligand Interactions.,  60  (12): [PMID:28165741] [10.1021/acs.jmedchem.6b01309]

20. Institute for Molecular Medicine Finland - High Throughput Biomedicine Unit.  (2023)  ECBD screening data for assay EOS300108,  [10.6019/EOS300108]

Source

Source(7):

• Scientific Literature
• AstraZeneca Deposited Data
• SARS-CoV-2 Screening Data 2020-21
• EUbOPEN Chemogenomic Library
• IMI-CARE SARS-CoV-2 Data
• Fraunhofer HDAC6
• EU-OPENSCREEN dataset