N-(1-(2-cyano-3-(quinolin-5-yl)guanidino)-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide

ID: ALA255787

Chembl Id: CHEMBL255787

Cas Number: 861393-28-4

PubChem CID: 23232014

Max Phase: Preclinical

Molecular Formula: C26H30N6O3

Molecular Weight: 474.57

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Synonyms: A-740003 | A-740003|861393-28-4|UNII-532OV6WA05|532OV6WA05|Benzeneacetamide, N-(1-(((cyanoamino)(5-quinolinylamino)methylene)amino)-2,2-dimethylpropyl)-3,4-dimethoxy-|Benzeneacetamide, N-(1-(((cyanoamino)(5-quinolinylimino)methyl)amino)-2,2-dimethylpropyl)-3,4-dimethoxy-|A 740003|(E)-N-(1-((cyanamido(quinolin-5-ylamino)methylene)amino)-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide|N-[1-[(E)-[(cyanoamino)-(quinolin-5-ylamino)methylidene]amino]-2,2-dimethylpropyl]-2-(3,4-dimethoxyphenyl)aceShow More

Canonical SMILES:  COc1ccc(CC(=O)NC(N/C(=N/C#N)Nc2cccc3ncccc23)C(C)(C)C)cc1OC

Standard InChI:  InChI=1S/C26H30N6O3/c1-26(2,3)24(31-23(33)15-17-11-12-21(34-4)22(14-17)35-5)32-25(29-16-27)30-20-10-6-9-19-18(20)8-7-13-28-19/h6-14,24H,15H2,1-5H3,(H,31,33)(H2,29,30,32)

Standard InChI Key:  PUHSRMSFDASMAE-UHFFFAOYSA-N

Associated Targets(Human)

P2RX7 Tchem P2X purinoceptor 7 (5534 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
P2RY2 Tclin Purinergic receptor P2Y2 (1109 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
P2RX4 Tchem P2X purinoceptor 4 (516 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
P2RX3 Tclin P2X purinoceptor 3 (1991 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
THP-1 (11052 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC6 Tclin Histone deacetylase 6 (20808 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HT-29 (80576 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
RKO (1376 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HEK-293T (167025 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Fibroblast (163371 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
U2OS (164939 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

P2rx7 P2X purinoceptor 7 (1132 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Rattus norvegicus (775804 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
P2rx7 P2X purinoceptor 7 (169 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Peritoneal macrophage (1554 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SARS-CoV-2 (38078 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
rep Replicase polyprotein 1ab (11336 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 474.57Molecular Weight (Monoisotopic): 474.2379AlogP: 3.82#Rotatable Bonds: 7
Polar Surface Area: 120.66Molecular Species: NEUTRALHBA: 6HBD: 3
#RO5 Violations: HBA (Lipinski): 9HBD (Lipinski): 3#RO5 Violations (Lipinski):
CX Acidic pKa: 12.46CX Basic pKa: 4.35CX LogP: 4.08CX LogD: 4.08
Aromatic Rings: 3Heavy Atoms: 35QED Weighted: 0.21Np Likeness Score: -0.96

References

1. Morytko MJ, Betschmann P, Woller K, Ericsson A, Chen H, Donnelly-Roberts DL, Namovic MT, Jarvis MF, Carroll WA, Rafferty P..  (2008)  Synthesis and in vitro activity of N'-cyano-4-(2-phenylacetyl)-N-o-tolylpiperazine-1-carboximidamide P2X7 antagonists.,  18  (6): [PMID:18272365] [10.1016/j.bmcl.2008.01.094]
2. Perez-Medrano A, Donnelly-Roberts DL, Honore P, Hsieh GC, Namovic MT, Peddi S, Shuai Q, Wang Y, Faltynek CR, Jarvis MF, Carroll WA..  (2009)  Discovery and biological evaluation of novel cyanoguanidine P2X(7) antagonists with analgesic activity in a rat model of neuropathic pain.,  52  (10): [PMID:19397270] [10.1021/jm8015848]
3. Guile SD, Alcaraz L, Birkinshaw TN, Bowers KC, Ebden MR, Furber M, Stocks MJ..  (2009)  Antagonists of the P2X(7) receptor. From lead identification to drug development.,  52  (10): [PMID:19191585] [10.1021/jm801528x]
4. Gunosewoyo H, Coster MJ, Bennett MR, Kassiou M..  (2009)  Purinergic P2X(7) receptor antagonists: Chemistry and fundamentals of biological screening.,  17  (14): [PMID:19540765] [10.1016/j.bmc.2009.05.083]
5. Gonzaga DTG, Ferreira LBG, Moreira Maramaldo Costa TE, von Ranke NL, Anastácio Furtado Pacheco P, Sposito Simões AP, Arruda JC, Dantas LP, de Freitas HR, de Melo Reis RA, Penido C, Bello ML, Castro HC, Rodrigues CR, Ferreira VF, Faria RX, da Silva FC..  (2017)  1-Aryl-1H- and 2-aryl-2H-1,2,3-triazole derivatives blockade P2X7 receptor in vitro and inflammatory response in vivo.,  139  [PMID:28858765] [10.1016/j.ejmech.2017.08.034]
6. Faria RX, Oliveira FH, Salles JP, Oliveira AS, von Ranke NL, Bello ML, Rodrigues CR, Castro HC, Louvis AR, Martins DL, Ferreira VF..  (2018)  1,4-Naphthoquinones potently inhibiting P2X7 receptor activity.,  143  [PMID:29133043] [10.1016/j.ejmech.2017.10.033]
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. Pacheco PAF, Galvão RMS, Faria AFM, Von Ranke NL, Rangel MS, Ribeiro TM, Bello ML, Rodrigues CR, Ferreira VF, da Rocha DR, Faria RX..  (2019)  8-Hydroxy-2-(1H-1,2,3-triazol-1-yl)-1,4-naphtoquinone derivatives inhibited P2X7 Receptor-Induced dye uptake into murine Macrophages.,  27  (8): [PMID:30528164] [10.1016/j.bmc.2018.11.036]
9. Park JH, Williams DR, Lee JH, Lee SD, Lee JH, Ko H, Lee GE, Kim S, Lee JM, Abdelrahman A, Müller CE, Jung DW, Kim YC..  (2016)  Potent Suppressive Effects of 1-Piperidinylimidazole Based Novel P2X7 Receptor Antagonists on Cancer Cell Migration and Invasion.,  59  (16): [PMID:27427902] [10.1021/acs.jmedchem.5b01690]
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. 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]
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. 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]
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. Zhao Y, Chen X, He C, Gao G, Chen Z, Du J..  (2021)  Discovery of bilirubin as novel P2X7R antagonist with anti-tumor activity.,  51  [PMID:34543755] [10.1016/j.bmcl.2021.128361]
16. Hopper AT, Juhl M, Hornberg J, Badolo L, Kilburn JP, Thougaard A, Smagin G, Song D, Calice L, Menon V, Dale E, Zhang H, Cajina M, Nattini ME, Gandhi A, Grenon M, Jones K, Khayrullina T, Chandrasena G, Thomsen C, Zorn SH, Brodbeck R, Poda SB, Staal R, Möller T..  (2021)  Synthesis and Characterization of the Novel Rodent-Active and CNS-Penetrant P2X7 Receptor Antagonist Lu AF27139.,  64  (8.0): [PMID:33822617] [10.1021/acs.jmedchem.0c02249]
17. EUbOPEN.  (2023)  EUbOPEN Chemogenomics Library - IncuCyte,  [10.6019/CHEMBL5303304]