4-(7-Chloro-2-methoxy-benzo[b][1,5]naphthyridin-10-ylamino)-2,6-bis-pyrrolidin-1-ylmethyl-phenol

ID: ALA35228

Cas Number: 74847-35-1

PubChem CID: 107771

Product Number: P613028, Order Now?

Max Phase: Phase

Molecular Formula: C29H32ClN5O2

Molecular Weight: 518.06

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Malaridine | Pyronaridine | Pyronaridine|74847-35-1|Malaridine|Pyronaridine [INN]|2-Methoxy-7-chloro-10-(3',5'-bis(pyrrolin-1-ylmethyl)-4'-hydroxyphenylamino)benzo(b)-1,5-naphthyridine|TD3P7Q3SG6|4-((7-Chloro-2-methoxybenzo(b)-1,5-naphthyridin-10-yl)amino)-2,6-bis(1-pyrrolidinylmethyl)phenol|4-[(7-chloro-2-methoxybenzo[b][1,5]naphthyridin-10-yl)amino]-2,6-bis(pyrrolidin-1-ylmethyl)phenol|Benzonaphthyridine 7351|UNII-TD3P7Q3SG6|4-((7-chloro-2-methoxybenzo[b][1,5]naphthyridin-10-yl)amino)-2,6-bis(Show More⌵

Synonyms from Alternative Forms(3): Pyronaridine tetraphosphate | Pyronaridine phosphate | NSC-759834

Canonical SMILES:  COc1ccc2nc3cc(Cl)ccc3c(Nc3cc(CN4CCCC4)c(O)c(CN4CCCC4)c3)c2n1

Standard InChI:  InChI=1S/C29H32ClN5O2/c1-37-26-9-8-24-28(33-26)27(23-7-6-21(30)16-25(23)32-24)31-22-14-19(17-34-10-2-3-11-34)29(36)20(15-22)18-35-12-4-5-13-35/h6-9,14-16,36H,2-5,10-13,17-18H2,1H3,(H,31,32)

Standard InChI Key:  DJUFPMUQJKWIJB-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 37 42  0  0  0  0  0  0  0  0999 V2000
   -4.3159   -2.5141    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    1.3999   -0.8641    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.3999    1.6109    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4580   -2.5141    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4580   -0.0391    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0291   -0.8641    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.6854    2.8484    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.1143    0.3734    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4580   -0.8641    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7436   -1.2766    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1725   -1.2766    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7436   -2.1016    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1725   -2.1016    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7436    0.3734    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8870   -0.8641    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8870   -2.5141    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0291   -2.5141    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6854   -1.2766    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0291    1.6109    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6854    0.3734    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6854    1.1984    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6014   -2.1016    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7436    1.1984    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0291   -0.0391    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6854   -2.1016    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6014   -1.2766    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0291    2.4359    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3999   -0.0391    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7716    3.6689    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4391    2.5128    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2006    1.1939    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8680    0.0378    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1143   -1.2766    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5786    3.8404    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9911    3.1259    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0075    1.3654    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4200    0.6509    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1 22  1  0
  2 18  1  0
  2 33  1  0
  3 21  1  0
  4 12  1  0
  4 13  2  0
  5  9  1  0
  5 14  1  0
  6 10  2  0
  6 18  1  0
  7 27  1  0
  7 29  1  0
  7 30  1  0
  8 28  1  0
  8 31  1  0
  8 32  1  0
  9 10  1  0
  9 11  2  0
 10 12  1  0
 11 13  1  0
 11 15  1  0
 12 17  2  0
 13 16  1  0
 14 23  2  0
 14 24  1  0
 15 26  2  0
 16 22  2  0
 17 25  1  0
 18 25  2  0
 19 21  2  0
 19 23  1  0
 19 27  1  0
 20 21  1  0
 20 24  2  0
 20 28  1  0
 22 26  1  0
 29 34  1  0
 30 35  1  0
 31 36  1  0
 32 37  1  0
 34 35  1  0
 36 37  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA35228

   pyronaridine

2. Alternative Forms:

   

   ALA35228

   ---
3. 

   ALA35228

   Pyronaridine tetraphosphate

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: Yes

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 518.06

Molecular Weight (Monoisotopic): 517.2245

AlogP: 6.09

#Rotatable Bonds: 7

Polar Surface Area: 73.75

Molecular Species: BASE

HBA: 7

HBD: 2

#RO5 Violations: 2

HBA (Lipinski): 7

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 7.96

CX Basic pKa: 10.08

CX LogP: 4.22

CX LogD: 2.08

Aromatic Rings: 4

Heavy Atoms: 37

QED Weighted: 0.23

Np Likeness Score: -0.83

References

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3. Price RN, Marfurt J, Chalfein F, Kenangalem E, Piera KA, Tjitra E, Anstey NM, Russell B..  (2010)  In vitro activity of pyronaridine against multidrug-resistant Plasmodium falciparum and Plasmodium vivax.,  54  (12): [PMID:20876370] [10.1128/aac.00801-10]

4. Siswantoro H, Russell B, Ratcliff A, Prasetyorini B, Chalfein F, Marfurt J, Kenangalem E, Wuwung M, Piera KA, Ebsworth EP, Anstey NM, Tjitra E, Price RN..  (2011)  In vivo and in vitro efficacy of chloroquine against Plasmodium malariae and P. ovale in Papua, Indonesia.,  55  (1): [PMID:20937779] [10.1128/aac.01122-10]

5. Qi J, Wang S, Liu G, Peng H, Wang J, Zhu Z, Yang C..  (2004)  Pyronaridine, a novel modulator of P-glycoprotein-mediated multidrug resistance in tumor cells in vitro and in vivo.,  319  (1): [PMID:15194484] [10.1016/j.bbrc.2004.05.099]

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13. Deyou T, Gumula I, Pang F, Gruhonjic A, Mumo M, Holleran J, Duffy S, Fitzpatrick PA, Heydenreich M, Landberg G, Derese S, Avery V, Rissanen K, Erdélyi M, Yenesew A..  (2015)  Rotenoids, Flavonoids, and Chalcones from the Root Bark of Millettia usaramensis.,  78  (12): [PMID:26651537] [10.1021/acs.jnatprod.5b00581]

14. Gilson PR, Tan C, Jarman KE, Lowes KN, Curtis JM, Nguyen W, Di Rago AE, Bullen HE, Prinz B, Duffy S, Baell JB, Hutton CA, Jousset Subroux H, Crabb BS, Avery VM, Cowman AF, Sleebs BE..  (2017)  Optimization of 2-Anilino 4-Amino Substituted Quinazolines into Potent Antimalarial Agents with Oral in Vivo Activity.,  60  (3): [PMID:28080063] [10.1021/acs.jmedchem.6b01673]

15. Nyandoro SS, Munissi JJ, Gruhonjic A, Duffy S, Pan F, Puttreddy R, Holleran JP, Fitzpatrick PA, Pelletier J, Avery VM, Rissanen K, Erdélyi M..  (2017)  Polyoxygenated Cyclohexenes and Other Constituents of Cleistochlamys kirkii Leaves.,  80  (1): [PMID:28001067] [10.1021/acs.jnatprod.6b00759]

16. Senadeera SPD, Duffy S, Avery VM, Carroll AR..  (2017)  Antiplasmodial β-triketones from the flowers of the Australian tree Angophora woodsiana.,  27  (11): [PMID:28400231] [10.1016/j.bmcl.2017.03.065]

17. Robertson LP, Duffy S, Wang Y, Wang D, Avery VM, Carroll AR..  (2017)  Pimentelamines A-C, Indole Alkaloids Isolated from the Leaves of the Australian Tree Flindersia pimenteliana.,  80  (12): [PMID:29236492] [10.1021/acs.jnatprod.7b00587]

18. Senadeera SPD, Lucantoni L, Duffy S, Avery VM, Carroll AR..  (2018)  Antiplasmodial β-Triketone-Flavanone Hybrids from the Flowers of the Australian Tree Corymbia torelliana.,  81  (7): [PMID:29969262] [10.1021/acs.jnatprod.8b00154]

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20. Unpublished dataset, 

21. Katie Heiser, Peter F. McLean, Chadwick T. Davis, Ben Fogelson, Hannah B. Gordon, Pamela Jacobson, Brett Hurst, Ben Miller, Ronald W. Alfa, Berton A. Earnshaw, Mason L. Victors, Yolanda T. Chong, Imran S. Haque, Adeline S. Low, Christopher C. Gibson.  (2020)  Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2,  [10.1101/2020.04.21.054387]

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Source

Source(8):

• Scientific Literature
• PubChem BioAssays
• Clinical Candidates
• TP-search Transporter Database
• Open Source Malaria Screening
• SARS-CoV-2 Screening Data 2020-21
• IMI-CARE SARS-CoV-2 Data
• Fraunhofer HDAC6