3,10-Dihydroxy-13-(4-hydroxy-3-methoxy-phenyl)-2,11-dimethoxy-5-oxa-6b-aza-dibenzo[a,i]fluoren-6-one

ID: ALA373114

Chembl Id: CHEMBL373114

Cas Number: 97614-65-8

PubChem CID: 9892144

Max Phase: Preclinical

Molecular Formula: C28H21NO8

Molecular Weight: 499.48

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Lamellarin D | Lamellarin-D | Lamellarin D|Lamellarine D|97614-65-8|YEF6XD93VE|UNII-YEF6XD93VE|3,11-dihydroxy-14-(4-hydroxy-3-methoxyphenyl)-2,12-dimethoxy-6H-chromeno[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one|Lamellarin-D|6H-[1]Benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one, 3,11-dihydroxy-14-(4-hydroxy-3-methoxyphenyl)-2,12-dimethoxy-|CHEMBL373114|SCHEMBL14106879|DTXSID501031665|AKOS040752394|Q18344928|3,11-DIHYDROXY-14-(4-HYDROXY-3-METHOXYPHENYL)-2,12-DIMETHOXY-6H-(1)BENZOPYRANO(4',3':Show More⌵

Canonical SMILES:  COc1cc(-c2c3c4cc(OC)c(O)cc4oc(=O)c3n3ccc4cc(O)c(OC)cc4c23)ccc1O

Standard InChI:  InChI=1S/C28H21NO8/c1-34-21-9-14(4-5-17(21)30)24-25-16-11-23(36-3)19(32)12-20(16)37-28(33)27(25)29-7-6-13-8-18(31)22(35-2)10-15(13)26(24)29/h4-12,30-32H,1-3H3

Standard InChI Key:  ATHLLZUXVPNPAW-UHFFFAOYSA-N

Alternative Forms

1. Parent:

   

   ALA373114

   LAMELLARIN D

Molecule Features

Natural Product: Yes

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: 499.48

Molecular Weight (Monoisotopic): 499.1267

AlogP: 5.16

#Rotatable Bonds: 4

Polar Surface Area: 123.00

Molecular Species: NEUTRAL

HBA: 9

HBD: 3

#RO5 Violations: 1

HBA (Lipinski): 9

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 7.94

CX Basic pKa: ┄

CX LogP: 3.73

CX LogD: 3.62

Aromatic Rings: 6

Heavy Atoms: 37

QED Weighted: 0.28

Np Likeness Score: 0.93

References

1. Marco E, Laine W, Tardy C, Lansiaux A, Iwao M, Ishibashi F, Bailly C, Gago F..  (2005)  Molecular determinants of topoisomerase I poisoning by lamellarins: comparison with camptothecin and structure-activity relationships.,  48  (11): [PMID:15916431] [10.1021/jm049060w]

2. Pla D, Marchal A, Olsen CA, Francesch A, Cuevas C, Albericio F, Alvarez M..  (2006)  Synthesis and structure-activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D.,  49  (11): [PMID:16722644] [10.1021/jm0602458]

3. Ishibashi F, Tanabe S, Oda T, Iwao M..  (2002)  Synthesis and structure-activity relationship study of lamellarin derivatives.,  65  (4): [PMID:11975488] [10.1021/np0104525]

4. Cananzi S, Merlini L, Artali R, Beretta GL, Zaffaroni N, Dallavalle S..  (2011)  Synthesis and topoisomerase I inhibitory activity of a novel diazaindeno[2,1-b]phenanthrene analogue of Lamellarin D.,  19  (16): [PMID:21783369] [10.1016/j.bmc.2011.06.056]

5. Neagoie C, Vedrenne E, Buron F, Mérour JY, Rosca S, Bourg S, Lozach O, Meijer L, Baldeyrou B, Lansiaux A, Routier S..  (2012)  Synthesis of chromeno[3,4-b]indoles as Lamellarin D analogues: a novel DYRK1A inhibitor class.,  49  [PMID:22305342] [10.1016/j.ejmech.2012.01.040]

6. Yoshida K, Itoyama R, Yamahira M, Tanaka J, Loaëc N, Lozach O, Durieu E, Fukuda T, Ishibashi F, Meijer L, Iwao M..  (2013)  Synthesis, resolution, and biological evaluation of atropisomeric (aR)- and (aS)-16-methyllamellarins N: unique effects of the axial chirality on the selectivity of protein kinases inhibition.,  56  (18): [PMID:23981088] [10.1021/jm400719y]

7. Pla D, Albericio F, Alvarez M.  (2011)  Progress on lamellarins,  2  (8): [10.1039/C1MD00003A]

8. Shen L, Xie N, Yang B, Hu Y, Zhang Y..  (2014)  Design and total synthesis of Mannich derivatives of marine natural product lamellarin D as cytotoxic agents.,  85  [PMID:25189362] [10.1016/j.ejmech.2014.08.038]

9. Fukuda T, Nanjo Y, Fujimoto M, Yoshida K, Natsui Y, Ishibashi F, Okazaki F, To H, Iwao M..  (2019)  Lamellarin-inspired potent topoisomerase I inhibitors with the unprecedented benzo[g][1]benzopyrano[4,3-b]indol-6(13H)-one scaffold.,  27  (2): [PMID:30553626] [10.1016/j.bmc.2018.11.037]

10. Zheng L,Gao T,Ge Z,Ma Z,Xu J,Ding W,Shen L.  (2021)  Design, Synthesis and Structure-Activity Relationship Studies of Glycosylated Derivatives of Marine Natural Product Lamellarin D.,  214  [PMID:33582387] [10.1016/j.ejmech.2021.113226]

11. Talukdar A, Kundu B, Sarkar D, Goon S, Mondal MA..  (2022)  Topoisomerase I inhibitors: Challenges, progress and the road ahead.,  236  [PMID:35413618] [10.1016/j.ejmech.2022.114304]

12. Salehian F, Nadri H, Jalili-Baleh L, Youseftabar-Miri L, Abbas Bukhari SN, Foroumadi A, Tüylü Küçükkilinç T, Sharifzadeh M, Khoobi M..  (2021)  A review: Biologically active 3,4-heterocycle-fused coumarins.,  212  [PMID:33276991] [10.1016/j.ejmech.2020.113034]

Source

Source(1):

• Scientific Literature