ID: ALA79513

Max Phase: Preclinical

Molecular Formula: C20H15NO6

Molecular Weight: 365.34

Molecule Type: Small molecule

Representations

Synonyms (1): NSC-341622
Synonyms from Alternative Forms(1):

Canonical SMILES:  COc1cc2c3c(n(C)c(=O)c2cc1OC)-c1cc2c(cc1C3=O)OCO2

Standard InChI:  InChI=1S/C20H15NO6/c1-21-18-10-5-15-16(27-8-26-15)6-11(10)19(22)17(18)9-4-13(24-2)14(25-3)7-12(9)20(21)23/h4-7H,8H2,1-3H3

Standard InChI Key:  LWLNFIXOPOZENE-UHFFFAOYSA-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: 365.34

Molecular Weight (Monoisotopic): 365.0899

AlogP: 2.50

#Rotatable Bonds: 2

Polar Surface Area: 75.99

Molecular Species: NEUTRAL

HBA: 7

HBD: 0

#RO5 Violations: 0

HBA (Lipinski): 7

HBD (Lipinski): 0

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa:

CX LogP: 1.43

CX LogD: 1.43

Aromatic Rings: 3

Heavy Atoms: 27

QED Weighted: 0.54

Np Likeness Score: 0.48

References

1. Jayaraman M, Fox BM, Hollingshead M, Kohlhagen G, Pommier Y, Cushman M..  (2002)  Synthesis of new dihydroindeno[1,2-c]isoquinoline and indenoisoquinolinium chloride topoisomerase I inhibitors having high in vivo anticancer activity in the hollow fiber animal model.,  45  (1): [PMID:11754595] [10.1021/jm000498f]

2. Fox BM, Xiao X, Antony S, Kohlhagen G, Pommier Y, Staker BL, Stewart L, Cushman M..  (2003)  Design, synthesis, and biological evaluation of cytotoxic 11-alkenylindenoisoquinoline topoisomerase I inhibitors and indenoisoquinoline-camptothecin hybrids.,  46  (15): [PMID:12852757] [10.1021/jm0300476]

3. Morrell A, Antony S, Kohlhagen G, Pommier Y, Cushman M..  (2004)  Synthesis of nitrated indenoisoquinolines as topoisomerase I inhibitors.,  14  (14): [PMID:15203138] [10.1016/j.bmcl.2004.05.022]

4. Cushman M, Jayaraman M, Vroman JA, Fukunaga AK, Fox BM, Kohlhagen G, Strumberg D, Pommier Y..  (2000)  Synthesis of new indeno[1,2-c]isoquinolines: cytotoxic non-camptothecin topoisomerase I inhibitors.,  43  (20): [PMID:11020283] [10.1021/jm000029d]

5. Strumberg D, Pommier Y, Paull K, Jayaraman M, Nagafuji P, Cushman M..  (1999)  Synthesis of cytotoxic indenoisoquinoline topoisomerase I poisons.,  42  (3): [PMID:9986716] [10.1021/jm9803323]

6. Nagarajan M, Xiao X, Antony S, Kohlhagen G, Pommier Y, Cushman M..  (2003)  Design, synthesis, and biological evaluation of indenoisoquinoline topoisomerase I inhibitors featuring polyamine side chains on the lactam nitrogen.,  46  (26): [PMID:14667224] [10.1021/jm030313f]

7. Nagarajan M, Morrell A, Fort BC, Meckley MR, Antony S, Kohlhagen G, Pommier Y, Cushman M..  (2004)  Synthesis and anticancer activity of simplified indenoisoquinoline topoisomerase I inhibitors lacking substituents on the aromatic rings.,  47  (23): [PMID:15509164] [10.1021/jm040025z]

8. Ioanoviciu A, Antony S, Pommier Y, Staker BL, Stewart L, Cushman M..  (2005)  Synthesis and mechanism of action studies of a series of norindenoisoquinoline topoisomerase I poisons reveal an inhibitor with a flipped orientation in the ternary DNA-enzyme-inhibitor complex as determined by X-ray crystallographic analysis.,  48  (15): [PMID:16033260] [10.1021/jm050076b]

9. Xiao X, Miao ZH, Antony S, Pommier Y, Cushman M..  (2005)  Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines.,  15  (11): [PMID:15911256] [10.1016/j.bmcl.2005.03.101]

10. Morrell A, Jayaraman M, Nagarajan M, Fox BM, Meckley MR, Ioanoviciu A, Pommier Y, Antony S, Hollingshead M, Cushman M..  (2006)  Evaluation of indenoisoquinoline topoisomerase I inhibitors using a hollow fiber assay.,  16  (16): [PMID:16750365] [10.1016/j.bmcl.2006.05.048]

11. Nagarajan M, Morrell A, Ioanoviciu A, Antony S, Kohlhagen G, Agama K, Hollingshead M, Pommier Y, Cushman M..  (2006)  Synthesis and evaluation of indenoisoquinoline topoisomerase I inhibitors substituted with nitrogen heterocycles.,  49  (21): [PMID:17034134] [10.1021/jm060564z]

12. Morrell A, Placzek MS, Steffen JD, Antony S, Agama K, Pommier Y, Cushman M..  (2007)  Investigation of the lactam side chain length necessary for optimal indenoisoquinoline topoisomerase I inhibition and cytotoxicity in human cancer cell cultures.,  50  (9): [PMID:17402722] [10.1021/jm0613119]

13. Morrell A, Placzek M, Parmley S, Grella B, Antony S, Pommier Y, Cushman M..  (2007)  Optimization of the indenone ring of indenoisoquinoline topoisomerase I inhibitors.,  50  (18): [PMID:17676830] [10.1021/jm070307+]

14. Morrell A, Placzek M, Parmley S, Antony S, Dexheimer TS, Pommier Y, Cushman M..  (2007)  Nitrated indenoisoquinolines as topoisomerase I inhibitors: a systematic study and optimization.,  50  (18): [PMID:17696418] [10.1021/jm070361q]

15. Cinelli MA, Morrell A, Dexheimer TS, Scher ES, Pommier Y, Cushman M..  (2008)  Design, synthesis, and biological evaluation of 14-substituted aromathecins as topoisomerase I inhibitors.,  51  (15): [PMID:18630891] [10.1021/jm800259e]

16. Cinelli MA, Cordero B, Dexheimer TS, Pommier Y, Cushman M..  (2009)  Synthesis and biological evaluation of 14-(aminoalkyl-aminomethyl)aromathecins as topoisomerase I inhibitors: investigating the hypothesis of shared structure-activity relationships.,  17  (20): [PMID:19783447] [10.1016/j.bmc.2009.08.066]

17. Song Y, Shao Z, Dexheimer TS, Scher ES, Pommier Y, Cushman M..  (2010)  Structure-based design, synthesis, and biological studies of new anticancer norindenoisoquinoline topoisomerase I inhibitors.,  53  (5): [PMID:20155916] [10.1021/jm901649x]

18. Kiselev E, Dexheimer TS, Pommier Y, Cushman M..  (2010)  Design, synthesis, and evaluation of dibenzo[c,h][1,6]naphthyridines as topoisomerase I inhibitors and potential anticancer agents.,  53  (24): [PMID:21090809] [10.1021/jm101048k]

19. PubChem BioAssay data set, 

20. Peterson KE, Cinelli MA, Morrell AE, Mehta A, Dexheimer TS, Agama K, Antony S, Pommier Y, Cushman M..  (2011)  Alcohol-, diol-, and carbohydrate-substituted indenoisoquinolines as topoisomerase I inhibitors: investigating the relationships involving stereochemistry, hydrogen bonding, and biological activity.,  54  (14): [PMID:21710981] [10.1021/jm101338z]

21. Kiselev E, DeGuire S, Morrell A, Agama K, Dexheimer TS, Pommier Y, Cushman M..  (2011)  7-azaindenoisoquinolines as topoisomerase I inhibitors and potential anticancer agents.,  54  (17): [PMID:21823606] [10.1021/jm200719v]

22. PubChem BioAssay data set, 

23. Kiselev E, Agama K, Pommier Y, Cushman M..  (2012)  Azaindenoisoquinolines as topoisomerase I inhibitors and potential anticancer agents: a systematic study of structure-activity relationships.,  55  (4): [PMID:22329436] [10.1021/jm201512x]

24. Rahman KM, Tizkova K, Reszka AP, Neidle S, Thurston DE..  (2012)  Identification of novel telomeric G-quadruplex-targeting chemical scaffolds through screening of three NCI libraries.,  22  (8): [PMID:22421021] [10.1016/j.bmcl.2012.02.020]

25. Kiselev E, Sooryakumar D, Agama K, Cushman M, Pommier Y..  (2014)  Optimization of the lactam side chain of 7-azaindenoisoquinoline topoisomerase I inhibitors and mechanism of action studies in cancer cells.,  57  (4): [PMID:24502276] [10.1021/jm401471v]

26. Lv PC, Agama K, Marchand C, Pommier Y, Cushman M..  (2014)  Design, synthesis, and biological evaluation of O-2-modified indenoisoquinolines as dual topoisomerase I-tyrosyl-DNA phosphodiesterase I inhibitors.,  57  (10): [PMID:24800942] [10.1021/jm500294a]

Source

Source(2):

• Scientific Literature
• PubChem BioAssays