ID: ALA293096

Max Phase: Preclinical

Molecular Formula: C13H14N2O3

Molecular Weight: 246.27

Molecule Type: Small molecule

Representations

Canonical SMILES:  COc1cc2c(cc1O)N=C[C@@H]1CCCN1C2=O

Standard InChI:  InChI=1S/C13H14N2O3/c1-18-12-5-9-10(6-11(12)16)14-7-8-3-2-4-15(8)13(9)17/h5-8,16H,2-4H2,1H3/t8-/m0/s1

Standard InChI Key:  LQDGLTOVYOUCRG-QMMMGPOBSA-N

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

Properties

Molecular Weight: 246.27

Molecular Weight (Monoisotopic): 246.1004

AlogP: 1.72

#Rotatable Bonds: 1

Polar Surface Area: 62.13

Molecular Species: NEUTRAL

HBA: 4

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 8.53

CX Basic pKa: 4.07

CX LogP: 0.94

CX LogD: 0.90

Aromatic Rings: 1

Heavy Atoms: 18

QED Weighted: 0.82

Np Likeness Score: 0.71

References

1. Thurston DE, Bose DS, Howard PW, Jenkins TC, Leoni A, Baraldi PG, Guiotto A, Cacciari B, Kelland LR, Foloppe MP, Rault S..  (1999)  Effect of A-ring modifications on the DNA-binding behavior and cytotoxicity of pyrrolo[2,1-c][1,4]benzodiazepines.,  42  (11): [PMID:10354403] [10.1021/jm981117p]

2. Tercel M, Stribbling SM, Sheppard H, Siim BG, Wu K, Pullen SM, Botting KJ, Wilson WR, Denny WA..  (2003)  Unsymmetrical DNA cross-linking agents: combination of the CBI and PBD pharmacophores.,  46  (11): [PMID:12747786] [10.1021/jm020526p]

3. Kamal A, Reddy PS, Reddy DR..  (2004)  The effect of C2-fluoro group on the biological activity of DC-81 and its dimers.,  14  (10): [PMID:15109675] [10.1016/j.bmcl.2004.02.063]

4. Kamal A, Ramesh G, Ramulu P, Srinivas O, Rehana T, Sheelu G..  (2003)  Design and synthesis of novel chrysene-linked pyrrolo[2,1-c][1,4]-benzodiazepine hybrids as potential DNA-binding agents.,  13  (20): [PMID:14505647] [10.1016/s0960-894x(03)00743-1]

5. Kamal A, Ramulu P, Srinivas O, Ramesh G..  (2003)  Synthesis and DNA-binding affinity of A-C8/C-C2 alkoxyamido-linked pyrrolo[2,1-c][1,4]benzodiazepine dimers.,  13  (22): [PMID:14592483] [10.1016/j.bmcl.2003.08.071]

6. Wilson SC, Howard PW, Forrow SM, Hartley JA, Adams LJ, Jenkins TC, Kelland LR, Thurston DE..  (1999)  Design, synthesis, and evaluation of a novel sequence-selective epoxide-containing DNA cross-linking agent based on the pyrrolo[2, 1-c][1,4]benzodiazepine system.,  42  (20): [PMID:10514273] [10.1021/jm981124d]

7. Baraldi PG, Leoni A, Cacciari B, Manfredini S, Simoni D, Bergomi M, Menta E, Spinelli S..  (1994)  Synthesis and antitumor activity of a new class of pyrazolo[4,3-e]pyrrolo[1,2-a][1,4]diazepinone analogues of pyrrolo[1,4][2,1-c]benzodiazepines.,  37  (25): [PMID:7996544] [10.1021/jm00051a009]

8. Kamal A, Ramesh G, Laxman N, Ramulu P, Srinivas O, Neelima K, Kondapi AK, Sreenu VB, Nagarajaram HA..  (2002)  Design, synthesis, and evaluation of new noncross-linking pyrrolobenzodiazepine dimers with efficient DNA binding ability and potent antitumor activity.,  45  (21): [PMID:12361394] [10.1021/jm020124h]

9. Kamal A, Ramesh G, Srinivas O, Ramulu P..  (2004)  Synthesis and antitumour activity of pyrene-linked pyrrolo [2,1-c]benzodiazepine hybrids.,  14  (2): [PMID:14698184] [10.1016/j.bmcl.2003.10.050]

10. Kamal A, Srinivas O, Ramulu P, Ramesh G, Kumar PP..  (2004)  Synthesis of C8-linked pyrrolo[2,1-c][1,4]benzodiazepine-acridone/acridine hybrids as potential DNA-binding agents.,  14  (15): [PMID:15225736] [10.1016/j.bmcl.2004.04.087]

11. Kamal A, Ramu R, Khanna GB, Saxena AK, Shanmugavel M, Pandita RM..  (2004)  Pyrrolo[2,1-c][1,4]benzodiazepine-anthraquinone conjugates. Synthesis, DNA binding and cytotoxicity.,  14  (19): [PMID:15341949] [10.1016/j.bmcl.2004.07.036]

12. Kamal A, Reddy PS, Reddy DR, Laxman E, Murthy YL..  (2004)  Synthesis of fluorinated analogues of SJG-136 and their DNA-binding potential.,  14  (22): [PMID:15482951] [10.1016/j.bmcl.2004.08.050]

13. Wang JJ, Shen YK, Hu WP, Hsieh MC, Lin FL, Hsu MK, Hsu MH..  (2006)  Design, synthesis, and biological evaluation of pyrrolo[2,1-c][1,4]benzodiazepine and indole conjugates as anticancer agents.,  49  (4): [PMID:16480280] [10.1021/jm050956q]

14. Wells G, Martin CR, Howard PW, Sands ZA, Laughton CA, Tiberghien A, Woo CK, Masterson LA, Stephenson MJ, Hartley JA, Jenkins TC, Shnyder SD, Loadman PM, Waring MJ, Thurston DE..  (2006)  Design, synthesis, and biophysical and biological evaluation of a series of pyrrolobenzodiazepine-poly(N-methylpyrrole) conjugates.,  49  (18): [PMID:16942018] [10.1021/jm051199z]

15. Kamal A, Khan MN, Reddy KS, Ahmed SK, Kumar MS, Juvekar A, Sen S, Zingde S..  (2007)  1,2,4-benzothiadiazine linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates: synthesis, DNA-binding affinity and cytotoxicity.,  17  (19): [PMID:17723301] [10.1016/j.bmcl.2007.08.018]

16. Kamal A, Rajasekhar Reddy D, Murali Mohan Reddy PS..  (2007)  Synthesis and DNA-binding ability of C2R-fluoro substituted DC-81 and its dimers.,  17  (3): [PMID:17113291] [10.1016/j.bmcl.2006.10.070]

17. Baraldi PG, Preti D, Fruttarolo F, Tabrizi MA, Romagnoli R..  (2007)  Hybrid molecules between distamycin A and active moieties of antitumor agents.,  15  (1): [PMID:17081759] [10.1016/j.bmc.2006.07.004]

18. Wells G, Suggitt M, Coffils M, Baig MA, Howard PW, Loadman PM, Hartley JA, Jenkins TC, Thurston DE..  (2008)  Fluorescent 7-diethylaminocoumarin pyrrolobenzodiazepine conjugates: synthesis, DNA interaction, cytotoxicity and differential cellular localization.,  18  (6): [PMID:18280154] [10.1016/j.bmcl.2008.01.083]

19. Kamal A, Shankaraiah N, Devaiah V, Laxma Reddy K, Juvekar A, Sen S, Kurian N, Zingde S..  (2008)  Synthesis of 1,2,3-triazole-linked pyrrolobenzodiazepine conjugates employing 'click' chemistry: DNA-binding affinity and anticancer activity.,  18  (4): [PMID:18207392] [10.1016/j.bmcl.2007.12.063]

20. Kamal A, Shankaraiah N, Prabhakar S, Reddy ChR, Markandeya N, Reddy KL, Devaiah V..  (2008)  Solid-phase synthesis of new pyrrolobenzodiazepine-chalcone conjugates: DNA-binding affinity and anticancer activity.,  18  (7): [PMID:18325766] [10.1016/j.bmcl.2008.02.047]

21. Kamal A, Kumar PP, Sreekanth K, Seshadri BN, Ramulu P..  (2008)  Synthesis of new benzimidazole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates with efficient DNA-binding affinity and potent cytotoxicity.,  18  (8): [PMID:18378445] [10.1016/j.bmcl.2008.03.039]

22. Kamal A, Tekumalla V, Raju P, Naidu VG, Diwan PV, Sistla R..  (2008)  Pyrrolo[2,1-c][1,4]benzodiazepine-beta-glucuronide prodrugs with a potential for selective therapy of solid tumors by PMT and ADEPT strategies.,  18  (13): [PMID:18538566] [10.1016/j.bmcl.2008.05.038]

23. Kamal A, Kumar PP, Seshadri BN, Srinivas O, Kumar MS, Sen S, Kurian N, Juvekar AS, Zingde SM..  (2008)  Phosphonate-linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates: synthesis, DNA-binding affinity and cytotoxicity.,  16  (7): [PMID:18262426] [10.1016/j.bmc.2008.01.040]

24. Hu WP, Liang JJ, Kao CL, Chen YC, Chen CY, Tsai FY, Wu MJ, Chang LS, Chen YL, Wang JJ..  (2009)  Synthesis and antitumor activity of novel enediyne-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrids.,  17  (3): [PMID:19131253] [10.1016/j.bmc.2008.12.036]

25. Kamal A, Ramu R, Tekumalla V, Khanna GB, Barkume MS, Juvekar AS, Zingde SM..  (2008)  Remarkable DNA binding affinity and potential anticancer activity of pyrrolo[2,1-c][1,4]benzodiazepine-naphthalimide conjugates linked through piperazine side-armed alkane spacers.,  16  (15): [PMID:18656370] [10.1016/j.bmc.2008.06.034]

26. Kamal A, Khan MN, Srikanth YV, Reddy KS, Juvekar A, Sen S, Kurian N, Zingde S..  (2008)  Synthesis, DNA-binding ability and evaluation of antitumour activity of triazolo[1,2,4]benzothiadiazine linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates.,  16  (16): [PMID:18657979] [10.1016/j.bmc.2008.06.056]

27. Kamal A, Vijaya Bharathi E, Janaki Ramaiah M, Surendranadha Reddy J, Dastagiri D, Viswanath A, Sultana F, Pushpavalli SN, Pal-Bhadra M, Juvekar A, Sen S, Zingde S..  (2010)  Synthesis, anticancer activity and apoptosis inducing ability of anthranilamide-PBD conjugates.,  20  (11): [PMID:20444601] [10.1016/j.bmcl.2010.04.037]

28. Kamal A, Sreekanth K, Kumar PP, Shankaraiah N, Balakishan G, Ramaiah MJ, Pushpavalli SN, Ray P, Bhadra MP..  (2010)  Synthesis and potential cytotoxic activity of new phenanthrylphenol-pyrrolobenzodiazepines.,  45  (6): [PMID:20171761] [10.1016/j.ejmech.2010.01.054]

29. Kamal A, Reddy KS, Khan MN, Shetti RV, Ramaiah MJ, Pushpavalli SN, Srinivas C, Pal-Bhadra M, Chourasia M, Sastry GN, Juvekar A, Zingde S, Barkume M..  (2010)  Synthesis, DNA-binding ability and anticancer activity of benzothiazole/benzoxazole-pyrrolo[2,1-c][1,4]benzodiazepine conjugates.,  18  (13): [PMID:20627593] [10.1016/j.bmc.2010.05.007]

30. Kamal A, Dastagiri D, Ramaiah MJ, Bharathi EV, Reddy JS, Balakishan G, Sarma P, Pushpavalli SN, Pal-Bhadra M, Juvekar A, Sen S, Zingde S..  (2010)  Synthesis, anticancer activity and mitochondrial mediated apoptosis inducing ability of 2,5-diaryloxadiazole-pyrrolobenzodiazepine conjugates.,  18  (18): [PMID:20732817] [10.1016/j.bmc.2010.07.067]

31. Kamal A, Balakishan G, Ramakrishna G, Shaik TB, Sreekanth K, Balakrishna M, Rajender, Dastagiri D, Kalivendi SV..  (2010)  Synthesis and biological evaluation of cinnamido linked pyrrolo[2,1-c][1,4]benzodiazepines as antimitotic agents.,  45  (9): [PMID:20554354] [10.1016/j.ejmech.2010.05.041]

32. Kamal A, Reddy JS, Ramaiah MJ, Dastagiri D, Bharathi EV, Azhar MA, Sultana F, Pushpavalli SN, Pal-Bhadra M, Juvekar A, Sen S, Zingde S..  (2010)  Design, synthesis and biological evaluation of 3,5-diaryl-isoxazoline/isoxazole-pyrrolobenzodiazepine conjugates as potential anticancer agents.,  45  (9): [PMID:20557981] [10.1016/j.ejmech.2010.05.047]

33. Kamal A, Reddy MK, Ramaiah MJ, Rajender, Reddy JS, Srikanth YV, Dastagiri D, Bharathi EV, Pushpavalli SN, Sarma P, Pal-Bhadra M..  (2011)  Synthesis and biological evaluation of estradiol linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates as potential anticancer agents.,  19  (8): [PMID:21459581] [10.1016/j.bmc.2011.03.015]

34. Kamal A, Reddy JS, Ramaiah MJ, Bharathi EV, Dastagiri D, Reddy MK, Pushpavalli SN, Pal-Bhadra M..  (2010)  Synthesis and biological evaluation of anilino substituted pyrimidine linked pyrrolobenzodiazepines as potential anticancer agents.,  20  (17): [PMID:20673627] [10.1016/j.bmcl.2010.06.147]

35. Kamal A, Vijaya Bharathi E, Janaki Ramaiah M, Dastagiri D, Surendranadha Reddy J, Viswanath A, Sultana F, Pushpavalli SN, Pal-Bhadra M, Srivastava HK, Narahari Sastry G, Juvekar A, Sen S, Zingde S..  (2010)  Quinazolinone linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates: Design, synthesis and biological evaluation as potential anticancer agents.,  18  (2): [PMID:20031423] [10.1016/j.bmc.2009.12.015]

36. Kamal A, Prabhakar S, Janaki Ramaiah M, Venkat Reddy P, Ratna Reddy Ch, Mallareddy A, Shankaraiah N, Lakshmi Narayan Reddy T, Pushpavalli SN, Pal-Bhadra M..  (2011)  Synthesis and anticancer activity of chalcone-pyrrolobenzodiazepine conjugates linked via 1,2,3-triazole ring side-armed with alkane spacers.,  46  (9): [PMID:21676506] [10.1016/j.ejmech.2011.05.050]

37. Kamal A, Ramakrishna G, Lakshma Nayak V, Raju P, Subba Rao AV, Viswanath A, Vishnuvardhan MV, Ramakrishna S, Srinivas G..  (2012)  Design and synthesis of benzo[c,d]indolone-pyrrolobenzodiazepine conjugates as potential anticancer agents.,  20  (2): [PMID:22209733] [10.1016/j.bmc.2011.12.003]

38. Kamal A, Srikanth YV, Ramaiah MJ, Khan MN, Kashi Reddy M, Ashraf M, Lavanya A, Pushpavalli SN, Pal-Bhadra M..  (2012)  Synthesis, anticancer activity and apoptosis inducing ability of bisindole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates.,  22  (1): [PMID:22104151] [10.1016/j.bmcl.2011.10.080]

39. Chen CY, Lee PH, Lin YY, Yu WT, Hu WP, Hsu CC, Lin YT, Chang LS, Hsiao CT, Wang JJ, Chung MI..  (2013)  Synthesis, DNA-binding abilities and anticancer activities of triazole-pyrrolo[2,1-c][1,4]benzodiazepines hybrid scaffolds.,  23  (24): [PMID:24161833] [10.1016/j.bmcl.2013.10.004]

40. Kamal A, Ramakrishna G, Ramaiah MJ, Viswanath A, Rao AVS, Bagul C, Mukhopadyay D, Pushpavalli SNCVL, Pal-Bhadra M.  (2013)  Design, synthesis and biological evaluation of imidazo[1,5-a]pyridinePBD conjugates as potential DNA-directed alkylating agents,  4  (4): [10.1039/C2MD20219K]

41. Kamal A, Shetti RVCRNC, Ramaiah MJ, Swapna P, Reddy KS, Mallareddy A, Rao MPN, Chourasia M, Sastry GN, Juvekar A, Zingde S, Sarma P, Pushpavalli SNCVL, Pal-Bhadra M.  (2011)  Carbazolepyrrolo[2,1-c][1,4]benzodiazepine conjugates: design, synthesis, and biological evaluation,  2  (8): [10.1039/C1MD00072A]

Source

Source(1):

• Scientific Literature