(S)-8-Hydroxy-7-methoxy-1,2,3,11a-tetrahydro-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one

ID: ALA293096

Chembl Id: CHEMBL293096

PubChem CID: 11107626

Max Phase: Preclinical

Molecular Formula: C13H14N2O3

Molecular Weight: 246.27

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

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

Associated Targets(Human)

CH1 (841 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PC-6 (212 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SK-OV-3 (52876 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A2058 (690 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
K562 (73714 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Panel NCI-60 (60 carcinoma cell lines) (1088 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Jurkat (10389 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ZR-75-1 (953 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KB (17409 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A2780 (11979 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
COLO 205 (50209 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A549 (127892 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PC-3 (62116 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SiHa (2051 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MCF7 (126967 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HT-29 (80576 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
NCI-H1355 (159 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A-375 (9258 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HOP-62 (47048 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CCND1 Tchem G1/S-specific cyclin D1 (19 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A-431 (6446 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
TUBB4B Tclin Tubulin (5180 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Ca9-22 (362 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HEK-293T (167025 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

L1210 (27553 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Calf thymus DNA (4845 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CHO-AA8 (574 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
UV4 (255 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
EMT6 (738 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Bos taurus (956 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
DNA (1199 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
B16 (5829 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: YesOral: 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: 246.27Molecular Weight (Monoisotopic): 246.1004AlogP: 1.72#Rotatable Bonds: 1
Polar Surface Area: 62.13Molecular Species: NEUTRALHBA: 4HBD: 1
#RO5 Violations: HBA (Lipinski): 5HBD (Lipinski): 1#RO5 Violations (Lipinski):
CX Acidic pKa: 8.53CX Basic pKa: 4.07CX LogP: 0.94CX LogD: 0.90
Aromatic Rings: 1Heavy Atoms: 18QED Weighted: 0.82Np 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): [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,  (8): [10.1039/C1MD00072A]

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