(11aS) methyl 4-({4-[4-(7-methoxy-5-oxo-2,3,5,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-8-yloxy)butyrylamino]-1-methyl-1H-pyrrole-2-carbonyl}amino)-1-methyl-1H-pyrrole-2-carbxylate

ID: ALA215032

Chembl Id: CHEMBL215032

Cas Number: 909415-27-6

PubChem CID: 16082652

Max Phase: Preclinical

Molecular Formula: C30H34N6O7

Molecular Weight: 590.64

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  COC(=O)c1cc(NC(=O)c2cc(NC(=O)CCCOc3cc4c(cc3OC)C(=O)N3CCC[C@H]3C=N4)cn2C)cn1C

Standard InChI:  InChI=1S/C30H34N6O7/c1-34-16-18(11-23(34)28(38)33-19-12-24(30(40)42-4)35(2)17-19)32-27(37)8-6-10-43-26-14-22-21(13-25(26)41-3)29(39)36-9-5-7-20(36)15-31-22/h11-17,20H,5-10H2,1-4H3,(H,32,37)(H,33,38)/t20-/m0/s1

Standard InChI Key:  AYJUTKQNHHVYAL-FQEVSTJZSA-N

Alternative Forms

1. Parent:

   

   ALA215032

   Ahj9FJ6lhp

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

Calculated Properties

Molecular Weight: 590.64

Molecular Weight (Monoisotopic): 590.2489

AlogP: 3.53

#Rotatable Bonds: 10

Polar Surface Area: 145.49

Molecular Species: NEUTRAL

HBA: 10

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 13

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 13.64

CX Basic pKa: 4.06

CX LogP: 2.06

CX LogD: 2.06

Aromatic Rings: 3

Heavy Atoms: 43

QED Weighted: 0.27

Np Likeness Score: -0.48

References

1. 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]

2. Brucoli F, Hawkins RM, James CH, Wells G, Jenkins TC, Ellis T, Hartley JA, Howard PW, Thurston DE..  (2011)  Novel C8-linked pyrrolobenzodiazepine (PBD)-heterocycle conjugates that recognize DNA sequences containing an inverted CCAAT box.,  21  (12): [PMID:21570842] [10.1016/j.bmcl.2011.04.054]

3. Rahman KM, Vassoler H, James CH, Thurston DE..  (2010)  DNA Sequence Preference and Adduct Orientation of Pyrrolo[2,1-c][1,4]benzodiazepine Antitumor Agents.,  1  (8): [PMID:24900228] [10.1021/ml100131b]

4. Rahman KM, Jackson PJ, James CH, Basu BP, Hartley JA, de la Fuente M, Schatzlein A, Robson M, Pedley RB, Pepper C, Fox KR, Howard PW, Thurston DE..  (2013)  GC-targeted C8-linked pyrrolobenzodiazepine-biaryl conjugates with femtomolar in vitro cytotoxicity and in vivo antitumor activity in mouse models.,  56  (7): [PMID:23514599] [10.1021/jm301882a]

5. Brucoli F, Hawkins RM, James CH, Jackson PJ, Wells G, Jenkins TC, Ellis T, Kotecha M, Hochhauser D, Hartley JA, Howard PW, Thurston DE..  (2013)  An extended pyrrolobenzodiazepine-polyamide conjugate with selectivity for a DNA sequence containing the ICB2 transcription factor binding site.,  56  (16): [PMID:23889553] [10.1021/jm4001852]

6. Corcoran DB, Lewis T, Nahar KS, Jamshidi S, Fegan C, Pepper C, Thurston DE, Rahman KM..  (2019)  Effects of Systematic Shortening of Noncovalent C8 Side Chain on the Cytotoxicity and NF-κB Inhibitory Capacity of Pyrrolobenzodiazepines (PBDs).,  62  (4): [PMID:30688457] [10.1021/acs.jmedchem.8b01849]

7. Picconi P, Hind CK, Nahar KS, Jamshidi S, Di Maggio L, Saeed N, Evans B, Solomons J, Wand ME, Sutton JM, Rahman KM..  (2020)  New Broad-Spectrum Antibiotics Containing a Pyrrolobenzodiazepine Ring with Activity against Multidrug-Resistant Gram-Negative Bacteria.,  63  (13): [PMID:32515951] [10.1021/acs.jmedchem.0c00328]

8. Joseph AM, Nahar K, Daw S, Hasan MM, Lo R, Le TBK, Rahman KM, Badrinarayanan A..  (2022)  Mechanistic insight into the repair of C8-linked pyrrolobenzodiazepine monomer-mediated DNA damage.,  13  (12.0): [PMID:36561066] [10.1039/d2md00194b]

Source

Source(1):

• Scientific Literature